Organ at Risk Dose Constraints in Stereotactic Ablative Radiotherapy: A Systematic Review of Active Clinical Trials

Abstract

Organ at risk (OAR) dose constraints are a critical aspect of stereotactic ablative radiotherapy (SABR) treatment planning. As clinicians must balance tumor control and potential toxicities, knowledge and application of optimal dose constraints are essential to the safe and effective delivery of SABR. While standardized dose constraints have been studied and reported upon for conventionally fractionated radiotherapy, SABR dose constraints have not been as extensively studied, with limited evidence supporting preferred dose constraints for most OARs. Our objective was to report on OAR dose constraints used in ongoing clinical trials involving SABR for oligometastatic disease to help inform institutional practices.Clinicaltrials.gov was searched from inception to February 2020 to capture actively accruing clinical trials using SABR in oligometastatic disease. Full protocols (or at minimum, a list of dose constraints utilized) were obtained by contacting principal investigators or from publicly available sources. OAR constraints were abstracted by two authors and synthesized to report in a standardized manner. Variability of OAR constraints was assessed by comparing the width of the interquartile range and the difference between the maximum and minimum dose to a volume.Fifty-three of 85 eligible clinical trials contributed OAR constraints used in analysis. Dose constraints for 1-8 fractions of SABR were collected for 33 OARs. Variability was found in the absolute allowable OAR doses, use of planning OAR volumes (PRV), and whether constraints were optional vs. mandatory. For many OARs, the most common dose constraints (i.e., the mode) often matched a pre-existing publication, but no single pre-existing publication matched the modes of all OAR dose constraints. Organs with the most variability were the rectum, penile bulb, and chest wall and ribs. The esophagus, stomach, duodenum, and small bowel also possessed high variability for at least one constraint. OARs previously evaluated by HyTEC (High Dose per Fraction, Hypofractionated Treatment Effects in the Clinic), such as spinal cord and optic pathway, appeared to have less variability among study protocols.We found substantial variability in many OAR dose constraints used in ongoing clinical trials evaluating SABR in oligometastatic disease. Future research and recommendations for standardized OAR dose constraints, as well as consistency in implementing PRV margins, should be a priority for the field of radiation oncology.