Continuing Education Activity

Medulloblastoma is the most common malignant brain tumor in children, accounting for approximately 25% of pediatric central nervous system tumors. It typically arises in the cerebellum in children younger than 10 years and is classified as a WHO grade 4 embryonal tumor. Despite advances in therapy, it carries significant morbidity and mortality, with 5-year survival rates of 65% to 70%. The 2021 WHO classification defines 4 molecular subgroups: WNT-activated, SHH-activated (TP53-wildtype and TP53-mutant), and non-WNT/non-SHH (groups 3 and 4), each with distinct prognostic and clinical features. This activity reviews the clinical presentation, diagnostic evaluation (including neuroimaging and cerebrospinal fluid analysis), and risk-adapted management with surgery, radiation, and chemotherapy. Emphasis is placed on early recognition, molecular classification, interprofessional care, and strategies to reduce treatment-related complications and support long-term outcomes.

Objectives:

• Differentiate the molecular subgroups of medulloblastoma according to the WHO Classification.
• Identify the typical clinical presentation of medulloblastoma.
• Apply risk stratification criteria to determine the appropriate treatment approach for patients with medulloblastoma diagnostic features.
• Collaborate effectively within the interprofessional care team by coordinating treatment planning for patients with medulloblastoma to improve outcomes.

Introduction

Medulloblastoma represents the most common malignant brain tumor in children, accounting for approximately 25% of all pediatric central nervous system (CNS) tumors.[1][2][3] Classified as a World Health Organization (WHO) grade 4 embryonal tumor, medulloblastoma arises primarily in the posterior fossa, most often from the cerebellum. Pediatric populations account for the majority of cases, with 70% diagnosed in children younger than 10 years. Although rare in adults, medulloblastoma constitutes less than 1% of adult CNS tumors.[4] Annual incidence in children younger than 19 years old is 0.39 per 100,000, peaking between ages 3 and 7.[2][3][5] Despite advances in multimodal therapy, including surgical resection, craniospinal irradiation, and chemotherapy, medulloblastoma remains a leading cause of cancer-related morbidity and mortality in children. Overall, 5-year survival ranges from 65% to 70%, with survivors frequently experiencing long-term neurocognitive and neuroendocrine complications.

The 2021 World Health Organization (WHO) Classification categorizes medulloblastoma by molecular subgroup: WNT-activated, SHH-activated/TP53-wildtype, SHH-activated/TP53-mutant, and non-WNT/non-SHH (encompassing groups 3 and 4), incorporating integrated molecular-histologic diagnostics. Each subgroup carries distinct histologic, genetic, clinical, and prognostic features.[6]

Etiology

The etiology of medulloblastoma remains incompletely understood. Approximately 5% of cases arise in the setting of an underlying germline mutation in a cancer predisposition gene, most commonly within the WNT-activated and SHH-activated molecular subtypes.[7][8] Syndromic associations include Turcot syndrome (APC mutation), Rubinstein-Taybi syndrome (CREBBP mutation), Gorlin syndrome (PTCH1 or SUFU mutations), Li-Fraumeni syndrome (TP53 mutation), and Fanconi anemia (BRCA2 mutations).[9][10][11][12][13] Germline APC variants are exclusively associated with the WNT-activated subtype, whereas germline TP53 variants are confined to the SHH–activated subtype.[7][12]

The majority of medulloblastomas are believed to arise sporadically due to somatic mutations that affect subgroup-specific signaling pathways. WNT-activated tumors harbor activating CTNNB1 mutations in approximately 90% of cases. SHH-activated tumors frequently demonstrate alterations in PTCH1, SMO, or amplifications of GLI1 or GLI2. Group 3 medulloblastomas are characterized by MYC amplification and marked genomic instability, whereas group 4 tumors commonly exhibit MYCN and CDK6 amplifications along with isochromosome 17q.[14][15]

Epidemiology

The overall incidence of medulloblastoma is approximately 0.39 per 100,000 children younger than 19 years, based on data from 2017 to 2021.[2] Children are 10 times more likely to be diagnosed with medulloblastoma than adults, with a peak incidence between the ages of 3 and 7.[3][5] Overall, medulloblastoma demonstrates a male predominance and is more frequently diagnosed in the White population.[16][17] Epidemiologic features vary substantially across molecular subgroups, including differences in age distribution, sex predilection, and relative incidence.

The WNT-activated subtype accounts for approximately 10% of medulloblastomas and occurs primarily in children older than 4 years and adolescents. This subgroup affects males and females at similar rates.[18][19] The SHH-activated subtype comprises approximately one-third of medulloblastomas and exhibits a bimodal age distribution, with peak incidence in infancy and adulthood. The sex distribution in this subgroup is approximately equal.[19] Group 3 medulloblastomas represent roughly 25% of cases and occur almost exclusively in infants and young children. This subgroup demonstrates a male predominance, with an approximate male-to-female ratio of 2:1.[19] Group 4 medulloblastomas account for approximately 35% of cases and typically present in childhood and adolescence. This subgroup shows the strongest male predominance, with an estimated male-to-female ratio of 3:1.[19]

Pathophysiology

Medulloblastoma is an embryonal malignant tumor of the cerebellum arising from dysregulated proliferation and impaired differentiation of neural precursor cells within the developing hindbrain. Its pathophysiology is defined by aberrant activation of distinct molecular signaling pathways, most commonly the WNT and SHH pathways, as well as MYC- or MYCN-driven oncogenesis in groups 3 and 4. These molecular alterations lead to uncontrolled cell cycle progression, genomic instability, and resistance to apoptosis. Medulloblastoma is a highly malignant posterior fossa tumor with a propensity for local invasion, as well as metastatic spread within the brain and spinal cord.[20]

Histopathology

Using the WHO 2021 guidelines, a tumor is classified as "medulloblastoma, histologically defined" if no molecular testing has been performed.[6] Histologic subtypes include classic, desmoplastic/nodular, medulloblastoma with extensive nodularity (MBEN), and large cell/anaplastic (LC/A). 

Classic medulloblastoma histology is characterized by a small, round, blue-cell tumor with poorly differentiated cells, a high nuclear-to-cytoplasmic ratio, and high mitotic activity (See Image. Medulloblastoma Histology). Homer-Wright rosettes are seen in less than half of the samples.[21] Classic histology is the most common pattern and is represented among all subgroups. 

