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David Harpole



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    GR02 - Management of N2 NSCLC - A Case Based Discussion (ID 778)

    • Event: WCLC 2018
    • Type: Grand Rounds Session
    • Track: Treatment of Locoregional Disease - NSCLC
    • Presentations: 3
    • Moderators:
    • Coordinates: 9/25/2018, 15:15 - 16:45, Room 107
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      GR02.02 - Panel Discussion (ID 11394)

      15:25 - 15:45  |  Presenting Author(s): David Harpole

      • Abstract

      Abstract not provided

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      GR02.04 - Panel Discussion (ID 14533)

      15:55 - 16:15  |  Presenting Author(s): David Harpole

      • Abstract

      Abstract not provided

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      GR02.06 - Panel Discussion (ID 14534)

      16:25 - 16:45  |  Presenting Author(s): David Harpole

      • Abstract

      Abstract not provided

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    P1.04 - Immunooncology (Not CME Accredited Session) (ID 936)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.04-23 - Expression of Emerging Immunotherapy Targets in Early-Stage Squamous Lung Carcinoma (ID 13520)

      16:45 - 18:00  |  Author(s): David Harpole

      • Abstract
      • Slides

      Background

      Anti-PD1/PD-L1 immunotherapy has demonstrated response in approximately 20% of unselected advanced non-small cell lung cancer (NSCLC) patients. Strategies involving combination immunotherapies are under investigation to improve the overall response to immunotherapy. The objective of this study was to identify the expression of emerging immune targets in a cohort of early-stage squamous lung carcinoma (SqLC), which may be used to design combinatorial immunotherapy approaches.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      202 early stage (I-II) SqLC resected patient tumors and corresponding clinical data were collected from 6 cancer centers as part of the SPECS II program. Fourteen emerging immune targets or targeted axis were selected based on their advanced stage of development in preclinical/clinical studies. The mRNA expression level of these targets and PD-1/PD-L1 were determined by Affymetrix U133A gene expression profiling. The correlations among these targets and the overall survival were evaluated.

      4c3880bb027f159e801041b1021e88e8 Result

      The mRNA levels of the immune molecules which were grouped on PD-L1 protein expression in early stage SqLC are shown in Figure 1. No correlation was found between the mRNA level of PD-L1 and the other immune targets expressed on APC/tumor cells, except PD-L2 (r2= 0.41, p<0.00001). We found that the immune cell receptor, CD226, correlated with CD96 and CD112R respectively (r2= 0.514, p<0.00001; r2= 0.476, p<0.00001), and CD96 correlated with CD112R (r2= 0.644, p<0.00001) as well. In addition, higher expression of GAL-9, CD48 and ICOS were associated with better prognosis [p= 0.0358, HR=0.249 (0.068, 0.912); p= 0.0309, HR=1.61 (1.04, 2.49); p= 0.0429, HR=2.47 (1.03, 5.93)].

      figure 1.tif

      8eea62084ca7e541d918e823422bd82e Conclusion

      Several emerging immune targets were expressed at higher levels than PD-L1 in this early stage SqLC cohort. The mRNA levels of all immune targets evaluated were independent of PD-L1 expression, except PD-L2. The expression of GAL-9, CD48 and ICOS were identified as prognostic. These results may provide important information in the design of future combination immunotherapies for early-stage SqLC.

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    P1.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 948)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.16-50 - The Role of Adjuvant Therapy for Patients with Early Stage Large Cell Neuroendocrine Lung Cancer: A National Analysis (ID 13077)

      16:45 - 18:00  |  Author(s): David Harpole

      • Abstract
      • Slides

      Background

      Although large cell neuroendocrine lung cancer (LCNEC) generally has a worse prognosis than other non-small cell lung cancer histologies, data regarding the role of adjuvant therapy in completely resected stage I LCNEC are extremely limited and current guidelines do not routinely recommend adjuvant therapy. This U.S. National Cancer Data Base (NCDB) analysis was performed to improve the evidence guiding decision-making regarding postoperative therapy for early stage LCNEC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Overall survival of patients with pathologic T1-2aN0 LCNEC who underwent resection in the NCDB from 2003 to 2015 was evaluated using Kaplan-Meier and multivariable Cox proportional hazard analysis. Patients who died within 30 days of surgery were excluded. These prospective data were acquired by certified tumor registrars, and include over 80% of cancer diagnoses annually in the U.S.

