Virtual Library

Abstract:
Difficulties of surgery after induction chemoradiotherapy (CRT) Surgery after induction therapy can be very challenging. From my own observations, this may particularly be an issue when the patient had nodal involvement at presentation and experienced a good response to the induction treatment (induction CRT or even induction C alone) where fibrosis of the responding lymph nodes may make the hilar vascular mobilization more difficult. The following lines will describe some tips on how to minimize the risks of such resections. Preoperatively: One should always take advantage of the induction therapy period (12 weeks or more) to achieve absolute smoking cessation in these patients. After induction therapy, one should obtain a fresh set of PFTs including a DCO measurement as both radiation and some of the induction chemotherapy agents may have caused significant pneumonitis with resulting altered lung function. If there is a possibility that a pneumonectomy will be required, prepare yourself. (QVQ, stress echo). Radiation esophagitis may have brought some nutritional issues, consider an alimentary “boost” when a significant weight loss has occurred during the induction phase of therapy. If there may be a risk that the SVC will be clamped, repaired or replaced, discontinue the port-o-cath preoperatively. Finally, make sure to review all imaging, particularly the pre-induction therapy CT. Surgery Personally, I approach these cases via open thoracotomy, though some have reported successful resections on MIS platforms. All patients get an epidural catheter preop. If one anticipates, issues with the SVC with a R upper lobar resection, get infra diaphragmatic IV access preop. Emphasize w anesthesia, in the preoperative area, the absolute need to keep these patients dry: an irradiated mediastinum cannot handle excess fluid. At entry, I prepare/ harvest the intercostal muscle, without dividing it. (I now keep the omentum for “later”, if needed to manage for a complication, and spare the serratus anterior in all cases). If accessible, I usually clear zone 7 first, with frozen section read. (The frozen section information/ feedback during this type of surgery can be very useful to have when one gets into a tough surgical corner…) If one is attempting a lobectomy and anticipates possible difficulties in the hilum, one should consider obtaining early circumferential control of the main veins and main PA (if possible), and even do so intrapericardially if needed. Similarly, early division of the azygos vein on the right, may help when one anticipates difficulties accessing the main R PA and surrounding structures. One may have to alter their “routine” sequence of dividing the central structures. With both upper lobes, when bulky fibrotic changes are present in the suprahilar areas, proceeding retrograde, from the fissures up is often very helpful. As well, dividing open the upper lobe bronchi from the back can help access and control the often fibrosed and foreshortened proximal lobar PA branches. On the left, I will identify the vagus nerve low down, away from the fibrotic field and follow it up into the AP window to minimize the risks of inadvertently injuring the recurrent nerve. During the case, I constantly remind anesthesia to keep these patients dry. For pneumonectomies, we give a steroid bolus before dividing the main PA , similarly we initiate amiodorone prophylaxis by infusion. In a R pneumonectomy, when we have stapled the bronchial stump, I add an additional non resorbable monofilament stitch to reinforce both ends of the bronchial stapled line. Finally, we cover all of our bronchial stumps with the IC muscle flap. POSTOP Remember to keep the patient dry. We give amidorone prophylaxis for 72 hours after pneumonectomies’ or other patients considered at elevated risk of going into atrial fibrillation post op. Beware of possible left vocal cord palsy after L pneumonectomy and left upper lobectomy: we keep these patients NPO until we are confident that their cords are OK. If there are any concerns, we get an immediate laryngoscopy. If the left cord is found to be paretic, we immediately get VC medialization (not negotiable)

Abstract:
Surgery for Stage IIIA NSCLC - Surgeon's Perspective Gail E Darling MD FRCSC, University Health Network, University of Toronto, Toronto Canada Outline Indications for operating on IIIA Choice of Induction regimen: chemotherapy vs chemoradiation Restaging the mediastinum: why or why not? how (EBUS vs med, redo med?) , Factors in decision making whether or not to proceed with surgery after induction Salvage resection after definitive chemoradiation Indications for Surgery for Stage IIIA NSCLC 1.T3N1M0, T4N0M0, T4N1M0: if primary is resectable with R0 resection 2.T1-3N2M0: single station microscopic N2, resectable with R0 resection, selected multistation N2 if microscopic N2 and nodal disease is resectable with R0 3.Patient is fit for planned resection Contraindications to surgery for Stage IIIA NSCLC 1. Extracapsular N2 2. Fixed bulky nodes 3. Inability to achieve an R0 resection 4. T4N2 5. Patient not fit for planned resection (right pneumonectomy required?) Choice of Induction: Chemotherapy alone vs Chemoradiation 1. Intergroup 0139 trial: concurrent cisplatin + etoposide + 45 Gy improved disease free survival over surgery alone 2. SAKK trial: RCT Chemo vs chemoRT ( sequential) →No difference in survival 3. Concurrent chemoRT higher rates of mediastinal downstaging compared to chemotherapy alone 4. Radiation may be undesirable if sleeve resection of bronchus or artery is planned Restaging after Induction therapy 1. CT scan: to assess response but primarily to confirm resectability and exclude progression 2. PET: to rule out progression; assess response to determine if surgery is required? 3. Mediastinum: a) restage only if surgeon will not operative if persistent N2. Intergoup 0139 trial reported best survival if mediastinum was sterilized by induction but even if persistent disease survival was better with surgery than chemoRT alone. B) Restaging: if first mediastinal staging was performed by mediastinoscopy PET is most accurate; EBUS/EUS not reliable (sampling error); redo mediastinoscopy difficult, not reliable. If first staging was performed by EBUS/EUS then mediastinoscopy is appropriate and reliable for restaging. Factors in Decision Making to Proceed with Surgery after Induction 1. Patient is fit ( recovered fully from induction, good performance status) 2. Cancer has not progressed 3. Lack of radiographic response is not a contraindication to resection 4. R0 resection is possible Salvage Surgery after Definitive Chemoradiation 1. Patient is fit with good performance status 2. Primary site is only site of disease

Abstract:
In the WHO 2015 classification, neuroendocrine tumors (NETs) have become one of the 4 major histological types of lung cancer. NET includes typical carcinoid (TC), atypical carcinoid (AC), small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC). In this presentation, I’ll talk about problems of diagnosis of SCLC, and challenge “common knowledges” of NETs as follows: 1. SCLC is highly malignant and only very rarely the patients survive after 5 years. What are pathological characteristics of tumors with longer survival? 2. There are no subtypes of SCLC, only combined SCLC is described in the WHO 2015. Isn’t subtyping of pure SCLC needed? Also, is SCLC a hilar-type cancer? 3. Diagnosis of SCLC doesn’t require immunohistochemistry (IHC) although IHC is used to diagnose even adenocarcinoma and squamous cell carcinoma. Isnt’ IHC useful for SCLC? 4. NET includes TC, AC, SCLC and LCNEC. Is this a spectrum of NET, showing progression of NET? In other words, does AC progress to LCNEC? 5. For adenocarcinoma diagnosis, transcription factor TTF-1 is useful even when the tumor doesn’t express glandular phenotypes such as mucin and CEA. In case of NET, we usually pay attention to NE phenotypes such as synaptophysin and NCAM, not to transcription factors. Aren’t transcription factors such as ASCL1 and INSM 1 useful for SCLC diagnosis? 6. Is the Kulchitsky an origin of SCLC? I’d like to answer these questions, mainly based on our own experiences.

Abstract:
Neuroendocrine tumors (NETs) are a distinct subgroup of neoplasms arising from the neuroendocrine cells. Due to the peculiar morphological, immunohistochemical and molecular characteristics, NETs are usually classified as a separate group of tumors among solid malignancies. Thoracic NETs include the pulmonary and the thymic NET. Pulmonary NETs (PNETs) comprise well-differentiated neuroendocrine tumors (typical carcinoid), moderately-differentiated neuroendocrine tumors (atypical carcinoid), the latter two grouped as Bronchial Carcinoids (BCs); large cell neuroendocrine carcinoma (LCNEC) and small-cell lung carcinoma (SCLC). There are also two preneoplastic conditions, the Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH) and the tumorlets whose role in the neuroendocrine carcinogenesis are yet to be fully clarified. PNETs represent about 25% of all lung cancers, most of them represented by SCLC. Thymic NETs (NeuroEndocrine Thymic Tumors, NETT) are considered as a subgroup of thymic carcinoma, although in most series they are classified separately, and are further classified as well-differentiated NETT (typical carcinoid), moderately-differentiated NETT (atypical carcinoid) and poorly-differentiated NETT (Large cell and small cell neuroendocrine carcinoma). NETTs are exceedingly rare and represent about 5% of all thymic tumors. The present lecture will focus on PNETs and NETTs, with a particular insight in the surgical management of these tumors. 1, Pulmonary NETs. The most recent TNM staging classifications of lung cancer (7[th] and 8[th] edition) suggest that PNETs should be staged similarly to Non-Small Cell Lung Cancer (NSCLC). Surgical indications largely depend on histology and stage. Bronchial carcinoids (BCs) represent about 10% of PNETs. The vast majority are typical carcinoids (TC, well-differentiated neuroendocrine tumors); they are usually located centrally in the lung parenchyma/airways (70%), and they are frequently confined to the lung without evidence of loco-regional or distant spread, which occur in about 5-10% of the cases. Atypical carcinoids (AT) share most of the characteristics of typical carcinoids, although they present a higher rate of mytoses and necrosis. They are more aggressive than TCs and they present with lymphnodal metastatic involvement in 30%-50% of the cases. LCNEC are usually diagnosed after resection, since a preoperative characterization on small biopsies is challenging. They are aggressive tumors, and more than 50% of the patients present with an advanced disease at diagnosis, for whom surgery is not indicated. As for SCLC, the vast majority of the patients present at an advanced stage, with hematogenous spread. The role of surgery in the treatment of PNETs is similar to what is currently employed for NSCLC. BCs are often amenable to surgery, due to the early stage at presentation. Anatomical resections (segmentectomy, lobectomy or more extended resections) offer the best outcome, while sublobar wedge resection should be avoided in fit patients, and should be reserved only for patients not amenable to anatomical resections. Parenchymal-sparing techniques (bronchial/vascular sleeve resection) should be employed whenever possible to avoid pneumonectomy in centrally-located tumors. Lymphadenectomy should be carried out according to the current guidelines (IASLC/ESTS), including a minimum of 6 nodes/stations of which 3 mediastinal including the subcarinal one. Endoscopic resection may have a role only in case of lobar/lung atelectasis to restore the bronchial patency before definite surgical resection Endobronchial resection is also employed with palliative intent in unresectable disease. Survival after resection of BCs is excellent, with more than 90% of the patients with typical carcinoids alive at 10 years, and 70% and 50% with atypical carcinoids alive at 5 and 10 years. The role of adjuvant therapy after complete resection of BCs is not fully determined and it is often discussed on an individual basis in a multidisciplinary tumour board setting. LCNEC are poor candidates for surgery, because of the loco-regional and distant spread at presentation. Anatomical resections, including extended resection to neighboring organs are needed in order to achieve a complete resection. Despite this, local recurrence and distant metastases are frequent after surgery. Adjuvant therapy (chemotherapy or chemoradiotherapy) is almost always needed after surgery for the disease control. SCLC has customarily been considered nonsurgical because of the high aggressiveness and the chemosensitivity of this neoplasm. However, in carefully selected patients with limited disease (T1-T2N0) surgery as part of a multidisciplinary protocol (chemoradiotherapy) may be proposed after a careful assessment of loco-regional (including mediastinal) and distant spread. 2, Thymic NETs. Thymic NETs (NETTs) are usually aggressive thymic tumors, very often presenting atypical features (atypical carcinoid). They express somatostatin receptors which may justify the use of Octreotide scintigraphy for the diagnosis and follow-up. About 30-40% have metastases at presentation and in some cases they are associated with endocrinopaties (Cushing syndrome, MEN-1 syndrome, etc). The staging system for NETTs has traditionally been the Masaoka system. The 7[th] edition of the TNM of thymic tumors included also the NETTs. As for other thymic malignancies, surgery is the treatment of choice for local and loco-regional disease (Stage I/II and selected Stage III). The resectability rate for NETTs is far lower than that of thymoma, ranging between 30% and 100% in most series. Complete (R0) resection is the most important prognostic factor. Median sternotomy and open surgical approaches are the optimal accesses for NETTs. The role of minimally-invasive techniques (MIT) in the treatment of NETT is extremely limited, due to the aggressive nature of the tumor. The role of induction and adjuvant treatments (radiotherapy or chemotherapy) has not been established yet, due to the rarity of the condition. 3, The collaborative effort. As for many rare diseases, also for NETs a collaborative, multi-Institutional, society-based effort is the single most important factor that can provide a real advancement in the research and management of this condition. The European Society of Thoracic Surgeons (ESTS) launched in 2012 a Neuroendocrine Tumors Working Group with the aim of collecting data from interested Institutions across the world. An amazing database collating more than 2100 patients has been designed which represents a tremendous opportunity for the study of these rare conditions. A number of studies have been published so far which constitute a solid backbone for the management of NETs.

Abstract:
Squamous cell lung cancers (SQCLC) account for between 15-25% of non-small cell lung cancer (NSCLC) cases. They are, biologically, quite distinct from lung adenocarcinomas, though this remains a fact that has had little positive effect to date in the management of this disease. Indeed, despite the FDA approval of a handful of new drugs for patients with SQCLCs since 2014, progress has been, for most, limited, reflecting the modest gains in survival achieved by these new agents. Navigating the treatment landscape has been, by turns, straight-forward and frustrating. This is most evident in the first-line setting where, apart from patients whose tumors exhibit high expression of PD-L1, a variety of platinum-based chemotherapy options are available, all with more or less equivalent efficacy as shown in Table 1:

	cisplatin + gemcitabine + necitumumab(1)	cisplatin + gemcitabine(1)	carboplatin + nab-paclitaxel(2)	carboplatin + paclitaxel(2)	cisplatin + docetaxel(3)
ORR (%)	31	29	41	24	37
Median PFS (mo)	5.7	5.5	5.6	5.7	-
Median OS (mo)	11.5	9.9	10.7	9.5	11.3

Second-line therapy is dictated then largely through exclusion. Patients who received pembrolizumab as first-line treatment will cycle through platinum-based chemotherapy. Patients who received platinum-based chemotherapy will, by and large, cycle through any one of a number of FDA-approved PD-1/PD-L1 antibody therapies, all with equivalent efficacy (pembrolizumab, nivolumab, atezolizumab). Docetaxel +/- ramucirumab is thus relegated to the de facto third-line option. There are, arguably, few clinically meaningful therapeutic options beyond this; the data behind these options will be discussed in further detail. Most recently, attempts have been made to target putative oncogenic drivers in this disease, based on larger scale genomic analyses and pre-clinical experiments generated TCGA and others.(4-6) Three relatively large-frequency signaling pathways and targets have been tested in early phase trials, including FGFR1 amplification, PI3K pathway alterations, and G1/S checkpoint aberrations both by individual groups and SWOG (LUNG-MAP, S1400). In short, there has been modest to no efficacy in targeted therapy trials to date. These studies are summarized in Table 2:

Target	Frequency	Drug	ORR
FGFR1 amplification	Up to 20%	AZD4547(7)	8%
		BGJ-398(8)	15%
		Dovitinib(9)	11.5%
PI3K pathway	Up to 50%	BKM120(10)	0%
		GDC-0032(ASCO 2017)	5%
G1/S checkpoint	Up to 50%	Abemaciclib(11)	17%

Most of these studies have lacked detailed molecular analyses of patient tumor samples, hampering our ability to determine why these targeted efforts have largely failed. One exception is the study of AZD4547 in FGFR1 amplified SQCLCs, where correlative tests demonstrated that focal amplification of FGFR1 in the 8p11 amplicon does not occur in the majority of cases, commensurate with relatively low mRNA and protein expression of the gene.(7) Overall, heterogeneity with regard to aberrations in overlapping signaling pathways and clonal diversity remains a concern. The rationale for and data from other studies will also be discussed, including early data from combination chemotherapy plus PD-1/L1 inhibition trials as well as potential future directions for research. References 1. Thatcher N, Hirsch F, Luft A, Szczesna A, Ciuleanu T, Szafranski W, et al. A randomized, multicenter, open-label, phase III study of gemcitabine-cisplatin (GC) chemotherapy plus necitumumab (IMC-11F8/LY3012211) versus GC alone in the first-line treatment of patients (pts) with stage IV squamous non-small cell lung cancer (sq-NSCLC). J Clin Oncol. 2014:abstr 8008. 2. Socinski MA, Bondarenko I, Karaseva NA, Makhson AM, Vynnychenko I, Okamoto I, et al. Weekly nab-Paclitaxel in Combination With Carboplatin Versus Solvent-Based Paclitaxel Plus Carboplatin as First-Line Therapy in Patients With Advanced Non–Small-Cell Lung Cancer: Final Results of a Phase III Trial. Journal of Clinical Oncology. 2012;30:2055-62. 3. Kubota K, Watanabe K, Kunitoh H, Noda K, Ichinose Y, Katakami N, et al. Phase III Randomized Trial of Docetaxel Plus Cisplatin Versus Vindesine Plus Cisplatin in Patients With Stage IV Non-Small-Cell Lung Cancer: The Japanese Taxotere Lung Cancer Study Group. Journal of Clinical Oncology. 2004;22:254-61. 4. TCGA Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature. 2012;489(7417):519-25. 5. Paik PK, Shen R, Won H, Rekhtman N, Wang L, Sima CS, et al. Next-Generation Sequencing of Stage IV Squamous Cell Lung Cancers Reveals an Association of PI3K Aberrations and Evidence of Clonal Heterogeneity in Patients with Brain Metastases. Cancer Discovery. 2015;5:610-21. 6. Kim Y, Hammerman PS, Kim J, Yoon J-a, Lee Y, Sun J-M, et al. Integrative and Comparative Genomic Analysis of Lung Squamous Cell Carcinomas in East Asian Patients. Journal of Clinical Oncology. 2014;32:121-8. 7. Paik PK, Shen R, Berger MF, Ferry D, Soria J-C, Mathewson A, et al. A Phase 1b Open Label Multicentre Study of AZD4547 in Patients with Advanced Squamous Cell Lung Cancers. Clinical Cancer Research. 2017. 8. Nogova L, Sequist LV, Garcia JMP, Andre F, Delord J-P, Hidalgo M, et al. Evaluation of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Kinase Inhibitor, in Patients With Advanced Solid Tumors Harboring Genetic Alterations in Fibroblast Growth Factor Receptors: Results of a Global Phase I, Dose-Escalation and Dose-Expansion Study. Journal of Clinical Oncology. 2017;35:157-65. 9. Lim SH, Sun J-M, Choi Y-L, Kim HR, Ahn S-M, Lee JY, et al. Efficacy and Safety of Dovitinib in Pretreated Advanced Squamous Non-small Cell Lung Cancer with FGFR1 Amplification: A Single-arm, Phase II Study. Cancer. 2016. 10. Vansteenkiste JF, Canon J-L, De Braud F, Grossi F, De Pas T, Gray JE, et al. Safety and Efficacy of Buparlisib (BKM120) in Patients With PI3K Pathway-Activated Non-Small Cell Lung Cancer (NSCLC): Results From the Phase II BASALT-1 Study. Journal of Thoracic Oncology. 2015;Publish Ahead of Print. 11. Patnaik A, Rosen LS, Tolaney SM, Tolcher AW, Goldman JW, Gandhi L, et al. Efficacy and Safety of Abemaciclib, an Inhibitor of CDK4 and CDK6, for Patients with Breast Cancer, Non–Small Cell Lung Cancer, and Other Solid Tumors. Cancer Discovery. 2016.

Abstract:
Malignant central airway obstruction (mCAO) occurs in patients with lung cancer and in patients with pulmonary metastases from other malignancies, including thyroid, breast, renal cell, and colon(1). It is loosely defined as obstruction of >50% of the central airways(2). Malignant CAO results in dramatic alterations to quality of life (QOL), decreased functional status, bleeding, post-obstructive pneumonia, and a poor prognosis(3, 4). The principle goal in the management of mCAO is to restore airway patency, palliate, improve QOL and symptoms, spirometric values, and survival(1, 5-7). There are 3 classifications of mCAO: endobronchial, extrinsic, or mixed. Multiple ablative bronchoscopic tools are available to relieve endobronchial or mixed obstructions(8). Ablative techniques include lasers, electrocautery, argon plasma coagulation, photodynamic therapy, microdebriders, and cryotherapy(1). Stents are primarily used to treat patients with mixed and extrinsic airway obstruction(1). Lasers have no role in the management of extrinsic airway obstruction(9). Ost and colleagues(1) showed that among 26 physicians from 15 centers, performing over 1,100 procedures, there was significant practice pattern variability. They also report that there was no single best ablative technique with regard the primary goal of improvements in dyspnea or QOL. There are no large clinical trials comparing various ablative modalities head-to-head and thus, superiority of one technique over another remains undefined(3). However, all ablative techniques can be used alone or in combination(8). In order to obtain optimal treatment outcomes, physicians should be competent and versatile in the use of multiple complementary modalities. Herein, we provide a clinical review of lasers, a technique that delivers a non-contact heat energy by light via catheter(9, 10), in the management of mCAO. The effectiveness of lasers in achieving relief of obstruction and symptomatic improvement from mCAO in very large series established credibility of this modality(11). Although outcome data is limited, laser therapy appears to be effective in providing rapid relief of endobronchial obstruction with symptomatic improvement in 70-80%(9, 12-15). One-year survival following treatment was around 30%(9). Local disease recurrence with mCAO is typical unless tumor debulking is followed by adjunctive therapies(16). Several types of lasers exist and each use different media to generate light(10). The details and specific role of each laser is beyond the scope of this discussion. Special focus has been placed on the Neodymium:Yttrium Aluminum Garnet (Nd:YAG) laser because it has become the most frequently used nonsurgical technique in the management of malignant and benign endobronchial disorders(12, 13, 17-19). One significant advantage of the Nd:YAG laser is its balanced properties in its ability to photocoagulate or vaporize tumor and cut stenotic lesions. Its ability to photocoagulate and vaporize before mechanical debulking allows for improved control of hemorrhage in the airway during bronchoscopy(9, 10). Dumon et al. and Cavaliere et al were among the first to report their experience of the Nd:YAG laser in benign and mCAO(12, 13). Cavaliere and colleagues showed an improvement in airway lumen in 92% of patients with mCAO(12). In a follow up article, the largest series to date, radiographic improvement was noted in 93% of patients with bronchogenic carcinoma, and their overall complication rate was 2.3%(20). A disadvantage of the Nd:YAG laser is the associated considerable set-up, maintenance costs, and its bulky size. The power and distance of the fiber from the lesions as well as the ration of absorption and scattering coefficients of laser determine the tissue effect(10). Lower power or the farther the distance between the laser fiber and the lesion lead to a shallow effect and cause superficial tissue coagulation. Conversely, higher power settings or a shorter distance between the laser and lesion result in deeper penetration causing tissue carbonization and vaporization(10). Safety of Nd:YAG laser in airway procedures has been well established and with appropriate precautions, the safety record of laser therapy is excellent. Protective eyewear is mandatory when the laser beam is activated(17). A “timeout” should be performed to confirm that the fraction of inspired oxygen setting is <40%, which reduces the risk of airway fire. Literature suggests that complications can be minimized if particular attention is paid to keeping the power settings to less than 40W, pulse duration of 0.5-1 second, and always having the laser beam aimed parallel to the airway(9). Complete or nearly complete mCAO without adequate visualization of distal lumen is a relative contraindication due to a possible risk of perforation(4). Significant complications develop in fewer than 5% of cases. One study showed that in 7,000 laser treatments, the reported overall complication rate was 0.99%(16). Reported complications include marked fluctuations in oxygen saturations and end-tidal CO2, massive hemorrhage, airway perforation, pneumothorax, pneumomediastinum, airway fire, gas embolism, myocardial infarction, cardiac arrest, and death. Air embolism is a result of high flow of air coolant and contact probes. It is recommended that a non-contact mode be used while keeping the coaxial coolant air flow at a minimum level(21). Continuous suction is used during the procedure to remove smoke. Continuous inspection of the airways is performed to remove any debris and to optimize ventilation. Both rigid and flexible bronchoscopes are used successfully. With flexible bronchoscope, the lesion is either photocoagulated or carbonized prior to removal, or the whole lesion is vaporized(17). Flexible bronchoscope allows easier access to areas that may require acute angulation. Rigid bronchoscopy provides a wide operating channel allowing simultaneous use of multiple tools. Specifically, the patient can be ventilated, blood and secretions aspirated, and laser coagulation utilized. The aim is to devascularize the tumor and subsequently core out the tumor with the tip of the rigid bronchoscope(17). Additionally, mechanical sequential rigid bronchoscopic dilations can also be performed. When skilled in both techniques, the rigid technique is generally favored by many due to its multiple stated advantages(11, 13, 17, 22). However, in the absence of randomized controlled trials, expert opinion continues to guide therapeutic approaches. Most patients are managed in a multimodality fashion for the optimal outcome. Selection of a specific modality remains operator and institution specific. Irrespective of the type of ablative technique or choice of laser, the goal of treating mCAO remains the same, relieve the obstruction.

