After more than a decade of work, genomic correlates of radiotoxicity have now been identified, and the research infrastructure is in place to identify more loci predictive of a patient’s risk of experiencing radiation-associated adverse effects. The long-sought goal of risk-stratification prognostic biomarkers for personalized radiotherapy planning, is finally within sight.

Radiotherapy, a key treatment modality for cancer, is administered to half of cancer patients around the world.1 However, its tumor-eradicating potential is frequently limited by toxicities associated with irradiation of patients’ healthy, normal tissues. Major advances in conformal and intensity-modulated radiotherapy have sought to reduce irradiation of nontarget tissue, but acute radiotoxicities and late radiation effects remain a significant treatment challenge. Acute toxicities can limit therapeutic dose delivery or curtail radiotherapy efforts, and with increasing numbers of long-term cancer survivors, the number of patients suffering from late effects is growing.1

Personalizing radiotherapy planning through risk stratification, by identifying which patients have increased intrinsic healthy-tissue radiosensitivity, and who are therefore more likely to suffer from radiotoxicities, has therefore long been seen as a Holy Grail of radiobiology.2

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Now, after more than a decade of research, that Holy Grail might finally be within sight, thanks to international research collaborations, says radiogenomics pioneer Barry S. Rosenstein, PhD, at the Department of Radiation Oncology at the Icahn School of Medicine at Mount Sinai, New York, New York.

“We have made a great deal of progress in the past couple of years, and I am now cautiously optimistic this work will translate into the clinic in the near future,” Rosenstein says. The field’s primary goal is to develop “a genomic assay in which the results of a simple and rapid blood test will predict with a high level of accuracy the likelihood that a particular cancer patient will develop complications from treatment with radiotherapy,” Rosenstein tells Oncology Nurse Advisor. Such a test will help cancer treatment teams and patients make optimal treatment decisions for each patient, Rosenstein believes.

Because radiotherapy tolerance doses are based on the most radiosensitive segment of the patient population, the ability to identify those patients before treatment, should allow development of separate, risk-stratified guidelines that would protect them while allowing dose-escalated radiotherapy regimens for other patients.1

“For people predicted to suffer complications from treatment with radiation, then possibly a strictly surgical option would be most appropriate, or the use of modified radiation dose parameters,” Rosenstein explains. “For prostate cancer patients, possibly active surveillance may represent the best option. Alternatively, for those patients predicted to be at low risk for developing injuries from radiation, possibly a more aggressive form of radiotherapy using a higher dose could be considered, which may improve the chance for a cure of their cancer.”

Better understanding the molecular pathways involved in health tissue radiotoxicities is another goal of radiogenomics.1 New insights into those pathways might facilitate the development of novel radioprotective agents and possibly even novel combination-modality therapies.