Proposed Additions to the NCCN Guidelines for Adult Medulloblastoma

View More View Less
  • 1 Neuro-Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
Restricted access

Medulloblastoma is a rare brain tumor that occurs in both children and adults, with patients aged 15 to 39 years accounting for 30% of all cases. In adults, guidelines for diagnosis and treatment are often based on retrospective data and extrapolated from the pediatric experience due to limited availability of prospective trials or registries involving adults. Importantly, adult patients differ from pediatric patients in many aspects, including the molecular features of the tumor and tolerance to treatment. In 2017, the NCI was granted support from the Cancer Moonshot initiative to address the challenges and unmet needs of adults with rare central nervous system (CNS) tumors through the NCI Comprehensive Oncology Network for Evaluating Rare CNS Tumors (NCI-CONNECT). On November 25, 2019, NCI-CONNECT convened a multidisciplinary workshop on adult medulloblastoma. Working groups identified unmet needs in clinical care and research and developed specific action items, including a proposal for inclusion of new items in the NCCN Guidelines for Adult Medulloblastoma, delineated in this review along with the evidence supporting their incorporation. Recommendations included facilitating referral of patients to centers of excellence; promoting patient participation in clinical trials or registries; encouraging use of DNA methylation for confirmation of diagnosis and subgrouping; offering counseling on contraception and fertility preservation; evaluating patients for symptoms and medical management of endocrine, vision, hearing, and neurocognitive deficits; providing psychosocial support and referral to neurorehabilitation; minimizing delays in therapy; and incorporating imaging standards and criteria for progression.

Submitted June 11, 2020; accepted for publication September 2, 2020.

Disclosures: The authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.

Funding: This work was supported by funding from Cancer Moonshot (M.R.G.).

Correspondence: Marta Penas-Prado, MD, Neuro-Oncology Branch, National Cancer Institute, 9030 Old Georgetown Road, Building 82-213, Bethesda, MD 20892. Email: marta.penas-prado@nih.gov
  • 1.

    Nabors LB, Portnow J, Ahluwalia M, . NCCN Clinical Practice Guidelines in Oncology: Central Nervous System Cancers. Version 2.2020. Accessed May 23, 2020. To view the most recent version, visit NCCN.org

  • 2.

    Cosman R, Brown CS, DeBraganca KC, . Patterns of care in adult medulloblastoma: results of an international online survey. J Neurooncol 2014;120:125129.

  • 3.

    Penas-Prado M, Theeler BJ, Cordeiro B, . Proceedings of the Comprehensive Oncology Network Evaluating Rare CNS Tumors (NCI-CONNECT) Oligodendroglioma Workshop. Neurooncol Adv 2020;2:vdaa097.

    • Search Google Scholar
    • Export Citation
  • 4.

    Theeler BJ, Dalal Y, Monje M, . NCI-CONNECT: Comprehensive Oncology Network Evaluating Rare CNS Tumors—Histone Mutated Midline Glioma Workshop Proceedings. Neurooncol Adv 2020;2:vdaa007.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Mansouri A, Zadeh G. NCI-CONNECT rare CNS tumor initiative: current progress and anticipated future impact. Neurooncol Adv 2020;2:vdaa022.

  • 6.

    Penas-Prado M, Theeler BJ, Cordeiro B, . Proceedings of the Comprehensive Oncology Network Evaluating Rare CNS Tumors (NCI-CONNECT) Adult Medulloblastoma Workshop [published online August 17, 2020]. Neurooncol Adv, doi.org/10.1093/noajnl/vdaa097

    • Search Google Scholar
    • Export Citation
  • 7.

    Truitt G, Gittleman H, Leece R, . Partnership for defining the impact of 12 selected rare CNS tumors: a report from the CBTRUS and the NCI-CONNECT. J Neurooncol 2019;144:5363.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Majd N, Mastall M, Hess K, . RARE-47. Characterization of adult medulloblastoma: a retrospective review of 200 patients at MD Anderson Cancer Center [abstract]. Neuro Oncol 2019;21(Suppl 6):vi231232.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Majd N, Penas-Prado M. Updates on management of adult medulloblastoma. Curr Treat Options Oncol 2019;20:64.

