Virtual Library

Abstract not provided

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Background:
TAILOR (NCT00637910) was a phase 3 randomized trial comparing erlotinib over docetaxel in second line treatment in EGFR wild-type patients. The prognostic and predictive value of KRAS is still debatable. Taking advantage from the available tissue samples and clinical data of this trial, we performed sequencing of a customized gene panel in order to identify novel biomarkers and new potential therapeutic targets specifically associated to KRAS.

Methods:
NGS was performed on PGM Ion Torrent platform and involved 111 genes. 5% of frequency was used to define mutations. Association with clinical features or between genes was performed with non-parametric test. Cox regression model was used to define the prognostic role of mutated genes on survival.

Results:
188 out of 222 randomized patients had available tissue. 134 tissues were successfully sequenced. 3 were EGFR mutated, 47 were KRAS mutated (36%). 68 were in erlotinib arm and 63 in docetaxel arm. Biomarkers associated to KRAS were 21 LKB1 (16%) and 61 p53 (46%). Survival results are described in the table.rnTable: LBA3rn

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rn	PFS	PFS	OS	OS
	Univariate	Multivariate	Univariate	Multivariate
	HR (95%CI) p-value	HR (95%CI) p-value	HR (95%CI) p-value	HR (95%CI) p-value
KRASwt/LKB1wt	reference	rn	rn	rn
KRASmut/LKB1wt	0.76 (0.51-1.15) p 0.19	0.79 (0.51-1.22) p 0.29	0.78 (0.51-1.19) p 0.25	0.75 (0.49-1.17) p 0.21
KRASwt/LKB1mut	1.42 (0.68-2.95) p 0.35	1.43 (0.67-3.08) p 0.35	1.69 (0.81-3.52) p 0.16	1.59 (0.75-3.4) p 0.23
KRASmut/LKB1mut	1.18 (0.64-2.19) p 0.59	1.29 (0.67-2.49) p 0.45	1.32 (0.72-2.45) p 0.37	1.34 (0.69-2.61) p 0.38
KRASwt/tp53wt	reference	rn	rn	rn
KRASmut/tp53wt	0.80 (0.49-1.31) p 0.37	0.87 (0.51-1.46) p 0.86	0.88 (0.53-1.46) p 0.61	0.85 (0.50-1.46) p 0.56
KRASwt/tp53mut	1.23 (0.79-1.91) p 0.35	1.41 (0.88-2.26) p 0.15	1.38 (0.88-2.16) p 0.15	1.55 (0.95-2.55) p 0.81
KRASmut/tp53mut	1.07 (0.62-1.82) p 0.81	1.11 (0.64-1.94) p 0.70	1.14 (0.66-1.98) p 0.64	1.12 (0.63-1.97) p 0.70

rn

Conclusions:
In TAILOR, KRAS was not prognostic. The association with LKB1 and p53 does not affect prognosis, while LKB1 mutation could be a negative prognostic factor (HR = 1.39). Further research is needed to prospectively assess this pathway.

Clinical trial identification:


Legal entity responsible for the study:
Fondazione IRCCS Istituto Nazionale Tumori, Milan

Funding:
AIRC (Associazione Italiana Ricerca Cancro)

Disclosure:
All authors have declared no conflicts of interest.

Background:
EGFR inhibitors are approved for use in patients with EGFR mutant NSCLC. The cobas® platform is a companion diagnostic test used in clinical practice on tumour tissue, and is approved for ctDNA EGFR testing from plasma samples. We evaluated the diagnostic performance of this platform on ctDNA in a prospective single centre study.

Methods:
Patients diagnosed with advanced NSCLC at the Royal Marsden Hospital between November 2015 - November 2016 were included. Patients had to have tissue EGFR result available. Peripheral blood samples were collected in cfD tubes (Roche Molecular Solutions CA, USA) and analysed using the cobas® platform following manufacturer’s instructions.

Results:
201 samples were analysed; median age 68 years. 89% of patients had adenocarcinoma, followed by poorly differentiated carcinoma (4%), squamous cell carcinoma (3%), adenosquamous (2.5%) and other (1.5%). 30% of patients were never smokers, whereas 58% were ex-smokers and 10% were current smokers (2% unknown smoking history). 93% of patients had stage 4 disease, whereas 7% had stage 3 disease. 42% of patients had thoracic-only disease. 79% of patients had their tissue EGFR analysis performed on the cobas[®] platform (others included Illumina NGS (7.5%); Therascreen[TM] (1%)). 10% of patients did not have available tumour tissue. All plasma samples were tested on the cobas[®] platform. Concordance rate between ctDNA and tumor was 87%, with sensitivity 65%, specificity 98%, positive predictive value 95%, and negative predictive value 85%. Concordance rate in patients with an EGFR mutation was 55% for thoracic-only disease and 75% for extra-thoracic disease. The mean time to EGFR result was shorter for ctDNA than tissue (8.4 vs 11.2 days; P=0.07) with a ctDNA failure rate of only 2.4%. Two tissue failures resulted in an EGFR mutation being picked up in plasma (Exon 19 and T790M).

Conclusions:
We demonstrate that ctDNA can be used for diagnosis of an EGFR mutation in advanced NSCLC with excellent specificity, despite moderate sensitivity. The cobas[®] test for ctDNA should be incorporated into clinical practice to triage patient care.

Clinical trial identification:
Not applicable

Legal entity responsible for the study:
The Institute of Cancer Research and the Royal Marsden NHS Foundation Trust

Funding:
Roche Molecular Solutions CA, USA

Disclosure:
T.A. Yap: Received research funding from Roche. S. Popat: Consultant to Roche and has received honoraria from Roche. J. Palma: Employee of Roche Molecular Solutions CA, USA. All other authors have declared no conflicts of interest.

