Assessing tumor heterogeneity: Integrating tissue and circulating tumor DNA (ctDNA) analysis in the era of immuno-oncology-blood TMB is not the same as tissue TMB

Stanislav Fridland, Jaeyoun Choi, Myungwoo Nam, Samuel Joseph Schellenberg, Eugene Kim, Grace Lee, Nathaniel Yoon, Young Kwang Chae*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations

Abstract

Tissue tumor mutational burden (tTMB) is calculated to aid in cancer treatment selection. High tTMB predicts a favorable response to immunotherapy in patients with non-small cell lung cancer. Blood TMB (bTMB) from circulating tumor DNA is reported to have similar predictive power and has been proposed as an alternative to tTMB. Across many studies not only are tTMB and bTMB not concordant but also as reported previously by our group predict conflicting outcomes. This implies that bTMB is not a substitute for tTMB, but rather a composite index that may encompass tumor heterogeneity. Here, we provide a thorough overview of the predictive power of TMB, discuss the use of tumor heterogeneity alongside TMB to predict treatment response and review several methods of tumor heterogeneity assessment. Furthermore, we propose a hypothetical method of estimating tumor heterogeneity and touch on its clinical implications.

Original languageEnglish (US)
Article numbere002551
JournalJournal for immunotherapy of cancer
Volume9
Issue number8
DOIs
StatePublished - Aug 30 2021

Keywords

  • biomarkers
  • immunotherapy
  • tumor
  • tumor biomarkers

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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