title: Re-irradiation with stereotactic body radiation therapy as a novel treatment option for isolated local recurrence of pancreatic cancer after multimodality therapy: experience from two institutions.
abstract: Limited treatment options exist for isolated local recurrence of pancreatic ductal adenocarcinoma (PDA) following surgical resection accompanied by neoadjuvant or adjuvant chemoradiation therapy (CRT). While select patients are eligible for re-resection, recurrent lesions are often unresectable. Stereotactic body radiation therapy (SBRT) represents a possible minimally invasive treatment option for these patients, although published data in this setting are currently lacking. This study examines the safety, efficacy, and palliative capacity of re-irradiation with SBRT for isolated local PDA recurrence. All patients undergoing SBRT at two academic centers from 2008-2012 were retrospectively reviewed to identify those who received re-irradiation with SBRT for isolated local recurrence or progression of PDA after previous conventionally fractionated CRT. Information regarding demographics, clinicopathologic characteristics, therapies received, survival, symptom palliation, and toxicity was obtained from patient charts. Kaplan-Meier statistics were used to analyze survival and the log-rank test was used to compare survival among patient subgroups. Eighteen patients were identified. Fifteen had previously undergone resection with neoadjuvant or adjuvant CRT, while 3 received definitive CRT for locally advanced disease. Median CRT dose was 50.4 Gy [interquartile range (IQR), 45.0-50.4 Gy] in 28 fractions. All patients subsequently received gemcitabine-based maintenance chemotherapy, but developed isolated local disease recurrence or progression without evidence of distant metastasis. Locally recurrent or progressive disease was treated with SBRT to a median dose of 25.0 Gy (range, 20.0-27.0 Gy) in 5 fractions. Median survival from SBRT was 8.8 months (95% CI, 1.2-16.4 months). Despite having similar clinicopathologic disease characteristics, patients who experienced local progression greater than vs. less than 9 months after surgery/definitive CRT demonstrated superior median survival (11.3 vs. 3.4 months; P=0.019) and progression-free survival (10.6 vs. 3.2 months; P=0.030) after SBRT. Rates of freedom from local progression at 6 and 12 months after SBRT were 78% (14 of 18 patients) and 62% (5 of 8 patients), respectively. Effective symptom palliation was achieved in 4 of 7 patients (57%) who reported symptoms of abdominal or back pain prior to SBRT. Five patients (28%) experienced grade 2 acute toxicity; none experienced grade ≥3 acute toxicity. One patient (6%) experienced grade 3 late toxicity in the form of small bowel obstruction. In conclusion, re-irradiation with hypofractionated SBRT in this salvage scenario appears to be a safe and reasonable option for palliation of isolated local PDA recurrence or progression following previous conventional CRT. Patients with a progression-free interval of greater than 9 months prior to isolated local recurrence or progression may be most suitable for re-irradiation with SBRT, as they appear to have a better prognosis with survival that is long enough for local control to be of potential benefit.
authors.affiliation: Department of Radiation Oncology & Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA;
authors.forename: Aaron T
authors.initials: AT
authors.lastname: Wild
authors.forename: Susan M
authors.initials: SM
authors.lastname: Hiniker
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Chang
authors.forename: Phuoc T
authors.initials: PT
authors.lastname: Tran
authors.forename: Mouen A
authors.initials: MA
authors.lastname: Khashab
authors.forename: Maneesha R
authors.initials: MR
authors.lastname: Limaye
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Laheru
authors.forename: Dung T
authors.initials: DT
authors.lastname: Le
authors.forename: Rachit
authors.initials: R
authors.lastname: Kumar
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Pai
authors.forename: Blaire
authors.initials: B
authors.lastname: Hargens
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Sharabi
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Shin
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Pawlik
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Wolfgang
authors.forename: Albert C
authors.initials: AC
authors.lastname: Koong
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Herman
keywords: Stereotactic body radiation therapy (SBRT); local recurrence; pancreatic cancer; re-irradiation