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David Harpole
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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): David Harpole
- 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 19.09 - The Role of Neoadjuvant Chemotherapy in Patients with Malignant Pleural Mesothelioma (ID 10187)
11:00 - 12:30 | Presenting Author(s): David Harpole
- Abstract
- Presentation
Background:
The treatment of localized malignant pleural mesothelioma (MPM) involves multimodality therapy, however, there is no standard of care with respect to operative procedure and timing of chemotherapy. We analyzed data from a single institution to identify whether the use of pemetrexed-platinum neoadjuvant chemotherapy impacts survival.
Method:
Patients with histologically-proven MPM who had surgery from 1996 to 2016 were identified. Follow-up was complete for a median of 24 months. Survival was calculated from time of diagnosis to last follow up or death. Univariate and multivariate Cox proportional hazards were used.
Result:
From 1996 to 2016 we identified 376 patients. Mean age was 66+/-8 years and 54 (14%) were female. There was no difference in survival for pleurectomy/decortication or extrapleural pneumonectomy. Neoadjuvant chemotherapy significantly improved survival compared to surgery followed by chemotherapy (table 1). Multivariate analysis was significantly associated for increased survival for epithelioid histology, T-status, node positivity, and neoadjuvant chemotherapy (table 2).Table 1. Univariate Analysis
Variable (n) Median survival (mo.) P value Gender Male (322) Female (54) 13.6 17.2 P=0.043 Histology Epithelial (252) Mixed (91) Sarcomatoid (26) 18.3 12.1 6.5 P<0.0001 T stage T 1-2 (33) T 3-4 (343) 42.6 14.3 P=0.0002 N status N 0 (129) N 1-2 (113) 23.1 11.3 P<0.0001 Neoadjuvant chemotherapy Yes (153) No (223) 19.8 11.3 P<0.0001 Table 2. Cox Proportional Hazards Model
Cox proportional hazards model including histology, t-status, n-status, and neoadjuvant chemotherapy C-index: 0.69Covariate Hazard Ratio 95% CI p-value Histology (ref: Epithelioid) Biphasic Sarcomatoid ref 1.66 4.24 [ref] [1.17-2.36] [1.77-10.1] ref 0.005 0.001 T-status 3-4 vs 1-2 3.07 [1.32-7.15] 0.009 Node-positivity 1.93 [1.40-2.66] <0.001 Neoadjuvant chemotherapy 0.65 [0.47-0.91] 0.011
Conclusion:
Our results suggest that neoadjuvant chemotherapy increases survival and likely enhances the complete resection rate. These data are being evaluated in a multi-institutional cohort of five major mesothelioma programs in North America to improve guidelines for mesothelioma therapy.
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MS 24 - Management of GGO-Containing Nodule (ID 546)
- Event: WCLC 2017
- Type: Mini Symposium
- Track: Radiology/Staging/Screening
- Presentations: 1
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MS 24.03 - When to Operate GGO-Containing Tumors? (ID 7756)
14:30 - 16:15 | Presenting Author(s): David Harpole
- Abstract
- Presentation
Abstract:
With the advent of Chest CT screening, the identification of abnormalities has increased substantially. In addition to very small nodules of indeterminate significance, “ground glass opacities” (GGO) are often seen. Numerous series have been collected around the world attempting to define characteristics that predict the malignant potential of these GGOs. It is clear that a substantial fraction includes a component of invasive adenocarcinoma and warrant resection for cure prior to developing disseminated cancer. This presentation will review the literature for developing a rational algorithm for selection of those patients requiring which operation, as well as review outcomes. 