Virtual Library

Abstract not provided

Background:
Combination therapy with agents that target the molecular and cellular mechanisms of resistance to checkpoint inhibitor therapy (CIT) is a rational approach to restoring or improving the efficacy of CIT in patients with immunotherapy resistant NSCLC. Sitravatinib is a spectrum-selective TKI which targets TAM receptors (Axl, MER), split family receptors (VEGFR2 and KIT), and MET. Inhibition of these target classes by sitravatinib may enhance anti-tumor activity through targeted depletion of immunosuppressive Type 2 tumor associated macrophages, regulatory T cells and myeloid-derived suppressor cells (MDSCs) and increasing antigen presentation capacity of dendritic cells in the tumor microenvironment (TME) thereby enhancing anti-tumor T effector and NK cell responses. Given these pleiotropic immune activating effects, the combination of sitravatinib with nivolumab is a rational approach to restoring or enhancing the clinical activity of CIT in patients with immunotherapy resistant NSCLC.

Method:
MRTX-500 is a Phase 2 Study of sitravatinib in combination with nivolumab in non-squamous NSCLC patients who have experienced progression of disease on or after treatment with CIT. The primary objective is to assess the clinical activity of the combination using ORR by RECIST 1.1. Enrollment into the Phase 2 treatment arm is stratified by prior outcome of CIT (e.g., clinical benefit versus progression of disease in ≤12 weeks). The investigational agent sitravatinib is administered orally in continuous regimen; nivolumab is administered intravenously, 240 mg every 2 weeks. The sample sizes for the treatment arms are based on two-stage Simon Optimal Design.

Result:
The recommended phase 2 dose of the combination is 120 mg of sitravatinib orally, once daily with nivolumab given at a flat dose of 240 mg IV Q 2 weeks. As of June 20, 2017, the study has enrolled 11 patients and 6/11 patients have had at least one on-study tumor assessment. Two patients out of 6 have achieved PR by RECIST. The first patient is a 72 yo female with pan-wild type metastatic NSCLC with history of treated brain metastases with multiple prior therapies who previously received pembrolizumab (stable disease for 14 months) and obtained confirmed PR at first disease evaluation. The second patient is a 71 yo female with pan-wild type metastatic NSCLC with multiple prior therapies who previously received nivolumab (progressive disease as best overall response) but who obtained unconfirmed PR at first disease evaluation. Treatment has been associated with manageable side effects to date.

Conclusion:
This study is ongoing and actively accruing patients.

Background:
Studies have demonstrated that epigenetic modifiers, such as azacitidine, may sensitize tumor cells to treatment with checkpoint inhibitors, such as pembrolizumab (pembro). Efficacy and safety results from a phase 2, randomized, double-blind study of pembro in combination with CC-486, an oral formulation of azacitidine, vs pembro+placebo (PBO) for 2L treatment of advanced NSCLC are reported.

Method:
Patients aged ≥ 18 years with stage IIIB/IV NSCLC with only 1 prior platinum-based chemotherapy were randomized 1:1 (stratified by histology) to pembro 200 mg day 1 plus either CC-486 300 mg or placebo days 1-14 of a 21-day cycle. Primary endpoint was PFS. Key secondary endpoints included OS, ORR and safety.

Result:
51 and 49 patients were randomized to the pembro+CC-486 and pembro+PBO arms. Baseline characteristics were generally balanced between treatment groups. Efficacy results are shown in Table 1. Median duration of treatment for pembro+CC-486 vs pembro+PBO was 14 vs 24 weeks, and median number of cycles was 5 vs 7. The most common grade 3/4 TEAEs associated with pembro+CC-486 were nausea (14%), vomiting (12%), asthenia (10%), and diarrhea (8%), vs diarrhea (6%), asthenia (6%) and pneumonia (6%) with pembro+PBO. Patients treated with pembro+CC-486 vs pembro+PBO experienced a higher rate of pembro dose interruptions (29% vs 16%) and discontinuations (20% vs 10%), and a higher rate of CC-486 or PBO dose interruptions (61% vs 24%) and discontinuations (33% vs 12%). Gastrointestinal events, asthenia/fatigue, and elevated transaminase levels were the most common TEAEs leading to discontinuations.

Conclusion:
The addition of CC-486 to pembro did not improve the primary endpoint of PFS compared with pembro+PBO. PD-L1 expression did not appear to be predictive of CC-486 treatment efficacy. The increase in TEAEs in the combination arm, particularly gastrointestinal (nausea and vomiting), which are known to be associated with CC-486, may have influenced treatment exposure.

Efficacy Endpoints	Pembro + CC-486 n = 51	Pembro + PBO n = 49
Overall
PFS, median, months	3.1	4.0
ORR, n (%)	10 (19.6)	7 (14.3)
By PD-L1 Level at Baseline	n = 45	n = 44
PFS, median, months ≥ 50% ≥ 1%-49% 0%	5.5 1.6 3.6	8.0 1.4 3.9
ORR, % ≥ 50% ≥ 1%-49% 0%	37.5 20.0 18.5	37.5 0.0 7.1

Background:
ACY-241, an oral inhibitor of histone deacetylase 6, has demonstrated activity in preclinical NSCLC models in combination with immunotherapy. The objectives of this study are to evaluate safety, dose-limiting toxicities (DLTs), the maximum-tolerated dose (MTD), and preliminary antitumor activity of ACY-241 in combination with the immune checkpoint inhibitor nivolumab.

Method:
In the 3+3 dose-escalation design, previously treated patients with advanced NSCLC and ECOG PS of 0 or 1 will receive ACY-241 on days 1 to 28 of each 28-day cycle at 3 dose levels (180, 360, and 480 mg) in combination with nivolumab 240 mg on day 15 of cycle 1 and days 1 and 15 of each subsequent cycle. Antitumor activity will be assessed per RECIST v1.1 and immune-related response criteria (irRC).

Result:
As of 16 June 2017, 13 patients have been treated in the 3 dose-escalation cohorts. All patients had received first-line treatment with platinum-based chemotherapy. The median age of all patients was 66 years, 62% were male, 54% had an ECOG PS of 0, 54% had stage IV disease, and 85% had adenocarcinoma (15% had squamous histology). No DLTs were observed in the 180- or 360-mg ACY-241 cohorts. The 480-mg cohort is currently under investigation. The most common all-grade adverse events (AEs) in all cohorts were cough (15%), arthralgia (15%), and fatigue (15%, including grade 3 in 1 patient). One patient experienced a grade 3 cerebrovascular accident related to a brain metastasis but unrelated to study drug. No immune-related AEs have been observed. Six patients were evaluable for response: 2 experienced objective responses (1 complete and 1 partial); 2 patients had stable disease; 2 patients had disease progression. Two patients were not evaluable for efficacy, and 5 patients have not yet undergone a response assessment.

Conclusion:
No DLTs have been observed with ACY-241 at 180 or 360 mg. Preliminary antitumor activity has been observed with the combination treatment. Updated pharmacokinetic data will be presented at the meeting. NCT02635061

Abstract not provided

Background:
Nivolumab significantly improved overall survival (OS) versus docetaxel in patients (pts) with previously treated non-squamous non small cell lung cancer (non-Sq-NSCLC) in the Checkmate 057 study. In a pre-specified subgroup analysis of this trial, this advantage was confirmed also in patients (pts) with KRAS-mutation (KRAS+). However, since the number of KRAS+ pts enrolled in the trial was too small to draw definitive conclusions, the Italian nivolumab expanded access program (EAP) for non-Sq-NSCLC might represent an important source of information about this subpopulation. Here we report the results of the use of nivolumab in pts with KRAS mutation treated in the Italian EAP.

Method:
Nivolumab was provided upon physicians’ request for pts aged ≥18 years who had relapsed after a minimum of one prior systemic treatment for stage IIIB/stage IV non-Sq-NSCLC. Nivolumab 3 mg/kg was administered intravenously every 2 weeks for <24 months. Pts included in the analysis received ≥1 dose of nivolumab and were monitored for adverse events (AEs) using Common Terminology Criteria for Adverse Events.

Result:
Overall, 1588 pts with advanced non-Sq-NSCLC, enrolled in 168 sites, received at least one dose of nivolumab in the Italian EAP. Among 532 pts evaluated for KRAS mutation, 206 (39%) resulted positive. In this subgroup of pts, the best overall response rate (BORR) was 20%, including 2 pts with complete response and 39 pts with partial response. The median OS was 10.7 months (8.6-12.8), with a median follow-up of 7.7 months (0.1-21.2) and a median number of 8 doses (1-45). These results were in line with those ones showed in the overall population (18% BORR and 11 months median OS, respectively). Overall, among pts with KRAS mutation, 166 discontinued treatment for any reason, with only 14 (8%) pts who discontinued treatment due to adverse events, in line with what observed in the general population and in previous studies.

Conclusion:
To date, no direct targeted therapy is available for pts with KRAS mutation. This analysis seems to confirm, in a real word setting and in a larger number of pts, the results obtained with nivolumab in KRAS-positive pts in CheckMate 057, thus representing a potentially effective therapeutic option for this subpopulation.

Background:
The efficacy of immune check-point inhibitors (ICPi) in BRAF mutant non-small cell lung cancer (NSCLC) is largely unknown. The correlation with different parameters predicting efficacy of ICPi (e.g., PD-L1 expression, tumor mutational burden (TMB) and microsatellite instability status (MSI) in these tumors needs further evaluation.

Method:
A retrospective analysis of 30 patients with BRAF mutant advanced NSCLC treated between Aug 2013 and May 2017 was performed. The patients were divided into 2 groups: BRAF V600 E (Group A, N=16), non-V600E BRAF (Group B, N=14). PD-L1 was assessed by immunohistochemistry using 22C3 Dako antibody clone on Dako or Ventana's platform in 16 patients. TMB and MSI were assessed in 9 and 11 patients, respectively. Median progression-free survival (mPFS) with ICPi and targeted agents as well as median overall survival (mOS) were assessed in each group by Kaplan-Meier method.

Result:
Baseline characteristics of the cohort: median age 66y (range 39-98); males 53%; current/past smokers/never smokers/NA 13%/44%/40%/3%; adenocarcinoma/other histology 80%/20%; ECOG PS 0/1/2/3/4/NA 27%/33%/10%/13%/0%/17%. The distribution of TMB, PD-L1 expression and MSI status between the 2 groups is presented in Table 1. Ten patients received ICPi (nivolumab-8, pembrolizumab-2), and thirteen patients received anti-BRAF therapy (dabrafenib+trametinib-6, dabrafenib-4, vemurafenib-3). mOS and mPFS with ICPi and anti-BRAF therapy are summarized in Table 1. Four patients with BRAF V600 E PD-L1 ≥ 50% tumors were included in the series; one patients responded to dabrafenib+trametinib combination (response ongoing, 7.1months+); in two patients ICPi were initiated, response assessment pending. One patient with a non-V600E BRAF mutant NSCLC responded to dabrafenib for 6.7 months.Figure 1



Conclusion:
BRAF mutant NSCLC tumors are associated with high level of PD-L1 expression, low/intermediate TMB and MSI stable status. ICPi may induce prolonged responses both in BRAF V600E and non-V600E BRAF mutant NSCLC. Some non-V600E BRAF mutant NSCLC may benefit from anti-BRAF targeted therapy.

