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A. Boros
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MINI 07 - ChemoRT and Translational Science (ID 110)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:D. Raben, B. Kavanagh
- Coordinates: 9/07/2015, 16:45 - 18:15, 201+203
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MINI07.08 - Mutation Profile Prognostic Value in Stage III Non Small Cell Lung Cancer (NSCLC) Patients Treated with Chemo-Radiotherapy (CRT) (ID 2262)
17:25 - 17:30 | Author(s): A. Boros
- Abstract
- Presentation
Background:
Molecular profiling is a standard procedure in advanced non squamous NSCLC. Gene alteration in EGFR, BRAF or ALK gene can lead to prescription of targeted therapies and prolongs survival. The influence of molecular abnormalities on the survival of stage III NSCLC patients definitely treated by CRT is unknown.
Methods:
We reviewed all consecutive patients that received CRT or RT with a curative intent for stage III NSCLC in a single institution. Paraffin embedded tissue block were collected. DNA was extracted for gene mutation analysis by next generation sequencing and ALK, ROS1 and RET rearrangements were detected by FISH analysis. Kaplan-Meier methods, log-rank test, and Cox proportional hazards models were used for survival analysis, adjusting for performance status (0, ≥1), stage (IIIA, IIIB) and thoracic surgery (yes, no). Median follow-up was estimated by the Schemper method.
Results:
Between January2002 and June 2013, clinical data from 190 patients were collected. Median dose of RT was 66 Gy (46-70). Platinum-based chemotherapy was administrated concomitantly in 108 patients, as induction/consolidation treatment in 170 patients, and 15 patients did not receive any chemotherapy. Seventy-eight patients were evaluable for mutation profile, 20 (26%) were female, 47 (60%) were current smoker, 40 (51%) had adenocarcinoma and there were 47/31 stage IIIA/IIIB. Mutations were positive as follow: EGFR 12% (9/78), KRAS 15% (12/78), BRAF 5% (3/66), PI3KCA 2% (1/58), HER2 0% (0/65), NRAS 3% (1/32), CTNNB1 3% (1/32). FISH was positive for ALK in 5% (3/56) of the NSCLC. In 32 NSCLC for which the test was performed, there was no alteration in ROS1, RET, HRAS and AKT1. Median Follow-up was 3.1 years (minimum 0.9 year). EGFR mutated or ALK+ (EGFR/ALK) group (n=11) and other mutation group (n=17) had a poorer progression free survival (median 0.8[95%CI: 0.6 ; 0.9] year and 0.5 [0.4 ; 0.8] year ; multivariate hazard ratio (HR)= 1.8 [0.8 ; 3.8] and 2.8 [1.5 ; 5.1] respectively, p=0.004) compared to the wild group (n=50) (median 1 year [0.9;1.3]). There was no significant difference (p=0.23, multivariate Cox) in overall survival: median 2.4 years [1.3 ; NR] for EGFR/ALK group, 1.1 [0.6 ; 2.5] for other mutation group and 1.9 [1.5 ; 2.5] for wild type. In multivariate analysis, only the dose of radiotherapy was significantly associated with overall survival (HR=0.5 [0.3 ; 1.0], p=0.04 in contrast with performance status or stage.
Conclusion:
This study suggests that selected gene alterations could be associated with a poorer survival in stage III NSCLC patients treated by combined modality treatment or radiotherapy alone. Their prognostic and/or predictive value should be further evaluated in a larger population.
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ORAL 36 - Translational Science/Radiation (ID 151)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:E. Vokes, B. Kavanagh
- Coordinates: 9/09/2015, 16:45 - 18:15, Mile High Ballroom 2c-3c
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ORAL36.02 - Efficacy of Chemo-Radiotherapy (CRT) in Stage III Non-Small Cell Lung Cancer (NSCLC) and PD-L1 Expression (ID 2432)
16:56 - 17:07 | Author(s): A. Boros
- Abstract
- Presentation
Background:
Inhibition of the PD1/PD-L1 axis has been successfully developed in advanced NSCLC, and its role in locally advanced NSCLC is under investigation. The prognostic and predictive values of PD-L1 expression is still debated in advanced NSCLC and unknown in stage III NSCLC patients definitely treated by CRT
Methods:
We reviewed all consecutive patients that received CRT or RT with a curative intentfor stage III NSCLC in a single institution. Paraffin embedded tissue block were collected, immunohistochemistry was performed on a Ventana Benchmarck Ultra platform using the E1L3N clone (Cell Signaling Technologies). All tumors were centrally reviewed and tumor cells were scored accordingly (Herbst et al., Nature 2014).Kaplan-Meier methods, log-rank test, and Cox proportional hazards models were used for survival analysis, adjusting for performance status (0, ≥1), stage (IIIA, IIIB) and thoracic surgery (yes, no). Median follow-up was estimated by the Schemper method
Results:
Between January 2002 and June 2013, clinical data from 190 patients were collected. Median dose of RT was 66 Gy (46-70). Chemotherapy, mostly based on doublets with platin salt was administrated concomitantly in 108 patients, as induction/consolidation treatment in 170 patients, and 15 patients did not receive any chemotherapy. Fifty NSCLC were evaluable for PD-L1 expression, 22 (44%) being positive. Fourteen (28%) were female, 24 (48%) were current-smoker, 17 (34%) had adenocarcinoma and there were 23/27 stage IIIA/IIIB. Evaluable and unevaluable populations for PD-L1 were not different. There were no clinical or pathological factors related to PD-L1 positivity. Median follow-up was 7.6 years (minimum: 0.7 year). Median OS was 1.1year(95% confidence interval (CI) 0.6-1.5) in PD-L1 positive (pos) and 2.0 years (95% CI 1.5-3.8) in PD-L1 negative (neg) (p=0.01), HR=2.3 (95% CI 1.2-4.5, p=0.01). Median PFS was 0.7 year (95% CI 0.6-0.8) in PD-L1pos and 1.0 year (95% CI 0.8-1.5) in PD-L1neg (p=0.04), HR=2.1 (95% CI1.1-4.0, p=0.03). There was no difference in terms of acute toxicity according to PD-L1 status (positive or negative):25 had oesophagitis (grade≥2) and 16 had pneumonitis (p=0.57 and p=0.23 respectively).
Conclusion:
PD-L1 positivity was associated to a poorer survival in stage III NSCLC patients treated by definitive chemo-radiotherapy. Its prognostic and/or predictive value should be further evaluated in this population.
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