1. Radiological determinants of malignancy using high-resolution CT and CT/PET 2. Criteria for patient section for resection or observation 3. Techniques for pre-resection localization for intraoperative identification of lesion 4. Appropriate selection lesions for extent of resection (lobe, segment or non-anatomic wedge) 5. Approach for resection 6. Outcomes after treatment Selected References Matsunaga T, Suziki K, Takamochi K, Oh S. What is the radiological definition of part-solid tumor in lung cancer? Eur J Cardiothorac Surg 2017; 51:242-247 Eguchi T, Kondo R, Kakkami S, Matsushita M, Yoshizawa A, Hara D, Matsuoka S, Tkeda T, et al. CT attenuation predicts the growth of pure GGO nodules Lung Can 2014;84:242-247 Suzuki K, Asamura H, Kusumoto M, Kondo H, Tsuchiya R. Early peripheral lung cancer: prognostic significance of GGO on thin section CT scan Ann Thorac Surg 2002;74:1635-9 Lee S, Leem C, Kim T, Lee K, Chung J, Jheon WS, Lee C. The long term follow-up of GGO detected on thin-section CT Respir Med 2013;107:904-10 Suzuki K, Shimohira M, Hashizume T, Ozawa Y, Sobue R, Mimura M, Mori Y, Ijima H, Watanabe K, Yano M, Yoshioka H, Shibamoto Y. Usefulness of CT-guided hookwire marking before VATS for small pulmonary lesions J Med Imag Rad Oncol 2014; 58:657-662. Mong-Wei L, Yao-Hui T, Yee-Fan L, Min-Shu H, Wei-Chun K, Jo-Yu C, Hsao-Hsun H, Yeun-Chung C, Jin-Shing C. Comuted tomography-guided patent blue vital dye localization of pulmonary nodules in uniportal thoracoscopy J Cardiovasc Surg 2016; 152:535-44 Fukui M, Suziki K, Matsunaga T, Oh S, Takamochi K. Surgical intervention for GGO-dominant lesions: observation or outright resection? Pan J Clin Oncol 2017;18:1-6 Cao C, Gupta S, Chandrakumar D, Tian D, Black D, Yan T. Meta-analysis of intentional sublobar resections versus lobectomy for very early stage non-small cell lung cancer Ann Cardiothorac Surg 2014; 3:134-141 Kodama K, Higashiyayma M, Tkami K, Oda K, Okami J, Maeda J, Koyama M, Nakayama T. Treatment strategy for patients with small peripheral lung lesions: Prospective study Eur J Cardiothoracic Surg2008; 34:1068-74 Yoshioka M, Ichiguchi O. Selection of sublobar resection for c-stage1A non-small cell lung cancer based on a combination of structural imaging by CT and functional imaging by FDG-PET Ann Thorac Cardiovasc Surg 2009; 15:82-8. Kohno T, Fujimoro S, Kishi K, Fujii T. Safe and effective minimally invasive approaches for small GGOs Ann Thorac Surg 2010; 89; 1114-7 Tsutani Y, Miyata Y, Nakayama H, Okurmura S, Adachi S, Yoshimura M, Okada M. Appropriate sublobar resection choice for GGO-dominant clinical stage 1A lung Adenocarcinoma Chest 2014; 145:66-71 Sook Y, Sung S, Mankoong M, Park K. The effectiveness of mediastinal node evaluation in a patient with GGO tumor J Thorac Dis 2016; 8:2617-2623 Wei S, Khao K, Guo C, Mei J, Pu Q, Ma L, Che G, Chen G, Wu Z, Wang Y, Kuo Y, Lin Y, Li W Lui L. Diagnosis and surgical treatment of lung GGO: a review of 663 cases. Sichan Da Xue Bao Yi Xue Ban 2017:48:359-362 Moon Y, Lee K, Moon S, Park J. Sublobar resection margin does not affect recurrence of clinical N0 non-small cell lung cancer presenting as GGO. World J Surg 2017;41:472-9 Hattori A, Matsunaga T, Takamochi K, Oh S, Suzuki K. Surgical Management of Multifocal Ground-Glass Opacities of the Lung: Correlation of Clinicopathologic and Radiologic Findings Thorac Cardiovasc Surg 2017; 65:142-14 Shimada Y, Saji H, Otani K, Maehara S, Maeda J, Yoshida K, Kato Y, Hagiwara M, Kakihana M, Kajiwara N, Ohira T, Akata S, Ikeda N. Survival of a surgical series of lung cancer patients with synchronous multiple ground-glass opacities, and the management of their residual lesions Lung Cancer 88 (2015) 174-180
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