Abstract:
The fact that an early cancer is early in its nature implies that a curative therapy should be offered. However, radical treatments such as surgery and radiotherapy might not be the best options for various reasons. Firstly, the amount of normal tissue that has to be removed or denaturalized can contraindicate the treatment, secondly the unresectabilitiy for some central tumors, and finally the concern that metachronous lesions can occur and might need further intervention. Thus, the use of bronchoscopic therapies in the management of lung cancer limited to the airways has brought light to the management of early lung cancer. Several techniques are available to treat endoluminal superficial lesions, including laser, electrocautery, argon-plasma coagulation, photodynamic therapy, cryotherapy and brachytherapy. The curative potential of all these therapies has been demonstrated, as all of them are able to effectively destroy the depth of an early lung central cancer, which counts no more than 5 mm of malignant tissue. The definition of early lung cancer used in the studies of bronchoscopic therapies does not exactly correspond with the actual definitions of the TNM classification and differs among authors. Nagamoto et al. observed that squamous cell carcinoma (SCC) ≤ 3 mm thick and with longitudinal extension ˂ 20 mm was associated with no nodal involvement (1). Konaka et al. suggested that hypertrophic lesions of ˂ 1 cm are either carcinoma in-situ (CIS) or micro-invasive tumor within the muscle layer, while nodular and polypoid lesions ≥ 1 cm are more likely invasive beyond the cartilaginous layer (2). According to these, Mathur et al. defined early stage cancer as radiographically occult SCC that is endoscopically superficial, ˂ 2 cm in surface area with clearly visible margins and not invading beyond the bronchial cartilage (3). Later, the Japan Lung Cancer Society defined the bronchoscopic criteria of central type early stage lung cancer as that located subsegmental or more proximal, ˂ 2 cm with bronchoscopically recognizable margin and proven SCC (4). The new 8th edition of the TNM classification incorporates new definitions in the early stages including some special situations. Superficial spreading tumors in the central airways are those confined to the tracheal or bronchial wall regardless of size and location, and are labeled T1a ss. Carcinoma in situ (classified as Tis) now includes both squamous cell carcinoma in situ (SCIS, or squamous dysplasia) and adenocarcinoma in situ (AIS, which is localized, ≤ 3 cm and shows pure lepidic growth, lacking stromal, vascular, alveolar space or pleural invasion). Minimally invasive adenocarcinoma is classified as T1a(mi) and corresponds to solitary adenocarcinoma ≤ 3 cm with a predominantly lepidic pattern and ≤ 0.5 cm invasion. The invasive component is defined as histologic type other than lepidic or tumor cells infiltrating myofibroblastic stroma. In our setting, it is important to remark that examination of small biopsy specimens cannot exclude or quantify invasive components for AIS and T1a(mi) respectively. Although AIS can be highly suspected from biopsies with pure lepidic pattern together with a CT correlation of the ground glass component, AIS and T1a(mi) require examination of the entire resection specimen. The accuracy of the diagnostic techniques for early lung cancer represents the first step for defining the lesions suitable for endobronchial therapy. High definition bronchoscopy, autofluorescence bronchoscopy (AFB) and narrow band imaging (NBI) have been used for defining the margins of the lesion, the latter having a higher specificity. To evaluate the shallowness of the tumor, radial endobronchial ultrasound (rEBUS) and optical coherence tomography (OCT) have been used (6). Also, the combination of AFB and OCT have shown good results for both detection and characterization of premalignant lesions of the centrals airways (7). Thin-section CT (≤ 1 mm) and PET-CT might also be useful in the evaluation of premalignant lesions (8,9). Treatment success is directly dependent on lesion accessibility and the capability to correctly delineate the margins and shallowness of the lesions (10). Once the boundaries of the lesion are defined, choosing a technique over another depends mainly on the expertise of the bronchoscopist and availability of the therapy. Bibliography: 1. Nagamoto N, Saito Y, Ohta S, et al. Relationship of lymph node metastasis to primary tumor size and microscopic appearance of roentgenographically occult lung cancer. Am J Surg Pathol. 1989;13(12):1009-13. 2. Konaka C, Hirano T, Kato H, et al. Comparison of endoscopic features of early-stage squamous cell lung cancer and histological findings. Br J Cancer. 1999;80(9):1435-9. 3. Mathur PN, Edell E, Sutedja T, et al. Treatment of early stage non-small cell lung cancer. Chest. 2003;123(1 Suppl):176S-80S. 4. The Japan Lung Cancer Society Classification of Lung Cancer Kanehara. Tokyo. 2010. 5. Travis WD, Brambilla E, Nicholson AG, et al. The 2015 World Health Organization Classification of Lung Tumors. J Thorac Oncol. 2015;10:1243-60. 6. Kurimoto N, Murayama M, Yoshioka S, et al. Assessment of usefulness of endobronchial ultrasonography in determination of depth of tracheobronchial tumor invasion. Chest. 1999;115:1500-6. 7. Lam S, Standish B, Baldwin C, et al. In vivo optical coherence tomography imaging of preinvasive bronchial lesions. Clin Cancer Res. 2008;14:2006-11. 8. Sutedja TG, Codrington H, Risse EK, et al. Autofluorescence Bronchoscopy Improves Staging of Radiographically Occult Lung Cancer and Has an Impact on Therapeutic Strategy. Chest. 2001;120:1327-32. 9. Pasic A, Brokx HA, Comans EF, et al. Detection and staging of preinvasive lesions and occult lung cancer in the central airways with 18F-fluorodeoxyglucose positron emission tomography: a pilot study. Clin Cancer Res. 2005;11(17):6186-9. 10. Sutedja TG, van Boxem AJ, Postmus PE. The curative potential of intraluminal bronchoscopic treatment for early-stage non-small-cell lung cancer. Clin Lung Cancer. 2001;2:264-70; discussion 71-2 Figure 1 Figure 2 Endobronchial therapies for early lung cancer

Therapy	Principle	Depth	Main Risks	Considerations
LASER	Thermal ablation with laser light	+++ (but variable)	Airway perforation, hemorrhage, airway fire, respiratory failure.	Those of thermal therapies*
Electrocautery	Thermal ablation through electric flow current	+++ (but variable)	Airway perforation, hemorrhage, airway fire, respiratory failure.	Those of thermal therapies*. Caution with pacemakers. Cheaper than laser.
Argon Plasma Coagulation (APC)	Thermal ablation with electric current through argon gas	2-3 mm	Airway fire, respiratory failure.	Those of thermal therapies*. Caution with pacemakers.
PDT	Non-thermal ablation with light in previously photosensitized tissues	3 mm	Respiratory failure. Skin sun burn.	Produces intense photosensitivity. Delayed results and need for repeat bronchoscopy.
Cryotherapy	Thermal cellular damage though freezing and tawing	3 mm	Respiratory failure. Superficial bleeding	Delayed results.
Brachytherapy	Radiation therapy applied directly to tumor through endobronchial catheter	Variable	Ulcera, fibrosis, stenosis, haemoptysis	Accumulative radiation dose. High-complexity and need for multidisciplinary team.

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Abstract:
Genotyping of plasma cell-free DNA (cfDNA) is rapidly changing our management approach for genotype-defined lung cancers. Widely available assays now have the ability to noninvasively identify driver mutations in cfDNA, monitor response to therapy, and characterize emerging resistance. However, such liquid biopsies also have clear limitations – existing assays are unlikely to replace tumor biopsies completely. This presentation will discuss an optimal approach for integrating liquid biopsies into lung cancer care, while also envisioning how liquid biopsies may become a routine part of lung cancer treatment in the years ahead.

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Background:
Durvalumab, an engineered human IgG1 anti-PD-L1 mAb, demonstrated an improvement in PFS vs placebo and favorable benefit/risk profile in the Phase 3 PACIFIC study in locally advanced, unresectable NSCLC. Here we summarize patient-reported outcomes from PACIFIC.

Method:
In the randomized, double-blind, Phase 3 PACIFIC study (NCT02125461), patients who had previously received ≥2 cycles of platinum-based concurrent chemotherapy with definitive dose radiation without disease progression were randomized (2:1) to durvalumab 10 mg/kg i.v. q2w or placebo for up to 12 months. Secondary endpoints included evaluation of symptoms, function and global health status/QoL using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 v3 questionnaire and its lung cancer module, QLQ-LC13. Patients completed the questionnaires at baseline, Week 4, Week 8, q8w until Week 48, then q12w until disease progression. Changes from baseline for key symptoms were analyzed using a mixed model for repeated measures (MMRM). Time to deterioration (TTD) and odds of improvement were analyzed. Deterioration or improvement was defined as a change in score from baseline ≥10. Hazard ratios (HR) were calculated using a stratified log-rank test and odds ratios (OR) using logistic regression.

Result:
Compliance with completing the questionnaires was high in both durvalumab (n=476) and placebo (n=237) groups (>80% up to Week 48). There were no differences between groups at baseline in symptoms, function or global health status/QoL. MMRM analysis showed no statistically significant differences between treatment groups in adjusted mean changes from baseline (average over 12 months) in the prespecified symptoms of dyspnea, cough, chest pain, fatigue and appetite loss, and for global health status/QoL and physical functioning. Clinically relevant improvements from baseline were observed throughout the study in both durvalumab and placebo groups for dysphagia (mean [SD] change at Week 48, −14.2 [26.1] and −14.8 [25.3], respectively) and alopecia (−22.1 [33.0] and −21.4 [29.5]). There were no differences in median TTD between groups except ‘other pain’ (9.2 months with durvalumab vs 5.6 months with placebo [HR 0.72; 95%CI 0.58, 0.89]). The only difference in improvement rates between groups was for appetite loss (26.1% improvement rate with durvalumab vs 24.9% with placebo [OR 1.72; 95%CI 1.04, 2.85]). Other symptoms, function and health-related QoL remained stable throughout with no between-group differences in TTD or improvement rates.

Conclusion:
Durvalumab treatment did not worsen symptoms, function or health-related QoL. Clinically relevant improvement in alopecia and dysphagia with durvalumab and placebo was likely due to resolution of toxicities related to prior chemoradiation.

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Background:
Postop platinum-based CT is considered standard of care in resected NSCLC with lymph node involvement. BRCA1 and BRCA2 are important DNA repair factors primarily involved in the repair of double strand DNA breaks. BRCA-1 functions may act as a differential regulator of response to cisplatin (Cis) and antimicrotubule agents. BRCA1 defficiency enhances Cis resistance and loss of BRCA1 function is associated to sensitivity to DNA-damaging CT and may also be associated with resistance to spindle poisons.

Method:
SCAT randomized phase III multicenter trial tests individualized optimal CT based on expression of BRCA1. After surgery patients (p) with St II and Iii NCSLC were random 1:3 to control arm (3 cycles Cis-Docetaxel) or to experimental arm with treatment assigned according BRCA1 expression levels (low levels: Cis-Gemcitabine; intermediate levels: Cis-Doc; high levels: Docetaxel alone). Stratification factors: N1 vs N2; age < or > 65 y; non-Squamous vs Squamous (Sq) histology; lobectomy vs pneumonectomy). Planned PORT in N2. Primary end-point OS. Secondary end-points DFS, toxicity profile (CTCAE v 3.0) /compliance, recurrence pattern. Statistical hypothesis: 5y survival rate control group (45%) could be increase 20% in experimental arm.

Result:
From June/2007 to May/2013, a total of 591 p were screened and 500 of them were randomized in the study, 108 in control arm, 392 in experimental arm. In experimental arm 110 p received Cis-Gem, 127 Cis-Doc and 110 Doc alone. There were no significant differences between arm for known prognostic factors: Median age 64 y; 79% males, 21% females; 43% Sq, 49% Adenoca, 8% others; 57% former smokers, 32% current smokers, 11% never smokers; pneumonectomy 26%; N1 58%, N2 48%. Median tumor size 4.4 cm (0.8-15.5 cm). Median mRNA BRCA1 levels 15.78 (0.73-132). Mean BRCA1 levels 6.95 in Adenoca vs 20.29 in Sq (p<0.001). Compliance of CT was better in experimental arm with less dose-reductions and without differences according extent of surgery. CT compliance was lower in patients older 70 y. Median PFS: 38.7 m (control), 32.2 m Cis-Gem, 34.3 m Cis-Doc and 41 m Doc. At 5 years, event-free rate is 54% in control arm and 56% in experimental arm and median OS 73.3 m (control) vs 77.5 m (exp) (p=0.75). In experimental arm: Docetaxel alone 80.2 m, Cis-Doc 80.5 m and Cis-Gem 74 m.

Conclusion:
Higher survival than expected in patients with lymph node involvement. No significant difference in survival achieved with the experimental arm. In case of high levels BRCA CT treatment without cisplatin is not detrimental. (Eudract:2007-000067-15; NCTgov: 00478699)

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Background:
The residual tumor (R) classification describes the tumor status after treatment. It reflects the effectiveness of treatment, has prognostic impact and may affect further treatment. We analyzed existing and potential R status criteria, including the proposed IASLC definition for “uncertain” resection margin status (2005), from data collected for the IASLC Lung Cancer Staging Project.

Method:
This analysis is based on 14,712 patients undergoing NCSLC surgery, for whom full R status and survival data were available. R status criteria and the following data were evaluated: number of N2 stations explored; lobe-specific systematic lymph node dissection (SLND); extra-capsular extension (ECE); status of the highest station; bronchial carcinoma in situ (cis) at bronchial resection margin (BRM); pleural lavage cytology (PLC). Revised categories of R0, R(un), R1 and R2 were designated and tested for survival impact.

Result:
There were 14,293 R0, 263 R1 and 156 R2 cases, with median survival not reached, 33 and 29 months (p<0.0001). R status correlated with T and N stages (p<0.0001). Greater or equal to 3 N2 stations were explored for 9,290 cases (63%) and lobe-specific SLND in 6,619 (45%), with positive associations for increasing pN2 stage (p<0.0001). ECE was recorded in 61 (20%) of 304 N+ cases evaluated. The highest station was positive in 942 (6.4%) cases. PLC was positive in 59 (3.6%) of 1,646 cases and there was BRM cis in 13 cases. After reassignment according to the IASLC proposed definition, there were 6,103 R0 cases, 8,203 R(un), 250 R1 and 156 R2. Figure 1



Conclusion:
These data confirm the proposed criteria for Uncertain R status, R(un), with a prognosis stratifying between R0 and R1. Further detailed prospective data collection is required to characterize fully the prognostic impact of these criteria. Detailed evaluation of R status is of particular importance in the design and analyses of clinical trials of adjuvant therapies.

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Background:
There have been few data on the chemotherapy in elderly advanced non-small cell lung cancer (NSCLC) patients with poor performance status (PS), and usefulness of chemotherapy for such patients remains unclear.

Method:
All consecutive patients with advanced NSCLC, elerly (≥75 years old), ECOG PS ≥2, EGFR mutation negative/unknown, and newly diagnosed from January 2009 to December 2012 at Kurashiki Central Hospital, were retrospectively reviewed to clarify the factors which predicts the survival benefit of chemotherapy.

Result:
59 patients were enrolled. 31 patients received at least one chemotherapy regimen (chemotherapy group), whereas 28 patients received best supportive care (BSC) alone (BSC group). The proportion of PS 2 and serum albumin level were significantly higher in the chemotherapy group than in the BSC group. The overall survival (OS) was longer in the chemotherapy group than in the BSC group (median OS of 4.7 months and 3.1 months, p = 0.0119). In the chemotherapy group, log-rank testing did not show statistically significant differences in OS between single-agent therapy group and carboplatin-based doublet therapy group, whereas the OS of the patients who received chemotherapy for only 1 cycle was significantly better than those of the patients who received chemotherapy for ≥ 2 cycles. Hypoalbuminemia was not only the risk factor for the early termination of chemotherapy, but also the independent prognostic factor in the chemotherapy group. A receiver operating characteristic curve analysis showed that the best cut-off value was 3.40 g/dl. In the patients with serum albumin ≥ 3.40 g/dl, OS was significantly longer in chemotherapy group than that in BSC group (p=0.0156), whereas, the patients with serum albumin < 3.40 g/dl exhibited poor prognosis regardless of presence/absence of chemotherapy. Figure 1



Conclusion:
In the elderly advanced NSCLC patients with poor PS, serum albumin level may help identify the patients who are more likely to benefit from chemotherapy.

Background:
In 2012, lung cancer was the leading cause of death from malignancy in Thailand. The management of advanced non-smll cell lung carcinoma (NSCLC) was rapidly developed in the last decade. The patients were tailored treated according to their histology and molecular profiles, which contributed to significant improvement of survival, especially in the molecular-selected patient.

Method:
This retrospective study was conducted by reviewing medical records of stage IIIB-IV NSCLC patients treated at Chonburi Cancer Hospital, from July 2013 to June 2016. To study the survival of the patient, also focus on an epidermal growth factor receptor (EGFR) mutation testing including an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy in clinical practice and to find a prognostic factor for the survival.

Result:
This study enrolled 148 patients with median follow up time 7.90 months. Median age was 60.5 (range 25-91). There were male 64%, non-smokers 37%, stage IIIB/IV 17/83% and adenocarcinoma/squamous cell carcinoma 74/13 %. The Eastern cooperative oncology group (ECOG) 0-1, 2-4 and no record were found 35%, 36% and 29 %, respectively. The median survival time of all patients was 8.04 months. Median survival times of patients receiving and not receiving systemic therapy were 10.60 months and 3.00 months, respectively (p <0.001). However, a median survival of the EGFR mutation patient was not reach. One hundred twenty one patients (121/148, 81.7%; chemotherapy118, EGFR-TKI 3) received first-line systemic therapy.Fifty patients (50/148, 33.8%) and fifteen patients (15/148, 10.1%) received second- and third-line systemic therapies, respectively. The most common first-and second-line systemic therapies were platinum doublet (116/121) and docetaxel (32/50), respectively. Eighteen percent (27/148) of the patients were tested for EGFR mutations. Fifty five percent (15/27) of the patients tested for EGFR status were sensitive mutations. Unfortunately, only some of sensitive EGFR mutation patients could really access to an EGFR-TKI therapy and mostly received it as a late-line of treatment. Multivariate analysis showed that ECOG performance status 2-4 (p<0.001), no record for ECOG (p=0.001), no lung metastasis (p=0.012) and unknown EGFR (p=0.001) indicated significantly unfavorable prognostic factors for the survival.

Conclusion:
The survival time of advanced NSCLC in our institute was comparable to pivotal studies. Obviously, in real-life clinical practice in Thailand, EGFR mutation testing was quite low because of financial limitation to get access to a targeted therapy. The poor ECOG performance status, no record for ECOG performance status, no lung metastasis and unknown EGFR mutation were poor prognostic factors for the overall survival.

Background:
We aimed to determine whether Astragalus membranaceus root extract (AmE), which has immunomodulatory activities mainly on macrophages and Th1 type immune response, improve the overall survival (OS) of patients with metastatic non-small cell lung cancer (NSCLC).

Method:
The medical charts of 117 patients with metastatic NSCLC were retrospectively assessed. Thirty-four patients (A group) using AmE during systemic anti-cancer treatment were compared with 83 controls (C group) who did not use AmE following the diagnosis of NSCLC. The histological subtype, performance status, age, gender, smoking status, comorbidities, chemotherapeutics (CT), and erlotinib that were received in any line of treatment were recorded. We compared the OS of the patients in the A and C groups.

Result:
The median (±SD) age of the patients was 61(±7) years and all patients were administered systemic treatment (CT or erlotinib). The histological subtype, performance status, age, gender, smoking status, comorbidities, usage of different type of CT agents and erlotinib were similar in the A and C groups. The median follow-up period was longer for the A group than the C group (18 vs 11 months, p <0.001). At the time of the analysis, 83.8% of the patients had died. In the univariate analysis, the median OS (±SE) was significantly longer in the A group compared with the C group (21±4.2 vs 11 ±0.9 months, p= 0.004) (Fig 1). In addition to AmE usage, female gender, smoking status, presence of hypertension and erlotinib usage had also significant impact on OS (p <0.05 for all). In the multivariate analysis, only AmE (HR: 0.46, 95% CI: 0.27-0.76, p= 0.003) and erlotinib (HR: 0.45, 95% CI: 0.22-0.89, p= 0.02) usage had significant benefit on OS. Figure 1 Fig 1. The Kaplan-Meier curves of OS according to AmE usage.



Conclusion:
The use of AmE during systemic anti-cancer treatment may significantly prolong OS of patients with metastatic NSCLC.

Background:
A subanalysis of a phase III registrational trial demonstrated a 9.5-month survival benefit with nab-paclitaxel/carboplatin vs paclitaxel/carboplatin for patients ≥70 years with advanced NSCLC. ABOUND.70+ evaluated 2 schedules of nab-paclitaxel/carboplatin to determine whether a 1-week break could improve tolerability.

Method:
Patients ≥70 years with locally advanced/metastatic NSCLC were randomized to receive first-line nab-paclitaxel 100mg/m[2] on days 1, 8, 15 and carboplatin AUC 6 on day 1 of a 21-d cycle (Arm A) or the same regimen with a 1-week break between cycles (Arm B). Primary endpoint: the percentage of patients with grade ≥2 peripheral neuropathy or grade ≥3 myelosuppression; key secondary endpoints: progression-free survival (PFS), overall survival (OS), and overall response rate (ORR), for which statistical analyses did not control for type I error (P values unadjusted).

Result:
At interim evaluation, the primary endpoint was similar across treatment arms leading to early closure of enrollment. Baseline characteristics were well balanced between arms (Arm A, n = 71; Arm B, n = 72). Primary endpoint results are presented in the table. Overall, confirmed ORR was 23.9% vs 40.3% (P = 0.038), median PFS was 3.6 vs 7.0 months (HR 0.48 [95% CI, 0.30-0.76]; P = 0.002), and median OS was 15.2 vs 16.2 months (HR 0.72 [95% CI, 0.44-1.19]; P = 0.197). Among patients who received second-line therapy across treatment arms (n = 61), median OS from start of first-line treatment was 22.7 months (95% CI, 11.79-not estimable [NE]) and 16.4 months (95% CI, 12.12-NE) in patients receiving chemotherapy and immunotherapy, respectively.

Conclusion:
nab-Paclitaxel/carboplatin was well tolerated and efficacious in elderly patients with advanced NSCLC. Incidence of grade ≥2 peripheral neuropathy or grade ≥3 myelosuppression (primary endpoint) was similar in both treatment arms. A signal of improvement was observed in PFS and ORR in Arm B. NCT02151149

Primary Endpoint
Event, n (%)	Arm A n = 68	Arm B n = 70
Patients with either grade ≥ 2 peripheral neuropathy or grade ≥ 3 myelosuppression	52 (76.5)	54 (77.1)
Grade ≥ 2 peripheral neuropathy	25 (36.8)	25 (35.7)
Grade ≥ 3 myelosuppression	48 (70.6)	45 (64.3)
Neutropenia	39 (57.4)	39 (55.7)
Anemia	14 (20.6)	17 (24.3)
Thrombocytopenia	17 (25.0)	12 (17.1)

Background:
Because of the improved efficacy of first and second-line therapy in patients (pts) with non-small cell lung cancer (NSCLC) with wild type EGFR, a high proportion of patients receive third-line therapy and beyond. When this study was planned, erlotinib, an EGFR tyrosine kinase inhibitor, was recommended as standard second-line therapy, irrespective of EGFR status, based on the results of BR 21 study. We conducted the Hokkaido Lung Cancer Clinical Study Group (HOT) 1002 trial, to compare erlotinib (E) with S-1 (S) for NSCLC as third or fourth-line therapy.

Method:
This study was a multicenter, randomized phase II study in Japan. All eligible pts had a recurrent or advanced NSCLC with wild type or unknown EGFR and had progressed after two or three previous chemotherapies. Pts were randomly assigned and treated with E or S until either disease progression or unacceptable toxicity. The primary endpoint was the disease control rate (DCR). The secondary endpoints included the overall survival (OS), progression-free survival (PFS), response rate (RR), toxicity and quality of life (QOL).

Result:
From May 2011 to March 2016, 37 pts were randomly assigned to receive erlotinib (n=19) or S-1 (n=18). This study was terminated immaturely because of the poor pts accrual. The median number of treatment cycles was 3 (range 1-10) in E and 4 (range 1-11) in S. DCR/RR was 42.1%/15.8% in E and 66.7%/16.7% in S. Median PFS/OS (months) was 1.6 (95% CI; 0.8-3.7)/ 8.0 (95% CI; 4.2-13.3) in E and 3.3 (95% CI; 1.5-5.8)/12.2 (95% CI; 5.5-16.3) in S (p=0.094/0.42). Although the patient number was too small for statistical comparison, S group showed better PFS than E group both as third-line (1.5 vs 2.7 months) and fourth-line (3.3 vs.5.9 months). In both treatment groups, the most commonly reported Gr 3-4 non-hematological toxicities were fatigue, anorexia and nausea. There was one Gr 5 event pneumonitis in S. No significant difference was seen in QOL.

