Acute toxicity and quality of life in dose-escalated proton reirradiation for locally recurrent rectal cancer: The prospective ReRad II trial

BACKGROUND AND PURPOSE: 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.

MATERIALS AND METHODS: 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.

RESULTS: Among 25 patients, 49 gross tumour volumes resulted in 29 clinical target volumes (median: 84.2 cm3). Median Dmean to bladder, bowel bag, and bowel loops were 7.5, 1.8, and 11.5 Gy(RBE); corresponding D0.03cc 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 D0.03cc(Gy). PROs showed stable global health scores over time, with improvements in emotional and cognitive function.

CONCLUSION: 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.