A Phase I dose escalation trial using Intensity-Modulated Radiotherapy with simultaneous integrated boost in Pelvic Chemoradiotherapy for Metastatic Rectal Cancer
Author(s): Thibaut Lizée, Valérie Seegers, Julien Blanchecotte, Emmanuel Rio, Olivier Capitain, Véronique Guérin-Meyer, Florence Legouté, Damien Autret, Marc-André Ma
Background: In unresectable metastatic rectal cancers, surgery of primary tumor remains highly debated. Pelvic Chemoradiotherapy (CRT) could allow sufficient local control in order to avoid major and sometimes mutilating surgery. Dose escalated CRT could increase local control. The aim of this study was to evaluate the feasibility and tolerance of a CRT with radiation dose escalation using intensity modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB), in metastatic low and middle rectal cancers.
Methods: This multicenter phase I study included six patients treated for unresectable synchronous metastatic low and middle rectal adenocarcinoma in two dose levels. Radiotherapy was delivered using IMRT with SIB. The dose escalation was 52.5 Gy (level 1) and 56.25 Gy (level 2) in the gross tumoral volume (GTV), in 25 fractions of 2.1 Gy and 2.25 Gy, respectively. High-risk clinical target volume (CTV) and low-risk CTV received respectively 50 Gy and 45 Gy in 25 fractions in the two levels. Concomitant chemotherapy was oral capecitabine and CRT was performed after four cycles of mFOLOX6 chemotherapy. The dose-limiting toxicity (DLT) was defined as toxicity requiring the interruption of radiotherapy for more than five consecutive fractions.
Results: All six patients received the full course of treatment at scheduled doses. No patients had acute toxicity requiring interruption of radiotherapy, therefore no DLT has been reported. No patients had acute toxicity ≥3. Concerning late toxicity, three patients experienced grade 3. No local progression occurred.
Conclusions: Dose escalation at 56.25 Gy to the GTV was possible. This radiotherapy schedule needs to be evaluated in a larger study, in order to avoid mutilating surgery for metastatic patients. Trial registration: NCT03634202. Registered 16 August 2018- retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT03634202.