Session Item

The prospective THeragnostic Utilities for Neoplastic DisEases of the Rectum by MRI guided radiotherapy (MRgRT) -Thunder 2 clinical trial aims to evaluate the impact of radiotherapy (RT) dose escalation in intermediate risk locally advanced rectal cancer (LARC) poor responder patients identified by the Early Tumour Regression Index (ERI). The aim of the study is to assess the increased probability of both pathological and clinical complete response (pCR and cCR) and the feasibility of the approach. The purpose of this interim analysis is to assess the safety and feasibility of the dose escalation MRgRT approach in the clinical trial.

Patients affected by LARC cT2-3, N0-2 or cT4 for anal sphincter involvement N0-2a, M0 without high risk features were enrolled in the trial. All patients received MRgRT treatment. The initial RT treatment consist in delivering 55 Gy in 25 fractions on Gross Tumor Volume (GTV) plus the corresponding mesorectum and 45Gy in 25 fractions on the drainage nodes. Chemotherapy with 5-fluoracil (5-FU) or oral capecitabine was administered continuously. As planned for the Thunder 2 trial, a 0.35 Tesla MRI was acquired at simulation and every day during MRgRT. At fraction 10, ERI was calculated: if ERI was < 13.1, the patient continued the original treatment; if ERI was > 13.1, the patient was considered as “non responder” and underwent a re-optimisation of the treatment plan, intensifying the dose to the residual tumour from the 11th fraction to reach 60.1 Gy. Acute toxicity according to the CTCAE version 5.0 scale were retrospectively collected and analysed.

From March 2021 to October 2022, 33/63 (52.4%) patients were enrolled, of whom 16/33 (48.5%) underwent replanning with boost up to 60.1 Gy. The treatment was well tolerated, with only 2 (6.1%) cases of acute G3 diarrhoea, proctitis and cystitis observed in the standard treatment group.  There were no toxicity differences in the boost patient group versus patients receiving conventional treatment as reported in Table 1.

Our results support that MRgRT treatment with dose escalation up to 60.1 Gy on the tumour, prescribed on the basis of predicted response according to the ERI index for LARC patients, is well tolerated. We are awaiting the end of enrolment for the analysis of primary and secondary outcomes.