Desmoplastic/nodular histology is characterized by highly proliferative, reticulin-rich areas surrounding reticulin-free nodules with reduced mitotic activity.[6][22] This histologic pattern is exclusive to the SHH subgroup.[19] MBEN histology is similar to desmoplastic/nodular but differs in having larger reticulin-free zones.[6][22] MBEN histology is a rare variant seen almost exclusively in infants with SHH-activated tumors and has a favorable prognosis.

LC/A histology demonstrates a combination of large cell and anaplastic features. These features are large tumor cells with abundant cytoplasm, pleomorphic nuclei, and prominent nucleoli. Tumors with LC/A histology are typically located in the cerebellar vermis and are highly aggressive, exhibiting marked mitotic and apoptotic activity with extensive necrosis. This pattern is most commonly seen in group 3 tumors and SHH-activated TP53-mutant tumors and is associated with the poorest prognosis.[23]

History and Physical

The most common presentation of medulloblastoma is signs and symptoms of increased intracranial pressure, including headache, nausea, and vomiting. As the majority of tumors arise in the fourth ventricle, many patients present with obstructive hydrocephalus. Others may present with a combination of cerebellar signs, eg, clumsiness or gait disturbance. Infants may present with fussiness, an increasing head circumference, delayed or missed milestones, or lethargy.

Physical examination should include a thorough neurological assessment with particular attention to cerebellar function (gait, coordination, Romberg test, finger-to-nose testing), a cranial nerve examination (especially extraocular movements for sixth nerve palsy due to increased intracranial pressure), and a fundoscopic examination for papilledema.

Evaluation

The evaluation of suspected medulloblastoma requires a comprehensive approach that integrates neuroimaging, cerebrospinal fluid (CSF) analysis, histopathology, and molecular profiling to establish the diagnosis, determine the extent of disease, and guide risk stratification. Because many patients present to the emergency department, computed tomography (CT) is often the first imaging modality obtained. Medulloblastomas are typically hyperdense on CT due to their extensive cellularity.[24]

Magnetic resonance imaging (MRI), with or without contrast, is the recommended imaging modality for suspected medulloblastoma.[25] Initial imaging should include MRI of both the brain and craniospinal axis to evaluate for metastatic disease (see Image. Primary Medulloblastoma). This evaluation should be performed preoperatively to avoid confusion with blood products or other postoperative changes. Medulloblastoma typically presents as a large, heterogeneous posterior fossa mass occupying the fourth ventricle or cerebellar hemisphere. These masses typically show restricted diffusion on diffusion-weighted imaging (DWI).

Advanced imaging with MR spectroscopy (MRS) can help differentiate medulloblastomas from other posterior fossa tumors, as high levels of taurine at 3.4 ppm are almost exclusively found in medulloblastomas.[24] Depending on the molecular subtype, imaging findings may vary. SHH-activated tumors are more likely to be found in the cerebellar hemispheres compared to the more frequent midline location of WNT, group 3, and group 4 tumors. Furthermore, SHH-activated tumors are more likely to have peritumoral edema compared to other subtypes. WNT-activated tumors often arise in the brainstem, which explains their typical midline location.[24] After neurosurgical intervention, a postoperative brain MRI should be obtained within 24 to 72 hours. Lumbar puncture for CSF cytology is a mandatory component of staging and should be performed at least 10 to 14 days postoperatively to avoid false-positive results after surgical resection.[25]

Treatment / Management

Current treatment modalities for medulloblastoma combine surgical resection with craniospinal irradiation (CSI) and chemotherapy. All patients should be treated by an interprofessional team with experience managing pediatric CNS tumors, with early referral to radiation oncology and pediatric neuro-oncology.

Intervention begins with maximal safe resection, aiming for gross total resection (GTR) or near-total resection (NTR), followed by risk-stratified adjuvant therapy for patients aged 3 years and older. See the staging section below for more details on risk stratification. Average-risk patients (localized disease, GTR/NTR, classic or desmoplastic histology, non-MYC-amplified) receive CSI at 23.4 Gy with an involved-field boost to 54 Gy, followed by adjuvant chemotherapy.[NCCN. Pediatric Central Nervous System Cancers. 2026][26][27] 

High-risk patients (metastatic disease, subtotal resection, large-cell/anaplastic histology, MYCN amplification, or TP53 mutation) receive high-dose CSI to 36 Gy, with a boost to 54 to 55.8 Gy, plus adjuvant chemotherapy.[NCCN. Pediatric Central Nervous System Cancers. 2026][28] Very high-risk Group 3 tumors with MYC amplification may receive concurrent carboplatin with radiation, as it has been shown to improve event-free survival in this group.[28] Chemotherapy regimens for both average and high-risk groups include cisplatin, cyclophosphamide, lomustine, and vincristine administered during and after radiation therapy.

CSI is not recommended for children younger than 3 years due to severe neurodevelopmental toxicity; radiation-sparing chemotherapy strategies are preferred.[29] No standard chemotherapy approach has been established for these patients. Those younger than 3 years of age often fall into the SHH and group 3 subgroups. Various regimens include Head Start protocols, which use intensive, radiation-sparing chemotherapy with high-dose consolidation and autologous stem cell rescue.[30][31][Dhall G, et al. MDB-83. Outcomes of Infants and Young Children With Newly Diagnosed SHH Medulloblastoma Treated on the Next Consortium "Head Start" 4 Protocol. 2024] St. Jude infant protocols also emphasize radiation avoidance with multi-agent chemotherapy, incorporating molecular risk stratification and selective radiation for high-risk or progressive disease.[32] The Children's Oncology Group's ACNS0334 trial evaluated intensive chemotherapy with high-dose consolidation, with or without isotretinoin, in young children and demonstrated benefit in select nonmetastatic patients, particularly those with SHH-activated disease.[33] Outcomes remain poor for infant group 3 tumors, highlighting the need for novel therapeutic approaches in this population.[34]

For recurrent or progressive medulloblastoma, treatment options include repeated operation followed by adjuvant temozolomide/irinotecan with bevacizumab, temozolomide/topotecan (TOTEM), metronomic antiangiogenic therapy (MEMMAT regimen), or carboplatin/etoposide.[25] 

Table

A 6-year-old child undergoes maximal safe resection of a posterior fossa medulloblastoma. Postoperative MRI demonstrates minimal residual disease, and cerebrospinal fluid cytology is negative for metastatic spread. Molecular testing identifies a WNT-activated (more...)