  • 10.

    Franceschi E, Hofer S, Brandes AA, . EANO-EURACAN clinical practice guideline for diagnosis, treatment, and follow-up of post-pubertal and adult patients with medulloblastoma. Lancet Oncol 2019;20:e715728.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Penas-Prado M, Armstrong TS, Gilbert MR. Progress in rare central nervous system tumors. Curr Opin Neurol 2019;32:895906.

  • 12.

    Elrod JK, Fortenberry JL Jr. Centers of excellence in healthcare institutions: what they are and how to assemble them. BMC Health Serv Res 2017;17(Suppl 1):425.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Zhu P, Du XL, Zhu JJ, . Improved survival of glioblastoma patients treated at academic and high-volume facilities: a hospital-based study from the National Cancer Database. J Neurosurg 2020;132:491502.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14.

    Raj R, Seppä K, Luostarinen T, . Disparities in glioblastoma survival by case volume: a nationwide observational study. J Neurooncol 2020;147:361370.

  • 15.

    Zhu P, Du XL, Blanco AI, . Impact of facility type and volume in low-grade glioma outcomes [published online September 27, 2019]. J Neurosurg, doi:10.3171/2019.6.JNS19409 https://doi.org/10.3171/2019.6.JNS19409

    • Search Google Scholar
    • Export Citation
  • 16.

    Hauser A, Dutta SW, Showalter TN, . Impact of academic facility type and volume on post-surgical outcomes following diagnosis of glioblastoma. J Clin Neurosci 2018;47:103110.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Haque W, Verma V, Butler EB, . Definitive chemoradiation at high volume facilities is associated with improved survival in glioblastoma. J Neurooncol 2017;135:173181.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Patil VM, Pande N, Chandrasekharan A, . Shadow study: randomized comparison of clinic with video follow-up in glioma undergoing adjuvant temozolomide therapy. CNS Oncol 2018;7:CNS14.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Reider-Demer M, Raja P, Martin N, . Prospective and retrospective study of videoconference telemedicine follow-up after elective neurosurgery: results of a pilot program. Neurosurg Rev 2018;41:497501.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Abu Arja MH, Stanek JR, Morales La Madrid AE, . The Latin American Brain Tumor Board teleconference: results of a web-based survey to evaluate participant experience utilizing this resource. Childs Nerv Syst 2019;35:257265.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21.

    Qaddoumi I, Mansour A, Musharbash A, . Impact of telemedicine on pediatric neuro-oncology in a developing country: the Jordanian-Canadian experience. Pediatr Blood Cancer 2007;48:3943.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22.

    Lee EQ, Weller M, Sul J, . Optimizing eligibility criteria and clinical trial conduct to enhance clinical trial participation for primary brain tumor patients. Neuro Oncol 2020;22:601612.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Friedrich C, von Bueren AO, von Hoff K, . Treatment of adult nonmetastatic medulloblastoma patients according to the paediatric HIT 2000 protocol: a prospective observational multicentre study. Eur J Cancer 2013;49:893903.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24.

    von Bueren AO, Friedrich C, von Hoff K, . Metastatic medulloblastoma in adults: outcome of patients treated according to the HIT2000 protocol. Eur J Cancer 2015;51:24342443.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25.

    Louis DN, Perry A, Reifenberger G, . The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 2016;131:803820.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26.

    Capper D, Jones DTW, Sill M, . DNA methylation-based classification of central nervous system tumours. Nature 2018;555:469474.

  • 27.

    Siegel C, Armstrong T, Chung HJ, . PATH-40. Standardized molecular analysis of primary central nervous system (CNS) tumors in a research based clinical practice. An introduction to the CNS tumor next generation sequencing (NGS) panel. Neuro Oncol 2017;19(Suppl 6):vi179180.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28.

    Capper D, Stichel D, Sahm F, . Practical implementation of DNA methylation and copy-number-based CNS tumor diagnostics: the Heidelberg experience. Acta Neuropathol 2018;136:181210.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    D’Arcy CE, Nobre LF, Arnaldo A, . Immunohistochemical and nanoString-based subgrouping of clinical medulloblastoma samples. J Neuropathol Exp Neurol 2020;79:437447.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Korshunov A, Chavez L, Northcott PA, . DNA-methylation profiling discloses significant advantages over NanoString method for molecular classification of medulloblastoma. Acta Neuropathol 2017;134:965967.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31.

