How does neoadjuvant chemo-immunotherapy impact your decision on hypofractionation/dose fractionation for locally advanced NSCLC, now getting RT alone?

If a patient has already received 3-4 months of a platinum-doublet chemotherapy during the chemo-immunotherapy phase, then it's always my preference to omit further chemotherapy and recommend RT alone. The rationale for this recommendation is that we don't administer additional chemotherapy to patients undergoing surgery; therefore, why administer additional chemotherapy to patients undergoing RT? Particularly as the benefit of chemotherapy is marginal, at best, after 3-4 cycles, yet it is destined to increase the risk of pneumonitis, esophagitis, and bone marrow suppression. RT alone is also generally safer and improves the safety of consolidation durvalumab so that these patients receive a complete PACIFIC regimen after having surgery abo...

I still try for 60 Gy in 15 fractions if radiation alone, though I will dose adjust based on my OARs and at times underdose the PTV to maybe 52.5 Gy and try for 60 Gy to the ITV.

After a full course of neoadjuvant chemo‑immunotherapy, I would be cautious about increasing BED when treating locally advanced NSCLC with RT alone. Several observations from prior trials favor this approach.

In RTOG 0617, dose intensification did not improve outcomes and was associated with worse survival, even though the heart doses between the 60 Gy and 74 Gy arms were not statistically different. The survival decrement was more pronounced in patients without pre‑existing cardiac disease, suggesting that factors beyond baseline cardiac comorbidity may influence treatment‑related cardiac vulnerability. For this reason, in patients with dose escalation primarily to the tumor despite observing dose constraints to the OARs, I would still be ...

I like the opportunity to give patients a break from systemic therapy, as I've never been convinced that temporary interruptions make all that much of a difference. Thus, I am a fan of RT alone and prefer to deliver it at 4 Gy/day. The key, though, is to never exceed the esophagus dose limits. Other than that, I also push my dosimetrists to make the 50% IDL as compact as possible and keep an eye on the V10 to minimize that as much as possible as well. #ALARA

I would base this decision on the extent of central disease and PTV overlap of the esophagus, favoring conventional fractionation in these cases (I would try for at least 66 Gy in 33 treatments with RT alone). The bulk of residual disease and history of pneumonitis would also be a factor, as you are treating post-IO lung. If you are comfortably meeting lung constraints on a small peripheral tumor, 60/15 seems very reasonable, but there are many other scenarios that I would be cautious about. I don't think dose reduction based on response makes sense (other than perhaps treating small mediastinal nodes to 60 and the primary tumor to 66-70 without chemo), but smaller CTVs might. If you are choosing between dose reducing a 15 fraction regimen ...