Would you offer any degree of hypofractionation with concurrent chemotherapy for NSCLC?

I typically wouldn't, given limited data. CALGB 31102 (phase 1 trial) looked into this and found the maximal tolerated dose (MTD) to be at 60 Gy in 24 fractions (i.e., 2.5 Gy/fx). There's another phase 1 trial from Wisconsin which showed similar results (i.e., 2.5 Gy/fx). With these results in mind, I definitely wouldn't go above 2.5 Gy/fx (the CALGB study had 3 deaths in a cohort of 22 patients).

There is an ASTRO clinical practice guideline recommending "moderate hypofractionation" (specifically 3000 cGy/10 fx @ 300 cGy/fx and 4200 cGy/15 fx @ 280 cGy/fx) WITH concurrent chemotherapy in patients with stage III NSCLC deemed "unsuitable for curative intent therapy" (with many appropriate caveats about defining that population). So I would factor in your treatment intent and total dose delivered, not just the dose per fraction.

55 Gy in 20 fractions of 2.75 Gy can be considered with reasonable evidence suggesting efficacy and safety for most patients. SOCCAR (Maguire et al., PMID 25304298) randomized 130 patients with inoperable stage III NSCLC to 55 Gy in 20 fractions over 4 weeks with either sequential or concurrent cisplatin vinorelbine and reported 2-year OS 46% vs 50%, treatment-related mortality 1.7% vs 2.9%, and similar grade 3 esophagitis 8.5-8.8%. Two subsequent studies reported similar outcomes. Patibandla and colleagues, PMID 32665103 reported their experience of 163 patients and reported no 30- or 90-day treatment-related deaths, median survival of 31.2 months, and 1-/2-/3-year OS 75%/56%/45%. Iqbal and colleagues, PMID 30415784 also reported 2-year PF...

I do not routinely offer this as it is not currently SOC, and do all I can to do standard 30 fractions. However, I have done it a few times because of a few reasons, to name a few:

1. Patient refusal/inability to come for 30 fractions (usually tied to point 2)
2. Social issues that cannot be mitigated by generous help available at our center (very affordable sponsored housing, robust social services, gas cards)
3. Patient losing insurance

In these rare cases, I caution the patient about the possibility of higher toxicities, based on the data discussed above. There was a recent Phase I paper with protons (Contreras et al., PMID 35074432) with the conclusion “Hypofractionated proton beam radiation therapy and chemotherapy up to 60 Gy in 15 fractions i...