Grab some popcorn.

Top Line: The next saga of photons versus protons awaits.

The Study: A post-hoc retrospective analysis of prospectively obtained cognitive data on patients enrolled in clinical protocols for medulloblastoma asked if there were differences between those who received craniospinal irradiation (CSI) with photons versus protons (either was fine per protocols). Now, this is a somewhat peculiar question as cognition should be influenced by radiation dose to the brain—the target in this instance, which was intended to receive equivalent biologic doses with either treatment modality. Included were 79 patients ≤18 years old enrolled on either SJMB03 or SJMB12 in Toronto (n=42, all received photon CSI) or Houston (n=37, all received proton CSI). At the end of the day, the photon group suffered significant declines in global IQ, working memory, and processing speed (in line with almost all previous photon and proton CSI data), while the proton group rather remarkably achieved stable scores over time in everything except processing speed. This led the authors to make the provocative conclusion that there is an “intellectual-sparring advantage” with proton CSI. Now, some have taken issue with such an inferential leap, primarily due to (1) the unplanned nature of the comparison between non-randomized patients treated in two different countries and (2) the complete lack of reported dosimetric differential between cohorts, much less a plausible biologic rationale. For example, variations in the posterior fossa boost volume and dose sequential to CSI could at least theoretically impact cognition. And, indeed, smaller margin and dose were significantly more common in the proton cohort, though the authors state “boost dose/margin did not account for significant variance in our models.” So, the most this can do is support adding IQ as another endpoint in a much needed randomized trial on the subject.

TBL: High-level prospective randomized data is needed before asking pediatric patients and their families to embrace proton therapy for medulloblastoma as the standard of care, especially if there are potential dosimetric pearls that can be replicated with more affordable and accessible photon therapy. | Kahalley J Clin Oncol 2019 & Milgrom J Clin Oncol 2020