Salvage therapies for first relapse of SHH medulloblastoma in early childhood.

Abstract

Background: Sonic hedgehog (SHH) medulloblastoma is the most common molecular group of infant and early childhood medulloblastoma (iMB) and has no standard of care at relapse. This work aimed to evaluate the post-relapse survival (PRS) and explore prognostic factors of patients with nodular desmoplastic (ND) and/or SHH iMB.

Methods: This international retrospective study included 147 subjects diagnosed with relapsed Nodular Desmoplastic/SHH iMB between 1995 and 2017, < 6 years old at original diagnosis, and treated without initial craniospinal irradiation (CSI). Univariable and multivariable Cox models with propensity score analyses were used to assess PRS for those in the curative intent cohort.

Results: The 3-year PRS was 61.6% (95% CI, 52.2 to 69.6). The median age at relapse was 3.4 years (IQR, 2.6-4.1). Those with local relapse (40.8%) more often received salvage surgery (p <0.001), low-dose CSI (≤ 24 Gy; p < 0.001), or focal radiotherapy (p = 0.008). Patients not receiving CSI (40.5%) more often received salvage marrow-ablative chemotherapy (HDC+AuHCR [p <0.001]). On multivariable analysis, CSI was associated with improved survival (Hazard Ratio [HR] 0.33 [95% CI, 0.13 to 0.86], p =0.04). Salvage HDC+AuHCR, while clinically important, did not reach statistical significance (HR 0.24 [95% CI, 0.0054 to 1.025], p =0.065).

Conclusions: Survival of patients with relapsed SHH iMB is not satisfactory and relies on treatments associated with toxicities including CSI and/or HDC+AuHCR. Upfront cure to avoid relapse is crucial. For patients with localized relapse undergoing resection, alternative salvage regimens that avoid high-dose CSI (> 24 Gy) can be considered.