Differential Diagnosis

The differential diagnosis for a posterior fossa mass in a child includes pilocytic astrocytoma, ependymoma, atypical teratoid/rhabdoid tumor (AT/RT), and diffuse midline glioma. Pilocytic astrocytoma is typically a cystic cerebellar hemispheric mass with a nodular component, in contrast to medulloblastoma's generally solid, heterogeneous appearance. Ependymomas arise from the floor of the fourth ventricle and classically extend through the foramina of Luschka and Magendie. AT/RT occurs predominantly in children younger than 3 years and is associated with greater invasion of the brainstem and middle cerebellar peduncle. Diffuse midline glioma typically involves the brainstem or thalamus and exhibits infiltrative growth patterns.[35] Ultimately, tumor sampling is required to distinguish these entities.

Surgical Oncology

Maximal safe resection is the first-line intervention for medulloblastoma to relieve presenting symptoms, establish histopathologic and molecular diagnosis, and maximize local control.[36][NCCN. Pediatric Central Nervous System Cancers. 2026] The goal of initial surgical intervention is gross total resection, or at least near total resection with less than 1.5 cm² of tumor remaining.[36][37] For those with residual tumors greater than 1.5 cm² on postoperative MRI, a second-look surgery is recommended, as the extent of resection is important in overall staging and prognosis. In some cases, surgical management of obstructive hydrocephalus may be necessary via an endoscopic third ventriculostomy or ventriculoperitoneal shunt.[38][39][40]

Posterior fossa syndrome, also known as cerebellar mutism syndrome, is a significant complication occurring in up to 30% of children following medulloblastoma resection.[41] The syndrome typically develops 1 to 2 days postoperatively and consists of diminished speech progressing to complete mutism, severe ataxia, emotional lability, and hypotonia. Recovery is often spontaneous, but many patients have long-term speech and neurocognitive difficulties.[42][43] The reasons some patients develop posterior fossa syndrome remain unclear, but vermis incision, superior cerebellar peduncle involvement, and gross total resection are notable intraoperative risk factors.[44]

Radiation Oncology

CSI is the backbone of medulloblastoma treatment for children older than 3 years, targeting both the primary tumor site and potential microscopic leptomeningeal disease. CSI is generally not recommended for children younger than 3 years due to severe neurodevelopmental toxicity; radiation-sparing chemotherapy strategies are preferred in this population.

Radiation dosing is risk-stratified. Average-risk patients receive CSI at 23.4 Gy with a tumor bed boost to 54 Gy, while high-risk patients receive CSI at 36 Gy with additional boosts to metastatic sites.[25] The Children's Oncology Group ACNS0331 trial demonstrated that reducing the boost volume from whole posterior fossa to involved-field radiation therapy is safe, whereas reducing the CSI dose from 23.4 Gy to 18 Gy resulted in inferior outcomes.[26] Proton therapy is recommended when available to reduce toxicity to the heart, lungs, cochlea, and developing brain.[45]

Late effects of radiation therapy are substantial and include neurocognitive decline, endocrinopathies (growth hormone deficiency in nearly all patients receiving 36 Gy CSI), hearing loss, and secondary malignancies.[46]

Treatment Planning

Craniospinal irradiation is commonly delivered using proton beam therapy or intensity-modulated radiotherapy to minimize exposure of normal tissues to radiation and spare organs at risk. Treatment is commonly delivered in fractions of 180 cGy. Target volumes consist of the craniospinal axis, with subsequent cone-down boosts to areas of resected or gross disease.

Staging

Staging of medulloblastoma depends on neuroimaging, CSF analysis, the extent of surgical resection, histopathology, and molecular profiling. The findings from brain and spine MRI, CSF analysis, and histopathology guide staging and risk stratification. Patients were traditionally categorized as standard- or high-risk, with high-risk defined by age younger than 3, residual tumor greater than 1.5 cm², or metastatic disease at presentation.[47][48] 

Current NCCN guidelines stratify patients older than age 3 by molecular subgroup, though metastatic disease, subtotal resection, or MYC amplification still indicate high-risk status.[25] Low-risk tumors are defined as gross or near-totally resected WNT-activated medulloblastomas with classic histology and without metastasis or MYC amplification. Standard-risk tumors include select patients from the SHH-activated and non-WNT/non-SHH subgroups. In the SHH-activated subgroup, standard-risk disease is defined by TP53–wild-type status, absence of metastatic dissemination, gross or near-total resection, and absence of MYCN amplification or large-cell/anaplastic histology.

Similarly, patients with non-WNT/non-SHH medulloblastoma are considered standard risk when the disease is nonmetastatic, any residual tumor is minimal following surgery, and neither MYC amplification (group 3) nor MYCN amplification (group 4) is observed. No large-cell/anaplastic histology is observed. High-risk features include TP53 mutation in SHH-activated medulloblastoma, MYC amplification in group 3 tumors, and MYCN amplification in group 4 tumors. Group 3 medulloblastomas with MYC amplification are among the highest-risk phenotypes and are associated with particularly poor outcomes.[25][49]

Children younger than 3 are classified as infantile medulloblastoma and do not use the above staging—they are a biologically diverse group prone to recurrence and vulnerable to neurotoxicity from craniospinal irradiation.[29]

Prognosis

The overall 5-year survival rate for pediatric medulloblastoma is around 70%, though outcomes vary dramatically by molecular subgroup and risk stratification. Key prognostic factors include age at presentation (<3 years associated with worse outcomes), presence of metastatic disease, extent of resection, histologic subtype, molecular subgroup, and specific molecular alterations, including MYC/MYCN amplification and TP53 mutation status.

Molecular subgroup is the most important prognostic determinant. WNT-activated tumors have the best prognosis, with overall survival approaching 100% in children; these patients are candidates for treatment de-escalation trials.[50][51] SHH-activated, TP53-wild-type tumors have an intermediate prognosis, with more than 80% survival in the absence of high-risk features, whereas SHH-activated, TP53-mutant tumors have poor outcomes, with approximately 40% 5-year overall survival.[14] 

In breaking down the non-WNT/non-SHH group, group 3 tumors carry the worst prognosis with 5-year survival of 20% to 50%, particularly when associated with MYC amplification or metastatic disease. Group 4 tumors have an intermediate prognosis with a 5-year overall survival of 75% to 90%.[14][6][22][25]

Complications

Complications of medulloblastoma arise from both the disease itself and its multimodal treatment. Acute treatment-related complications include posterior fossa syndrome (cerebellar mutism) occurring in up to 30% of patients following surgical resection. Radiation-related acute toxicities include headache, nausea/vomiting, and skin erythema. Acute toxicities from chemotherapy include cytopenias, nausea, vomiting, constipation, ototoxicity, nephrotoxicity, and increased risk of infection. 

