-
Frontiers in Oncology 2023Treatment of children with medulloblastoma (MB) includes surgery, radiation therapy (RT) and chemotherapy (CT). Several treatment protocols and clinical trials have been...
INTRODUCTION
Treatment 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.
METHODS
We 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.
RESULTS
1. 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.
CONCLUSION
Survival 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.
PubMed: 37456257
DOI: 10.3389/fonc.2023.1229853 -
Frontiers in Oncology 2022Conventional parameters show limited and unreliable correlations with medulloblastoma prognosis.
BACKGROUND
Conventional parameters show limited and unreliable correlations with medulloblastoma prognosis.
AIM
To evaluate the factors influencing overall survival (OS), event-free survival (EFS), and progression-free survival (PFS) in patients with medulloblastoma.
METHODS
PubMed, EMBASE, the Cochrane Library, and Web of Science were searched for studies published up to May 2021. The associations between various clinical and treatment factors and survival parameters were assessed.
RESULTS
Twenty-nine studies (8455 patients) were included. Desmoplastic medulloblastoma (HR=0.41, 95%CI: 0.31-0.56), M0 disease (HR=2.07, 95%CI: 1.48-2.89), WNT, SSH, group 4 (all P<0.05 vs. group 3), GTR vs. STR (HR=1.37, 95%CI: 1.04-1.08), radiotherapy (HR=0.45, 95%CI: 0.20-0.80), craniospinal irradiation (HR=0.49, 95%CI: 0.38-0.64), and high 5hmC levels (HR=2.90, 95%CI: 1.85-4.55) were associated with a better OS. WNT, SSH, group 4 (all P<0.05 vs. group 3), residual tumor ≤1.5 cm (HR=2.08, 95%CI: 1.18-3.68), GTR vs. STR (HR=1.31, 95%CI: 1.03-1.68), craniospinal irradiation (HR=0.46, 95%CI: 0.37-0.57), high 5hmC levels (HR=3.10, 95%CI: 2.01-4.76), and <49 days between resection and radiotherapy (HR=2.54, 95%CI: 1.48-4.37) were associated with better PFS. Classic vs. desmoplastic medulloblastoma (HR=1.81, 95%CI: 1.04-3.16), SSH, WNT (both P<0.05 vs, non-SSH/non-WNT), GTR vs. STR (HR=2.01, 95%CI: 1.42-2.85), and radiotherapy (HR=0.31, 95%CI: 0.15-0.64) were associated with a better EFS.
CONCLUSION
Histology, molecular subgroup, GTR, and radiotherapy are significantly associated with survival parameters in patients with medulloblastoma. Nevertheless, high-quality prospective cohort studies are necessary to improve the conclusions.
PubMed: 35311074
DOI: 10.3389/fonc.2022.827054 -
Advances in Radiation Oncology 2023The aim of this study was to comprehensively review all studies examining clinical outcomes of craniospinal irradiation with proton radiotherapy for medulloblastoma (MB)... (Review)
Review
PURPOSE
The aim of this study was to comprehensively review all studies examining clinical outcomes of craniospinal irradiation with proton radiotherapy for medulloblastoma (MB) to determine whether theoretical dosimetric advantages have translated into superior clinical outcomes (including survival and toxicities) compared with traditional photon-based techniques.
METHODS AND MATERIALS
We performed a systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles reporting on clinical outcomes of pediatric and/or adult patients with MB treated with proton radiotherapy were included. Evidence quality was assessed using a modified Newcastle Ottawa scale and GRADE score.