Background:
Pembrolizumab, a humanized monoclonal antibody that inhibits the interaction between programmed cell death 1 (PD-1) and programmed death-ligand 1 (PD-L1) has demonstrated significant antitumor activity and produced durable responses in non-small cell lung cancer (NSCLC). However, data to date suggests that responses are less frequent in patients whose tumors harbor mutations in the epidermal growth factor receptor (EGFR) gene. Our single center experience with the KEYNOTE-001 trial suggested that EGFR mutation positive NSCLC patients with a history of prior tyrosine kinase inhibitor (TKI) therapy had worse clinical outcomes than those who were TKI naïve. However, that analysis was limited by small sample size. As a result of this observation, we are currently enrolling an open-label, phase II trial, of front-line pembrolizumab in EGFR mutation positive NSCLC patients that are PD-L1+.

Method:
This is an open-label, phase II trial of pembrolizumab in patients with EGFR mutation positive NSCLC whose tumors are PD-L1 positive [>1% tumor membranous staining by immunohistochemistry (IHC), 22C3 pharmDx test in a CLIA certified laboratory]. Patients receive pembrolizumab 200mg by IV infusion every three weeks and are evaluated every 9 weeks +/- 1 week with radiographic imaging to assess response to treatment for a maximum of 35 trial treatments of pembrolizumab. After progression on pembrolizumab, patients are followed for evaluation of EGFR TKI efficacy. The primary end point of the study is objective response rate (ORR) to pembrolizumab, per RECIST 1.1. Secondary endpoints include safety and efficacy [progression-free survival (PFS), overall survival (OS)] of front-line pembrolizumab in this population, as well as efficacy [PFS, OS, ORR] of subsequent EGFR TKI after progression on pembrolizumab. Correlative analyses include whole exome sequencing and IHC of patient specimens. To date, 8 out of the 25 planned patients have been enrolled.

Result:
Section not applicable

Conclusion:
Section not applicable

Abstract not provided

Background:
BGB324 is an orally available selective inhibitor of the receptor tyrosine kinase AXL (Biochemical IC50 0.4nM). In animal models of NSCLC exposure, BGB324 restricts cellular plasticity and prevents the development of resistance to Epithelial Growth Factor Receptor (EGFR) inhibitors through mesenchymal transformation.

Method:
BGB324 was administered at an oral loading dose (600 mg) on days one and two followed by a daily maintenance dose (200 mg) to eight patients with previously treated NSCLC (EGFR mutant or wildtype). The tolerability of two different loading doses BGB324 (600 mg on days one and two or 400 mg on days one two and three) were then explored in combination with erlotinib at a dose of 150 mg daily in patients with EGFR mutated NSCLC.

Result:
Two of eight patients treated with BGB324 monotherapy achieved at least six months of stable disease. Both dose levels of BGB324 were tolerated in combination with erlotinib although most patients experienced a transient worsening in gastrointestinal toxicity during the loading dose prior to returning to baseline. A three day loading dose was preferred. Treatment with BGB324 was accompanied by increases in patient serum levels of soluble AXL receptorconsistent with receptor inhibition. One patient who previously experienced progression during treatment with another EGFR inhibitor remains on treatment with erlotinib plus BGB324 for more than eighteen months with a best response of stable disease. The most common treatment related adverse events were increased serum creatinine, diarrhea, nausea and dysguesia.

Conclusion:
Conclusion BGB324 can be safely administered to patients with advanced NSCLC for prolonged periods at doses that abrogate AXL signalling either as monotherapy or in combination with erlotinib. A proportion of patients achieve durable disease stabilisation following treatment with BGB324 alone further exploration of the efficacy of the combination is ongoing.

Background:
The c-Met receptor is overexpressed in ~50% of patients (pts) with non-small cell lung cancer (NSCLC). ABBV-399 is a first-in-class antibody-drug conjugate composed of ABT-700, an anti–c-Met antibody, conjugated to monomethyl auristatin E (a microtubule inhibitor). Preclinical data demonstrate that ABBV-399 can deliver a potent cytotoxin directly to c-Met+ tumor cells.

Method:
ABBV-399 was administered at doses ranging from 2.4 to 3.0 mg/kg (dose expansion and combination cohorts at 2.7 mg/kg) once every 21 days to 29 pts with advanced c-Met+ (immunohistochemistry [IHC] H-score ≥150) NSCLC both as monotherapy (ABBV-399/monotherapy; 16 pts) and in combination with oral erlotinib 150 mg daily (ABBV-399/ERL; 13 pts) (NCT02099058). c-Met expression was assessed by IHC utilizing the SP44 antibody (Ventana; Tucson, AZ, USA).

Result:
As of April 26, 2017, 16 pts with c-Met+ NSCLC received ≥1 dose of ABBV-399/monotherapy. Monotherapy treatment-related adverse events (TRAEs) occurring in ≥10% of pts (all dose levels and all grades) were fatigue (43.8%), nausea (37.5%), neuropathy (25.0%), vomiting (18.8%), anemia, constipation, and diarrhea (12.5% each). Three of 16 (19%) ABBV-399–treated c-Met+ NSCLC pts had a confirmed partial response (PR) with duration of response (DOR) 3.1, 4.8, and 11.1 months. At week 12, 9 of 16 pts (56.3%) had disease control. TRAEs in ABBV-399/ERL occurring in ≥10% of pts (all grades) were neuropathy (46.2%), nausea (23.1%), fatigue, acneiform rash, dry skin, and diarrhea (15.4% each). Four of 13 (31%) evaluable ABBV-399/ERL–treated c-Met+ pts had a PR (3 confirmed, 1 unconfirmed) with DOR 2.8, 5.3, 4.2+, and 9.1+ months. Three of the 4 pts with PR had EGFR-mutated tumor and recently progressed on TKI. At week 12, 10 of 13 pts (76.9%) had disease control. There were no treatment-related deaths as monotherapy or in combination with erlotinib. Responses were seen in both squamous and non-squamous histology.

Conclusion:
ABBV-399 is well tolerated at 2.7 mg/kg once every 21 days and has demonstrated antitumor activity in pts with c-Met+ NSCLC both as monotherapy and in combination with erlotinib. Early evidence suggests that ABBV-399 represents a novel treatment paradigm effective against multiple c-Met+ NSCLC molecular subtypes and histologies. Updated efficacy/safety data and c-Met IHC status will be presented. Safety and efficacy data from Q2week dosing of ABBV-399 will also be presented.

Background:
Onalespib (AT13387) is a non-ansamycin small molecule that inhibits heat shock protein-90 (Hsp90). Hsp90 inhibitors (Hsp90i) preferentially degrade overexpressed and mutated oncoproteins including those that mediate resistance to EGFR-TKIs. Previous Hsp90i studies demonstrated activity in EGFR-mutant NSCLC including EGFR Exon 20 insertions (EGFRex20ins) - uncommon EGFR mutations typically refractory to 1[st] and 2[nd] generation EGFR-TKIs. A phase I study of onalespib plus erlotinib was conducted to determine the MTD, DLT, RP2D, pharmacokinetics (PK) and preliminary antitumor activity for a planned phase 2 trial in EGFR-mutant NSCLC including EGFRex20ins.

Method:
Using a 3 + 3, dose escalation design, onalespib was examined at 2 dose levels (DL) from 150 (DL0) to 120 (DL-1) mg/m[2] IV weekly (D1, D8, D15 on a q28 day cycle). Daily erlotinib was given at 150 mg at both DL. Key eligibility: NSCLC with EGFR activating mutation including EGFRex20ins, age ≥ 18, ECOG PS≤2, acceptable organ function, and ≥1 systemic therapy for advanced disease (platinum-based chemotherapy for EGFRex20ins and EGFR-TKI for other EGFR-mutations). Plasma for PK and ctDNA for next-generation sequencing of ~70 cancer related genes was collected at relevant timepoints.

Result:
9 pts have been treated on 2 DL (3 DL0, 6 DL-1). Pt characteristics: median age 65, M/F (2/7), ECOG PS 0-1 (4/5), EGFRex20ins (8), EGFR E19del (1). 7 pts completed ≥1 cycle. Two DLTs (grade (Gr) 3 maculopapular rash and Gr 3 hypophosphatemia) occurred in DL0. Common drug-related adverse events (AE) of any Gr were diarrhea (100%) and rash (44%), fatigue (55%), increased bilirubin (22%), nausea (44%) and vomiting (33%). Drug-related Gr 3 AEs were diarrhea (55%), maculopapular rash (11%) and hypophosphatemia (11%). At the planned 2-month evaluation, 5 pts had SD, 3 PD, and 1 had withdrawn for toxicity. Of the 5 pts continuing, 2 had SD and 1 PD at the 4-month evaluation. Kaplan-Meier estimate on therapy without progression at the second evaluation is 30% (95% CI: 10 to 87%).

Conclusion:
In patients with EGFR-mutant NSCLC, onalespib plus erlotinib is feasible, tolerable and demonstrates disease control in EGFRex20ins, thereby addressing a key unmet need in NSCLC. The RP2D is erlotinib 150 mg PO daily and onalespib 120 mg/m[2] weekly (D1, D8, D15 q28days). Diarrhea was the most common AE, and generally manageable with supportive care and dose reduction to DL-1. Updated results including PK as well as ctDNA for EGFR-mutation and relevant bypass tracts mediating EGFR-TKI resistance will be presented.

Abstract not provided

Background:
The Kent Oncology Centre has been instrumental and innovative in the development of nurse-led services since 2005. The Lung CNS’s have been conducting oncology clinics since 2009 reviewing patients on TKI’s and chemotherapy. With Immunotherapy now available to some lung cancer patients, the Lung CNS's needed to incorporate immunotherapy review into their established clinics. The Lung CNS's worked collaboratively to develop a patient-centred electronic assessment tool. The tool would ensure standardised practise, patient safety and assess toxicities whilst on Immunotherapy. The aim is for the Lung CNS’s to utilise the electronic tool and roll out through an educational programme thus increasing knowledge and confidence and empowering nurses to safely review patients on immunotherapy.

Method:
To incorporate immunotherapy patients to an established CNS Nurse-led review clinic: Agreement between Consultant and Senior Nurses. Discussions with Computer Sciences, Lung Cns's, Oncologists, Chemotherapy Lead Nurse. Educational Requirements - Consultation and Physical Examination Skills, Non-Medical Prescribing, Chemotherapy Competence, IRMER. Protocols - Agreed for the Nurse Led Oncology review clinic. Competence - The Lung CNS requires a set of practice and competence in judgement and decision making. How the clinic works Consent by the consultant. Consultant toxicity assessment pre cycle 2. Reviewed thereafter by lung CNS or Chemotherapy Nurse prior to each treatment. Electronic Toxicity assessment completed. Weight/Observations recorded. Bloods FBC, U&E's, LFT's. Thyroid 8 weekly. 9am cortisol LH and FSH Direct access to consultant. Consultant review with CT scan.

