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

462s Lung Cancer—Non-small Cell Local-Regional/Small Cell/Other Thoracic Cancers
7044 General Poster Session (Board #35C), Sat, 1:15 PM-5:15 PM
Higher incidence of EGFR exon 19 deletion in younger (age 40 or younger)
patients with adenocarcinoma of the lung. Presenting Author: Eri Sugiyama,
Division of Thoracic Oncology, National Cancer Center Hospital East,
Kashiwa, Chiba, Japan
Background: The proportion of younger patients (� 40 years) with lung
cancer is reported to be 2-5%. The most frequent histologic type of them is
adenocarcinoma, however little is known about the pathological and
molecular characteristics of younger patients with lung adenocarcinoma.
Methods: Between July 1992 and April 2011, a total of 7443 patients were
diagnosed as lung cancer in National Cancer Center Hospital East and 165
patients of whom (2.2%) who were 40 years or younger were identified.
Among them, 44 patients with adenocarcinoma who underwent surgical
resection were selected for this study. In addition, 185 elderly patients with
� 40 years who underwent surgical resection matching gender and
smoking status were selected as a control group. Histological predominant
growth pattern and any coexisting variant pattern, the status of EGFR
mutations were compared between these two groups. Results: The median
age in � 40 years patients was 37 years (range, 21 to 40 years) and that in
elderly patients was 68 years (range, 42 to 83 years). Between these two
groups, there were no significant differences in the distribution of histological
predominant growth patterns (lepidic; 31.8% vs. 26.5%, papillary;
34.1% vs. 37.3%, acinar; 9.1% vs. 16.2%, and solid; 25.0% vs. 20.0%,
p�0.78) and the incidence of EGFR mutations (40.9% vs. 45.9%;
p�0.55). However, signet-ring cell component were significantly found in
the younger patients than elderly (11.4% vs. 0%; p�0.01). The incidence
of EGFR exon 19 deletion was significantly higher in younger patients than
elderly, in contrast, that of EGFR exon 21 L858R was significantly higher in
elderly patients (exon 19 del; 31.7% vs. 18.9%, L858R; 4.6% vs. 25.4%,
p�0.0091). Three of 17 adenocarcinomas (17.7%) with EGFR-wild type
in younger patients showed positive for ALK translocation. Conclusions:
Younger patients with lung adenocarcinoma showed significantly higher
proportion of EGFR exon 19 deletion genotype and containing histologically
signet-ring cell component comparing with elderly patients. EGFR
exon 19 deletion genotype may be related to pathogenesis of lung
adenocarcinoma in younger patients.
7046 General Poster Session (Board #35E), Sat, 1:15 PM-5:15 PM
Molecular profiling of patients with non-small cell lung cancer (NSCLC)
using bronchoscopic ultra-micro sampling. Presenting Author: Yuichi
Sakairi, Department of General Thoracic Surgery, Graduate School of
Medicine, Chiba University, Chiba, Japan
Background: Genetic information is essential for molecular targeted therapy
for personalized medicine, although tissue sampling for genetic analysis
remains challenging. In this study, we investigated the utility of bronchoscopic
ultra-micro samples compared with conventional histological materials
for multiple gene analyses for NSCLC. Methods: Patients with NSCLC
proven by on-site cytological examinations during bronchoscopic survey
were eligible. Following conventional needle aspiration biopsy by flexible
bronchofiberscope (from primary lesion) or convex probe endobronchial
ultrasound (from lymph nodes), the used needle was rinsed with 20 ml of
saline and this ultra-micro sample (MS) was used for both cytological
diagnosis and genetic analysis. DNA and RNA were extracted from each
sample. Gene mutations [EGFR (epidermal growth factor receptor), K-ras,
BRAF] and anaplastic lymphoma kinase (ALK) fusion genes were examined
by high resolution melting analysis and direct sequencing. The results of
cytological diagnoses and gene profiles using MS were compared to
conventional histological diagnoses. Results: A total of 79 lesions (30
primary and 49 metastatic nodes) from 76 patients were eligible. Adenocarcinoma
(N � 46), squamous cell carcinoma (N � 25), and NSCLC (N � 8)
were pathologically confirmed in histological lesion cores; however, only 29
malignancies (37%) were detected with MS. DNA and RNA could be
extracted from all histological samples and MS. In 35 cases, genetic
disorders were identified, including EGFR mutations (N � 12), K-ras
mutations (N � 5), BRAF mutation (N � 1), ALK fusion genes (N � 3), and
silent mutations (N � 13); these results were identical for both histological
samples and MS. Conclusions: Bronchoscopic ultra-micro samples (biopsy
needle rinse fluids) are useful for multiple genetic examinations.
