Skip to main content

Spatial and Temporal Heterogeneity of PD-L1 Expression and Tumor Mutational Burden in Gastroesophageal Adenocarcinoma at Baseline Diagnosis and after Chemotherapy.

Publication ,  Journal Article
Zhou, KI; Peterson, B; Serritella, A; Thomas, J; Reizine, N; Moya, S; Tan, C; Wang, Y; Catenacci, DVT
Published in: Clinical cancer research : an official journal of the American Association for Cancer Research
December 2020

Intrapatient heterogeneity of programmed death ligand 1 (PD-L1) expression and tumor mutational burden (TMB) in gastroesophageal adenocarcinoma (GEA) could influence their roles as predictive biomarkers for response to immune checkpoint inhibitors (ICI). In this retrospective analysis, we evaluated the spatiotemporal heterogeneity and prognostic relevance of PD-L1 expression and TMB in GEA.A cohort of 211 patients with stage II-IV GEA was retrospectively reviewed for a total of 407 tumor samples with PD-L1 expression data and 319 tumor samples with TMB data. PD-L1 status was defined as positive if combined positive score (CPS) ≥1 using the 22C3 pharmDx assay. TMB levels were categorized as low, intermediate, or high (≤5, 5-15, or >15 mutations/Mb), or using a single threshold (<10 or ≥10 mutation/Mb), determined by next-generation sequencing using a targeted gene panel.Of 407 tumors, 56% were PD-L1 negative and 44% PD-L1 positive. Of 319 tumors, 50% were TMB-low, 45% TMB-intermediate, and 5% TMB-high; 86% had <10 and 14% ≥10 mutations/Mb. TMB level was significantly associated with MSI-status. PD-L1 expression and TMB exhibited marked spatial heterogeneity between baseline primary and metastatic tumors (61% and 69% concordance), and temporal heterogeneity between tumors before and after chemotherapy (57%-63% and 73%-75% concordance). PD-L1 expression and TMB were not significantly associated with overall survival.PD-L1 expression and TMB exhibit marked spatial and temporal heterogeneity in GEA. This heterogeneity should be considered when obtaining tumor samples for molecular testing and when deciding whether ICI therapy is appropriate.See related commentary by Klempner et al., p. 6401.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Clinical cancer research : an official journal of the American Association for Cancer Research

DOI

EISSN

1557-3265

ISSN

1078-0432

Publication Date

December 2020

Volume

26

Issue

24

Start / End Page

6453 / 6463

Related Subject Headings

  • Young Adult
  • Survival Rate
  • Stomach Neoplasms
  • Retrospective Studies
  • Prognosis
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Humans
  • Follow-Up Studies
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zhou, K. I., Peterson, B., Serritella, A., Thomas, J., Reizine, N., Moya, S., … Catenacci, D. V. T. (2020). Spatial and Temporal Heterogeneity of PD-L1 Expression and Tumor Mutational Burden in Gastroesophageal Adenocarcinoma at Baseline Diagnosis and after Chemotherapy. Clinical Cancer Research : An Official Journal of the American Association for Cancer Research, 26(24), 6453–6463. https://doi.org/10.1158/1078-0432.ccr-20-2085
Zhou, Katherine I., Bryan Peterson, Anthony Serritella, Joseph Thomas, Natalie Reizine, Stephanie Moya, Carol Tan, Yan Wang, and Daniel V. T. Catenacci. “Spatial and Temporal Heterogeneity of PD-L1 Expression and Tumor Mutational Burden in Gastroesophageal Adenocarcinoma at Baseline Diagnosis and after Chemotherapy.Clinical Cancer Research : An Official Journal of the American Association for Cancer Research 26, no. 24 (December 2020): 6453–63. https://doi.org/10.1158/1078-0432.ccr-20-2085.
Zhou KI, Peterson B, Serritella A, Thomas J, Reizine N, Moya S, et al. Spatial and Temporal Heterogeneity of PD-L1 Expression and Tumor Mutational Burden in Gastroesophageal Adenocarcinoma at Baseline Diagnosis and after Chemotherapy. Clinical cancer research : an official journal of the American Association for Cancer Research. 2020 Dec;26(24):6453–63.
Zhou, Katherine I., et al. “Spatial and Temporal Heterogeneity of PD-L1 Expression and Tumor Mutational Burden in Gastroesophageal Adenocarcinoma at Baseline Diagnosis and after Chemotherapy.Clinical Cancer Research : An Official Journal of the American Association for Cancer Research, vol. 26, no. 24, Dec. 2020, pp. 6453–63. Epmc, doi:10.1158/1078-0432.ccr-20-2085.
Zhou KI, Peterson B, Serritella A, Thomas J, Reizine N, Moya S, Tan C, Wang Y, Catenacci DVT. Spatial and Temporal Heterogeneity of PD-L1 Expression and Tumor Mutational Burden in Gastroesophageal Adenocarcinoma at Baseline Diagnosis and after Chemotherapy. Clinical cancer research : an official journal of the American Association for Cancer Research. 2020 Dec;26(24):6453–6463.

Published In

Clinical cancer research : an official journal of the American Association for Cancer Research

DOI

EISSN

1557-3265

ISSN

1078-0432

Publication Date

December 2020

Volume

26

Issue

24

Start / End Page

6453 / 6463

Related Subject Headings

  • Young Adult
  • Survival Rate
  • Stomach Neoplasms
  • Retrospective Studies
  • Prognosis
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Humans
  • Follow-Up Studies