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Ralph A Schmid



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    P1.04 - Immuno-oncology (ID 164)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.04-05 - PD-L1 Expression (SP263) in Lung Cancer and Paired Brain Metastases – A Single Center Study in 211 Patients (ID 384)

      09:45 - 18:00  |  Author(s): Ralph A Schmid

      • Abstract
      • Slides

      Background

      Lung cancer presents with brain metastases (BM) in a significant number of cases and resected BM are often the only tissue available for analysis of predictive biomarkers. Studies have shown some molecular divergence between BM and primary lung tumor, but data on paired samples is rare. Here we analyzed the expression of the predictive biomarker programmed cell death ligand 1 (PD-L1) in BM and paired primary tumors.

      Method

      In a single-center retrospective study, we assembled a cohort of consecutive BM resected and diagnosed at our University hospital between 2000 and 2015. We analyzed PD-L1 expression (Ventana SP263 kit) on full slides of lung cancer BM (N=211) and available paired primary tumors (N=87), using the increments <1%, 1-49% and ≥50%.

      Result

      Our BM cohort comprised 145 (68.7%) adenocarcinomas, 24 (11.4%) squamous cell carcinomas, 34 (16.1%) small cell carcinomas and large cell neuroendocrine carcinomas and 8 (3.8%) others. PD-L1 staining was evaluable in 193 BM and 87 paired primary tumors. There was no tumoral PD-L1 expression in the high-grade neuroendocrine carcinomas.

      Among the non-neuroendocrine cancer BM, 86/165 (52.1%) expressed <1% PD-L1, 36/165 (21.8%) 1-49%, and 43/165 (26.1%) ≥50%.

      PD-L1 scores significantly correlated between BM and primary tumors (p<0.001), with a complete congruence in 62/77 cases (80.5%). Clinically significant discrepancies (cut-off 50%) were present in 9/77 (11.7%) cases: 6 cases were primary tumor-positive/BM-negative, and 3 cases BM-positive/primary tumor-negative. Only 4/9 patients with discrepant PD-L1 scores received chemotherapy in between tissue acquisition of BM and primary tumor, failing to serve as an explanation.

      Tissue from at least 2 separate brain metastases was available in 12 patients, with discrepant PD-L1 scores regarding the 50% cut-off in only 1 patient (8.3%), and regarding the 1% cut-off in 2 patients (16.7%). There was no association between PD-L1 expression in the BM and overall survival (p=0.95).

      Conclusion

      In conclusion, we show that PD-L1 scores are concordant in most of paired BM and primary tumors. The discordant cases could not be explained by longer time lapses or chemotherapy or radiotherapy in between tissue acquisition, nor by scarce tissue availability of the primary tumor, e.g. due to biopsies only, and may be due to tumor heterogeneity.

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    P2.09 - Pathology (ID 174)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Pathology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.09-19 - Effect of Neoadjuvant (Radio)chemotherapy on PD-L1 Expression in Resected Non-Small Cell Lung Cancers (ID 366)

      10:15 - 18:15  |  Author(s): Ralph A Schmid

      • Abstract
      • Slides

      Background

      Programmed cell death ligand 1 (PD-L1) expression has been established as a predictive biomarker for checkpoint-inhibitor treatment in advanced non-small-cell lung carcinomas (NSCLC). Inclusion of PD1/PD-L1 inhibitors into existing neoadjuvant regimens is currently evaluated in clinical trials. However, data on the impact of neoadjuvant regimens on tumoral PD-L1 expression is rare. We aimed to assess the PD-L1 expression in NSCLC before/after neoadjuvant treatment, including its prognostic relevance.

      Method

      Our single-center, retrospective study cohort comprised 131 consecutive patients with NSCLC resected after neoadjuvant therapy, diagnosed 2000-2016, including 63 available pretreatment biopsies. Tumor types comprised 59 squamous cell carcinomas (SQCC), 66 adenocarcinomas (ADC) and 7 others. The pathological slides and clinical records were reevaluated assessing tumor-size according to current IASLC-recommendations by multiplying the vital tumor percentage with the macroscopic tumor bed. Biologically matched cohorts of 60 locally advanced (pN2) primary resected ADC and 54 SQCC served as controls. PD-L1 was immunohistochemically stained using the Ventana SP263 KIT and tumoral expression was assessed on whole slides by two investigators using the increments: <1%, 1-<25%, 25-<50%, 50%. The results were correlated with clinico-pathological parameters.

      Result

      PD-L1 could be evaluated in 112 specimens after neoadjuvant chemotherapy, including 24 following neoadjuvant radiochemotherapy: 53 cases scored <1%, 31 1-<25%, 4 25-<50% and 24 ≥50%. In pre-treatment biopsies, 50/63 (79.4%) cases scored <50%, 13/63 (20.6%) ≥50%. Eight/63 (12.7%) cases were discordant regarding the clinically relevant cut-off 50%, 4 cases (2 ADC, 2 SQCC) having a higher expression and 4 cases (2 ADC, 2 SQCC) with lower expression after neoadjuvant radiochemotherapy.

      PD-L1 expression was significantly higher in primary resected SQCC (n=53) compared to neoadjuvantly treated SQCC (n=52, p=0.014; n=41 neoadjuvant chemotherapy only, p=0.033), with 14 cases scoring <1%, 21 1-<25%, 4 25-49% and 14≥50%.

      There was no significant difference regarding PD-L1 expression for the paired ADC-groups.

      In neoadjuvantly treated NSCLC, there was no correlation between PD-L1 expression (increments or 50% cut-off) and ypT, ypN, UICC/AJCC-stage, histological tumor regression, tumor size or the size of the tumor bed. PD-L1 expression was not associated with overall survival nor progression free survival in any cohort.

      Conclusion

      We document a discordance of 12.7% regarding the cut-off 50% between pre-treatment biopsies and resections after neoadjuvant therapy, which may be due to tumor-heterogeneity. The higher PD-L1 expression in primary resected SQCC compared to SQCC resected after treatment provides evidence that the influence of neoadjuvant therapy on PD-L1 expression might depend on the histological tumor type.

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