Conclusion:
Although this trial had no statistical power to draw any conclusions, treatment with S-1 as a third-/fourth-line showed numerically better clinical outcomes compared with erlotinib.

Background:
Lung cancer is the first cause of death by cancer in Mexico, the chemotherapy based on platin is the regular treatment for the advanced stages of this disease; adding bevacizumab to the chemotherapy gave better results in the average response and the progression-free survival. A common strategy is the maintenance therapy, which is used to maintain the response to the initial therapy after the chemotherapy. The objective is to evaluate and to contrast the effect on the progression-free survival of the combined scheme of “Bevacizumab and Pemetrexed” versus the use of only “Pemetrexed” as a maintenance therapy in patients with advanced lung cancer in non-small cells.better results in progression-free survival.

Method:
Observational, analytic, transversal, retrospective studies. Patients with advanced lung adenocarcinoma negative EGFR and ALK who received maintenance therapy with pemetrexed/bevacizumab after have shown response at the first line of chemotherapy based on platin/pemetrexed.

Result:
Twenty-two patients were analyzed. Eleven of them received pemetrexed/carboplatin and bevacizumab at the first line followed by pemetrexed/bevacizumab. And, the other eleven received pemetrexed/carboplatin followed by a maintenance therapy with pemetrexed. All of them were in the clinic stage IV. 45% of the patients in both groups showed distance metastasis (meaning more frequent). The progression-free survival was the same in both groups of treatment with an average of sixteen months (HRE 0.76 (IC 95% 0.24-2.35), Log Rank P=0.62)Figure 1.



Conclusion:
Patients having lung adenocarcinoma without activating mutations using bevacizumab as maintenance therapy do not have better results in progression-free survival.

Background:
NSCLC is the leading cause of cancer-related deaths in Argentina. NSCLC is rarely observed in young adults (aged 18-40 years) and presents distinctive molecular characteristics. This study analyzed the prevalence of oncogenic molecular alterations in tumor samples from young adults treated at our institution. Different molecular biology techniques were used and treatment outcomes were reported.

Method:
Retrospective observational study of FFPE tumor samples from individuals aged 18-40 years, presenting stage IV lung adenocarcinoma. ALK fusions were studied by IHC (clone-D5F3) and confirmed with FISH-Vysis. The areas selected for molecular studies were micro-dissected, and DNA/RNA were purified. EGFR mutations were studied by Sanger. If available, targeted NGS was done with Colon and Lung. Cancer Research Panel v2 (CLRP) for DNA analysis; and/or Oncomine™ Panel Focus Assay (OFA) for DNA/RNA analysis. Both panels were performed in an Ion 520 chip sequenced in the Ion S5 Next Generation Sequencing Systems. The sequences obtained were analyzed in the Ion Reporter™ Software 5.2.1. The OFA was informed by Ion Torrent™ Oncomine™ Knowledgebase Reporter.

Result:
Six patients were included, 5/6 tumors were lung adenocarcinoma and 1/6, poorly differentiated carcinoma. The male:female ratio was 2:1. Median age was 35y (range 32-37) and all subjects had stage IV disease. EGFR and ALK were tested in all patient's samples, and 4/6 had NGS analysis. Five samples (83%) harbored known targetable oncogenic drivers: EGFR sensitizing mutations occurred in 3/5, ALK translocation with KRAS co-mutation in 1/5, and HER2 exon 20 insertions in 1/5. Only one sample without NGS was negative for the studied oncogenes. Targeted therapies were administered to 4/5 patients. Figure 1



Conclusion:
Our series shows a high prevalence of known actionable oncogenic drivers in young patients with NSCLC tumor. In this population an extensive molecular profiling of tumors is required to improve the treatment strategy.

Background:
Lung cancer is one of the worst prognostic cancers. The survival rate of patients with stage 4 lung cancer is low, especially when invading major organs such as the liver and adrenal glands. Bevacizumab, anti-angiogenesis monoclonal antibody, showed better prognosis combination with conventional chemotherapy of lung adenocarcinoma. We compared progression of liver metastasis and overall survival, the patients who had lung cancer with liver metastasis, conventional chemotherapy or target agents and adding bevacizumab to conventional chemotherapy.

Method:
From 2010 to 2016, we analyzed the differences in treatment outcome between classic chemotherapy or target agents and adding bevacuzimab with conventional chemotherapy among patients with hepatic metastasis in lung cancer patient. Compare the overall survival, response to liver metastasis, and progression of liver metastasis.

Result:
There are 10 patients with conventional chemotherapy or target agents and 5 patients with adding bevacizumab to conventional chemotherapy. Both of them are male predominance, more elderly at adding bevacizumab group. The time taken to worsen the hepatic metastasis was 77.7 days in conventional chemotherapy or target agents group and 174 days in the group with bevacizumab. Overall survival was 134 days in the chemotherapy or target agents group and 332 days in the bevacizumab combination group.

Conclusion:
In lung cancer patients with hepatic metastasis, the efficacy of inhibition of hepatic metastasis was better in patients with combined angiogenesis inhibitor therapy than cytotoxic chemotherapy. We suggest that individual metastatic organ, as like liver, which has poor prognosis, has to reevaluate response to therapy, because of tumor microenvironment.

Background:
Bevacizumab (bev) is used as a standard first-line treatment in combination with doublet platinum-based chemotherapy and as the maintenance therapy with either bev alone or bev with single agent chemotherapy for advanced non-small cell lung cancer (NSCLC). However, it was not well established which is the best chemotherapy of bev combination regimen and which is the optimal dose of bev in this setting.

Method:
Phase II-III RCTs of bev containing regimens of a first line and maintenance treatment of advanced NSCLC were identified from PubMed and Scopus databases until 20 February 2017. Data was independently reviewed and extracted by two oncologists. Network meta-analysis was performed to assess the efficacy of bev in both the induction and maintenance phase. We estimate the probability of being the best combination regimen with bev using surface under the cumulative ranking curve (SUCRA) analysis. This analysis was registered with PROSPERO (CRD42016027171).

Result:
All 4,108 studies were identified from PubMed and Scopus databases. After removal of duplications and exclude ineligible studies, 27 RCTs were included. Studies were analyzed by the period of treatment as at induction period and at maintenance period. Induction treatment with platinum+pemetrexed (pem) showed a strongest benefit to control disease [RR 1.33 (95% 1.05-1.70)]. Bev is best to combine with platinum+taxane [RR 1.26 (95%CI 1.06- 1.50)]. Low dose bev (7.5 mg/kg) and standard dose bev+doublet of platinum and taxane are comparable for controlling disease [(RR 1.00 (95%CI 0.73-1.36)]. Maintenance treatment with pem+bev could be the most effective regimen to prevent disease progression and to improve response rate, however the regimen was the first rank of increasing death from adverse event [RR 3.2 (95%CI 1.11-9.21)]. Maintenance with low dose bev could control disease and also decrease both cancer-specific death and all causes of death. Risk-of-bias assessment was done and the majority of the included RCTs are low risk of bias.

Conclusion:
Bev is best to combine with doublet of platinum and taxane for induction treatment. Adding bev to doublet platinum with pem may not enhance more efficacy of induction treatment. Maintenance with low dose bev is applicable given that it had lower toxicity profiles than a conventional dose (15 mg/kg) without significant differences of benefit. Maintenance with pem+bev could decrease death from cancer and all cause of death, however there was a very high toxicity profile. Therefore, pem+bev might be the option for only selected patients with good performance status in maintenance treatment.

Background:
Fatal acute exacerbation (AE) of interstitial pneumonia (IP) may occur after chemotherapy for lung cancer. We developed and evaluated a scoring system for assessing the risk of AE after chemotherapy in patients with lung cancer associated with IP.

Method:
A review of medical records identified 107 patients with primary lung cancer associated with IP who had received chemotherapy during the period from June 2007 through September 2017. We developed a model to scoring AE risk after chemotherapy in lung cancer patients with IP, and logistic regression was used to evaluate this model.

Result:
The general score for anti-cancer agents was determined by using rates of AE reported in past studies. The risk score was calculated by using the following formula: (1 × anti-cancer agent general score) + (3 × smoking history [>70 pack-years]) + (4 × history of steroid medication) + (3 × %diffusing capacity of the lung carbon monoxide [<50%]). Patients were then classified into three groups. The AE rate was 12% for a risk score of 0–5, 47% for a score of 6–10, and 66.7% for a score ≥11. This sensitivity of the scoring system was 78.6%, and specificity was 67.8%.

Conclusion:
The present scoring system could identify IP patients at high risk for AE after chemotherapy for lung cancer.

Background:
There is no standard treatment strategy for patients with advanced squamous cell lung carcinoma who experienced progression with one or more lines of chemotherapy. Apatinib, a new tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 (VEGFR-2), has been shown confirming antitumor activity and manageable toxicities in gastric cancers and other solid tumor. Moreover, clinical trials of S-1 on squamous cell lung carcinoma shows curative effect and lighter adverse reactions. This prospective study tried to investigate the efficacy and safety of apatinib plus S-1 as second- or third-line treatment in patients with advanced squamous cell lung carcinoma.

Method:
In this open-label single-arm study(ChiCTR-OPC-16009048), patients were treated oral apatinib, at a dose of 250-500 mg daily, and S-1, at a dose of 60mg/m[2] daily D1-14, repeat every 3 weeks, in the second- or third-line setting. The primary endpoint was progression-free-survival (PFS) and the tumor response was determined according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. Treatment was continued until disease progression or unacceptable toxicity occurs.

Result:
From August 19, 2016 to May 31, 2017, 16 patients were enrolled. In 16 patients, there were 7 patients available for efficiency evaluation and 12 patients available for safety evaluation. Computed tomography (CT) scan evaluation revealed that partial response (PR) occurred in 1 of 7 patients and other 6 showed stable disease (SD). However with 2 patients of 6 patients showed stable disease (SD), the tumor demonstrates central cavitation. Hypertension is one of the most frequent adverse reactions, which appeared in 3 of 12 patients who were getting to be normal under oral antihypertensive agent. Others like hand-foot syndrome, proteinuria, diarrhea and fatigue appeared in 1 of 12 patients respectively and could be better controlled. No treatment-related hemorrhage occurred.

Conclusion:
Apatinib plus S-1 exhibits superior activity and acceptable toxicity for evaluable patients with advanced squamous cell lung carcinoma. The research team will continue the study.

Background:
It is well documented that brain metastases negatively impact the prognosis for patients with A-NSCLC. However, it is less well known how secondary brain tumours impact health status, quality of life (QoL) and productivity in these patients. As such, an analysis of data from A-NSCLC patients was conducted to evaluate whether the metastatic site (brain vs non-brain) impacts the burden of disease.

Method:
Data were collected between May 2015 and June 2016 from adult patients with Stage IIIB or IV NSCLC via medical chart reviews and patient self-completion forms as part of a multicentre, cross-sectional study conducted in France, Germany and Italy. Health status was measured using the EQ-5D-3L (including the visual analogue scale, EQ-VAS), QoL using the EORTC QLQ-C30 and work/activity impairment using the WPAI:GH questionnaire. Outcomes were stratified by metastatic site (brain vs non-brain); no adjustments were made for possible confounding factors. Statistical significance was assessed using Mann–Whitney U tests.

Result:
1030 patients were recruited: mean patient age, 64.5 years; male, 65.9%; current/former smokers, 77.9%. Most patients had Stage IV NSCLC (88.4%), non-squamous histology (70.3%) and/or were receiving first-line therapy (70.5%). Patients were largely receiving chemotherapy, regardless of line of therapy. Of 910 evaluable Stage IV patients, 111 had brain metastases and 799 had non-brain metastases. Significant differences were observed between patients with brain metastases versus non-brain metastases for health status, QoL and activity-related impairments (TABLE). The percentage of work-related impairment was also numerically higher in patients with brain metastases. Figure 1



Conclusion:
Patients with A-NSCLC and secondary brain tumours had significantly worse health status and QoL, and experienced greater work- and activity-related impairments, compared with A-NSCLC patients with non-brain metastases. These findings may indicate a need for specific management/support programmes for patients with A-NSCLC and brain metastases.

Background:
ABOUND.70+ evaluated 2 schedules of first-line nab-paclitaxel/carboplatin in patients ≥70 years with advanced NSCLC to determine whether a 1-week break can improve tolerability. Safety and QoL by cycle are reported.

Method:
Patients ≥70 years with locally advanced/metastatic NSCLC were randomized to first-line nab-paclitaxel 100mg/m[2] on d1, 8, 15 and carboplatin AUC 6 on d1 of a 21-d cycle (Arm A) or the same regimen with a 1-week break between cycles (Arm B). Primary endpoint: percentage of patients with grade ≥2 peripheral neuropathy (PN) or grade ≥3 myelosuppression (laboratory values). QoL (exploratory endpoint) was assessed using Lung Cancer Symptom Scale (LCSS) on d1 of each cycle. Safety analyses included patients receiving ≥1 dose of study medication. AEs/QoL were analyzed at each of the first 6 cycles.

Result:
At interim evaluation, primary endpoint was similar across arms, resulting in early closure of enrollment. Of 143 randomized patients, 68 and 70 in Arms A and B received ≥1 dose of study drug. Table lists primary endpoint and key safety results by cycle. Grade ≥2 PN occurred earlier in Arm A. Incidence of grade ≥3 myelosuppression was highest in the first 2 cycles, progressively declining after cycle 3 (both arms). Dose reductions occurred in earlier cycles for Arm A; at the start of cycle 4, 36% vs 47% of patients received the maximum dose (100mg/m[2]) of nab-paclitaxel in Arms A and B. Generally, QoL was maintained throughout treatment. LCSS item of cough improved with each cycle; mean change from baseline at the end of cycle 6 was 25.4 and 13.8mm (visual analog scale).

Conclusion:
Although the overall rate of grade ≥2 PN and grade ≥3 myelosuppression was similar between arms, analysis by cycle showed that grade ≥2 PN and dose reductions occurred earlier in Arm A. QoL was maintained in both arms. NCT02151149

	Arm A n = 68		Arm B n = 70
Safety
Primary endpoint, %	76		77
P value	0.9258
Peripheral neuropathy, %	Grade ≥ 2[a]	Grade ≥ 3[a]	Grade ≥ 2[a]	Grade ≥ 3[a]
All cycles	37	13	36	17
Cycle 1	6	0	0	0
Cycle 2	6	4	1	0
Cycle 3	7	4	9	1
Cycle 4	4	0	7	1
Cycle 5	6	3	4	1
Cycle 6	4	1	4	9
Myelosuppression, %	Grade ≥ 3		Grade ≥ 3
All cycles	71		64
Cycle 1	35		37
Cycle 2	22		10
Cycle 3	3		10
Cycle 4	6		1
Cycle 5	1		3
Cycle 6	3		3
[a ]Calculated by first occurrence of adverse event of respective grade.

.

Background:
Patients with advanced NSCLC with poor ECOG PS can benefit from platinum-based doublet chemotherapy, although limited data exist from recent, randomized prospective trials. ABOUND.PS2 evaluated the safety and efficacy of nab-paclitaxel/carboplatin induction followed by nab-paclitaxel monotherapy in patients with advanced NSCLC and ECOG PS 2.

Method:
Chemotherapy-naive patients with histologically/cytologically confirmed stage IIIB/IV NSCLC and ECOG PS 2 received 4 cycles of nab-paclitaxel 100 mg/m[2] on days 1 and 8 plus carboplatin AUC 5 on day 1 q3w. Patients not progressing could receive monotherapy with nab-paclitaxel 100 mg/m[2] on days 1 and 8 q3w until progression or unacceptable toxicity. Primary endpoint: percentage of patients discontinuing within the first 4 cycles due to treatment-emergent adverse events (TEAEs). Other endpoints: progression-free survival (PFS), disease control rate (DCR), overall survival (OS), overall response rate (ORR), and quality of life (QoL) by Lung Cancer Symptom Score (LCSS).

Result:
Forty patients were treated. Median age was 67.5 years, 60.0% were male, 92.5% were white, and 62.5% had nonsquamous histology. During induction, 11 of 40 patients (28%) discontinued due to TEAEs (primary endpoint). In total, 16 of 40 patients (40.0%) received nab-paclitaxel as monotherapy. In all treated patients, the median percentage of per-protocol dose of nab-paclitaxel was 78.3% and the median nab-paclitaxel dose intensity was 52.2 mg/m[2]/week (planned, 66.7 mg/m[2]/week). See table for additional safety, efficacy, and QoL results.

Conclusion:
These results support the role of this nab-paclitaxel–based regimen in patients with NSCLC and ECOG PS 2. The regimen was well tolerated and appears to have resulted in a clinically meaningful improvement in QoL. Compared with historical data, this regimen is active in patients with stage IIIB/IV NSCLC and ECOG PS 2. NCT02289456

	All Treated Patients N = 40
Safety
Grade ≥ 3 TEAEs of special interest, n (%) Neutropenia Anemia Thrombocytopenia Peripheral neuropathy	9 (22.5) 7 (17.5) 2 (5.0) 1 (2.5)
Efficacy
PFS, median (95% CI), months	4.4 (2.99-7.00)
OS, median (95% CI), months	7.66 (4.93-13.17)
ORR (RECIST v1.1), n (%)	12 (30.0)
DCR, % Complete response Partial response Stable disease Progressive disease, % Patients with no postbaseline tumor assessment	30 (75.0) 0 12 (30.0) 18 (45.0) 2 (5.0) 8 (20.0)
QoL
Mean maximum improvement from baseline
LCSS Global QoL item, mm[a]	16.91

[a] A ≥ 10-mm improvement was considered clinically meaningful.

Background:
ABOUND.PS2 evaluated nab-paclitaxel/carboplatin induction followed by nab-paclitaxel monotherapy in patients with advanced NSCLC and ECOG PS 2. Concordance between patient- and physician-reported PS as well as change in PS with chemotherapy were assessed longitudinally.

Method:
Chemotherapy-naive patients with histologically/cytologically confirmed stage IIIB/IV NSCLC and ECOG PS 2 received 4 cycles of nab-paclitaxel 100 mg/m[2] on days 1 and 8 plus carboplatin AUC 5 on day 1 q3w. Patients not progressing could receive monotherapy with nab-paclitaxel 100 mg/m[2] on days 1 and 8 q3w until progression or unacceptable toxicity. Primary endpoint was the percentage of patients discontinuing within the first 4 cycles due to treatment-emergent adverse events. ECOG PS was assessed by patients on day 1 of each cycle and at treatment discontinuation, and ECOG PS and spirometry were assessed by physicians at screening, on day 1 of each cycle, and at treatment discontinuation.

Result:
Forty patients were treated. Baseline ECOG PS was reported as 2 by 48% and 95% of patients and physicians, respectively. Only 53% of patients rated their ECOG PS the same as the physician at cycle 1 day 1. For patients with both pre- and post-treatment ECOG assessments, 14 of 33 patients (42%) and 12 of 38 physicians (32%) reported an improvement from baseline at least once during treatment (Figure). At baseline, physicians believed that ECOG PS would be reversible with treatment in the majority of patients (80%). Mean FEV1 was 1.29 L and mean PEF was 2.66 L/s at baseline; exploratory investigations of spirometry data indicate that lung function (FEV1 and PEF) remained stable over the course of treatment.

Conclusion:
These results from the ABOUND.PS2 study suggest that patient-reported PS assessments may differ from physician assessments. Improvements in ECOG PS were reported by both patients and physicians during treatment. NCT02289456Figure 1

Background:
Various studies have reported that the neutrophil-to-lymphocyte ratio in the serum (sNLR) may serve as a cost-effective and useful prognostic factor in patients with various cancer types. However, no study has reported the prognostic impact of the NLR in malignant pleural effusion (MPE). To address this gap, we investigated the clinical impact of NLR as a prognostic factor in MPE (mNLR) and a new scoring system that uses NLRs in the serum and MPE (smNLR score) in lung cancer patients

Method:
We retrospectively reviewed all of the patients who were diagnosed with lung cancer and who presented with pleural effusion. To maintain the quality of the study, only patients with malignant cells in the pleural fluid or tissue were included. The patients were classified into three smNLR score groups, and clinical variables were investigated for their correlation with survival.

Result:
In all, 158 patients were classified into three smNLR score groups as follows: 84 (53.2%) had a score of 0, 58 (36.7%) had a score of 1, and 16 (10.1%) had a score of 2. In a univariate analysis, high sNLR, mNLR, and increments of the smNLR score were associated with shorter overall survival (p < 0.001, p = 0.004, and p < 0.001, respectively); moreover, age, Eastern Cooperative Oncology Group performance status (ECOG PS), histology, M stage, hemoglobin level, albumin level, and calcium level were significant prognostic factors. A multivariable analysis confirmed that ECOG PS (p < 0.001), histology (p = 0.001), and smNLR score (p < 0.012) were independent predictors of overall survival.

Conclusion:
The new smNLR score is a useful and cost-effective prognostic factor in lung cancer patients with MPE. Although further studies are required to generalize our results, this information will benefit clinicians and patients in determining the most appropriate therapy for patients with MPE.

Background:
No definitive chemotherapeutic regimen has been established in patients with non-small-cell lung cancer (NSCLC) who failed second-or third-line treatment. The study of this aim is to investigate the effect of apatinib in advanced non-small cell lung cancer.

Method:
72 patients with advanced non-small cell lung cancer treated in our hospital from March 2014 to March 2016 were selected and given oral apatinib (750mg, qd) to tumor progression, death or toxicity intolerance so far. The objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), and toxic side effects were observed and observed. Single factor analysis was used to compare the relationship between the clinical features and PFS.

Result:
The median PFS of the patients was 4.8 months (95%CI:4.7-5.0). The results of single factor analysis showed that there were no significant differences between different gender, age, PS score, histological type, drive gene mutation and metastasis foci, the number of metastasis, metastasis, treatment history, line number and duration of treatment in patients with PFS (P>0.05). The ORR of this group was 13.89%, DCR was 83.33%. According to the clinical data of 72 patients in the treatment of patients with the clinical efficacy of the waterfall plot, we can see that there are 54 cases of patients with lesions to reduce the diameter of tumor lesions as the effective treatment of the standard, there were 10 patients with of PR. There are various types of adverse events occurred in 60 patients, the incidence rate was 83.33%, including 22 cases (30.55%) for the aged III.

Conclusion:
Apatinib is a effective and safe treatment in advanced non-small cell lung cancer, and can be carried out more in-depth research and application in clinic.

Background:
Pathological (p) N1 or N2 non-small cell lung cancer (NSCLC) patients may experience poor prognosis despite complete resection; therefore, adjuvant chemotherapy is recommended for them. In this study, we investigated the risk factors for pN1 or N2 NSCLC.

Method:
From March 2005 to December 2015, we retrospectively reviewed 93 patients with completely resected pN1 or N2 NSCLC. Patients with synchronous or metachronous multiple lung cancer, malignancies from other organs, or who received neoadjuvant chemoradiotherapy were excluded. Clinicopathological factors analyzed included: age, sex, serum carcinoembryonic antigen levels, surgical procedures, histology, size of invasive tumor, pathological N status, pleural invasion, lymphatic invasion, vascular invasion, and histological grade. Univariate and multivariate analyses of disease-free survival and overall survival were conducted.

Result:
The study group comprised 93 patients (64 men, 29 women; age range: 38–86 years; mean: 68±9.9 years). The median follow-up period was 35.1 months. The preoperative serum carcinoembryonic antigen level was elevated in 36 patients. Complete resection was performed in all patients, comprising pneumonectomy in two patients (including sleeve pneumonectomy), bilobectomy in three, and lobectomy in 87 (including lobectomy with bronchoplasty or resection adjacent organs). Adenocarcinoma, squamous cell carcinoma, and other histology were observed in 59, 22, and 12 patients, respectively. The maximum diameter of invasive diameter was >30 mm in 39 patients and ≤30 mm in 54. There were 52 patients with pN1 and 41 with pN2. Forty-four were with pleural invasion, 52 with lymphatic invasion, and 48 with vascular invasion. Multivariate analysis showed histology to be an independent factor for recurrence, whereas older age (>70 years), pleural invasion, and adjuvant chemotherapy were independent factors for poor survival. There were 24 patients with no adjuvant chemotherapy, 10 could not receive it because of poor postoperative performance status, and 3 were ineligible because of older age. The 5-year overall survival in patients with adjuvant chemotherapy was 61.8%, compared with 23.8% for those without (p =0.002).

Conclusion:
Older age, pleural invasion, and adjuvant chemotherapy were found to be independent factors for poor survival in pN1 or N2 NSCLC. Adjuvant chemotherapy is a potential consideration for pN1 or N2 patients. Surgery to maintain performance status may be useful in relation to undergoing adjuvant chemotherapy.