Abstract not provided

Background:
PD-1/PD-L1 axis blockade is of pivotal interest in NSCLC, where the relative antibodies have shown relevant activity. Detection of markers able to predict the activity of these treatments is an importance issue. The predictive role of PD-L1 evaluated by IHC is debated in NSCLC, also, considering that small biopsies or cytological specimens represent often the only tumor material available. This study aimed to assess a circulating immuno-profile as predictor of outcome in NSCLC patients treated with nivolumab.

Methods:
A peripheral blood immuno-profile evaluation was performed at three different times: At baseline (T0), after 2 cycles (T1) and after 4 cycles (T2) of Nivolumab in 54 advanced pre-treated NSCLC patients treated in an Expanded Access Program in two Italian institutions. Tumor assessment was performed after 4 cycles and every 2 months. FACS analysis of lymphocyte subpopulations [CD3, CD4, CD8, NK (CD56) and Treg (FOXP3)] was performed. In addition to changes in absolute number and % of these populations, they were also characterized for their functional and proliferative activity. Quali-quantitative leucocyte composition at baseline and its change during therapy were correlated with tumor response and overall survival.

Results:
Baseline Neutrophil-to-Lymphocyte Ratio, baseline NK count, lymphocyte count and CD4 variations during therapy showed a statistically significant prognostic role (p < 0.001; p = 0.012; p < 0.001; p = 0.010, respectively). Preliminary results on 31 patients with all 3 time-points samples, showed: A significant increase of NK cells and a significant decrease of CD4% from T0 to T2; a significant increase from T0 to T2 of NK subpopulation CD56dim (with reduction of CD56bright); considering two groups of patients (19 responders vs. 12 non-responders), a NK increase (overall and of CD56dim) and CD4% decrease was observed in responders and non-responders, respectively; absolute number and % of NK at baseline was statistically different in the two groups; absolute number and % of CD8+/PD1+ at baseline was significantly higher in responders vs. non-responders.

Conclusions:
These data show that it is possible to identify predictive peripheral immuno-biomarkers, such as NK and CD8, for nivolumab therapy in advanced NSCLC.

Clinical trial identification:
NA

Legal entity responsible for the study:
University Hospital of Parma

Funding:
AIRC

Disclosure:
All authors have declared no conflicts of interest.

Background:
Response patterns following cancer immunotherapy (CIT) treatment are often non-classical due to tumor immune infiltration and increase in tumor burden prior to response. As such, RECIST-based endpoints may not adequately predict the potential OS benefit with CIT. In an updated analysis of POPLAR, PFS and ORR improvement with atezolizumab (atezo) vs docetaxel (doc) was restricted to patients (pts) with high PD-L1 expression, whereas OS benefit was seen in the PD-L1–unselected ITT population (HR, 0.69; mOS 12.6 mo vs 9.7 mo with atezo vs doc), suggesting that many pts derive atezo benefit after radiographic progression.

Methods:
287 NSCLC (2L/3L) pts were randomized 1:1 to receive atezo (1200 mg IV q3w) until loss of clinical benefit or doc (75 mg/m[2] IV q3w) until PD per RECIST v1.1 (RECIST). The primary endpoint was OS; secondary endpoints included PFS and ORR per RECIST. Atezo arm pts were evaluated per immune-modified RECIST (imRECIST) and post-PD radiographic changes. Both arms were evaluated for OS post-PD (data cutoff, Dec 1, 2015; minimum follow-up, 20 mo).

Results:
Among 144 pts in the atezo arm, ORR per imRECIST vs RECIST was 17% vs 15%, disease control rate (CR+PR+SD) was 65% (imRECIST) vs 52% (RECIST) and mPFS was 4.3 mo (imRECIST) vs 2.7 mo (RECIST). In 61 atezo pts continuing treatment post-PD, 8% had a subsequent ≥ 30% decrease in target lesions relative to the time of PD, and 74% had a best change between +20% and −30%. mOS post-PD in both arms is shown (Table).

Conclusions:
Increased ORR and PFS per imRECIST vs RECIST in atezo pts highlight the utility of imRECIST as response evaluation criteria to assess efficacy of atezo/CIT. 82% of pts continuing atezo post-PD had subsequent stable ( ≤ +20% change) or decreased target lesions. The nearly 1-yr mOS in pts continuing atezo vs other treatment post-PD is suggestive of atezo benefit lasting beyond PD. Table.rnTable: 96PD_PRrn

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Patients Receiving Therapy Post-PD per RECIST v1.1	n	mOS from time of first RECIST v1.1 PD
Atezo arm pts continuing atezo	61	11.8 mo
Atezo arm pts receiving non-protocol anti-cancer therapy	30	9.2 mo
Doc arm pts receiving non-protocol anti-cancer therapy	46	9.7 mo

rn

Clinical trial identification:
NCT01903993

Legal entity responsible for the study:
F. Hoffmann-La Roche Ltd/Genentech Inc., a member of the Roche Group

Funding:
F. Hoffmann-La Roche Ltd/Genentech Inc., a member of the Roche Group

Disclosure:
A. Artal-Cortes: Advisory boards for Roche, BMS, MSD and travel fees from Roche. A. Rittmeyer: Grants as an advisor or speaker from Astra Zeneca, BMS, Boehringer Ingelheim, Eli Lilly, Pfizer and Roche Genentech. K. Park: Consulting/advisory from Astellas Pharma, AstraZeneca, BI, Clovis Oncology, Lilly, Hanmi, Kyowa Hakko Kirin, Novartis, Ono Pharmaceutical, Roche; speakers\' bureau fees from BI; research funding from AstraZeneca. C. Lewanski: Consulting/Advisory: Roche, Celgene, Amgen. S. Liu: Employed by Genentech and holds Roche stocks. M. Ballinger: A Genentech employee and has Roche stock. All other authors have declared no conflicts of interest.

Abstract not provided

Background:
Lung cancers mostly present at a clinically advanced stage. Predicting the invasiveness of tumors might help in planning treatment and prophylaxis. We aim to investigate the patterns of lung cancer metastasis and determine possible clinical predictors of those patterns in population based study.

