How would you treat recurrent unresectable sarcoma in previously irradiated maxillary region, with no distant metastatic disease?

This is a rare and challenging case (though I’ve actually seen this exact scenario a few times). I don’t think there’s a great answer, unfortunately. Re-irradiation with protons may be the best choice. Depending on the sarcoma histologic subtype, I would suggest clinical trial and/or NGS to determine potential systemic therapy options.

As often, the devil is in the details -- histology of current sarcoma, time from and the dose of prior RT, prior tx for this diagnosis, etc -- but in general I agree with @Dr. First Last. Any reasonable chance of long-term control for unresected sarcoma requires dose escalation (Kepka et al., PMID 16199316), which is obviously challenging in the re-irradiation setting. Thus, I would generally favor systemic therapy before re-RT. If my hand was forced into re-irradiation, protons are certainly an appropriate consideration if available. Unfortunately, unresectable sarcomas are a situation for which we just don't have a great solution currently.