Ultra rad.

Top Line: How can we take ablative radiation for oligomets to the next level?

The Study: Ultra-high dose radiation, of course. By that we mean 24 Gy x 1, a dose delivery that seems to break any heretofore seen radbio mold. Apparently that’s not the case with a puny 9 Gy x 3, though, so the two regimens were boldly tested head to head in a phase 3 trial. All patients had PET or MRI staging showing 5 or fewer mets total, and all targets for the trial were non-mobile bone or nodal mets ≤6 cm that could safely receive either prescription with a 2-3 mm PTV margin (no CTV). Of note, patients receiving 24 Gy x 1 for bone mets also received dex 4 mg twice the day prior and a third time 3 hours prior to treatment; otherwise prophylactic dex was at physician discretion. Among the 117 patients with 154 mets randomized, the primary endpoint of local recurrence was nearly quadrupled with 9 Gy x 3. At two years it was 2.7% versus 9.1%, respectively, and at three years it was 5.8% versus 22%. Even more intriguing was the significant difference in rate of new distant mets, which at three years was 5.8% versus 22.5%. A landmark analysis demonstrated no association between adjuvant systemic therapies and these rates. Grade 3+ toxicity occurred in 7.8% after 24 Gy x 1 and 3.9% after 9 Gy x 3, a non-significant difference. Of note, while 11 various primary cancers were represented, 47% of enrollees had prostate cancer primaries, likely contributing to the overall goodness of outcomes.

TBL: Phase 3 data demonstrates a significant advantage in both local control and rate of new metastases when 24 Gy x 1 rather than 9 Gy x 3 is delivered to bone and nodal oligomets. | Zelefsky, Int J Radiat Oncol Biol Phy 2021