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Top Line: What is the optimal prescription dose for lung cancer?

The Study: Has any other radiation trial led to more hand-wringing than RTOG 0617? You could spend days hypothesizing why 74 Gy resulted in worse survival than 60 Gy, but the main hypothesis is that any tumor control benefit from dose escalation was outweighed by detrimental normal tissue effects. Here’s an interesting study that takes a deep dive into explaining that hypothesis. It presents a model that incorporates a cancer cell line-derived radiosensitivity index (RSI) and the efficacy of a certain dose for a given RSI (aka the genomically adjusted radiation dose, GARD) to calculate the optimal personalized prescription dose in a cohort of >1700 patients. The model was able to simulate the results of 0617 by showing that only a minority of patients benefit from dose escalation from 60 → 74 Gy while a larger proportion either a) experience more toxicity with no additional tumor control benefit or b) still don’t receive an adequate dose. For instance, the model predicts that ~40% of patients receive optimal tumor control with a 60 Gy prescription. Dose escalation to 74 Gy benefits another 20%, but it also exposes the original 40% to excess toxicity while still not achieving a high enough dose for the remaining 40%. Why else would we need biologically effective doses in excess of 100 Gy to achieve 90+% local control with lung SBRT?

TBL: Modest dose escalation applied to a uniform population of NSCLC patients is unlikely to show benefit because the majority of patients likely receive a non-optimal radiation dose. | Scott, J Thorac Oncol 2020

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