Abstract IA05: Intratumor genetic heterogeneity as a predictive biomarker in head and neck squamous cell carcinoma

Abstract

Abstract The presence of heritable genetic differences among cancer cells within a tumor, called intratumor genetic heterogeneity, has long been suspected of playing a role in the poor responses of some tumors to traditional therapies. Research over the past decade has now documented the existence of genetic heterogeneity within tumors of individual patients and acknowledged its potential clinical significance. The research methods for identifying intratumor genetic heterogeneity were not readily adaptable to widespread clinical application until the development of a quantitative measure (MATH—mutant allele tumor heterogeneity) based on whole-exome sequencing of individual tumor samples. MATH values could be readily derived from biopsy or surgical specimens prior to the decision to utilize adjuvant radiation or chemotherapy. MATH analysis has now been used in HNSCC genomic data sets, along with clinical outcome data, to document a relation of high intratumor genetic heterogeneity to shorter overall survival (OS) in a large, multi-institutional study. Recent analysis examining the impact of high and low heterogeneity as measured by MATH suggests that the relation of intratumor heterogeneity to OS likely depends on the specific type of adjuvant therapy used. Our results demonstrate that patients with high intratumor heterogeneity (high MATH scores) would benefit from adjuvant radiation even when NCCN clinical treatment guidelines suggest that it could be omitted. In contrast, patients with low MATH tumors should likely adhere to these guidelines. Our results also support that patients with high MATH tumors will likely not benefit from the addition of adjuvant chemotherapy to radiotherapy, and thus could be spared the additional morbidity of complications from combination therapy. Current HNSCC NCCN treatment guidelines are based on either clinical or pathologic tumor stage and in the postoperative setting the presence or absence of high-risk pathologic features such as positive or close margins and tumor extra nodal extension. Intratumor genetic heterogeneity as measured by MATH analysis has the potential to further inform stage- and pathology-based treatment decisions and consequently should be evaluated in controlled prospective trials that compare adjuvant radiation against chemoradiation following surgery for HNSCC. Citation Format: Edmund A. Mroz, James W. Rocco. Intratumor genetic heterogeneity as a predictive biomarker in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr IA05.