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Annual Meeting Proceedings Part 1 - American Society of Clinical ...

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1530 Poster Discussion Session (Board #19), Sun, 8:00 AM-12:00 PM and<br />

11:30 AM-12:30 PM<br />

Potential risk <strong>of</strong> asbestos exposure among Japanese general population:<br />

Japanese general screening study for asbestos-related diseases (JGSARD).<br />

Presenting Author: Nobuhiko Seki, Teikyo University School <strong>of</strong> Medicine,<br />

Tokyo, Japan<br />

Background: The number <strong>of</strong> patients with pleural mesothelioma and lung<br />

cancer associated with asbestos exposure has recently been increasing in<br />

Japan. The aim <strong>of</strong> this study was to evaluate the results <strong>of</strong> screening for<br />

asbestos-related diseases in a group <strong>of</strong> Japanese general population.<br />

Methods: This prospective study was approved by the institutional review<br />

board. From 2006 to 2008, 9810 subjects (5283 men and 4527 women;<br />

mean age, 57 years) underwent chest radiography and low-dose CT<br />

examinations in 26 institutions in Japan. Among them, 6286 (64.1%)<br />

subjects underwent subsequent CT examinations after 2 years <strong>of</strong> interval.<br />

<strong>Clinical</strong> information such as histories <strong>of</strong> smoking and asbestos exposure<br />

was reviewed. Images were interpreted independently by 15 experienced<br />

pulmonologists or chest radiologists. Results: The history <strong>of</strong> asbestos<br />

exposure was definitely present in 1253 (12.8%) subjects, possibly<br />

present in 2058 (21.0%), and absent in 6499 (66.2%). On chest<br />

radiograph, pleural plaque and thickening were seen in 61 (0.6%) and 65<br />

(0.6%) subjects, respectively. On low-dose CT, pleural plaque and thickening<br />

were identified in 264 (2.7%) and 245 (2.5%) subjects, respectively,<br />

and non-calcified pulmonary nodule/mass was seen in 1003 (10.2%).<br />

Furthermore, lung cancer was identified in 29 (0.3%) subjects. The history<br />

<strong>of</strong> asbestos exposure was not confirmed in 77 out <strong>of</strong> 264 subjects (29.2%)<br />

having pleural plaques on low-dose CT. Based on the logistic regression<br />

analysis, pleural plaque on low-dose CT was significantly correlated with<br />

male, age more than 60 years, smoking, and a history <strong>of</strong> asbestos exposure.<br />

Especially, total residential period in asbestos factory area as well as<br />

asbestos exposure work period showed significantly increased relative risk<br />

every 10 years. Similarly, lung cancer was significantly correlated with age<br />

more than 60 years, a history <strong>of</strong> asbestos exposure, and presence <strong>of</strong> pleural<br />

plaques. Conclusions: Our results indicate the presence <strong>of</strong> pleural plaques<br />

on low-dose CT among Japanese general population is closely associated<br />

with potential risk <strong>of</strong> asbestos exposure. However, about 30% <strong>of</strong> such<br />

subjects are not aware <strong>of</strong> a history <strong>of</strong> asbestos exposure.<br />

1533 Poster Discussion Session (Board #22), Sun, 8:00 AM-12:00 PM and<br />

11:30 AM-12:30 PM<br />

<strong>Clinical</strong> characteristics and natural history <strong>of</strong> patients with squamous cell<br />

lung carcinoma with FGFR1 amplification. Presenting Author: Marc Bos,<br />

Lung Cancer Group Cologne, Department I <strong>of</strong> Internal Medicine and Center<br />

for Integrated Oncology, University Hospital Cologne, Cologne, Germany<br />

Background: FGFR1 amplifications have been described as a promising<br />

oncogenic target in squamous cell lung cancer. Here we aimed at<br />

describing the clinical characteristics and natural history <strong>of</strong> FGFR1amplified<br />

squamous cell lung cancer patients. Methods: From 01/2011 to 01/2012<br />

we screened 553 squamous cell lung cancer patients in our Network for<br />

Molecular Screening <strong>of</strong> Lung Cancer for the presence <strong>of</strong> FGFR1 amplifications<br />

by FISH analysis in accordance with the local ethics committee.<br />

FGFR1 was defined as amplified if the ratio <strong>of</strong> FGFR1 copies to centromeric<br />

