Clinical outcomes after online adaptive MR-guided stereotactic body radiotherapy for pancreatic tumors on a 1.5 T MR-linac

Abstract

IntroductionOnline adaptive magnetic resonance-guided radiotherapy (MRgRT) is a promising treatment modality for pancreatic cancer and is being employed by an increasing number of centers worldwide. However, clinical outcomes have only been reported on a small scale, often from single institutes and in the context of clinical trials, in which strict patient selection might limit generalizability of outcomes. This study presents clinical outcomes of a large, international cohort of patients with (peri)pancreatic tumors treated with online adaptive MRgRT.MethodsWe evaluated clinical outcomes and treatment details of patients with (peri)pancreatic tumors treated on a 1.5 Tesla (T) MR-linac in two large-volume treatment centers participating in the prospective MOMENTUM cohort (NCT04075305). Treatments were evaluated through schematics, dosage, delivery strategies, and success rates. Acute toxicity was assessed until 3 months after MRgRT started, and late toxicity from 3–12 months of follow-up (FU). The EORTC QLQ-C30 questionnaire was used to evaluate the quality of life (QoL) at baseline and 3 months of FU. Furthermore, we used the Kaplan–Meier analysis to calculate the cumulative overall survival.ResultsA total of 80 patients were assessed with a median FU of 8 months (range 1–39 months). There were 34 patients who had an unresectable primary tumor or were medically inoperable, 29 who had an isolated local recurrence, and 17 who had an oligometastasis. A total of 357 of the 358 fractions from all hypofractionated schemes were delivered as planned. Grade 3–4 acute toxicity occurred in 3 of 59 patients (5%) with hypofractionated MRgRT and grade 3–4 late toxicity in 5 of 41 patients (12%). Six patients died within 3 months after MRgRT; in one of these patients, RT attribution could not be ruled out as cause of death. The QLQ-C30 global health status remained stable from baseline to 3 months FU (70.5 at baseline, median change of +2.7 [P = 0.5]). The 1-year cumulative overall survival for the entire cohort was 67%, and that for the primary tumor group was 66%.ConclusionOnline adaptive MRgRT for (peri)pancreatic tumors on a 1.5 T MR-Linac could be delivered as planned, with low numbers of missed fractions. In addition, treatments were associated with limited grade 3–4 toxicity and a stable QoL at 3 months of FU.

Advancing the frontiers of MR-guided radiotherapy for pancreatic cancer

“…Early studies on patient-reported outcomes indicate a stable quality of life after MR-guided SBRT. 18,159,162 This last point brings us to the role that CBCT-guided radiotherapy might still play in future treatment of pancreatic cancer, which might not be confined to MR-guided systems after all. Cone-beam guided adaptive radiotherapy has only just begun to emerge, 168,169 and clinicians may be hesitant to the prescribe the ablative dose levels on these systems.…”

“…Early results from large cohorts demonstrate that MR-guided SBRT for pancreatic cancer can safely be delivered in high dose regimens, with low acute toxicity rates and no loss of quality of life. [15][16][17][18][19] However, now that MR-guided radiotherapy has been established as a feasible and safe therapy, it has become clear that there are several technical hurdles with regards to treatment planning and delivery that will play increasingly dominant roles as dose is further escalated and PTV margins reduced. 20,21 This section will further outline these limitations and challenges, and set the scene for the work presented in this thesis.…”

“…Early clinical outcomes demonstrated that stereotactic treatment with prescribed doses of up to 50 Gy in five fractions (equivalent to a biologically effective dose for α/β = 10 (BED 10 ) of 100 Gy) can safely be delivered while maintaining low acute toxicity rates. 15,17,18,40,43,63 These high dose levels in a complex anatomical region make SBRT treatment planning for pancreatic tumors a complex task. There are currently notable differences between documented institutional protocols with regards to prescribed dose, organ at risk (OAR) constraints and safety margins, see Table 3.1.…”

“…in Medicine & Biology (2022), 67(18):185016 A B S T R A C T Background and purpose -Intrafraction motion is a major concern for the safety and effectiveness of high dose stereotactic body radiotherapy (SBRT) in the upper abdomen. In this study, the impact of the intrafraction motion on the delivered dose was assessed in a patient group that underwent MR-guided radiotherapy for upper abdominal malignancies with an abdominal corset.Materials and methods -Fast online 2D cine MRI was used to extract tumor motion during beam-on time.…”