Result:
Figure 1 Reported Toxicities. Adisonian Crisis Hypothyroidism Diarrhoea/Colitis Fatigue Hepatitis Skin Reactions Pneumonitis



Conclusion:
The number of patients on Immunotherapy treatment is set to rise. Incorporating the review of Immunotherapy into an established Lung CNS Nurse-led Review clinic enabled standardised practise, enhanced patient safety and provided continuity of care. Through education and training and by using an electronic assessment tool; chemotherapy nurses can be empowered to review patients on Immunotherapy.

Background:
Cisplatin, a systemic treatment component for many lung cancer types, is highly emetogenic (HEC). The guideline-recommended antiemetic combination for patients receiving HEC includes a NK~1~ receptor antagonist (NK~1~RA), a 5-HT~3~RA, and dexamethasone (DEX). NEPA is the first oral fixed combination of an NK~1~RA (netupitant) and a 5-HT~3~RA (palonosetron). The approval of oral NEPA was based on studies demonstrating superior prevention of chemotherapy-induced nausea and vomiting (CINV) over oral palonosetron; an intravenous formulation of NEPA is under FDA evaluation. A new Phase 3 study in Asia has reached its primary objective: a single day oral dose of NEPA is non-inferior to a 3-day regimen of aprepitant (APR) and granisetron (GRAN) [both combined with DEX] in preventing CINV in patients receiving cisplatin. This post-hoc analysis explores the efficacy of NEPA vs APR/GRAN within the lung cancer subset of that study.

Method:
Chemotherapy-naïve lung cancer patients in this double-blind, parallel group study received either a single oral dose of NEPA prior to cisplatin-based HEC or a 3-day regimen of APR/GRAN, both with oral DEX on days 1-4. Efficacy endpoints were complete response (CR: no emesis/no rescue medication), no emesis, and no significant nausea (<25 mm on 100 mm visual analog scale) during the acute (0-24h), delayed (25-120h) and overall (0-120h) phases post-chemotherapy. The risk difference for NEPA – APR/GRAN and associated 95% confidence intervals (CIs) were analyzed for each endpoint using the Cochran-Mantel-Haenszel test.

Result:
542 (65%) of the 828 patients had lung cancer. Mean age was 56.1; 73% males. Response rates were comparable for both arms during the acute phase, and favored NEPA in delayed phase (Table). Figure 1



Conclusion:
As a fixed oral combination of an NK~1~RA and 5HT~3~RA in a single capsule/cycle, NEPA offers a convenient and effective prophylactic antiemetic in lung cancer patients receiving cisplatin-based HEC regimens.

Background:
Increasing numbers of patients are being treated with potentially curative surgery for lung cancer. Pathological staging gives an indication of 5-year survival and whether further treatment is recommended. Patients undergo a period of post-operative clinical surveillance to monitor for potential recurrence of cancer. The process of discussing potential recurrence and its early warning signs has not been well researched. This study examines how clinical teams and patients manage information disclosure about possible cancer recurrence following lung cancer surgery. The aim is to identify some of the practice implications for lung cancer teams.

Method:
This qualitative project used case study methodology to explore how information regarding possible recurrence was presented to patients. Twelve patients were recruited at two thoracic surgical centres. Observation of the first post-operative surgical and subsequent oncology or follow-up clinic was conducted and consultations audio recorded. In-depth, one-to-one interviews were completed with clinical staff (surgeon, oncologist, physician and/or nurse specialist) who saw the patients to ascertain their perspective and understand rationale for particular information giving. Framework Analysis methods were used to identify key themes.

Result:
Staff varied in the extent and explicitness that long-term surgical outcomes were communicated to patients. Explicit information was presented in terms of recurrence risk or survival and the terms were frequently used interchangeably. Clinicians were often reluctant to give a numerical estimate of risk of recurrence or survival at the post-operative clinic. Information about early warning signs of recurrence was sporadic, with some clinicians preferring to delay such discussions until later on in the follow-up pathway, due to fear of damaging patients’ perceived fragile hope for cure. Information was aimed at supporting hope, aiding treatment understanding, or facilitating decision-making. Choices made by staff regarding information giving were complex and largely tacit, but appeared to be linked to individual professionals’ underlying optimistic or realistic approach. Staff talked about the importance of balancing hope and realism.

Conclusion:
These findings give unique insight and reveal how challenging and complex it is for clinicians to discuss recurrence following lung cancer surgery. The next stage of the project will examine the patient’s perspective of this process. These data will then be combined to identify ways to improve communication of recurrence

Abstract not provided

Background:
Using evidence based follow up guidelines, our nurse led follow-up clinic was established in December 2012. All post-operative thoracic surgery patients are seen, including patients with primary lung cancer. We evaluated problems and issues patients identified related to their post-operative recovery and follow-up period

Method:
Data was collected prospectively from December 2012 to March 2017. This included information for each patient on surgery, pathology, TNM stage, follow-up plan and smoking status. We recorded additional issues raised by patients. Data was analysed to generate descriptive statistics of post-operative problems. There were 546 patient episodes in 189 clinics for 285 patients with primary lung cancer

Result:
Of the 285 patients 70 (25%) were smokers in the 6 weeks prior to surgery. 171 (60%) were ex-smokers and 44 (15%) had never smoked. 32 (11%) patients smoked after surgery, all except one were pre-operative smokers. Smoking cessation was a concern after surgery with 44% of the pre-operative smokers restarting smoking post-operatively. The number of patients seen at each follow-up interval and the issues identified are shown in the table below. The most frequent issues reported by patients after thoracic surgery are pain, respiratory issues and anxiety. 80% of patients report problems at their first follow-up appointment after surgery, decreasing to 59% at five years. Respiratory issues are common in this group of patients who often have co-existing lung disease. Anxiety, most commonly associated with fears about recurrence of disease, remains a problem throughout the follow-up period. 31% of patients had abnormal imaging at one or more appointments.

Issues identified in the nurse led thoracic surgery follow-up clinic

	Number of patients % of the total patients seen in each survillance period
Time since surgery	Total	Pain	Respiratory issues	Anxiety	Imaging issues	Other issues	No issues
1st follow-up	120	33 27.5%	23 19%	24 20%	18 15%	16 13%	24 20%
6 months	118	21 18%	20 17%	11 9%	33 28%	14 12%	31 26%
12 months	79	10 13%	20 25%	8 10%	19 24%	8 10%	14 18%
18 months	66	9 14%	15 23%	8 12%	14 21%	7 11%	22 33%
2 years	65	9 14%	12 18%	7 11%	10 15%	10 15%	19 29%
3 years	48	7 15%	7 15%	7 15%	11 23%	8 17%	13 27%
4 years	28	0	7 25%	5 18%	5 18%	8 29%	7 25%
5 years	22	0	6 27%	2 9%	4 18%	2 9%	9 41%
Totals	546	89 16%	110 20%	72 13%	114 21%	71 13%	139 25%

Conclusion:
The findings indicate the extent of physical, psychological and lifestyle (e.g. smoking) concerns in post-operative follow-up. A new telephone follow-up clinic has recently been introduced to address these needs. Further investigation with objective assessment and scoring of symptoms would improve the quality of the data collected.

Background:
Research shows people diagnosed with lung cancer have greater unmet supportive care, physical and emotional needs compared to those diagnosed with other cancers. Much of this research is older and primarily focused on small numbers of newly diagnosed patients. Other research has focused on the relative lack of treatment options and does not address practical and psychosocial needs.

Method:
To more fully understand the current unmet needs of lung cancer survivors, an online survey was distributed between 11/9/2015 and 2/8/2016. Of 820 respondents, 471 were lung cancer patients/survivors with 349 loved ones. Queried on treatment histories, respondents were asked to identify the most prevalent and problematic symptoms and side effects experienced during treatment, shortly after treatment ended and at 5+ years post-diagnosis. They were also asked which were most problematic during each time period.

Result:
The survey had an overall 72% completion rate with 21% of survivor-respondents indicating a diagnosis 5+ years prior. Patients/survivors rated anxiety, fatigue and shortness of breath as most challenging in the immediate, post-treatment, and long-term. During treatment, gastrointestinal issues including constipation, diarrhea and nausea were also highly problematic. All groups reported physical effects were significantly more problematic during treatment but deemed emotional effects more difficult to manage post-treatment and in the long-term. In open-ended questions, nearly 25% of respondents indicated they received inadequate information/assistance to manage physical and emotional reactions, both during and after treatment. Only 27% of respondents had a discussion about palliative care with just over 20% having received it. The survey affirmed that assistance to manage lung cancer’s symptoms and treatment side effects is an unmet need in the lung cancer community. In response, a four-part educational series, including webinars and accompanying print materials, was developed. The series is the only to focus specifically on lung cancer and helps participants understand the causes of the top four reported symptoms and side effects, including potential medical interventions and holistic, practical tips that can used immediately.

Conclusion:
Those diagnosed with lung cancer are the experts and we can only understand their unmet needs by asking them. This large, extensive survey provided insight into their needs during, immediately after and long after treatment. Our initial four-part webinar series is only the beginning--through our results and querying webinar participants, we are developing additional educational programming to help those diagnosed with lung cancer and their loved ones understand and manage their specific disease and treatment-related challenges.

Background:
The National Lung Cancer Audit 2015 reported 40% of patients with Lung cancer are diagnosed following an emergency admission. The National Lung Cancer Forum for Nurses Workshop 2016 undertook a review of how the Lung Cancer CNS’s (LCNS) early intervention can have a positive impact on the reduction in the length of stay for those patients admitted via the emergency route at their first presentation.

Method:
A prospective and a retrospective review of a cohort of patients admitted by the emergency route was undertaken, n=51 in both cohorts, across 13 UK sites over a 2 month period. A standardised Data Collection Tool was developed to ensure consistency and avoid bias. In the prospective cohort the LCNS actively identified patients at an early stage following their admission, whereas the retrospective cohort was a random sample of patients admitted and diagnosed via the emergency route irrespective of the LCNS involvement.

Result:
Demographics and baseline characteristics were found to be similar in both cohorts. 31% of patients were never seen by the LCNS in the retrospective cohort whereas all patients were seen in the prospective cohort 76% of patients in the prospective cohort were seen within 0-5 days following admission by a LCNS compared with 43% in the retrospective cohort Average length of stay in the prospective cohort was 9.7 days V 17.6 days in the retrospective cohort.

Conclusion:
This review suggests the early intervention of a LCNS is associated with a reduced length of stay following an emergency admission when Lung Cancer/Mesothelioma is diagnosed.

Abstract not provided

Background:
Video-assisted thoracoscopic surgery (VATS) is now increasingly performed and recommended in early-stage NSCLC resection. Early postoperative mobilisation, rehabilitation and physiotherapy can improve subsequent reduction in lung volumes, aid clearance of secretions and independent mobility, although there is much variation in how lung cancer patients are currently managed in this respect. The objective of this study was to observe capability for early mobility and frequency of issues potentially amenable to physiotherapy rehabilitation following VATS lobectomy for lung cancer. Any preoperative factors associated with increased rehabilitation needs were also identified, thus enabling early recognition of lung cancer patients needing rehabilitation.

Method:
A prospective observational study was performed including all consecutive cancer patients undergoing VATS lobectomy in a regional centre over 4 years (2012-2016). Standard postoperative care included early mobilisation where patients were sat out by nursing staff from postoperative day 1 (POD1) and assisted to mobilise as able. Physiotherapy assessment of all patients on POD1 determined presence of issues potentially amenable to rehabilitation, and this was commenced as deemed necessary. Outcome measures included development of postoperative pulmonary complication (PPC), hospital and high dependency unit (HDU) length of stay (LOS) and intensive therapy unit admission (ITU).

