Lockney Natalie A, Henderson Randal H, Swarts Steven G, Zhang Zhenhuan, Zhang Bingrong, Li Jennifer, Zlotecki Robert A, Morris Christopher G, Casey-Sawicki Katherine A, Okunieff Paul G
Department of Radiation Oncology, University of Florida College of Medicine, Gainesville and Jacksonville, FL, USA.
Int J Part Ther. 2021 Jul 27;8(3):28-35. doi: 10.14338/IJPT-D-21-00008. eCollection 2022 Winter.
After radiation therapy (RT), circulating plasma cell-free DNA (cfDNA) released in response to RT damage to tissue can be measured within hours. We examined for a correlation between cfDNA measured during the first week of therapy and early and late gastrointestinal (GI) and genitourinary (GU) toxicity.
Patients were eligible for enrollment if they planned to receive proton or photon RT for nonmetastatic prostate cancer in the setting of an intact prostate or after prostatectomy. Blood was collected before treatment and on sequential treatment days for the first full week of therapy. Toxicity assessments were performed at baseline, weekly during RT, and 6 months and 12 months after RT. Data were analyzed to examine correlations among patient-reported GI and GU toxicities.
Fifty-four patients were evaluable for this study. Four (7%) and 3 (6%) patients experienced acute and late grade 2 GI toxicity, respectively. Twenty-two (41%) and 18 (35%) patients experienced acute and late grade 2 GU toxicity, respectively. No patients developed grade 3 or higher toxicity. Grade 2 acute GI toxicity, but not grade 2 acute GU toxicity, was significantly correlated with pre-RT cfDNA levels and on all days 1, 2, 3, 4, and 5 of RT ( < .005). Grade 2 late GI toxicity, but not GU toxicity, was significantly correlated with pre-RT cfDNA levels ( = .021).
Based on this preliminary study, cfDNA levels can potentially predict the subset of patients destined to develop GI toxicity during prostate cancer treatment. Given that the toxicity profiles of the various fractionations and modalities are highly similar, the data support the expectation that cfDNA could provide a biological estimate to complement the dose-volume histogram. A test of this hypothesis is under evaluation in a National Cancer Institute-funded multi-institutional study.
放射治疗（RT）后，因组织受到RT损伤而释放到循环血浆中的游离DNA（cfDNA）可在数小时内检测到。我们研究了治疗第一周测得的cfDNA与胃肠道（GI）和泌尿生殖系统（GU）早期及晚期毒性之间的相关性。
计划接受质子或光子RT治疗非转移性前列腺癌（前列腺完整或前列腺切除术后）的患者符合入组条件。在治疗前以及治疗第一周的连续治疗日采集血液。在基线、RT期间每周、RT后6个月和12个月进行毒性评估。分析数据以检验患者报告的GI和GU毒性之间的相关性。
54例患者可纳入本研究。分别有4例（7%）和3例（6%）患者发生急性和晚期2级GI毒性。分别有22例（41%）和18例（35%）患者发生急性和晚期2级GU毒性。无患者发生3级或更高级别的毒性。2级急性GI毒性而非2级急性GU毒性与RT前cfDNA水平以及RT第1、2、3、4和5天的cfDNA水平显著相关（P<0.005）。2级晚期GI毒性而非GU毒性与RT前cfDNA水平显著相关（P=0.021）。
基于这项初步研究，cfDNA水平可能预测前列腺癌治疗期间注定会发生GI毒性的患者亚组。鉴于各种分割方式和治疗模式的毒性特征高度相似，这些数据支持cfDNA可提供生物学评估以补充剂量体积直方图的预期。美国国立癌症研究所资助的一项多机构研究正在对这一假设进行验证。
