Main Session
Sep
28
PQA 03 - Digital Health Innovation and Informatics, Patient Safety & Quality, and Radiation and Cancer Biology
2418 - Neoadjuvant Pulsed Low-Dose-Rate (PLDR) Chemoradiation for Pancreatic Adenocarcinoma Not Eligible for Upfront Resection: A Phase I Trial
Presenter(s)
Alexander Campbell, MD - Fox Chase Cancer Center, Philadelphia, PA
A. W. Campbell1, S. S. Reddy2, E. Dotan3, N. E. Vijayvergia4, E. Handorf5, and J. E. Meyer1; 1Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA, 2Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA, 3Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, 4Fox Chase Cancer Center, Philadelphia, PA, 5Department of Biostatistics and Bioinformatics, Fox Chase Cancer Center, Philadelphia, PA
Purpose/Objective(s):
Radiation with radiosensitizing chemotherapy (CRT) is used preoperatively for pancreatic adenocarcinoma not eligible for upfront resection to facilitate R0 resection, a key survival determinant. Conventional doses are limited to 45–54 Gy by the radiation tolerance of adjacent bowel structures. PLDR delivers each fraction in multiple low-dose-rate pulses, exploiting differential repair kinetics between normal and malignant tissues. This trial evaluated CRT safety, surgical feasibility, and pathologic response of dose escalation.
Materials/Methods:
This Phase I trial evaluated PLDR CRT with concurrent gemcitabine (600 mg/m²/wk) in patients with pancreatic adenocarcinoma not eligible for upfront resection. Twelve patients were enrolled from 2020-2023: ten met NCCN criteria for borderline resectable disease, one was classified as resectable with high risk for a positive margin, and one had locally advanced disease with potential for downstaging. Prior to CRT, all patients received 6–12 cycles of induction chemotherapy (FOLFIRINOX or gemcitabine/nab-paclitaxel). Cohort 1 (n=6) received 56 Gy over 6 weeks; cohort 2 (n=6) received 66 Gy over 7 weeks, with escalation contingent on =1 grade 3+ GI toxicity in cohort 1 within 90 days of treatment. Following CRT, patients underwent restaging CT to determine surgical candidacy. The primary endpoint was acute grade 3+ GI toxicity. Secondary endpoints included R0 resection rate and pathologic response assessed by percent tumor fibrosis.
Results:
Grade 2 toxicities were most common (n=18 events, 62%), followed by grade 3 (n=8, 28%), grade 4 (n=2, 7%), and grade 5 (n=1, 3%). One death occurred in cohort 2 due to acute GI hemorrhage 40 days post-CRT, adjudicated as possibly treatment-related; restaging CT one week prior showed persistent tumor abutment of the SMV without invasion or arterial/GI structure involvement. Among grade 3+ events (n=11), hematologic toxicities were most common (n=6, 55%), including one grade 4 thrombocytopenia requiring treatment interruption. One cohort 1 patient experienced grade 3 nausea/vomiting requiring hospitalization. Four patients per cohort (67%) underwent resection; all achieved R0 resection. Cohort 1 showed fibrosis rates of 89-100% (mean 95%) versus 70-97% (mean 86%) in cohort 2, with an overall mean of 89%.
Conclusion:
Neoadjuvant PLDR CRT is feasible in patients with pancreatic adenocarcinoma not eligible for upfront resection, with a surgical resection rate of 67%, R0 resection in all resected patients, and high pathologic responses with mean fibrosis rate of 89%. With the exception of one possibly treatment-related grade 5 event, treatment and dose escalation were generally well tolerated, with grade 2 toxicities comprising the majority of adverse events. Clinical outcomes data will be forthcoming. These findings support a potential role for PLDR in enabling dose escalation and warrant further prospective investigation.