copies was above 2 or if more than 50% <strong>of</strong> tumor cells showed 5 copies or if<br />

more than 15% <strong>of</strong> tumor cells demonstrated clusters <strong>of</strong> FGFR1. <strong>Clinical</strong><br />

data were collected by extracting information from medical records, the<br />

local cancer registry and by questioning treating physicians and patients.<br />

Results: FGFR1FISH analysis could be performed in 95% <strong>of</strong> the cases and<br />

was amplified in 16%. Of the amplified cases 75 % were male and 25%<br />

female without significant enrichment for male or female. The median age<br />

<strong>of</strong> the patients at diagnosis was 67 yrs (range 46 - 82). Stage at<br />

presentation was: 16% I; 17.3% II; 26.7% IIIa, 40% IIIb/IV. 97,3% <strong>of</strong> the<br />

patients were former or active smokers with a median <strong>of</strong> 40 pack years. The<br />

median progression free survival <strong>of</strong> patients with stage IIIb/IV disease was<br />

11 months (95% CI 8-14; n�14). The median overall survival was not yet<br />

reached after a median follow-up time <strong>of</strong> 14 months (95% CI 11 - 17;<br />

n�24). We further screened for co-existing genetic lesions such as<br />

mutations in EGFR, BRAF, KRAS, PIK3CA as well as translocations <strong>of</strong> ALK<br />

and amplifications <strong>of</strong> ERBB2. Two patients demonstrated co-occurring<br />

PIK3CA mutations and one a BRAFmutation. Conclusions: Screening for<br />

FGFR1 is feasible under routine clinical conditions. By implementation <strong>of</strong> a<br />

regional molecular screening network the ability to screen for FGFR1<br />

amplification was successfully expanded to non-academic centers and<br />

private practices. FGFR1 amplifications in squamous cell cancer <strong>of</strong> the<br />

lung are frequent (16%) and associated with smoking history. Screening for<br />

FGFR1 might pave the way for the application <strong>of</strong> new FGFR1 directed<br />

targeted drugs in squamous cell lung cancer.<br />

Cancer Prevention/Epidemiology<br />

93s<br />

1531 Poster Discussion Session (Board #20), Sun, 8:00 AM-12:00 PM and<br />

11:30 AM-12:30 PM<br />

Never-smoking women with lung cancer from the Spanish WORLD07<br />

database. Presenting Author: Dolores Isla, Hospital Lozano Blesa, Zaragoza,<br />

Spain<br />

Background: Gender differences in lung cancer (LC) have been reported,<br />

but with many unresolved issues yet. Tobacco causes the majority <strong>of</strong><br />

women lung cancer (WLC), although the rate <strong>of</strong> never-smoking WLC is<br />

higher than in men. Several factors may play etiologic roles, and an<br />

in-depth understanding is needed. Methods: WORLD07 is a Spanish<br />

prospective, multicenter, epidemiologic female-specific LC database sponsored<br />

by ICAPEM, a pr<strong>of</strong>essional association committed with WLC research.<br />

In order to improve the knowledge on never-smoking WLC,<br />

information has been extracted from WORLD07 database. Results: From<br />

October/2007 to October/2011, 1371 newly diagnosed WLC were included<br />

in an e-database from 32 centers, 539 (39.3%) never-smoking.<br />

Patient (p) characteristics: median age 71.1 years(y); median age <strong>of</strong><br />

menarche 13y.; motherhood 91.2% (median 2.3 children, median age at<br />

first child 26.4y); oral contraceptive use 11.9%; postmenopausal 88.9%<br />

(median age <strong>of</strong> menopause 49y); HRT 5.2%; second-hand smokers 40%<br />

(work-exposure 17.1%, home-exposure 88.8%); obesity 16.3%; familiar<br />

history <strong>of</strong> cancer 39.9% (LC 29.8%); previous history <strong>of</strong> cancer 13%<br />

(breast/lung/cervix: 41.4/5.7/2.9%); current LC histology(%): adenocarcinoma/SqCC/LCC/SCLC:<br />

