Medulloblastoma of Brain at Relapse: What to Do After Intermediate-Risk First-Line Treatment Did Not Achieve Its Target
This protocol applies to patients with medulloblastoma of the brain who present at or after relapse following first-line intermediate-risk treatment, in a specific clinically and molecularly defined subgroup.
Patient Scenario
Residual tumour less than 1.5 cm² after surgery, metastatic stage M0 or M1, classic or desmoplastic histology, WNT or SHH molecular subgroup.
Previous Treatment & Escalation Trigger
The first-line intermediate-risk regimen — including corticosteroids before surgery, surgical resection, craniospinal irradiation, and the Packer chemotherapy regimen (vincristine, lomustine, and cisplatin) — aimed to achieve a residual tumour volume of less than 1.5 cm² on postoperative MRI within 48 hours. This protocol represents the structured next step when that target was not met, or when the disease has subsequently progressed or relapsed.
Next-Line Approach (Partial Overview)
Management at relapse may involve reassessment for further surgery, radiotherapy options matched to the pattern of relapse, and systemic chemotherapy, with molecular subgroup data informing certain decisions — the full structured protocol specifies the complete clinical algorithm.
References
DOI: 10.1016/S1470-2045(19)30669-2
- Intermediate risk • Residual tumour <1·5 cm² • M0, M1 • Classic or desmoplastic histology • WNT or SHH molecular subgroup
- Second surgery should be done if a total resection appears possible and in cases of disseminated tumour if symptoms can be relieved (level III A; eg, if the spinal cord is compressed by solid intraspinal metastases).
- In selected paediatric cases who initially received reduced dose craniospinal irradiation, salvage treatment with a second craniospinal irradiation appears feasible.
- In cases of focal relapse, focal radiotherapy can be used also in adults (level III B).
- Intravenous chemotherapy with carboplatin and etoposide was explored in the HIT-REZ-2005 study (NCT00749723); an oral alternative consists of a combination chemotherapy with etoposide and trofosfamide.
- Other regimens, such as metronomic and targeted anti-angiogenesis therapy (NCT01356290), topotecan and temozolomide (NCT00918320) or temozolomide and irinotecan, some of them supplemented with bevacizumab can be considered on an individual basis.
- If molecular data are available, sonidegib or vismodegib, with or without cytostatic therapy, can be considered in recurrent or refractory adult patients with SHH medulloblastoma on the basis of their biology, despite the scarce available data that show individual objective responses in small cohorts.
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