放疗后局部复发在局部晚期头颈癌（HNC）患者中很常见。再次照射可以改善局部疾病控制，但疾病进展仍然频繁。因此，需要预测性生物标志物来根据患者的个体风险调整治疗强度。我们对连续血浆样本中的循环肿瘤 DNA (ctDNA) 进行了定量，并将 ctDNA 水平与疾病结果相关联。在再放疗基线、5 次和 10 次放疗后、放疗结束时以及常规随访时，收集了来自 16 名局部晚期 HNC 患者和 57 名健康捐献者的 94 份纵向血浆样本。对血浆 DNA 进行低覆盖度全基因组测序，进行拷贝数变异 (CNV) 分析，以量化 ctDNA 负荷。在 8/16 名患者和 25/94 份血浆样本中检测到基于 CNV 的 ctDNA 负荷。通过追踪早期连续血浆样本中发现的患者特异性 CNV，鉴定出另外 10 个 ctDNA 阳性样本。 5 次和 10 次放疗后（均为对数秩，p = .050）以及放疗结束时的 ctDNA 阳性与短期无进展生存期相关（对数秩，p = .006）。此外，再次放疗终止时 ctDNA 的显着下降与较差的治疗结果相关（对数秩，p = .005）。再次放射治疗之外的连续血浆中的动态 ctDNA 追踪反映了治疗反应和即将发生的疾病进展。在五名患者中，根据临床影像在肿瘤进展之前检测到分子进展。我们的研究结果强调，在再次放疗期间量化 ctDNA 可能有助于疾病监测以及辅助治疗、随访间隔和剂量处方的个性化。© 2024 作者。约翰·威利出版的《国际癌症杂志》

Local recurrence after radiotherapy is common in locally advanced head and neck cancer (HNC) patients. Re-irradiation can improve local disease control, but disease progression remains frequent. Hence, predictive biomarkers are needed to adapt treatment intensity to the patient's individual risk. We quantified circulating tumor DNA (ctDNA) in sequential plasma samples and correlated ctDNA levels with disease outcome. Ninety four longitudinal plasma samples from 16 locally advanced HNC patients and 57 healthy donors were collected at re-radiotherapy baseline, after 5 and 10 radiation fractions, at irradiation end, and at routine follow-up visits. Plasma DNA was subjected to low coverage whole genome sequencing for copy number variation (CNV) profiling to quantify ctDNA burden. CNV-based ctDNA burden was detected in 8/16 patients and 25/94 plasma samples. Ten additional ctDNA-positive samples were identified by tracking patient-specific CNVs found in earlier sequential plasma samples. ctDNA-positivity after 5 and 10 radiation fractions (both: log-rank, p = .050) as well as at the end of irradiation correlated with short progression-free survival (log-rank, p = .006). Moreover, a pronounced decrease of ctDNA toward re-radiotherapy termination was associated with worse treatment outcome (log-rank, p = .005). Dynamic ctDNA tracking in serial plasma beyond re-radiotherapy reflected treatment response and imminent disease progression. In five patients, molecular progression was detected prior to tumor progression based on clinical imaging. Our findings emphasize that quantifying ctDNA during re-radiotherapy may contribute to disease monitoring and personalization of adjuvant treatment, follow-up intervals, and dose prescription.© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.