Methods:
The records of all patients (2010-2013) were extracted from SEER database of the National Cancer Institute. Data was extracted to SPSS. Univariate and multivariate logistic regression were used for analysis.

Results:
We have identified 76254 (54.5%M, 45.5F) patients with metastatic lung cancer (2010-2013).17% were small cell tumors (SCLC), while 83% of tumors were non-small cell tumors (NSCLC). Tumor was found more frequently on the right (54%) than the left (38%), and was bilateral in 8% of cases. Our analysis showed that NSCLC had higher rates of metastasis to bone than SCLC (37% Vs 34%) (P < 0.001, 95% CI: 1.097-1.190), SCLC had higher rates of metastasis to liver than NSCLC (46% Vs 20%) (p < 0.001 95%CI: 0.27-0.29), both SCLC and NCLC had almost similar rates of brain metastasis at the time of diagnosis (25% Vs 26%, respectively) (P = 0.003, 95% CI: 1.024-1.120). Following adenocarcinoma and small cell, squamous cell histology was 3rd most common tumor histology for both brain and liver metastasis. Although rare, carcinoid tumor had high rates of metastasis to brain at diagnosis (44.8%). Predictors for liver metastasis were small cell and adenocarcinoma histology (p < 0.001, 95% CI:0 .245-0.304), Tumors with upper lobe location (P = 0.028, 95% CI: 0.839-0.990), and high grade tumors (P < 0.001, 95% CI: 1.334-1.618). Predictors for metastasis to brain were advanced age at diagnosis (P < 0.001, 95% CI: 0.970 -0.976), Adenocarcinoma and small cell histology (P < 0.001, 95% CI: 1.254-1.561), Lower lobe, and main bronchus locations (p = 0.004, 95% CI: 0.689-0.930), and tumors of higher grade (P < 0.001, 95%CI: 1.250-1.463).

Conclusions:
Lung cancer subtypes are associated with distinct patterns of metastatic spread. SCLC has significantly higher rates of liver metastases, while NSCLC has higher rates of bone metastasis. Further investigation needed to evaluate the role of primary tumor location on metastatic behavior of lung cancer.

Clinical trial identification:


Legal entity responsible for the study:
Mohamed Hendawi

Funding:
N/A

Disclosure:
The author has declared no conflicts of interest.

Background:
The clinical and radiologic presentation of lung cancer in women differs from men, especially in Asia. The aim of this study is to identify potential gender-related differences of newly developed lung cancer and provide the optimal CT screening intervals for the patients who are managed in the health care center.

Methods:
Between January 2000 and February 2016, a total of 46,766 consecutive patients who underwent screening chest CT in Health Care Center at Asan Medical Center of Korea were retrospectively reviewed. During the study period, 282 patients (M:F=205:77) were finally diagnosed by lung cancer. Among them, lung cancers were detected by initial screening CT in 186 patients (excluded in this study), and 96 patients (M:F=85:11, age range M:F=62.7±12.9: 62.7±8.7 years, respectively) have been clinically diagnosed as newly developed lung cancers using subsequent screening CT follow-up. Using the 96 patients, CT screening intervals, stage, and pathology (with subtype and mutation) of cancers were evaluated and analyzed to find any gender-related differences.

Results:
In the 96 patients, mean age is not significantly different between genders. Most of the men were smokers (74/85, 87%). Adenocarcinoma is the most common type (36/85, 42%), followed by squamous cell carcinoma (35%), small cell lung cancer (18%), and others (5%) in men. All female patients were adenocarcinoma. The mean time interval of screening CT was relatively longer in women (5.6±3.1 years) than in men (3.6±2.4 years) (p=0.02). However, lung cancer stages are significantly higher in men. Minimum CT screening interval to detect stage I lung cancer was longer in women (5 years) compared to that in men (1 year).

Conclusions:
The interval of screening CT could be longer in women than men. To detect most of stage I lung cancer, a 3-year interval screening for women and 1-year interval for men are optimal in our study for minimizing radiation hazard and worry.

Clinical trial identification:


Legal entity responsible for the study:
None

Funding:
N/A

Disclosure:
All authors have declared no conflicts of interest.

Abstract not provided

Abstract not provided

Abstract not provided

Background:
Integrated 18F-FDG, PET-CT has shown somewhat variable sensitivity and specificity for nodal staging in tuberculosis endemic areas. This variation is mainly because PET scans show falsely increased 18F-FDG uptake in inflammatory nodes, which may be observed in lymph nodes containing calcification or showing higher attenuations than those of surrounding vessels on unenhanced CT scans. The AIM of the study was to evaluate the efficacy of PET-CT for mediastinal nodal staging in non-small cell lung cancer (NSCLC) patients in a tuberculosis-endemic country.

Methods:
From February 2012 to February 2016, a total of 160 patients underwent surgery for pathologically proven NSCLC. Patients who received neoadjuvant treatment were excluded from the study. Assessment of the diagnostic efficacy of integrated PET- CT for detecting nodal metastasis was performed in 46 patients (Male to Female ratio:4; mean age- 55 years). Patients underwent an integrated PET/CT examination and subsequent surgical nodal staging. Nodes showing greater 18F-FDG uptake at PET without benign calcification or high attenuation >70 household unit (HU) at unenhanced CT were regarded as being positive for malignancy. All patients underwent hilar and mediastinal lymph node dissection according to the AJCC lymph node map after resection of the main tumour. The histologic nodal assessment results were used as reference standards. Of these 46 patients, 10 (20%) had a past medical history of pulmonary tuberculosis as determined by clinical or imaging studies.

Results:
A total of 230 mediastinal nodal stations were evaluated in 46 patients; 5 (2%) stations in 4 (8%) patients proved to be malignant by histopathology. Mean number of lymph node stations were 5. On a per-nodal station basis, PET CT for mediastinal lymph nodes staging has sensitivity: 60%; specificity: 97%; accuracy: 96%; positive predictive value (PPV): 38%; negative predictive value (NPV): 99%.

