Medulloblastoma in adults: evaluation of the Dutch society for neuro-oncology treatment protocol

L. Bleeker; M. C. M. Kouwenhoven; I. de Heer; B. I. Lissenberg-Witte; A. H. Gijsbers; H. J. Dubbink; J. M. Kros; J. M. M. Gijtenbeek; E. Kurt; C. C. D. van der Rijt; A. T. Swaak-Kragten; F. Y. de Vos; H. L. van der Weide; P. J. French; M. J. van den Bent; P. Wesseling; J. E. C. Bromberg

doi:10.1007/s11060-023-04285-8

Medulloblastoma in adults: evaluation of the Dutch society for neuro-oncology treatment protocol

L. Bleeker^*
, M. C. M. Kouwenhoven
, I. de Heer
, B. I. Lissenberg-Witte
, A. H. Gijsbers
, H. J. Dubbink
, J. M. Kros
, J. M. M. Gijtenbeek
, E. Kurt
, C. C. D. van der Rijt
, A. T. Swaak-Kragten
, F. Y. de Vos
, H. L. van der Weide
, P. J. French
, M. J. van den Bent
, P. Wesseling
, J. E. C. Bromberg

^*Corresponding author for this work

Department of Surgery, Amsterdam UMC, Amsterdam, the Netherlands
Erasmus University Rotterdam
The Nationwide Network and Registry of Histo- and Cytopathology in the Netherlands (PALGA, Houten, The Netherlands
Radboud University Medical Center
University Medical Center Utrecht
University of Groningen, University Medical Center Groningen
Amsterdam UMC - University of Amsterdam
Princess Máxima Center for Pediatric Oncology
Amsterdam Cardiovascular Sciences Research Institute, Amsterdam UMC, Amsterdam, The Netherlands
Erasmus MC Cancer Institute
Dutch Nationwide Network and Registry of Histo- and Cytopathology
Radboud University Nijmegen
Utrecht University
University of Groningen
Amsterdam University Medical Centers

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Abstract

Purpose: Medulloblastoma is a rare tumor in adults. The objective of this nationwide, multicenter study was to evaluate the toxicity and efficacy of the Dutch treatment protocol for adult medulloblastoma patients. Methods: Adult medulloblastoma patients diagnosed between 2010 and 2018 were identified in the Dutch rare tumors registry or nationwide pathology database. Patients with intention to treat according to the national treatment protocol were included. Risk stratification was performed based on residual disease, histological subtype and extent of disease. All patients received postoperative radiotherapy [craniospinal axis 36 Gy/fossa posterior boost 19.8 Gy (14.4 Gy in case of metastases)]. High-risk patients received additional neoadjuvant (carboplatin-etoposide), concomitant (vincristine) and adjuvant chemotherapy (carboplatin-vincristine-cyclophosphamide) as far as feasible by toxicity. Methylation profiling, and additional next-generation sequencing in case of SHH-activated medulloblastomas, were performed. Results: Forty-seven medulloblastoma patients were identified, of whom 32 were treated according to the protocol. Clinical information and tumor material was available for 28 and 20 patients, respectively. The histological variants were mainly classic (43%) and desmoplastic medulloblastoma (36%). Sixteen patients (57%) were considered standard-risk and 60% were SHH-activated medulloblastomas. Considerable treatment reductions and delays in treatment occurred due to especially hematological and neurotoxicity. Only one high-risk patient could complete all chemotherapy courses. 5-years progression-free survival (PFS) and overall survival (OS) for standard-risk patients appeared worse than for high-risk patients (PFS 69% vs. 90%, OS 81% vs. 90% respectively), although this wasn’t statistically significant. Conclusion: Combined chemo-radiotherapy is a toxic regimen for adult medulloblastoma patients that may result in improved survival.

