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Background: The role of neoadjuvant stereotactic body radiation therapy (SBRT) in the treatment of pancreatic adenocarcinoma (PDAC) is controversial and the optimal target volumes and dose-fractionation are unclear. The aim of this study is to report on treatment outcomes and patterns of failure of patients with borderline resectable (BL) or locally advanced (LA) pancreatic cancer following preoperative chemotherapy and SBRT., Methods: We conducted a single-institution, retrospective study of patients with BL or LA PDAC. Patients received neoadjuvant chemotherapy and SBRT was prescribed to 30 Gy over 5 fractions to the pancreas planning tumor volume (PTV). A subset of patients received a simultaneous integrated boost to the high risk vascular PTV and/or elective nodal irradiation (ENI). Following neoadjuvant chemoradiation, all patients underwent subsequent resection. Overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMPFS), and locoregional control (LRC) estimates were obtained using Kaplan-Meier analysis., Results: Twenty-two patients with BL (18) or LA (4) PDAC were treated with neoadjuvant chemotherapy and SBRT followed by resection from 2011-2022. Following neoadjuvant treatment, 5 patients (23%) achieved a pathologic complete response (pCR) and 16 patients (73%) had R0 resection. At 24 months, there were no isolated locoregional recurrences (LRRs), 9 isolated distant recurrences (DRs), and 5 combined LRRs and DRs. Two LRRs were in-field, 2 LRRs were marginal, and 1 LRR was both in-field and marginal. 2-year median LRC, LRRFS, DMPFS, PFS, and OS were 77.3%, 45.5%, 31.8%, 31.8%, and 59.1%, respectively. For BL and LA cancers, 2-year LRC, DMPFS, and OS were 83% vs. 75%, (p = 0.423), 39% vs. 0% (p = 0.006), and 61% vs. 50% (p = 0.202), respectively. ENI was associated with improved LRC (p = 0.032) and LRRFS (p = 0.033). Borderline resectability (p = 0.018) and lower tumor grade (p = 0.027) were associated with improved DMPFS., Conclusions: Following preoperative chemotherapy and SBRT, locoregional failure outside of the target volume occurred in 3 of 5 recurrences; ENI was associated with improved LRC and LRRFS. Further studies are necessary to define the optimal techniques for preoperative radiation therapy., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Despite improvement in systemic therapy, patients with pancreatic ductal adenocarcinoma (PDAC) frequently experience local recurrence. We sought to determine the safety of hypofractionated proton beam radiation therapy (PBT) during adjuvant chemotherapy., Methods and Materials: Nine patients were enrolled in a single-institution phase 1 trial (NCT03885284) between 2019 and 2022. Patients had PDAC of the pancreatic head and underwent R0 or R1 resection and adjuvant modified FOLFIRINOX (mFFX) chemotherapy. The primary endpoint was to determine the dosing schedule of adjuvant PBT (5 Gy × 5 fractions) using limited treatment volumes given between cycles 6 and 7 of mFFX. Patients received PBT on days 15 to 19 in a 28-day cycle before starting cycle 7 (dose level 1, DL1) or on days 8 to 12 in a 21-day cycle before starting cycle 7 (DL2)., Results: The median patient age was 66 years (range, 52-78), and the follow-up time from mFFX initiation was 12.5 months (range, 6.2-37.4 months). No patients received preoperative therapy. Four had R1 resections and 5 had node-positive disease. Three patients were enrolled on DL1 and 6 patients on DL2. One dose-limiting toxicity (DLT) occurred at DL2 (prolonged grade 3 neutropenia resulting in discontinuation of mFFX after cycle 7). No other DLTs were observed. Four patients completed 12 cycles of mFFX (range, 7-12; median, 11). No patients have had local recurrence. Five of 9 patients had recurrence: 3 in the liver, 1 in the peritoneum, and 1 in the bone. Six patients are still alive, 4 of whom are recurrence-free. The median time to recurrence was 12 months (95% CI, 4 to not reached [NR]), and median overall survival was NR (95% CI, 6 to NR; 2-year survival rate, 57%)., Conclusions: PBT integrated within adjuvant mFFX was well tolerated, and no local recurrence was observed. These findings warrant further exploration in a phase 2 trial., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The majority of patients with pancreatic cancer are diagnosed with metastatic disease at presentation. Nevertheless, local progression is responsible for up to 30% of deaths and can lead to significant morbidity. As a consequence, further exploration of effective methods of local control and palliation is essential. Stereotactic body radiation therapy (SBRT) is a widely utilized technique for the treatment of localized pancreatic cancer. Here, we report our experience with SBRT and chemotherapy for the local treatment of the metastatic patient population., Methods: This single institution retrospective review analyzed 20 patients with pathologically diagnosed metastatic adenocarcinoma of the pancreas. All patients underwent fiducial placement under endoscopic ultrasound (EUS) guidance. SBRT was delivered in five fractions to a total dose of 25 to 30 Gy. Patients received concurrent (given within 1 week of the start of SBRT) or sequential chemotherapy. Local tumor control was evaluated using Response Evaluation Criteria in Solid Tumors. Toxicity was graded using Common Terminology Criteria for Adverse Events version 4.03. Local control and overall survival were reported using the Kaplan-Meier method., Results: Patient median age was 64 years, and the median pre-treatment Eastern Cooperative Oncology Group performance status was 1. All patients received chemotherapy and half of the patients (10 of 20) received concurrent chemotherapy with folinic acid, fluorouracil, and oxaliplatin or fluorouracil, leucovorin, irinotecan, and oxaliplatin. Nearly all patients (19 of 20) received post-SBRT chemotherapy. Median time from pathological diagnosis to SBRT was 3.9 months. The twelve-month local control and overall survival were 43 and 53%, respectively. However, in patients with planning target volume (PTV) targets smaller than the population median, the 12-month local control was 78%. Median time to local progression (17.8 vs. 3.0 months, p = 0.02) and overall survival (24.9 vs. 8.8, p = 0.001) were also significantly improved in this smaller PTV cohort. Though not statistically significant, there was a trend towards improvement in local control (17.8 vs. 4.3 months, p = 0.17) and overall survival (16.7 vs. 9.7 months, p = 0.087) for those who received concurrent versus sequential chemotherapy, respectively. Lastly, there were no reported grade 3-5 late toxicities., Conclusions: As systemic therapies improve, the local management of pancreatic cancer will become increasingly important. Here, we report significantly improved local control with SBRT of smaller PTV tumors with concurrent chemotherapy. Five-fraction SBRT offers a quick and effective modality of local tumor control with minimal toxicity in the metastatic pancreatic cancer population.