Long-term complications are substantial and affect nearly all survivors. Neurocognitive impairment is one of the most pervasive late effects; younger age at treatment is associated with more severe deficits. Endocrinopathies are common, with growth hormone deficiency occurring in nearly all patients receiving 36 Gy craniospinal irradiation and 50% of those receiving 23.4 Gy; hypothyroidism affects up to 75% of survivors.[52][53] 

Secondary malignancies represent a significant long-term risk when compared to the general population. The 10-year cumulative incidence of secondary neoplasms is approximately 5% to 7%, with the central nervous system being the most common site (high-grade gliomas and meningiomas), followed by thyroid carcinoma and bone/soft tissue tumors.[54] Risk is higher in patients treated at younger ages and those receiving craniospinal irradiation. These significant late effects have driven efforts toward molecularly informed treatment de-escalation for favorable-risk subgroups.

Deterrence and Patient Education

Patients and families should be counseled that medulloblastoma requires intensive multimodal treatment, including surgery, radiation therapy, and chemotherapy, with treatment duration typically spanning 12 to 18 months. Education regarding the importance of adherence to surveillance schedules is essential, as recurrence surveillance includes serial brain and spine MRI, CSF analysis, and clinical examinations at regular intervals for at least 5 years. Families should be informed about the substantial risk of long-term complications, including neurocognitive decline, endocrinopathies, hearing loss, and secondary malignancies, which necessitate lifelong interprofessional follow-up. Referral for fertility preservation counseling should be offered before initiating treatment.

Enhancing Healthcare Team Outcomes

Medulloblastoma represents the most common malignant brain tumor in children, arising predominantly in the cerebellum and accounting for roughly 25% of pediatric central nervous system tumors. Most cases occur in children younger than 10 years old, with peak incidence between ages 3 and 7. Diagnosis relies on neuroimaging and histopathologic evaluation, while molecular subgrouping, WNT-activated, SHH-activated/TP53-wildtype, SHH-activated/TP53-mutant, and non-WNT/non-SHH, guides prognosis and treatment planning. Standard therapy combines maximal safe surgical resection with craniospinal irradiation and chemotherapy. Despite advances, medulloblastoma continues to cause significant morbidity, and survivors frequently experience long-term neurocognitive, neuroendocrine, and psychosocial challenges.

Optimal management requires an interprofessional approach integrating pediatric oncologists, neurosurgeons, radiation oncologists, pathologists, radiologists, and nurses, with pharmacists, dietitians, genetic counselors, fertility specialists, and psychosocial professionals involved as needed. Physicians and advanced practitioners coordinate diagnosis, treatment planning, and ongoing monitoring, while nurses assess and manage acute toxicities during therapy. Pharmacists assist with safe, individualized chemotherapy dosing. Interprofessional communication through tumor boards, shared records, and family liaisons enhances care coordination. Long-term survivorship planning ensures monitoring for late effects and supports a smooth transition to adult care, improving patient-centered outcomes and safety.

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References

1.

Ostrom QT, Price M, Neff C, Cioffi G, Waite KA, Kruchko C, Barnholtz-Sloan JS. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2015-2019. Neuro Oncol. 2022 Oct 05;24(Suppl 5):v1-v95. [PMC free article: PMC9533228] [PubMed: 36196752]

2.

Price M, Ballard C, Benedetti J, Neff C, Cioffi G, Waite KA, Kruchko C, Barnholtz-Sloan JS, Ostrom QT. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2017-2021. Neuro Oncol. 2024 Oct 06;26(Supplement_6):vi1-vi85. [PMC free article: PMC11456825] [PubMed: 39371035]

3.

Orr BA. Pathology, diagnostics, and classification of medulloblastoma. Brain Pathol. 2020 May;30(3):664-678. [PMC free article: PMC7317787] [PubMed: 32239782]

4.

van den Bent MJ, Geurts M, French PJ, Smits M, Capper D, Bromberg JEC, Chang SM. Primary brain tumours in adults. Lancet. 2023 Oct 28;402(10412):1564-1579. [PubMed: 37738997]

5.

Smoll NR, Drummond KJ. The incidence of medulloblastomas and primitive neurectodermal tumours in adults and children. J Clin Neurosci. 2012 Nov;19(11):1541-4. [PubMed: 22981874]

6.

Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, Hawkins C, Ng HK, Pfister SM, Reifenberger G, Soffietti R, von Deimling A, Ellison DW. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021 Aug 02;23(8):1231-1251. [PMC free article: PMC8328013] [PubMed: 34185076]

7.

Waszak SM, Northcott PA, Buchhalter I, Robinson GW, Sutter C, Groebner S, Grund KB, Brugières L, Jones DTW, Pajtler KW, Morrissy AS, Kool M, Sturm D, Chavez L, Ernst A, Brabetz S, Hain M, Zichner T, Segura-Wang M, Weischenfeldt J, Rausch T, Mardin BR, Zhou X, Baciu C, Lawerenz C, Chan JA, Varlet P, Guerrini-Rousseau L, Fults DW, Grajkowska W, Hauser P, Jabado N, Ra YS, Zitterbart K, Shringarpure SS, De La Vega FM, Bustamante CD, Ng HK, Perry A, MacDonald TJ, Hernáiz Driever P, Bendel AE, Bowers DC, McCowage G, Chintagumpala MM, Cohn R, Hassall T, Fleischhack G, Eggen T, Wesenberg F, Feychting M, Lannering B, Schüz J, Johansen C, Andersen TV, Röösli M, Kuehni CE, Grotzer M, Kjaerheim K, Monoranu CM, Archer TC, Duke E, Pomeroy SL, Shelagh R, Frank S, Sumerauer D, Scheurlen W, Ryzhova MV, Milde T, Kratz CP, Samuel D, Zhang J, Solomon DA, Marra M, Eils R, Bartram CR, von Hoff K, Rutkowski S, Ramaswamy V, Gilbertson RJ, Korshunov A, Taylor MD, Lichter P, Malkin D, Gajjar A, Korbel JO, Pfister SM. Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort. Lancet Oncol. 2018 Jun;19(6):785-798. [PMC free article: PMC5984248] [PubMed: 29753700]

8.

