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Top Line: Leptomeningeal disease (LMD) is a particularly devastating diagnosis, not only because of the neurologic deficits at stake but also due to the difficulty of safely and adequately treating it in its entirety with current drugs or conventional radiation.
The Study: What if craniospinal irradiation (CSI) could be delivered more safely? Now that's a holy grail opportunity for proton investors everywhere. Because there’s actually a really good potential clinical benefit to harnessing the stoppage power of the oft-hyped Bragg peak anterior to the entire length of the CNS. Here’s a promising single-arm phase 1 trial of 20 evaluable patients with LMD from solid tumors who all received proton CSI to 30Gy/10. All patients had to have plans for further systemic therapy (a great surrogate for adequate performance status, by the way) and sufficient blood counts. All systemic therapy outside endocrine and HER2 therapy was held one week before and during treatment. The primary endpoint was ”dose-limiting" events defined as grade 3+ non-heme or grade 4+ heme toxicity within 4 weeks of CSI. That was seen in only 2 of 20 patients, who experienced some combo of grade 4 lymphopenia, grade 4 thrombocytopenia, and grade 3 fatigue, all of which resolved without intervention. More exciting is that two-thirds of patients remained without CNS progression at 6 months and one-fifth at a whopping 12 months. Median time alive without CNS progression was 7 months and median overall survival 8 months. While the latter is not a duration typically to be celebrated, it’s notably more than double that achieved in a phase 2 trial reported this month evaluating pembro monotherapy for LMD in an almost identical cohort of 20 patients.
TBL: Proton CSI delivered in just 10 fractions appears a safe and quite promising palliative treatment for LMD. | Yang, Neuro Oncol 2020 & Brastianos, Nat Med 2020