Genomic-adjusted radiation dose to personalise radiotherapy

In The Lancet Oncology, Jacob Scott and colleagues 1 Scott JG Sedor G Ellswroth P et al. Pan-cancer prediction of radiotherapy benefit using genomic-adjusted radiation dose (GARD): a cohort-based pooled analysis. Lancet Oncol. 2021; (published Aug 4.)https://doi.org/10.1016/S1470-2045(21)00347-8 Summary Full Text Full Text PDF Scopus (17) Google Scholar describe an algorithm using the genomic-adjusted radiation dose (GARD) to personalise radiotherapy dose prescription on the basis of the biological effect of the dose rather than on physical dose alone. GARD is a preclinically and clinically validated combination of a gene expression assay, which assumes pan-tissue biological networks of radiosensitivity and radioresistance, with a linear quadratic model for estimation of total radiation dose in tissues. In previous work, the investigators identified a tumour molecular signature based on the expression of ten genes (AR, cJun [JUN], STAT1, PKC-β [PRKCB], RelA [RELA], cABL [ABL], SUMO1, PAK2, HDAC1, and IRF1) that correlated with radiosensitivity (expressed as tumour cell survival fraction per 2 Gy fraction) in a number of cancer cell lines, called the radiosensitivity index (RSI). 2 Eschrich S Zhang H Zhao H et al. Systems biology modeling of the radiation sensitivity network: a biomarker discovery platform. Int J Radiat Oncol Biol Phys. 2009; 75: 497-505 Summary Full Text Full Text PDF PubMed Scopus (157) Google Scholar , 3 Eschrich SA Pramana J Zhang H et al. A gene expression model of intrinsic tumor radiosensitivity: prediction of response and prognosis after chemoradiation. Int J Radiat Oncol Biol Phys. 2009; 75: 489-496 Summary Full Text Full Text PDF PubMed Scopus (191) Google Scholar , 4 Scott JG Berglund A Schell MJ et al. A genome-based model for adjusting radiotherapy dose (GARD): a retrospective, cohort-based study. Lancet Oncol. 2017; 18: 202-211 Summary Full Text Full Text PDF PubMed Scopus (219) Google Scholar Later, RSI was validated on various tumour types that led to the GARD algorithm. 4 Scott JG Berglund A Schell MJ et al. A genome-based model for adjusting radiotherapy dose (GARD): a retrospective, cohort-based study. Lancet Oncol. 2017; 18: 202-211 Summary Full Text Full Text PDF PubMed Scopus (219) Google Scholar In the current publication, 1 Scott JG Sedor G Ellswroth P et al. Pan-cancer prediction of radiotherapy benefit using genomic-adjusted radiation dose (GARD): a cohort-based pooled analysis. Lancet Oncol. 2021; (published Aug 4.)https://doi.org/10.1016/S1470-2045(21)00347-8 Summary Full Text Full Text PDF Scopus (17) Google Scholar Scott and colleagues validated GARD in 1615 patients with seven cancer types from 11 study cohorts. They found that GARD was associated with time to first recurrence and overall survival for patients receiving radiotherapy and that, by contrast with physical dose, it predicted radiotherapy benefit. Consequently, GARD is a model that can potentially serve as a tool to individualise prescribed radiation doses in clinical practice. The efforts of Scott and colleagues need to be applauded worldwide, because radiotherapy is considerably lagging compared with the enormous progress done in the field of personalised medicine that currently mainly applies to decisions on the use of systemic therapy or targeted agents. Pan-cancer prediction of radiotherapy benefit using genomic-adjusted radiation dose (GARD): a cohort-based pooled analysisThe biological effect of radiotherapy, as quantified by GARD, is significantly associated with time to first recurrence and overall survival for patients with cancer treated with radiation. It is predictive of radiotherapy benefit, and physical dose of radiation is not. We propose integration of genomics into radiation dosing decisions, using a GARD-based framework, as the new paradigm for personalising radiotherapy prescription dose. Full-Text PDF