Background:
To evaluate the effect of pre-biopsy contrast-enhanced CT scanning on hemorrhage complicating percutaneous transthoracic needle biopsy

Method:
This retrospective study was approved by the institutional review board. We reviewed 1282 biopsy procedures, Chi-square test and multivariate analysis. We conduct propensity score matching by using MatchIt package in R with nearest-neighbor 1-to-1, 2-to-1 and 3-to-1 matching ,respectively

Result:
The incidence of pulmonary hemorrhage was 20.2% (259/1282), including 247(19.2%) mild hemorrhage, 7 (0.5%) moderate hemorrhage, and 5 (0.4%) severe hemorrhage. Pre-biopsy CECT scan was significantly associated with pulmonary hemorrhage, and had a positive effect (p=0.008, OR=0.671, 95% CI: 0.499-0.902). When matching hemorrhage and non-hemorrhage cases in proportion of 1 to 1, 1 to 2, and 1 to 3, the correlation of CECT and hemorrhage showed significancy and CECT was indeed a protective factor (p=0.039, 0.028 and 0.013, respectively). Additionally, biopsy position (p=0.016,OR=2.734, 95% CI: 1.207-6.194 for supine, lateral as reference), lesion sizes (p=0.005, OR=0.990, 95% CI: 0.983-0.997), puncture depth (P=0.000, OR=1.017, 95% CI: 1.009-1.025), number of pleural passes (P<0.05, for twice, third, fourth, OR= 1.546, 1.673, 8.746, 95% CI: 1.065-2.244, 1.082-2.588, 2.891-26.456, respectively ) were also related with hemorrhage.

Conclusion:
Pre-biopsy contrast-enhanced CT scan is a protective factor for hemorrhage. To reduce the incidence of hemorrhage to the greatest extent. We strongly suggest the patients scheduled to perform percutaneous transthoracic needle biopsy do pre-biopsy contrast-enhanced CT scan routinely.

Background:
The treatment options of metastatic non-squamous non-small cell lung cancer patient who not harboring abnormal genes are very limited due to the inapplicability of targeting agents. Luckily, recombinant human endostatin (rh-endostatin) as an angiogenetic drug named endostar was approved in treating non-small cell lung cancer (NSCLC) combined with doublet chemotherapy in China. Administration of rh-endostatin is optimized from 3-4 hours intravenous infusion to continuous intravenous infusion in order to improve the compliance. In this study, we observed the efficacy and safety of continuous intravenous infusion rh-endostatin combined with pemetrexed and cisplatin in first-line treatment of non-squamous NSCLC without any gene alternatives.

Method:
The main criteria for patient enrollment includes KPS≥80, stage IV non-squamous histology, EGFR negative, ALK-EML4 negative, ROS1 and MET negative. Forty-six patients were enrolled and received endostar 30mg day1 to day7 continuous intravenous infusion, pemetrexed 500mg/m2 day1, cisplatin 25mg/m2 day1 to day3, 21 days each cycle. All patient received this regimen at least 2 but no more than 6 cycles. The assessment (RECIST 1.1) was applied every 2 cycles during treatment process and then every 3 months afterwards. The primary endpoint is progression free survival (PFS). Secondary endpoints are overall response rate (ORR), disease control rate (DCR) and safety.

Result:
The efficacy of this regimen showed that 2 (4.34%) patients achieving complete response (CR). Nineteen (41.30%) patients have their tumors reach partial response (PR), while 11 (23.91%) patients have a stable disease (SD). The overall response rate was 45.65%. Disease control rate was 69.56%. The median time of progression free survival is 301 (95% CI, 250 – 352) days. Severe adverse events caused by hematological toxicity were rare for this regimen, only 2 cases of myelosuppression were found. The non-hematological side effects, particularly nausea and vomiting were observed in 6 patients during their treatment. There is no severe cardiotoxicity showed related to the regimen used in this trial.

Conclusion:
Continuous intravenous infusion endostar combined with pemetrexed plus cisplatin could be an efficient regimen as a first-line treatment for Chinese patients with metastatic non-squamous NSCLC but without any gene mutants. Patients received this regimen could have a relatively long progression free survival time and well-tolerance.

Background:
Recently, some retrospective studies suggested improvement of clinical outcome of patients with non-small cell lung cancer (NSCLC) receiving chemotherapy after immune checkpoint inhibitor.

Method:
We performed a single-center, retrospective study to compare overall response rate (ORR) and progression-free survival (PFS) in NSCLC patients who received single-agent cytotoxic chemotherapy after nivolumab (Group A) with those in NSCLC patients who received single-agent cytotoxic chemotherapy as 3[rd]-line or 4[th]-ine treatment without preceding nivolumab treatment (Group B). Patients with EGFR mutation or ALK rearrangement were excluded from this study.

Result:
Fourteen and 61 patients were were included in Group A and Group B, respectively. There were no significant difference of clinical characteristics between the two groups in terms of age, sex, smoking history, performance status and histology. Nab-paclitaxel was most frequently used in group A, while docetaxel was most commonly used in group B. Docetaxel or gemcitabine was significantly highly used in group B (7.1% vs. 54.1%, p < 0.01). The median administered line of nivolumab in Group A was 4. ORR was higher in Group A, but not significantly (14.3% vs. 8.1%, p = 0.610). Median PFS was compatible between the two groups (median, 56 days vs. 63 days, p = 0.425).

Conclusion:
Nivolumab might improve the efficacy of subsequent chemotherapy.

Background:
Both antiangiogenic agents (nintedanib and ramucirumab) in combination with docetaxel and monotherapy with anti-PD-1/ PD-L1 immunotherapy have demonstrated efficacy as second-line (2L) treatment of patients with stage IV lung adenocarcinoma. However, selection of optimal candidates and the most appropriate therapeutic sequence is under discussion. Herein, we report on the efficacy of the nintedanib/docetaxel combination following first-line (1L) platinum-based chemotherapy and subsequent immunotherapy in a real-world setting.

Method:
From May 2014 to December 2015, 390 patients in 108 Spanish centers enrolled in the nintedanib Named Patient Use (NPU) program. NPU inclusion criteria were advanced lung adenocarcinoma with progressive disease following at least one line of platinum-based doublet chemotherapy. We retrospectively assessed patients that received immunotherapy (available through clinical trials or the nivolumab NPU program) prior to nintedanib/docetaxel. The aim of this analysis was to evaluate the efficacy of the nintedanib/docetaxel combination in this new clinical setting.

Result:
Eleven patients met the inclusion criteria for this analysis: 64% were men; median age of 67 years (range, 44–74); ECOG performance status 0-1 in 100% of patients; median number of treatment lines before inclusion in the nintedanib NPU program was 2 (range, 2-3); PD-L1 expression was positive (unknown cut-off) in 6 patients and was not determined in 5 patients. Median progression-free survival (PFS) of first-line platinum-based chemotherapy was 3.3 months (range 1.4-9.4): 9 patients (82%) had progressed <6 months since start of first-line treatment and 4 patients (36%) had progressed <3 months. Second-line immunotherapy was pembrolizumab (36.5%), atezolizumab (36.5%) and nivolumab (27%). Median PFS of second-line immunotherapy was 2.3 months (range, 0.7-11). The overall response rate (ORR) to second-line immunotherapy was 18% with a disease-control rate (DCR) of 45%. The median number of treatment cycles of nintedanib/docetaxel was 4.5 (range, 2-22). Median PFS of nintedanib/docetaxel post first-line chemotherapy and second-line immunotherapy was 3.2 months (range, 1.4-14.6). Best response was partial response in 4 patients (36%), stable disease in 5 patients (46%), and progressive disease in 2 patients (18%), for an ORR of 36% and a DCR of 82%.

Conclusion:
Our experience in the Spanish nintedanib NPU program in patients with adenocarcinoma NSCLC pretreated with platinum-based doublet chemotherapy and immunotherapy suggests an encouraging ORR and DCR of nintedanib/docetaxel as compared with clinical trial results. These results reinforce the importance of an optimal therapeutic sequence for managing advanced lung adenocarcinoma: 1) Nintedanib/docetaxel should be the recommended second-line treatment in early progressors and 2) Possible chemosensitization effect by immunotherapy.

Background:
Inspite of being the commonest cause of death among all cancer deaths, approximately 25% of Stage IV Lung cancer receive systemic therapy; although more than 60% of NSCLC present with Stage IV disease. Prospective randomised studies and meta-analysis have demonstrated survival and quality of life improvement in patients receiving systemic therapy. With significant advancement of molecular pathophysiology have opened up access to new systemic therapy like anti-EGFR, anti-ALK, and Immunotherapy. We conducted the study in Kolkata - to define the rates of patient referral to Medical Oncologists after diagnosis of Stage IV NSCLC. the rates of systemic therapy administration both standard chemotherapy and targeted therapy. the reason why a Stage IV NSCLC may not be referred to a Medical Oncologist or receive standard systemic therapy.

Method:
We performed chart review on Stage IV patients in Single Institute (Community Hospital) between 2004 to 2007 and 2010 to 2013. Staging was based on the 7th Edition of American Joint Committee for Cancer Staging. The 2 stages are based on availability and non-availability of TKIs freely. We collected baseline patient characters and compared median overall survival, referrals and treatment in these 2 cohorts.

Result:
900 patients from the period 2004 to 2007 and 800 patients for the period 2010 to 2013 were included (n=1700) in the 2 cohorts, In the 2 cohorts 60% vs 82% were referred for cancer care and 28% vs 74% received traditional therapy. There was a correlation between referral for cancer care and Medical Oncology with use of systemic therapy and survival, mOS = 11.2 months vs 1 month in those receiving systemic therapy. In those not receiving systemic chemotherapy the OS was 2 months vs 4 months. The major reasons for no referrals to Medical Oncology included poor functional status, rapid decline and doctors’ preference and patients’ preference. These were the similar reasons for patients not given systemic therapy. 9% vs 60% received EGFR inhibitors, those who received EGFR inhibitors had a mOS of 16.8 months. Multivariate analysis showed male sex (HR 1.16 p=0.008) and pulmonary embolism (HR 1.2 p=0.002) correlated with worse survival, while receiving chemotherapy (HR 1.2 p=<0.001) and having been enrolled in clinical trials (HR 0.76 p=0.049) correlated with better survival.

Conclusion:
We confirm that systemic therapy improves survival but as yet not been optimally used. Some modifiable factors would be improving referral guidelines, advocacy and patient teaching. There is a need for safe and effective therapy.

Background:
Lung cancer is one of the most leading cause of death. One of the prognostic factors that affect survival in lung cancer is weight loss. İn this study, we aimed to investigate the effect of body fat mass ratio on prognosis and survival in advanced stage small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) patients.

Method:
Between September 2014 and July 2015, 200 patients who were diagnosed with advanced lung cancer and whose body fat mass percentage and Body Mass Index (BMI) were determined by using Tanita Body Composition Analyzer during the admission in our institution were included in the study. All patients were analyzed for survival in terms of body fat mass ratio and BMI and other parameters.

Result:
One hundred and sixty four of the patients (82%) were male. The median age was 56.5 (28-93) years. Forty seven (23.5%) of the patients were diagnosed with SCLC and 153 (76.5%) were diagnosed with NSCLC. In univariate analysis; There was no statistically significant on survival effect of, gender, age (<65,> 65), histological diagnosis (SCLC, NSCLC), smoking history, performance status, weight loss during the last 6 months and BMI (>30, <30) (p> 0.05). In the univariate analysis the survival was effected by comorbid disease presence [median 11.4 months in patients with comorbid disease and 19.2 months in patients without comorbid disease (p = 0.012)], and body fat mass ratio [median 16.4 months in <30% and 29.2 months in >30% (p = 0.038)], and they were found statistically significant. In multivariate analysis; There was no statistically significant on survival effect of gender, age (<65 ,> 65), histological diagnosis (SCLC and NSCLC), BMI (<25 and> 25), performance status, however comorbid disease (p = 0.01) and body fat mass ratio (p = 0.033) were found to have a significant effect on survival.

Conclusion:
In patients with advanced lung cancer, body fat mass ratio were found to be independent prognostic factor for over all survival.

Background:
We conducted a study to explore the application of carboplatin in carboplatin–pemetrexed therapy and determine the recommended dose of carboplatin in Chinese patients with chemo-naive advanced nonsquamous nonsmall-cell lung cancer (NSCLC).

Method:
From January 2014 to April 2016, 151 patients with chemo-naive NSCLC, who were treated with carboplatin plus pemetrexed (500 mg/m2), was conducted. The area under the curve (AUC) of carboplatin was back-calculated from actual dosages using the Calvert formula. Patients were divided into two groups according to an AUC ≥4 or an AUC <4, respectively. The primary efficacy endpoint were overall response rate (ORR) and disease control rate (DCR). Adverse events (AEs) were evaluated with NCI-CTCAE 3.0.

Result:
The median AUC of carboplatin was 4.0 (1.8-5.5). A total of 79 patients had an AUC ≥4 and 72 patients had an AUC <4. The ORR and DCR of all patients were 33.8% and 90.1%, respectively. The ORR and DCR were 35.4% and 86.1%, respectively, in the AUC ≥4 group, 31.9% and 94.4%, respectively, in the AUC <4 group. No difference was observed in ORR (p=0.650) and DCR (p=0.086) in the AUC ≥4 or AUC <4 group. Furthermore, no significant difference was observed in all grade or grade ≥3 AEs in the two groups.

Conclusion:
Our study suggested that compared to Western populations, the calculating dosages of carboplatin using the Calvert formula was common insufficient for Chinese populations, fortunately, therapeutic efficacy remained equally. In addition, it was not increased by maintaining the AUC of carboplatin at ≥4.

Background:
Lung cancer is the leading cause of cancer deaths among men and women in Canada. Many non-small cell lung cancer (NSCLC) patients have metastatic disease at the time of diagnosis, which is associated with poor survival outcomes. However, there appears to be a small subset of patients with advanced disease that live substantially longer than anticipated. Studies have examined the association of various clinical parameters, such as metastatic disease, with survival in cancer patients. Our study aims to determine the impact of metastatic disease burden and distribution on survival in survival outliers with stage IV NSCLC.

Method:
Data on stage IV NSCLC patients diagnosed between 1999-2011 was obtained from the Glans Look Lung Cancer database. Survival outliers were defined as patients who lived > 5 years, or greater than 2 standard deviations from mean survival (adenocarcinoma, 47.5 months; squamous cell carcinoma, 57.4 months); patients not meeting survival outlier criteria were defined as average survivors. Clinical characteristics such as age, gender, smoking history, and treatments were compared between survival outliers and patients with average survival. Metastatic disease was evaluated by comparing differences in organ sites, number of metastatic sites, and local versus distant metastases. Fisher's exact test was used to analyze categorical factors, and Wilcoxon rank-sum test was performed to study continuous factors. Statistical analyses were implemented by R v3.3.0.

Result:
1803 stage IV NSCLC patients (1291 adenocarcinoma and 512 squamous cell carcinoma) were identified. In the adenocarcinoma group, there were 29 patients who lived >5 years, and 49 who lived >47.5 months. There were 13 squamous cell carcinoma patients who lived greater than 5 years and >57.4 months. Survival outliers tended to be younger, and had a smaller smoking history. Metastatic disease distribution differed significantly between adenocarcinoma and SCC survival outliers. Among adenocarcinoma patients, longer survival was associated with local metastatic disease (stage M1a), ≤1 site of metastasis at diagnosis, the presence of solitary bone metastasis, and the absence of liver metastasis (all p-values <0.05). In comparison, M1a disease, and the presence of solitary bone metastasis and solitary brain metastasis was associated with longer survival in SCC patients (all p-values <0.05).

Conclusion:
Survival outliers with local metastatic disease lived longer than patients with distant metastases. There were marked differences in the sites of distant metastases between adenocarcinoma and squamous cell carcinoma patients, and this was associated with differences in survival outcomes. The present study helps us better understand the role of metastatic disease distribution on survival, in hopes of determining important prognostic factors for lung cancer patients in the future.

Background:
Amrubicin (AMR) is one of treatment options in patients with previously treated advanced non-small cell lung cancer (NSCLC). Although topoisomerase-I (Topo-I) and topoisomerase-II (Topo-II) are identified as a targeting molecular of AMR, it remains unclear about the relationship between the efficacy of AMR and the expression level of these markers.

Method:
Between April 2004 and May 2014, 56 patients with advanced NSCLC who had received AMR were retrospectively analyzed. Clinical data including histological type, response to treatment, and survival were collected from medical records. The expression level of Topo II within tumor cell were evaluated by immunohistochemical staining.

Result:
The majority of enrolled patients were men (66.1%) and median age was 69 years (range, 43-78 years). The tumor samples consist of adenocarcinoma (69.6%), squamous cell carcinoma (21.4%), poorly differentiated carcinoma (3.6%), pleomorphic carcinoma (1.8%) and unclassified NSCLC (3.6%) Twenty percent of tumors had EGFR mutations. Percentages of tumors overexpressing Topo-I and Topo-II were 57% and 30%, respectively. Median progression-free survival (PFS) and overall survival (OS) for all patients was 2.4 and 10.9 months, respectively. Patients with low Topo-II expression had significantly longer OS than those with high Topo-II expression (12.9 months vs. 7.0 months, p<0.05) whereas there was no significant association between Topo-II expression status and PFS. The number of AMR treatment cycles, poor performance status, advanced stage and elevated Topo-II expression were significantly associated with unfavorable OS (P<0.05). Meanwhile, Topo-I expression status was not significantly associated with PFS or OS in the patients with NSCLC.

Conclusion:
The present study suggests that the expression levels of Topo-II (but not Topo-I) are associated with in patients with NSCLC receiving AMR.

Background:
Increasing emerging studies on circulating tumor cells (CTCs) suggest that CTCs become more and more important in tumor area. However, the difficulty in isolating and enriching CTCs from the billions of blood cells in peripheral blood restricts its development. Recently, we found a new method with high sensitivity and efficiency for CTCs detection. This study aimed to utilize a new method to evaluate the correlation with the CTCs enumeration and chemotherapy efficacy in the human lung cancer patients with stage III or stage IV.

Method:
Blood samples collected from 38 patients with advanced lung cancer before and after treatment were conducted to detect CTCs by new magnetic nanospheres with prominent magnetic/fluorescence properties (Fig.1), which was different from CellSearch. The information of CTCs enumeration was recorded and analyzed with respect to after and before chemotherapy, and clinicopathological features. Figure 1



Result:
High level of CTCs number was found in 15 of 38(39.5%) samples with advanced lung cancer, and it related with stage (p=0.030) and metastasis (p=0.030). Our results suggested that CTCs enumeration could be a marker in reflecting the efficacy of chemotherapy in cases of partial responses (P=0.046) and progressive disease (P <0.001). There was no significant difference in stable disease group (p=0.549).

Conclusion:
This nanosphere-based one-step strategy enables viable CTC detection. These findings showed the change of CTCs enumeration could reflect efficacy of chemotherapy, providing an easier method to evaluate and adjust promptly therapy regimen.

Background:
Bevacizumab combined therapy has been demonstrated superior efficacy and well tolerability in first-line and later-line treatment by various scales of prospective control trials. But it is still lack of direct evidence endorsing bevacizumab as first-line (1L) over later-line (LL) use.

Method:
We retrospectively evaluated the effectiveness of bevacizumab contained therapy as 1L or LL treatment in patients with advanced NSCLC. Primary outcome was progression-free survival (PFS), and the secondary objectives were objective response rate (ORR), disease control rate (DCR) and safety. Subsequently, an exploratory analysis was conducted in subgroups regarding to patients drive genes status including EGFR and ALK.

Result:
From Jul. 2009 to Dec. 2016, a total of 159 patients with NSCLC were enrolled. Baseline characteristics were well balanced between 1L and LL groups. The median follow-up time was 10.7 months. Comparing to LL, the median PFS in 1L was significant longer (9.7 months vs 4.1 months, HR=0.28, 95% CI 0.15-0.52, P＜0.0001). Short term effects of ORR and DCR both had improved trends in 1L than LL. Interestingly in subgroups, WT group (median PFS 11.3 vs 3.4 months, HR 0.2, 95% CI 0.08-0.48, P<0.0001) and WT+UN group (median PFS 11.3 vs 3.4 months, HR 0.25, 95% CI 0.12- 0.51, P<0.0001) had better effectiveness as 1L than LL over the whole population. The ORR and DCR had consistently similar response in subgroups comparison (Table 1). There was no unexpected safety issue documented. Figure 1



Conclusion:
Although it was limited in retrospective design, this precious real world evidence indeed exhibited superior clinical effectiveness in first-line use of bevacizumab indicating a better choice rather than later line use, particularly to EGFR&ALK wild type or unknown patients.

Background:
Bevacizumab has been demonstrated significant survival benefits in addition to chemotherapy in patients with advanced NSCLC from several large scale randomized control trials. We aimed to explore the clinical impact of first-line bevacizumab-contained regimen (B+) versus non-bevacizumab regimen (non-B) for patients with advanced non-squamous non-small cell lung cancer (NS-NSCLC) in the real world setting.

Method:
From July 2009 to December 2016, patients with advanced NS-NSCLC who received first-line therapy with or without bevacizumab were retrospectively collected from Cancer Hospital Chinese Academy of Medical Sciences. Primary outcome was progression-free survival (PFS), and the secondary objectives were objective response rate (ORR), disease control rate (DCR) and safety. Meanwhile exploratory analysis was conducted in each sub-groups regarding to EGFR and ALK status.

Result:
149 patients met selection criteria, 62 in B+ group and 87 in non-B group. Chemotherapy was the based treatment in each group, 57/62 and 71/87 respectively. Median follow-up time was 10.7 months. The baseline characteristics were well balanced. In overall population, median PFS were significantly longer in B+ than in the non-B group: 9.7 vs 7.0 months, HR 0.52, 95% CI 0.30-0.91, P=0.0184. Both ORR and DCR had improved trends in B+ group. In wild type patients, median PFS of B+ group was 11.3 months compared with 5.5 months in the non-B group (HR, 0.43; 95% CI, 0.20-0.91; P=0.0234). In wild-type and unknown population, median PFS was 11.3 months (B+ group) comparing to 6.0 months (non-B group) (HR, 0.53; 95% CI, 0.28-1.02; P=0.0520). The ORR and DCR had consistently similar response in subgroups comparison (Table 1). Safety profile was acceptable in both groups and no new unexpected findings were found. Figure 1



Conclusion:
Our real world analysis further confirmed that bevacizumab-contained therapy as first line treatment was indeed superior in clinical benefits than non-bevacizumab regimen in Chinese patients with advanced NS-NSCLC in a real world.

Background:
Geriatric assessment is strongly recommended to assess the health status of older cancer patients. It can detect multiple health issues, even in patients with good performance status. However, its integration into clinical practice is very slow. In order to engage Medical oncologist on Oncogeriatrics, we developed a prospective protocol to assess GA in clinical practice.

Method:
Elderly patients (> 70 ), stage IV NSCLC wild type, underwent GA. Classified according to GA into fit and medium fi (candidates for antitumoral treatment), and unfit (best supportive care). Data from four teaching hospitals in Comunitat Valenciana (Spain) were entered into a prospective database. The institution’s ethical review board approved the study. Spanish Medicine Agency classified it as a post-authorization study: GIDO-ONC-2015-01. All patients provided written informed consent.

Result:
From 01/2014 to 01/2017, 93 patients with stage IV NSCLC wild type were identified. Median age: 76 (70-92); 30% older than 80 years old. Gender (M/F): 88%/12%. Histology (SCC/AD/NOS): 52%/38%/10%. PS 0-1: 83%. PS was unrelated to GA (p:0.006). 19 PS 0, 10 (52%) were fit, 7 medium-fit (37%) and 2 were frail (11%). PS 1 (57), 47% (27) were fit, 33% (19) medium-fit and 19% (11) frail. Main reasons for medium-fit were comorbidities and dependence in IADL. Frailty patients were those unable for ADL and geriatric syndromes (depression and dementia). GA group was related to overall survival (13 m vs 7,2 m vs 2,2 m,p:0.000) (figure), treatment decision (p:0.0001) and toxicity (p:0.0001). 100% of fit patients were treated with chemotherapy (90%% platinum-combinations), 48% of medium-fit (42% platinum-combinations) and only 8% of frail patients received chemotherapy, none platinum-combinations (p:0.000). Multivariate analysis is pending Figure 1



Conclusion:
Our results suggest that GA identified patients with a poor natural prognosis. Despite generally good performance status, the prevalence of geriatric impairments was high. More research on GA-stratified treatment decisions is needed.

Background:
Selumetinib (SEL), an oral inhibitor of MEK 1 and 2, could be particularly effective in tumours with an activated Ras/Raf/MEK/ERK pathway, but has not been fully studied in KRAS WT nor in the first-line setting. The scheduling of SEL with chemotherapy might impact efficacy and/or toxicity.

