Strictly speaking.

We’re all familiar with the commonly referenced dosimetric lung constraints of lung volume receiving at least 20 Gy (V20) and mean lung dose (MLD) for estimating the risk of pneumonitis. But how does prior receipt of immune checkpoint inhibition (ICI) affect previously accepted thresholds? After all, we know ICI itself confers risk of pneumonitis, which is likely to recur with subsequent thoracic radiation. And things don’t look great for thoracic radiation concurrent with ipilimumab. Here is a Chinese retrospective dosimetric analysis of 40 patients receiving thoracic radiation for lung (n=32) or esophageal (n=8) cancer following prior receipt of PD-1 axis inhibition. The median equivalent dose in 2 Gy fractions (EQD2) was 60 Gy. First of all, the rate of grade 3+ pneumonitis (9/40, 22.5%) was higher than typically expected. Secondly, the continuous variables of V20 and MLD stood out as the only significant predictors of pneumonitis, with V20 as the stand-alone predictor of grade 2+ pneumonitis. Per resulting models, a V20 of only 9%+ or MLD of 5.6 Gy+ predicted a 50% risk of any pneumonitis, and a V20 ≥ 21% predicted a 50% risk of grade 2+ pneumonitis. In other words, in this small series, thresholds were clearly lowered, leading the authors to encourage in the setting of prior ICI “a more generous utilization of a variety of techniques that could reduce dose exposure to the normal lung, such as deep-inspiration breath hold technique, intensity-modulated or proton therapy, smaller target margins, and high-quality volumetric image guidance.” | Bi, Front Immunol 2022