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

Lung Cancer—Non-small Cell Local-Regional/Small Cell/Other Thoracic Cancers
7064 General Poster Session (Board #37G), Sat, 1:15 PM-5:15 PM
Survival following segmentectomy and lobectomy for stage I non-small cell
lung cancer. Presenting Author: Cardinale B. Smith, Division of Hematology
and Medical Oncology, The Tisch Cancer Institute, Mount Sinai School
of Medicine, New York, NY
Background: Although lobectomy is considered the standard surgical
treatment forstage IA non–small cell lung cancer (NSCLC), limited resections
are frequently performed for patients with poor lung function or high
operative risk. Recent studies suggest that segmentectomy may be the
superior limited resection procedure. The objective of this study was to
compare survival among patients with stage IA (�3cm) NSCLC undergoing
lobectomy vs. segmentectomy. Methods: Using theSurveillance, Epidemiology
and End Results registry we identified 15,180 cases of stage IA NSCLC
that underwent lobectomy or segmentectomy. We used logistic regression
to determine propensity scores for patients undergoing segmentectomy
based on the patient’s preoperative characteristics. Overall and lung
cancer-specific survival of patients treated with lobectomy versus segmentectomy
was compared after adjusting, stratifying, or matching patients
based on their propensity score. We also performed secondary analyses in
subgroups of age (�70 vs. �70 years) and tumor size �2 cm. Results:
Overall, 1,200 (8%) patients underwent segmentectomy. Among the entire
cohort, analyses adjusting for propensity scores did not demonstrate a
difference in outcomes among patients treated with lobectomy versus
segmentectomy, (adjusted hazard ratio [HR] for overall survival 1.11, 95%
confidence interval [CI]: 0.94 – 1.30 and lung cancer-specific survival
1.11, 95% CI: 0.98 – 1.25). Similarly, secondary analyses showed no
difference in overall (HR: 1.12, 95% CI: 0.90 – 1.40) and lung cancerspecific
survival (HR: 1.04, 95% CI: 0.88 – 1.24) among patients with
tumors �2 cm (T1a tumors). For patients �70 years of age, no difference
in overall survival was observed (HR: 0.97, 95% CI: 0.73 – 1.28); however,
a lung cancer-specific survival advantage of lobectomy was observed (HR:
1.19, 95% CI: 1.00 – 1.40). Finally, among those �70 years overall
survival (HR: 1.03, 95% CI: 0.87 – 1.22) and lung cancer-specific survival
(HR: 1.18, 95% CI: 0. 97 – 1.44) showed equivalence of the two surgical
groups. Conclusions: Segmentectomy and lobectomy may lead to equivalent
survival rates among patients with stage IA NSCLC. These study
findings should be confirmed in prospective studies.
7066 General Poster Session (Board #38A), Sat, 1:15 PM-5:15 PM
Prospective study of tumor suppressor gene (TSG) methylation as a
prognostic biomarker in surgically resected non-small cell lung cancer
(NSCLC). Presenting Author: Christopher G. Azzoli, Memorial Sloan-
Kettering Cancer Center, New York, NY
Background: In the New England Journal of Medicine, Brock et al. (2008)
published a nested case-control study which tested the association
between early recurrence of NSCLC after surgical resection, and TSG
promoter methylation in tumor and lymph nodes detected by methylationspecific
PCR (MSP). They reported that promoter methylation of the TSGs
p16, CDH13, RASSF1A, and APC was significantly associated with early
recurrence in 51 patients with stage I NSCLC compared to matched
patients without early recurrence. We attempted to confirm these findings.
Methods: In a prospective study, fresh frozen tumor tissue was acquired
after surgical resection in 107 patients with stage I-IIIA NSCLC between
2003-2008. The promoter methylation status of the same 4 genes
examined by Brock, et al (p16, CDH13, RASSF1A, APC), as well as 6
additional TSGs (MGMT, WIF-1, METH-2, GSTP1, SOCS3, DAPK) were
assessed in the tumor tissue using quantitative MSP (MethyLight assay),
with any amount of methylation scored as positive. Methylation status was
correlated with clinical features, pathologic stage, disease-free survival
(DFS), and overall survival (OS). Results: No significant associations were
observed between promoter methylation of individual TSGs and DFS. No
significant associations were observed between the number of methylated
TSGs and DFS, or OS. Increased RASSF1A methylation was observed in
poorly-differentiated and undifferentiated tumors compared to tumors that
were well- or moderately-differentiated (p�0.031). Increased WIF-1 methylation
and GSTP1 methylation were associated with increasing T (p�0.01)
and N stage (p�0.028), respectively. Squamous cell carcinomas (SQCCs)
were characterized by increased p16 methylation (p�0.0314) and decreased
APC methylation (p�0.0146) compared to tumors of non-SQCC
histologies. Conclusions: In this prospective study, we did not confirm that
the promoter methylation of p16, CDH13, RASSF1A, and APC, or 6 other
TSGs, was prognostic for early recurrence in surgically resected NSCLC.