Conclusions:
Integrated PET-CT provides high specificity and high accuracy, but low sensitivity for mediastinal staging of NSCLC. The high specificity is achieved at the expense of sensitivity by interpreting calcified nodes or nodes with high attenuation at CT, even with high FDG uptake at PET, as benign in a tuberculosis-endemic region.

Clinical trial identification:


Legal entity responsible for the study:
Dr. Bhim Rao Ambedkar Institute Rotary Cancer Hospital, All India Institute Medical Sciences, New Delhi

Funding:
Dr. Bhim Rao Ambedkar Institute Rotary Cancer Hospital, All India Institute Medical Sciences, New Delhi

Disclosure:
All authors have declared no conflicts of interest.

Background:
The newly revised TNM classification shows that cT and pT are to be evaluated with solid component on CT and pathological invasive size in adenocarcinoma of the lung. We evaluated the predictive factors for invasiveness, lymph node metastasis and recurrence in patients with adenocarcinomas of the lung, particularly pathological tumor diameters both of gross and invasive size, and solid component diameter using computed tomography (CT) both with lung window settings and mediastinal window settings.

Methods:
We evaluated 533 patients with lung adenocarcinomas (diameter, 6–132 mm) who underwent surgical resections. 447 of the 533 have been underwent systematic node dissection. Tumors were examined using CT with thin section conditions (1.25-mm thick: high-resolution CT), with tumor dimensions evaluated under two conditions: lung window (LD) and mediastinal window (MD) settings. Both of the tumor size on CT (LD, MD), consolidation component size on CT with lung window settings (C), preoperative serum carcinoembryonic antigen (CEA) levels, pathological tumor diameter both of gross(GS) and invasive lesion(IS), and pathological status [invasion of lymphatic vessels (ly), vascular vessels (v), pleura (pl), lymph node metastasis] were examined. Area under the curve (AUC) of Receiver Operating Characteristic (ROC) was used for evaluation.

Results:
AUCs according to the variables.rnTable: 46PDrn

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Variables	ly(N = 533)	v(N = 533)	pl (N = 533)	Lymph node metastasis (N = 447)	Recurrence (N = 447)	Correlation coefficient IS and other variables
GS	0.73	0.71	0.72	0.72	0.83	N.A
IS	0.86	0.82	0.79	0.79	0.86	N.A
LD	0.71	0.70	0.70	0.71	0.79	0.65
MD	0.87	0.82	0.81	0.80	0.85	0.80
C	0.83	0.80	0.79	0.79	0.83	0.78
C/LD	0.81	0.78	0.75	0.73	0.69	N.A
CEA	0.68	0.66	0.69	0.70	0.72	N.A

rnGS: pathological gross tumor size, IS: Pathological invasive size, LD: Diameter with lung window settings on CT, MD: diameter with mediastinal window settings on CT, C: consolidation diameter with lung window settings on CT.rn

Conclusions:
The solid component evaluated on computed tomography especially by MD and C can predict the invasiveness and lymph node metastasis in lung adenocarcinoma as well as pathological invasive size.

Clinical trial identification:
N.A.

Legal entity responsible for the study:
Yukinori Sakao

Funding:
N/A

Disclosure:
All authors have declared no conflicts of interest.

Abstract not provided

Background:
The presence of solid histologic pattern in lung adenocarcinoma (ADC) is associated with early recurrence. However, individualized prognosis in patients with solid component is still unclear. This study aimed to develop a nomogram predicting the recurrence probability in stage I lung ADC patients with solid component.

Methods:
A total of 5904 patients with stage I lung ADC who underwent curative surgical resection from January 2008 through December 2014 at Shanghai Chest Hospital were retrospectively reviewed. Tumors were subtyped by using the IASCL/ATS/ERS classification. Of these patients, 708 contained a solid component. Prognostic value of gender, age at diagnosis, smoking history, operation type, tumor location, tumor size, pathological subtype, cell differentiation, lymphovascular and visceral pleural invasion were investigated. Multivariate Cox regression analysis of recurrence-free survival (RFS) in patients with solid component was performed and a nomogram to predict RFS was constructed. The nomogram was internally validated.

Results:
The overall recurrence rate in patients with solid component was 25.0% (177/708), with predominant solid subtype and minor solid component in 49.2% (87/177) and 50.8% (90/177) of cases, respectively. Larger tumor size (P = 0.002), predominant solid component (P = 0.003), advanced age at diagnosis (P = 0.015), and visceral pleural invasion (P = 0.040) were associated with an increased risk of recurrence and were included in the nomogram. The predictive model had a concordance index of 0.643 (95% confidence interval, 0.601-0.685) and showed good calibration.

Conclusions:
The nomogram model including identified risk factors for RFS is applicable in treatment decision-making for early stage lung ADC with pathological solid component. External validation is required to recommend this nomogram in routine practice.

Clinical trial identification:


Legal entity responsible for the study:
Shanghai Chest Hospital

Funding:
Shanghai Chest Hospital

Disclosure:
All authors have declared no conflicts of interest.

Background:
The aim of the present study was to assess outcomes among non-small cell lung cancer (NSCLC) patients treated with preoperative chemotherapy followed by Video-Assisted Thoracic Surgery (VATS) lobectomy from a National multi-institutional Registry.

Methods:
A National Registry established in 2013 was used to collect data from 65 Thoracic Surgery Units (>3,700 patients enrolled); only information from Units with >100 VATS lobectomies enrolled were analysed. A retrospective analysis was performed on patients with NSCLC who received preoperative chemotherapy followed VATS lobectomy within one year and compared to a propensity score matched population without preoperative chemotherapy. Propensity score (greedy 5 to 1 digit matching algorithm) estimated with multiple logistic regressions based on selection bias and potential confounding variables produced 221 patients (control group). After propensity score matching, data were compared with the paired Student’s t-test, Pearson’s χ[2] and Fisher’s exact test. Differences were considered to be statistically significant when the p - value was <0.05.

