JROSG 99-1 (Aoyama): stereotactic radiosurgery with or without whole-brain radiotherapy

Whole-brain radiotherapy after stereotactic radiosurgery had been standard on the reasoning that micrometastases invisible on scans would otherwise grow. JROSG 99-1 randomised 132 patients with one to four brain metastases, each under 3 cm, at 11 Japanese hospitals between October 1999 and December 2003 to whole-brain radiotherapy with radiosurgery (65) or radiosurgery alone (67).

Median survival was 7.5 months with the combination against 8.0 months with radiosurgery alone, and one-year survival 38.5 against 28.4 percent (p=0.42): no survival difference. Twelve-month brain recurrence was 46.8 percent with whole-brain radiotherapy against 76.4 percent without, so salvage treatment was needed far more often when whole-brain radiotherapy was omitted.

The trial, with the later Alliance N0574 trial that measured cognition directly, moved practice to radiosurgery alone with close MRI surveillance for patients with a limited number of brain metastases, accepting more salvage in exchange for better cognitive function. For lung cancer specifically, the further change is that several targeted drugs, osimertinib, lorlatinib, alectinib and selpercatinib among them, control brain disease by themselves, so radiotherapy is increasingly deferred. QUARTZ separately showed that whole-brain radiotherapy adds nothing to steroids and supportive care in patients with non-small-cell lung cancer unsuitable for surgery or radiosurgery.