How do you approach medically inoperable pleural mesothelioma confined to a single hemithorax and symptomatic for chest wall pain, not responsive to first-line systemic therapy?

In these settings, our convention has been to use 20 Gy in 5 fractions. This is based on studies that have shown palliative benefit in mesothelioma with doses at or exceeding 4 Gy per fraction, and also following the phase 2 SYSTEMS trial (MacLeod JTO 2015) using the 20 Gy in 5 fraction regimen. In that study, 35% of patients had improvement in pain at 5 weeks, with 12.5% of patients having complete resolution of pain. Whether a higher dose could provide additional palliative benefit with 36 Gy ...

I would consider dose escalation if possible, extrapolating from post op data. 45/15 or 50/25 with SIB to 60 as per this recent RCT, if the patient has a good PS.

Trovo et al., PMID 33259933

In addition to radiation option, immunotherapy can be tried as well.