Results:
56/1679 (3.34%) patients met study inclusion criteria. There were no significant differences in baseline characteristics between groups (Table 1a). The majority of patients were clinical stage IIIA, although a small percentage of clinical stage II patients had preoperative therapy. Anatomic distribution of lobectomies and the number of resected lymph nodes not significantly differed between groups. Table 1b presents postoperative histology in the neoadjuvant groups. Table 1c reports short-term perioperative outcomes. No perioperative mortality was recorded in both groups. Overall morbidity (pneumonia, atrial fibrillation) was significantly higher in the neoadjuvant group, but interestingly, all the other variables were not influenced (conversion rate, operative time, blood loss, air leak duration, length of stay).rnTable: 72PDDemographics, postoperative histology/stage of the neoadjuvant group, and selected perioperative/postoperative outcomes. NA = not applicable, SD = standard deviationrn

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Table 1a. Demographics characteristics
Characteristics	Neoadjuvant Group (N = 56)	Propensity Matched Group (N = 221)	p - value
M/F (%)	50	61.99	0.938
Age (mean ± SD)	64.14 ± 10.64	67.44 ± 11.93	0.888
Charlson Index (mean ± SD)	4.19 ± 1.75	4.43 ± 1.85	0.530
ECOG score	0	0	NA
Preoperative stage (N, %) • IIA • IIB • IIIA	13 (23.21) 18 (32.14) 25 (44.64)	64 (28.96) 59 (26.70) 98 (44.34)	0.877 0.568 0.964
Surgical procedure (N, %) • Left upper lobectomy • Left lower lobectomy • Right upper lobectomy • Right lower lobectomy • Lower bilobectomy	8 (14.29) 10 (17.86) 25 (44.64) 12 (21.43) 1 (1.79)	43 (19.46) 29 (13.12) 89 (40.27) 36 (16.29) 3 (1.36)	0.808 0.124 0.628 0.663 0.882

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Table 1b. Postoperative histology and stage of the Neoadjuvant Group (N, %)
Postoperative histology • Adenocarcinoma • Squamous cell carcinoma • Other	25 (44.64) 12 (21.43) 21 (37.5)
Stage • IA • IB • IIA • IIB • IIIA	7 (12.5) 12 (21.43) 22 (39.29) 1 (1.79) 14 (25)

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Table 1c. Selected perioperative and postoperative outcomes
Characteristics	Neoadjuvant Group (n = 56)	Propensity Matched Group (n = 221)	p - value
Duration of surgical operation, minutes (mean ± SD)	182.14 ± 65.69	182.76 ± 66.17	0.933
Intraoperative blood loss, mL (mean ± SD)	148.93 ± 153.57	154.19 ± 126.09	0.163
Resected lymph nodes (mean ± SD)	17.54 ± 10.37	14.04 ± 7.65	0.890
Overall conversion to thoracotomy (N, %) • Lymph nodes on pulmonary artery • Anomalies of anatomy • Bleeding	6 (10.71) 3 (5.36) 1 (1.79) 2 (3.57)	20 (9.05) 11 (4.98) 1 (0.45) 8 (3.62)	0.0634 0.193 0.517 0.195
Postoperative air leaks (N, %)	6 (10.71)	12 (5.43)	0.0396
Postoperative complications (N, %) • Pneumonia • Atrial fibrillation	6 (10.71) 4 (7.14)	7 (3.17) 10 (4.52)	0.0398 0.0419
Hospital length of stay, days (mean ± SD)	8.73 ± 6.60	9.54 ± 8.92	0.759

rn

Conclusions:
VATS lobectomy after induction chemotherapy in stage II/IIIA NSCLC is feasible with a favourable profile regarding overall morbidity and mortality. This preliminary report shows that neoadjuvant treatment may not represent per se a contraindication to the VATS approach.

Clinical trial identification:


Legal entity responsible for the study:
Italian VATS Group

Funding:
Italian VATS Group

Disclosure:
All authors have declared no conflicts of interest.

Abstract not provided

Background:
Previous studies have shown that primary tumor metabolic volume (PT-MV) on 18F-FDG-PET/CT could serve as a prognostic factor in patients treated with definitive chemoradiotherapy (CRT). We analyzed a correlation between pre- to posttreatment PT-MV reduction during the course of CRT and overall survival.

Methods:
Sixty-five patients with histologically confirmed NSCLC IIIA-B, treated with definitive CRT in the sequential (21/65 pts, 32.3%) or concurrent (44/65 pts, 67.7%) mode, who underwent 18F-FDG-PET/CT before and about 4-6 weeks after the CRT, were analyzed. Histology yielded 22 (33.8%) adenocarcinomas, 34 (52.3%) squamous cell carcinomas, 8 (12.3%) large-cell carcinomas and 1(1.5%) NSCLC not otherwise specified (NOS). Thirty-five patients (35/65, 53%) were enrolled in randomized clinical trials (16 pts in GILT, 10 pts in InCoDor and 9 pts in BROCAT study CTRT 99/97). The most common concurrent chemotherapy regimen (18/65 pts, 27.7%) consisted of cisplatin given intravenously at a dose of 20mg/m[2] on days 1-4 and oral vinorelbine 50mg/m[2] on days 1, 8 and 15, every 4 weeks for two courses.

Results:
Median OS for the entire cohort was 16 months (95% [CI],11.5–20.5). Complete remission (CR) was reached in 20 (31%), whereas partial and non-response occurred in 31 (48%) and 14 (22%) patients, respectively. The mean change from pre- to posttreatment PT-MV was -51% (range: +125% to -100%). Various cutoffs of PT-MV reduction (100- 90-85-80-70-60 and 50%) after the CRT were analyzed. CR(n = 20) had a median OS of 26 (95 CI: 5-47) vs. 13 months (95 CI:9-16) observed in the rest of treated group (p = 0.01, log-rank test). The results also showed a significant difference in OS favoring patients with PT-MV reduction >90% (n = 18) vs. the rest with a median survival of 24 vs. 13 months, respectively (p = 0.04, log-rank test). However, the association between PT-MV reduction at 80% and 70% and survival showed borderline significance (p = 0.07 and 0.09, log-rank test). PT-MV reduction at 60 and 50% failed to show an effect on OS.