Zhang J, Walsh MF, Wu G, Edmonson MN, Gruber TA, Easton J, Hedges D, Ma X, Zhou X, Yergeau DA, Wilkinson MR, Vadodaria B, Chen X, McGee RB, Hines-Dowell S, Nuccio R, Quinn E, Shurtleff SA, Rusch M, Patel A, Becksfort JB, Wang S, Weaver MS, Ding L, Mardis ER, Wilson RK, Gajjar A, Ellison DW, Pappo AS, Pui CH, Nichols KE, Downing JR. Germline Mutations in Predisposition Genes in Pediatric Cancer. N Engl J Med. 2015 Dec 10;373(24):2336-2346. [PMC free article: PMC4734119] [PubMed: 26580448]

9.

Hamilton SR, Liu B, Parsons RE, Papadopoulos N, Jen J, Powell SM, Krush AJ, Berk T, Cohen Z, Tetu B. The molecular basis of Turcot's syndrome. N Engl J Med. 1995 Mar 30;332(13):839-47. [PubMed: 7661930]

10.

Bourdeaut F, Miquel C, Richer W, Grill J, Zerah M, Grison C, Pierron G, Amiel J, Krucker C, Radvanyi F, Brugieres L, Delattre O. Rubinstein-Taybi syndrome predisposing to non-WNT, non-SHH, group 3 medulloblastoma. Pediatr Blood Cancer. 2014 Feb;61(2):383-6. [PubMed: 24115570]

11.

Smith MJ, Beetz C, Williams SG, Bhaskar SS, O'Sullivan J, Anderson B, Daly SB, Urquhart JE, Bholah Z, Oudit D, Cheesman E, Kelsey A, McCabe MG, Newman WG, Evans DG. Germline mutations in SUFU cause Gorlin syndrome-associated childhood medulloblastoma and redefine the risk associated with PTCH1 mutations. J Clin Oncol. 2014 Dec 20;32(36):4155-61. [PubMed: 25403219]

12.

Kolodziejczak AS, Guerrini-Rousseau L, Planchon JM, Ecker J, Selt F, Mynarek M, Obrecht D, Sill M, Autry RJ, Stutheit-Zhao E, Hirsch S, Amouyal E, Dufour C, Ayrault O, Torrejon J, Waszak SM, Ramaswamy V, Pentikainen V, Demir HA, Clifford SC, Schwalbe EC, Massimi L, Snuderl M, Galbraith K, Karajannis MA, Hill K, Li BK, Walsh M, White CL, Redmond S, Loizos L, Jakob M, Kordes UR, Schmid I, Hauer J, Blattmann C, Filippidou M, Piccolo G, Scheurlen W, Farrag A, Grund K, Sutter C, Pietsch T, Frank S, Schewe DM, Malkin D, Ben-Arush M, Sehested A, Wong TT, Wu KS, Liu YL, Carceller F, Mueller S, Stoller S, Taylor MD, Tabori U, Bouffet E, Kool M, Sahm F, von Deimling A, Korshunov A, von Hoff K, Kratz CP, Sturm D, Jones DTW, Rutkowski S, van Tilburg CM, Witt O, Bougeard G, Pajtler KW, Pfister SM, Bourdeaut F, Milde T. Clinical outcome of pediatric medulloblastoma patients with Li-Fraumeni syndrome. Neuro Oncol. 2023 Dec 08;25(12):2273-2286. [PMC free article: PMC10708940] [PubMed: 37379234]

13.

Sönksen M, Obrecht-Sturm D, Hernáiz Driever P, Sauerbrey A, Graf N, Kontny U, Reimann C, Langhein M, Kordes UR, Schwarz R, Obser T, Boschann F, Schüller U, Altendorf L, Goschzik T, Pietsch T, Mynarek M, Rutkowski S. Medulloblastoma in children with Fanconi anemia: Association with FA-D1/FA-N, SHH type and poor survival independent of treatment strategies. Neuro Oncol. 2024 Nov 04;26(11):2125-2139. [PMC free article: PMC11534319] [PubMed: 38919026]

14.

Schwalbe EC, Lindsey JC, Nakjang S, Crosier S, Smith AJ, Hicks D, Rafiee G, Hill RM, Iliasova A, Stone T, Pizer B, Michalski A, Joshi A, Wharton SB, Jacques TS, Bailey S, Williamson D, Clifford SC. Novel molecular subgroups for clinical classification and outcome prediction in childhood medulloblastoma: a cohort study. Lancet Oncol. 2017 Jul;18(7):958-971. [PMC free article: PMC5489698] [PubMed: 28545823]

15.

Northcott PA, Buchhalter I, Morrissy AS, Hovestadt V, Weischenfeldt J, Ehrenberger T, Gröbner S, Segura-Wang M, Zichner T, Rudneva VA, Warnatz HJ, Sidiropoulos N, Phillips AH, Schumacher S, Kleinheinz K, Waszak SM, Erkek S, Jones DTW, Worst BC, Kool M, Zapatka M, Jäger N, Chavez L, Hutter B, Bieg M, Paramasivam N, Heinold M, Gu Z, Ishaque N, Jäger-Schmidt C, Imbusch CD, Jugold A, Hübschmann D, Risch T, Amstislavskiy V, Gonzalez FGR, Weber UD, Wolf S, Robinson GW, Zhou X, Wu G, Finkelstein D, Liu Y, Cavalli FMG, Luu B, Ramaswamy V, Wu X, Koster J, Ryzhova M, Cho YJ, Pomeroy SL, Herold-Mende C, Schuhmann M, Ebinger M, Liau LM, Mora J, McLendon RE, Jabado N, Kumabe T, Chuah E, Ma Y, Moore RA, Mungall AJ, Mungall KL, Thiessen N, Tse K, Wong T, Jones SJM, Witt O, Milde T, Von Deimling A, Capper D, Korshunov A, Yaspo ML, Kriwacki R, Gajjar A, Zhang J, Beroukhim R, Fraenkel E, Korbel JO, Brors B, Schlesner M, Eils R, Marra MA, Pfister SM, Taylor MD, Lichter P. The whole-genome landscape of medulloblastoma subtypes. Nature. 2017 Jul 19;547(7663):311-317. [PMC free article: PMC5905700] [PubMed: 28726821]

16.

