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C. Caramella
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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)
16:45 - 18:15 | Author(s): C. Caramella
- 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)
16:45 - 18:15 | Author(s): C. Caramella
- 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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P1.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 224)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.08-025 - Tumor Control of Advanced Pulmonary Neuroendocrine Tumors (Carcinoids) with Somatostatin Analogs: Experience at Gustave Roussy (ID 2758)
09:30 - 17:00 | Author(s): C. Caramella
- Abstract
Background:
Pulmonary carcinoids are rare neuroendocrine tumors (puNETs) of the lung with no standard therapeutic option. Antitumor control benefit of somatostatin analogs (SSAs) has been demonstrated in gastroeneropancreatic (GEP)-NETs, but only a few data have been published in puNETs.
Methods:
Data from advanced puNETs patients treated with SSAs in monotherapy between 1986 and 2014 at Gustave Roussy were retrospectively collected. Demographical, clinical and tumor-related features were recorded. Patients had a tumor evaluation by CT-scan and/or MRI every 3 months. Progression-free survival (PFS) and Overall survival (OS) were estimated using Kaplan-Meier. Response rate and toxicity were assessed according to RECIST (v1.0 until 2008 and v1.1 since 2009) and NCI.CTC v4.03 criteria respectively.
Results:
Sixty-one metastatic patients with a median follow-up of 5.8 yrs (0.4-13.0 yrs) were included, with a median age of 55 yrs (13-84 yrs), 55.7% were male, 29% current or former smokers, and 95% had PS ≤1. At diagnosis, 20 patients were classified as typical carcinoids (TCs) and 41 as atypical carcinoids (ACs) according to 2004 WHO classification. Before SSAs initiation, 49 patients (80%) showed uptake at somatostatin receptor scintigraphy (SRS) (grade ≥2) and 29 (52%) showed hormone-related symptoms. The majority of patients (75.4%) presented at least two metastatic sites, liver being the most frequent one (80.3%). Forty-six (75%) patients received SSAs as first-line therapy: 32 patients (70%) for disease progression and 14 patients (30%) for symptomatic carcinoid syndrome. The median duration of SSAs was 13.7 months (3.0-155.1). Overall, median PFS (mPFS) and OS (mOS) were 17.4 [95% CI=8.7-26.0] and 58.4 months [44.2-102.7], respectively. Best response was stable disease (SD) for 43 patients (70.5%) and progression disease (PD) for 14 patients (23%). All PD were ACs. The number of events and deaths was 46 (75%) and 29 (48%), respectively. mPFS was 24.8 months [10.1-36.3] for the TCs and 12.8 months [6.2-26.0] for the ACs patients (p=0.32). mPFS was significantly longer in functional puNETs with a mPFS of 28.7 months [13.2-55.6] vs. 8.7 months [5.8-21.2] in non-functional tumors (p=0.01). The most common adverse event was grade 1 diarrhea in 43% of patients. Only one grade 3 (abdominal pain) was reported with a consequent withdrawal of treatment.
Conclusion:
In the real-world setting, SSAs are safe and potentially effective for the antitumor control of puNETs. Our results suggest that patients with typical carcinoids and functional puNETs seem to benefit most from SSAs therapy.
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-042 - Evaluation of Texture Analysis Parameters in EGFR Mutated or ALK-Positive Advanced Non-Small Cell Lung Cancer (NSCLC) (ID 1394)
09:30 - 17:00 | Author(s): C. Caramella
- Abstract
Background:
The quantitative assessment of heterogeneity in tumor images through Texture Analysis is an emerging tool that can potentially provide a non-invasive prognostic biomarker. We investigated if Texture Analysis parameters derived from contrast-enhanced CT (CTTA) were associated with EGFR/ALK status and have a prognostic value in NSCLC patients treated with tyrosine-kinase inhibitors.
Methods:
The CT images of patients with EGFR mutated or ALK rearranged advanced NSCLC treated with tyrosine-kinase inhibitors were retrospectively reviewed. CTTA using the filtration-histogram method was applied to the region of interest (ROI) in the primary tumor of the enhanced-CT by two independent operators to examine the inter-individual reproducibility. A wilcoxon test was used to correlate CTTA with EGFR / ALK status and a Cox model to evaluate the prognostic value of CTTA for overall survival. A p-value cutoff of 0.01 was used to adjust for multiple testing.
Results:
CTTA parameters were evaluated in CT scan from 68 patients recruited in 2 centers between 2008 and 2013, of them, 80.9% (n=55) were EGFR mutated and 19.1 % (n=13) ALK+ NSCLC, 48.5% received treatment with gefitinib (n=33), 33.8% with erlotinib (n=23) and 17.7% with crizotinib (n=12). The CTTA measures were highly reproducible between the 2 operators as indicated by Bland-Altman plots and correlation values. The skewness of the distribution was significantly different between EGFR mutated and ALK+ tumors for coarse texture with spatial filter value 3.3 (p= 0.002), filter value 2.8 (p=0.001) and medium texture with spatial filter value 2.2 (p=0.004). The median follow-up time was 35 months; 39 deaths occurred. The A unit increase in skewness in coarse texture (2.8 spatial filter) was significantly associated with better survival with an univariate cox analysis (HR: 0.36 [0.2-0.69] p=0.002). A multivariate analysis adjusted by prognostic factors (PS, lymphocyte count, hepatic and adrenal metastasis) indicate a similar trend for better survival (HR: 0.40 [0.2-0.8] p=0.01).
Conclusion:
CTTA parameters were reproducible between the 2 operators. The skewness was significantly different between EGFR mutated and ALK rearranged advanced NSCLC and may have a prognostic value.
