Ablative Five-Fraction Stereotactic Body Radiation Therapy for Inoperable Pancreatic Cancer Using Online MR-Guided Adaptation

Abstract

Purpose Patients with inoperable pancreatic adenocarcinoma have limited options, with traditional chemoradiation providing modest clinical benefit and an otherwise poor prognosis. Stereotactic body radiation therapy for pancreatic cancer is limited by proximity to organs-at-risk (OAR). However, stereotactic magnetic resonance-guided adaptive radiation therapy (SMART) has shown promise in delivering ablative doses safely. We sought to demonstrate the benefits of SMART using a 5-fraction approach with daily on-table adaptation. Methods and Materials Patients with locally advanced, nonmetastatic pancreatic adenocarcinoma were treated with 50 Gy in 5 fractions (biologically effective dose 10 100 Gy) with a prescribed goal of 95% planning target volume coverage by 95% of prescription, prioritizing hard OAR constraints. Daily online adaptation was performed using magnetic resonance-guidance and on-table reoptimization. Patient outcomes, treatment factors, and daily adaptation were evaluated. Results Forty-four patients were treated with SMART at our institution from 2014 to 2019. Median follow-up from date of diagnosis was 16 months (range, 6.7-51.6). Late toxicity was limited to 2 (4.6%) grade 3 (gastrointestinal ulcers) and 3 (6.8%) grade 2 toxicities (duodenal perforation, antral ulcer, and gastric bleed). Tumor abutted OARs in 35 patients (79.5%) and tumor invaded OARs in 5 patients (11.1%). Reoptimization was performed for 93% of all fractions. Median overall survival was 15.7 months (95% confidence interval, 10.2-21.2), while 1-year and 2-year overall survival rates were 68.2% and 37.9%, respectively. One-year local control was 84.3%. Conclusions This is the first reported experience using 50 Gy in 5 fractions for inoperable pancreatic cancer. SMART allows this ablative dose with promising outcomes while minimizing toxicity. Additional prospective trials evaluating efficacy and safety are warranted.

Ablative 5-Fraction Stereotactic Magnetic Resonance–Guided Radiation Therapy With On-Table Adaptive Replanning and Elective Nodal Irradiation for Inoperable Pancreas Cancer

“…MRgRT is a novel technique that facilitates dose escalation in the abdomen beyond what has been historically feasible using CT. 5,17,22,38 SMART delivered with Co-60 was tolerated remarkably well in an analysis by Rudra et al of 44 pancreas patients, with 25 receiving dose escalation to 40 to 67.5 Gy over 5 to 15 fractions. 5 The minority received 5 fractions although it was not specified how many received at least 50 Gy (BED 10 100 Gy 10 ); it was likely a small number given the median prescribed BED 10 was 77.6 Gy 10 .…”

“…There has recently become greater enthusiasm in radiation dose escalation for inoperable pancreas cancer to potentially improve clinical outcomes. 4e8, 10,17 Investigators from MD Anderson Cancer Center reported that LAPC patients, typically treated in 28 fractions with daily CT guidance, had higher median survival (17.8 vs 15.0 months; P Z .03) and local-regional relapse free survival (10.2 vs 6.2 months; P Z .05) when a biologically effective dose (BED 10 ) >70 Gy 10 was prescribed (Table 4). 4 Dose intensification was considered, typically with fractionation over multiple weeks to mitigate toxicity, if there was !1 cm between tumor and luminal GI structures.…”

“…Earlier this year, a retrospective analysis of SMART prescribed to 50 Gy in 5 fractions without ENI was published by investigators at Washington University in St. Louis that included 44 inoperable pancreas cancer patients, most (86%) treated on a Co-60 system. 17 With median follow-up of 16 months from pancreas cancer diagnosis, outcomes included 2-year LC, PFS, and OS of 59.3%, 13.9%, and 37.9%, respectively. Treatment was very well tolerated with limited grade 3 toxicity.…”

“…Still, we believe that our median follow-up of 10.3 months is long enough to provide meaningful comparison to other studies, especially given that the median survival for LAPC patients is approximately 12 to 16 months. 4 In addition, whereas other analyses with longer follow-up measured outcomes from the time of diagnosis, 17,36 which then is routinely followed by at least several months of chemotherapy, our analysis began from the initiation of SMART. Lastly, although most fractions were adapted the cumulative dose was not assessed with respect to clinical outcomes.…”

“…5 These outcomes are supported by a recent single institution report of 5-fraction SMART, mostly delivered using Co-60. 17 The first MR-linear accelerator (LINAC) became clinically operational in 2017, offering improved dosimetry with multifield intensity modulated radiation therapy (IMRT) compared with Co-60 and achieving comparable plan quality to a conventional c-arm linac. 18,19 Higher dose conformality made feasible by the MR-LINAC increases the potential for higher target doses previously not achieved with the first-generation MRgRT Co-60 machines.…”