What is the primary treatment approach for an adult patient diagnosed with medulloblastoma?

Adult Medulloblastoma Treatment

The primary treatment approach for adult medulloblastoma is maximal safe surgical resection followed by risk-stratified craniospinal irradiation (CSI) with concurrent and adjuvant chemotherapy, with treatment intensity determined by molecular subtype, extent of resection, and metastatic status. 1

Immediate Referral to Specialized Centers

• Adults with medulloblastoma must be referred to specialized centers or "centers of excellence" at diagnosis or recurrence, as treatment at academic high-volume centers is associated with longer survival rates, reduced 30-day readmission (22% decrease), and lower 90-day mortality (16% decrease). 2
• These centers should provide multidisciplinary expertise including neurosurgery, neuropathology, radiation oncology, neuro-oncology, advanced molecular testing capabilities, regular tumor boards, access to proton therapy, and clinical trial programs. 2
• For patients in remote areas, utilize telehealth consultations and web-based tumor boards to facilitate expert guidance while receiving local care. 2

Surgical Management

• Pursue maximal safe surgical resection aiming for gross total resection (GTR) while minimizing neurologic deficits, as extent of resection correlates with survival. 1, 3
• Surgery goals include maximal cytoreduction, relief of hydrocephalus, reduction of mass effect, and obtaining adequate tissue for both histologic and molecular classification. 1
• Obtain sufficient tissue at initial surgery for DNA methylation testing and molecular characterization, which is critical for risk stratification and treatment planning. 2, 1

Molecular Testing and Risk Stratification

• Routinely conduct DNA methylation testing for diagnosis and molecular subgrouping in all adult patients, as this is superior to immunohistochemistry for accurate classification. 2, 1
• Molecular subgroups have distinct prognoses: WNT-activated (>90% long-term survival), SHH-activated TP53-wild-type (intermediate prognosis), SHH-activated TP53-mutant (very poor prognosis), Group 3 (20-30% 5-year survival), and Group 4 (75-90% 5-year survival). 1
• Nuclear β-catenin expression in adults does not confer the same favorable prognosis as in children, highlighting the importance of DNA methylation over immunohistochemistry. 2

Timing of Treatment Initiation

• Initiate craniospinal irradiation within 30-42 days of tumor resection, as delays beyond this timeframe are associated with worse outcomes in pediatric studies, and similar principles likely apply to adults. 2
• Expedite referrals between local and specialized centers for surgical intervention, molecular testing, and CSI planning to minimize treatment delays. 2
• Utilize telehealth resources to facilitate rapid multidisciplinary treatment planning across centers. 2

Radiation Therapy

• Average-risk patients (no metastases, residual tumor <1.5 cm²) should receive 23.4 Gy CSI with involved field boost to 54 Gy, plus concurrent weekly vincristine during radiotherapy. 1
• High-risk patients (metastatic disease or large residual tumor) should receive 36 Gy CSI with involved field boost to 54-55.8 Gy. 1
• Very high-risk patients with MYC amplification should receive 36 Gy CSI with boost to 54-55.8 Gy, plus carboplatin prior to each radiation fraction as a radiosensitizer, which improved event-free survival by 19% in high-risk Group 3 medulloblastoma. 1
• Use RAPNO committee imaging standards including 3D postcontrast T1-weighted imaging, diffusion-weighted imaging, and postcontrast FLAIR imaging for treatment planning and response assessment. 2

Chemotherapy

• Administer concurrent weekly vincristine during radiotherapy for all risk groups. 1
• Follow with maintenance chemotherapy using either COG protocol or St. Jude protocol (cisplatin-etoposide regimens are commonly used in Europe). 1, 4
• Monitor for vincristine-associated neuropathy and cisplatin-associated ototoxicity throughout treatment, as these are the most common dose-limiting toxicities. 1

Baseline and Ongoing Supportive Care

• Discuss contraception and fertility preservation before initiating therapy, given the young age of most adult patients and high risk of treatment-induced infertility. 2
• Evaluate patients at baseline and throughout treatment for endocrine dysfunction, vision and hearing deficits, and neurocognitive impairment. 2
• Provide psychosocial support including participation in support groups and offer referral to neurorehabilitation at diagnosis and throughout the disease course. 2
• Adults tolerate CSI and chemotherapy worse than children despite most being young adults aged <40 years, necessitating proactive symptom management. 2

Surveillance Imaging

• Use MRI with gadolinium contrast of brain and spine for surveillance, as this is superior to other modalities for detecting leptomeningeal dissemination. 1
• Include cerebrospinal fluid cytology, neurologic examination, and steroid use assessment in response evaluation. 2
• Inadequate imaging practices are linked to worse event-free survival, emphasizing the importance of standardized protocols. 2

Clinical Trial Participation

• Strongly encourage enrollment in clinical trials or registries at diagnosis and recurrence, as information from every patient carries great value given the rarity of adult medulloblastoma (only ~140 new cases annually in patients ≥15 years in the United States). 2

Recurrent Disease Management

• Recurrent medulloblastoma after first-line therapy occurs in approximately one-third of patients and carries survival rates <10%. 1
• For recurrence after 3-5 years, rebiopsy the tumor to distinguish between recurrent medulloblastoma and secondary malignancy, and to identify actionable molecular findings. 1
• Treatment options include: targeted therapy based on molecular alterations, reirradiation if feasible, reresection for single focal posterior fossa recurrence, high-dose chemotherapy with stem cell transplantation for fit patients with CNS-contained disease, or palliative care for poor performance status. 1, 5
• High-dose chemotherapy with stem cell transplantation may be considered for a small proportion of fit adult patients unlikely to benefit from conventional chemotherapy, but requires discussion at a multidisciplinary tumor board including hematologic oncologists and transplant specialists. 5

Critical Pitfalls to Avoid

• Do not delay molecular testing or treatment initiation while awaiting results, as the 30-42 day window from resection to CSI is critical. 2
• Do not rely solely on immunohistochemistry for molecular classification, as DNA methylation is more accurate and IHC interpretation can be operator-dependent. 2
• Do not underestimate treatment toxicity in adults compared to children, as adults experience worse tolerance despite younger age. 2
• Do not use inadequate imaging protocols, as this is linked to worse event-free survival. 2