Total neoadjuvant treatment of rectal cancer by MRI-guided radiotherapy

Short-course radiotherapy (5 x 5 Gy) followed by chemotherapy before total mesorectal excision (TME) decreased the probability of disease-related treatment failure and became the new standard of care in high-risk locally advanced rectal cancer (Bahadoer et al, Lancet Oncol. 2021). A-five-year follow-up of the RAPIDO trial recently confirmed the reduction in disease-related treatment failure and distant metastases, but revealed an increase in locoregioal recurrence compared to long-course chemoradiotherapy (Dijkstra et al, Ann Surg. 2023). The aim of this study was to evaluate the safety of dose-escalation till 5 x 6 Gy on the gross tumor volume (GTV) using MRI-guided radiotherapy.

33 patients with a locally advanced rectal cancer were treated between July 2021 and March 2023 by MRI-guided radiotherapy on the MRIdian (Viewray, Denver, Colorado). Patients received 5 fractions of 5 Gy on the classic clinical target volume, with a simultaneous integrated boost till 6 Gy on the GTV. Patient were treated with daily adaptive radiotherapy and active tumor tracking in cine MRI-mode. Radiotherapy was followed by 9 cycles of FOLFOX or 6 cycles of CAPOX. Patient underwent response evaluation by rectoscopy and MRI, mid-chemotherapy and 2 weeks after its completion. This analysis is part of a clinical study that received approval from the ethical committee of UZ Brussel (EC1010135).

Of the 33 patients, 16 patients displayed grade I toxicity (48%) and 17 showed no toxicity (52%) at the end of radiotherapy. Eight patients were excluded from the current response analysis: 2 received no chemotherapy because of comorbidities, 3 did not complete chemotherapy yet and 3 had missing data (e.g. waiting for the definitive pathology report). Of the 25 remaining patients, 11 (44%) had a complete clinical remission and were offered a watchful waiting approach. 14 patients underwent a TME. 1 patient displayed a Dworak regression score 0 (4%), 1 a Dworak score 1 (4%), 2 a Dworak score 2 (8%), 4 a Dworak score 3 (16%) and 6 a Dworak score 4 (24%).

MRI-guided total neoadjuvant treatment with a simultaneous integrated boost resulted in a high clinical and pathological complete remission of 68%, within this pilot study. This may be an emerging strategy to improve local control and organ preservation in the future.

This analysis is part of a clinical study that received approval from the ethical committee of UZ Brussel (EC1010135).

The authors.

This study was partly funded by SRP-Onderzoekszwaartepunt Vrije Universiteit Brussel SRP53: Societal Benefit of Markerless Stereotactic Body Radiotherapy: a Statistical Support based on Quantitative Imaging.

All authors have declared no conflicts of interest.