Objectives: The role of radiation therapy in the management of unresectable pancreatic cancer is controversial. One concern about concurrent chemoradiation relates to the timing of chemotherapy. In contrast to conventional radiation therapy, stereotactic body radiation therapy (SBRT) delivers high doses in a shorter duration resulting in minimal disruption in chemotherapy. Here, we report our results of patients treated with SBRT and chemotherapy for inoperable pancreatic cancer., Materials and Methods: Thirty-eight patients treated with SBRT and chemotherapy for locally advanced, borderline resectable, and medically inoperable pancreatic cancer at our institution from January 2008 to December 2012 were included in this retrospective analysis. Treatment was delivered in 5 fractions of 5 or 6 Gy per fraction over 5 days. Toxicities were scored using the Common Terminology Criteria for Adverse Events version 3. Survival was calculated using the Kaplan-Meier method., Results: The median age was 70 years (range, 45 to 90 y). Eastern Cooperative Oncology Group performance status ranged from 0 to 3. Thirty-four patients received concurrent chemotherapy. Four patients received sequential chemotherapy. Median overall survival was 14.3 months and median progression-free survival was 9.2 months from diagnosis. From radiation, overall survival and progression-free survival were 12.3 and 6.8 months, respectively. The overall local control rate was 79%. Acute toxicity was minimal. Severe late SBRT-related toxicities included 1 grade 3 gastric outlet obstruction, 1 grade 4 biliary stricture, and 1 grade 5 gastric hemorrhage., Conclusions: SBRT combined with chemotherapy for unresectable pancreatic cancer is convenient, feasible, and generally well tolerated. Outcomes of SBRT combined with chemotherapy compare favorably to results obtained with chemotherapy and conventional radiation therapy.

Background: The purpose of this retrospective study was to evaluate the efficacy of incorporating trans-arterial radioembolization (TARE) with systemic chemotherapy in the treatment of liver-dominant metastatic pancreatic ductal adenocarcinoma, with the aim of destroying liver metastases and improving patient outcomes., Methods: We retrospectively evaluated 16 patients with liver-dominant metastatic pancreatic ductal adenocarcinoma who underwent TARE between February 2012 and August 2015; 15 of these patients also underwent concurrent systemic chemotherapy. Patient outcomes were assessed using Response Evaluation Criteria In Solid Tumors (RECIST), Version 1.1 and included disease response, median overall survival from the time of diagnosis of metastatic disease, and median overall survival following receipt of TARE. Treatment-related adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03., Results: The median overall survival from the time of diagnosis of metastatic disease and following receipt of TARE was 22.0 and 12.5 months, respectively. Overall and liver specific disease response were assessed for 13 patients with follow-up imaging available at the time of study (range 2-13 weeks post TARE). Four patients (31 %) demonstrated partial response and five patients (38 %) had stable disease in the liver at follow-up. One patient developed grade 3 elevation of total bilirubin three months post-treatment and another patient developed radiation cholecystitis directly following TARE. No treatment-related grade 4 or 5 toxicities were seen., Conclusion: TARE can be safely combined with systemic chemotherapy for the treatment of liver-dominant metastatic pancreatic cancer. Patient outcomes following this treatment strategy are promising but prospective evaluations are needed to validate these preliminary findings.

Background: Local control rates are poor in the treatment of pancreatic cancer. We investigated the role of hypofractionated stereotactic body radiation therapy (SBRT) for salvage or boost treatment after conventional doses of external beam radiation therapy., Methods: All patients treated with SBRT for pancreatic adenocarcinoma at Georgetown University from June 2002 through July 2007 were examined. Eligible patients had prior external beam radiation therapy to the pancreas. Treatment parameters and clinical and radiographic follow-up were evaluated., Results: Twenty-eight patients were identified who received SBRT after a median prior external beam radiotherapy dose of 50.4 Gy. The median patient age was 63 years old and the median follow-up was 5.9 months. Twelve of fourteen (85.7%) evaluable patients were free from local progression, with three partial responses and nine patients with stable disease. Toxicity consisted of one case of acute Grade II nausea/vomiting, and two cases of Grade III late GI toxicity. The median overall survival was 5.9 months, with 18% survival and 70% freedom from local progression at one year., Conclusions: Hypofractionated SBRT reirradiation of localized pancreatic cancer is a well-tolerated treatment. Most patients are free from local progression, albeit with limited follow-up, but overall survival remains poor.