Objectives
The goal of this study was to compare outcomes of patients with borderline and resectable pancreatic cancer treated with neoadjuvant stereotactic body radiation therapy (SBRT) versus fractionated chemoradiation.
Methods
Patients with borderline or resectable pancreatic cancer treated with neoadjuvant intent between November 2011 and December 2017 were reviewed. The SBRT volume/dose was 33 Gy in 5 fractions to gross tumor plus abutting vessel with or without 25 Gy in 5 fractions to pancreatic head/body and celiac/superior mesenteric artery. Fractionated chemoradiation volume/dose was 50.4 Gy in 28 fractions to gross tumor, superior mesenteric/celiac arteries, and enlarged lymph nodes with concurrent bolus 5-FU, leucovorin, oxaliplatin, irinotecan or gemcitabine/nab-paclitaxel. Failure patterns, local recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival were assessed.
Results
Forty-three patients were reviewed (18 SBRTs and 25 fractionated). Among patients who underwent resection, patients treated with fractionated chemoradiation had improved LRFS (12-month LRFS, 86% vs 62%, P = 0.003) and PFS (median PFS, 23 months vs 11 months, P = 0.006) compared with SBRT. There was no difference in overall survival.
Conclusions
Stereotactic body radiation therapy may result in inferior LRFS and PFS compared with fractionated chemoradiation, likely because of under coverage of high-risk vascular targets.
ObjectiveThe objectives of this study were to evaluate whether dose to the vasculature is associated with local control after surgery in patients with borderline resectable (BLR) and resectable pancreatic cancer (PCA) receiving neoadjuvant radiation therapy (RT) and to identify a dose threshold for clinical use.MethodsPatients with BLR and resectable PCA treated with neoadjuvant RT were retrospectively reviewed. During this period, the institutional paradigm shifted from standard fractionation to hypofractionation/stereotactic body radiation therapy (SBRT). A vasculature clinical target volume (Vasc CTV) was contoured for each patient and defined as a 5-mm margin around the superior mesenteric artery (SMA) from its origin to the pancreatic head, the celiac artery from its origin to the level of the trifurcation and any involved vein. The Vasc CTV D95 was normalized to a 2-Gy equivalent dose to determine the optimal dose associated with optimal local failure-free survival (LFFS).ResultsForty-seven patients were included in the analysis. A Vasc CTV D95 of 32.7 Gy was the optimal cutoff for LFFS. Patients with Vasc CTV D95 Equivalent dose in 2 Gy per fraction (EQD2) >32.7 Gy had significantly longer LFFS compared to patients with Vasc CTV D95 EQD2 ≤32.7 Gy at 12 months (91% vs. 51%, respectively) and 24 months (86% vs. 12%, respectively). The median disease-free survival (DFS) for patients with EQD2 >32.7 Gy was 30.4 months compared to 14.0 months in patients with EQD2 ≤32.7 Gy (p = 0.01). There was no significant difference in overall survival (OS) between the two groups.ConclusionsDuring neoadjuvant treatment, dose to the Vasc CTV is associated with durability of local control (LC) after resection and should be intentionally included in the treatment volume with an EQD2 goal of 31–33 Gy.
protocol. Stopping guidelines were established for number of allowable DLTs in each treatment arm as enrollment increased. Secondary endpoints included response as assessed using iRECIST criteria. Pre-SBRT and post-SBRT biopsies of the radiated lesion were obtained for exploratory analyses. Results: 14 patients received SBRT plus at least one cycle of Ipi/Nivo (n Z 8) or Nivo (n Z 6); the study was terminated early for slow accrual. 13 patients had CP Score A5 and one had A6. 6 patients had extra-hepatic disease at enrollment. The median mean liver dose was 11.21 Gy and the median V30 Liver was 13%. Only 2 patients had dose-limiting toxicity in first 6 months of treatment (grade 3 hepatotoxicity). 9 DLTs would have been deemed unsafe for number enrolled. Overall response was 36% PR, 36% SD, and 28% PD. Rates of PR/SD/PD were 50%/37.5%/12.5% for Ipi/Nivo and were 12.5%/37.5%/50% for Nivo alone. All 5 patients with response are alive at last follow-up; 4 of the responders (all on Ipi/Nivo arm) have durable response of least 18 months (18.2 mo. e 27.2 mo.) after SBRT. With a median follow-up of 8.3 months, median OS in the nivo arm was 6.7 months whereas the median OS in ipi/nivo arm was not reached. 2 of 6 in Nivo arm and 1 of 8 in Ipi/Nivo arm died of disease progression in the first six months after SBRT. Overall, only one patient progressed in the radiated lesion, which was noted at first post-SBRT imaging, and the patient died of progressive disease. Conclusion: The addition of SBRT to immunotherapy was well-tolerated. SBRT followed by combined checkpoint blockade with Ipi/Nivo was associated with a high rate of durable response in a population with advanced disease. Local control in radiated field was excellent. Pre/post-SBRT tissue analysis may help provide biomarkers for response. SBRT with combined Ipi/Nivo warrants further prospective study in HCC.
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