Hypofractio-wait.

Toxicity can be high when using hypofractionated radiation for locally advanced non-small cell lung cancer (NSCLC)—see the hesitancy to hypofractionate RT for stage III NSCLC even during COVID. Here we have a phase I trial of hypofractionated proton therapy with concurrent chemo for stage II (28%) or III (72%, including 56% N2) NSCLC from the Proton Collaborative Group. The trial was essentially a biologically effective dose (BED)-escalation trial. The standard total dose was 60 Gy delivered in fewer and fewer fractions per arm. These included: 2.5 Gy x 24 → 3 Gy x 20 → 3.53 Gy x 17→ and 4 Gy x 15. The target was gross tumor and nodes on 4D-CT with an additional 6 mm ITV margin on the lung tumor (not nodes) and a 5-10 mm PTV margin. Passive-scatter, uniform-scanning, and pencil-beam techniques were used. A supplemental table compares dose constraints for each arm. The primary outcome was grade 3+ dose-limiting esophageal or pulmonary toxicity at 3 months. The trial was small (n=18), but there were no dose-limiting radiation toxicities. Importantly, accrual was slow/incomplete for the 4 Gy x 15 arm due to strict but important dose constraints that were difficult to meet. TBL: If strict normal tissue constraints can be met, hypofractionation (with protons..?) may not be off the table for advanced-stage NSCLC. | Hoppe, Int J Radiat Oncol Biol Phys 2020