Conclusions:
In this inoperable locally-advanced NSCLC cohort, a PT-MV reduction of at least 90% after definitive CRT correlated with improved OS.

Clinical trial identification:


Legal entity responsible for the study:
Deparment of Radiation Oncology, LMU Munich

Funding:
N/A

Disclosure:
All authors have declared no conflicts of interest.

Background:
Validated outcome prediction models with high discriminative power are important for a cost-effective deployment of proton therapy for locally-advanced non-small cell lung cancer (NSCLC). We validated a model predicting lung toxicity 6 months after radiotherapy (RT) treatment.

Methods:
The model published by Appelt et al. (Acta Oncol 2014) was selected from a literature search. It relies on a review of radiation pneumonitis reports and retained the most important predictors, Mean Lung Dose (MLD) as dosimetric factor and 6 factors influencing the patient’s susceptibility: pre-existing pulmonary comorbidity, age>63 years, mid/inferior tumor location and sequential chemotherapy as risk factors, and current smoking and smoking history as protective factors. A dataset of 109 NSCLC patients treated at MAASTRO Clinic using 1.8 Gy fraction doses (two fractions per day) up to 79.2 Gy was studied. The required parameters were retrospectively collected together with the dyspnea endpoint (CTC 3.0 scoring) at baseline and at 6 months after RT. All treatments were performed using 3D-conformal RT techniques as it was the case in the study of Appelt et al. Odds ratios were calculated using logistic regression modelling.

Results:
19.3% of patients presented post RT dyspnea≥2. Our dataset confirmed current smoking and pulmonary comorbidity as prognostic factors for this endpoint, with similar odds ratios (OR = 0.28 (p = 0.02) and OR = 2.95 (p = 0.02), respectively). Tumor location OR was outside of the reported 95% CI. When predicting the change in dyspnea with respect to the baseline score (delta dyspnea≥1, prevalence of 18.6%), the two prognostic factors were not significant anymore (OR = 0.56 (p = 0.27) and OR = 0.47 (p = 0.21), respectively). Both factors exhibited strong correlation with the baseline patient status: worse baseline dyspnea is often a manifestation of existing comorbidities and it determines the probability to stop smoking. MLD was not associated with outcome in any of our models.

Conclusions:
It is crucial to consider delta toxicity endpoints in prediction modeling in order to obtain meaningful models reflecting radiotherapy outcome. Acknowledgement: This project has received funding from the EU under grant agreement no 601826 (REQUITE).

Clinical trial identification:


Legal entity responsible for the study:
KU Leuven

Funding:
EU

Disclosure:
All authors have declared no conflicts of interest.

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Background:
Although smoking is the major risk factor for lung cancer worldwide, approximately 1.5% of annual lung cancer deaths are attributed to exposure to carcinogens from indoor solid fuel use. Biomass fuels is classified as a probable carcinogen. Data on lung cancer risk associated with the exposition magnitude of biomass fuel smoke in women are limited. The objective was to estimate the risk of lung cancer in women according to the magnitude of exposure to biomass cooking fuel smoke.

Methods:
We designed a hospital-based case-control study. We included 136 cases of primary lung cancer anatomopathologically confirmed and 137 hospital controls of which 50 (27%) had interstitial lung diseases, 46 (25%) pulmonary tuberculosis, 43 (24%) pneumonia, 33 (18%) pulmonary embolism and 11(6%) had ear, nose and throat ailments. Exposure to wood smoke was assessed as a continuous variable based on the calculation of hour-years (years of exposure multiplied by average hours of exposure per day), as a categorical variable broken down in three categories (<100, 101–299, and >300 hour/years), and as any or none. We used unconditional logistic regression to compute odds ratio (OR) and 95% Confidence Intervals (95% CI) for lung cancer risk associated with biomass cooking fuel smoke exposure, adjusting for potential confounders (tobacco use, age, gender, and socioeconomic level. We repeated the same analysis but only including non-smoking women.

Results:
Cases were older than the controls, 65 vs. 62 years old (p < 0.05) with higher rate of exposure to wood smoke (REWS), 144 vs 88 hour-years (p < 0.05), and the risk of lung cancer increased linearity with hour-years, OR 1.02 (95% CI 1.00–1.00) p = 0.019. Crude and adjusted odds ratios for an exposure >100 hour-years were OR 1.66 (95% CI 0.76–3.64) and OR 2.19 (95% CI 0.89–5.40) respectively, and for >300 hour-years OR 1.78 (IC95% 0.77–4.13) and OR 3.01 (95% CI 1.12–8.36). The association persisted after adjusting for sex, smoking, socioeconomic status and housing with asbestos sheet roof. In non-smoking women at an REWS >300 hour-years the risk increased to an OR 5.71 (95% CI 1.33–24.60).

Conclusions:
These results provide novel evidence that the magnitude of exposure to biomass smoke in hour-years may play a crucial role in the chain of causation of lung cancer. The size of the pooled effect shows that the risk of lung cancer is higher in non-smoking women.

Clinical trial identification:


Legal entity responsible for the study:
Instituto Nacional de Enfermedades Respiratorias

Funding:
Has not received any funding

Disclosure:
All authors have declared no conflicts of interest.

Background:
We investigated the efficacy of early lung cancer screening with low-dose spiral computed tomography(LDCT) based on the current situation of hospital health service, with integration of superior resources of medical institutions at top levels in Shanghai.

Methods:
From November 2012 to November 2017, we screened 6303 (male 2516; female 3787) individuals in three major hospitals in Shanghai City, for early diagnosis of lung cancer with LDCT combined with multidisciplinary comprehensive treatment pattern including minimally invasive surgery, exploring the medical service network covering prevention, diagnosis, treatment, rehabilitation and follow-up.