    Pietsch T, Schmidt R, Remke M, . Prognostic significance of clinical, histopathological, and molecular characteristics of medulloblastomas in the prospective HIT2000 multicenter clinical trial cohort. Acta Neuropathol 2014;128:137149.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32.

    Korshunov A, Remke M, Werft W, . Adult and pediatric medulloblastomas are genetically distinct and require different algorithms for molecular risk stratification. J Clin Oncol 2010;28:30543060.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Gondim DD, Gener MA, Curless KL, . Determining IDH-mutational status in gliomas using IDH1-R132H antibody and polymerase chain reaction. Appl Immunohistochem Mol Morphol 2019;27:722725.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Roshandel AK, Busch CM, Mullekom JV, . The predictive capability of immunohistochemistry and DNA sequencing for determining TP53 functional mutation status: a comparative study of 41 glioblastoma patients. Oncotarget 2019;10:62046218.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35.

    Brown AP, Barney CL, Grosshans DR, . Proton beam craniospinal irradiation reduces acute toxicity for adults with medulloblastoma. Int J Radiat Oncol Biol Phys 2013;86:277284.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Beier D, Proescholdt M, Reinert C, . Multicenter pilot study of radiochemotherapy as first-line treatment for adults with medulloblastoma (NOA-07). Neuro Oncol 2018;20:400410.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37.

    Harrison RA, Kesler SR, Johnson JM, . Neurocognitive dysfunction in adult cerebellar medulloblastoma. Psychooncology 2019;28:131138.

  • 38.

    Dirven L, Luerding R, Beier D, . Neurocognitive functioning and health-related quality of life in adult medulloblastoma patients: long-term outcomes of the NOA-07 study. J Neurooncol 2020;148:117130.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39.

    Landier W, Bhatia S, Eshelman DA, . Development of risk-based guidelines for pediatric cancer survivors: the Children’s Oncology Group Long-Term Follow-Up Guidelines from the Children’s Oncology Group Late Effects Committee and Nursing Discipline. J Clin Oncol 2004;22:49794990.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40.

    Coccia PF, Papo AS, Beaupin L, . NCCN Clinical Practice Guidelines in Oncology: Adolescent and Young Adult (AYA) Oncology. Version 2.2018. Accessed May 23, 2020. To view the most recent version, visit NCCN.org

  • 41.

    Amidei C. Symptom-based interventions to promote quality survivorship. Neuro Oncol 2018;20(Suppl 7):vii2739.

  • 42.

    Leeper H, Milbury K. Survivorship care planning and implementation in neuro-oncology. Neuro Oncol 2018;20(Suppl 7):vii4046.

  • 43.

    Leeper HE, Acquaye AA, Bell S, . Survivorship care planning in neuro-oncology. Neurooncol Pract 2018;5:39.

  • 44.

    Abacioglu U, Uzel O, Sengoz M, . Medulloblastoma in adults: treatment results and prognostic factors. Int J Radiat Oncol Biol Phys 2002;54:855860.

  • 45.

    Taylor RE, Bailey CC, Robinson K, . Results of a randomized study of preradiation chemotherapy versus radiotherapy alone for nonmetastatic medulloblastoma: the International Society of Paediatric Oncology/United Kingdom Children’s Cancer Study Group PNET-3 Study. J Clin Oncol 2003;21:15811591.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 46.

    Warren KE, Vezina G, Poussaint TY, . Response assessment in medulloblastoma and leptomeningeal seeding tumors: recommendations from the Response Assessment in Pediatric Neuro-Oncology committee. Neuro Oncol 2018;20:1323.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 47.

    Ellingson BM, Bendszus M, Boxerman J, . Consensus recommendations for a standardized brain tumor imaging protocol in clinical trials. Neuro Oncol 2015;17:11881198.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 48.

    Packer RJ, Gajjar A, Vezina G, . Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma. J Clin Oncol 2006;24:42024208.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 531 531 531
PDF Downloads 156 156 156
EPUB Downloads 0 0 0