Result:
285 lung cancer patients were observed; 76 (27%) patients did not requiring specialised rehabilitation or physiotherapy, and engaged with nursing staff successfully in early mobility and becoming independently mobile. These patients had a significantly lower hospital and HDU length of stay (p<0.001), reflecting uncomplicated recovery. The remaining 209 patients (73%) received physiotherapy rehabilitation to assist/improve reduced mobility. Of these patients 23 (8%) also received chest physiotherapy for sputum clearance and 65 (23%) for lung volume loss. amongst those requiring this therapy were all patients who developed PPC, and all those admitted to the ITU. Despite surgery being non-invasive the frequency of development of PPC was higher than that for other VATS surgery at 7%, and this was associated with poorer outcomes. Logistic regression identified that COPD, BMI, preoperative mobility and age were associated with increased postoperative rehabilitation needs for mobility or respiratory issues (p=0.013).

Conclusion:
We recommend that all lung cancer patients receive early mobilisation and routine postoperative rehabilitation following this surgery ensuring issues amenable to physiotherapy and the need for rehabilitation is detected early. Associated preoperative baseline factors included COPD, poor preoperative mobility, and increasing BMI and age; such patients may benefit from preoperative rehabilitation as well as routine physiotherapy for better postoperative outcome.

Background:
Early-palliative care (EPC) after lung cancer diagnosis is essential for a better quality-of-life (QoL), and even offers a substantial improvement in survival outcomes. We prospectively assessed the effect of EPC in overall survival (OS) and patient-reported outcomes in non-small cell lung cancer (NSCLC) patients.

Method:
Newly-diagnosed and treatment-naïve NSCLC patients were included and randomly assigned (1:1) to receive either EPC with oncologic, nutritional, and psychological care, or standard oncologic care alone. Assessments were performed at baseline, second, fourth and sixth cycle of chemotherapy, with evaluations including: QoL, evaluated by The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, depression and anxiety which were evaluated using the Hospital Anxiety and Depression Scale, and oncologic symptomatology, which was evaluated with the Edmonton System Assessment Scale. NCT01631565 [013/020ICI(CV773/13)].

Result:
Ninety-six NSCLC patients were enrolled; 42 patients were allocated to EPC while 54 patients were allocated to standard-care. Overall, patients receiving EPC have lower self-reported symptoms, depression and anxiety. Median OS of patients with EPC was 11.1 months (95% CI: 8.4–13.9), while in patients with standard-care was 5.9 months (95% CI: 4.8 – 7.1); p=0.049. In the multivariate analysis, factors associated with worse OS were: patients in standard-care arm (HR, 95% CI 1.6 (0.9 – 2.7); p=0.05), male patients (HR, 95% CI 1.8 (1.1 – 3.0); p=0.028) and worse ECOG performance status (≥2) (HR, 95% CI 1.9 (1.0 – 3.5); p=0.039).In a subgroup analysis, patients who reaped the most benefit from EPC included those with better ECOG performance status (<2) (8.9 vs. 5.7 months; p=0.05); those without depression at baseline (14.8 vs. 6.5 months; p=0.05) and those Corroborar que si sea mayor ansiedad basal-mayor beneficio Figure 1



Conclusion:
EPC might provide benefit in the clinical symptomatic burden and OS of NSCLC patients. Benefits from EPC in OS might be associated to favorable global clinical status.

Background:
While many thousands of patients per year receive chemotherapy for advanced NSCLC with first-line or subsequent chemotherapy, little is known about patients’ views on their decision to receive that treatment. In that median survival results generally do not exceed one year, there are many potential risks for regret. Given the highly symptomatic nature of NSCLC coupled with patient, family and oncologist desires to decide rapidly on treatment, many challenges exist affecting quality decision making for patients and their supporters facing treatment. Among 59 studies dealing with regret in a recent systematic review (Becerra Perez 2016), none analyzed patients with lung cancer (66% of studies were in oncology). A clinical profile of the extent of regret, and factors contributing to that regret is lacking in those undergoing chemotherapy for lung cancer.

Method:
All patients were entered into a phase III, two-arm, prospective, randomized trial in patients receiving chemotherapy for lung cancer. Patients were randomly assigned to either usual care (UC), or enhanced care (EC) using the DecisionKEYS decision aid coupled with every 3 week PRO assessment using the electronic LCSS measure. All patients were offered the Decision Regret Scale (“DRS,” O’Connor 1999), at 11 weeks (+/- 2 weeks) after starting treatment. The DRS is a categorical scale with 5-items in 5 categories (ranging from “strongly disagree” to “strongly agree”). Patients completed assessment for decisional conflict; the patients’ supporters completed similar measures.

Result:
164 patients were entered, 160 received chemotherapy. Characteristics: 43% women; 92% Stage IV; 73% first-line therapy. Means: age 63; KPS 81. ECOG 1 = 56%; ECOG 2 = 42%. 46% represented minority groups. 22 different chemotherapy regimens were used. First-line patients received combination regimens with the majority being platinum-based with 2 or 3 drugs. 128 patients (80%) completed the DRS. Results combined the two top categories indicating the greatest extent of regret. Only 9 patients (7%) expressed regret as the maximum of the 5 DRS questions. 94% expressed that the decision for chemotherapy was a wise one. This low degree of regret did not differ by first-line or subsequent chemo or by EC versus UC groups.

Conclusion:
Patients receiving chemotherapy for advanced NSCLC, at 3 months after starting treatment, rarely (7%) have regret, and 98% expressed that they made the right decision. Other factors associated with the few patients with regret, such as decisional conflict or reduced quality of life, will also be presented. Support: NIH/NCI R01 CA-157409

Abstract not provided

Background:
Substantial evidence exists that quitting smoking after a cancer diagnosis can result in improved treatment efficacy and safety, decreased risk of recurrence and second primary cancers, and lower mortality. Based on this evidence, Cancer Care Ontario (CCO) implemented a smoking cessation program for new ambulatory cancer patients in Ontario’s 14 Regional Cancer Centres (RCCs) in 2014. Implementation is monitored centrally by CCO using performance indicators and monthly discussions with regional champions. Significant variation in implementation processes and performance metrics amongst RCCs highlighted a need for quality improvements.

Method:
Funding received from the Canadian Partnership Against Cancer enabled CCO to undertake a series of initiatives to enhance provider and patient education and to standardize processes. Based on program learnings and emerging evidence, the program model was revised from 5As (Ask, Advise, Assess, Assist, Arrange) to 3As (Ask, Advise, Act), and site-specific recommendations were provided to support consistency in implementation. Patient-facing materials, an on-line learning module, scripts and videos were developed to educate healthcare providers and patients on the health benefits of smoking cessation in order to improve rates of screening and referrals to cessation services. Importantly, two performance indicators have been included on CCO’s Regional Scorecard, which measures performance against targets and determines an RCC’s overall performance ranking within the province.

Result:
Performance on the Tobacco Use Screening indicator (proportion of new cancer patients screened for tobacco use) was 42.0% across Ontario in April 2015 when first included on the Scorecard. By March 2017, performance had improved to 62.7%, with significant improvements seen among the lowest-performing RCCs. The Accepted a Cessation Referral indicator (proportion of tobacco users who accepted referral to cessation services) improved only modestly from 19.7% in Q1 of 2016/17 to 23.4% in Q4. This indicator will be added to the Regional Scorecard starting in 2017/18. Both indicators are discussed at the quarterly performance reviews with the Regional Vice-Presidents responsible for cancer services. In 2016/17, lung cancer patients accounted for the largest percentage of current users of tobacco by tumour site (21.9%); in addition, almost a quarter of all patients accepting a referral (24.3%) were lung cancer patients.

Conclusion:
The CCO performance Scorecard is a strong driver of quality improvement. CCO is encouraged by regional enthusiasm to adopt the refined 3As model, and anticipates further improvements in the performance metrics, especially in the number of tobacco users who accept referral to cessation services.

Background:
The National Lung Screening Trial demonstrated that lung screening reduces lung cancer mortality. In our lung screening program, the incidence of lung cancer is a small percentage (2.3% (10/440)). A more common, treatable, and potentially overlooked condition in this population is nicotine addiction (70.2% smoking (309/440) in our program). It has been widely postulated that lung cancer screening provides a “teachable moment” for smoking cessation. Smoking cessation counseling has been integrated in our lung cancer screening program since 2014. The goal is to report outcomes of integrating smoking cessation in the lung screening program.

Method:
In our lung screening program, all scheduling is done by a single coordinator who is both a Nurse Practitioner and a Certified Tobacco Treatment Specialist (CTTS). A call to schedule the scan is done and initial basic tobacco cessation intervention is integrated into every call. Further follow up as in depth face-to-face counseling is offered at the point of the scan, by the coordinator or other CTTS. Tobacco cessation follow up may be further integrated into telephone calls to give patients screening results. Patients noted to be smoking at the time of the screen (n=103) were surveyed by telephone by a researcher to determine whether they had quit smoking, reduced, or made no changes. Further chart review yielded 107 additional patients unable to be reached by the researcher, but data regarding smoking was available from medical records.

Result:
Of the patients able to be contacted by telephone, 11.7% (12/103) quit smoking, 53.4% (55/103) had reduced the amount they were smoking, and 35.0% (36/103) had made no changes. Additional chart review yielded 107 patients screened and 14.0% (15/107) had documented cessation at least one year after screening.

Conclusion:
Integration of tobacco cessation counseling into our lung screening program led to an overall quit rate of 12.9% (27/210) and of those interviewed, 60.4% (55/91) of those who did not quit, reduced the amount that they smoked. While this may sound modest, this population is heavily addicted, and unaided cessation has poor success rates, often cited as less than 4%. This supports integration of cessation counseling as a potential model for improving smoking cessation in the lung screening population. Further work with integrating pharmacotherapy and more frequent regular follow up may yield even higher success rates.

Background:
Although the best way for smokers to avoid the health risks associated with smoking is to quit smoking altogether, for those who do continue to smoke the application of a harm reduction strategy could result in substantial reductions in mortality and morbidity. One such approach for continuing smokers would be to promote the substitution of alternative, less toxic means of delivering nicotine, assuming that these were proven to be less hazardous than tobacco smoking and did not cause any additional health risks. Electronic cigarettes, commonly called "e-cigarettes", represent a new stage in which nicotine is delivered in a method that simulates smoking but without involving a tobacco combustion process.

Method:
We measured levels of selected carcinogens and toxicants in aerosol generated from e‑cigarettes. Using in vitro systems, we studied toxicological effects of e-cigarette aerosol on bronchial epithelial cells. In a longitudinal within-subjects observational study, we assessed exposure to nicotine and selected carcinogens in cigarette smokers who switched to e-cigarettes. In a cross-sectional study, we compared exposure to nicotine and carcinogens among smokers of combustible cigarettes only, e-cigarette user, former smokers with long-term nicotine replacement therapy (NRT) use, and dual users of both combustible cigarettes and e-cigarettes.