Original language	English
Pages (from-to)	225-235
Number of pages	11
Journal	Journal of neuro-oncology
Volume	162
Issue number	1
Early online date	2023
DOIs	https://doi.org/10.1007/s11060-023-04285-8
Publication status	Published - 1 Mar 2023

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Adults
Medulloblastoma
Methylation array
Toxicity
Treatment

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Medulloblastoma-in-adults.pdfFinal published version, 1.1 MBLicence: CC BY

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Bleeker, L., Kouwenhoven, M. C. M., de Heer, I., Lissenberg-Witte, B. I., Gijsbers, A. H., Dubbink, H. J., Kros, J. M., Gijtenbeek, J. M. M., Kurt, E., van der Rijt, C. C. D., Swaak-Kragten, A. T., de Vos, F. Y., van der Weide, H. L., French, P. J., van den Bent, M. J., Wesseling, P., & Bromberg, J. E. C. (2023). Medulloblastoma in adults: evaluation of the Dutch society for neuro-oncology treatment protocol. Journal of neuro-oncology, 162(1), 225-235. https://doi.org/10.1007/s11060-023-04285-8

@article{880747a3e7e3411c991fc7250d7c7cb7,

title = "Medulloblastoma in adults: evaluation of the Dutch society for neuro-oncology treatment protocol",

abstract = "Purpose: Medulloblastoma is a rare tumor in adults. The objective of this nationwide, multicenter study was to evaluate the toxicity and efficacy of the Dutch treatment protocol for adult medulloblastoma patients. Methods: Adult medulloblastoma patients diagnosed between 2010 and 2018 were identified in the Dutch rare tumors registry or nationwide pathology database. Patients with intention to treat according to the national treatment protocol were included. Risk stratification was performed based on residual disease, histological subtype and extent of disease. All patients received postoperative radiotherapy [craniospinal axis 36 Gy/fossa posterior boost 19.8 Gy (14.4 Gy in case of metastases)]. High-risk patients received additional neoadjuvant (carboplatin-etoposide), concomitant (vincristine) and adjuvant chemotherapy (carboplatin-vincristine-cyclophosphamide) as far as feasible by toxicity. Methylation profiling, and additional next-generation sequencing in case of SHH-activated medulloblastomas, were performed. Results: Forty-seven medulloblastoma patients were identified, of whom 32 were treated according to the protocol. Clinical information and tumor material was available for 28 and 20 patients, respectively. The histological variants were mainly classic (43\%) and desmoplastic medulloblastoma (36\%). Sixteen patients (57\%) were considered standard-risk and 60\% were SHH-activated medulloblastomas. Considerable treatment reductions and delays in treatment occurred due to especially hematological and neurotoxicity. Only one high-risk patient could complete all chemotherapy courses. 5-years progression-free survival (PFS) and overall survival (OS) for standard-risk patients appeared worse than for high-risk patients (PFS 69\% vs. 90\%, OS 81\% vs. 90\% respectively), although this wasn{\textquoteright}t statistically significant. Conclusion: Combined chemo-radiotherapy is a toxic regimen for adult medulloblastoma patients that may result in improved survival.",

keywords = "Adults, Medulloblastoma, Methylation array, Toxicity, Treatment",

author = "L. Bleeker and Kouwenhoven, \{M. C. M.\} and \{de Heer\}, I. and Lissenberg-Witte, \{B. I.\} and Gijsbers, \{A. H.\} and Dubbink, \{H. J.\} and Kros, \{J. M.\} and Gijtenbeek, \{J. M. M.\} and E. Kurt and \{van der Rijt\}, \{C. C. D.\} and Swaak-Kragten, \{A. T.\} and \{de Vos\}, \{F. Y.\} and \{van der Weide\}, \{H. L.\} and French, \{P. J.\} and \{van den Bent\}, \{M. J.\} and P. Wesseling and Bromberg, \{J. E. C.\}",

note = "Funding Information: C.C.D. van der Rijt received grants from the Netherlands Organization for Health Research and Development and KWF personal fees from Lilly (via her institution) both outside the work described in the manuscript. Other authors have no conflicts of interest. Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = mar,

day = "1",

doi = "10.1007/s11060-023-04285-8",

language = "English",

volume = "162",

pages = "225--235",

journal = "Journal of neuro-oncology",

issn = "0167-594X",

publisher = "Kluwer Academic Publishers",

number = "1",

}

Bleeker, L, Kouwenhoven, MCM, de Heer, I, Lissenberg-Witte, BI, Gijsbers, AH, Dubbink, HJ, Kros, JM, Gijtenbeek, JMM, Kurt, E, van der Rijt, CCD, Swaak-Kragten, AT, de Vos, FY, van der Weide, HL, French, PJ, van den Bent, MJ, Wesseling, P & Bromberg, JEC 2023, 'Medulloblastoma in adults: evaluation of the Dutch society for neuro-oncology treatment protocol', Journal of neuro-oncology, vol. 162, no. 1, pp. 225-235. https://doi.org/10.1007/s11060-023-04285-8

TY - JOUR

T1 - Medulloblastoma in adults

T2 - evaluation of the Dutch society for neuro-oncology treatment protocol

AU - Bleeker, L.

