[R01] Radiation therapy damage to airways and vessels: determining impact on ventilation, perfusion, and radiation-induced lung injury

Ente: National Cancer Institute

Scadenza: 2031-08-31

Importo max: $576,328

Paese: US

Descrizione

Title: Radiation therapy damage to airways and vessels: determining impact on ventilation, perfusion, and radiation-induced lung injury The primary goal of this proposal is to reduce pulmonary toxicity for patients receiving radiation therapy (RT) for treatment of non-small cell lung cancer (NSCLC). The NCI has prioritized supporting research studies designed to address adverse sequelae of cancer therapies that persist and become chronic co-morbidities or develop as delayed posttreatment effects (see PAR-25-145). This is a serious problem for lung cancer patients, and public health in the United States. The American Cancer Society estimates in 2025 the US will experience over 225,000 new cases of lung cancer, nearly half of whom will receive RT during their course of care, and approximately 30% of the surviving patients will experience Grade 2+ toxicity including fibrosis. The mechanisms of radiation induced lung injury (RILI) are poorly understood. Over the last five years our research team has found that RILI depends on the spatial locations and radiosensitivity of tissues receiving high radiation doses, and preliminary data that suggests substantial damage occurs even in low-dose areas due to (a) spatial variation of ventilation and perfusion, and (b) the consequences of irradiating supplying airways and vessels. We believe rigorous evaluation of medical images can illuminate the mechanisms of RILI and lead to modification of existing therapeutic approaches to minimize their prevalence. In this proposal we intend to do so by: (i) verifying both direct and indirect radiation damage to lung ventilation and perfusion, (ii) modeling the mechanisms of this damage by characterizing RILI in lung substructures (parenchyma, pulmonary airways, and vessels), and (iii) identifying radiation dose thresholds for these substructures to prevent and/or minimize RILI. We believe the specific aims outlined herein are essential for Functional Lung Avoidance Radiation Therapy to be successfully implemented as standard of care. The novel image acquisition methods and analysis techniques proposed will be needed for these findings to be reproducible in broad clinical application. Without rigorous image analysis methods, the nuanced lung architecture and functional dependencies cannot be understood nor incorporated impactfully in RILI minimization efforts. Istituzione: OREGON HEALTH & SCIENCE UNIVERSITY PI: John Bayouth, GARY E CHRISTENSEN, JOSEPH M REINHARDT Progetto: 1R01CA309192-01

Settori: National Cancer Institute

Vai al bando originale

Registrati gratis su Bandolo per trovare bandi compatibili con la tua azienda.