Result:
Nicotine solutions used in e-cigarettes vary with respect to concentrations of toxicants. We identified a number of toxicants in e-cigarettes; however the levels of these toxicants were orders of magnitude lower than those found in cigarette smoke. In vitro studies showed that cell viability and metabolic activity were more adversely affected by conventional cigarettes than e-cigarettes. In longitudinal observational study of smokers, we found that after switching from tobacco to e-cigarettes nicotine exposure is unchanged while exposure to toxicants is substantially reduced. Long-term e-cigarette use, but not dual use of e-cigarettes with combustible cigarettes, is associated with substantially reduced exposure levels to carcinogens relative to smoking combustible cigarettes.

Conclusion:
Although it cannot be said that currently marketed e-cigarettes are safe, e-cigarette aerosol is likely to be much less toxic than cigarette smoke. The devices likely pose less direct hazard to the individual smoker than tobacco cigarettes and might help smokers quit smoking or reduce harm by smoking fewer cigarettes. The use of e-cigarettes as a harm reduction strategy among cigarette smokers who are unable to quit, warrants further studies. Further research is needed to evaluate long term effects of switching, including the health effects of continued use of e-cigarettes.

Background:
Lung cancer screening might be a ‘teachable moment’ for smoking cessation or conversely could provide a ‘license to smoke’. Such effects should be considered in the overall benefits and harms of screening. Existing evidence of the impact of screening on smoking is mixed.

Method:
A randomised controlled trial of a blood autoantibody test (EarlyCDT-Lung) for the early detection of lung cancer was conducted in 12,210 smokers and ex-smokers in Scotland, UK. The test allowed risk stratification for targeting of a chest X-ray and repeat CT scans. Sub-samples of positive test (n = 321), negative test (n = 361) and control (n = 350) participants completed questionnaires before screening, after receipt of blood test results and at 3, 6 and 12 months post-screening. They self-reported smoking point prevalence, attempts to quit, number of cigarettes smoked per day and the Heaviness of Smoking Index. Multi-level regression analyses, adjusted for confounders, explored differences in smoking over time between screened and control arms and between positive test, negative test and control groups.

Result:
Preliminary results show no statistically significant differences in smoking prevalence between the screened and control arms over time. There was a reduction in smoking prevalence of borderline statistical significance in the positive test group versus controls across all time points (OR 0.46, 95% CI 0.21-1.03). This difference reduced when assuming non-responding smokers were still smoking (OR 0.55, 95% CI 0.25-1.19). Significantly more smokers in the positive test group had recently attempted to stop smoking at 3 months compared to controls (OR 2.29, 95% CI 1.04-5.04). Positive test group smokers were significantly less likely to report smoking 20 or more cigarettes a day than controls across all time points (OR 0.32, 95% CI 0.14-0.69). Negative test group smokers were more likely to score moderate/high/very high on the Heaviness of Smoking Index compared to controls at 6 months. This difference was statistically significant before adjusting for confounders but the adjusted model was no longer significant (OR 2.51, 95% CI 0.90-6.97).

Conclusion:
There was no effect of lung cancer screening on smoking prevalence. The findings indicate a positive test result can be a teachable moment for smoking cessation. They also highlight the short term risk of heavier smoking after a negative test result. This is an important area for further research to ensure negative lung cancer screening test results do not inadvertently promote continued and heavier smoking.

Abstract not provided

Background:
The median age at diagnosis of lung cancer is 70 years. Older patients are often not prescribed standard therapy. Due to multiple competing causes of death, older patients often do not demonstrate a benefit in overall survival (OS). It is important to know which older patients would actually be candidates for aggressive therapy based on their prognosis, and to develop a simple prognostic model that can help clinicians determine individual prognosis.

Method:
Data on patients enrolled on 38 NCI-sponsored cooperative group clinical trials of advanced non-small cell lung cancer (NSCLC) from 1991 to 2011 were analyzed. Multivariable Cox PH model was built with a stepwise procedure with all potential predictors: age, sex, race, ethnicity (Hispanic or non-Hispanic), performance status, initial stage, BMI, and weight loss in the past 3/6 months. We derived a prognostic score using the estimated Cox PH regression coefficient in the training set. To assess the performance of our prognostic model, we calculated the area under receiver operating characteristic (ROC) curve of 1- and 2-year survival in the testing set.

Result:
The final analysis included 1454 NSCLC patients ≥70 years of age. These patients were randomly divided into a training set (n=962) and a testing set (n=492). The prognostic risk score was calculated as: 3 (if male) + 3 (if PS=1) + 8 (if PS=2) + 11 (if initial stage=IV) + 4 (if weight loss). Patients were classified into three prognostic groups by tertiles: good (0-6), intermediate (7-14) and poor (≥15). The median OS in the three groups in the testing set were: 14.6 months (95% CI, 12.2-18.5); 12.2 months (95% CI, 10.7-14.4) and 7.0 months (95% CI, 5.6-8.9), respectively. Despite its simplicity, the present model had area under the 1-year and 2-year ROCs (0.63 and 0.68, respectively) that were higher than existing models.

Conclusion:
Male gender, poor performance status, distant metastases and weight loss immediately prior to diagnosis predict for poor OS in older patients with advanced NSCLC. This study proposes a simple prognostic model for older adults with advanced NSCLC based on basic clinical characteristics that are part of the routine evaluation process for every patient with NSCLC.

Background:
Overall survival and in-hospital mortality in resectable non-small cell lung cancer (NSCLC) patients varies with race. Asian patients have a better overall survival compared with White and Black patients, however, the prognostic factors contributing to these differences are still under studied. The aim of this study was to identify race-specific prognostic factors of overall mortality and in-hospital mortality in resectable NSCLC patients.

Method:
Using the Surveillance, Epidemiology, and End Results Registry linked to Medicare claims between 1991-2010, 35,461 NSCLC patients who underwent pulmonary resection were extracted. Factors associated with in-hospital mortality and overall mortality stratified by Asian and White were analyzed by multivariable logistic regression analysis and multivariable cox regression analysis, respectively.

Result:
Factors associated with in-hospital mortality in Asian patients were age ≥ 80 years (adjusted odd ratios (OR~adj~)=5.8, 95% Confidence interval (CI)=1.59-21.23), stage III disease (OR~adj~=3.93, 95%CI=1.55-9.96), lower lobe lesion (OR~adj~=3.52, 95%CI=1.54-8.02), pneumonectomy (OR~adj~=11.12, 95%CI=2.61-47.34), postoperative pulmonary complication (OR~adj~=5.39, 95%CI=2.51-11.56), postoperative infections (OR~adj~=28.19, (95%CI=10.62-74.83), and intraoperative complication (OR~adj~=10.87, 95%CI=2.64-44.79). In White patients factors associated with in-hospital mortality were old age, male gender, higher comorbidity index, advanced stage, non-teaching hospital, lower hospital volume, pneumonectomy, preoperative radiotherapy, postoperative and intraoperative complications. Factors associated with overall mortality in Asian patients were age ≥ 80 years (HR~adj~=1.63, 95%CI=1.23-2.16), higher Elixhauser comorbidity index (HR~adj~=1.02, 95%CI=1.01-1.04), lower median income, stage (HR~adj~(95%CI) =1.89(1.41-2.54) for stage II, 2.19(1.69-2.83) for stage III, and 3.85(2.59-5.73) for stage IV versus stage I), non-teaching hospital, and receiving radiotherapy (HR~adj~=1.76,95%CI=1.35-2.30). In White patients, factors associated with overall mortality included old age, male gender, single status, higher comorbidity index and score, lower median income, higher stage, non-squamous cell carcinoma, higher tumor differentiation, location of tumor, lower hospital volume, pneumonectomy, no mediastinal lymph node dissection, and receiving chemotherapy or radiotherapy.

Conclusion:
Race specific differences in number and type of prognostic factors for in-hospital and overall mortality point at biological differences in the tumor as well as differences in treatment.

Background:
While most cancer therapies are associated with toxicities, a major component of cancer treatment is to reduce cancer-related symptoms and impairment of function. Assessing how well this goal is achieved is dependent on accurate assessments of baseline symptoms prior to initiation of therapy. The objectives of this study were to describe the symptom burden of treatment-naïve lung cancer patients and to examine demographic and disease factors that correlate with symptom severity.

Method:
Symptom data from 460 treatment-naïve patients with lung cancer were obtained using the validated MD Anderson Symptom Inventory via a 0-10 numeric rating scale. Descriptive statistics were used to summarize patient demographic and clinical characteristics. Differences in symptom severity, symptom interference and quality of life by disease stage and histology were examined using either t-test or ANOVA. Multiple linear regression analysis was performed using age, gender, tumor stage and histology to determine significant predictors of pain and shortness of breath.

Result:
The most severe symptoms were fatigue, disturbed sleep, distress, pain, shortness of breath, sadness and drowsiness. About 62% of patients had at least one moderate to severe (rated 5 or greater) symptom, while 48% had at least one severe (rated 7 or greater) symptom. Disturbed sleep, distress, shortness of breath, sadness, and drowsiness were reported to be severe by at least 16% of the patients. As expected, patients with advanced stage had significantly more severe symptoms. Patients with small-cell carcinoma reported the most severe pain and shortness of breath. Multiple linear regression analysis showed that stage was a significant predictor of pain severity while controlling for histology, age and gender. Patients with advanced stage had a pain level that was 1.2 higher than patients with early stage disease (95% CI= 0.5 – 1.8, p<0.001. For shortness of breath, both histology and stage were significant predictors of severe levels while controlling for age and gender. Patients with advanced stage had a shortness of breath level that was 0.9 higher than patients with early stage disease (95% CI= 0.4 – 1.6, p<0.001). Patients with small cell carcinoma had a shortness of breath level that was 1.5 higher than those with adenocarcinoma (95% CI= 0.35 – 2.6, p<0.01).

Conclusion:
In conclusion, as much as 62% of treatment-naïve patients with lung cancer reported at least one moderate-to-severe symptoms prior to initiation of cancer therapy. This high burden suggests that symptoms should be assessed routinely and tracked in parallel with cancer treatment.

Background:
Despite multiple efforts led by the National Cancer Institute (NCI) specific patient populations remained underrepresented in cancer clinical trials (CT). Therefore, we determined the representation of minorities, the elderly, and women in lung cancer CT in the past 16 years.

Method:
Clinicaltrials.gov was queried on December 31[st], 2016 for all completed therapeutic lung cancer trials from 2000 to 2016. Trials with recruitment outside of the U.S. were excluded. Enrollment fraction (EF) was defined as the number of enrollees divided by the 2013 SEER cancer prevalence. Geographic location was classified within the 5 major U.S. regions: Northeast, Southeast, Midwest, Northwest and Southwest.

Result:
Out of 320 CT, only 88 trials (27.5%) reported race/ethnicity comprising 11, 723 enrollees. Industry sponsored 65% of the trials. Non-Hispanic whites (NHW) were more likely to be enrolled in CT (EF 2.8%) than African Americans (AA) (EF 1.5%, p<0.001) and Hispanics (EF 2.1% p<0.03). Asian patients were well represented (EF 9.2 %). Distribution by race and sex is described on Table 1. Only 44 (50%) trials divided participants by age (<65 or ≥65 years). The representation of trial participants was heavily skewed towards the younger age group. Median age was 62 years and 8,440 (72%) participants were <65 years of age (p<0.001). Industry sponsored trials were less likely to enroll Hispanic patients than NCI sponsored trials (1.1% vs. 3.8%). African Americans were less likely to be recruited in first line trials compared to NHW (11% vs. 36%, p<0.0001). Underrepresentation of minorities was not affected by recruitment site geographic location.