RESULTS
Thirty-five studies were included, with a total of 2059 patients reported (representing an estimated 630-654 unique patients). None of the studies were randomized, 12 were comparative, 9 were prospective, 3 were mixed, and 22 were retrospective. Average mean/median follow-up was 5.0 years (range, 4 weeks to 12.6 years). The majority of studies (n = 19) reported on treatment with passive scatter proton beams exclusively. Average study quality was 6.0 out of 9 (median, 6; standard deviation, 1.6). Nine studies scored ≥8 out of 9 on the modified Newcastle Ottawa Scale; an overall "moderate" GRADE score was assigned. Well-designed comparative cohort studies with adequate follow-up demonstrate superior neurocognitive outcomes, lower incidence of hypothyroidism (23% vs 69%), sex hormone deficiency (3% vs 19%), greater heights, and reduced acute toxicities in patients treated with protons compared to photons. Overall survival (up to 10 years), progression-free survival (up to 10 years), brain stem injury, and other endocrine outcomes were similar to those reported for photon radiation. There was insufficient evidence to make conclusions on endpoints of quality of life, ototoxicity, secondary malignancy, alopecia, scoliosis, cavernomas, and cerebral vasculopathy.
CONCLUSIONS
Moderate-grade evidence supports proton radiotherapy as a preferred treatment for craniospinal irradiation of MB based on equivalent disease control and comparable-to-improved toxicity versus photon beam radiation therapy.
PubMed: 37008255
DOI: 10.1016/j.adro.2023.101189 -
Brain & Spine 2022Pediatric Brain Tumors (PBT) are a common cause of cancer-related mortality globally. Contrary to high-income countries (HIC), survival rates in low-and-middle income... (Review)
Review
BACKGROUND
Pediatric Brain Tumors (PBT) are a common cause of cancer-related mortality globally. Contrary to high-income countries (HIC), survival rates in low-and-middle income countries (LMIC) remains low despite advances in neurosurgical care and diagnostics over the past decades. The aim of this systematic review was to investigate the surgical outcomes for PBT in Sub-Saharan Africa, and the distribution of PBT types.
METHODS
A systematic review was conducted on PubMed, for all available literature on the surgical outcomes of PBT in Sub-Saharan Africa, published before May 3, 2022. Two reviewers performed abstract, full text screening and data collection independently, resolving any conflicts by consensus.
RESULTS
The search yielded 256 studies, of which 22 met the inclusion criteria, amounting to a total of 243 patients. Nigeria was the country with most data. Only subgroups of patients could be extracted from 12 studies, and variables of interest in 6 studies had inconsistent sample sizes. The age centered around 9 years, and there were approximately equal number of girls and boys. The most common tumor was medulloblastoma, followed by craniopharyngioma and astrocytoma. There was large heterogeneity in the reporting of outcomes, and a trend was difficult to discern, considering the large number of different tumor types and different extents of resection.
DISCUSSION AND CONCLUSION
Data is insufficient and inconsistent, precluding statistical conclusions. There is a need for more studies in the field.
PubMed: 36248098
DOI: 10.1016/j.bas.2022.100912 -
Neuro-oncology Advances 2022Medulloblastoma is a rare diagnosis among adolescents and young adults (AYA). Though prognostic factors and treatment are well characterized among children with... (Review)
Review
BACKGROUND
Medulloblastoma is a rare diagnosis among adolescents and young adults (AYA). Though prognostic factors and treatment are well characterized among children with medulloblastoma, equivalent data for AYA are sparse. We conducted a systematic review to identify predictors of survival among AYA with medulloblastoma.
METHODS
We searched for primary studies of AYA (age 15-39 at diagnosis) with medulloblastoma in high-income countries within OVID MEDLINE, EMBASE, and EBM Reviews-Cochrane library databases from inception to August 2020. Patient demographics, primary outcomes, and univariate and multivariable data on all prognostic factors were collected from included studies. Prognosticators were characterized as patient, disease, or treatment-related.
