How do we approach the management of medulloblastoma in young children?

Abstract

Therapeutic strategies avoiding craniospinal irradiation were developed for young children with medulloblastoma to improve survival while protecting the neurocognitive outcomes of these vulnerable patients. These strategies most commonly rely on highdose chemotherapy with stem cell rescue or conventional chemotherapy combined with intraventricular chemotherapy or conventional chemotherapy with adjuvant focal irradiation. Over the past decade, our growing understanding of the molecular landscape of medulloblastoma has transformed how we risk stratify and allocate treatment in this young age group. We present the results of the most recent approaches and clinical trials for medulloblastoma of early childhood, according to the different molecular subgroups. Overall, young children with sonic hedgehog medulloblastoma treated with intensive adjuvant chemotherapy achieve excellent survival and can safely be spared from radiotherapy. For patients with group 3 and 4 medulloblastomas, the interplay between molecular alterations and treatment intensity still needs to be further delineated. While recent clinical trials point toward more encouraging survival figure for a sizeable number of them, patients identified with very high-risk feature desperately needs innovative therapies.

Posterior Fossa Tumors in Infants: 13-year single center retrospective review.

“…Aiming to delay radiotherapy due to unacceptable consequences as developmental deficits and endocrinologic disturbances, most recent trials explored strategies as high-dose chemotherapy with ABMT, intraventricular chemotherapy and focal radiation (13). For MB, these more intensive approaches have resulted in better survival, and the molecular understanding is refining the prognostic characteristics for each subgroup (13,14), however, for CNS embryonal tumors other than MB the outcome remains unsatisfactory (13) The prognostic implications of molecular sub-groups ATRT-TYR, -SHH and -MYC are still under evaluation (12). For the ependymomas, despite the small number of patients in our cohort, due to the image characteristics and unfavorable outcome, associated with histone loss in immunohistochemistry, it suggests that they belong to subgroup A, which generally demonstrates worse survival with surgery and focal radiotherapy as standard of care (12).…”

Evolution of Systemic Therapy in Medulloblastoma Including Irradiation-Sparing Approaches

“…Due to the devastating consequences of craniospinal irradiation in infants and young children, there is a general consensus to use a radiation-sparing approach in this age group. Postoperative treatment is therefore based on intensive/high-dose chemotherapy associated in some protocols with intraventricular injections of chemotherapy via an Ommaya reservoir [12]. In older children, postoperative treatment consists of a combination of craniospinal irradiation and chemotherapy.…”

“…With a follow-up of 4.8 years, the median IQ of these survivors was 62 (range 44-86), with an average annual decline of IQ of −3.9. However, while the benefit of this radiation sparing approach in terms of neurocognitive outcome has been demonstrated, the results of treatments in young children with medulloblastoma treated with postoperative chemotherapy only are inferior to those reported in older children treated with surgery, craniospinal irradiation, and chemotherapy [12]. Evidence that young children can be successfully treated with surgery followed by chemotherapy without radiotherapy stems from the so-called Baby POG1 protocol [13].…”