Conclusion:
NHW were more likely to be enrolled in clinical trials than African American and Hispanics, independent of the recruitment site geographic location. Collaboration between investigators, NCI, industry, and the community is necessary to ensure broad access of unrepresented populations to clinical trials.

Race/Ethnicity	2000-2016 Trial Participants n/%	Enrollment Fraction %	2013 Lung Cancer Prevalence %
Non-Hispanic White	9,350 (79.8)	2.8	82.7
African American	638 (5.4)	1.5	10.6
Hispanic	314 (2.7)	2.1	3.6
Asian/PI	1083 (9.2)	8.7	3.1
Native American	75 (0.6)	N/A	N/A
Other	263 (2.2)
Sex
Female	4,571 (39)	2.0	55.2
Male	7,152 (61)	3.8	44.8

Abstract not provided

Background:
In recent years, clinical studies on screening for lung cancer have demonstrated an initial lung cancer detection rate of 0.8-2.2%, with a total of 2.4-4.7% in 34-78 months of follow up. The National Lung Screening Trial (NLST), which compared screening by LDCT to annual chest X-ray, showed a 20% decrease in mortality in the screened population. Transitional cell carcinoma of the bladder (TCC) has a high survival rate, and has similar risk factors to lung cancer. Thus, TCC patients may stand to benefit from lung cancer screening.

Method:
The SEER (Statistics, Epidemiology and End Results) database was used to determine the incidence, Person-years at risk and the average time to diagnosis of lung cancer in patients with localized TCC of the bladder (American Joint Committee on cancer, 6[th] ed., stages 0-1) in years 2000-2013. Cumulative Incidence rates were calculated and stratified by age, sex and county level smoking data.

Result:
Based on 88,564 patients with localized TCC (F:M ratio 1:3.3), the 5 year incidence of lung cancer was 3.16%, and 10 year incidence was 5.85%. among patients over 40 from counties with a high percentage of smokers, the 5 year incidence of lung cancer was 3.46%, and 10 year incidence was 6.64%. The median time until diagnosis of lung cancer was 3.89 years for men and 3.16 years for women for ages 60-79, the age group with the highest incidence. Figure 1



Conclusion:
Incidence of lung cancer is high in localized TCC patients and comparable to results seen in the high risk groups currently being screened. Early stage TCC patients may therefore stand to gain from lung cancer screening, and should be considered as potential screening candidates.

Background:
Epidemiological studies commonly use data from clinical (i.e. medical records) and administrative (i.e. claims data) datasets for the purposes of exploratory analyses, as well as clinical and quality reporting, benchmarking, risk adjustment, and machine learning. Validity is contingent on accurate and detailed reporting of data, demanding robust methodological validation.

Method:
Single centre retrospective comparative study assessing completeness and agreement (kappa-statistic (κ)) of data reporting for key prognostic variables across three independent data sources, among patients with lung cancer. The study population was formed by random selection of patients from an Australian single centre prospective study. Prospectively collected research study-data (SD) was extracted, and then compared to data extracted from individual patient medical records (MR) as well as International Classification of Diseases (ICD) coding from administrative data (AD).

Result:
The study population included 10% of patients from an Australian lung cancer cohort (n=111/1090), and represented the overall cohort in terms of patient demographics and disease characteristics. Prognostic data for stage, comorbidities, smoking history, performance status, and weight loss at diagnosis, was reported for >96% of patients in SD. Comparatively, AD did not report any prognostic data for 42% (47/111) of patients treated in ambulatory settings, and indeed when reported was grossly inaccurate. By way of examples, according to AD, 23% of patients had ≥1 comorbidity versus 68% by MR and 64% by SD; 38% had positive smoking history versus 78% by MR and 81% by SD; 2% had respiratory comorbidity versus 28% by MR and 37% by SD. Similar patterns were observed for other comorbid conditions. Complete TNM staging was captured in only 45% of MR at the time of first treatment, although with good concordance with SD (κ=0.9, 95%CI 0.7, 1.0). Equally when factors were documented in MR they were reasonably concordant with SD: smoking status (completeness 96.4%, κ=0.9, 95%CI 0.8, 1.0), performance status (completeness 82.0%, κ=0.5, 95%CI 0.4, 0.7) and weight loss (completeness 71.1%, κ=0.3, 95%CI 0.1, 0.5).

Conclusion:
Poor capture of factors (either omission or inaccuracy) limit the potential contribution of both MR and AD for use in clinical, epidemiological, and machine learning research – particularly when being utilised to derive diagnostic, prognostic and classification systems. Use of this data for purposes other than intended may misinform estimates of comorbidity disease burden and fail to appropriately adjust for competing mortality risks in models that inform outcomes reporting and ensuing policy decisions.

Background:
Mutations of epidermal growth factor receptor (EGFR) gene have been proved as the strongest predictor of response to EGFR-tyrosine kinase inhibitor (TKI) treatment in NSCLC. Currently, 7 most common somatic mutations of EGFR have been reported, among which, L858R and exon 19 deletion theoretically confer sensitivity to EGFR TKIs, other primary EGFR mutations may confer resistance. The EGFR mutation profile showed significant geographical differences (about 35% in East-Asia and 10% in Caucasian population) but very limit data have been reported from China. In addition, we carried liquid biopsy and next generation DNA sequencing analysis on 180 samples from NSCLC patients. We hereby reported the mutation profile EGFR gene in a large scale, real world cohort of 2,666 Chinese NSCLC patients.

Method:
From January 2016 to June 2017, 7 primary EGFR mutations (L858R, Exon 19 del, G719X, L861Q, Exon 20 ins, S768I and T790M) were assayed in tumor tissue (paraffin-embedded or fresh) of 2,666 Chinese patients with NSCLC by a commercial TaqMan PCR kit (Human EGFR Gene Mutations Detection Kit（ACCB）). For liquid biopsy analysis, cell-free DNA is extracted from plasma, a panel of 96-targeted genes was assayed, and genomic alterations in cancer-associated somatic variants are analyzed by massively parallel sequencing.

Result:
Among the 2,666, 1,601(45.9%) were female and 1,447(54.1%) were male, 2,446 (91.7%) had adenocarcinoma (ADC) and 220(8.3%) had squamous carcinoma (SC).The median age of patients was 63 yr (range 17yr-91yr). The detailed EGFR mutation profile was shown in Table 1, the overall incidence of EGFR mutation was 1,319(49.5%). Compare to female patients, male patients showed significant lower rate of EGFR mutation (67.2% vs. 34.6%, p<0.01). More than 50% of patients with ADC showed EGFR mutation while the rate was only 10% in patients with SC. Exon 19 del and L858R, 2 markers for potential better response of TKI, account for the vast majority of all the EGFR mutations. We found the mutation profiles from samples analyzed by NGS is similar to those analyzed by PCR method.

Conclusion:
In Chinese NSCLC female patients with lung adenocarcinoma, exon 19 del and L858R represented more than 90% of the total EGFR mutations, thus, for those whose EGFR status was unable to be determined, direct TKI treatment many has an odd of 60% to benefit the patients. About 5% of SC patients also showed exon 19 del and L858R mutation which means they could be subjects for TKI treatment.

Background:
As the lung cancer treatment landscape evolves, it is important to understand changes in care and outcomes of patients with NSCLC. SCAN-LEAF objectives include describing NSCLC disease, treatments and health outcomes in Scandinavia (Denmark, Norway and Sweden). The present analyses examined treatment proportions and temporal trends in overall survival, drawing on national registry data.

Method:
NSCLC patients diagnosed 2005-2013 (follow-up until 2014) were included in the present analyses of this retrospective longitudinal cohort study. Patient characteristics and treatment described included demographics, disease stage at initial diagnosis [resectable: I-IIIA; locally advanced: IIIA-B (radiation therapy within 3 months); advanced: IIIB (no radiation therapy within 3 months)-IV], histology, non-drug treatment (surgery and radiation: present analyses include Norway and Sweden 2008-2014 only), and survival. Overall survival (OS) (%+95% CI) was calculated 1, 3, and 5 years post-diagnosis, by stage, and by diagnosis year.

Result:

Table 1. Proportion NSCLC patients from Denmark, Norway and Sweden diagnosed during 2005-2013 who survived 1, 3 and 5 years after diagnosis, by stage and calendar year of diagnosis.
Stage at diagnosis & Calendar year of diagnosis	% survived 1-, 3- and 5-years after NSCLC diagnosis
	1-year	3-year	5-year
Resectable disease
Overall	81.0% (80.4%, 81.6%)	56.8% (55.9%, 57.7%)	43.5% (42.5%, 44.6%)
2005	74.7% (72.5%, 77.0%)	51.0% (48.5%, 53.6%)	40.0% (37.4%, 42.5%)
2006	77.0% (74.8%, 79.2%)	53.3% (50.7%, 55.9%)	42.3% (39.7%, 44.8%)
2007	78.6% (76.6%, 80.7%)	55.0% (52.5%, 57.5%)	43.5% (41.1%, 46.0%)
2008	80.6% (78.6%, 82.5%)	56.4% (53.9%, 58.8%)	44.2% (41.7%, 46.7%)
2009	79.7% (77.7%, 81.7%)	57.4% (55.0%, 59.8%)	45.8% (43.3%, 48.2%)
2010	81.4% (79.6%, 83.2%)	59.1% (56.8%, 61.4%)
2011	83.1% (81.4%, 84.7%)	61.2% (59.0%, 63.4%)
2012	85.5% (84.0%, 87.0%)
2013	84.2% (82.7%, 85.8%)
p-value trend	<0.0001	<0.0001	0.0008
Locally advanced disease
Overall	52.0% (51.0%, 53.0%)	18.4% (17.5%, 19.3%)	10.8% (9.9%, 11.6%)
2005	45.7% (42.4%, 49.0%)	13.9% (11.6%, 16.2%)	7.8% (6.1%, 9.6%)
2006	45.7% (42.3%, 49.1%)	15.4% (12.9%, 17.8%)	10.7% (8.6%, 12.9%)
2007	51.5% (48.2%, 54.7%)	18.6% (16.0%, 21.1%)	11.0% (9.0%, 13.1%)
2008	50.0% (46.7%, 53.3%)	17.0% (14.5%, 19.4%)	10.3% (8.3%, 12.3%)
2009	50.9% (47.8%, 54.0%)	19.8% (17.4%, 22.3%)	12.9% (10.8%, 15.0%)
2010	51.1% (48.1%, 54.1%)	18.9% (16.5%, 21.2%)
2011	55.9% (53.1%, 58.7%)	21.2% (18.9%, 23.5%)
2012	57.0% (54.2%, 59.9%)
2013	56.1% (53.2%, 59.0%)
p-value trend	<0.0001	<0.0001	0.0021
Advanced disease
Overall	26.2% (25.7%, 26.6%)	6.3% (6.0%, 6.6%)	3.4% (3.2%, 3.7%)
2005	24.4% (23.1%, 25.8%)	6.3% (5.5%, 7.0%)	3.5% (2.9%, 4.1%)
2006	24.2% (22.8%, 25.5%)	6.1% (5.4%, 6.9%)	3.4% (2.8%, 4.0%)
2007	25.7% (24.4%, 27.0%)	5.9% (5.2%, 6.6%)	3.1% (2.6%, 3.7%)
2008	25.0% (23.7%, 26.3%)	6.0% (5.3%, 6.7%)	3.3% (2.8%, 3.9%)
2009	26.5% (25.0%, 28.0%)	6.9% (6.0%, 7.8%)	3.9% (3.2%, 4.5%)
2010	26.3% (24.9%, 27.7%)	7.0% (6.2%, 7.8%)
2011	27.4% (26.1%, 28.8%)	6.2% (5.4%, 6.9%)
2012	28.1% (26.7%, 29.5%)
2013	27.9% (26.6%, 29.3%)
p-value trend	<0.0001	0.2480	0.5359

66,012 NSCLC patients were diagnosed during 2005-2013 in Scandinavia (53.6% male, mean age 68.9 years); diagnosis stage: resectable (26%), locally advanced (15%), advanced (59%). In Norway and Sweden, surgery was performed on 58.5%, 9.9% and 1.9% of patients at resectable, locally advanced and advanced stage, respectively; radiation therapy in 28.0%, 58.0% and 30.4%, respectively. 1-yr OS gradually and significantly improved by calendar year of diagnosis for all disease stages. At 3 and 5 years post-diagnosis, OS was positively and significantly associated with calendar year of diagnosis for patients with resectable and locally advanced, but not advanced disease (Table 1).