467s
7065 General Poster Session (Board #37H), Sat, 1:15 PM-5:15 PM
Phase II study of concurrent cetuximab (C225) plus definitive thoracic
radiotherapy (XRT) followed by adjuvant docetaxel in poor prognosis
patients with locally advanced non-small cell lung cancer (LA-NSCLC).
Presenting Author: Thomas J. Dilling, H. Lee Moffitt Cancer Center &
Research Institute, Tampa, FL
Background: Recursive partitioning analysis has shown that ECOG PS � 2,
male gender, or age � 70 are prognostic of poor outcome in LA-NSCLC pts.
Concurrent chemoradiotherapy improves survival, but toxicity is concerning
in this frail pt cohort. We therefore opened this trial of concurrent
definitive-dose XRT (70 Gy in 35 fractions) and C225 (250 mg/m2 /dose),
followed by adjuvant C225 and docetaxel (60 mg/m2 q3weeks x 3 cycles).
Methods: Eligible patients had pathologically-proven LA-NSCLC (stage IIA –
“dry” IIIB), not surgically resectable. They had ECOG PS 2 OR weight loss
�5% in 3 months OR age �70. The primary objective was progression-free
survival (PFS). Secondary objectives included overall survival (OS) and
overall response rate (ORR). Results: From 5/2008 to 11/2010, 32 pts were
evaluated for our single-institution, IRB-approved prospective clinical trial.
3 pts were screen-failures and 2 more withdrew consent prior to treatment,
leaving 27 evaluable patients. 1 was removed due to poor therapy
compliance and 2 were taken off trial due to grade 3 toxicity from the C225
loading dose, but were followed under intent-to-treat analysis. Median
follow-up and OS was 10.5 months. Median PFS was 7.8 months. ORR �
59.3%. 8 early/sudden deaths were reported, so the trial closed early:
radiation pneumonitis (RP) was the apparent cause in 1 and probably/
possibly in 4 others, with insufficient information in 2 additional pts; 1 pt
died of failure to thrive. Of the remaining pts, 3 developed grade 3� RP and
2 had grade 2 RP. Conclusions: Pts enrolled on this trial had improved OS
compared with poor-PS historical controls (10.5 vs 6.3 months) and
comparable OS compared with good-PS historical controls (10.5 vs 11.9
months) treated with RT (Werner-Wasik M et al. Int J Radiat Oncol Biol
Phys. 2000;48:1475-82). However, pulmonary toxicity is a concern.
Analysis of RP events is ongoing. Updated results will be presented at the
meeting.
7067 General Poster Session (Board #38B), Sat, 1:15 PM-5:15 PM
Preoperative survivin, ERCC1, and PTEN expression in stage III non-small
cell lung cancer (NSCLC) patients (pts) treated with neoadjuvant and
definitive chemoradiation and association with overall survival (OS).
Presenting Author: Marta Batus, Rush University Medical Center, Chicago,
IL
Background: Thoracic radiation and concurrent chemotherapy consisting of
platinum based doublets has produced modest improvement in long term
survival for patient with locally advanced (LA) NSCLC. There is relatively
little information regarding molecular profiles and outcome in LA-NSCLC
patients (pts) treated with chemoradiation. The objective of this retrospective
study is to evaluate potential relationships between expression of DNA
repair enzyme ERCC1 and enzymes involved in cell survival – survivin and
PTEN. Methods: Stage III NSCLC pts who were treated with chest radiation
(40-60Gy) and concurrently with platinum doublet and who had sufficient
pretreatment tissue were included in this study. Immunohistochemistry
was used to detect nuclear and cytoplasmic expression (frequency 0-4 and
intensity 0-4) of survivin, and PTEN, and for nuclear expression of ERCC1.
Product of intensity and frequency was calculated for all markers and
correlated with overall survival (OS). Results: 97 pts had adequate tumor
samples for analysis. 53 women, median age 67. 48 pts with ERCC1 prod
��6 had longer OS than 41 pts with ERCC1 prod �6 (19.6 vs 1.0 months,
p�0.034). 16 pts with ERCC1 prod �6, PETN prod ��6 and survivin prod
�4 had significantly lower OS than 68 pts with ERCC1��6, PETN �6 and
survivin ��4 (17.2 vs 40.2 months, p�0.001). Conclusions: The association
of inferior survival in LA-NSCLC pts whose tumors express high
survivin, low PTEN, and high ERCC1, suggests that combining inhibitors of
survivin and or of PI3KCA with chemoradiation and developing strategies to
inhibit DNA repair might improve outcomes in this group of pts.
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