Proton FLASH Radiotherapy Ameliorates Radiation-induced Salivary Gland Dysfunction and Oral Mucositis and Increases Survival in a Mouse Model of Head and Neck Cancer.

Autor:	Chowdhury P; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Velalopoulou A; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Verginadis II; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Morcos G; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.; Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania., Loo PE; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.; Stanford University, Stanford, California., Kim MM; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Motlagh SAO; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Shoniyozov K; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Diffenderfer ES; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Ocampo EA; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.; University of California, Los Angeles, California., Putt M; Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Assenmacher CA; Penn Vet comparative Pathology Core, Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Radaelli E; Penn Vet comparative Pathology Core, Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Lu J; Department of Orthopedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Qin L; Department of Orthopedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Liu H; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Leli NM; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Girdhani S; IBA (Ion Beam Applications S.A.), Ottignies-Louvain-la-Neuve, Belgium., Denef N; IBA (Ion Beam Applications S.A.), Ottignies-Louvain-la-Neuve, Belgium., Vander Stappen F; IBA (Ion Beam Applications S.A.), Ottignies-Louvain-la-Neuve, Belgium., Cengel KA; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Busch TM; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Metz JM; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Dong L; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Lin A; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Koumenis C; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Jazyk:	angličtina
Zdroj:	Molecular cancer therapeutics [Mol Cancer Ther] 2024 Jun 04; Vol. 23 (6), pp. 877-889.
DOI:	10.1158/1535-7163.MCT-23-0663
Abstrakt:	Head and neck cancer radiotherapy often damages salivary glands and oral mucosa, severely negatively impacting patients' quality of life. The ability of FLASH proton radiotherapy (F-PRT) to decrease normal tissue toxicity while maintaining tumor control compared with standard proton radiotherapy (S-PRT) has been previously demonstrated for several tissues. However, its potential in ameliorating radiation-induced salivary gland dysfunction and oral mucositis and controlling orthotopic head and neck tumor growth has not been reported. The head and neck area of C57BL/6 mice was irradiated with a single dose of radiotherapy (ranging from 14-18 Gy) or a fractionated dose of 8 Gy × 3 of F-PRT (128 Gy/second) or S-PRT (0.95 Gy/second). Following irradiation, the mice were studied for radiation-induced xerostomia by measuring their salivary flow. Oral mucositis was analyzed by histopathologic examination. To determine the ability of F-PRT to control orthotopic head and neck tumors, tongue tumors were generated in the mice and then irradiated with either F-PRT or S-PRT. Mice treated with either a single dose or fractionated dose of F-PRT showed significantly improved survival than those irradiated with S-PRT. F-PRT-treated mice showed improvement in their salivary flow. S-PRT-irradiated mice demonstrated increased fibrosis in their tongue epithelium. F-PRT significantly increased the overall survival of the mice with orthotopic tumors compared with the S-PRT-treated mice. The demonstration that F-PRT decreases radiation-induced normal tissue toxicity without compromising tumor control, suggests that this modality could be useful for the clinical management of patients with head and neck cancer. (©2024 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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