Conclusion:
These analyses showed modest improvements in survival for patients with earlier stage disease over time. However, the majority of patients were diagnosed with advanced stage disease for which no improvement in temporal trends of survival was found, beyond one year post-diagnosis. This suggests an unmet need for effective treatments still remains, particularly for patients with advanced disease.

Abstract not provided

Abstract:
Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide. For many years, NSCLC has been considered an easy to treat disease, with few chemotherapeutic agents producing a limited survival improvement in unselected patients. In the last decade, identification of key genetic events driving tumor growth and metastatic spread led to postulate the concept of oncogene-addiction. According to this model, the inhibition of certain molecular drivers by targeted agents could be effective in reducing tumor burden and improving patient outcome. This is the case of Epidermal Growth Factor Receptor (EGFR) and its activating mutations. Strategies against EGFR mutant (EGFR[mut]) NSCLC represent a relevant example on how genomic discoveries dramatically changed clinical practice. The most common – also named classic - EGFR mutations are inframe deletions in exon 19 or the Leu858Arg (L858R) point mutation in exon 21. Nine large randomized trials conducted in more than 1900 patients harboring classical EGFR mutations clearly demonstrated the superiority of EGFR tyrosine kinase inhibitors (TKIs), such as gefitinib, erlotinib or afatinib, when compared to conventional platinum-based chemotherapy. Additional rare EGFR mutations, such as point mutations in exon 18, have been associated with some sensitivity to first and second generation EGFR TKIs, although their ability to predict radiological and clinical response to such drugs is less striking than that of classic EGFR mutations. However, despite an initial dramatic response, virtually all EGFR[mut+ ]NSCLC progress due to the occurrence of acquired resistance. So far, several mechanisms underlying acquired resistance to EGFR-TKIs have been elucidated and they conventionally belong to two categories. The first group of mechanisms is considered as target-dependent, because they preserve the dominance of EGFR signaling and occur preferentially through secondary mutations in the kinase domain of the receptor. The first and most well characterized is the T790M mutation, also called ‘gatekeeper’ mutation for its ability to interfere with the ligand site of EGFR TKIs. The second group includes non-target dependent mechanisms, as they determine i) activation of other oncogenes, such as BRAF and PIK3CA, ii) up-regulation of other signaling pathways, such as MET, HER2, fibroblast growth factor receptor (FGFR), and AXL and iii) histologic transformation, mainly represented by small cell transformation or epithelial to mesenchymal transition. Identification of the molecular mechanisms responsible for resistance to EGFR-TKIs is of crucial relevance in clinical practice so that new effective therapeutic strategies may be developed for our patients. As the T790M accounts for approximately 60% of the EGFR TKIs failures, investigations have focused on the potential efficacy of a new class of drugs that irreversibly inhibit mutant EGFR, in particular T790M, with minimal or no activity against wild-type EGFR. This new class of agents includes several new drugs, with osimertinib (Tagrisso, AZD9291) as the most promising. Osimertinib is a mutant-specific EGFR-TKI currently approved for the treatment of pretreated EGFR[T790M+] patients. In the AURA 3 trial, 419 EGFR[T790M+] patients who had disease progression after first-line EGFR-TKI therapy, were randomized to receive either osimertinib or chemotherapy. The study demonstrated that osimertinib was superior to standard chemotherapy in terms of response rate (RR, 71% versus 31%, p<0.001) and progression-free survival (PFS, 10.1 versus 4.4 months, p<0.001). Among 144 patients with metastases to the central nervous system, the median duration of progression-free survival was longer among patients receiving osimertinib than among those receiving platinum therapy plus pemetrexed (8.5 months vs. 4.2 months). The proportion of patients with adverse events of grade 3 or higher was lower with osimertinib (23%) than with platinum therapy plus pemetrexed (47%). An ongoing study evaluating osimertinib versus first-generation TKIs as first-line treatment for patients with EGFR mutation-positive NSCLC may help to define the role of the drug as front-line therapy (FLAURA trial). Unfortunately, acquired resistance to osimertinib therapy also occurs and identification of mechanisms responsible for drug failure is of clinical relevance. A report first describing the development of a resistance mutation, C797S, in a patient enrolled in the AURA phase I trial was submitted for publication 10 months prior to the FDA approval of osimertinib. Interestingly, preclinical models harboring an EGFR activating mutation alone (exon 19 deletions or L858R point mutations) that develop resistance through C797S are still sensitive to gefitinib or afatinib. The immediate clinical consequence is that the latter EGFR-TKIs could be offered to patients developing resistance after initial therapy with osimertinib. By contrast, models harboring three EGFR mutations (Del 19 or L858R plus T790M plus C797S) were resistant to all currently available EGFR-TKIs, with cetuximab still retaining some activity. Similarly to first or second-generation EGFR-TKIs, additional mechanisms of resistance have been described, including small-cell lung cancer transformation, activation of the NRAS pathway, MET amplification or FGFR3 mutation. Therefore, identification of mechanisms of resistance to EGFR-TKIs is of crucial relevance for defining which agent should be used first and the best sequencing of treatment. In conclusion, discovery of EGFR mutations led to a dramatic change in approaching NSCLC therapy. Several additional molecular events have been more recently identified, including ALK or ROS1 rearrangements, providing evidence that investigations at the genomic level are crucial in defining new and more effective strategies against cancer.

Abstract:
Small cell lung cancer (SCLC) is a neuroendocrine subtype of lung cancer characterized by a fast growth rate, extensive dissemination, and rapid resistance to chemotherapy. Survival rates are dismal and have not significantly improved in the past few decades. Sequencing the genomes of over 100 human SCLC demonstrates universal inactivation of p53 and RB and identified inactivating recurrent mutations in NOTCH family genes (1). Accordingly, we found that activation of Notch signaling in a pre-clinical SCLC mouse model dramatically reduces the number of tumors and extends the survival of the mutant mice (1). Thus, Notch plays a key tumor suppressive role in SCLC and strategies to re-activate Notch in SCLC tumors may be beneficial to patients. We will present recent work focusing on the possible role of Notch-negative and Notch-positive cells in SCLC tumors during cancer progression and in response to chemotherapy (2). We will discuss how these results may be translatable to the clinic. At the histological level, SCLC tumor cells are often viewed as homogeneous. Our new studies and previous studies (3) identify several levels of intra-tumor heterogeneity in SCLC, which may contribute significantly to SCLC aggressive nature and resistance to therapy. 1. George J, Lim JS, Jang SJ, et al. Comprehensive genomic profiles of small cell lung cancer. Nature 2015;524:47-53. 2. Lim JS, Ibaseta A, Fischer MM, et al. Intratumoural heterogeneity generated by Notch signalling promotes small-cell lung cancer. Nature 2017;545:360-364. 3. Calbo J, van Montfort E, Proost N, et al. A functional role for tumor cell heterogeneity in a mouse model of small cell lung cancer. Cancer Cell 2011;19:244-256.

Abstract not provided

Background:
Low-dose CT (LDCT) screening of smokers at high risk of developing lung cancer has been shown to reduce LC-specific and overall mortality. A retrospective analysis of the National Lung Screening Trial (NLST) data suggests that smoking cessation contributed to the mortality reduction. Pilot LDCT screening programs are being implemented in Ontario with smoking cessation integrated. The Canadian Partnership Against Cancer with Statistics Canada have developed a microsimulation model (OncoSim-LC, version 2.5) that projects the impact of cancer control measures on LC incidence, mortality and cost. Assuming that each annual visit for LDCT is a teachable moment to promote smoking cessation, we have modelled the potential cost and cost-effectiveness of integrating cessation into an organized screening program.

Method:
OncoSim-LC incorporates Canadian demographic characteristics, risk factors, cancer management approaches and outcomes and resource utilization to assess clinical, economic and healthcare system impacts. We compare a base case of organized screening with no cessation to various scenarios of screening with cessation. Modelling assumptions included: annual screening of 55-74 year olds with 30+ pack year smoking history, target participation rate reached over 10 years; one cessation intervention (nicotine replacement therapy + varenicline + 12 weeks of counselling) costs $490; up to 10 cessation attempts per eligible individual dependent on screening encounters; a permanent quit rate of 5% per cessation attempt. Cost-effectiveness was estimated with a lifetime horizon, health system perspective and 1.5% discount rate. Costs are in 2016 CAD.

Result:
Cessation within a screening program with 60% recruitment and 70% rescreening (adherence) would cost approximately $76 million (undiscounted) per year for 2017-2036 or 8% of the total cost of screening, treatment and cessation. Compared to screening with no cessation, approximately 110 fewer incident cases and 50 fewer lung cancer deaths would occur on average per year for 2017-2036 and cost $14,000/QALY (lifetime horizon). 90% recruitment and 80% rescreening would result in 260 fewer deaths and cost of $24,000/QALY. At a doubled permanent quit rate of 10%, screening with cessation would cost $6,000/QALY. A 50% increase in the cost of the cessation intervention would decrease cost-effectiveness to $22,000/QALY.

Conclusion:
Based on the OncoSim-LC model, a cessation program within an organized LDCT screening program would cost well under $50,000/QALY even over multiple quit attempts. Integrating robust smoking cession initiatives within a LDCT screening program could save lives and be relatively cost-effective.

Background:
Anecdotal reports of families carrying germline EGFR mutations force us to reconsider our understanding of inherited lung cancer risk in non-smokers. We launched this prospective trial (NCT01754025; ALCMI-002) to remotely enroll and characterize these rare families.

Method:
Eligible subjects were recruited at participating cancer centers or through an online referral system. Following consent (in person or by phone), subjects received genetic counseling and sequencing of saliva or blood for germline EGFR mutations. Cancer specimens and CT scans were additionally analyzed when available.

