Department of Otolaryngology-Head and Neck Surgery, James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, Ohio.
Cancer. 2020 Jan 1;126(9):1895-1904. doi: 10.1002/cncr.32742. Epub 2020 Feb 21.
After surgery for head and neck squamous cell carcinoma (HNSCC), decisions regarding adjuvant radiotherapy (RT) or chemoradiotherapy (CRT) are based on staging and the presence of high-risk pathology. Because higher mutant allele tumor heterogeneity (MATH; a measure of intratumor genetic heterogeneity) is associated with shorter overall survival (OS) in patients with HNSCC, the authors sought to determine whether MATH analysis might further inform these decisions.
Adjuvant therapy-associated relationships between MATH and OS were analyzed for 389 patients with HNSCC who were treated surgically. Data were obtained from The Cancer Genome Atlas and analyzed with Cox proportional hazards multiple regression accounting for 7 other patient characteristics.
The relationship between MATH and OS differed with adjuvant therapy in a way that could inform therapy decisions. Adjuvant RT alone was found to provide substantial benefit for patients having high-MATH tumors (RT vs no adjuvant therapy: hazard ratio, 0.29 [95% CI, 0.17-0.51]) but no benefit for those having low-MATH tumors. In contrast, adjuvant CRT provided no benefit beyond that of adjuvant RT for patients with high-MATH tumors but substantially improved OS among patients with low-MATH tumors (CRT vs no adjuvant therapy: hazard ratio, 0.34 [95% CI, 0.15-0.78]).
The results of the current analysis suggested that patients with HNSCC with high-MATH tumors who underwent surgical treatment could benefit from adjuvant RT, even when current clinical guidelines indicate otherwise. The addition of adjuvant chemotherapy for patients with high-MATH tumors would not be indicated. Adding chemotherapy might be necessary to radiosensitize low-MATH tumors to adjuvant RT. This potential predictive role of tumor MATH analysis should be evaluated in prospective clinical trials.
头颈部鳞状细胞癌（HNSCC）手术后，辅助放疗（RT）或放化疗（CRT）的决策基于分期和高危病理学特征。由于较高的突变等位基因肿瘤异质性（MATH；衡量肿瘤内遗传异质性的指标）与 HNSCC 患者的总生存期（OS）缩短相关，作者试图确定 MATH 分析是否可以进一步为这些决策提供信息。
作者分析了 389 例接受手术治疗的 HNSCC 患者的辅助治疗相关 MATH 和 OS 之间的关系。数据来自癌症基因组图谱（The Cancer Genome Atlas），并使用 Cox 比例风险多变量回归进行分析，考虑了 7 个其他患者特征。
MATH 与 OS 的关系因辅助治疗而不同，这可以为治疗决策提供信息。单独接受辅助 RT 对高 MATH 肿瘤患者有显著获益（RT 与无辅助治疗相比：危险比，0.29[95%CI，0.17-0.51]），但对低 MATH 肿瘤患者无获益。相比之下，对于高 MATH 肿瘤患者，辅助 CRT 并未提供 RT 之外的获益，但对于低 MATH 肿瘤患者，OS 显著改善（CRT 与无辅助治疗相比：危险比，0.34[95%CI，0.15-0.78]）。
当前分析的结果表明，接受手术治疗的 HNSCC 且具有高 MATH 肿瘤的患者可能受益于辅助 RT，即使当前临床指南表明并非如此。对于高 MATH 肿瘤患者，添加辅助化疗是不合适的。对于低 MATH 肿瘤，添加化疗可能有助于对辅助 RT 增敏。应该在前瞻性临床试验中评估肿瘤 MATH 分析的这种潜在预测作用。
