A prospective trial of stereotactic body radiation therapy for unresectable pancreatic cancer testing ablative doses

Abstract

Background: We explored the safety and efficacy of ablative doses of stereotactic body radiation therapy (SBRT) for unresectable pancreatic cancer.Methods: This phase I/II trial included patients with unresectable pancreatic cancer previously treated with any number of cycles of induction chemotherapy. Patients were enrolled according to a 3+3 dose escalation design at 10, 12.5, and 15 Gy ×3, with subsequent patients at the maximally tolerated dose (MTD).Treatment was delivered to gross tumor delineated with MRI fusion using image-guidance to fiducial markers. Dose-limiting toxicity (DLT) was defined as grade 3+ toxicity within 30 days. Secondary endpoints included late gastrointestinal (GI) toxicity, freedom from local failure (FFLF), and survival.Results: Fifteen patients received a median 10 cycles of chemotherapy. There were no DLTs, and the MTD was 15 Gy ×3. Thirty-day toxicity included grade 2 nausea (46%) and grade 2 diarrhea (7%). Median survival after SBRT was 12.8 months (23 months after diagnosis) and median relapse-free survival was 7 months. At 1-year, FFLF was 80%. Four patients had grade 3+ GI bleeding after 30 days (median 6 months). Grade 3+ GI bleeding was associated with tumor volume (P=0.01), heterogeneity of dose within the planning target volume (PTV) (V120, P=0.03), and duodenal dose (V26-30 Gy, P<0.2). Conclusions:This aggressive SBRT regimen demonstrated limited 30-day morbidity, a moderate degree of local control, and a moderate risk for late GI bleeding. Further work is necessary to define the most appropriate hypofractionated radiation therapy (RT) regimen in the ablative dose range.

Upfront Chemotherapy Followed by Stereotactic Body Radiation Therapy with or without Surgery in Older Patients with Localized Pancreatic Cancer: A Single Institution Experience and Review of the Literature

“…One area of active investigation, which may be relevant to older patients, is dose escalation for inoperable pancreatic cancer. Retrospective data has shown that increased radiation dose can improve both OS and LPFS [ 26 , 27 , 28 , 29 ]. Studies, including the current one, demonstrate that SBRT to conventional doses is safe and feasible, but that outcomes can be suboptimal especially in older patients who cannot undergo surgical resection or receive systemic therapy [ 14 , 15 , 16 , 17 , 18 ].…”

Risk Adapted Ablative Radiotherapy After Intensive Chemotherapy for Locally Advanced Pancreatic Cancer

“…Remarkably, patients were treated with ablative doses, with different fractionations (75 Gy/25 fractions, 67.5 Gy/15 fractions, or 50 Gy/5 fractions) according to the distance between pancreatic tumor and the gastro-intestinal tract. In addition, in a more recent prospective trial of SAbR (30-45 Gy/3 fractions) for unresectable pancreatic cancer, the Authors found a median survival of 23 months from the time of diagnosis (33). Notably, patients were enrolled regardless of the number of cycles and systemic therapy schedule, emphasizing the synergistic potential role of the ablative RT doses.…”

Role of stereotactic body radiation in the enhancement of the quality of life in locally advanced pancreatic adenocarcinoma: a systematic review

“…Concerning pain as one of the main complaints in patients with LAPC, all eleven studies comprising 292 patients reported on it in significantly more detail. Generally, pain appears to be improved by SBRT therapy [19][20][21][22][23][24][25][26][27][28][29][30]. It also appeared that the maximum pain palliation effect was achieved at approx.…”

“…All eleven studies reported on any patient-reported outcomes [19][20][21][22][23][24][25][26][27][28][29][30]. Only five reported quality of life [19,20,23,[27][28][29].…”

“…Comito [22], Ji [24], Liauw [26] and Tozzi [30] evaluated pain using the Numerical Rating Scale (NRS) scoring system. According to Comito [22], 39% of their 45 patients experienced pain before SBRT according to the Numerical Rating Scale (NRS) scoring system.…”