Researchers from Cleveland Clinic, Case Western Reserve University School of Medicine, and Moffitt Cancer Center have found that the genomic adjusted radiation dose (GARD) may be used to personalize radiotherapy (RT) to maximize the therapeutic effect of a given physical RT dose, according to a news release from Moffitt.
The research, published in The Lancet Oncology, validates the association between GARD and radiation therapy outcome in a large cohort of patients, across seven different cancer types.
“As opposed to physical RT dose, which is the measure of what comes out of the machine and is delivered to the patient, GARD quantifies the biological effect on an individual patient of that delivered dose,” said Cleveland Clinic Radiation Oncologist and Case Western Reserve University School of Medicine Associate Professor Jacob G. Scott, MD, DPhil, the first author of the study.
The study represents the validation of a quantifiable parameter of the clinical effect of radiation; a parameter that serves as a predictor of the therapeutic benefit of RT for each individual patient.
Moffitt said the field of radiation oncology has been trailing behind in the translation of the new biology learned through genomics into treatment benefits and has not entered the precision medicine era, where patient-specific genomic data drives therapeutic decision-making. In an attempt to move the field forward, and away from a one-size-fits-all approach, the team of collaborators successfully devised and introduced the concept of GARD in a previous study.
GARD is derived from the gene-expression-based radiation-sensitivity index (RSI) and the physical dose given to a patient using the canonical linear quadratic model used to describe the biological response to radiation. Put simply, GARD is a reflection of the effect of a given physical dose on an individual patient.
Currently, measuring the dose of RT is done at the machine and up until now the field has assumed the clinical or biological effect of a given dose is uniform. This paper demonstrates that GARD is associated with clinical outcome while radiation dose is not.
The current study used previously published data on cancers of the breast, head and neck, endometrium, melanoma, glioma, pancreas, and lung (NSCLC) to test the association between GARD, RT dose and patient outcomes using two endpoints: time to first recurrence and overall survival. The study included 1,615 patients from 11 separate cohorts — from seven disease sites — in the analysis. To test whether the GARD-based RT dosing paradigm is associated with the outcomes, a pooled pan-cancer analysis was performed.
The test is now available from a CLIA laboratory at Moffitt Cancer Center and researchers hope to make it available more widely by engaging with a large-scale genomics company.