Feasibility of Total Neoadjuvant Treatment Using Short-Course MRI-Guided Radiotherapy with an Integrated Boost in Locally Advanced Rectal Cancer: A Pilot Study

Background: The RAPIDO trial demonstrated that short-course radiotherapy (5 × 5 Gy) followed by chemotherapy and surgery decreased disease-related treatment failure compared to long-course chemoradiotherapy. However, at 5-year follow-up, an increase in locoregional recurrence was observed. A strategy to improve local control is to increase radiotherapy dose. We present a retrospective analysis of a patient cohort treated with intensified MRI-guided radiotherapy. Methods: Between November 2021 and January 2024, 28 patients with cT3-4 N0-2 rectal cancer were included. Treatment consisted of adaptive MRI-guided external beam radiotherapy 5 × 5 Gy on the mesorectum with a simultaneous integrated boost (SIB) of 5 × 6 Gy on the gross tumor volume (GTV) followed by chemotherapy consisting of 18 weeks of CAPOX or FOLFOX. In case of a complete clinical response (cCR) following neoadjuvant treatment, a watchful-waiting approach was considered. The primary outcome was local and distant recurrence. Results: 27 patients were included in the analysis, with a median follow-up of 39 months. One patient was excluded due to loss to follow-up. Six patients had a pathological complete response (pCR) on surgery, and seven in the watch-and-wait protocol had persistent cCR. Locoregional failure was observed in one patient and four patients developed distant metastasis, leading to death in one patient. Conclusions: Total neoadjuvant treatment (TNT) in locally advanced rectal cancer using an MRI-guided integrated boost on the GTV is tolerable and resulted in a high rate of pCR (22%) and persistent cCR (26%), with limited locoregional failure (4%) and distant relapse (15%).