Williams LA, Richardson M, Marcotte EL, Poynter JN, Spector LG. Sex ratio among childhood cancers by single year of age. Pediatr Blood Cancer. 2019 Jun;66(6):e27620. [PMC free article: PMC6472964] [PubMed: 30815990]

17.

Muskens IS, Feng Q, Francis SS, Walsh KM, Mckean-Cowdin R, Gauderman WJ, de Smith AJ, Wiemels JL. Pediatric glioma and medulloblastoma risk and population demographics: a Poisson regression analysis. Neurooncol Adv. 2020 Jan-Dec;2(1):vdaa089. [PMC free article: PMC7447139] [PubMed: 32864610]

18.

Taylor MD, Northcott PA, Korshunov A, Remke M, Cho YJ, Clifford SC, Eberhart CG, Parsons DW, Rutkowski S, Gajjar A, Ellison DW, Lichter P, Gilbertson RJ, Pomeroy SL, Kool M, Pfister SM. Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol. 2012 Apr;123(4):465-72. [PMC free article: PMC3306779] [PubMed: 22134537]

19.

Juraschka K, Taylor MD. Medulloblastoma in the age of molecular subgroups: a review. J Neurosurg Pediatr. 2019 Oct 01;24(4):353-363. [PubMed: 31574483]

20.

Raffel C. Medulloblastoma: molecular genetics and animal models. Neoplasia. 2004 Jul-Aug;6(4):310-22. [PMC free article: PMC1502113] [PubMed: 15256053]

21.

Crawford JR, MacDonald TJ, Packer RJ. Medulloblastoma in childhood: new biological advances. Lancet Neurol. 2007 Dec;6(12):1073-85. [PubMed: 18031705]

22.

Mahajan S, Suri V, Sahu S, Sharma MC, Sarkar C. World Health Organization Classification of Tumors of the Central Nervous System 5^th Edition (WHO CNS5): What's new? Indian J Pathol Microbiol. 2022 May;65(Supplement):S5-S13. [PubMed: 35562129]

23.

Kleihues P, Louis DN, Scheithauer BW, Rorke LB, Reifenberger G, Burger PC, Cavenee WK. The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol. 2002 Mar;61(3):215-25; discussion 226-9. [PubMed: 11895036]

24.

Dangouloff-Ros V, Varlet P, Levy R, Beccaria K, Puget S, Dufour C, Boddaert N. Imaging features of medulloblastoma: Conventional imaging, diffusion-weighted imaging, perfusion-weighted imaging, and spectroscopy: From general features to subtypes and characteristics. Neurochirurgie. 2021 Feb;67(1):6-13. [PubMed: 30170827]

25.

Gajjar A, Mahajan A, Bale T, Bowers DC, Canan L, Chi S, Cluster A, Cohen K, Cole B, Coven S, Darlington W, Dorris K, Elster J, Ermoian R, Franson A, George E, Helgager J, Landi D, Lin C, Metrock L, Nanda R, Palmer J, Partap S, Plant A, Pruthi S, Reynolds R, Stearns D, Storm P, Wang A, Wang LD, Whipple N, Zaky W, McMillian N, Ramakrishnan S. Pediatric Central Nervous System Cancers, Version 2.2025, NCCN Clinical Practice Guidelines In Oncology. J Natl Compr Canc Netw. 2025 Mar;23(3):113-130. [PubMed: 40073837]

26.

Michalski JM, Janss AJ, Vezina LG, Smith KS, Billups CA, Burger PC, Embry LM, Cullen PL, Hardy KK, Pomeroy SL, Bass JK, Perkins SM, Merchant TE, Colte PD, Fitzgerald TJ, Booth TN, Cherlow JM, Muraszko KM, Hadley J, Kumar R, Han Y, Tarbell NJ, Fouladi M, Pollack IF, Packer RJ, Li Y, Gajjar A, Northcott PA. Children's Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy With Chemotherapy for Newly Diagnosed Average-Risk Medulloblastoma. J Clin Oncol. 2021 Aug 20;39(24):2685-2697. [PMC free article: PMC8376317] [PubMed: 34110925]

27.

Donahue B, Marymont MA, Kessel S, Iandoli MK, Fitzgerald T, Holmes E, Kocak M, Boyett JM, Gajjar A, Packer RJ. Radiation therapy quality in CCG/POG intergroup 9961: implications for craniospinal irradiation and the posterior fossa boost in future medulloblastoma trials. Front Oncol. 2012;2:185. [PMC free article: PMC3540930] [PubMed: 23316474]

28.

Leary SES, Packer RJ, Li Y, Billups CA, Smith KS, Jaju A, Heier L, Burger P, Walsh K, Han Y, Embry L, Hadley J, Kumar R, Michalski J, Hwang E, Gajjar A, Pollack IF, Fouladi M, Northcott PA, Olson JM. Efficacy of Carboplatin and Isotretinoin in Children With High-risk Medulloblastoma: A Randomized Clinical Trial From the Children's Oncology Group. JAMA Oncol. 2021 Sep 01;7(9):1313-1321. [PMC free article: PMC8299367] [PubMed: 34292305]

29.

Rutkowski S, Cohen B, Finlay J, Luksch R, Ridola V, Valteau-Couanet D, Hara J, Garre ML, Grill J. Medulloblastoma in young children. Pediatr Blood Cancer. 2010 Apr;54(4):635-7. [PubMed: 20146217]

30.

Dhall G, Grodman H, Ji L, Sands S, Gardner S, Dunkel IJ, McCowage GB, Diez B, Allen JC, Gopalan A, Cornelius AS, Termuhlen A, Abromowitch M, Sposto R, Finlay JL. Outcome of children less than three years old at diagnosis with non-metastatic medulloblastoma treated with chemotherapy on the "Head Start" I and II protocols. Pediatr Blood Cancer. 2008 Jun;50(6):1169-75. [PubMed: 18293379]

31.

