Main Session
Sep
27
PQA 01 - Gastrointestinal Cancer and Central Nervous System
2043 - Phase I Study of Radiation Dose Intensification with Accelerated Hypofractionated Intensity Modulated Radiation Therapy and Concurrent Carboplatin and Paclitaxel for Inoperable Esophageal Cancer
Presenter(s)
Alden D'Souza, MD, MPHS - Washington University in St. Louis School of Medicine, St Louis, MO
A. D'Souza1, C. G. Robinson1, P. Samson1, P. Grierson2, R. Jin2, M. R. Waters1, S. N. Badiyan3, and G. R. Vlacich1; 1WashU Medicine, Department of Radiation Oncology, St. Louis, MO, 2WashU Medicine, Division of Oncology, St. Louis, MO, 3University of Texas Southwestern Medical Center, Department of Radiation Oncology, Dallas, TX
Purpose/Objective(s):
Locoregional control with conventional chemoradiation for locally advanced (LA) esophageal cancer are suboptimal with complete response rates of 20-30%. We evaluate the safety of concurrent chemoradiation with hypofractionation and simultaneous integrated boost (SIB) dose escalation for patients with medically inoperable, locally advanced esophageal cancer.Materials/Methods:
A Phase I trial was designed to determine the maximum tolerated dose (MTD) of hypofractionated IMRT plus SIB with concurrent weekly carboplatin and paclitaxel (PC) for inoperable LA esophageal cancer. Time-to-event continual reassessment was used for patient arm allocation. Patients received 40.05 Gy in 15 fractions to planning target volume (PTV) 1, which included gross tumor with conventional expansions of primary and nodal disease. Dose escalation with SIB was applied to the gross tumor with margin (PTV2). Dose level (DL) 1 was set at 50.00 Gy, with escalation to 55.05 Gy (DL2) and 60.00 Gy (DL3). MTD was defined as the DL with a 20% probability of CTCAE V5.0 grade (G) 3+ cardiovascular, neurologic or pulmonary, G4+ gastrointestinal or skin, or any G5 toxicities within six months of treatment completion (Dose limiting toxicity - DLT). Clinical response (CR) was assessed by endoscopy 6-8 weeks post radiation and confirmed with PET.Results:
From 2020 to 2024, 12 patients were enrolled: DL1 – 6, DL2 – 3, and DL3 – 3 with a median follow-up of 12.6 months (IQR 6.6 – 26.4). Median age was 76.5 (range 62-85) and most were male (66%), stage III (83%), and adenocarcinoma histology (92%). All patients completed radiation treatment. The sole DLT was at DL1, a G3 upper gastrointestinal hemorrhage in the setting of anticoagulation. DL3 had 1 patient unable to tolerate their 3rd cycle of PC and 1 patient developed a G3 esophageal stricture after the DLT window. Complete CR was observed in 8 patients and seen in 67% at each DL. Median overall survival is 25.4 months with local and distant failure in 3 and 6 patients respectively.Conclusion:
In this elderly population, the MTD for hypofractionated SIB dose escalation to gross tumor with concurrent PC for inoperable LA esophageal cancer was 60 Gy in 15 fractions. Preliminarily, hypofractionated SIB showed improved locoregional control rates but treatment at this dose level may result in late (> 6 months) toxicity, limiting its use over lower dose levels. Future studies should confirm if a hypofractionated SIB regimen may be a viable alternative to conventional chemoradiation for inoperable disease.