Evaluation of hypofractionated adaptive radiotherapy using the MR Linac in localised pancreatic cancer: protocol summary of the Emerald-Pancreas phase 1/expansion study located at Oxford University Hospital, UK.

INTRODUCTION: Online adaptive MR-guided radiotherapy allows for dose escalation to pancreatic cancer while sparing surrounding critical organs. We seek to evaluate the safety of delivering hypofractionated five-fraction, three-fraction and single-fraction MR-guided stereotactic ablative radiotherapy (SABR) to the pancreas. METHODS AND ANALYSIS: This is a single-centre three-arm phase 1 non-randomised safety study. Patients with localised pancreatic cancer will receive either 50 Gy in five (biological equivalent dose (BED10)=100 Gy), 39 Gy in three (BED10=90 Gy) or 25 Gy in a single fraction (BED10=87.5 Gy) MR-guided daily online adaptive radiotherapy. Each fractionation regimen will be assessed as independent cohorts to determine tolerability, assessed continuously using Bayesian conjugate posterior beta distributions. The primary endpoint of the study is to establish the safety of five-fraction, three-fraction and single-fraction MR-guided hypofractionation SABR in localised pancreatic cancer by assessing dose-limiting toxicities. Secondary endpoints include overall survival, progression-free survival, local control rates, overall control rate, resection rates, long-term toxicities and freedom from second-line chemotherapy. This study plans to also explore imaging and immune biomarkers that may be useful to predict outcome and personalise treatment. The trial will recruit up to 60 patients with a safety run-in. ETHICS AND DISSEMINATION: The trial is approved by the West Midlands-Black Country Research Ethics Committee 22/WM/0122. The results will be disseminated via conference presentations, peer-reviewed scientific journals and submission to regulatory authorities. The data collected for the study, including individual participant data, will be made available to researchers on request to the study team and with appropriate reason, via octo-enquiries@oncology.ox.ac.uk. The shared data will be deidentified participant data and will be available for 3 years following publication of the study. Data will be shared with investigator support, after approval of a proposal and with a signed data access agreement. TRIAL REGISTRATION NUMBER: ISRCTN10557832.

Superior outcomes of nodal metastases compared to visceral sites in oligometastatic colorectal cancer treated with stereotactic ablative radiotherapy.

BACKGROUND: Stereotactic ablative radiotherapy (SBRT) is a radical option for oligometastatic colorectal cancer (CRC) patients, but most data relate to visceral metastases. METHODS: A prospective, multi-centre database of CRC patients treated with SBRT was interrogated. Inclusion criteria were ECOG PS 0-2, ≤3 sites of disease, a disease free interval of >6 months unless synchronous liver metastases. Primary endpoints were local control (LC), progression free survival (PFS) and overall survival (OS). RESULTS: 163 patients (172 metastases) were analysed. The median FU was 16 months (IQR 12.2-22.85). The LC at 1 year was 83.8% (CI 76.4%-91.9%) with a PFS of 55% (CI 47%-64.7%) respectively. LC at 1 year was 90% (CI 83%-99%) for nodal metastases (NM), 75% (63%-90%) for visceral metastases (VM). NM had improved median PFS (9 vs 19 months) [HR 0.6, CI 0.38-0.94, p = 0.032] and median OS (32 months vs not reached) [HR 0.28, CI 0.18-0.7, p = 0.0062] than VM, regardless of whether the NM were located inside or outside the pelvis. On multivariate analysis, NM and ECOG PS 0 were significant good prognostic factors. An exploratory analysis suggests KRAS WT is also a good prognostic factor. CONCLUSION: Nodal site is an important prognostic determinant of SBRT that should incorporated into patient selection. We hypothesise this may have an immunoediting basis.