T Jonathan Yang1,2,3, Neil A Wijetunga1, Josh Yamada1,2, Suzanne Wolden1, Michelle Mehallow1, Debra A Goldman4, Zhigang Zhang4, Robert J Young5, Mark G Kris6, Helena A Yu6, Andrew D Seidman7, Igor T Gavrilovic8,3, Andrew Lin8,3, Bianca Santomasso8, Christian Grommes8,3, Anna F Piotrowski8,3, Lauren Schaff8,3, Jacqueline B Stone8,3, Lisa M DeAngelis8,3, Adrienne Boire8,3,9, Elena Pentsova8,3. 1. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. 2. PROMISE (Precision Radiation for OligoMetastatIc and MetaStatic DiseasE) Program, Memorial Sloan Kettering Cancer Center, New York, New York. 3. Brain Tumor Center, Memorial Sloan Kettering Cancer Center, New York, New York. 4. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York. 5. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York. 6. Division of Solid Tumor Oncology, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York. 7. Division of Solid Tumor Oncology, Breast Medicine Service, Memorial Sloan Kettering Cancer Center, New York, New York. 8. Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York. 9. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
Abstract
BACKGROUND: Leptomeningeal metastases (LM) are associated with limited survival and treatment options. While involved-field radiotherapy is effective for local palliation, it lacks durability. We evaluated the toxicities of proton craniospinal irradiation (CSI), a treatment encompassing the entire central nervous system (CNS) compartment, for patients with LM from solid tumors. METHODS: We enrolled patients with LM to receive hypofractionated proton CSI in this phase I prospective trial. The primary endpoint was to describe treatment-related toxicity, with dose-limiting toxicity (DLT) defined as any radiation-related grade 3 non-hematologic toxicity or grade 4 hematologic toxicity according to the Common Terminology Criteria for Adverse Events that occurred during or within 4 weeks of completion of proton CSI. Secondary endpoints included CNS progression-free survival (PFS) and overall survival (OS). RESULTS: We enrolled 24 patients between June 2018 and April 2019. Their median follow-up was 11 months. Twenty patients were evaluable for protocol treatment-related toxicities and 21 for CNS PFS and OS. Two patients in the dose expansion cohort experienced DLTs consisted of grade 4 lymphopenia, grade 4 thrombocytopenia, and/or grade 3 fatigue. All DLTs resolved without medical intervention. The median CNS PFS was 7 months (95% CI: 5-13) and the median OS was 8 months (95% CI: 6 to not reached). Four patients (19%) were progression-free in the CNS for more than 12 months. CONCLUSION: Hypofractionated proton CSI using proton therapy is a safe treatment for patients with LM from solid tumors. We saw durable disease control in some patients.
BACKGROUND: Leptomeningeal metastases (LM) are associated with limited survival and treatment options. While involved-field radiotherapy is effective for local palliation, it lacks durability. We evaluated the toxicities of proton craniospinal irradiation (CSI), a treatment encompassing the entire central nervous system (CNS) compartment, for patients with LM from solid tumors. METHODS: We enrolled patients with LM to receive hypofractionated proton CSI in this phase I prospective trial. The primary endpoint was to describe treatment-related toxicity, with dose-limiting toxicity (DLT) defined as any radiation-related grade 3 non-hematologic toxicity or grade 4 hematologic toxicity according to the Common Terminology Criteria for Adverse Events that occurred during or within 4 weeks of completion of proton CSI. Secondary endpoints included CNS progression-free survival (PFS) and overall survival (OS). RESULTS: We enrolled 24 patients between June 2018 and April 2019. Their median follow-up was 11 months. Twenty patients were evaluable for protocol treatment-related toxicities and 21 for CNS PFS and OS. Two patients in the dose expansion cohort experienced DLTs consisted of grade 4 lymphopenia, grade 4 thrombocytopenia, and/or grade 3 fatigue. All DLTs resolved without medical intervention. The median CNS PFS was 7 months (95% CI: 5-13) and the median OS was 8 months (95% CI: 6 to not reached). Four patients (19%) were progression-free in the CNS for more than 12 months. CONCLUSION: Hypofractionated proton CSI using proton therapy is a safe treatment for patients with LM from solid tumors. We saw durable disease control in some patients.
Authors: Shuncong Wang; Yuanbo Feng; Lei Chen; Jie Yu; Chantal Van Ongeval; Guy Bormans; Yue Li; Yicheng Ni Journal: Am J Cancer Res Date: 2022-09-15 Impact factor: 5.942
Authors: Catherine A O'Connor; Jennifer S Park; Thomas Kaley; Brie Kezlarian; Marcia Edelweiss; T Jonathan Yang; Wungki Park; Diane Reidy; Anna M Varghese; Kenneth H Yu; Eileen M O'Reilly Journal: Pancreatology Date: 2021-02-06 Impact factor: 3.996
Authors: Maria Diaz; Priya Singh; Ivan S Kotchetkov; Anna Skakodub; Alicia Meng; Christel Tamer; Robert J Young; Anne S Reiner; Katherine S Panageas; Lakshmi V Ramanathan; Elena Pentsova Journal: J Neurooncol Date: 2022-02-03 Impact factor: 4.506