Treatment of Medulloblastoma When High-Risk First-Line Therapy Fails to Achieve Adequate Tumour Reduction
This protocol covers patients with medulloblastoma who carry one or more high-risk features and in whom the preceding treatment line did not reach the required tumour control target, necessitating escalation to the next therapeutic step.
Clinical scenario
The patient presents with high-risk disease defined by one or more of the following: residual tumour greater than 1.5 cm² after surgery, metastatic stage beyond M1, large cell or anaplastic medulloblastoma histology, group 4 molecular subgroup, or SHH-activated TP53-mutant medulloblastoma.
Why this protocol applies — prior treatment failure
The preceding high-risk treatment line — encompassing craniospinal irradiation and the Packer chemotherapy regimen — did not achieve the critical target: residual tumour volume less than 1.5 cm² on postoperative MRI within 48 hours after surgery. Failure to reach this goal is the trigger that escalates care to the present protocol.
Treatment approach (partial overview)
At relapse, the strategy re-evaluates surgical and radiotherapy options alongside systemic chemotherapy. Both intravenous and oral chemotherapy approaches may be considered, and in patients with relevant molecular findings, targeted therapy represents an additional individualized avenue. The complete decision algorithm and full range of options are available in the structured protocol.
References
DOI: 10.1016/S1470-2045(19)30669-2
- High risk • Residual tumour >1·5 cm² • >M1 • Large cell/anaplastic histology • Group 4 molecular subgroup • SHH TP53mut
- 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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