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Raphael Bueno
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MA 13 - New Insights of Diagnosis and Update of Treatment (ID 674)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:S. Ishikura, H. Nakayama
- Coordinates: 10/17/2017, 15:45 - 17:30, Room 311 + 312
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MA 13.02 - Comprehensive Genetic Analysis Related to PD-L1 Expression in Early-stage Lung Squamous Cell Carcinoma (ID 9077)
15:45 - 17:30 | Author(s): Raphael Bueno
- Abstract
- Presentation
Background:
Recently, anti PD-1/PD-L1 immunotherapies have yielded promising outcomes in advanced squamous NSCLC. Several studies have suggested that tumor PD-L1 protein expression status might correlate with outcome and response to treatment. The aim of this study is to identify mRNA gene signatures and microRNAs associated with tumor PD-L1 expression in early-stage lung squamous cell carcinoma (SCC).
Method:
Early stage (I-II) SCC resected patient tumors were collected from 6 cancer centers as part of the SPECS II program. Gene expression profiling was performed on the specimens. PD-L1 protein expression was evaluated by immunohistochemistry on SCC FFPE tissue using the Dako 22C3 PD-L1 antibody. The tumor proportion score (TPS) for PD-L1 protein expression was compared with comprehensive clinicopathological, mRNA and miRNA data.
Result:
The prevalence of PD-L1 expression in this cohort of 255 Stage I-II SCC patients was 46.7% with a TPS cutoff of ≥ 1%, and 9.8% with a cutoff of ≥ 50%. Among 202 cases with available clinical and expression data, no significant association was observed between PD-L1 expression and clinical outcome. We identified a 12-gene signature from mRNA microarray using the Minimax Concave Penalty (MCP) regression method with an AUC of 0.92 at ≥ 5% TPS cutoff. A subset of 138 miRNAs was shown to be significantly differentially expressed between PD-L1 positive and PD-L1 negative groups at false discovery rate (FDR) of 0.05 with TPS cutoffs of ≥ 1%, ≥ 5% and ≥ 10%. No miRNAs were found to be significantly differentially expressed between the groups using a TPS cutoff of ≥ 50%. Gene Set Enrichment Analysis (GSEA) identified two pathways with gene sets that were significantly enriched (FDR < 0.05) in the PD-L1 negative group. No significant association was found between tumor mutation burden and PD-L1 expression level.
Conclusion:
PD-L1 expression prevalence is lower in early-stage lung SCC than in advanced NSCLC. No significant association was found between PD-L1 expression and prognosis in this cohort. Both mRNA gene signatures and miRNAs were identified to be predictive of PD-L1 expression. Through GSEA, two distinct gene sets were identified with expression correlated to PD-L1, one comprising genes related to ovary and another related to collagens and extracellular matrix (ECM). No significant association was found between tumor mutation burden and PD-L1 expression level. Following validation, these predictive signatures could be used to select patients with positive PD-L1 expression who may benefit from immunotherapy.
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MA 19 - Mesothelioma: Bench to Bedside (ID 680)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Mesothelioma
- Presentations: 1
- Moderators:Dean A Fennell, Hedy Lee Kindler
- Coordinates: 10/18/2017, 11:00 - 12:30, Room 315
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MA 19.10 - Comparative Value of MR and CT for Tumor Volumetric and Clinical Staging of Malignant Pleural Mesothelioma (ID 10122)
11:00 - 12:30 | Author(s): Raphael Bueno
- Abstract
- Presentation
Background:
Tumor volumetrics is currently being explored as a means of enhancing the accuracy of clinical staging of malignant pleural mesothelioma (MPM). In a recent multicenter study (JTO 2016, 11(8):1335-1344) evaluating feasibility of volume estimation using CT (VolCT), clinical staging by CT was poorly correlated between readers and underestimated pathological stage, but correlation of VolCT estimates between two experienced readers was high (rho = 0.82). MR has been found superior to CT in evaluating certain staging parameters, and may enhance volumetrics based on improved contrast. Here we evaluate the relative performance and reproducibility of MR for volumetrics (VolMR) and clinical staging of MPM in a single institution cohort.
Method:
Patients with MPM who underwent surgical resection between 2009 and 2014 with preoperative CT and MR imaging were studied. MR images were acquired using a uniform clinical protocol. VolMR was performed independently by two observers, one an experienced radiologist and one fellow. Vitrea (Vital Images) software was used for volumetric calculations and estimates were compared using Spearman correlation. Clinical staging accuracy (AJCC 7[th] edition criteria; versus pathological stage) and interobserver variability were also evaluated. VolMR and VolCT were performed for all cases by the experienced radiologist and qualitatively compared.
Result:
The study cohort comprised 139 patients, 113 (81%) men, median age 68 (30-82), with 74 (53%) epithelioid subtype tumors. Pathological stage was I: 14 (10%); II: 16 (12%); III: 75 (54%); IV: 34 (24%). Clinical staging by MR was concordant between reviewers for 86 (62%) cases, and with pathological stage for 65 (47%) and 63 (45%) respectively. VolMR was significantly correlated both between reviewers (rho = 0.99) and with VolCT (rho = 0.68). VolMR tended to result in higher volume estimates (median 633, IQR 365-885 cc) than VolCT (median 239, IQR 75-597 cc).
Conclusion:
VolMR was found to be feasible and reproducible, independent of observer experience. Clinical AJCC staging by MR was found to compare favorably to staging by CT in terms of both interobserver variablilty and prediction of pathological stage. Although MR is not yet universally available and has the disadvantages of higher cost, requirement for optimization and longer scan times, it may neverthheless offer improved accuracy and reproducibility of clinical staging and volumetric analysis. Further evaluation in larger multi-institutional cohorts is warranted.
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MS 08 - Novel Treatment for Mesothelioma (ID 530)
- Event: WCLC 2017
- Type: Mini Symposium
- Track: Mesothelioma
- Presentations: 1
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MS 08.03 - Basic Science and Surgical Advances in MPM (ID 7677)
15:45 - 17:30 | Presenting Author(s): Raphael Bueno
- Abstract
- Presentation
Abstract not provided
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