Result:
Between 12/2012-6/2017, 105 participants were enrolled from 30 US states. Germline EGFR mutations were found in 63% of patients (31 of 49) with EGFR T790M in their lung cancer at diagnosis, and in 62% (16 of 27) and 44% (4 of 9) of first- and second-degree relatives of germline carriers. Pedigrees were available for 32 unrelated kindreds (31 germline T790M, 1 germline R776H): 4 with no family history of lung cancer, 8 with a family history of lung cancer in non-smokers, 18 with multiple relatives with lung cancer. Characteristics of 31 lung cancer probands: median age of lung cancer diagnosis was 57 (range 28-82); 81% white, 19% black; 52% never-smokers; 65% stage IV at diagnosis; 65% were from states in or bordering the US Southeast. Tumor genotyping revealed somatic EGFR co-mutations in 29 (94%) of probands: 6 exon 19 del, 12 L858R, 6 G719X, 1 exon 19 del & G719R, 1 L861Q, 2 H773R, 1 V774M. Imaging analysis suggests a unique pattern of cancer evolution including an indolent multi-focal nodular phase which then progresses to lymph nodes and then remote metastatic disease. Of 8 probands with sensitizing EGFR co-mutations treated with osimertinib, no unexpected toxicities were seen, and 4 have had durable benefit exceeding 12 months. Of 9 relatives with germline EGFR mutations and CT imaging available, 2 have a lung cancer diagnosis and 6 others have lung nodules.

Conclusion:
This study confirms the high likelihood of a germline mutation in lung cancer patients with EGFR T790M detected at diagnosis, and suggests a risk of lung nodules and lung cancer in germline carriers. The regional enrichment in the US Southeast suggests a possible founder effect; haplotyping is planned. A registry is under development to continue follow-up of these rare individuals. Further investigation of germline risk alleles associated with lung cancer risk in non-smokers is needed. Funding: Bonnie J. Addario Lung Cancer Foundation, Conquer Cancer Foundation of ASCO.

Background:
In the National Lung Screening Trial (NLST), annual CT screening reduced lung cancer-specific mortality by 20% and all-cause mortality by 7% relative to chest x-ray (CXR) screening. However, in contrast to other screening approaches, recommendations for CT screening for lung cancer is limited to older heavy smokers, where the risk of death from all smoking-related complications is high, relative to the unscreened population. In the NLST, airflow limitation affects 35% of screening participants and is associated with a 2-4 fold increase risk of lung cancer. We have recently shown that for screening participants with COPD, the reduction in lung cancer-specific mortality with CT screening is only half that seen in those with no COPD (15% vs 28%). We hypothesise that this reduction is due in part to a “competing cause of death” effect.

Method:
Using 10,054 subjects from the ACRIN-NLST sub-study, the current study aimed to compare disease-specific mortality according to the severity of airflow limitation at baseline to better understand it’s relationship with dying of lung cancer and dying of other smoking-related diseases. We also examined this relationship according to baseline risk of lung cancer, using the Brock (Lung cancer risk) Model, and outcomes from screening.

Result:
After 6.4 years of follow-up, there were 699 deaths; 189 (27%) attributed to lung cancer, 166 (24%) to cardiovascular disease, 61 (9%) to respiratory disease and 150 (21%) to other cancers. After stratifying the 10,054 subjects according to severity of airflow limitation (baseline FEV1%predicted and GOLD grade), we found that the risk of dying of lung cancer and risk of dying of other diseases diverged favouring a stronger relationship with non-lung cancer causes. After stratifying the 10,054 subjects according to their risk of lung cancer (tertiles), we found that CT screening in those at highest risk (highest tertile) had only a 12% reduction in lung cancer-specific deaths compared to 23-24% in other lower risk tertiles. This was associated with higher deaths from cardiovascular disease, respiratory disease and other cancers.

Conclusion:
In a CT screening study, where smokers were followed for a mean of 6.4 years, we found worsening lung function and higher underlying risk for lung cancer was associated with a greater tendency to die of causes other than lung cancer. We suggest smokers at the greatest risk for lung cancer, and those with worse lung function, benefit less from CT screening due to a “competing cause of death” effect.

Abstract not provided

Background:
Disparities exist in cancer outcomes. NSCLC outcomes have improved in recent years but effects of socioeconomic factors have not been reported.

Method:
The National Cancer Database with NSCLC incident cases between 2004-2013 was analyzed. Overall survival (OS) was explored by several available factors with a focus on race and socioeconomic factors.

Result:
A total of 1,150,722 NSCLC patients were included with majority White (86.4%) followed by Black (10.6%) and a smaller proportion of Asians and Hispanics. Patients were evenly distributed among income quartiles and majority were insured (96.7%), lived in a metro area (81.7%) and treated at non-academic facilities (68.5%). Overall median OS was 13.1 months and significantly better for Asians (18.2 months) and Hispanics (16.6 months) as compared to Whites (13.2 months) and Blacks (11.5 months). (Figure 1, p<0.001) Outcomes were worse with higher comorbidity score, TNM stage and treatment at community or high-volume facility. Socioeconomic factors other than race associated with worse outcome included lower education and median income, uninsured status and Central geographic region. (Table 1) Figure 1 Figure 2





Conclusion:
In this largest analysis thus far, patient race and socioeconomic factors were found to significantly influence NSCLC survival. These must be addressed for equitable healthcare benefit and outcomes.

Background:
Several large genetic studies have consistently linked the cholinergic nicotinic receptor polymorphism (CHRNA3/5, rs 16969968) to lung cancer and smoking addiction. However, we have shown that this genetic variant was also independently associated with susceptibility to chronic obstructive pulmonary disease (COPD). To date this observation, independently linking CHRNA3/5 polymorphism to both COPD and lung cancer, has not been tested prospectively in a cohort study. Using 10,054 subjects from the ACRIN-NLST cohort, a sub-study of the NLST that recruited high risk smokers and followed them for an average of 6.4 years, we examined the association between the CHRNA3/5 variant in the development of lung cancer relative to its role in COPD and lifelong smoking exposure.

Method:
We compared the frequency of the high risk AA genotype in our cohort of 10,054 high risk smokers according to their smoking status, lung function and COPD status. We also compared the lung cancer incidence rate according to the CHRNA3/5 genotype. Lastly we used stepwise logistic regression and mediation analysis to examine the role of the AA genotype of the CHRNA3/5 variant in smoking exposure, COPD and lung cancer.

Result:
Relative to healthy smoking controls, the AA genotype was associated with the presence of COPD (OR=1.3, P<0.001) and the development of lung cancer overall (OR=1.5, P<0.01), lung cancer with pre-existing COPD (OR=1.5, P=0.04), lung cancer with no COPD (OR=1.5, P=0.04). Compared to the GG and AG genotypes, the AA genotype was associated with (a) lower FEV1%pred, lower FEV1/FVC and a 19% increase in risk of COPD; and (b) greater cigs/day, pack years exposure and a 47% increased risk of lung cancer. No differences were found for age, gender, smoking duration, years since quitting and current smoking status. In stepwise logistic regression, we found that age, BMI, AA genotype, smoking exposure and lung function were independently associated with getting lung cancer. In the mediation analyses we found that the AA genotype was independently associated with smoking (OR=1.42,P<0.05), COPD (OR=1.25,P<0.05) and getting lung cancer (OR=1.37, P<0.05).

Conclusion:
This is the first prospective study to confirm that while the CHRNA3/5 variant is associated with lung cancer, more importantly this variant is also independently associated with airflow limitation (COPD). It is also the first cohort study to show that while this genetic variant is also associated with smoking exposure (triple whammy effect), this is independent of its effects on predisposition to both COPD and lung cancer.

Background:
Treatment of NSCLC is rapidly advancing and academic centers are considered equipped with better expertise. NSCLC outcome trends in novel therapeutic era and impact of initial treatment at academic centers have not been reported.

Method:
The National Cancer Database (NCDB) with NSCLC incident cases between 2004-2013 was used. Overall survival (OS) was plotted by year of diagnosis and type of treatment facility, accounting for several available factors in NCDB.

Result:
A total of 1,150,722 NSCLC patients were included and separated by initial treatment facility type (academic: 31.5%, non-academic: 68.5%). Several characteristics were significantly different between the two cohorts (Table 1). Median OS for all patients was 13.1 months and improved significantly for those diagnosed in 2010-2013 (14.8 months) as compared to 2004-2009 (12.4 months) (p<0.001). Treatment at academic centers was associated with reduced risk of death [Multivariate HR=0.91 (95% CI 0.906-0.919), P<0.001]. Four-year OS for academic and non-academic cohorts was 25% and 19%, respectively (p<0.001), the difference more pronounced in stage 1-3. (Figure 1) Figure 1 Figure 2





Conclusion:
In this largest analysis thus far, NSCLC survival has improved over time and type of treatment facility significantly influences survival. Factors influencing treatment facility choice should be addressed for easier access to academic centers.

Background:
Lung cancer screening can reduce lung cancer mortality by 20%. It is currently recommended in the USA, but not in the UK and ensuring any potential psychological harm is minimised is important. Current evidence is limited to the psychological impact of CT lung cancer screening. This study assesses psychological responses in the Early Cancer Detection Test - Lung Cancer Scotland Study (ECLS Study), whose participants have a tumour antibody blood test (Early CDT®-Lung test) and CT scans only for those with positive blood tests.

Method:
ECLS study participants were randomised to an Early CDT®-Lung test group or a control group. A sample (n=1032) participated in a nested psychological outcomes study. Questionnaires measured psychological responses (positive and negative affect scale (PANAS), lung cancer worry scale (LCWS) and impact of events scale (IES)) at baseline and 1, 3, 6 and 12 months post-trial recruitment. Psychological responses over time were assessed using multilevel modelling and compared between those in the control group, the test-positive group and the test‑negative group.

Result:
In total, 350, 361 and 321 participants were in the control, test-negative and test-positive groups respectively. Follow-up questionnaire completion rates were ≥90% at all time-points. Baseline psychological measures did not differ significantly between groups. Significant differences were found between PANAS scores, but absolute differences between the groups were very small and unlikely to be clinically significant. The IES avoidance and intrusion scores were significantly higher in the positive than the negative group at all time-points and at 1, 3 and 6 months respectively. However, median scores for both subscales at all the time-points were in the subclinical range. Anxiety about future tests and treatment at 1 month was significantly higher in the test-positive group than the control (OR (95%CI) 3.55 (1.70, 7.41)), or the negative group (OR (95%CI) 5.74 (2.69, 12.2)). Worry about getting lung cancer in the future was significantly higher in the test-positive than the test-negative group at 1 month (OR (95%CI) 2.61 (1.35, 5.02)), 3 months (OR (95%CI) 2.52 (1.30, 4.87)) and 6 months ((OR (95%CI) 2.98 (1.53, 5.82)).

Conclusion:
Lung cancer screening using a blood test followed by CT scanning for test-positive individuals does not appear to impact on affect, intrusive thoughts or avoidant behaviour to a clinically important degree. However, anxiety about future tests and treatment and future worry about lung cancer needs to be addressed if lung cancer screening is implemented in the UK.

Abstract not provided