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

Journal for immunotherapy of cancer 2021 Aug

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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. © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Citation

Stanislav Fridland, Jaeyoun Choi, Myungwoo Nam, Samuel Joseph Schellenberg, Eugene Kim, Grace Lee, Nathaniel Yoon, Young Kwang Chae. 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. Journal for immunotherapy of cancer. 2021 Aug;9(8)