Precision Radiotherapy: Reduction in Radiation for Oropharyngeal Cancer in the 30 ROC Trial
Precision Radiotherapy: Reduction in Radiation for Oropharyngeal Cancer in the 30 ROC Trial
复制标题
精确放射治疗：30个ROC试验中口咽癌放射治疗的减少
DOI：
10.1093/jnci/djaa184
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发表时间：
2021-01-12
影响因子：
10.3
通讯作者：
Lee, Nancy
中科院分区：
文献类型：
--
作者：
Riaz, Nadeem;Sherman, Eric;Lee, Nancy
背景资料：人乳头瘤病毒相关口咽癌患者预后良好，但在接受标准化放疗（70戈伊）治疗时会出现临床显著毒性。我们假设功能成像可以识别出可以安全地将放疗剂量降至30戈伊的患者。研究方法：在19例患者中，治疗前和治疗中动态氟-18-标记氟咪唑正电子发射断层扫描（PET）用于评估肿瘤缺氧。基线或治疗期间无缺氧的患者接受30戈伊;持续缺氧的患者接受70戈伊。在4个月时对降级患者进行颈清扫术，以评估病理反应。进行磁共振成像（每周一次）、循环血浆游离DNA、RNA测序和全基因组测序（WGS），以确定缓解的潜在分子决定因素。从一项独立的前瞻性研究中获得样本，以重现分子结果。所有统计检验均为双侧检验。结果：19例患者中有15例在基线PET上无缺氧或在治疗中PET上消退，并将剂量降至30戈伊。在这15例患者中，11例病理学完全缓解。2年局部控制率和总生存率分别为94.4%（95%置信区间= 84.4%-100%）和94.7%（95%置信区间= 85.2%-100%）。未观察到急性3级辐射相关毒性。与肿瘤负荷指标或循环血浆无细胞DNA相比，系列成像的微环境特征与病理反应的相关性更好。基于WGS的DNA修复缺陷与应答相关（P = .02），并在独立队列中重现（P = .03）。结论：根据治疗内缺氧成像将放射治疗降级至30戈伊是可行的、安全的，并且毒性最小。通过WGS鉴定的DNA修复缺陷可预测反应。化放疗的个体化治疗可促进放射治疗的显著降级。
Background: Patients with human papillomavirus-related oropharyngeal cancers have excellent outcomes but experience clinically significant toxicities when treated with standard chemoradiotherapy (70 Gy). We hypothesized that functional imaging could identify patients who could be safely deescalated to 30 Gy of radiotherapy. Methods: In 19 patients, pre- and intratreatment dynamic fluorine-18-labeled fluoromisonidazole positron emission tomography (PET) was used to assess tumor hypoxia. Patients without hypoxia at baseline or intratreatment received 30 Gy; patients with persistent hypoxia received 70 Gy. Neck dissection was performed at 4 months in deescalated patients to assess pathologic response. Magnetic resonance imaging (weekly), circulating plasma cell-free DNA, RNA-sequencing, and whole-genome sequencing (WGS) were performed to identify potential molecular determinants of response. Samples from an independent prospective study were obtained to reproduce molecular findings. All statistical tests were 2-sided. Results: Fifteen of 19 patients had no hypoxia on baseline PET or resolution on intratreatment PET and were deescalated to 30 Gy. Of these 15 patients, 11 had a pathologic complete response. Two-year locoregional control and overall survival were 94.4% (95% confidence interval = 84.4% to 100%) and 94.7% (95% confidence interval = 85.2% to 100%), respectively. No acute grade 3 radiation-related toxicities were observed. Microenvironmental features on serial imaging correlated better with pathologic response than tumor burden metrics or circulating plasma cell-free DNA. A WGS-based DNA repair defect was associated with response (P = .02) and was reproduced in an independent cohort (P = .03). Conclusions: Deescalation of radiotherapy to 30 Gy on the basis of intratreatment hypoxia imaging was feasible, safe, and associated with minimal toxicity. A DNA repair defect identified by WGS was predictive of response. Intratherapy personalization of chemoradiotherapy may facilitate marked deescalation of radiotherapy.