P Travis Courtney1, Anthony J Paravati2, Todd F Atwood3, Nandita Raja4, Collin T Zimmerman4, Paul T Fanta5, Andrew M Lowy6, Daniel R Simpson1, Ronghui Xu7, James D Murphy8. 1. University of California San Diego School of Medicine, La Jolla, California; Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California. 2. Kettering Cancer Care Department of Radiation Oncology, Kettering Health Network, Kettering, Ohio. 3. Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California. 4. Department of Hematology and Oncology, Kaiser Permanente Southern California, San Diego, California. 5. Center for Personalized Cancer Therapy and Division of Hematology and Oncology, Department of Medicine, University of California San Diego Moores Cancer Center, La Jolla, California. 6. Department of Surgery, University of California San Diego Moores Cancer Center, La Jolla, California. 7. Department of Family Medicine and Public Health and Department of Mathematics, University of California San Diego, La Jolla, California. 8. University of California San Diego School of Medicine, La Jolla, California; Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California. Electronic address: j2murphy@health.ucsd.edu.
Abstract
PURPOSE: Stereotactic body radiation therapy (SBRT) has demonstrated encouraging local tumor control rates in the treatment of pancreatic cancer, yet we lack prospective clinical trials evaluating dose-escalation strategies among patients treated with 5-fraction SBRT. This phase 1 dose-escalation trial was conducted to determine the maximum tolerated dose of SBRT in patients with pancreatic cancer. METHODS AND MATERIALS: Thirty patients with pancreatic cancer were enrolled and treated with 40, 45, or 50 Gy SBRT in 5 fractions with doses determined using a time-to-event continual reassessment method trial design. Systemic therapy was permitted before and after SBRT, but not mandated by the study protocol. Toxicity was the primary study endpoint, and any grade ≥3 acute or late toxicity potentially attributable to SBRT was considered a dose-limiting toxicity. Secondary endpoints included local progression, distant progression, and overall survival. RESULTS: The median follow up from SBRT was 8.9 months (range, 1.7-62.6 months). Nineteen patients (63%) had locally advanced disease, 3 patients (10%) had metastatic disease, and 8 patients (27%) had medically unresectable disease. Three patients (10%) received 40 Gy, 16 patients (53%) received 45 Gy, and 11 patients (37%) received 50 Gy. Seven patients (23%) experienced grade ≤2 acute toxicity, and 2 patients (6.7%) experienced grade 4 to 5 late toxicity, both of which occurred in the 45 Gy group. Median survival time was 17.1 months from the time of diagnosis and 9.8 months from SBRT. The 1-year cumulative incidence of local progression was 14.2% (95% confidence interval, 4.2%-30%). CONCLUSIONS: This dose-escalation trial evaluated high-dose SBRT delivered in 5 fractions, and overall demonstrated favorable local control and survival, but was associated with nontrivial rates of severe late gastrointestinal toxicity potentially attributable to radiation. Further prospective studies are needed to define the safety and efficacy of high-dose SBRT in patients with pancreatic cancer.
PURPOSE: Stereotactic body radiation therapy (SBRT) has demonstrated encouraging local tumor control rates in the treatment of pancreatic cancer, yet we lack prospective clinical trials evaluating dose-escalation strategies among patients treated with 5-fraction SBRT. This phase 1 dose-escalation trial was conducted to determine the maximum tolerated dose of SBRT in patients with pancreatic cancer. METHODS AND MATERIALS: Thirty patients with pancreatic cancer were enrolled and treated with 40, 45, or 50 Gy SBRT in 5 fractions with doses determined using a time-to-event continual reassessment method trial design. Systemic therapy was permitted before and after SBRT, but not mandated by the study protocol. Toxicity was the primary study endpoint, and any grade ≥3 acute or late toxicity potentially attributable to SBRT was considered a dose-limiting toxicity. Secondary endpoints included local progression, distant progression, and overall survival. RESULTS: The median follow up from SBRT was 8.9 months (range, 1.7-62.6 months). Nineteen patients (63%) had locally advanced disease, 3 patients (10%) had metastatic disease, and 8 patients (27%) had medically unresectable disease. Three patients (10%) received 40 Gy, 16 patients (53%) received 45 Gy, and 11 patients (37%) received 50 Gy. Seven patients (23%) experienced grade ≤2 acute toxicity, and 2 patients (6.7%) experienced grade 4 to 5 late toxicity, both of which occurred in the 45 Gy group. Median survival time was 17.1 months from the time of diagnosis and 9.8 months from SBRT. The 1-year cumulative incidence of local progression was 14.2% (95% confidence interval, 4.2%-30%). CONCLUSIONS: This dose-escalation trial evaluated high-dose SBRT delivered in 5 fractions, and overall demonstrated favorable local control and survival, but was associated with nontrivial rates of severe late gastrointestinal toxicity potentially attributable to radiation. Further prospective studies are needed to define the safety and efficacy of high-dose SBRT in patients with pancreatic cancer.
Authors: Michael D Chuong; Roberto Herrera; Adeel Kaiser; Muni Rubens; Tino Romaguera; Diane Alvarez; Rupesh Kotecha; Matthew D Hall; James McCulloch; Antonio Ucar; Fernando DeZarraga; Santiago Aparo; Sarah Joseph; Horacio Asbun; Ramon Jimenez; Govindarajan Narayanan; Alonso N Gutierrez; Kathryn E Mittauer Journal: Front Oncol Date: 2022-06-23 Impact factor: 5.738