The field of radiation cancer treatment needs to be brought into the precision medicine era, with patient-specific genomic data driving therapeutic decision-making rather than a one-size-fits-all approach, according to an expert from Cleveland Clinic, and his team of collaborators.
Jacob G. Scott, MD, DPhil – a Cleveland Clinic radiation oncologist and associate professor at Case Western Reserve University School of Medicine – explained that radiation oncology is lagging behind the field of medical oncology in leveraging recent advances in cancer genomics. He noted that radiation therapy is still largely prescribed by taking into account only the location of the cancer diagnosis or tumour to decide on standard dosing, assuming the biological effect will be the same across all patients, tumours and cancer types.
In an attempt to move the field forward, Dr. Scott and his collaborators from Case Western Reserve University School of Medicine and Moffitt Cancer Center in the U.S. have been working to demonstrate the benefits of a genomic-adjusted radiation dose (GARD) model for several years. They successfully devised and introduced the concept of adjusting the radiotherapy dose based on biological differences between or within tumours and published their proposed GARD paradigm in The Lancet Oncology journal in 2017.
Subsequently, in August 2021, they published a study in The Lancet Oncology journal confirming the effectiveness of using GARD to maximize the therapeutic effect of a given physical radiotherapy dose. Dr. Scott, a member of the cancer research team at Cleveland Clinic, was first author on the study that validated the asso-
ciation between GARD and radiotherapy outcome in a large cohort of patients, across seven different cancer types.
This study used previously published data on cancers of the breast, head and neck, endometrium, melanoma, glioma, pancreas and lung to test the association between GARD, radiotherapy dose and patient outcomes using two endpoints: time to first recurrence and overall survival. Contrary to past assumptions, the study showed that the effect of radiation therapy on tumour response, toxicity, carcinogenesis and similar factors is not uniform across patients.
“As opposed to physical radiotherapy dose, which is the measure of what is delivered to the patient, GARD quantifies the biological effect on an individual patient of that delivered dose,” explained Dr. Scott. “What we found by looking at 1,600-plus patients is that the physical dose of radiation is not associated with outcome, but GARD is. It offers us a quantifiable parameter of the clinical effect of radiation.”
He added that the numerical parameter offered by GARD gives oncologists an objective way to understand the relative therapeutic benefit of prescribed radiotherapy, and allows them to modify the physical dose of radiation therapy in order to optimize its benefit for each individual patient.
“The important part is that GARD is not a standalone biomarker; rather, it is a dynamic parameter that changes based on the prescribed radiotherapy dose, which allows the clinician to directly modulate it,” said Dr. Scott. The higher the GARD value, the higher the predicted therapeutic benefit of radiotherapy at that specific dose will be, however, these increases may not always be worth the risk of dose escalation. “The point is that some patients have large increases in GARD with more dose, and some patients do not respond as well near the range of standard of care. The discussion with the clinician, as well as the treating oncologist’s understanding of the risk-benefit balance of dose-escalation’s benefits vs. increased toxicity, remain paramount.”
Leaving behind a decades-old way of pre-scribing radiotherapy to cancer patients will take time, Dr. Scott said, but he is optimistic that the field will soon embrace GARD as a valuable tool for personalizing radiotherapy.