Bradford S Hoppe1, Romaine C Nichols2, Stella Flampouri3, Zuofeng Li2, Christopher G Morris2, Dat C Pham4, Pranshu Mohindra5, William Hartsell6, Nasiruddin Mohammed6, Brian H Chon7, Charles B Simone8. 1. Department of Radiation Oncology, Mayo Clinic, Jacksonville, Florida. Electronic address: Hoppe.Bradford@mayo.edu. 2. Department of Radiation Oncology, University of Florida College of Medicine, Jacksonville, Florida. 3. Department of Radiation Oncology, Emory Winship Cancer Institute, Atlanta, Georgia. 4. Department of Medical Oncology, University of Florida College of Medicine, Jacksonville, Florida. 5. Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland. 6. Department of Radiation Oncology, Northwestern Medicine, Chicago, Illinois. 7. ProCure Proton Therapy Center, New Jersey, Somerset, New Jersey. 8. New York Proton Center, New York, New York.
Abstract
PURPOSE: We report the safety data from the first multicenter phase 1 trial investigating the use of hypofractionated proton therapy with concurrent chemotherapy for patients with stage II or III non-small cell lung cancer. METHODS AND MATERIALS: From 2013 through 2018, patients with newly diagnosed stage II or III non-small cell lung cancer were enrolled in a multicenter phase 1 clinical trial evaluating concurrent chemotherapy with increasing dose-per-fraction proton therapy. This was a stepwise 5 + 2 dose-intensification protocol with the following dose arms: (1) 2.5 GyRBE per fraction to 60 GyRBE; (2) 3.0 GyRBE per fraction to 60 GyRBE; (3) 3.53 GyRBE per fraction to 60.01 GyRBE; and (4) 4.0 GyRBE per fraction to 60 GyRBE. A dose arm was considered tolerable if no radiation therapy-attributable severe adverse event (SAE) occurred within 90 days of treatment among 5 patients enrolled on the arm or if 1 SAE occurred among 7 patients enrolled. Dose constraints to the heart, brachial plexus, and spinal cord were more conservative at higher doses per fraction. RESULTS: The study closed early because of slow accrual and competing enrollment in NRG 1308 before accrual was met, with no maximum tolerated dose identified. Eighteen patients were treated, including 5 patients on arms 1 and 2, 7 patients on arm 3, and 1 patient on arm 4. Two SAEs occurred among 7 patients treated at 3.53 GyRBE per fraction; however, per outside expert review, both were attributed to chemotherapy and unrelated to radiation therapy. CONCLUSIONS: Hypofractionated proton therapy delivered at 2.5 to 3.53 GyRBE per fraction to a dose of 60 GyRBE with concurrent chemotherapy has an acceptable toxicity profile. Further exploration of this regimen is warranted on a phase 2 clinical trial.
PURPOSE: We report the safety data from the first multicenter phase 1 trial investigating the use of hypofractionated proton therapy with concurrent chemotherapy for patients with stage II or III non-small cell lung cancer. METHODS AND MATERIALS: From 2013 through 2018, patients with newly diagnosed stage II or III non-small cell lung cancer were enrolled in a multicenter phase 1 clinical trial evaluating concurrent chemotherapy with increasing dose-per-fraction proton therapy. This was a stepwise 5 + 2 dose-intensification protocol with the following dose arms: (1) 2.5 GyRBE per fraction to 60 GyRBE; (2) 3.0 GyRBE per fraction to 60 GyRBE; (3) 3.53 GyRBE per fraction to 60.01 GyRBE; and (4) 4.0 GyRBE per fraction to 60 GyRBE. A dose arm was considered tolerable if no radiation therapy-attributable severe adverse event (SAE) occurred within 90 days of treatment among 5 patients enrolled on the arm or if 1 SAE occurred among 7 patients enrolled. Dose constraints to the heart, brachial plexus, and spinal cord were more conservative at higher doses per fraction. RESULTS: The study closed early because of slow accrual and competing enrollment in NRG 1308 before accrual was met, with no maximum tolerated dose identified. Eighteen patients were treated, including 5 patients on arms 1 and 2, 7 patients on arm 3, and 1 patient on arm 4. Two SAEs occurred among 7 patients treated at 3.53 GyRBE per fraction; however, per outside expert review, both were attributed to chemotherapy and unrelated to radiation therapy. CONCLUSIONS: Hypofractionated proton therapy delivered at 2.5 to 3.53 GyRBE per fraction to a dose of 60 GyRBE with concurrent chemotherapy has an acceptable toxicity profile. Further exploration of this regimen is warranted on a phase 2 clinical trial.
Authors: Jennifer S Chiang; Nathan Y Yu; Thomas B Daniels; Wei Liu; Steven E Schild; Terence T Sio Journal: J Thorac Dis Date: 2021-02 Impact factor: 2.895
Authors: Florian Amstutz; Silvia Fabiano; Louise Marc; Damien Charles Weber; Antony John Lomax; Jan Unkelbach; Ye Zhang Journal: Med Phys Date: 2022-05-25 Impact factor: 4.506