Method:
IND219 is an open-label three-arm study of PEM-C±SEL. Arm A: PEM-C+SEL days 2-19; Arm B: PEM-C+SEL days 1-21; Arm C: PEM-C alone. Primary objective was response rate (ORR); secondary objectives were tolerability and progression-free survival (PFS). Pts were stratified by KRAS WT versus unknown and cisplatin versus carboplatin. Before the planned interim analysis (60 pts), pts were allocated 1:1:1 to arm A, B or C, with a plan to continue either Arm A or B plus Arm C a 3:1 ratio to ensure that the final analysis includes Arm A or B and Arm C in a 2:1 ratio. The trial would stop if neither Arm A or B had > 4 responses; if both did, the arm would be selected based on response and toxicity data. Correlative studies included genomic testing.

Result:
Arm A/B/C enrolled 20/21/21 pts. PEM-C exposure was lower with SEL (median cycles 5 versus 6 for Arm C). Seven pts on Arm A (35%; 95% CI 15-59% median duration 3.8m), 13 on Arm B (62%; 95% CI 38-82%; median duration 6.3m), and 5 on Arm C (24%; 95% CI 8-47%; median duration 11.6m) had PR, meeting the criteria to continue. PFS was 7.5m (95% CI 4.0 to 9.0 m) for Arm A, 6.7m (95% CI 4.1 to 8.2 m) on Arm B, and 4.0m on Arm C (95% CI 1.4 to 6.8 m). HR for PFS of Arm A over Arm C was 0.76 (95% CI 0.38 to 1.51, 2-sided p=0.42); HR for PFS of Arm B over Arm C was 0.75 (95% CI 0.37 to 1.54, p=0.43). After adjusting for age, performance status, gender and KRAS, PFS comparisons remained NS. Toxicity was most commonly grade 1-2, but more frequent with SEL especially mucositis, diarrhea, anorexia, dehydration, edema and rash. A high rate of venous thromboembolism (VTE) was seen in all arms, highest in Arm A (Arm A 45 % versus 14 % [p=0.11])

Conclusion:
SEL+PEM-C is associated with higher, but less durable ORR. In this small study, PFS is numerically prolonged adding SEL to PEM-C with expected additive toxicity. Further exploration of these intriguing results is ongoing.

Background:
Leptomeningeal carcinomatosis（LM）is a rare type of metastatic tumors of the central nervous system. In recent years, with the improvement of neoplasms therapies and longer survival of patients by better systemic control , incidence of LM has increased every year.The incidence of LM in patients with non-small cell lung cancer（NSCLC） ranges from 1%-5%.However, no standard therapy has been established yet.This study is to investigate the clinical characteristics and prognostic factors of LM from NSCLC and to develop better treatment strategies.

Method:
We collected and reviewed retrospectively the clinical characteristics,treatment methods as well as the outcomes of 45 consecutive patients with LM from NSCLC diagnosed and treated in our hospital from 2002 to 2017.Survival rates were analyzed using the Kaplan-Meier method.The multi-variate Cox proportional hazards model was used to determine the independent prognostic factors associated with improved survival.

Result:
Figure 1Among 45 patients who were enrolled, 7(15.6%) had EGFR 19 deletion, 2(4.4%) had EGFR 20 mutation, 22(48.9%) had EGFR 21 mutation, 1(2.2%) had EGFR 18 and also EGFR 20 mutation(T790M negative), 2(4.4%) were ALK-positive, 5(11.1%) were EGFR wild-type, 6(13.3%) patients didn't perform EGFR test. The median overall survival from the diagnosis of LM for all the patients was 15（range, 1–34）months. Gender, gene mutation and Tyrosine kinase Inhibitors (TKIs) treatment were correlated with survival time for the patients(P<0.05 for all). Other prognostic variables such as age, initial ECOG, time to leptomeningeal dissemination, CSF cytology, CSF pressure, CSF biochemical, brain radiotherapy, chemotherapy and intrathecal chemotherapy were not statistically correlated to overall survival. In the multivariate analysis, Cox proportional hazard regression showed that TKIs treatment was the independent prognostic factor(P<0.05).



Conclusion:
TKIs treatment was the independent prognostic factor for leptomeningeal metastases from non-smalll cell lung cancer. We suggest that in LM patients from NSCLC giving TKIs treatment may prolong survival.

Background:
Although nab-paclitaxel (PTX) plus carboplatin is one of the standard treatment for chemo-naive advanced non-small cell lung cancer (NSCLC), the efficacy, safety and optimal schedule of nab-PTX monotherapy as 2nd or 3rd line for NSCLC patients without any driver mutations remains unknown.

Method:
This was a single arm phase I/II study. Eligible patients are advanced NSCLC without EGFR mutation and ALK rearrangement that progressed after platinum-doublet chemotherapy. The patients were received 100mg/m[2] of nab-PTX on day 1, 8, 15 and 22 (level 0) or on day 1, 8, and 15 (level -1) every 4-week in the phase I portion. Dose limiting toxicities (DLT) was assessed and the recommended schedule was determined. The primary endpoint was objective response rate (ORR), assuming that estimated ORR was 15% and threshold ORR was 5% with α error of 0.05 and β error of 0.2 in the phase II part. Total of 55 patients were planned to be enrolled.

Result:
The recommended schedule of nab-PTX was determined as the level -1, because the DLTs were found in 4 of 5 patients. The characteristics of the 55 patients enrolled in the phase II were as followings; median age, 66 years (range, 41–90 years), male/female=40/15, PS 0/1/2=12/39/4, 2nd/3rd line=34/21, adeno/squamous/large/others=34/17/2/2. The median number of treatment cycles was three (range, 1–10). The ORR was 7.3% (95% confidence interval [CI], 2.0–17.6%; 4 PR, 26 SD, 24 PD, 1 NE). At the median follow-up time of 5.3 months (range, 1.9–26.0 months) for all patients, the median PFS was 3.4 months (95% CI, 1.9–4.0 months). Treatment related grade 3 or 4 toxicities were neutropenia (36%), febrile neutropenia (5.5%) and pulmonary infection (3.6%). Three patients (5.5%) had grade 2 pneumonitis and one patient was died due to ARDS.

Conclusion:
This study failed to meet predefined primary endpoint although PFS was comparable and toxicity was acceptable for patients with advanced NSCLC without EGFR or ALK mutation as 2nd or 3rd line treatment. (UMIN registration number: 000012404).

Background:
Docetaxel monotherapy is one of the standard treatments for non-small-cell lung cancer in elderly patients. Docetaxel is usually administered as a 3-week schedule, yet there is significant toxicity with this therapy. There is increasing interest in Docetaxel weekly schedule to reduce its toxicity. In this phase II clinical study, we investigate the efficacy and safety of a weekly schedule of docetaxel monotherapy in a first-line chemotherapy for advanced squamous-cell non-small-cell lung cancer in elderly patients.

Method:
Patients with stage IIIb, or stage IV squamous-cell non-small-cell lung cancer aged 65 years or older who had not previously received cytotoxic chemotherapy were enrolled. Patients received docetaxel 25 mg/m2 days 1, 8, and 15, every 4 weeks. The primary endpoint of this study was objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity profile.

Result:
The patient characteristics are showed in table below. Among 12 eligible patients, the ORR was 0%, (5 patients were confirmed with stable disease, 7 patients were progressive disease. Median OS and PFS were each days and days. There were 3 adverse event of grade 3/4 (2 were dizziness and 1 was diarrhea). Neutropenia was reported on only 1 patients and was grade 1.

Patient Characteristics

Age (years)	78.16 ± 4.72
Sex (male / female)	18 / 1
Stage
IIIB (%)	6 (31.58)
IV (%)	13 (68.42)
Performance Status
0-1 (%)	15 (78.95)
2 (%)	4 (21.05)
Smoking
Never (%)	1 (5.26)
Former (%)	13 (68.42)
Current (%)	5 (26.32)
Amounts (pack years)	49.05 ± 28.22
FEV1 (mL)	1.53 ± 0.53

Conclusion:
Our data failed to demonstrate the efficacy of docetaxel weekly regimen. Because our patients were mostly elderly and of poor general conditions, our result might show poor overall response rate. However, the incidence of side effects include neutropenia was lower than docetaxel 3-week regimen as previous reported. Further larger studies are need to confirm the efficacy and safety of docetaxel weekly regimen.

Background:
Patient–reported symptoms have shown prognostic value for patients with advanced non-small-cell lung cancer (NSCLC). The value of persistently high levels of critical symptoms during chemotherapy for predicting survival is seldom addressed. We examined symptom trajectories during first 15 weeks of chemotherapy and their relations to 3-year overall survival (OS) in patients with advanced NSCLC.

Method:
Stage IIIB-IV NSCLC patients scheduled to receive either intravenous chemotherapy or the oral tyrosine kinase inhibitor erlotinib were enrolled in a multicenter longitudinal study. Patients rated 15 symptoms on the MD Anderson Symptom Inventory-Lung (MDASI-LC) before chemotherapy and weekly thereafter for 15 weeks, on 0-10 severity scales. Group-based trajectory analysis was used to categorize patients into groups according to the level and trajectory of symptom severity (either high or low) that patients experienced over time. The 3-year OS was compared between high/low groups via Kaplan-Meier analysis. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) were estimated by Cox regression modeling, with adjustment for demographic and clinical factors.

Result:
We analyzed data from 140 patients (90 died by end of study). High-severity trajectories of three symptoms (fatigue, shortness of breath (SOB), lack of appetite (LOA)) significantly predicted 3-year OS. Patients in the high-fatigue group (n=60) began with moderate fatigue (4.1±3.4) that increased significantly during weeks 1-4 of therapy (5.7±4.5 at week 4; estimated weekly change=0.33, p=0.0004) and remained at this level to week 15. Compared with patients in the low-fatigue group (mean=2.0±1.8, no significant change over time), high-fatigue patients had shorter OS (median=290 vs. 623 days, HR=2.3, 95%CI=1.4-3.8, p=0.001). The high-SOB group (n=62) maintained a moderate level of SOB (4.6±3.5) over 15 weeks and had lower 3-year OS rate than did patients in the low-SOB group (median=256 vs. 566 days; HR=2.7, 95%CI=1.6-4.4, p<0.0001). Compared with patients in the low-LOA group (n=66, mean=0.8±1.8, no change over time), high-LOA patients (n=74, mean=3.2±3.1, no change over time) had shorter OS (median=261 vs. 566 days, p=0.019). The prognostic value of LOA was insignificant after adjusting for other factors.

Conclusion:
Our results suggest that, through longitudinal patient-reported symptom profiling during chemotherapy, persistently high symptom burden can independently predict overall survival in patients with advanced NSCLC. Patients with persistently high symptoms should be targeted for alerts to providers about the need for symptom control during chemotherapy in routine care for advanced NSCLC. Such information could also be used as reference parameters for clinical trial/research design.

Background:
The advanced non-small cell lung cancer (NSCLC) is well known of poor survival. The advanced NSCLC patients with interstitial lung disease (ILD) to be expected poorer survival. The clinical features of patients with advanced NSCLC and interstitial lung disease (ILD) is not fully elucidated, and the role of chemotherapy in advanced NSCLC with ILD remain controversial. The aim of this study was to investigate the prevalence and clinical features of advanced NSCLC patients with ILD, particularly with idiopathic pulmonary fibrosis (IPF).

Method:
We retrospectively analyzed the patients diagnosed with advanced (i.e. stage IIIB and IV) NSCLC at Tosei general hospital, from January 2008 to December 2014. The diagnosis of ILD and IPF were made according to the 2013 and 2011 research statement respectively.

Result:
A total of 899 patients of lung cancer were reviewed, 282 patients were advanced NSCLC. Of these 282 patients, 34 (12%) received the diagnosis of ILD. 22 NSCLC patients (8%) had IPF in 34 ILD. 199/248 of non-ILD NSCLC patients (80%) and 26/34 of ILD NSCLC patients (76%), which includes 17 IPF patients, received chemotherapy. 49/248 (20%) of non-ILD NSCLC and 8 (24%) of ILD NSCLC were treated with best supportive care. There was no significant difference in disease control rate and objective response rate between non-ILD NSCLC and ILD NSCLC patients (72% vs 77%, p=0.696; 33% vs 23%, p=0.271). Overall survival in patients with ILD NSCLC was significantly worse than that in non-ILD NSCLC patients (median survival, 7 months vs 10.1 months; log-rank P=0.013). In patients who received chemotherapy, ILD NSCLC patients had significantly worse survival than non-ILD NSCLC patients (median survival, 7 months vs 10.1 months; log-rank P=0.013). However, there were no significant difference in overall survivals in ILD NSCLC patients between IPF and non-IPF (median survival, IPF-NSCLC vs non-IPF NSCLC: 6.1 months vs 8.2 months; log-rank P=0.375). Among ILD NSCLC patients who received chemotherapy, we found no significant difference in overall survival between IPF NSCLC and non-IPF (median survival, 9.6 months vs 9.7 months; log-rank P=0.275).

Conclusion:
Among advanced NSCLC patients in this cohort, 12% of them had a diagnosis of ILD including 8% with IPF. Survival in advanced NSCLC patients with ILD was worse than that without ILD. We found no significant difference between ILD NSCLC patients with IPF or without IPF in survival.

Background:
Platinum-based chemotherapy remains a first line treatment for advanced non-small-cell lung cancers (NSCLC). Despite better individualization of treatment, some patients will seek frequent medical attention because of cancer-related complications or treatment toxicity. This can negatively impact patient’s quality of life and health care resources. This study aimed to identify biological and clinical factors predictive of frailty and treatment toxicity among NSCLC patients eligible for first-line platinum-based chemotherapy.

Method:
Using our institutional medical charts, we retrospectively extracted data on stage III and IV NSCLC patients diagnosed between December 2011 and November 2015 who had received a first-line platinum based chemotherapy. The primary outcome is defined as any unplanned emergency visit and/or unplanned hospitalization for cancer or treatment related complications. Using multivariate logistic regression model with step by step method, we defined baseline biological and clinical determinants associated with the primary outcome.

Result:

Table 1. First Multivariate Analysis

Variable	OR	95% CI
Age ≥ 62 Years-old	1.61	0.70 - 3.68
Adenocarcinoma - Squamous Cell Carcinoma - NSCLC other	1 2.43 0.50	0.61- 9.61 1.45 – 1.74
Performance scale ≥ 1	1.35	0.57 – 3.18
Number of metastasis ≥ 2	1.36	0.58 – 3.18
Pleural metastasis	2.04	0.53 – 7.86
Weight loss ≥10% or ≥3 kg	1.00	0.41 – 2.43
≥ 3 prescription drugs per day	0.98	0.42 – 2.28
Current smoker - Former Smoker - Never smoker	1 0.56 1.10	0.24 – 1.30 0.24 – 5.11
Neutrophils count ≥ 7500/ mm[3]	1.57	0.70 – 3.54
Lymphocytes count ≤ 1000/ mm[3]	1.04	0.34 – 3.22
Albumin ≤ 35 g/L	2.70	0.93 – 7.69
LDH ≥ 247 U/L	0.93	0.37 – 2.30

We included 227 patients. Mean age was 60 years old, 65% were male, 46% current smokers, 10% PS 2-3 and 74% had adenocarcinoma histology. 20,7% patients had locally advanced disease (Stage III) treated by chemoradiation and 78,4% had metastatic disease treated by exclusive chemotherapy. Median overall survival (OS) was 15 months and PFS 6 months. Overall, 55 % (122/227) met the primary outcome. There were 14 variables (Table 1) included in the first multivariate analysis before computer based step by step approach. In the final model (not shown), albumin level <35 g/L (OR 2.24 95% IC 1.14- 4.38, p= 0.02) was an independent predictor of the primary outcome. There was also a trend for squamous cell carcinoma subtype (OR 2.27 95% IC 0.872- 5.914, p= 0.09).

Conclusion:
Low albumin level is a determinant of frailty in patients eligible for platinum-based chemotherapy. Early intervention in these subgroups could benefit patient’s quality of life and health care expenses. (Medicoeconomic analysis will be presented).

Background:
Erythropoiesis-stimulating agents (ESAs) are widely used for treatment of chemotherapy-induced anaemia (CIA) in patients with various solid tumors, mainly including lung cancer and gynaecological malignancies, but concerns regarding their potential effect on tumor growth and disease progression have been raised. We herein aimed to further investigate the efficacy, toxicity and correlation with overall survival (OS) of treatment with ESAs in a real-world cohort of lung cancer patients.

Method:
The medical records of all patients > 18 years old, with newly-diagnosed advanced-stage lung cancer (non-small cell lung cancer /NSCLC or small cell lung cancer/SCLC) and CIA, treated at the Oncology Unit of Sotiria Athens General Hospital from January 2007 to December 2016 were retrospectively reviewed. The ESAs administered in our cohort were epoetin alfa, epoetin zeta and darbepoetin alfa. Patients were stratified into two subgroups, according to use of ESAs (ESAs-treated vs. those not treated with ESAs). Demographic, laboratory and clinicopathological features, hematological response and toxicity, response to chemotherapy and overall survival (OS) of patients were compared between groups, using univariate and multivariate regression analysis.

Result:
A total of 138 patients (110 males/28 females; mean age ±SD : 66.4± 8.7 years) with baseline (pretreatment) hemoglobin (Hb) values <11 mg/dl and ECOG performance status (PS) 0-2 were included in final analysis. ESAs were administered in 70/138 patients (50.7 %). Age, sex, histological type of tumor (NSCLC vs. SCLC), baseline values of Hb and PS were evenly distributed between groups (p=0.672, p=0.155, p=0.078, p=0.01 and p=0.647, respectively). Hematological response rates and incidence of thromboembolic events were both increased in ESA-treated patients, albeit without reaching statistical significance (p=0.229 and p=0.288, respectively). Neither response to chemotherapy nor OS were found to be significantly correlated with use of ESAs (p=0.498 and p=0.119, respectively).

Conclusion:
According to our study results, administration of ESAs was not significantly correlated with hematological response, response to chemotherapy or OS. Furthermore, treatment of CIA with ESAs was, generally, well-tolerated, with no significantly increased risk of thromboembolic events. A trend for improved partial/complete hematological response and improved OS among ESA-treated patients in our cohort needs to be interpreted with caution. Further randomized trials and larger prospective studies are warranted to investigate the efficacy, toxicity and potential prognostic implications of CID treatment with ESAs in patients with lung cancer.

Background:
Pemetrexed/platinum doublet chemotherapy is under investigation in combination with various immunotherapeutic agents (atezolizumab, nivolumab, pembrolizumab) for treatment of advanced non-squamous (NS) NSCLC, with reported durable efficacy and tolerability in early-phase clinical trials. Recently, the combination of pembrolizumab plus pemetrexed/carboplatin received US FDA accelerated approval as front-line treatment for patients with this disease based on the data from a randomized phase II trial, KEYNOTE-021 Cohort G. We present our descriptive analysis of the safety outcomes of pemetrexed (combination) from 3 randomized trials (PRONOUNCE, PARAMOUNT, and KEYNOTE-021 Cohort G).

Method:
Criteria for selection of studies included randomized trials, first-line treatment for NS NSCLC patients with pemetrexed-based combination treatment, with or without immunotherapy, followed by continuation maintenance (at least one arm or cohort). Parameters such as baseline characteristics, dose exposure, and safety outcomes (AE, SAE, death, dose delay or discontinuation, AE management, and hospitalization) are compared.

Result:
Using data from PRONOUNCE (n=182), PARAMOUNT (n=359), and KEYNOTE-021 (Cohort G, n=123) we describe the safety outcomes of pemetrexed/platinum-based combination therapy. Median age of patients from 3 studies was 61- 66 years. The majority of patients in PRONOUNCE and PARAMOUNT were male, whereas female in KEYNOTE-021G; with ECOG PS 1, and adenocarcinoma. The number of patients who completed 4 cycles of induction were 70.8%, 67.8%, 88.1%, and 71.0% in PRONOUNCE, PARAMOUNT, and KEYNOTE 021G Combo arm and Pem+Cb only arm, with median number of treatment cycles of 6, 8, 11, 8, respectively. All pemetrexed combinations with/without immunotherapy had a reasonable and manageable safety profile in our analysis (Table 1). Figure 1



Conclusion:
This analysis provides a comprehensive safety overview of pemetrexed/platinum with or without immunotherapy in NS NSCLC. Ongoing phase 3 randomized studies of the combination could further inform the safety/efficacy of pemetrexed/platinum plus immunotherapy.

Background:
To explore the efficacy and safety of intrapleural bevacizumab plus cisplatin for malignant pleural effusions (MPEs) of non-squamous non-small-cell lung cancer (NSCLC) patients.

Method:
We retrospectively analyzed 14 patients with MPEs who received intrapleural bevacizumab (200mg) plus cisplatin (60mg) from May, 2015 to March, 2017. Treatment response was assessed according to RECIST 1.1

Result:
The patients included 6 (42.6%) men and 8 (57.1%) women, with a median age of 54 years (ranged, 41-71 years). Five (35.7%) patients had smoking history. Thirteen (92.9%) patients had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2. Driver gene alterations were detected in 4 (28.6%) patients, among them, 3 epidermal growth factor receptor mutations and 1 anaplastic lymphoma kinase arrangement. Four (28.6%) patients received first-line intravenous chemotherapy, and 10 (71.4%) had second or later line chemotherapy. In the management of MPEs, 8 (57.1%) patients achieved partial response (PR), 2 (14.3%) patients showed stable disease (SD) and 4 (28.6%) patients experienced progressive disease (PD). No one was seen complete response (CR). The overall response rate (ORR) and disease control rate (DCR) was 57.1% and 71.4%, respectively. There were 7 (50.0%) cases treated with bevacizumab and cisplatin as initial intrapleural therapy, another 7 (50.0%) patients as subsequent treatment. There were 4 (57.1%) PR for group with bevacizumab plus cisplatin as initial treatment and 4 (57.1%) PR for group with bevacizumab plus cisplatin as subsequent treatment. No significant difference was observed in the two groups (P=1.00). In addition, the adverse events we seen were myelosuppression (7.1%), nausea and emesis (28.5%), mainly in grade 1-2. No thrombosis or bleeding occurred in this study.

Conclusion:
Combined intrapleural therapy with bevacizumab and cisplatin was found to be effective for the non-squamous NSCLC patients with MPEs, and the adverse events were well tolerable.

Background:
Pulmonary large cell neuroendocrine carcinoma (LCNEC) is associated with poor prognosis, and its treatment strategy is still controversial, especially chemotherapy regimens.

Method:
Case Report: A 49-year-old Chinese male with primary pulmonary LCNEC treated by neoadjuvant and adjuvant chemotherapy with cisplation plus pemetrexed was presented in this paper. A suspected quasi-circular mass in the left lower pulmonary lobe and an enlarged mediastinal lymph node were found. The patient was diagnosed with adenocarcinoma with neuroendocrine differentiation based on CT guided percutaneous lung biopsy. EGFR gene mutation test showed negative results. Cisplatin and pemetrexed were administered as the neoadjuvant chemotherapy regimen. The primary lesion had remarkably reduced and the enlarged mediastinal lymph node had disappeared after two cycles of neoadjuvant chemotherapy. He was performed left lower lobectomy and mediastinal lymph node dissection. The lesion was confirmed as LCNEC based on postoperative histopathological analysis and immunohistochemical results.

Result:
The patient underwent four cycles of adjuvant chemotherapy with cisplation and pemetrexed for a month postoperatively, followed by postoperative adjuvant radiotherapy. The patient is still alive after a follow-up of 24 months, with no evidence of tumor recurrence.

Conclusion:
Cisplatin combined with pemetrexed is effective and safe for patients with pulmonary LCNEC.

Background:
The association of PD-L1 expression, KRAS and EGFR mutations, and survival in NSCLC patients who received 1L therapy was examined.

Method:
1L metastatic NSCLC patients diagnosed during 2001-2012 who had sufficient archival tumor tissue were selected from the Danish Lung Cancer Group Registry. Medical data from population-based medical registries and paraffin-embedded tumor tissue from pathology archives were retrieved. PD-L1 expression was assessed at two cut-offs (25% and >1%) using the Ventana IHC (SP263) assay, KRAS and EGFR genotyping was performed using PCR-based kits. Follow-up started at commencement of 1L therapy and continued to death, emigration, or 31/12/2014. Cox regression models were used to compute hazard ratios (HRs) and associated 95% confidence intervals (95%CI) for PD-L1, EGFR, and KRAS.

Result:
Among 491 patients, 280 (57%) were men and 334 (68%) were aged >60 years at diagnosis; 283 (58%) had adenocarcinoma, 152 (31%) had PD-L1 expression ≥25%, 23 (5%) had EGFR mutations, and 130 (26%) had KRAS mutations. In PD-L1 >25% tumors, 4% had EGFR and 30% had KRAS mutations. In PD-L1 <25% tumors, 16% had EGFR and 27% had KRAS mutations. Patients with a KRAS mutation had an increased risk of death and those with an EGFR mutation had a lower risk of death, but neither estimate was statistically significant (Table). Adjusted exploratory analyses indicated that tumor PD-L1 >25% was not associated with survival, however immune cell expression for PD-L1 at the 1% threshold and increasing tumor infiltration with immune cells were both significantly associated with a survival benefit.

