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

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7595-7595
Author(s):  
M. J. Fidler ◽  
A. Seba ◽  
E. C. Farlow ◽  
S. Basu ◽  
K. Kaiser-Walters ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Advanced Nsclc ◽  
Locally Advanced ◽  
Survivin Expression ◽  
Platinum Based Chemotherapy ◽  
Locally Advanced Nsclc ◽  
Thoracic Radiation ◽  
Pre Treatment ◽  
Nsclc Patients ◽  
Nuclear Survivin

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.

Thoracic radiation therapy in locally advanced NSCLC patients (pts) with EGFR mutations.

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. 7016-7016 ◽  
Author(s):  
R. H. Mak ◽  
E. Doran ◽  
A. Muzikansky ◽  
J. Kang ◽  
N. C. Choi ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Advanced Nsclc ◽  
Locally Advanced ◽  
Egfr Mutations ◽  
Locally Advanced Nsclc ◽  
Thoracic Radiation ◽  
Nsclc Patients

High efficacy of paclitaxel (P), carboplatin (C) and concurrent thoracic radiation therapy (TRT) for locally advanced non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17143-17143
Author(s):  
K. Kishi ◽  
A. Okazaki ◽  
H. Takaya ◽  
A. Miyamoto ◽  
S. Sakamoto ◽  
...  
Keyword(s):  
Weight Loss ◽  
Advanced Nsclc ◽  
Combined Modality Therapy ◽  
Locally Advanced ◽  
Chemotherapeutic Agents ◽  
Stage Iiia ◽  
Number Of Patients ◽  
Locally Advanced Nsclc ◽  
Thoracic Radiation ◽  
Grade 3

17143 Background: Combined modality therapy with P, C and radiation for locally advanced NSCLC is active, but its clinical data are limited in Japan. The aim of this study is to evaluate feasibility and efficacy of the therapy in a Japanese general hospital. Methods: Patients with previously untreated and locally advanced NSCLC with stage IIIA and IIIB (PS 0–1, weight loss less than 5% over past 3 months) were treated with P (40 mg/m2 on days 1,8,15, 22, 29, 36, 43), C (AUC 2 on days 1,8,15, 22, 29, 36, 43) and TRT (66 Gy/33fr over 6.5 weeks starting on day1). Results: Fifteen evaluable patients entered this study between December 2001 and March 2005. They were 12 males, 3 females, with median age 67 (57–76); 6 patients with ECOG PS 0, 9 with PS 1, 8 with stage IIIA, and 7 with IIIB. Chemotherapeutic agents were administered a median of 6 cycles (4–7) and 66 Gy of TRT done in 14 patients. It achieved 13 PRs, 1 SD and 1 PD with a response rate of 86.7%. Survival was 85.5% at 1 year, 66.0% at 2 year and 66.0% at 3 year. Eleven patients are still alive. A relapse occurred in 10 patients (66.7%) and 5 were disease-free (33.3%). The site of first relapse was distant in 5 patients, local in 3, and both local and distant in 2. Toxicity was mild: grade 3 neutropenia in 2 patients, grade 3 nausea in 1, and grade 3 esophagitis in 1. No grade 3/4 pneumonitis was observed. After completion of chemoradiotherapy scheduled, 2 patients received additional chemotherapy of PC and 1 underwent lobectomy. Conclusion: Although the number of patients is small in this study, concurrent PC and TRT for locally advanced NSCLC is feasible and highly effective for Japanese patients with good PS and minimal weight loss. No significant financial relationships to disclose.

Impact of chemoradiotherapy (CRT) on immune-related tumor microenvironment and the efficacy of anti-PD-1 therapy after the recurrence of CRT in unresectable locally advanced NSCLC patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21719-e21719
Author(s):  
Masayuki Shirasawa ◽  
Tatsuya Yoshida ◽  
Noriko Motoi ◽  
Yuji Matsumoto ◽  
Yuki Shinno ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Advanced Nsclc ◽  
Locally Advanced ◽  
Antibody Therapy ◽  
Progression Free Survival ◽  
Expression Levels ◽  
Locally Advanced Nsclc ◽  
The Status ◽  
History Of ◽  
Nsclc Patients

e21719 Background: Chemoradiotherapy (CRT) followed by durvalumab as maintenance therapy prolonged progression-free survival (PFS) and overall survival (OS) in unresectable locally advanced NSCLC (LA-NSCLC). Additionally, the history of radiotherapy and CRT has been reported to increase the efficacy of PD-1 blockade in advanced NSCLC patients. We evaluated the efficacy of anti-PD-(L)1 antibody therapy after CRT failure, and how CRT changes the status of PD-L1 expression on tumors and tumor infiltrated lymphocytes (TILs) in tumor microenvironment (TME) in unresectable LA-NSCLC patients. Methods: We retrospectively reviewed unresectable LA-NSCLC patients treated with CRT between December 2007 and December 2018, and evaluated the efficacy of PD-1 blockade after CRT failure. We also analyzed PD-L1 (clone: 22C3) expression on tumor cells, and CD8 positive TILs using the paired specimens that had been obtained pre-CRT and post-CRT failure. Results: We identified 422 patients who received CRT. Median follow-up was 36.1 months (range 2.7–138.1 months). Among these patients, sixty-five patients who had progressed post-CRT received anti-PD- (L)1 therapy (PD-1 therapy: 61 patients, PD-L1 therapy: 4 patients). Response rate (RR) and PFS of anti-PD-(L)1 therapy were 48% (95% CI, 35–60) and 8.7 (95% CI, 4.5–13.0) months. The RR and PFS did not differ according to PD-L1 expression levels (Table). Of the 18 patients, 9, 7, and 2 showed upregulation in PD-L1 expression or down- or no change, respectively, post-CRT. In contrast, the density of CD8 positive TILs in TME increased by CRT treatment ([pre-CRT]: median, 110 ± 239 /mm2 vs. [post-CRT]: median, 470 ± 533 /mm2, p = 0.025). Conclusions: The clinical outcome of anti-PD-(L)1 therapy after CRT failure in LA-NSCLC patients could be better than advanced NSCLC patients, but did not differ according to PD-L1 expression levels. The efficacy of PD-(L)1 therapy enhanced by CRT treatment could be due to the infiltration of CD8 T-cells into TME. [Table: see text]

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