Brain teaser.

Top Line: Anything new on the optimal treatment for resected brain mets?
The Study: Last year brought us results of two big trials on the post-op management of brain metastases. One demonstrated radiosurgery (SRS) was big-time superior to observation in terms of local control, and another more confusing one demonstrated whole brain radiation (WBRT), compared to SRS, achieved superior local and distant brain control at the expensive of neurocognition with no impact on overall survival (OS). Now we have one with a new twist. It looks at adjuvant WBRT versus salvage SRS for any post-op residual or recurrent disease. The phase 3 JCOG 0504 trial enrolled 271 patients with no more than 4 brain mets, at least one of those >3 cm and resected. Of note, roughly 60% in each arm had gross total resection of a solitary brain met, meaning over half of those assigned to the salvage SRS arm received no adjuvant treatment. The primary endpoint was to assess whether salvage SRS resulted in noninferior OS, which it did: OS was exactly 15.6 months in each arm. As expected, rate of grade 2-4 cognitive dysfunction was doubled with WBRT (16%) versus salvage SRS (8%). Also in line with last year’s comparison, time to intracranial progression was 11 months with WBRT and only 4 months with SRS. The most interesting results of all were relegated to the appendix: Table A2 outlines patterns of intracranial failures, with SRS having almost double the number of local failures as WBRT: 54 versus 28, respectively. TBH the results of this trial fall short of practice-changing. First, for a two-armed randomized trial, the actual treatments received are confusing af (we’re talking ESPAC-1 level confusing). More importantly, almost all the decipherable results are in line with what we already know.
Bottom Line: SRS results in worse intracranial disease control but better neurocognitive outcomes than WBRT for resected brain mets with no impact on survival. And whatever form of radiation is given, it should probably be done adjuvantly. | Kayama, J Clin Oncol 2018

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