Radiation-induced brain damage, impact of Michael Robbins’ work and the need for predictive biomarkers

Abstract

Purpose: To review the literature on radiation-induced normal tissue injury in the context of treatment of primary and metastatic brain tumors with a focus on Michael Robbins’ work on mechanisms of injury and approaches to mitigation, and also to identify other potential opportunities to improve treatment outcome and quality of life (QOL).

Background: Brain tumors remain a significant challenge for patients, their families, the physicians treating them, and researchers seeking more effective treatments. Current treatment of brain tumors involves combinations of radiotherapy with surgery, chemotherapy, and molecularly targeted agents. As patient survival improves with advances in treatment there is an increasing concern for the cognitive deficits that may become apparent months or years after treatment some of which are related to radiation-induced brain damage. One area of Michael Robbins’ research was unraveling the mechanisms of radiation-induced cognitive deficits, which formed the basis for the development of some mitigators of radiation injury. Extrapolating from this, new opportunities to identify and develop putative predictive biomarkers of radiation-induced brain damage can be explored.

Conclusions: Predictive biomarkers of radiation-induced brain injury may enable stratifying patients for customization of treatment and thus aid in improving the QOL and possibly prolonging survival. Here we discuss the challenges involved in leveraging recent advances in radiation-specific biomarker research and translating them to radiotherapy, which for the foreseeable future is likely to remain a cornerstone of the treatment of brain tumors.

Keywords::

• Radiotherapy
• radiation-induced brain damage
• mechanisms
• radiation mitigator
• predictive biomarkers

Acknowledgements

The authors appreciate insightful discussions with late Dr Michael Robbins, Wake Forest University and Dr Eric Bernhard, National Cancer Institute. National Cancer Institute's Radiation Research Program supported the manuscript preparation. The work is the opinion of the authors and not of the National Cancer Institute or Department of Health and Human Services.

Declaration of interest

M.P. Mehta reports consulting with Abbvie, Bristol-Meyers-Squibb, Celldex, Elekta, Novelos, Novocure, Phillips, Roche; stock options in Accuray, Pharmacyclics, and Stemina; serves on the Board of Directors of Pharmacyclics. The other authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.