RESULTS
We identified 18 articles. 5-year overall survival ranged between 40% and 89%, while disease-free survival ranged from 49% to 89%. Study quality was low as assessed by the Quality in Prognostic factor Studies tool. Though meta-analyses were not possible due heterogeneity, narrative summaries suggested that lower disease burden, superior postoperative functional status, and higher doses and larger fields of radiation were associated with improved survival. Reported chemotherapy regimens were heterogeneous in timing, agents, and relationship with radiation, precluding meaningful comparisons. Only one study included molecular subgroups for analysis, with the majority (76.5%) of tumors classified as Sonic Hedgehog (SHH).
CONCLUSIONS
Prognostication and treatment of AYA medulloblastoma is limited by a dearth of primary evidence and lack of specificity for patients aged 15-39. Dedicated prospective trials to delineate the benefit of various chemotherapy and radiation regimens are required in this population to identify prognosticators and ideal treatment regimens.
PubMed: 35669013
DOI: 10.1093/noajnl/vdac016 -
International Journal of Molecular... Dec 2021Medulloblastoma is a common fatal pediatric brain tumor. More treatment options are required to prolong survival and decrease disability. mTOR proteins play an essential... (Review)
Review
Medulloblastoma is a common fatal pediatric brain tumor. More treatment options are required to prolong survival and decrease disability. mTOR proteins play an essential role in the disease pathogenesis, and are an essential target for therapy. Three generations of mTOR inhibitors have been developed and are clinically used for immunosuppression and chemotherapy for multiple cancers. Only a few mTOR inhibitors have been investigated for the treatment of medulloblastoma and other pediatric tumors. The first-generation mTOR, sirolimus, temsirolimus, and everolimus, went through phase I clinical trials. The second-generation mTOR, AZD8055 and sapanisertib, suppressed medulloblastoma cell growth; however, limited studies have investigated possible resistance pathways. No clinical trials have been found to treat medulloblastoma using third-generation mTOR inhibitors. This systematic review highlights the mechanisms of resistance of mTOR inhibitors in medulloblastoma and includes IDO1, T cells, Mnk2, and eIF4E, as they prolong malignant cell survival. The findings promote the importance of combination therapy in medulloblastoma due to its highly resistant nature.
Topics: Antineoplastic Agents; Child; Drug Resistance, Neoplasm; Humans; Medulloblastoma; Protein Kinase Inhibitors; TOR Serine-Threonine Kinases
PubMed: 35008889
DOI: 10.3390/ijms23010464 -
Cancers Sep 2023Medulloblastoma (MB) is the most common malignant brain tumor in childhood. Although recent multi-omic studies have led to advances in MB classification, there is still... (Review)
Review
Medulloblastoma (MB) is the most common malignant brain tumor in childhood. Although recent multi-omic studies have led to advances in MB classification, there is still room for improvement with regard to treatment response and survival. Therefore, identification of new and less invasive biomarkers is needed to refine the diagnostic process and to develop more personalized treatment strategies. In this context, non-coding RNAs (ncRNAs) could be useful biomarkers for MB. In this article, we reviewed the role of two types of ncRNAs, long non-coding (lncRNAs) and circular RNAs (circRNAs), as biomarkers for the diagnosis, subgroup classification, and prognosis of MB. We also reviewed potential candidates with specific functions and mechanisms of action in the disease. We performed a search in PubMed and Scopus using the terms ("long non coding RNAs" OR "lncRNAs") and ("circular RNAs" OR "circRNAs") AND "medulloblastoma" to identify biomarker discovery or functional studies evaluating the effects of these ncRNAs in MB. A total of 26 articles met the inclusion criteria. Among the lncRNAs, the tumorigenic effects of the upregulated and were the most studied in MB. Among the circRNAs, the upregulation of and its functional impact in MB cell lines were the most consistent results, so this circRNA could be considered a potential biomarker in MB. Additional validation is required for many deregulated lncRNAs and circRNAs; therefore, further studies are warranted.
