While conventional dose-escalation for locally-advanced non-small cell lung cancer (NSCLC) has been disappointing to say the least, perhaps all it was missing was modern planning techniques. In this early-stage trial 28 patients with inoperable stage II-III NSCLC received 40 Gy in 4 fractions to to PET-avid gross disease on 4-D sim with a planning target volume of ≤5 mm. After 8-9 fractions re-staging PET was performed to plan a sequential ablative boost of 25 (n=10), 30 (n=9) or 35 (n=9) Gy in 5 fractions to ongoing PET-avid disease. This was all done with concurrent weekly carboplatin/paclitaxel, and only one patient received maintenance immune checkpoint inhibition. Local control rates at 2 years were 74% after 65 Gy total, 86% after 70 Gy, and 100% after 75 Gy, suggesting incremental tumor control benefit with increasing doses. However, two of nine patients experienced grade 5 toxicities in the 75 Gy cohort including acute pneumonitis and late hypoxic respiratory failure. The authors conclude, recognizing clearly limited numbers, “patients treated with 70 Gy in 15 fractions exhibited the most promising therapeutic ratio.” | Wu, JAMA Oncol 2024