	No of deaths during follow-up / N (%)	Median Survival (months) (95%CI)	Adjusted HR* (95%CI)
% Tumor expression[§]
PD-L1 < 25%	208/307 (67.8)	23.6 (18.1, 27.5)	ref.
PD-L1 > 25%	101/152 (66.4)	23.3 (16.9, 29.4)	0.96 (0.76, 1.22)
EGFR[§]
Wildtype	284/419 (67.8)	23.3 (18.4, 26.0)	ref.
Mutant	13/23 (56.5)	32.8 (18.2, 92.5)	0.75 (0.43, 1.32)
KRAS[§]
Wildtype	193/309 (62.5)	24.7 (20.0, 29.1)	ref.
Mutant	95/130 (73.1)	19.4 (15.3, 26.4)	1.28 (0.99, 1.65)
% Immune cell expression[§]
PD-L1 < 25%	264/387 (68.2)	21.8 (18.1, 25.1)	ref.
PD-L1 > 25%	45/72 (62.5)	30.2 (17.3, 44.2)	0.86 (0.61, 1.20)
% Immune cells (1% threshold)[ §]
PD-L1 < 1%	92/122 (75.4)	16.5 (13.3, 20.2)	ref.
PD-L1 > 1%	217/337 (64.4)	26.7 (23.2, 30.2)	0.62 (0.48, 0.80)
% Tumor with Immune Cells (‘infiltration’; continuous)	309/459 (67.3)	23.6 (18.5, 26.4)	0.98 (0.97, 0.99)

*Adjusted for age, sex, and histology (adenocarcinoma versus other). [§] Excluding those with missing PD-L1, KRAS or EGFR status, respectively

Conclusion:
Immune cell expression of PD-L1 and tumor infiltration by immune cells are associated with survival among 1L lung cancer patients. These findings are based on a small cohort and further study is warranted.

Background:
Primary lung cancer is still becomes a major public health problem and become the most common cause of death due to cancer in the developing countries. Lung cancer’s survival rate still low because the early symptoms of lung cancer mostly the same with other chronic lung disease such as tuberculosis and undetected metastases in most cases.Pleural effusion is the most common symptom of lung cancer in Indonesia. The Life expectancy is shorter in advanced lung cancer with the median of 4-6 month survival rate.

Method:
Objective: To determine the factors associated with 1 year survival of lung cancer patients. This study observed independent variables which assumed associated with a 1 year survival, i.e : age, gender, history smoking, performances status, histological types, managements and the presence of pleural effusion. Research design: This was a cohort retrospective study. The subjects were all lung cancer patients who were admitted in ward at Dr Moewardi hospital from January 1[st],2015- December 31,2015. There were 105 participants consists of 85 men and 25 women. Statistical analysis were done using Relative Risk (RR) analysis, Chi-square test, Fisher’s exact test and survival analysis.

Result:
The 1-year survival rate is 38.1%, Age {Chi-square test (p): 0.984: RR: 1.009 (95% CI: 0.435-2.340), Log rank test (p): 0.886, Gender {Chi-square test (P): 0.010: RR: 3.300 (95% CI: 1.303-8.359), Log rank test (p): 0.046, Smoking history {Chi-square test (p): 0.030: RR: 2.650 (95% CI: 1.082- (P): 0.301: RR: 3.368 (95% CI: 0.295-38.407, Log rank test (p): 0.080, Pleural Effusion {Chi-square test (p): 0.005: RR: 3.143 (95% CI: 1.386-7.127, Log rank test (p): 0.010, Performance status: Log rank test (p): 0,001,Histologycal types: Log rank test (p):0.039, Treatment: Log rank test (p): 0,000

Conclusion:
Gender, Pleural effusion, Performance status, Histological types, and Treatment were correlated with a one year survival rate statistically while age and smoking history were not correlated

Background:
There is no standard treatment strategy for patients with advanced non-small cell lung cancer (NSCLC) who experienced progression with three or more lines of chemotherapy. Apatinib, a new tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 (VEGFR-2), has been shown confirming antitumor activity and manageable toxicities in breast and gastric cancers. Clinical trials of apatinib on non-small cell lung cancer show that progression-free survival is improved, but the objective response rate is still low. However, It remains to be explored whether the combined treatment of apatinib plus S1 could be further effective on NSCLC.

Method:
We retrospectively assessed the efficacy and safety of apatinib plus S1 in patients with advanced NSCLC after the failure of second or third-line chemotherapy. The study group comprised 15patients who received oral apatinib, at a dose of 250 mg daily, and S1, at a dose of 40-60mg bid D1-14, repeat every 3 weeks, for progression after the failure of second or third-line chemotherapy for advanced NSCLC. Treatment was continued until disease progression.

Result:
Between Mar 30, 2016 and Jun 1, 2017, 15 patients were enrolled. In 15 patients, there were 12 patients available for efficacy and safety evaluation. 4/12 (33%) patients experienced dose reduction during treatment. Followed up to Jun 20, 2017, the median during time of treatment was 3 months. According to RECIST criteria, the disease control rate was 83%, 10/12 (partial response 50%, 6/12 and stable disease 33%, 4/10). The most frequent treatment-related adverse events were secondary hypertension (41.6%, 5/12), oral mucositis (50%, 6/12), hand-foot syndrome (33%, 4/12) and fatigue (33%, 4/12). Main grade 3 or 4 toxicities were hypertension (16.6%, 2/12), oral mucositis (8.3%, 1/12) and fatigue (8.3%, 1/12). Figure 1



Conclusion:
Apatinib plus S1 exhibits superior activity and acceptable toxicity for the heavily pretreated patients with advanced non-small cell lung cancer.

Background:
Metastatic non-small cell lung cancer (mNSCLC) can present as de novo or relapsed disease. This study aimed to determine the clinical prognostic factors impacting post-metastatic survival, specifically comparing outcomes in de novo versus relapsed early stage populations.

Method:
Retrospective review of mNSCLC patients diagnosed between January 1999 and December 2013 in the Glans-Look Lung Cancer Database was conducted to identify relapsed early stage and de novo cases. Fisher's exact and Wilcoxon rank-sum tests were used to analyze categorical and continuous factors, respectively. Survival outcomes were analyzed and compared via the Kaplan-Meier and log-rank tests. Cox regressions were used to determine the impact of de novo versus relapsed mNSCLC presentation on prognosis, while adjusting for multiple confounders. We excluded stage III patients.

Result:
3039 de novo and 185 relapsed patients were identified. Median post-metastatic survival was significantly longer for relapsed vs de novo, 8.90 (CI: 6.24-12.06) versus 3.71 (CI: 3.48-3.98) months, (p<0.001). Relapsed patients also demonstrated significant survival gains since 1999-2004. Different patterns of smoking history, histology, systemic anti-cancer therapy (SACT) usage and number of extra-pulmonary sites existed between the relapsed and de novo cohorts. Multivariate analysis demonstrated that de novo disease, male gender, ‘Never’ smoking history, ‘NOS’ histology, and the presence of extra-pulmonary metastases were significant factors in predicting a worse prognosis. SACT receipt and ‘Other’ histology were associated with better outcomes. In the relapsed subset, squamous cell histology also boded inferior survival. (Table 1) Figure 1



Conclusion:
Relapsed and de novo patients represent significantly different sub-populations within mNSCLC, with survival favoring relapsed patients. This finding may inform discussions around prognosis, reinforce the value of follow-up/surveillance of early stage patients, and provide support for screening initiatives aimed at reducing the burden of de novo disease.

Background:
AXL is a member of the TAM family of receptor tyrosine kinases that regulate multiple cellular responses including cell survival, proliferation, and migration. AXL expression is associated with a variety of human cancers including NSCLC, and is predictive of poor patient overall survival. AXL is associated with epithelial-to-mesenchymal transition (EMT) and is required to maintain invasiveness and metastasis. Importantly, AXL confers resistance to both chemotherapeutic agents as well as EGFR tyrosine kinase inhibitors. BGB324 is a selective clinical-stage small molecule AXL kinase inhibitor. We found in a colony formation assay with NCI-H1299 cells (AXL[+], EGFR wt) that BGB324 displayed anti-proliferative activity as single agent (IC50 348nM). In a 3D organotypic assay, BGB324 prevented 3D-growth, and formation of aggregates and migration. In a mouse xenograft NCI-H1299 model non-responsive to docetaxel, BGB324 treatment significantly enhanced the antitumor activity of docetaxel. This suggested that BGB324 could overcome acquired resistance in in vivo models of NSCLC and provided a translational rationale for combining AXL targeted therapy with docetaxel in NSCLC to enhance anti-cancer response

Method:
This is a multi-centre, open-label phase Ib study of BGB324 in combination with docetaxel in advanced NSCLC. The study consists of a dose escalation and expansion phase. BGB324 is administered as monotherapy for 1week after which BGB324 and Docetaxel are co-administered as a continuous treatment with 21‑day treatment cycles. It is anticipated that a maximum of two BGB324 dose levels will be evaluated, with up to 12 patients enrolled in the dose-escalation phase. BGB324 is administered orally with a loading dose/maintenance dose regimen with the first three doses (200mg or 400mg) in Cycle 1 serving as the ‘loading’ dose and a maintenance dose of either 100mg or 200mg daily thereafter. Docetaxel 75 mg/m[2 ]is administered as a one-hour IV infusion every 21 days. The BGB324 dose will be escalated in a standard 3+3 fashion until a MTD or RP2D is reached. DLT will be assessed using the NCI CTCAE version 4.03 during the first cycle of treatment (7-day lead-in plus 21 days of combination therapy). Efficacy endpoints include the response rate, progression-free survival and overall survival. Blood and archival tumor tissue samples are taken to assess the pharmacokinetic profile of BGB324 and docetaxel, and for the investigation of pharmacodynamic effects of BGB324, including tissue epithelial markers, mesenchymal markers, and AXL expression; circulating Gas6 (AXL ligand), and systemic immune response. Enrollment began in December 2016

Result:
Section not applicable

Conclusion:
Section not applicable

Background:
Weight loss adversely affects prognosis in metastatic NSCLC. However, the pattern of changes in muscle mass and adipose tissue during first cycle of chemotherapy and their relation to survival is unclear. Therefore, we analyzed changes in muscle cross-sectional area (CSA), inter- and intramuscular adipose tissue (IMAT), subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) on CT-images after three weeks of chemotherapy in patients with metastatic NSCLC and their influence on overall survival (OS).

Method:
In this post-hoc analysis of a subset of the randomized controlled NVALT12 trial (NCT01171170 [1]), body composition was characterized by CSA and distribution of both muscle and adipose tissue at the third lumbar level on CT-images obtained at baseline and three weeks after start of chemotherapy. Changes in body composition parameters were related to OS with Kaplan Meier and log-rank test. Cox multivariate analysis was performed to assess the relative contribution of muscle and adipose tissue CSA and distribution to OS.

Result:
Data were available of 103 patients. Cox regression analysis showed that loss of muscle CSA and IMAT independently affected survival while change in SAT and VAT did not. 74 patients (72%) exhibited muscle loss (group 1) versus 29 patients (28%) who had stable or gain of muscle CSA (group 2). Groups were comparable regarding age, WHO PS, TNM status, and Charlson comorbidity index. Median OS (95% CI) was 10.0 (7.9-12.2) months in group 1 and 15.3 (11.1-19.5) months in group 2 (p=0.004). Among muscle losing patients two sub-groups were distinguished based on IMAT change. Loss of muscle mass combined with loss of IMAT (group 1a, n=33) also showed significant loss of SAT and lower survival rates compared to loss of muscle mass with preserved IMAT (group 1b, n=40). Median OS (95% CI) was 7.3 (5.0-9.5) months in group 1a compared to 12.9 (9.2-16.6) months (p<0.001) in group 1b.

Conclusion:
Early changes in body composition patterns during the first cycle of chemotherapy in metastatic NSCLC are predictive for OS and might be useful for more personalised supportive intervention during follow-up treatment. Reference 1. Dingemans AM, Groen HJ, Herder GJ et al. A randomized phase II study comparing paclitaxel-carboplatin-bevacizumab with or without nitroglycerin patches in patients with stage IV nonsquamous nonsmall-cell lung cancer: NVALT12 (NCT01171170)dagger. Ann Oncol 2015; 26: 2286-2293.

Background:
Lung cancer is the first cause of death by cancer worldwide. Around 70% of patients are diagnosed in advances stages. The EGFR mutations (EGFRmut) are present in 15-20% of cases of lung adenocarcinoma. Most frequent mutations are exon 19 deletions and L858R (90%); in those patients, the TKI treatment have higher response rates (RR) and longer progression free survival (PFS) compared versus chemotherapy. However, the long time OS is low and the complete responses (CR) are achieved in 1-3% only. Nevertheless, contributing factors to long term survival are still unclear. Our objective was to describe long PFS and OS associated factors in patients with TKI treatment.

Method:
We analyzed patients with EGFRmut NSCLC, who received TKI between 2011 and 2017 in the Thoracic Tumors Clinic at Instituto Nacional de Cancerologia, Mexico. EGFR mutational test was performed by RT-PCR (SCORPION/ARMS therascreen). We search factors associated with CR and Major responses (MR; defined as tumor size reduction > 80%) and correlated with PFS and OS.

Result:
One-hundred sixty patients were analyzed. Median age was 62y (SD ±12.8), female 66%, never smoking 82%, adenocarcinoma 98%, exon 19 deletions 60.6% and L858R 34.4%, uncommon mutations 5%. The RR were 56.3%; 12/160 (7.5%) patients had CR (Group1), 16/160 (10%) patients had MR and received local control with Radiotherapy (Group2) and 132/160 (82.5%) had non-CR without radiotherapy (Group3). In the total population PFS and OS was 15months (CI95% 8.2-21.9mo) and 27.9mo (21.8-32.2mo) respectively; in group3 PFS/OS was 8.77 (CI95% 7.66-9.88mo)/24.7mo (CI95% 20.8-28.8mo); in Group1 PFS/OS was 38.7mo (CI 95% 35.7-41.6)/47.8mo (CI95% 40.1-55.5mo) and Group2 PFS/OS 28.1mo (0.43-56.4mo)/OS 36.1mo (CI95% 11.6-60.7mo). We found significant differences in PFS and OS compared group1 vs Group3 (p=0.003 and p=0.0001, respectively) and Group2 vs group3 (p=0.009 and 0.007, respectively). Was not significant differences in PFS/OS between Group1 vs Group2 (p=0.09/0.9, respectively). All patients with CR are alive, except one patient who died due to pneumoniae. In the multivariate analysis were not found association with CR and TKI or mutation subtype (Exon 19 vs L858R).

Conclusion:
Patients treated with TKI who reach CR or MR followed by local control with radiotherapy have longer PFS and OS. These findings support the importance to optimize TKI treatment, in order to achieve CR as well as the importance of local control in residual lesions to improve survival outcomes.

Background:
A leading factor of poor treatment outcomes and cost in cancer care is hospitalization. If hospitalization risk can be accurately predicted, preventive interventions can be effectively used and treatment regimen selection may be able to be refined. Currently, oncologists do not routinely use laboratory, molecular, PRO or imaging data to predict risk of hospitalization or its prevention. Prior research demonstrated that the 3-IGI (quality of life, activities, distress) of the LCSS at baseline, predicts survival more accurately than performance status and requires only two minutes for administration.

Method:
The objective was to determine if the 3-IGI measured at baseline accurately predicts cancer-related or treatment toxicity-related hospitalization risk. PROs were prospectively evaluated in 164 patients receiving chemotherapy for advanced NSCLC using the LCSS 3-IGI, with electronic assistance (“eLCSS-QL”). Patients were followed for hospitalization over three months. Hospitalizations were characterized as cancer-related, or treatment toxicity-related.

Result:
Characteristics: 57% men; 92% Stage IV; 73% first-line therapy; mean age 63; ECOG 1/2: 56%/42%. 77 hospitalizations occurred among 53 (33%) patients. Patients were placed into 3-IGI groups based on scores at baseline by thirds (tertiles; mean 3-IGI = 188 with 0=worst, 300=best; 33[rd] percentile <162, and 67[th] percentile > 239). Baseline 3-IGI significantly predicted risk of cancer-related hospitalizations (p<0.0001), but not treatment toxicity-related hospitalizations (27%, p=0.69). The table outlines marked differences in hospitalizations associated with baseline 3-IGI groups.

PERCENT OF HOSPITALIZATIONS BY 3-IGI GROUP AT BASELINE (p = 0.0001)

TIME FROM BASELINE:	LEAST-RISK GROUP	MEDIUM-RISK GROUP	HIGHEST-RISK GROUP
30-DAYS	0%	18%	23%
60-DAYS	10%	20%	39%
90-DAYS	12%	27% (HR 2.7)	41% (HR 4.6)

Additionally, in only those in the ECOG=1 group, the 3-IGI significantly identified cancer-related hospitalization risk (p=0.025).

Conclusion:
The 3-IGI of the LCSS significantly identifies risk of hospitalization in patients receiving chemotherapy for NSCLC, and is more accurate than ECOG PS. Interventions (including enhanced monitoring) focused on identifiable high risk groups is warranted to reduce hospitalization. These results may also help in appropriate regimen choice to reduce hospitalization. Such interventions could improve cancer care and reduce costs. Support: NIH/NCI R01 CA-157409

Background:
Maintenance treatment of locally advanced or metastatic non small cell lung cancer ( NSCLC ) other than predominantly Squamous cell histology in patients whose disease has not progressed following 4 to 6 cycles of platinum based doublet therapy has been standard of care . Pemetrexed and Erlotinib both have been used as either continuous maintenance or switch maintenance therapy.

Method:
All patients of NSCLC other than the Squamous cell carcinoma , who have completed either 4 or 6 cycles of platinum and pemetrexed and have either CR /PR/SD on response assessment scan post induction treatment and willing to participate in study ,were randomized to receive either pemetrexed or erlotinib . Quality of life (QoL) questioners were collected every 8 weeks till disease progression or unacceptable toxicities. Patients were followed up till death. PFS and OS were calculated for each arm and indirectly compared.

Result:
Two hundred patients were randomized to receive either pemetrexed or erlotinib) from November 2014 to March 2017. Median age of cohort was 55 (28-79).One hundred and thirty two patients were male and 68 were female. PS was 0-1 in 195 patients. Sixty three percent were smokers (126/200). Majority of patients (62.5 %) has stable disease post completion of induction chemotherapy (125 /200).Median number of cycle of maintenance pemetrexed was 4 (4-6). Median PFS in pemetrexed arm was 4.46 month ( 95 % confidence interval (CI); 3.98 to 4.95 ) while in erlotinib arm median PFS was 4.5 month ( 95 % CI ; 3.98 to 4.95),( hazard ratio , 0.98 ; 95% CI , 0.714 to 1.369 , p value 0.945).Median OS from starting induction chemotherapy in pemetrexed arm was 16.56 months ( 95 % CI ; 14.83 to 18.29 ) while in erlotinib arm median OS was 18.33 months ( 95% CI ; 13.74 to 22.92),(hazard ratio , 1.23 ; ( 95 % CI ; 0.829 to 1.831 , p value 0.0302)

Conclusion:
Maintenance treatment with pemetrexed and erlotinib has similar PFS and OS in indirect comparison. QoL analysis in both arms is ongoing.

Background:
Non small cell lung cancer (NSCLC) accounts for 85% of all the lung cancer worldwide. An accurate survival time prediction is important so that subject can plan his activities and also it aids physician in arriving at the best treatment plan. There have been multiple studies that are conducted to build the survival analysis model for lung cancer. The factors that are considered in most of the models includes age, gender, tumor size, weightloss, smoking history and TNM staging to arrive at the survival prediction. However, the current focus is to make the prediction of the survival analysis more personalized and accurate. With the advent of radiomics, which deals with extraction of quantifiable features from the CT images promises to aid in personalized medicine. The objective of this work is to validate the use of radiomic features and arrive at a radiomic signature, which has better prediction power. Also, to analyze the role of radiomic features in improving the accuracy of survival prediction in NSCLC.

Method:
The dataset consist of 237 subjects CT images with NSCLC with the follow up data of 5 years with different histologies (Adenocarcinoma-39;Large cell-102 and Squamous cell carcinoma-96). The data also contained, the clinical information such as age, gender, TNM staging and the survival status. Furthermore, 432 radiomic features were extracted from the gross tumor volume of the CT images for all the corresponding subjects. Assessment was performed using cox regression model between different groups of features (clinical information, radiomic features and combination of clinical information and radiomics features) to arrive at the survival prediction model. Also, unique radiomic signature was identified with 16 features that has maximum influence on the survival model.

Result:
The results showed that the concordance Harrell’s concordance index (c-index) for only clinical information was observed to be 0.56, with only radiomics features being 0.64 and with combination of radiomics features along with clinical information was observed to be 0.69.

Conclusion:
In this study we observed that the radiomic features along with clinical information aids in providing better survival prediction model for NSCLC. Also, a unique radiomic signature was obtained which is used as an input to the survival prediction model for improving the accuracy. The study also highlights the role of imaging features driving towards personalized treatment in NSCLC.

Background:
Most non-small cell lung cancer patients (NSCLC) patients are older than 70 years and therefore their management is challenging as it may be complicated by an increased number of comorbidities and greater risk of treatment-related complications. For these reasons, elderly patients tend to be undertreated. Our objective was to evaluate the efficacy of treatment in this population in comparison with younger patients.

Method:
Retrospective study of patients with unresectable stage IIIB and stage IV NSCLC diagnosed between 2011 and 2014 at Oncosalud AUNA, a private specialized cancer center, which were treated with chemotherapy. Data was collected from clinical files. Type of treatment among young and elders (>70) was compared, as well as benefit from treatment, in terms of objective response rate (ORR), progression free survival (PFS) and 1-year overall survival (OS).

Result:
83 patients were included (70.8% young, 29.2% elder). There were no significant differences in gender, among the 2 groups (male 56.1 vs 57.7% p= 1.00), histology (86% vs 82%, p=0.972), ECOG 2-3 (19% vs 30.8% p=0.383), metastatic disease (70.2% vs 69.2% p=0.16), brain metastases (15.8 vs 3.8%, p=0.16), for younger and elder, respectively. The both groups received same combinations treatment, the monotherapy in both groups was 7% vs 11.5% (p= 0.672). Carboplatin and pemetrexed was the most frequent chemotherapy regimen (56% vs 57% p=1.00) respectively. The cisplatin based regimens was (15.8% vs 7.7% p=0.489). The benefits of treatment were similar, regardless of age, ORR was 52.6% vs 46%(p 0.65). At 21 months of follow up, PFS was 5.5 vs 4.9 months (p=0.52), respectively. The 1-year OS was 19.2% and 5% respectively (p=0.199).

Conclusion:
In our clinical practice, the elderly tend to be treated the same. Treatment efficacy is similar among both groups. If medically fit, patients should be treated the same, regardless of age.

Background:
Central nervous system (CNS) metastases are commonly seen in lung cancer patients; up to 40% will have CNS involvement during the course of the disease. However, clinical trials often exclude this patient population due to the increased morbidity/mortality associated with CNS metastases, subsequent reduction of overall survival and poor CNS pharmacokinetics or uncertainty about CNS pharmacokinetics in humans. Therefore, we studied the effects of CNS metastases on the enrollment of lung cancer patients in early phase clinical trials.

Method:
Trials were extracted from ClinicalTrials.gov on April 1[st], 2017. Completed and active trials from 2000-2016 were included in the analysis. Exclusion of CNS metastasis was treated as a binary variable and grouped as strict exclusion vs. allowed. Logistic regressions were used for statistical analysis.

Result:
598 trials were reviewed, 308 (52%) were phase 2, 164 (27%) were phase 1, and 126 (21%) were combined phase 1/2 trials. 304 (51%) trials were conducted in the U.S., 82 (14%) in Asia, 74 (12%) in Europe and 138 (23%) internationally. Most trials were funded by industry (59%), followed by investigator initiated/institutional (23%) and NIH funded (18%). Patients with CNS metastasis were strictly excluded in 130 (22%) trials, allowed if controlled/asymptomatic in 156 (26%) and allowed with no prior treatment in 42 (7%) trials. Patient requiring steroids for their CNS metastasis were excluded in 156 (26%) trials. CNS criteria were not referenced in 114 (19%) trials and these were excluded from further analysis. Of the 194 trials that included survival as one of their end points, 121 (62%) excluded patients with CNS disease. On univariate analysis, the odds of CNS metastasis exclusion were significantly higher in immunotherapy trials (OR: 1.26, 95%CI: 1.07-1.50, p<0.006) and significantly lower in NIH funded trials (OR: 0.35 95% CI: 0.17-0.73, p<0.005). In multivariate analysis, U.S. based trials had higher odds of exclusion of CNS disease (OR: 1.18, 95%CI: 1.06-1.31, p<0.001) compared to European, Asian and International trials. 58 phase 1 trials were followed by phase 2 trials, when comparing exclusion criteria, no changes were made regarding CNS metastasis.