Dhall G, O'Neil SH, Ji L, Haley K, Whitaker AM, Nelson MD, Gilles F, Gardner SL, Allen JC, Cornelius AS, Pradhan K, Garvin JH, Olshefski RS, Hukin J, Comito M, Goldman S, Atlas MP, Walter AW, Sands S, Sposto R, Finlay JL. Excellent outcome of young children with nodular desmoplastic medulloblastoma treated on "Head Start" III: a multi-institutional, prospective clinical trial. Neuro Oncol. 2020 Dec 18;22(12):1862-1872. [PMC free article: PMC7746930] [PubMed: 32304218]

32.

Robinson GW, Rudneva VA, Buchhalter I, Billups CA, Waszak SM, Smith KS, Bowers DC, Bendel A, Fisher PG, Partap S, Crawford JR, Hassall T, Indelicato DJ, Boop F, Klimo P, Sabin ND, Patay Z, Merchant TE, Stewart CF, Orr BA, Korbel JO, Jones DTW, Sharma T, Lichter P, Kool M, Korshunov A, Pfister SM, Gilbertson RJ, Sanders RP, Onar-Thomas A, Ellison DW, Gajjar A, Northcott PA. Risk-adapted therapy for young children with medulloblastoma (SJYC07): therapeutic and molecular outcomes from a multicentre, phase 2 trial. Lancet Oncol. 2018 Jun;19(6):768-784. [PMC free article: PMC6078206] [PubMed: 29778738]

33.

Mazewski C, Leary SES, Kang G, Li BK, Kellie S, Hayes L, Shaw D, Ho B, Reddy A, Gossett J, Burger PC, Judkins AR, Aridgides P, Geyer JR, Gajjar A, Pollack IF, Fouladi M, Huang A. Phase 3 randomized trial of high-dose methotrexate for young children with high-risk embryonal brain tumors: A report from the Children's Oncology Group. Neuro Oncol. 2025 Oct 01;27(10):2726-2737. [PMC free article: PMC12833527] [PubMed: 40485042]

34.

Bagchi A, Dhanda SK, Dunphy P, Sioson E, Robinson GW. Molecular Classification Improves Therapeutic Options for Infants and Young Children With Medulloblastoma. J Natl Compr Canc Netw. 2023 Aug 28;21(10):1097-1105. [PMC free article: PMC10765405] [PubMed: 37643637]

35.

Dasgupta A, Maitre M, Pungavkar S, Gupta T. Magnetic Resonance Imaging in the Contemporary Management of Medulloblastoma: Current and Emerging Applications. Methods Mol Biol. 2022;2423:187-214. [PubMed: 34978700]

36.

Thompson EM, Hielscher T, Bouffet E, Remke M, Luu B, Gururangan S, McLendon RE, Bigner DD, Lipp ES, Perreault S, Cho YJ, Grant G, Kim SK, Lee JY, Rao AAN, Giannini C, Li KKW, Ng HK, Yao Y, Kumabe T, Tominaga T, Grajkowska WA, Perek-Polnik M, Low DCY, Seow WT, Chang KTE, Mora J, Pollack IF, Hamilton RL, Leary S, Moore AS, Ingram WJ, Hallahan AR, Jouvet A, Fèvre-Montange M, Vasiljevic A, Faure-Conter C, Shofuda T, Kagawa N, Hashimoto N, Jabado N, Weil AG, Gayden T, Wataya T, Shalaby T, Grotzer M, Zitterbart K, Sterba J, Kren L, Hortobágyi T, Klekner A, László B, Pócza T, Hauser P, Schüller U, Jung S, Jang WY, French PJ, Kros JM, van Veelen MC, Massimi L, Leonard JR, Rubin JB, Vibhakar R, Chambless LB, Cooper MK, Thompson RC, Faria CC, Carvalho A, Nunes S, Pimentel J, Fan X, Muraszko KM, López-Aguilar E, Lyden D, Garzia L, Shih DJH, Kijima N, Schneider C, Adamski J, Northcott PA, Kool M, Jones DTW, Chan JA, Nikolic A, Garre ML, Van Meir EG, Osuka S, Olson JJ, Jahangiri A, Castro BA, Gupta N, Weiss WA, Moxon-Emre I, Mabbott DJ, Lassaletta A, Hawkins CE, Tabori U, Drake J, Kulkarni A, Dirks P, Rutka JT, Korshunov A, Pfister SM, Packer RJ, Ramaswamy V, Taylor MD. Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis. Lancet Oncol. 2016 Apr;17(4):484-495. [PMC free article: PMC4907853] [PubMed: 26976201]

37.

Albright AL, Wisoff JH, Zeltzer PM, Boyett JM, Rorke LB, Stanley P. Effects of medulloblastoma resections on outcome in children: a report from the Children's Cancer Group. Neurosurgery. 1996 Feb;38(2):265-71. [PubMed: 8869053]

38.

Dewan MC, Lim J, Shannon CN, Wellons JC. The durability of endoscopic third ventriculostomy and ventriculoperitoneal shunts in children with hydrocephalus following posterior fossa tumor resection: a systematic review and time-to-failure analysis. J Neurosurg Pediatr. 2017 May;19(5):578-584. [PubMed: 28291428]

39.

Shabo E, Potthoff AL, Zeyen T, Layer JP, Ehrentraut S, Scorzin J, Lehmann F, Lehnen NC, Banat M, Weller J, Gessler F, Paech D, Hamed M, Borger V, Radbruch A, Herrlinger U, Weinhold L, Vatter H, Schneider M. Transient and permanent hydrocephalus following resection of brain metastases located in the posterior fossa: incidence, risk factors and the necessity of perioperative external ventricular drainage placement. J Neurooncol. 2025 Feb;171(3):681-689. [PMC free article: PMC11729202] [PubMed: 39607570]

40.

Lino-Filho AM, da Silva Andrade WM, de Morais WJ, Amorim JBS, Fernandes MNF, de O Teixeira Alvares GC, Morais BA, de Oliveira Júnior JP, Ribeiro PRJ. Endoscopic third ventriculostomy versus ventriculoperitoneal shunt in the treatment of hydrocephalus due to posterior fossa tumors in children: an updated meta-analysis. Childs Nerv Syst. 2026 Jan 06;42(1):9. [PubMed: 41491096]

41.