PubMed: 37835380
DOI: 10.3390/cancers15194686 -
Cancers May 2022Pediatric brain tumors are the most common solid tumor in children. Traditionally, tumor diagnosis and molecular analysis were carried out on tumor tissue harvested... (Review)
Review
BACKGROUND
Pediatric brain tumors are the most common solid tumor in children. Traditionally, tumor diagnosis and molecular analysis were carried out on tumor tissue harvested either via biopsy or resection. However, liquid biopsy allows analysis of circulating tumor DNA in corporeal fluids such as cerebrospinal fluid or blood.
METHODS
We performed a systematic review in Pubmed and Embase regarding the role of liquid biopsy in pediatric brain tumors.
RESULTS
Nine studies with a total of 570 patients were included. The preferred corporeal fluid for analysis with a relatively high yield of ct-DNA was cerebrospinal fluid (CSF). For high-grade glioma, liquid biopsy can successfully characterize H3K27mutations and predict tumor progression before it is radiographically detected. Moreover, liquid biopsy has the potential to distinguish between pseudo-progression and actual progression. In medulloblastoma, ct-DNA in the CSF can be used as a surrogate marker of measurable residual disease and correlates with response to therapy and progression of the tumor up to three months before radiographic detection.
CONCLUSION
Liquid biopsy is primarily useful in high-grade pediatric brain tumors such as diffuse midline glioma or medulloblastoma. Disease detection and monitoring is feasible for both tumor entities. More trials to standardize its use for pediatric brain tumors are necessary.
PubMed: 35681663
DOI: 10.3390/cancers14112683 -
Cancers Nov 2022: Posterior fossa tumors (PFTs) are a morbid group of central nervous system tumors that most often present in childhood. While early diagnosis is critical to drive... (Review)
Review
: Posterior fossa tumors (PFTs) are a morbid group of central nervous system tumors that most often present in childhood. While early diagnosis is critical to drive appropriate treatment, definitive diagnosis is currently only achievable through invasive tissue collection and histopathological analyses. Machine learning has been investigated as an alternative means of diagnosis. In this systematic review and meta-analysis, we evaluated the primary literature to identify all machine learning algorithms developed to classify and diagnose pediatric PFTs using imaging or molecular data. : Of the 433 primary papers identified in PubMed, EMBASE, and Web of Science, 25 ultimately met the inclusion criteria. The included papers were extracted for algorithm architecture, study parameters, performance, strengths, and limitations. : The algorithms exhibited variable performance based on sample size, classifier(s) used, and individual tumor types being investigated. Ependymoma, medulloblastoma, and pilocytic astrocytoma were the most studied tumors with algorithm accuracies ranging from 37.5% to 94.5%. A minority of studies compared the developed algorithm to a trained neuroradiologist, with three imaging-based algorithms yielding superior performance. Common algorithm and study limitations included small sample sizes, uneven representation of individual tumor types, inconsistent performance reporting, and a lack of application in the clinical environment. : Artificial intelligence has the potential to improve the speed and accuracy of diagnosis in this field if the right algorithm is applied to the right scenario. Work is needed to standardize outcome reporting and facilitate additional trials to allow for clinical uptake.
PubMed: 36428701
DOI: 10.3390/cancers14225608 -
Cureus Nov 2022Despite the optimal treatment given to children with medulloblastoma, many relapses are seen after combining treatments. Re-irradiation is part of salvage therapy for...
Despite the optimal treatment given to children with medulloblastoma, many relapses are seen after combining treatments. Re-irradiation is part of salvage therapy for children who relapse and might provide long-term disease control. Nevertheless, it is challenging because there is a concern about exceeding radiation tolerances and late treatment toxicities. Re-irradiation is an option for many brain tumors, including medulloblastoma in children. This study presents a case of recurrent medulloblastoma treated with re-irradiation. A systematic review of the literature provided up-to-date data on the re-irradiation of medulloblastoma in children. This study aims to contribute to the scarce literature on the treatment strategy, which may help improve patients' outcomes.
PubMed: 36540431
DOI: 10.7759/cureus.31585