Questions and answers in the management of children with medulloblastoma over the time. How did we get here? A systematic review

Abstract

IntroductionTreatment of children with medulloblastoma (MB) includes surgery, radiation therapy (RT) and chemotherapy (CT). Several treatment protocols and clinical trials have been developed over the time to maximize survival and minimize side effects.MethodsWe performed a systematic literature search in May 2023 using PubMed. We selected all clinical trials articles and multicenter studies focusing on MB. We excluded studies focusing exclusively on infants, adults, supratentorial PNETs or refractory/relapsed tumors, studies involving different tumors or different types of PNETs without differentiating survival, studies including <10 cases of MB, solely retrospective studies and those without reference to outcome and/or side effects after a defined treatment.Results1. The main poor-prognosis factors are: metastatic disease, anaplasia, MYC amplification, age younger than 36 months and some molecular subgroups. The postoperative residual tumor size is controversial.2. MB is a collection of diseases.3. MB is a curable disease at diagnosis, but survival is scarce upon relapse.4. Children should be treated by experienced neurosurgeons and in advanced centers.5. RT is an essential treatment for MB. It should be administered craniospinal, early and without interruptions.6. Craniospinal RT dose could be lowered in some low-risk patients, but these reductions should be done with caution to avoid relapses.7. Irradiation of the tumor area instead of the entire posterior fossa is safe enough.8. Hyperfractionated RT is not superior to conventional RT9. Both photon and proton RT are effective.10. CT increases survival, especially in high-risk patients.11. There are multiple drugs effective in MB. The combination of different drugs is appropriate management.12. CT should be administered after RT.13. The specific benefit of concomitant CT to RT is unknown.14. Intensified CT with stem cell rescue has no benefit compared to standard CT regimens.15. The efficacy of intraventricular/intrathecal CT is controversial.16. We should start to think about incorporating targeted therapies in front-line treatment.17. Survivors of MB still have significant side effects.ConclusionSurvival rates of MB improved greatly from 1940-1970, but since then the improvement has been smaller. We should consider introducing targeted therapy as front-line therapy.

The Role of CyberKnife Stereotactic Radiosurgery in Recurrent Cranial Medulloblastomas across Pediatric and Adult Populations

“…The study cohort comprised 8 (80%) pediatric patients (ages 3-18) and 2 (20%) adult patients (ages 19-75). The median age at the time of SRS was 13 years, with the pediatric group having a median age of 12 years (range: 9-16) and the adult group with a median age of 27 years (range: [25][26][27][28][29]. Nine (90%) patients underwent prior surgical resection of prior to SRS, with histological confirmation of WHO grade IV tumors.…”

“…Smaller tumor volumes may correlate with greater OS and PFS outcomes, highlighting the importance of accurately defining and targeting tumor boundaries during SRS [26]. Optimal margin doses play a crucial role in improving OS and PFS, with deviations potentially impacting outcomes [27].…”

The Role of CyberKnife Stereotactic Radiosurgery in Recurrent Cranial Medulloblastomas across Pediatric and Adult Populations

“…The study cohort comprised 8 (80%) pediatric patients (ages 3-18) and 2 (20%) adult patients (ages . The median age at the time of SRS was 13 years, with the pediatric group having a median age of 12 years (range: 9-16) and the adult group with a median age of 27 years (range: [25][26][27][28][29]. Nine (90%) patients underwent prior surgery prior to SRS, with histological confirmation of WHO grade IV recurrent medulloblastomas.…”

“…Smaller tumor volumes may correlate with greater OS and PFS outcomes, highlighting the importance of accurately defining and targeting tumor boundaries during SRS [26]. Optimal margin doses contribute to improved OS and PFS, and deviations from this may impact outcomes [27]. The nuanced interplay of these factors underscores the need for personalized treatment strategies, tailoring therapeutic approaches based on individual patient characteristics to optimize treatment outcomes.…”

The Role of CyberKnife Stereotactic Radiosurgery in Recurrent Cranial Medulloblastomas across Pediatric and Adult Populations

“…The study cohort comprised eight (80%) pediatric patients (ages 3-18) and two (20%) adult patients (ages . The median age at the time of SRS was 13 years, with the pediatric group having a median age of 12 years (range: 9-16) and the adult group with a median age of 27 years (range: [25][26][27][28][29]. Nine (90%) patients underwent surgical resection prior to SRS, with histological confirmation of WHO grade IV tumors.…”