Stereotactic MR-Guided Radiotherapy for Pancreatic Tumors: Dosimetric Benefit of Adaptation and First Clinical Results in a Prospective Registry Study

Abstract

IntroductionStereotactic MR-guided adaptive radiotherapy (SMART) is an attractive modality of radiotherapy for pancreatic tumors. The objectives of this prospective registry study were to report the dosimetric benefits of daily adaptation of SMART and the first clinical results in pancreatic tumors.Materials and MethodsAll patients treated in our center with SMART for a pancreatic tumor were included. Patients were planned for five daily-adapted fractions on consecutive days. Endpoints were acute toxicities, late toxicities, impact of adaptive treatment on target volume coverage and organs at risk (OAR) sparing, local control (LC) rate, distant metastasis-free survival (DMFS), and overall survival (OS).ResultsThirty consecutive patients were included between October 2019 and April 2021. The median dose prescription was 50 Gy. No patient presented grade > 2 acute toxicities. The most frequent grade 1–2 toxicities were asthenia (40%), abdominal pain (40%), and nausea (43%). Daily adaptation significantly improved planning target volume (PTV) and gross tumor volume (GTV) coverage and OAR sparing. With a median follow-up of 9.7 months, the median OS, 6-month OS, and 1-year OS were 14.1 months, 89% (95% CI: 70%–96%), and 75% (95% CI: 51%–88%), respectively, from SMART completion. LC at 6 months and 1 year was respectively 97% (95% CI: 79–99.5%) and 86% (95% CI: 61%–95%). There were no grade > 2 late toxicities. With a median follow-up of 10.64 months, locally advanced pancreatic cancer (LAPC) and borderline resectable pancreatic cancer (BRPC) patients (22 patients) had a median OS, 6-month OS, and 1-year OS from SMART completion of 14.1 months, 76% (95% CI: 51%–89%), and 70% (95% CI: 45%–85%), respectively. Nine patients underwent surgical resection (42.1% of patients with initial LAPC and 33.3% of patients with BRPC), with negative margins (R0). Resected patients had a significantly better OS as compared to unresected patients (p = 0.0219, hazard ratio (HR) = 5.78 (95% CI: 1.29–25.9)).ConclusionSMART for pancreatic tumors is feasible without limiting toxicities. Daily adaptation demonstrated a benefit for tumor coverage and OAR sparing. The severity of observed acute and late toxicities was low. OS and LC rates were promising. SMART achieved a high secondary resection rate in LAPC patients. Surgery after SMART seemed to be feasible and might increase OS in these patients.

Patterns of Failure in Patients With Borderline Resectable/Locally Advanced Pancreatic Cancer After Preoperative Chemotherapy and Stereotactic Body Radiation Therapy

“…In addition, new technologies such as stereotactic magnetic resonance-guided radiation therapy (SMART) may allow for dose-escalation to larger volumes of gross disease and elective volumes while limiting normal tissue toxicity. 27 , 40 …”

Dose Escalation for Pancreas SBRT: Potential and Limitations of using Daily Online Adaptive Radiation Therapy and an Iterative Isotoxicity Automated Planning Approach

“…In previous studies, doses of 70 to 100 Gy BED 10 (ie, BED with α:β ratio of 10) are required for an ablative effect and increase overall survival. 23 , 24 , 25 Current SBRT dose regimens of 35 to 40 Gy in 5 fractions (59.5-72 Gy BED 10 ) do not achieve this dosimetric threshold, but increasing BED without increasing normal structure toxicity could be achieved with our approach because of the inter- and intrafraction bowel and target motions, 6 although intrafraction tumor motion can be managed by adapting the breath hold technique with a more generous CTV-to-PTV margin, 26 as well as utilizing OAR margins to generate planning organ-at-risk volume. We have shown that DE-ART can achieve 110 to 125 Gy BED 10 for the GTV and TVI, and DE-PTV can achieve 85 Gy BED 10 .…”

Stereotactic Body Radiotherapy (SBRT) of Pancreatic Cancer—A Critical Review and Practical Consideration

“…A recent prospective study by Michalet et al [ 101 ] demonstrated the dosimetric benefit of MR-guided radiotherapy for pancreatic tumors. Thirty patients were treated with a mean dose of 50 Gy.…”