ABSTRACT
Background and purpose: Biomarkers for prediction of outcome in patients with pancreatic cancer are wanted in order to personalize the treatment. This study investigated the value of longitudinal diffusion-weighted magnetic resonance imaging (DWI) for prediction of overall survival (OS) in patients with locally advanced pancreatic cancer (LAPC) treated with stereotactic body radiotherapy (SBRT). Materials and methods: The study included 45 patients with LAPC who received 5 fractions of 10 Gy on a 1.5T MRI-Linac. DWI was acquired prior to irradiation at each fraction. The analysis included baseline values and time-trends of the apparent diffusion coefficient (ADC) and DWI parameters obtained using a decomposition method. A multivariable Cox proportional hazards model for OS was made using best-subset selection, using cross-validation based on Bootstrap. Results: The median OS from the first day of SBRT was 15.5 months (95% CI: 13.2-20.6), and the median potential follow-up time was 19.8 months. The best-performing multivariable model for OS included two decomposition-based DWI parameters: one baseline and one time-trend parameter. The C-Harrell index describing the model's discriminating power was 0.754. High baseline ADC values were associated with reduced OS, whereas no association between the ADC time-trend and OS was observed. Conclusion: Decomposition-based DWI parameters indicated value in the prediction of OS in LAPC. A DWI time-trend parameter was included in the best-performing model, indicating a potential benefit of acquiring longitudinal DWI during the SBRT course. These findings support both baseline and longitudinal DWI as candidate prognostic biomarkers, which may become tools for personalization of the treatment of patients with LAPC.
ABSTRACT
PURPOSE: Stereotactic body radiotherapy (SBRT) has emerged as a promising new modality for locally advanced pancreatic cancer (LAPC). The current study evaluated the efficacy and toxicity of SBRT in patients with LAPC (NCT03648632). METHODS: This prospective single institution phase II study recruited patients with histologically or cytologically proven adenocarcinoma of the pancreas after more than two months of combination chemotherapy with no sign of progressive disease. Patients were prescribed 50-60 Gy in 5-8 fractions. Patients were initially treated on a standard linac (n = 4). Since 2019, patients were treated using online magnetic resonance (MR) image-guidance on a 1.5 T MRI-linac, where the treatment plan was adapted to the anatomy of the day. The primary endpoint was resection rate. RESULTS: Twenty-eight patients were enrolled between August 2018 and March 2022. All patients had non-resectable disease at time of diagnosis. Median follow-up from inclusion was 28.3 months (95 % CI 24.0-NR). Median progression-free and overall survival from inclusion were 7.8 months (95 % CI 5.0-14.8) and 16.5 months (95 % CI 10.7-22.6), respectively. Six patients experienced grade III treatment-related adverse events (jaundice, nausea, vomiting and/or constipation). One of the initial four patients receiving treatment on a standard linac experienced a grade IV perforation of the duodenum. Six patients (21 %) underwent resection. A further one patient was offered resection but declined. CONCLUSION: This study demonstrates that SBRT in patients with LAPC was associated with promising overall survival and resection rates. Furthermore, SBRT was safe and well tolerated, with limited severe toxicities.