Conclusion:
Many patients with lung cancer and brain metastases are excluded from participation in early phase clinical trials. Broader inclusion of patients with CNS metastasis, or separate clinical trials for those with CNS disease would help determine the efficacy of novel agents for those with CNS metastasis and provide clinical trial options for this patient population.

Background:
The metabolome represents the endpoint of many cellular events; hence patients' baseline metabolomic profile may reveal specific prognostic markers of overall survival. In this study, we sought to characterize the serum metabolite signatures in patients with metastatic non-small cell lung cancer (mNSCLC) who underwent first-line therapy, using nuclear magnetic resonance (1H-NMR) spectroscopy and liquid chromatography mass spectrometry (LC-MS), and to explore their potential prognostic impact.

Method:
Serum samples were collected prospectively as part of a clinical trial in which patients were treated with systemic therapy including platinum-doublet chemotherapy. For each method of analysis, samples were divided into training (3/5) and validation (2/5) sets stratified by treatment received, stage (III vs. IV), and ECOG PS (0, 1, vs. ≥ 2). Exploratory analyses were performed to characterize the relationships between baseline lipid and polar levels and overall survival. Kaplan-Meier curves were used to estimate the distributions of time to event outcomes, and a Cox regression model was used to correlate marker levels while adjusting for baseline characteristics.

Result:
Using 1H-NMR, 16 out of 43 metabolites were significantly correlated with overall survival (OS) by univariate analysis (p < 0.025) and 4 metabolites were included in the final multivariate model. The median OS was 11.4 months in the low risk group vs. 6.6 months in the high risk group (HR=1.99, 95% C.I. 1.45 – 2.68; p<0.0001). Using LC-MS, 53 lipid species were correlated with OS by univariate analysis. Variables were then subjected to hierarchical cluster analysis resulting in 12 branches which were moderately to significantly correlated with lipid features. Principle component analysis (PCA) was performed and the first PC from each such branch was used (n=9). Using Cox regression modeling, median OS was 5.7 months vs. 11. 9 months for the low and high risk groups respectively, even after adjusting for baseline characteristics (HR: 2.23, 95% C.I. 1.55 – 3.20; p< 0.0001).

Conclusion:
Metabolite profiles from baseline pre-treatment serum samples have the potential to act as prognostic markers in patients with mNSCLC undergoing first-line chemotherapy. Serial metabolite measurements pre- and post-treatment may yield additional information and provide enhanced data for predicting clinical outcomes.

Background:
There is an unmet need to evaluate tumor response by other means than radiology tests. Cell-free circulating tumor RNA (cfRNA) can be extracted from plasma of cancer patients (pts); measuring dynamic changes in gene expression and levels of b-actin; cfRNA (per ml of plasma) as a proxy for total cfRNA in metastatic patients has shown great potential for evaluating disease status and predicting outcome to anti-tumoral therapy in advance of imaging. We have previously shown that high levels of PD-L1 cfRNA expression correlates well with positive response to immunotherapies including nivolumab in pts with NSCLC.

Method:
Blood was drawn from pts at approximately 6-week intervals under various therapies, with CT scans at 3-month intervals. Total cfRNA was extracted from patient plasma and reverse transcribed to cDNA. Levels of b-actin, ERCC1 and PD-L1 were quantitated across multiple blood draws by RT-qPCR and correlated with pt response (PR/SD/PD), as determined by CT scans.

Result:
A total of 24 NSCLC patients were enrolled in a 1-year clinical study. Non-SCC comprised 87% (21/24). 19 pts completed the first two cycles of therapy. 1 pt with PR had decreasing levels of cfRNA, 10 pts achieved SD with decreasing or no change while 6/8 pts with PD had increasing levels of cfRNA. CfRNA levels were predictive of disease status about 4 weeks in advance of imaging in 6/19 pts and matched with disease status in 8/19 pts (74% ). Dynamic changes in PD-L1 expression correlated with response to nivolumab in 3/4 pts. In 2/4 pts with SD, PD-L1 remained undetected after therapy, whereas 1 patient continued to have PD despite loss of PD-L1. PD-L1 was undetectable in a pt initially with PD on nivolumab who achieved SD after one cycle of nivolumab plus radiation. Changing ERCC1 expression correlated with platinum-based therapy outcome in 8/8 patients. 4/4 patients with PD on pemetrexed/carboplatin had an increase in ERCC1. 4/4 patients with lower or decreasing levels of ERCC1 achieved PR or SD. In the only patient achieving PR, ERCC1 became undetectable during treatment.

Conclusion:
We found significant concordance between clinical response and changes in plasma cfRNA levels in NSCLC pts (74%). Levels of PD-L1 expression correlated with response in 3/4 pts treated with nivolumab . ERCC1 levels were predictive of outcome to platinum based therapy for 8/8 patients. ERCC1 and PD-L1 expression in cfRNA can be used to monitor response to platinum-based and immuno-therapy.

Background:
Brain metastases (BM) are a common cause of morbidity and mortality in patients with non-small-cell lung cancer (NSCLC). For patients with wild-type EGFR genes, therapeutic options for BM are even limited. Besides local therapy, pemetrexed is the preferred chemotherapy in NSCLC, but the efficacy of this treatment is uncertain. This study evaluated the efficacy of wild-type and unknown status EGFR patients with BM receiving pemetrexed based chemotherapy and analyze the prognostic factors.

Method:
We retrospectively studied 138 EGFR wild-type and unknown EGFR status patients with BM, who had received first line pemetrexed based chemotherapy between 2010 and 2015 at Zhejiang Cancer Hospital. Unknown EGFR status patients were treated with EGFR TKIs after progression. Patient follow-up by telephone was done until January 2016. Treatment response was evaluated and survival data were collected and analyzed.

Result:
Among the 138 patients, 49(35.5%) were EGFR wild type and 89(64.5%) were unknown EGFR status. And 80(58.0%) received whole-brain radiotherapy (WBRT), 19(13.8%) received stereotactic radiosurgery (SRS)/surgery, 10(7.2%) were treated with WBRT plus SRS/surgery, 29(21.0%) didn’t receive any local therapy. The median overall survival (OS) from diagnosis of BM was 21.0 months for the whole cohort (95% CI, 17.2-24.8 months), the intracranial progression-free survival (iPFS) was 9.5 months (95% CI, 6.6-12.4 months) and extracranial PFS was 8.3 months (95% CI, 6.9-9.7 months). Patients with unknown EGFR status had a longer iPFS and OS than EGFR wild-type (11.7 vs. 7.6 months, P=0.23; 24.0 vs. 17.7 months, P=0.24). The combination of pemetrexed and platinum showed better iPFS than single agent of pemetrexed in patients, although it did not reach statistical significance (10.7 vs. 7.2 months, P=0.27). Patients with more than 6 cycles of chemotherapy tend to have longer iPFS and OS than those who received less than 6 cycles or 4 cycles (12.6 vs. 10.3 vs. 8.3 months, P=0.52; 47.9 vs. 27.9 vs. 19.2 months, P=0.18).

Conclusion:
Pemetrexed shows good tolerability and efficiency in EGFR wild-type and unknown EGFR status patients with brain metastases from advanced NSCLC, and have a good control of activity on brain localizations.

Background:
Docetaxel is the commonly used chemotherapy drugs of various types of tumors. However, the major adverse effect of which is the dose-limiting hematologic toxicity. In clinical practice, 3/4 grade neutropenia and febrile (FN) is the severe side effects threatening the patient life. This research aims to analyze the variability of docetaxel’s medicine area under the curve (AUC) between individuals and its relationship with hematological toxicity in advanced NSCLC, which sets up the mathematical model to predict its hematological toxicity by docetaxel AUC to lay the theoretical foundation for individual adjustment in future.

Method:
Select 32 patients with advanced NSCLC in Shandong Cancer Hospital that receiving docetaxel chemotherapy treatment from 2014-10 to 2015-12. Adopt Mycare® reagent kit to determine the blood concentration, and calculate the docetaxel AUC over model software of non-mixed effects. After standardized treatment, analyze the AUC variability between individuals, relationship of AUC with decreased amount of neutrophils before or after the chemotherapy, and the relationship of AUC with 3/4 grade neutropenia. And make the fitting with different methods to set up the mathematical model in relationship with decreased percentage of neutrophils after AUC prediction chemotherapy and incidence rate of 3/4 grade neutropenia

Result:
1. The AUC of 32 patients in the first cycle after standardized treatment that use docetaxel is between 1.8ug.h/ml-4.7ug.h/ml in average of 3.32±0.12ug.h/ml. The difference between the maximum value and minimum one is 2.6 times. 2. AUC value has the tendency that increases as cycle number increases. However, the number of chemotherapy cycle has no statistical significance of AUC influence（F=0.186, P=0.824）. 3. The model predicting the decreased percentage of neutrophils with docetaxel AUC is : y1 = 1.4812x[2] + 3.0217x + 29.061 (cycle 1), y2 = 4.3981x[2] + 14.006x + 50.532 (cycle 2), y3 = 2.0683x[2] + 2.1257x + 19.604(cycle 3), y4 = 4.683x[2] - 19.273 + 61.398 (cycle 4); The model predicting the incidence rate of 3/4 grade neutrophils is y=19.383ln(x)+2.4005. (x=AUC).

Conclusion:
This research sets up the mathematical model to predict the decreased percentage of neutrophils and incidence rate of 3/4 grade neutropenia by docetaxel AUC, which provides basis for screening high-risk patients who may suffer seriously hematological toxicity and lay the theoretical foundation for individualized adjustment based on doxetaxel AUC. In addition, as the first cycle of doxetaxel AUC has important reference value, it suggests that all patients receiving docetaxel chemotherapy at the first time must receive AUC test.

Abstract not provided

Background:
Breast metastasis from the lung malignancy is very rare. An incidence of 0.1% to 1.6 % . The most commonly of primary malignant disease that metastasize to the breast are lymphoid tissue malignancy ,malignant hemopoetic disease, and malignant melanoma.

Method:
In our experience we have had only one case with breast cancer metastazis from primary lung cancer. A 56-year-old female ex smoker ,manifested a right breast mass and limphonods in the right axillar region.She was treated for primary lung cancer stage IIB befor 4 months.Although she was treated for right spontaneous pneumothorax six years ago through right posterolateral thoracotomy ,wedge bulectomy superior dexter ,fruotazh and pleural drainage.After 3 years she was treated and for metastasectomy left lung and lateral chest wall resection coste 6/7.

Result:
The patient underwent right local mastectomy and right axillary dissection . After histological and immunohistochemical analyses showed that breast mass was metastasis from a primary lung carcinoma

Conclusion:
A accuracy treatment and prognosis of the breast metastasis from primary lung cancer is differentiation from the primary brest cancer and is very important to do this diferentation.

Background:
Gamma knife (GK) radiosurgery is a common treatment for brain metastases from non-small cell lung cancer (NSCLC). This study reports outcome results for patients with synchronous brain metastases and delayed brain metastases from NSCLC at Leeds Cancer Centre (LCC).

Method:
Data was obtained by retrospective case note review for 72 patients, who were all treated with GK from 2009 until 2014. Radical thoracic therapy (surgery, chemoradiotherapy or stereotactic ablative radiotherapy) was also undertaken for 58 patients. Statistical analysis using Kaplan-Meier curves was performed to estimate time to intracranial progression, survival from diagnosis of brain metastases, and overall survival.

Result:
Demographic data identified a median age of 65 years (range 43 – 83 years). For patients with delayed brain metastases (47 patients), TNM stage at diagnosis was stage I (7 patients), stage II (11 patients), stage IIIA (12 patients) or stage IIIB/IV (17 patients). Histology was majority adenocarcinoma (50%) or squamous cell carcinoma (22%). The median time to intracranial progression for all patients treated with GK was 9 months. In patients treated with radical thoracic therapy, of which 88% completed treatment, the median survival from diagnosis of brain metastases was 15 months for those with synchronous brain metastases (18 patients), and 14 months for those with delayed brain metastases (40 patients). In those with synchronous brain metastases, 83% received GK prior to radical thoracic therapy (median survival 18 months vs. 14 months for delayed GK). In those with intracranial progression following GK prior to death, 25% were treated with salvage GK with a median survival of 23 months. This compares to 18 months for those treated with salvage whole brain radiotherapy and 8 months for those not suitable for salvage treatment. The overall median survival for patients treated with combination radical thoracic therapy and GK at LCC was 21 months (median survival in synchronous brain metastases at diagnosis = 16 months vs. median survival in delayed brain metastases = 27 months).

Conclusion:
In conclusion, GK radiosurgery is an effective treatment for brain metastases in NSCLC. Beneficial effects are seen in patients with synchronous and delayed brain metastases, demonstrating its role in a wide subset of patients with advanced NSCLC. Use of GK, in combination with radical thoracic therapy, therefore has the potential to dramatically improve survival in patients who may not have previously been suitable for radical treatment.

Background:
NSCLC metastasize to lung parenchyma and airway, and occasionally they show characteristic CT findings according to the histological types and mutations. We will illustrate computed tomographic (CT) features of variable metastasis of lung parenchyma and air way of thorax depending on histologic types and mutations of NSCLC by the pattern approach. We are going to discuss about the early detection and the clues to radiologic diagnosis.

Method:
We used conventional chest CT protocol with ehnacement. Contents: 1) Hematogeneous metastasis -Scattered nodular metastasis (eg. the most common type) -Military metastasis (eg. EGFR mutant ADC) -Cavitary nodular metastasis (eg. ADC or squamous cell caricinoma) 2) Lymphangitic metastasis (eg. ALK mutant ADC) 3) Aerogenous metastasis (eg. mucinous ADC with airspace consolidation type) 4) Endobronchial metastasis (eg. squamous cell carcinoma) 5) Pulmonary thrombotic microangiopathy (eg. ADC)

Result:
Figure 1 miliary metastasis Figure 2 Aerogenous metastasis





Conclusion:
Knowing the CT findings according to the types of NSCLC and mutation will be helpful in differential diagnosis of metastasis in ’era of multicentric lung cancers or various secondary lung metastases in other primary sites’.

Background:
Lung cancer is the leading cause of cancer-related deaths worldwide with tobacco use and increasing age as the strongest risk factors. We report 2 uncommon cases of primary pulmonary adenocarcinoma with multiple metastases in young non-smoker, immunocompetent males diagnosed post-mortem.

Method:
Tissue sections taken during autopsy were fixed in 10% neutral buffered formalin and embedded in paraffin. Some 5-micrometer sections were stained with hematoxylin-eosin, mucicarmine and immunohistochemical stains for morphologic and immunohistochemical evaluation.

Result:
Case 1: The patient was a 23 year-old, non-smoker male, non-reactive with HIV test, who presented with several months of shortness of breath, exertional dyspnea and easy fatigability. Imaging studies revealed massive pleural and pericardial effusion and was admitted as a case of tuberculosis. Pericardial biopsy and cytology of pericardial and pleural fluid showed atypical cells. The patient’s condition progressed rapidly and he eventually died. On autopsy, the thoracic cavity was filled with a mass occupying the right hemithorax. The mass was a moderately differentiated adenocarcinoma that extensively infiltrated the left lung and other contiguous structures like the pericardium, ventricular wall, aorta and pulmonary trunk and peritoneal surface of the liver. IHC revealed the tumor cells as positive for CEA and CK7, but negative for CK20 and TTF-1. Mucicarmine stain was positive. Case 2: The patient was a 33-year old, non-smoker male, non-reactive with HIV test, who presented with progressive difficulty of breathing for 2 years and managed as a case of tuberculosis and pneumonia in a hospital and subsequently referred and admitted at our institution. Chest x-ray showed diffuse extensive hazy reticular densities and confluent densities in the left lung and managed as tuberculosis. His condition deteriorated rapidly and he eventually expired. Post-mortem examination revealed a mass located in the carina with several metastatic deposits in the mediastinum, peritoneum and retroperitoneum. The mass was a moderately differentiated adenocarcinoma of bilateral lung with extension to contiguous structures like the great vessels, pericardium, esophagus, distal trachea and with distant metastasis to adrenals. IHC revealed the tumor cells as positive for CEA, CK7 and TTF-1, but negative for CK20. Mucicarmine was focally positive.

Conclusion:
These cases are uncommon presentation of disseminated lung cancer. Clinicians should be wary in the clinical diagnosis of young, immunocompetent, non-smoker patients who present with difficulty of breathing and effusion. In such cases, a diagnosis of tuberculosis in a country with a high TB burden, might mask a greater evil in the form of an underlying lung malignancy.

Background:
Patients with oligometastatic non-small cell lung cancer (NSCLC) represent an indolent phenotype who may benefit from aggressive therapy and experience long-term overall survival (OS). Previous several small retrospective studies have showed that aggressive therapies for both the primary tumor and the metastases might be beneficial for patients with oligometastatic NSCLC compared with patients that did not receive aggressive treatment. The aim of this study was to determine the efficacy of aggressive treatment for patients with oligometastatic NSCLC.

Method:
We retrospectively analyzed 40 patients with oligometastatic NSCLC who were treated with aggressive treatments. Response rates, progression-free survival (PFS) and OS were evaluated.

Result:
Median age was 58 years, the majority of patients were male (67.5%), and have adenocarcioma histology (77.5%) and ECOG PS 0-1 (92.5%). Oligometastase locations were brain (55%), adrenal gland (22.5%), bone (15%), lung (5%), and other (2.5%). Oligometastatic disease was mostly limited: 80% of patients had metastases confined to one involved organ, and the majority of patients (57.5 %) presented with a solitary metastasis. Primary tumor treatments were concomitant chemoradiotherapy (60%), surgery (17.5%), chemotherapy (17.5%) and sequential radiotherapy (5%). On the other hand, metastase treatments were consisted of radiosurgery (77.5%), metastasectomy (17.5%) and radiosurgery and metastasectomy (5%). After agressive treatment objective response rate was 82.5%. At the median follow-up of 16.5 months, the median PFS and OS intervals were 15.5 (95% CI 9.3-21.7) and 21.9 (95% CI 13.5-30.2) months, respectively.

Conclusion:
Radically aggressive treatment for both the primary tumor and the metastases is reasonable and effective therapeutic option to provide long-term survival rates in selected patients with oligometastatic NSCLC. Further studies are needed, preferably prospective and randomized that analyze the efficacy and safety of aggressive ablative treatment for these patients.

Background:
Non-small cell lung cancer (NSCLC) is a common type of cancer with typically poor prognosis. As individual cancers exhibit unique mutation patterns, identifying and characterizing gene mutations in NSCLC might help predict patient outcomes and guide treatment. The aim of this study was to characterize the mutational landscape of NSCLC and identify biomarkers to predict patient outcome.

Method:
Archived DNA was extracted from formalin-fixed, paraffin-embedded, mostly small biopsy samples of 162 patients. Targeted sequencing of genomic alterations was conducted using Ion AmpliSeq Cancer Hotspot Panel v2.

Result:
The median age of patients was 64 years (range; 32-83 years) and the majority had stage IV NSCLC at the time of cancer diagnosis (90%). Among the 162 patients, 161 patients (99.4%) had novel or hotspot mutations (range: 1-16 mutated genes). Hotspot mutations were found in 20 genes. Three of the most frequently found hotspot mutations were in TP53 (82, 51.2%), EGFR (66, 40.8%), and STK11 (19, 11.7%). Given that 72.7% (48/66) of EGFR mutant patients were treated with EGFR TKIs, there was a significant difference in overall survival between EGFR mutant and EGFR wild-type patients. In EGFR wild-type subgroup analysis, TP53 status was associated with poor overall survival, while STK11 status was associated both poor progression-free survival and overall survival.

Conclusion:
These results suggest that targeted next-generation sequencing using small biopsy samples is feasible and allows for the detection of both common and rare mutations that have independent prognostic value.

Background:
Invasive mucinous adenocarcinoma of the lung which is well known as poor prognosis is often difficult to distinguish from pneumonia on the chest Computed Tomography (CT). However, the characteristics of lung adenocarcinoma resemble to pneumonia on the chest CT are not known well.

Method:
We retrospectively reviewed 607 patients with lung cancer pathologically diagnosed with adenocarcinoma in Saiseikai Suita Hospital from April 2007 to March 2017.

Result:
Of the 607 patients, 9 cases showed infiltration like pneumonia without any masses or nodules on the chest CT. The patients included 3 males and 6 females, mean age of 69.89 years (range 32-82 years). Many cases relatively needed time from the point of first contact to the medical institution to diagnosis: the average was 142.9 days (range 8-385 days). Furthermore, some of the cases were treated as pneumonia at first. Most of the cases diagnosed with invasive mucinous adenocarcinoma pathologically, but there were 2 cases presenting no or few mucin. These 2 cases also have EGFR major mutation. One patient died within 2 months after diagnosis, but more than half of the cases were confirmed the existence over one year.

Conclusion:
It is important to take lung adenocarcinoma into consideration when we see infiltration on the chest CT scan. We suppose early diagnosis and treatment could lead to relatively good survival.

Background:
Liquid biopsy provides a valuable source to guide the targeted therapy for lung cancer. However, the comparison between the liquid biopsy or tumor sampling guided therapy was lacking. Here we performed a case-control study to compare the clinical outcome of these two strategies.

Method:
In this retrospective study, the admitted patients from Jan 2015 to Feb 2016 were screened through a pre-established database. Patients with metastatic, pathologically-confirmed, and treatment naïve non-small cell lung cancer who were prescribed with epithelial growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) from the guidance of liquid biopsy were enrolled (Liquid group). The mutation status in tumors was not mandatory. During the same period, patients medicated with TKI based on tumor samples were included in the Control group. They were enrolled in an age-, gender-, performance-matched manner.

Result:
We screened 536 patients and enrolled 26 patients in the Liquid group. Another 52 patients were enrolled in a 1:2 ratio in the Control group. In the Liquid group, a high consistence (84.6%) in EGFR mutation status between liquid and tumor was observed. The best response was partial response in 19 patients (73.1 %), and followed by stable disease in 6 patients (23.1 %). The median progression-free survival was 10.0 months (95%CI: 4.2-15.8 months). In the Control group, a similar disease control rate (81.2%, P=0.679) and comparable PFS (7.8 months, 95% CI: 7.1-10.4 months, P=0.798), HR=0.713, 95% CI: 0.321-1.195) was found. In the Liquid group, 3 of 4 patients with discordant results between tumor and liquid biopsy showed treatment responses favoring the liquid biopsy.

Conclusion:
This study provided direct evidence supporting the liquid biopsy for guiding the targeted therapy for lung cancer.

Background:
Massive pleural effusion may cause the oncological emergencies in the patients with advanced lung cancer. We describe here the treatment experience of patients with the massive pleural effusion at the first visit.

Method:
Three patients had massive pleural effusion at the first visit from April 2016 to March 2017. We report these 3 patients treated with carboplatin, pemetrexed, and/or bevacizumab.

Result:
All of 3 patients urgently received the continuous chest tube drainage for several days (Table 1). Pleural effusion was examined for cytology. Patient A received pleurodesis therapy because of negative fluid cytology, while she was examined by CT guided needle biopsy. Patient B and C revealed malignant adenocarcinoma cytology in pleural effusion. Both of two received additional biopsy for EGFR-mutation and ALK-translocation. Patient A waited the result of the pathology of adenocarcinoma, EGFR-mutation of negative, and ALK-translocation of negative for 24 days. She received the chemotherapy of carboplatin and pemetrexed with pregressive disease and died of locally advanced lung cancer after 1 course of chemotherapy followed 20 days best supportive care. Patient B and C quickly began the first line chemotherapy of carboplatin, pemetrexed, and bevacizumab without waiting the result of EGFR-mutation and ALK-translocation. Patient B received the six-course of chemotherapy with partial remission, followed the one course of the maintenance chemotherapy of pemetrexed and bevacizumab, however, he died of brain metastasis 183 days after the first chemotherapy. Patient C received the six courses of chemotherapy, followed pemetrexed and bevacizumab maintenance therapy, and is living with partial remission more than 130 days.

Table 1

	Age	Sex	Pleural effusion cytology	Additional pathology	EGFR-mutation	Period to the first chemotherapy	1st line chemotherapy	Prognosis
Patient A	77	F	Class I	Dissemination, adenocarcinoma	wild	25 days	Carboplation, Pemetrexed	Dead, 58 days, Locally advancement
Patient B	60	M	Class IV	Lung, adenocarcinoma	wild	8 days	Carboplatin, Pemetrexed, Bevaxizumab	Dead, 183 days Brain metastasis
Patient C	69	F	Class IV	Dissemination, Adenocarcinoma	L858R	4 days	Carboplatin, Pemetrexed, Bevaxizumab	Alive, 130 days, PR

Conclusion:
Carboplatin, pemetrexed and bevcizumab treatment was well-tolerable in the patients with the oncological emergencies of massive pleural effusion. We should start the first line treatment as soon as possible. Two weeks of waiting period are so long for the patients with advanced lung cancer.

Background:
To aim of this study was to determine the clinical and biological prognostic factors for occult malignant pleural disease (MPD) first detected at thoracotomy in patients with non-small cell lung cancer (NSCLC) and evaluate the results of surgical intervention.

