Preventing or Reducing Late Cardiopulmonary Side Effects of Radiation Therapy: Radiation Meets Molecular Pathology

*Soren M. Bentzen, University of Wisconsin School of Medicine and Public Health 

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Recent advances in molecular pathology have dramatically improved our understanding of the radiation pathology of late effects of radiation therapy. Where classical radiobiology focused on cell killing of putative target cells, the current paradigm is centered on the processing of radiation damage as an orchestrated response to a trauma, in many aspects assembling a wound healing response, but with characteristic features that derives from the specific features of damage from ionizing radiation. Ideally, these novel insights should lead to new strategies for preventing or reducing side effects. However, although some progress has been made in this field, there are still no widely accepted molecular targeted agents with this indication. Risk stratification based on individual genomic signatures has attracted much attention, but also in this case the early enthusiasm has been tempered by a lack of validation in independent studies. This leaves the spatio-temporal modulation of radiation dose as the most effective current strategy for reducing radiation toxicity to the lung and heart. In the lecture, I will try to provide a broad overview of where we are in terms of understanding, preventing or ameliorating cardiopulmonary side effects of radiation therapy. Recent progress will be reviewed and research priorities will be proposed.