A Phase I dose escalation trial using Intensity-Modulated Radiotherapy with simultaneous integrated boost in Pelvic Chemoradiotherapy for Metastatic Rectal Cancer

BackgroundIn unresectable metastatic rectal cancers, the surgery of the primitive tumor remains highly debated. Chemoradiotherapy (CRT) of the primitive could allow sufficient local control in order to avoid major and sometimes mutilating surgery. Dose escalation during CRT could increase this local control. The aim of this study was to evaluate the feasibility and tolerance of a CRT with radiation dose escalation delivered in intensity modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB), in metastatic low and middle rectal cancers.MethodsThis 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 primary tumor, 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 by a toxicity requiring the interruption of radiotherapy for more than five consecutive fractions.ResultsAll 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. After CRT, four patients had a partial response and one patient had a complete clinical response. Two patients were considered in local progression at 9.4 months and 20.4 months of inclusion.ConclusionsDose escalation at 56.25 Gy in the tumor lesion was possible with good acute tolerance. It needs to be evaluated in a larger study. It could allow sufficient local control in order to avoid mutilating surgery in these metastatic patients.Trial registrationNCT03634202. Registered 16 August 2018 – retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT03634202