Results:
Screening resulted in a diagnosis of primary lung cancer in 126 participants. The detection rate is 170.9/100,000 among the male participants, and 219.2/100,000 among the female participants (P = 0.180). The detection rate is 207.6/100,000 among the non-smoker participants, and 183.5/100,000 among the smoker participants (P = 0.524). The detection rate is 181.7/100,000 among the participants above 60 years old, and 200.5/100,000 among the participants between the age of 22 and 40 (P = 0.703).

Conclusions:
Lung cancer patients in East Asia presents new demographic characteristics: the detection rates among females, non-smokers, and people between the age of 22 and 40 are at least not lower than the traditional-sense high risk population. Females, non-smokers, and people between the age of 22 and 40 should not be excluded from screening with LDCT.

Clinical trial identification:


Legal entity responsible for the study:
Fudan University Shanghai Cancer Center

Funding:
Has not received any funding

Disclosure:
All authors have declared no conflicts of interest.

Background:
Early detection of lung nodules may lead to prompt diagnosis and treatment of lung cancer, improving patient outcomes. We instituted and evaluated a lung nodule best practice initiative that would coordinate between the emergency department (ED) visits where a long nodule was detected and follow up care post discharge.

Methods:
CT scan of the chest was assessed after completion of ED evaluation. If a lung nodule was detected; patient was made aware of the findings by ED clinician. Documentation supported by ED clinician choosing a box reporting lung nodule detected prior to discharge in the ED electronic medical record (EMR). A daily email was automatically generated to the thoracic nurse navigator (TNN). TNN called the patients to offer: appointment to the lung nodule clinic, assignment with primary physician, or patient declined options. TNN documented conclusion in EMR. A certified letter was sent to the patient as a recommendation and summary.

Results:
287 patients were listed on the ED lung nodule report from 11/1/2016–12/31/2017. 45 patients listed did not have a true nodule and were excluded, resulting in 242 patients. 12 (4.9%) patients were referred to the Lung Center Nodular Clinic. 176 (72.7%) patients were referred to other physicians, such as pulmonary and primary care physicians. 78% of incidental pulmonary nodules from the ED was referred for follow up. 54 patients either declined follow up or were unable to be reached. There were 2 days of blank reports from the ED. A review of both RAD (report from radiology) and ED reports were compared for the week 11/20–11/27/17. 31 patients with nodules on RAD reports were missing from the ED version: 18 from the day shift and 13 on night shift. These missing patients indicate many more nodule patients were not accurately reported. Since the ED account relies on manual check box, the TNN now runs ED reports against the RAD versions for correct number of patients with incidental pulmonary nodules.

Conclusions:
Many incidental lung nodules are discovered nationwide through the emergency department. Many of these go without follow up. We demonstrate an initiative that implements a verifiable system along the pathway in the emergency department through discharge home.

Clinical trial identification:


Legal entity responsible for the study:
Jupiter Medical Center, Dept of Thoracic Surgery

Funding:
Has not received any funding

Disclosure:
The author has declared no conflicts of interest.

Background:
Brain is a common site of metastases with EGFR mutated lung cancer. Oral targeted therapies have broadened the treatment options in the advanced setting with the potential for periods of long term response. Literature on MR imaging metrics or feature analysis of NSCLC brain metastasis as a biomarker for predicting EGFR mutation is limited and less investigated. The purpose of the study was to study MRI imaging biomarkers of brain metastases NSCLC and their correlation with molecular subtyping (EFGR status). To correlate these imaging features with response to therapy and clinical outcomes.

Methods:
We analyzed clinical data on 75 patients who were tested for EGFR mutation and underwent brain MR imaging at diagnosis. Multiparametric MRI was performed in all cases. The associations between EGFR mutation status and clinical features, specifically age, sex, smoking, TNM stage, and imaging variables, as well as brain metastasis, were analyzed using logistic regression analysis. Clinical factors known to be associated with EGFR mutation status in NSCLC patients and staging factors of TNM were included in the logistic regression multivariate analysis.

Results:
38 EGFR positive and 37 EGFR negative cases. EGFR positive showed early and wide spread development of brain metastasis (within 6 months after 1st presentation) (p-0.00). Statistically significant difference (p-0.00) was observed in border/margins on T2W imaging, fuzzy and infiltrative borders in EGFR positive while well defined in EGFR negative. Lesions in EGFR wild group showed focal restriction on DW images (p-0.001). In EGFR wild cases showed good response to WBRT (p < 0.00). Incidence of recurrent metastatic disease, meningeal involvement was significantly higher in EGFR positive (p-0.00, 0.04). On multivariate analysis, statistically significant association was found between T2 border, number, restricted diffusion, meningeal positivity and TTP (p < 0.05).

Conclusions:
EGFR positive brain metastases have characteristic MR imaging features that can be potential non-invasive diagnostic, predictive and prognostic imaging biomarkers. These MR based Radiogenomic imaging biomarkers have potential role in personalized therapy of EGFR positive brain metastasis in NSCLC.

Clinical trial identification:


Legal entity responsible for the study:
IEC TMH

Funding:
Has not received any funding

Disclosure:
All authors have declared no conflicts of interest.

Background:
Multidisciplinary cancer conferences (MCCs) aim to improve the management of patients with cancer. We evaluated the rate and type of decision change that occurred at a thoracic MCC.

Methods:
The MCC took place from June-December 2017 at a Canadian tertiary cancer center and involved surgeons, oncologists, pathologists and radiologists. Cases were brought forward by treating physicians. Using a standardized MCC intake form, physicians articulated a clinical question, original treatment plan, and confidence in the original plan (rated on a 1–5 scale). Major changes were classified as: change from upfront surgery to neoadjuvant treatment, definitive chemotherapy/radiation, or Stereotactic Body Radiation Treatment/Radiofrequency Ablation (SBRT/RFA); change from neoadjuvant or definitive chemotherapy/radiation or SBRT/RFA to surgery; or palliation/observation instead of definitive treatment. Minor changes included additional imaging, further staging investigations, repeat consultations, or changes in planned oncologic or surgical approach. Data were reported as frequencies. Chi-square tests were used to compare groups at a p < 0.05 significance level.

