Researchers from the Cleveland Clinic, from the Case Western Reserve University School of Medicine and the Moffitt Cancer Center revealed that the dose of adjusted genomic radiation (GARD) can be used for one personalized radiotherapy (RT) to maximize the therapeutic effect of a given physical dose of RT.
There Research was published in the scientific journalThe Lancet Oncology.
Personalized radiotherapy: here are the benefits for cancer patients
“Unlike the physical dose RT, which is the measure of what comes out of the machine and is delivered to the patient, GARD quantifies the biological effect of that delivered dose on a single patient “, said the radiotherapist oncologist of the Cleveland Clinic and Case Western Reserve Associate Professor of the University School of Medicine Jacob G. Scott, the first author of the study. “What we found by looking at more than 1,600 patients is that the physical dose of radiation is not associated with outcome (time to first recurrence and overall survival), but the GARD or personalized radiotherapy, Yup”.
The study represents the validation of a quantifiable parameter of the clinical effect of radiation: a parameter that serves as predictor of the therapeutic benefit of RT for each individual patient. According to the radiotherapist oncologist from the Moffitt Cancer Center Javier Torres-Roca, this new study changes the field of radiotherapy.
“Historically, the RT field has accepted that radiotherapy, a physical treatment, causes a biological or clinical effect in patients regarding tumor response, toxicity, carcinogenesis, etc.”, Torres-Roca said. “However, until now, radiation therapists have always assumed that the biological effect was uniform among patients. GARD provides the first validated approach to quantify the biological effect of RT for each individual patient and tells you more about the clinical outcome and the benefit of RT over physical dose. “
Both scientists argue that the new paradigm for radiotherapy should incorporate GARD for all patients as it provides critical information on its therapeutic benefits. The field of radiation oncology lagged behind in translating the new biology learned through genomics in therapeutic benefits and has not entered the era of precision medicine, where patient-specific genomic data guide the therapeutic decision-making process. In an attempt to move the field forward, and away from a universal approach, the group of experts has successfully developed and introduced the concept of personalized radiotherapy better known as GARD.
GARD is derived from the gene expression-based radiation sensitivity index (RSI) and physical dose administered 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, the measurement of the dose of RT is performed at the machine and until now the field has assumed the uniformity of the clinical or biological effect of a given dose. This paper demonstrates that GARD is associated with clinical outcome while radiation dose is not.
“Modification of radiation doses near the range of the current standard of care is not associated with the result, but the effect of the dose is”, he said Torres-Roca. “GARD predicts the benefit of radiotherapy and quantifies the relative potential benefit of radiotherapy ”.
In explaining the usefulness of GARD, Scott noted that it quantifies the biological effect of radiation in a numerical parameter involving the physical dose of RT, giving oncologists an objective way to understand the relative therapeutic benefit of their prescribed RT and allowing them to modify the physical dose of RT in order to optimize the benefit of radiotherapy for each individual patient. GARD provides the first validated decision support tool where radiation therapists can use genomic information to modulate the potential benefit of radiation therapy for each patient.
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 results using two endpoint: time to first relapse and overall survival. The study included 1,615 patients from 11 separate cohorts from seven disease sites in the analysis. To verify whether the GARD-based RT assay paradigm is associated with the results, a pooled pan-cancer analysis was performed.
“The important part is that GARD is not a standalone biomarker; rather, it is a dynamic parameter that changes according to the prescribed RT dose, which allows the physician to modulate it directly“Said Scott. The higher the GARD value, the greater the anticipated therapeutic benefit of radiotherapy at that specific dose, but, he adds, these increases may not apply to the risk of an increase in dose for some radiation plans.
“The point is that some patients have large increases in GARD with a higher dose, and some patients don’t respond as well near the standard of care range. The discussion with the doctor, as well as the oncologist’s understanding of the risk-benefit balance between the benefits of dose escalation versus increased toxicity remains fundamental ”.
Torres-Roca believes that this analysis provides sufficient evidence to justify the initial clinical adoption of the GARD-based RT dose paradigm.
“This does not require a departure from the current standard of care“, He stressed. “Our view is that RSI / GARD is a decision support tool that provides insight into the effect of RT dose for each individual patient providing critical information for treating radiotherapists ”.