7045 General Poster Session (Board #35D), Sat, 1:15 PM-5:15 PM
A phase II trial of induction gefitinib monotherapy followed by cisplatindocetaxel
and concurrent thoracic irradiation in patients with EGFRmutant
locally advanced non-small-cell lung cancer (LA-NSCLC):
LOGIK0902/OLCSG0905 intergroup trial. Presenting Author: Akiko
Hisamoto, Department of Respiratory Medicine, Okayama University Hospital,
Okayama, Japan
Background: We previously reported efficacy and safety of cisplatindocetaxel
and concurrent thoracic radiotherapy (TRT) for LA-NSCLC
(Segawa Y and Kiura K. JCO 2010). However, its cure rate remains
unsatisfied, and further improvement in the treatment outcome is strongly
warranted. Recently, systemic chemotherapy has been individualized by
intensive anti-cancer researches through the discovery of certain molecular
targets in the metastatic NSCLC. Especially, gefitinib, EGFR tyrosine
kinase inhibitor, is quite active and now one of the standard chemotherapy
for untreated metastatic EGFR-mutant NSCLC (Maemondo M and Inoue A.
NEJM 2010). Even in the locally advanced setting, approximately 30% of
Japanese NSCLC patients possess EGFR-mutant tumors. Given all of these
backgrounds, investigation on the role of adding gefitinib monotherapy to
the standard concurrent chemoradiotherapy might cause a new paradigm
shift in this setting. Methods: Patients have to meet the following eligibility
criteria: LA-NSCLC; active tumor EGFR mutations (exons 19 and 21) but
without 790M; measurable lesions; performance status (PS) of 0 or 1; age
� 75 years; and V20 � 35%. The primary endpoint is set as 2-year
progression-free survival (PFS) rate; assuming that 75% in eligible patients
would indicate potential usefulness, whereas 60% would be the lower limit
of interest (� � 0.05, ß � 0.20), the estimated accrual number is 46
patients. The secondary endpoint includes toxicity, response rate and
overall survival. Patients will receive the induction treatment, specified as
gefitinib monotherapy (250 mg/body) for 8 weeks. Patients who have not
progressed during the induction therapy will receive cisplatin and docetaxel
(40 mg/m2 ; days 1, 8, 29, 36, each) and concurrent three-dimensional
conformal TRT (2-Gy, single, daily fractions for 5 consecutive days each
week to provide a total dose of 60 Gy). Enrollment began in 2010, and will
complete by 2015. UMIN registration number of 000005086.
7047 General Poster Session (Board #35F), Sat, 1:15 PM-5:15 PM
Relationship between tumor size and survival in non-small cell lung cancer
(NSCLC): An analysis of the Surveillance, Epidemiology, and End Results
(SEER) registry. Presenting Author: Jianjun Zhang, University of Texas
M. D. Anderson Cancer Center, Houston, TX
Background: Tumor size is a known prognostic factor for early stage (I and II)
NSCLC, but its significance in node positive or locally advanced NSCLC has
not been determined. We sought to evaluate its prognostic value in early
and locally advanced NSCLC and create a nomogram incorporating tumor
size and other prognostic variables to predict survival. Methods: The SEER
registry was queried for patients (pts) with NSCLC, aged 20-103 and
diagnosed between 1998 and 2003. Pts with extra-pulmonary metastases
or distant lymph node metastases were excluded. Tumor size was analyzed
as a continuous variable. Other demographic variables included age,
gender, race, histology, primary tumor extension, node status and primary
treatment modality (surgery vs radiation). Log-rank test was performed to
evaluate the relationship between these variables and overall survival (OS).
Cox proportional hazard model was used to evaluate whether tumor size was
an independent prognostic factor. Results: 52,287 eligible pts were divided
into 16 subgroups based on primary tumor extension and node status. For
example, in group 1, tumor was confined to one lung with no nodes
involved; pts in group 12 had tumor invading the mediastinum (T4 by
extent) and positive ipsilateral mediastinal nodes. Tumor size had a
significant effect on OS in almost all groups after adjustment for age, sex,
race, histology, node status, primary tumor extension and primary treatment
modality. Our model incorporating tumor size had significantly better
predictive accuracy (larger C index) than our alternative model not
including this information (p�0.0001). We then developed a nomogram
incorporating tumor size, age, gender, race, histology, nodule stage, and
tumor extension with the intent to predict OS. In subsequent bootstrap
verification, the predicted 2-year OS from the nomogram was almost
identical to the actual observed 2-year OS with a very slim biases of
estimates. Conclusions: Tumor size is an independent prognostic factor,
including pts with node positive or locally advanced NSCLC. We successfully
created a nomogram incorporating tumor size and other clinical
variables to predict survival.
Visit abstract.asco.org and search by abstract for the full list of abstract authors and their disclosure information.