Method:
A total of 123 patients diagnosed with MPD at consecutive 2894 thoracotomy from January 2006 to October 2016. Clinical and pathological characteristics were evaluated in 120 patients. Survival curves were estimated by the Kaplan–Meier method, and Cox regression analysis was performed to validate the selected risk factors.

Result:
With a median follow-up of 34 months, the 5-year overall survival of 120 patients was 28%. Multivariate analyses using the Cox proportional hazards model showed gender (p=0.066), T stages (p<0.001), N stages (p=0.032), pleural invasion in image (p=0.004), pleural effusion (p=0.027), surgery intervention (p=0.024) and EGFR status (p=0.001) were independent predictors of survival. The 5-year survival rate and median survival time (MST) for 21 patients with lobectomy were 71.6% and 62.6 months, compared with 25.6% and 40.0 months in 46 patients with sublobectomy. When 53 patients subjected to open-close surgery, their 5-year survival rate and MST were 23.4% and 30.2 months. There was significant prognostic difference between lobectomy and sublobectomy /open-close surgery (p=0.033/0.016), but no significant difference was found between sublobectomy and open-close surgery (p=0.679) Figure 1



Conclusion:
Lobectomy confers better prognosis compared to sublobectomy and exploratory thoracotomy for occult MPD patients with NSCLC.

Background:
In daily practice of chest radiology, radiologists encounter various cases of tumor involving both mediastinum and lung parenchyme, and often undergo difficulty determining the origin of tumor. We retrospectively collected 10 cases of tumor and the determinants of 15 radiologists’ decisions to inquire about the origin of tumor. There have been certain agreeable findings for the right expectations. Through the review of published articles, we re-estimated the findings that may be the factors providing appropriate diagnostic approach to the origin of tumor involving lung and mediastinum.

Method:
We retrospectively collected 16 cases of tumors involving the lung parenchyme and mediastinum. After excluding tumors with posterior mediastinum involvement, benign histology, and no histopathological confirmation, 10 cases were evaluated by 15 radiologists (6 residency trainees and 9 specialists in chest radiology). The inquiries included the expected origin of tumor and the determinants for the expectation. Then the review of collected determinants for each case was performed by 2 specialists in chest radiology (5 year and 22 years of experience in radiology) and the certain agreeable findings for the right expectations were analyzed.

Result:
Among the 10 cases of tumor, 8 cases were lung cancer (3 small cell lung cancer, 3 adenocarcinomas, 2 squamous cell carcinoma) and 2 cases were thymic carcinoma. The largest percentage of correct expectations was 87 % (9/9 of chest specialists and 4/6 residents) and the smallest percentage was 13 % (1/9 of chest specialist and 1/6 residents). For lung cancer, the determinants for the right expectation included open bronchus sign, involvement of middle mediastinum, and mediolateral displacement of mediastinum. On the other hand, findings such as epicenter of mass, irregular margin, angle of the mass with mediastinal contour, and pleural metastasis were not contributable.

Conclusion:
Findings helped to make the right expectations were open bronchus sign, involvement of middle mediastinum, and mediolateral displacement of mediastinum. Understanding the CT findings of tumor mass involving mediastinum and lung may be helpful to diagnosis.

Background:
Lung cancer has the highest death rate among cancer types and anorexia is reported by a high percentage of patients, but the prevalence values may vary according to form of diagnosis. Anorexia is associated with reduced food intake, weight loss and a negative affect in quality of life and worse outcome. There is no gold standard for anorexia diagnosis. The anorexia cachexia scale (AC/S) from FAACT instrument has been proposed as a tool for diagnoses anorexia but a validated cut-off value for NSCLC patients is required. This study validates a cut-off value of AC/S for anorexia diagnosis in NSCLC patients.

Method:
The AC/S were evaluated in Non-Small Cell Lung Cancer (NSCLC) patients to establish a cut-off value by ROC curve analysis and CutOff Finder program with the anorexia score from QLQ-C30 questionary as a standard reference and by X-tile based on survival. The cut-off value was associated with clinical parameters

Result:
Three hundred and twelve ambulatory NSCLC patients were evaluated, 67% with adenocarcinoma, 65% stage IV and 98% with ECOG ≤2. The mean of AC/S was 31 ± 9 and the identified cut-off value was 32.5, sensitivity 80.3% (85.7-73.3) and specificity 85% (90%-78.2). The proportion of anorexia based on cut-off value of 24 was 26% and with cut-off value of 32 was 50%. AC/S cut-off value 32 was associated significantly with clinical parameters, nutritional consumption and quality of life. Overall survival was determined in all patients, stage III/IV and stage IV. The overall survival was independently associated with the cut-off value of 32. Figure 1



Conclusion:
Lung cancer patients with the score of ≤32 in AC/S for anorexia diagnosis is proposed, clinically useful and this cut-off can improve the identification of patients with a risk of complications of cancer related malnutrition. Future treatments and follow ups of cancer-related anorexia should be focus in this patients.

Background:
Evidence from retrospective and small prospective trials suggested that local therapy might be beneficial for patients with oligometastatic non-small-cell lung cancer (NSCLC). The purpose of this study is to analyze the efficacy of thoracic radiotherapy in oligometastatic NSCLC patients harboring wild-type EGFR that did not progress after first-line chemotherapy in Asian population.

Method:
We retrospectively reviewed 181 stage IV NSCLC patients harboring wild-type EGFR with three or fewer metastatic lesions after first-line chemotherapy with an Eastern Cooperative Oncology Group(ECOG) performance status(PS) score of 2 or less. All the patients treated with first-line therapy of four to six cycles of platinum doublet therapy and did not progress. Patients were classified into two regimens: 89 patients received thoracic radiotherapy (arm A) with volumetric modulated arc therapy (VMAT) technology, 92 patients received maintenance treatment or observation only (arm B). Maintenance treatment used only one chemotherapy drug including gemcitabine or pemetrexed or docetaxel, and observation was defined as close surveillance without cytotoxic treatment. The progression-free survival (PFS) was defined as the interval from the date of treatment to the earliest date of disease progression or death. The overall survival (OS) was defined as the interval from the date of treatment to the date of death. PFS and OS were estimated by the Kaplan-Meier method and were compared by the log-rank test.

Result:
The median PFS of the thoracic radiotherapy arm was significantly longer than that of the maintenance treatment arm (7.5 vs. 4.3 months, p = 0.006). The median OS of the thoracic radiotherapy arm also slightly longer than that of maintenance treatment or observation arm (13.0 vs. 10.0 months, p=0.031). Multivariate analysis indicated that thoracic radiotherapy were independent predictors of PFS. Thoracic radiotherapy, ECOG PS (0-1) ,histology adenocarcinoma and no brain metastasis were correlated with longer OS.

Conclusion:
The thoracic radiotherapy could improve PFS and OS in oligometastatic unresectable NSCLC patients harboring wild-type EGFR that did not progress after first-line chemotherapy.

Background:
Stage IV NSCLC patients with oligometastasis may experience long-term survival when macroscopic tumour sites are treated radically. The aim of this abstract is to analyse our experience in local management of oligometastasis in NSCLC.

Method:
We retrospectively analysed 38 patients with oligometastatic NSCLC in terms of overall survival (OS), progression-free survival from diagnosis (SLP) and treatment (SLPT) of oligometastatic disease and the association with clinical features such as age, gender, histology, molecular profile, stage at diagnosis and metastatic sites. Kaplan Meier method was used.

Result:
We analysed 38 patients (25 men, 13 women). Mean age: 61 years (40-82). Histology: 60% adenocarcinoma, 8% squamous carcinoma, 13% large cell carcinoma, 19% NOS. 2 EGFR and 1 BRAF mutations. 60% patients (23/38) presented oligometastatic NSCLC at diagnosis, 34% after progression of early disease and 6% after response to initial systemic treatment for advanced disease. Mean number of metastasis: 1 (1-3). Most frequent location: brain (80%). 35% of patients (8/23) oligometastatic at diagnosis received local treatment for the primary tumour: 75% surgery, 25% radiotherapy. Systemic therapy was administrated in 65% of patients (15/23): 93% platinum-based chemotherapy, 7% EGFR-TKI. Table 1 shows local treatment for oligometastasis at diagnosis. No severe complications were observed.

Table 1	Brain (n=30, 80%)	Adrenal gland (n=4, 10%)	Lung (n=3, 8%)	Liver (n=1, 2%)
Surgery + Radiotherapy	87% (26/30)
Surgery	10% (3/30)	50% (2/4)	67% (2/3)
Radiotherapy			33% (1/3)
No local treatment	3% (1/30)	50% (2/4)		100% (1/1)

With a median follow up of 23 months (95%CI 0.9-78.2m), median SLPT was 8.5 months (95%CI 5.3-11.7m), median SLP was 8.7 months (95%CI 6.1 – 11.3m) and median OS was 9.9 months (95%CI 0-32). Median OS of brain metastasis was 9.7 months (95%CI 6.5-12m) vs not reached in patients without brain metastasis (p 0.019). Median OS patients with oligometastatic NSCLC at diagnosis was 8.7 months (95%CI 5'9-11) vs not reached in the rest of patients (p 0.025).

Conclusion:
Data collected demonstrate that survival rate in patients with oligometastatic NSCLC is similar to that reported in literature. Cerebral metastasis significantly worsen the prognosis.

Background:
There is a high incidence of brain metastases in non-small cell lung cancer， result in treatment failure. The usual outcome of untreated patients is very poor. How to improve living quality and extend the median survival is a hot item for clinical studies. Therefore, this study attempted to analyze the prognostic factors of the non-small cell lung cancer with brain metastases.

Method:
145 patients who were diagnosed for brain metastasis from Non-small cell lung primary cancer by MRI at the Cancer Hospital affiliated to Fujian Medical University from January 2010 to December 2013 were retrospectively reviewed．A number of potential influencing factors which might affect prognosis were evaluated，including age，gender, pathological type，Karnofsky performance score（KPS），tumor and lymph node staging, internal from diagnosis of lung cancer to the development of BM，symptoms at BM diagnosis，number of BM，region of BM，maximum diameter of BM，peritumoral brain edema，radiation boost following WBRT and the treatments．Survival time was recorded from BM diagnosed to die or final follow-up．Survival rate was calculated by Kaplan-Meier method．Log-rank method was adopted to compare the difference of each inferior group in survival rate．The multi-variate analysis about survival was performed with Cox’S regression proportional model．Statistical significance was defined as P<0.05．

Result:
There were 145 patients in the research，median survival time（MST） from BM diagnosed was 13.0 months，6-month，1-year and 2-year survival rates were82.8%， 52.4％and 25.8％,respectively。The univariate analysis showed KPS，the presence of extracranial metastases, symptoms at BM diagnosis , both side of the brain metastases , meningeal metastases and maximum diameter of BM had tendency to statistical differences(P value are 0.009、0.004、0.019、0.044、0.023、0.044,respectively). The multivariate analysis indicated that the presence of extracranial metastases, symptoms at BM diagnosis and meningeal metastases were closely related to the prognosis.

Conclusion:
Based on the results of our study, we confirmed that meningeal metastases, no extracranial metastasis and no Symptoms at BM diagnosis are independent prognostic factors in NSCLC with brain metastases.

Background:
Intrathoracic dissemination M1a disease has been reported to be a distinct lung cancer with favorable prognosis and contraindicated surgery may be beneficial to patients with NSCLC. This study aims to investigate treatments of r-M1a and s-M1a in real world and explore which kind of resection type of lung benefits s-M1a patients.

Method:
Patient characteristics, pathology, gene profiles and treatment were respectively collected for lung cancer patients who were diagnosed as r-M1a or s-M1a stage IV disease. Different therapies were evaluated by comparing progression free survival (PFS) and overall survival (OS) by Kaplan-Meier. A cox proportional hazards regression model was applied to evaluate the prognosis factors. Statistical analysis was performed in all subgroups.

Result:
Overall, 2304 consecutive lung cancer patients receiving thoracotomies at Guangdong general hospital were retrospectively analyzed. Eighty r-M1a patients (3.47% of all patients) and Seventy-three s-M1a patients (3.17% of all patients) were enrolled. Difference was observed in two groups among gene profiles and treatment. Compared to r-M1a group, s-M1a group contained more patients with EGFR mutation (18.3% VS 32.7%, P<0.001) and ALK overexpression (0.7% VS 1.3%, P=0.005), a higher proportion chemotherapy patients and lower local treated patients (19.0% VS 24.2%, 7.5% VS 0%, P=0.008). Median PFS of r-M1a and s-M1a patients in chemotherapy group (66, 43.14%), targeted therapy group (33, 21.57%), local treatment group (11, 7.19%) and wait-and-see group (43, 28.1%) were 14.7, 27.5, 39.3 and 44.1 months, respectively [95% confidence interval (CI),19.15-28.05; P<0.001. local treatment group VS wait and see group, P=0.924]. And median OS was 52.2, 47.9, 59.4 and 71.7 months, respectively [95% confidence interval (CI), 47.86-61.95; P=0.208]. In addition, no difference between lobectomy and limited resection was observed in patients with s-M1a in PFS [median 21.9 months, 95% confidence interval (CI),17.59 to 26.22; P=0.738] and OS [median 42.6 months, 95% confidence interval (CI),30.89 to 54.25; P=0.944]. Cox regression analysis revealed group (r-M1a VS s-M1a) and pathology were the independent prognostic factors.

Conclusion:
Wait and see strategy may be a favorable alternation for r-M1a and s-M1a patients with NSCLC. For s-M1a NSCLC patients, limited resection of lesions was recommended compared to lobectomy.

Background:
Chronic wood smoke exposure (WSE) is related to obstructive pulmonary disease and represents an increased risk of lung cancer. WSE is asociated with EGFR-mutations and low frequency of KRAS mutations. WSE signaling networks show better response to EGFR-TKIs, improving response rate and overall survival in NSCLC patients. Next-generation sequencing (NGS) has facilitated parallel analysis of multiple genes for treatment selection and monitoring response to treatment. We evaluated genomic alterations in patients with WSE based on tumor profiling by massive parallel sequencing.

Method:
52 patients with advanced lung cancer were evaluated. Fresh-frozen samples were used for DNA extraction with the Wizard Genomic DNA Purification Kit (Promega) including some formalin-fixed paraffin-embedded tissues (FFPE). The TruSeQ Cancer Panel (Illumina) was used for library construction in targeted sequencing of 48 genes spanning 212 amplicons in mutation hotspots.

Result:
WSE was more frequent in women (59% vs 41% p=0.038). We found diferent mutations in ATM (A1309H, G1679V, N1793I and T2749P), EGFR exon 7 (G288V), KDR (H267, Q1146S) and SMARCB1 (T72Q, G157A). WSE correlated with mutations in the genes KDR 89% vs. 11% (p=0.024), ATM 72% vs. 27% (p=0.040), SMARCB1 74% vs. 26% (p=0.020) and in exon 7 of EGFR 75% vs. 25% (p=0.034). Additionally, ATM mutations correlated with metastasis in CNS and bones 77% vs. 23% (p=0.006), also, patients with EGFR exon 7 presented major metastases in CNS and bones 67 vs. 33 % (p=0.084). SMARCB1 mutations were associated with worse overal survival (48 vs 5.6 months p=0.066). WSE patients carrying EGFR exon 7 mutations had better response showing either partial response or stable disease.

Conclusion:
Latin American patients of lung cancer and WSE present a distinctive mutation profile compared to non-WSE patients showing a positive correlation with KDR, ATM, EGFR exon 7, and SMARCB1 mutations. Figure 1

Abstract not provided

Background:
Nab-paclitaxel (nab-PTX) is used as primary therapy in the treatment of non-small cell carcinoma. However, we frequently use it as secondary or later therapy, or for patients with performance status (PS) of >=2. Therefore, we analyzed the response to and safety of nab-PTX therapy in the treatment for patients with non-small cell carcinoma in our hospital.

Method:
Between January 2014 and March 2017, 46 patients received chemotherapy with nab-PTX, or nab-PTX and carboplatin for non-small cell carcinoma in our hospital. We used the standard nab-PTX 100 mg/m[2] and carboplatin AUC5, except in older patients and those with PS of >=2, for whom we reduced the medication dose.

Result:
The median age of the patients was 66 years (range, 26–78 years), and 17 patients were older than 75 years. Of the patients, 39 were male and 7 were female, and 41 patients were smokers. Ten patients had preexisting pulmonary fibrosis, and 30 had preexisting emphysema. The tissue types of the tumors were squamous cell carcinoma, adenocarcinoma, other types, and not diagnosed in 32, 10, 2, and 2 of the patients, respectively. The PS of 7, 33, and 6 patients before treatment were 0, 1, and 2, respectively. The tumor stage was ⅡB, ⅢA, ⅢB, ⅣA, ⅣB, and postoperative recurrence was observed in 3, 4, 11, 15, 9, and 4 cases, respectively. The treatments were used as primary, secondary, or third or later therapy in 8, 25, and 13 patients, respectively. Twenty-five patients received the combination therapy. The median follow-up period was 8.5 months. The response rate (RR) was 11%. The disease control rate (DCR) was 20%. The median progression-free survival (PFS) was 3 months. Twenty patients experienced adverse events of grade 3 or higher. These events included leukocytopenia (14, 70%), anemia (3, 15%), anorexia (3, 15%), febrile neutropenia (3, 15%), fatigue (1, 5%), and thrombopenia (1, 5%). In addition, the data of the patients treated with nab-PTX as secondary or later therapy indicated a RR of 13%, DCR of 18%, and median PFS of 3 months. The data of the patients with PS of >=2 indicated a RR of 0%, DCR of 16.7%, and PFS of 1.5 months.

Conclusion:
Nab-PTX is used as secondary or later therapy in patients with non-small cell carcinoma and PS of >=2. Nab-PTX therapy is useful and safe at a constant rate. We will analyze more cases, including patients under observation, and will report the data during the presentation.

Background:
A major obstacle of NSCLC targeted treatment is the occurrence of resistance. Drug inhibiting the Epidermal Growth Factor Receptor (EGFR) has been a treatment for more than a decade and is given as first line treatment in EGFR mutated patients. However, up to 30 % of the patients with EGFR mutations experience no objective response to EGFR-TKIs and hence appear as intrinsic resistant. We and others have discovered, that increased FGFR1 expression occurs in the lung adenocarcinoma cell lines with acquired resistance to EGFR inhibitors, but no studies have investigated high FGFR1 expression as an intrinsic resistance mechanism to erlotinib.

Method:
CRISPR-Cas9 SAM was used for genetically upregulation of FGFR1 in the adenocarcinoma cell lines HCC827 and PC9. Proliferation and response to erlotinib was investigated with CellTiter 96® AQueous Non-Radioactive Cell Proliferation Assay (Promega). Protein expression and was investigated using western blotting. FGF2 levels was investigated in serum samples from 36 EGFR-mutated patients using the Quantikine HS ELISA kit for Human FGF basic Immunoassay (R&D) and FGFR1 expression will be investigated with IHC in a cohort of 30 EGFR mutated patients.

Result:
FGFR1 upregulation in PC9 and HCC827 (FGFR1+) did not by itself decrease the sensitivity to erlotinib. However, when the cells were treated with the FGFR1 ligand FGF2 the cells became significantly (p<0.05) more resistant compared to control cells. FGF2 in itself also made the control cells less sensitive to erlotinib, hence we hypothesized that serum levels of FGF2 may influence the response to erlotinib in EGFR mutated patients. FGF2 ELISA performed on 36 EGFR mutated patients, however, revealed that serum-FGF2 did not correlate with PFS. At this moment, we are conducting WB analysis of the FGFR1 pathway for FGFR1+ cells and control cells treated with FGF2 and erlotinib to reveal the functional bypass signalling. We are also preparing IHC for FGFR1 on tissue from EGFR mutated patients obtained prior to erlotinib treatment to confirm our in vitro findings.

Conclusion:
FGFR1 overexpression is a putative intrinsic resistance mechanism to erlotinib treatment. FGF2 levels may influence the activity and resistance mediation by FGFR1, but serum levels of FGF2 are not determining for erlotinib response in EGFR mutated patients.

Background:
In the Checkmate 057 trial, it was observed a slightly higher number of deaths in the nivolumab arm within the first 3 months of treatment. A post-hoc analysis from this study suggested that pts with poorer prognostic factors and/or more aggressive disease combined with low or no PD-L1 expression appeared to be at higher risk of death with nivolumab. Nevertheless, most of pts with these factors were still alive > 3 months in the nivolumab arm and no factors have been identified for selection. Here, we report a similar analysis conducted on pts treated with nivolumab in the Expanded Access Programme (EAP) in Italy.

Method:
Nivolumab was available upon physician request for pts aged ≥18 years who had relapsed after a minimum of one prior systemic treatment for stage IIIB/stage IV non-Squamous NSCLC. Nivolumab 3 mg/kg was administered intravenously every 2 weeks to a maximum of 24 months. Pts included in the analysis had received at least one dose of nivolumab and were monitored for adverse events (AE) using Common Terminology Criteria for Adverse Events.

Result:
In the Italian EAP, of 1559 pts with available survival data, 365 (23.4%) died within the first 3 months. This data is comparable to what observed in the 057 study where (nivolumab arm 20.2% pts died <3 months). Baseline characteristics of the two groups (deaths ≤3 or >3 months) are summarized in the table below. In univariate and multivariate analysis, factors associated with early death were:bone and liver metastases, ECOG PS2 and no prior maintenance therapy. However, majority of pts with these factors did not die within the first 3 months.

	OS >3 months (1194)	OS ≤3 months (n=365)
Gender, Male (%)	760 (64)	251 (69)
AGE (median; range) ≥70 yrs, n (%) ≥75 yrs, n (%)	66 (27-89) 397 (33) 181 (15)	65 (36-83) 116 (32) 48 (13)
SMOKING HABITS, n (%) Former/current smoker Never smoker NA	- 865 (79) 232 (21) 97	- 250 (78) 72 (22) 43
ECOG PS, n (%) 0 1 2 NA	- 538 (45) 591 (50) 53 (5) 12	- 101 (28) 207 (57) 53 (15) 4
METASTASIS, n (%) Brain Liver Bone Nodes	- 296 (25) 208 (17) 429 (36) 877 (73)	- 107 (29) 114 (31) 189 (52) 283 (77)
EGFR, n (%)	74/1065 (7)	23/312 (7)
Maintenance	303 (25)	69 (19)

Conclusion:
These results confirm the pivotal 057 trial suggesting that no single clinical factor can be used for pts selection. PS2, liver or bone metastastatic pts should be followed with attention after starting Nivolumab.

Abstract not provided

Background:
In patients with non-small cell lung cancer, the target therapy varies depending on the gene alteration. Recently, it is progressed therapy using ALK inhibitor for patients with resistance against EGFR TKI. The therapy is targeted patients with ALK or ROS1 fusion gene. In generally, two-step RT-PCR is used as a method for detecting EML4-ALK and ROS1.

Method:
Our method can be easily and quickly used by performing RT-PCR and real-time PCR in one step using PNA probe. In addition, a PNA probe is designed at the ALK and ROS1 kinase sites and the fusion target is detected as a melting curve to screen EML4-ALK and ROS1 gene. Using 43 of FFPE clinical samples, we compared our screening method with direct sequencing method.

Result:
This real-time PCR-based PNA probe-assisted fluorescent melting curve analysis assay(EML4-ALK and ROS1 screening) can detect a total of EML4-ALk 28 and ROS1 20 different Fusion gene. A total of 43 FFPE clinical samples and 3 cell lines(H2228, H3122 and HCC78) were used for EML4-ALK and ROS1 tests and results was good concordance. In case of discordance samples, we confirmed using direct sequencing.

Conclusion:
We have a simple and rapid method for detecting EML4-ALk or ROS1 Fusion genes within four hours. Therefore, it can be accomplished preventing experimental error, thus generating significant cost savings reductions.

Background:
Fusion partner of echinoderm microtubule-associated protein-like 4 (EML4) is frequently found in non-small-cell lung cancer (NSCLC). The EML4-ALK fusion gene has various variants depending on the exon region of the EML4 gene, and the tests are required to establish a new strategy for the treatment and prevention of disease according to the genotype.

Method:
EML4-ALK gene was identified by PNA assisted one step RT-real-time PCR using fluorescent melting curve analysis. This method is run cDNA synthesis, target amplification at a time. Genotyping technology confirmed concordance using existing screening method and direct sequencing method. Genotyping Probe can detect accurately break point between EML4 gene and ALK gene. Test was performed using 12 of standard RNA and 2 of EML4-ALK gene cell line(H2228 and H3122).

Result:
We have developed a simple and rapid RT-real time PCR method for detecting EML4-ALk genes within four hours using PNA. This method is able to detect 12 of standard RNA with detection limit as low as 1x10^3 copies and in H2228 and H3122 cell line concentration confirmed 10ng, 1ng, 0.1ng.

Conclusion:
This method can be easily and quickly detected EML4-ALK genes and have a high sensitivity and accuracy for genotyping. Therefore, it can be accomplished preventing experimental error, thus generating significant cost savings reductions.