18 New method of assessing tumor heterogeneity utilizing both circulating tumor DNA and tissue DNA to predict the response to immunotherapy

BackgroundTumor heterogeneity assessment may help predict response to immunotherapy. In melanoma mouse models, tumor heterogeneity impaired immune response.1 In addition, among lung cancer patients receiving immunotherapy, the high clonal neoantigen group had favorable survival and outcomes.2 Ideal methods of quantifying tumor heterogeneity are multiple biopsies or autopsy. However, these are not feasible in routine clinical practice. Circulating tumor DNA (ctDNA) is emerging as an alternative. Here, we reviewed the current state of tumor heterogeneity quantification from ctDNA. Furthermore, we propose a new tumor heterogeneity index(THI) based on our own scoring system, utilizing both ctDNA and tissue DNA.MethodsSystematic literature search on Pubmed was conducted up to August 18, 2020. A scoring system and THI were theoretically derived.ResultsTwo studies suggested their own methods of assessing tumor heterogeneity. One suggested clustering mutations with Pyclone,3 and the other suggested using the ratio of allele frequency (AF) to the maximum somatic allele frequency (MSAF).4 According to the former, the mutations in the highest cellular prevalence cluster can be defined as clonal mutations. According to the latter, the mutations with AF/MSAF