Neoadjuvant chemo-reirradiation followed by resection and intraoperative electron beam radiotherapy: outcomes of multimodality treatment for locally recurrent rectal cancer

Abstract Background Chemo-reirradiation has emerged as a feasible neoadjuvant therapy to improve resectability in locally recurrent rectal cancer (LRRC). However, its combination with surgery and intraoperative electron radiotherapy (IOERT) raises concerns regarding cumulative toxicity. This retrospective study aimed to evaluate acute and late toxicity profiles, local control and survival outcomes, following this multimodal approach in our institution. Methods LRRC patients who underwent chemo-reirradiation and surgery with IOERT (median cumulative tumour dose of 113 Gy, α/β = 10 Gy) between September 2021 to December 2024 were retrospectively analysed. Acute and late treatment-related toxicities (CTCAE) were recorded in a prospectively maintained database. Secondary outcomes were overall survival (OS) and local re-recurrence-free survival (LRFS). Results Among 40 patients, no grade 4 or 5 toxicities were observed. Acute cumulative treatment-related grade 3 toxicities occurred in 14/37 (38%) patients, predominantly consisting of erectile dysfunction (5/37, 14%), abscess formation (4/37, 11%) or peripheral neuropathy (2/37, 5%). Late grade 3 toxicities occurred in 13/30 (43%) patients, comprising mainly of erectile dysfunction (5/30, 17%), renal disorders (5/30, 17%) or peripheral neuropathy (2/30, 7%). After a median follow-up period of 21 months (IQR 12–32) after surgery, 2-year overall survival (OS) and local re-recurrence-free survival (LRFS) were 75.7% and 37.2%, respectively. Conclusion In previously irradiated LRRC patients, a multimodality approach combining chemo-reirradiation and extensive surgery with IOERT demonstrated acceptable treatment-related toxicities and favourable oncological outcomes for this high-risk population. Further research with longer follow-up is warranted to identify risk factors associated with treatment-related toxicity.