Truelsen C G, Rønde H S, Kallehauge J F, Szpejewska J E, Bahij R, Diness L V, Skriver S K, Poulsen L Ø, Havelund B M, Pedersen B G, Iversen L H, Spindler K G, Kronborg C S
Danish Centre for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark.
Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
Clin Transl Radiat Oncol. 2025 Jun 24;54:100999. doi: 10.1016/j.ctro.2025.100999. eCollection 2025 Sep.
Locally recurrent rectal cancer (LRRC) in pre-irradiated patients remains a clinical challenge. Intensity-Modulated Proton Therapy (IMPT) enables dose escalation with potential for improved tumour control without compromising dose to organs at risk (OAR). However, prospective data on toxicity and patient-reported outcomes (PROs) with quality of life (QoL) are limited.
This planned interim analysis from the prospective phase II ReRad II trial (NCT04695782) reports acute toxicity and PROs in the first 25 patients treated with dose-escalated IMPT for LRRC. Patients received either 55 Gy (relative biological effectiveness (RBE)) in 44 fractions (neoadjuvant) or 57.5-65 Gy (RBE) in 46-52 fractions (definitive). Acute toxicity was graded using NCI-CTCAE. PROs were assessed using EORTC QLQ-C30 and -CR29 questionnaires at pretreatment, during treatment, and at 3-month follow-up. A linear mixed model evaluated longitudinal PRO trajectories.
Among 25 patients, 49 gross tumour volumes resulted in 29 clinical target volumes (median: 84.2 cm). Median D to bladder, bowel bag, and bowel loops were 7.5, 1.8, and 11.5 Gy(RBE); corresponding D were 58.1, 59.9, and 59.3 Gy(RBE). Grade ≥3 acute toxicity (ileus) occurred in 2 patients with pre-existing ileus episodes. Urinary retention was associated with bladder D. PROs showed stable global health scores over time, with improvements in emotional and cognitive function.
Interim results support the feasibility of dose-escalated IMPT reirradiation for LRRC, with manageable acute toxicity and preserved QoL. Continuance of the trial will inform long-term outcomes and guide future treatment strategies for LRRC management.
曾接受过放疗的患者发生局部复发性直肠癌（LRRC）仍是一项临床挑战。调强质子治疗（IMPT）能够提高剂量，有可能在不影响危及器官（OAR）剂量的情况下改善肿瘤控制。然而，关于毒性和患者报告结局（PROs）以及生活质量（QoL）的前瞻性数据有限。
这项来自前瞻性II期ReRad II试验（NCT04695782）的计划中期分析报告了前25例接受剂量递增IMPT治疗LRRC患者的急性毒性和PROs。患者接受新辅助治疗时44次分割给予55 Gy（相对生物效应（RBE）），或根治性治疗时46 - 52次分割给予57.5 - 65 Gy（RBE）。急性毒性采用美国国立癌症研究所常见不良反应事件评价标准（NCI - CTCAE）进行分级。在治疗前、治疗期间和3个月随访时，使用欧洲癌症研究与治疗组织核心生活质量问卷（EORTC QLQ - C30）和直肠癌特异性问卷（- CR29）评估PROs。采用线性混合模型评估纵向PRO轨迹。
25例患者中，49个大体肿瘤体积产生了29个临床靶体积（中位数：84.2 cm）。膀胱、肠袋和肠袢的D中位数分别为7.5、1.8和11.5 Gy（RBE）；相应的D分别为58.1、59.9和59.3 Gy（RBE）。2例既往有肠梗阻发作的患者发生了≥3级急性毒性（肠梗阻）。尿潴留与膀胱D相关。PROs显示总体健康评分随时间稳定，情绪和认知功能有所改善。
中期结果支持剂量递增IMPT再程放疗治疗LRRC的可行性，急性毒性可控且生活质量得以保留。试验的继续进行将为长期结局提供信息，并指导LRRC管理的未来治疗策略。