Results:
A total of n = 116 cases were reviewed at the MCC. Ninety-six percent of cases required a re-review of imaging or pathology (111/116). Sixty percent (70/116) of cases resulted in a treatment change, with 41% (29/70) and 59% (41/70) of changes considered major and minor, respectively. High physician confidence in the original plan did not significantly correlate with the rate of change (53% no change; 47% change, p = 0.073) or type of change (30% major; 70% minor, p = 0.098). The most common major change was use of neoadjuvant or definitive chemotherapy/radiation instead of upfront surgery (38%, 11/29). Minor changes primarily involved further staging investigations (56%, 23/41).

Conclusions:
Sixty percent of cases discussed at the thoracic MCC resulted in a treatment change, with 41% considered major changes. High physician confidence did not significantly correlate with the rate or type of change. These data support the continued implementation and use of MCCs.

Clinical trial identification:


Legal entity responsible for the study:
McMaster University

Funding:
Has not received any funding

Disclosure:
All authors have declared no conflicts of interest.

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Background:
Malignant pleural mesothelioma (MPM) is no more considered a rare disease and its incidence is escalating. It became a must to develop innovative modalities for better survival rates. Up to date, there is no agreement on the effectiveness of multimodality in MPM patients. This study assesses the value of multimodality therapy and identify the demographic and pathological characteristics associated with better outcome.

Methods:
Using SEER database, we extracted the data of 681 patients with MPM from 2004 to 2013. We included all age groups and races, AJCC stages I-IV and all histopathological variants. Patients were divided into four groups according to the received intervention: surgery alone, surgery followed by radiotherapy, surgery and chemotherapy, and triple modality (combination of surgery, chemotherapy, and radiotherapy).

Results:
Out of 681 patients, 176 (25.8%) had surgery alone, 74 (10.9%) had surgery followed by radiotherapy, 307 (45.1%) had surgery and chemotherapy, and 124 (18.2%) had a combination of surgery, chemotherapy, and radiotherapy. Highest one-year survival rates were observed among patients had the triple modality (79.6%, p value 0.000) in comparison to surgery alone (37.9%), surgery followed by radiotherapy (70.3%) and combined surgery and chemotherapy (62.2%). There is a statistically significant relationship between receiving the triple modality and each of the race, age, histopathology and nodal involvement.Table:One year survival rates among patients received the triple modality

Variables	Survival rates	N	P value
Sex
Male	76.8%	97	0.504
Female	89.9%	27
Age
20–39	100%	1	0.000**
40–59	94.1%	31
60–79	76.5%	88
>80	26.9%	4
Race
White	79.7%	115	0.017*
Black	100%	3
Other	67.5%	6
Histopathology
Sarcomatoid	15.0%	7	0.000**
Epithelioid	81.9%	93
Biphasic	89.1%	24
N Stage
N0	77.7%	63	0.02*
N1	87.0%	35
N2	73.7%	22
N3	100%	3
AJCC Stage
II	82.4%	21	0.50
III	85.5%	57
IV	71.0%	46

Conclusions:
Survival rates of MPM patients are the highest when receiving combination of surgery, chemotherapy, and radiotherapy. Further investigations are needed to study the long-term outcomes.

Clinical trial identification:


Legal entity responsible for the study:
Mariam Hassan

Funding:
Has not received any funding

Disclosure:
All authors have declared no conflicts of interest.

Background:
Non-epithelioid malignant pleural mesothelioma (MPM) has a bad prognosis. We wished to evaluate the impact of multimodality therapy on survival in non-epithelioid MPM.

Methods:
Analysis of a prospective database of MPM patients operated on since September 2004. All patients had extended pleurectomy/decortication (ePD) and hyperthermic povidone-iodine pleural lavage (HPL), prophylactic radiotherapy and systemic platinum-based chemotherapy. All patients were followed up until death. PET–CT was used routinely to monitor patients. Survival and prognostic factors were analysed by the Kaplan–Meier method, log–rank test and Cox regression analysis.

Results:
139 patients had ePD and HPL. Median age was 64 years and 80% of patients were male.17% of patients had received systemic chemotherapy prior to surgery. 90–day mortality was nil and 39.6% of patients experienced postoperative complications. 9 patients had reoperation within 30 days. Final histopathology showed epithelioid type in 96 patients and non–epithelioid type in 43. Staging (8th ed. TNM classification) was as follows: I, 7.2%; II, 24.4%, III, 54%, IV, 14.4%. Five patients did not receive adjuvant chemotherapy and 4 received less than 4 cycles in total. All other patients received 4–6 cycles of chemotherapy. All patients received prophylactic radiotherapy (21 Gy). 52% of patients received second–line therapies. Two patients had cyberknife therapy and 3 patients had late reoperations for focal relapse. Median follow–up is 50 months and 92 patients have died. Median overall survival is 35 months (95% CI 26.3–43.7) for epithelioid histology versus 18 months (95% CI 15.1–20.9) for non-epithelioid histology (p = 0.000037). Macroscopic complete resection and epithelioid histology are independent prognostic factors of long–term survival at multivariate analysis.

Conclusions:
Multimodality therapy including ePD and HPL is safe and well-tolerated. Most patients can receive further therapies when disease progresses. Patients with epithelioid histology achieve prolonged survival. Patients with non-epithelioid histology have a modest survival benefit and radical surgery should be offered only to those with early-stage disease.

Clinical trial identification:


Legal entity responsible for the study:
Dr. Loic Lang-Lazdunski

Funding:
Has not received any funding

Disclosure:
All authors have declared no conflicts of interest.

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