Adult medulloblastoma: an overview on current and future strategies of treatment

ABSTRACT

Introduction: Medulloblastoma (MB) is the most common brain malignant tumor in children, conversely it is less frequent among adult population, accounting less 1% of adult intracranial tumors. Adult MB shows different characteristics and outcomes than pediatric MB.

Areas covered: This article compares epidemiology, pathology, radiologic features, prognosis, risk stratification, molecular genetics, current and future treatment strategies of adult and pediatric medulloblastoma (MB).

Expert opinion: The correct neuro-radiological diagnosis of adult MB remains a challenge, because of the lack of consensus about the choice of chemotherapeutic agents. Pediatric MB protocols have often limited application in adults, because of their less tolerance to chemotherapy. The added difficulty derives from the absence of a systematic description of the management and outcome of the relapses. Sonic Hedgehog Homolog (SHH) MB represents about 30% of all MB and is the first subgroup to be targeted by a molecularly focused therapy. Despite significant advances have been achieved in the development of SHH inhibitors, still the persistence of primary and acquired drug resistance represents an unresolved challenge. Prospective studies should be performed with international and multidisciplinary collaboration to guide future treatment choices.

KEYWORDS:

• Medulloblastoma
• SHH pathway
• adults
• children
• chemotherapy
• radiotherapy
• targeted therapy

Article highlights

• In adults, about 62% of tumors are SHH-activated; 30% are represented by group four tumors and 10% the WNT-activated tumors. Group 3 is rarely founded in adulthood.

• In adults, MB is almost located in the cerebellar hemispheres or infiltrate both hemispheres and median structures with a stronger contrast enhancement than pediatric cases; moreover, compared to children, adult MB often presents an inhomogeneous contrast enhancement.

• Due to its rarity, the experience of adult MB is less extensive. Clinicians have to take treatment decisions based on the results of retrospective case series, combined with the experience extrapolated from the pediatric literature.

• As a consequence of the potential late recurrences, a minimum of 5–10 years of follow-up is recommended for adult patients with MB.

• Based on the existing literature, adult patients with recurrent MB should be treated with a maximal safe re-resection, combined with chemotherapy and/or re-irradiation.

• The SHH pathway has become a major target in cancer therapeutics: in recent years, significant advances in the development of SHH inhibitors have been achieved. However, primary and acquired drug resistance are associated with SHH inhibitors. Further strategies to overcome drug resistance should be explored.

• Prospective adult studies are required, based on multidisciplinary and international collaboration.

This box summarizes the key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.