      4c3880bb027f159e801041b1021e88e8 Result

      Of the 5,177 patients who met study criteria, adjuvant therapy was given to 31% of patients (n=1585): 20% received chemotherapy (n=1039), 8% chemoradiation (n=400), and 3% radiation (n=146). In stage IA LCNEC, adjuvant chemotherapy was associated with improved survival when compared to no adjuvant therapy in unadjusted analysis (five-year survival 55% vs. 53%; p=0.03) but not after multivariable adjustment (hazard ratio [HR] 0.81; 95% CI 0.64 to 1.02). Of note, adjuvant chemoradiation (HR 1.66; 95% CI 1.11 to 2.48) and adjuvant radiation (HR 1.55; 95% CI 1.06 to 2.25) were associated with worse survival when compared to no adjuvant therapy. In stage IB LCNEC, adjuvant chemotherapy was associated with improved survival when compared with no adjuvant therapy in both univariate (five-year survival 60% vs. 43%; p<0.0001; Figure) and multivariable (HR 0.65; 95% CI 0.48 to 0.88) analyses.

      final wlc lcnec figure 05.04.18.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      In this NCDB study of resected stage I LCNEC, adjuvant chemotherapy was associated with improved survival after resection of stage IB but not stage IA LCNEC.

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    P2.09 - Pathology (Not CME Accredited Session) (ID 958)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.09-01 - Tumor-Associated Immune Cell Infiltration Patterns in Early Stage Squamous Lung Carcinoma (ID 13456)

      16:45 - 18:00  |  Author(s): David Harpole

      • Abstract
      • Slides

      Background

      With the recent clinical success of immunotherapy in non-small cell lung carcinoma, the character of the inflammatory infiltrate associated with these tumors is now the subject of increasing interest. Molecular studies have suggested that tumors can be stratified by the character of their inflammatory infiltrate. We now describe the detailed histological appearances of a multi-institutional series of early stage squamous carcinomas and correlate them with mutation burden, PDL1 expression patterns and clinical outcome.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Histologic sections of from 250 tumors were evaluated by two pathologists independently for squamous subtype (WHO classification), percentage and character of intratumoral inflammatory cells, percentage and character of para-tumoral infiltrate and presence or absence of scalloping at tumor cell/stromal interface by inflammatory cells along the edges of tumor cell nests, a feature possibly related to existing immune reaction. The ratios of infiltrating inflammatory cells to tumor cells were estimated in 10% increments by microscopic inspection. Quantity and character of infiltrates was assessed by Kaplan-Meir testing for effect on survival and by Pearson bivariate testing for relationships among variables.

      4c3880bb027f159e801041b1021e88e8 Result

      The character and extent of inflammatory infiltrates were highly heterogeneous. The infiltrates could be divided into intratumoral and paratumoral patterns according to their location in relation to microscopic tumor cell nests. Intratumoral infiltrates could be further subdivided into two patterns: one consisted exclusively lymphocytes, usually few in number; a second polymorphous pattern contained many inflammatory cell types including polymorphonuclear leukocytes (PMNs). In paratumoral tissue, three patterns could be discerned: lymphocytic, plasmacytic and polymorphous. Inflammatory cell infiltrate quantity or character did not correlate with survival for either intratumoral or paratumoral infiltrates and there was no evident relationship to mutational burden or to PDL1 expression by IHC. Scalloping at the tumor cell stromal interface was also not prognostically significant.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The inflammatory infiltrates in early stage squamous lung carcinoma are highly heterogenous and are not associated with outcome. However, the complexity of tumor infiltrating inflammatory cells is worthy of further evaluation in future immunotherapeutic trials.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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