The clinical manifestations and molecular pathogenesis of radiation fibrosis
Mackenzie Fijardo,
Jennifer Yin Yee Kwan,
Pierre-Antoine Bissey,
Deborah E. Citrin,
Kenneth W. Yip,
Fei-Fei Liu
Affiliations
Mackenzie Fijardo
Research Institute, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada
Jennifer Yin Yee Kwan
Research Institute, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
Pierre-Antoine Bissey
Research Institute, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
Deborah E. Citrin
Radiation Oncology Branch, National Cancer Institute, Bethesda, MD, United States of America
Kenneth W. Yip
Research Institute, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada
Fei-Fei Liu
Research Institute, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Corresponding author. Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, 610 University Avenue, Toronto M5G 2M9, Canada.
Summary: Advances in radiation techniques have enabled the precise delivery of higher doses of radiotherapy to tumours, while sparing surrounding healthy tissues. Consequently, the incidence of radiation toxicities has declined, and will likely continue to improve as radiotherapy further evolves. Nonetheless, ionizing radiation elicits tissue-specific toxicities that gradually develop into radiation-induced fibrosis, a common long-term side-effect of radiotherapy. Radiation fibrosis is characterized by an aberrant wound repair process, which promotes the deposition of extensive scar tissue, clinically manifesting as a loss of elasticity, tissue thickening, and organ-specific functional consequences. In addition to improving the existing technologies and guidelines directing the administration of radiotherapy, understanding the pathogenesis underlying radiation fibrosis is essential for the success of cancer treatments. This review integrates the principles for radiotherapy dosimetry to minimize off-target effects, the tissue-specific clinical manifestations, the key cellular and molecular drivers of radiation fibrosis, and emerging therapeutic opportunities for both prevention and treatment.
