Tumor survivin expression in locally advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based chemoradiation followed by surgical resection

Abstract

7595 Background: Recently tumor molecular markers have shown promise as prognostic and predictive indicators for survival in early and advanced stage NSCLC patients (pts.) treated with chemotherapy. The objective of this study was to correlate immunohistochemistry (IHC) markers of pre-treatment biopsies in locally advanced NSCLC patients treated with concurrent platinum based chemoradiation followed by surgical resection. Methods: This is a retrospective study that included stage III NSCLC pts who had adequate pre-treatment tumor specimens and were treated with platinum based chemotherapy regimens and concurrent thoracic radiation (40 Gy). Thirty three pts had sufficient pre-treatment tissue for IHC and were identified from a surgical database. Cells were stained by IHC for frequency (0–4) and intensity (0–4) of ERCC1, PTEN, and survivin and analyzed by log-rank and multivariate Cox PH regression for potential relationships to pathologic complete response (pCR), time to recurrence (TTR), and overall survival (OS). Results: Characteristics of 33 pts: 15 females; median age 61; 17 adenocarcinoma, 10 squamous(sq), 5 undifferentiated, 1 adeno-sq. Median OS was 23 months (mo) (5.9–140), and median TTR was 14.7 mo (3.5–121). Following chemoradiation, 9 patients had pCR. pCR was associated with improved TTR, p < .027. ERCC1 and PTEN were not significantly related to OS, TTR, or pCR. High nuclear survivin frequency (>2) was associated with worse OS, HR 0.4, p< .045 and lower nuclear survivin intensity (<4) was marginally associated with pCR, p< .10. Conclusions: In this exploratory analysis, higher survivin expression was associated with worse prognosis in locally advanced NSCLC patients treated with chemoradiation followed by surgery. These results suggest that additional studies of survivin are warranted in NSCLC and that adding survivin inhibitors to chemoradiation is a reasonable strategy for locally advanced NSCLC with high survivin expression. No significant financial relationships to disclose.