Korah MP, Esiashvili N, Mazewski CM, Hudgins RJ, Tighiouart M, Janss AJ, Schwaibold FP, Crocker IR, Curran WJ, Marcus RB. Incidence, risks, and sequelae of posterior fossa syndrome in pediatric medulloblastoma. Int J Radiat Oncol Biol Phys. 2010 May 01;77(1):106-12. [PubMed: 19695790]

42.

Schreiber JE, Palmer SL, Conklin HM, Mabbott DJ, Swain MA, Bonner MJ, Chapieski ML, Huang L, Zhang H, Gajjar A. Posterior fossa syndrome and long-term neuropsychological outcomes among children treated for medulloblastoma on a multi-institutional, prospective study. Neuro Oncol. 2017 Nov 29;19(12):1673-1682. [PMC free article: PMC5716082] [PubMed: 29016818]

43.

Robertson PL, Muraszko KM, Holmes EJ, Sposto R, Packer RJ, Gajjar A, Dias MS, Allen JC., Children's Oncology Group. Incidence and severity of postoperative cerebellar mutism syndrome in children with medulloblastoma: a prospective study by the Children's Oncology Group. J Neurosurg. 2006 Dec;105(6 Suppl):444-51. [PubMed: 17184075]

44.

Salman A, Fahim MAA, Sohail A, Bashir HH, Haizel-Cobbina J, Dewan MC, Shamim MS. Pre-operative and intra-operative risk factors of post-operative cerebellar mutism syndrome in pediatric patients undergoing posterior fossa tumor surgery: a systematic review. Childs Nerv Syst. 2026 Jan 19;42(1):36. [PubMed: 41549288]

45.

Unnikrishnan S, Yip AT, Qian AS, Salans MA, Yu JD, Huynh-Le MP, Reyes A, Stasenko A, McDonald C, Kaner R, Crawford JR, Hattangadi-Gluth JA. Neurocognitive Outcomes in Multiethnic Pediatric Brain Tumor Patients Treated With Proton Versus Photon Radiation. J Pediatr Hematol Oncol. 2023 Oct 01;45(7):e837-e846. [PMC free article: PMC10538429] [PubMed: 37539987]

46.

Bernier V, Klein O. Late effects of craniospinal irradiation for medulloblastomas in paediatric patients. Neurochirurgie. 2021 Feb;67(1):83-86. [PubMed: 30149928]

47.

Ramaswamy V, Remke M, Bouffet E, Bailey S, Clifford SC, Doz F, Kool M, Dufour C, Vassal G, Milde T, Witt O, von Hoff K, Pietsch T, Northcott PA, Gajjar A, Robinson GW, Padovani L, André N, Massimino M, Pizer B, Packer R, Rutkowski S, Pfister SM, Taylor MD, Pomeroy SL. Risk stratification of childhood medulloblastoma in the molecular era: the current consensus. Acta Neuropathol. 2016 Jun;131(6):821-31. [PMC free article: PMC4867119] [PubMed: 27040285]

48.

Lannering B, Rutkowski S, Doz F, Pizer B, Gustafsson G, Navajas A, Massimino M, Reddingius R, Benesch M, Carrie C, Taylor R, Gandola L, Björk-Eriksson T, Giralt J, Oldenburger F, Pietsch T, Figarella-Branger D, Robson K, Forni M, Clifford SC, Warmuth-Metz M, von Hoff K, Faldum A, Mosseri V, Kortmann R. Hyperfractionated versus conventional radiotherapy followed by chemotherapy in standard-risk medulloblastoma: results from the randomized multicenter HIT-SIOP PNET 4 trial. J Clin Oncol. 2012 Sep 10;30(26):3187-93. [PubMed: 22851561]

49.

Wang S, Zhang D, Wang C, Liu Y. MYC promotes group 3 medulloblastoma cell proliferation and alleviates ROS-induced cell death by upregulating transketolase. Acta Neuropathol Commun. 2025 Jun 28;13(1):139. [PMC free article: PMC12205496] [PubMed: 40581635]

50.

Northcott PA, Robinson GW, Kratz CP, Mabbott DJ, Pomeroy SL, Clifford SC, Rutkowski S, Ellison DW, Malkin D, Taylor MD, Gajjar A, Pfister SM. Medulloblastoma. Nat Rev Dis Primers. 2019 Feb 14;5(1):11. [PubMed: 30765705]

51.

Cohen KJ, Munjapara V, Aguilera D, Castellino RC, Stapleton SL, Landi D, Ashley DM, Rodriguez FJ, Hawkins C, Yang E, London W, Chi S, Bandopadhayay P. A Pilot Study Omitting Radiation in the Treatment of Children with Newly Diagnosed Wnt-Activated Medulloblastoma. Clin Cancer Res. 2023 Dec 15;29(24):5031-5037. [PubMed: 37498309]

52.

Coltin H, Pequeno P, Liu N, Tsang DS, Gupta S, Taylor MD, Bouffet E, Nathan PC, Ramaswamy V. The Burden of Surviving Childhood Medulloblastoma: A Population-Based, Matched Cohort Study in Ontario, Canada. J Clin Oncol. 2023 May 01;41(13):2372-2381. [PMC free article: PMC10150896] [PubMed: 36696605]

53.

Aktekin EH, Kütük MÖ, Sangün Ö, Yazıcı N, Çaylaklı F, Erol İ, Sarıalioğlu F. Late effects of medulloblastoma treatment: multidisciplinary approach of survivors. Childs Nerv Syst. 2024 Feb;40(2):417-425. [PubMed: 37698649]

54.

Nantavithya C, Paulino AC, Liao K, Woodhouse KD, McGovern SL, Grosshans DR, McAleer MF, Khatua S, Chintagumpala MM, Majd N, Zaky W, Yeboa DN. Observed-to-expected incidence ratios of second malignant neoplasms after radiation therapy for medulloblastoma: A Surveillance, Epidemiology, and End Results analysis. Cancer. 2021 Jul 01;127(13):2368-2375. [PubMed: 33721338]

Disclosure: Allison Guild declares no relevant financial relationships with ineligible companies.

Disclosure: Sidharth Mahapatra declares no relevant financial relationships with ineligible companies.

Disclosure: Chittalsinh Raulji declares no relevant financial relationships with ineligible companies.

Disclosure: Torin Karsonovich declares no relevant financial relationships with ineligible companies.

Disclosure: Mark Amsbaugh declares no relevant financial relationships with ineligible companies.