83.4/6.2/5.5/3.9; EGFR mut� (268 p analyzed):<br />

55.5% (exon 19/20/21(%): 61.1/7.4/36.9); TNM NSCLC I/II/III/IV(%):<br />

14/3.3/19.8/60.3. Treatment: EGFR-TKI in p EGFR mut�, stage IV(1st-/ 2nd-line)(%): 51.7/15.4; stage IV NSCLC (1st-line/2nd-line): platinumbased<br />

CT 42.5%, EGFR-TKI 33.5%, combinations with bevacizumab<br />

2.9% / EGFR-TKI 15.8%. Overall survival: median 27 months(m), 1/2y(%)<br />

74.8/55.2; stage IV NSCLC: median 20.5m, 1/2-y(%) 67/46;<br />

EGFR-mut� p: median 27.3m, 1/2-y(%) 75/54.3. Conclusions: According<br />

to our e-database, WLC showed high rates <strong>of</strong> never-smokers (39.3%), and<br />

<strong>of</strong> relatives diagnosed with malignant tumours (39.9%, �1/3 LC). Adenocarcinoma<br />

was the most frequent histology (76.1%), and more than half <strong>of</strong><br />

the cases analyzed harboured EGFR mutations. Although 40% were<br />

second-hand smokers, further investigations are warranted. Survival outcomes<br />

remain satisfactory, as expected from this selected subgroup <strong>of</strong> p.<br />

Additional epidemiologic and treatment data will be presented.<br />

1534 Poster Discussion Session (Board #23), Sun, 8:00 AM-12:00 PM and<br />

11:30 AM-12:30 PM<br />

Molecular epidemiological prospective study <strong>of</strong> EGFR mutations from<br />

Asian patients (pts) with advanced lung adenocarcinoma (PIONEER).<br />

Presenting Author: Pan-Chyr Yang, National Taiwan University Hospital,<br />

College <strong>of</strong> Medicine, Taipei, Taiwan<br />

Background: The epidemiological, multicenter prospective study<br />

(NCT01185314; PIONEER) assessed EGFR mutation (M) rates in pts from<br />

Asia with newly diagnosed advanced lung adenocarcinoma (ADC). Influence<br />

<strong>of</strong> demographic and clinical factors on EGFR M rates was investigated.<br />

Methods: Pts were aged �20 years, with treatment naïve stage<br />

IIIB/IV lung ADC. Tumor sample (biopsy, surgical specimen, cytology)<br />

EGFR M status (primary endpoint; positive [M�], negative [M-], undetermined<br />

[MU]) was determined using Scorpion ARMS (Therascreen EGFR<br />

RGQ kit). EGFR M frequency was calculated and compared between<br />

demographic/clinical factor subgroups (chi-square/Fisher’s exact test).<br />

Factors with p�0.05 in the univariate analysis were further analyzed by<br />

multivariate logistic regression at 1% significance level to take the large<br />

dataset into consideration. Results: Of 1482 pts from 7 Asian countries,<br />

43.4% were female, mean age was 60 years (range 17-94), and 52.6%<br />

were never-smokers. EGFR M status was evaluated in 1450 patients (32<br />

[2.2%] were MU): 746 (51.4%) were M�, 704 (48.6%) were M-. Country,<br />

gender, ethnicity, smoking status, pack years, metastasis, (all p�0.001)<br />

and disease stage (p�0.009) correlated significantly with EGFR M status.<br />

EGFR M� rate by country: Vietnam 64.2% (77/120), Taiwan 62.1%<br />

(108/174), Thailand 53.8% (63/117), Philippines 52.3% (34/65), China<br />

50.2% (372/741), Hong Kong 47.2% (76/161), India 22.2% (16/72).<br />

EGFR M� rates were 61.1% in females, 44.0% in males, 60.7% in never<br />

smokers, and 31.4% in heavy smokers (�50 pack years). EGFR M� rates<br />

were 37.5% in male regular smokers (113/301), 34.8% in female regular<br />

smokers (8/23), 56.5% in male never smokers (104/184) and 62.0% in<br />

female never smokers (358/577). Ethnic group (p�0.001) and pack years<br />

(p�0.001) were identified as important factors by logistic regression;<br />

gender was not significant when adjusted for smoking status. Conclusions:<br />

The overall EGFR M� rate in unselected ADC was 51.4%. Ethnicity and<br />

pack years were found to have a statistically significant association with<br />

EGFR M rates. There was no association between gender and EGFR M rates<br />

when adjusted for smoking status.<br />

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