AU - Kouwenhoven, M. C. M.

AU - de Heer, I.

AU - Lissenberg-Witte, B. I.

AU - Gijsbers, A. H.

AU - Dubbink, H. J.

AU - Kros, J. M.

AU - Gijtenbeek, J. M. M.

AU - Kurt, E.

AU - van der Rijt, C. C. D.

AU - Swaak-Kragten, A. T.

AU - de Vos, F. Y.

AU - van der Weide, H. L.

AU - French, P. J.

AU - van den Bent, M. J.

AU - Wesseling, P.

AU - Bromberg, J. E. C.

N1 - Funding Information: C.C.D. van der Rijt received grants from the Netherlands Organization for Health Research and Development and KWF personal fees from Lilly (via her institution) both outside the work described in the manuscript. Other authors have no conflicts of interest. Publisher Copyright: © 2023, The Author(s).

PY - 2023/3/1

Y1 - 2023/3/1

N2 - Purpose: Medulloblastoma is a rare tumor in adults. The objective of this nationwide, multicenter study was to evaluate the toxicity and efficacy of the Dutch treatment protocol for adult medulloblastoma patients. Methods: Adult medulloblastoma patients diagnosed between 2010 and 2018 were identified in the Dutch rare tumors registry or nationwide pathology database. Patients with intention to treat according to the national treatment protocol were included. Risk stratification was performed based on residual disease, histological subtype and extent of disease. All patients received postoperative radiotherapy [craniospinal axis 36 Gy/fossa posterior boost 19.8 Gy (14.4 Gy in case of metastases)]. High-risk patients received additional neoadjuvant (carboplatin-etoposide), concomitant (vincristine) and adjuvant chemotherapy (carboplatin-vincristine-cyclophosphamide) as far as feasible by toxicity. Methylation profiling, and additional next-generation sequencing in case of SHH-activated medulloblastomas, were performed. Results: Forty-seven medulloblastoma patients were identified, of whom 32 were treated according to the protocol. Clinical information and tumor material was available for 28 and 20 patients, respectively. The histological variants were mainly classic (43%) and desmoplastic medulloblastoma (36%). Sixteen patients (57%) were considered standard-risk and 60% were SHH-activated medulloblastomas. Considerable treatment reductions and delays in treatment occurred due to especially hematological and neurotoxicity. Only one high-risk patient could complete all chemotherapy courses. 5-years progression-free survival (PFS) and overall survival (OS) for standard-risk patients appeared worse than for high-risk patients (PFS 69% vs. 90%, OS 81% vs. 90% respectively), although this wasn’t statistically significant. Conclusion: Combined chemo-radiotherapy is a toxic regimen for adult medulloblastoma patients that may result in improved survival.

AB - Purpose: Medulloblastoma is a rare tumor in adults. The objective of this nationwide, multicenter study was to evaluate the toxicity and efficacy of the Dutch treatment protocol for adult medulloblastoma patients. Methods: Adult medulloblastoma patients diagnosed between 2010 and 2018 were identified in the Dutch rare tumors registry or nationwide pathology database. Patients with intention to treat according to the national treatment protocol were included. Risk stratification was performed based on residual disease, histological subtype and extent of disease. All patients received postoperative radiotherapy [craniospinal axis 36 Gy/fossa posterior boost 19.8 Gy (14.4 Gy in case of metastases)]. High-risk patients received additional neoadjuvant (carboplatin-etoposide), concomitant (vincristine) and adjuvant chemotherapy (carboplatin-vincristine-cyclophosphamide) as far as feasible by toxicity. Methylation profiling, and additional next-generation sequencing in case of SHH-activated medulloblastomas, were performed. Results: Forty-seven medulloblastoma patients were identified, of whom 32 were treated according to the protocol. Clinical information and tumor material was available for 28 and 20 patients, respectively. The histological variants were mainly classic (43%) and desmoplastic medulloblastoma (36%). Sixteen patients (57%) were considered standard-risk and 60% were SHH-activated medulloblastomas. Considerable treatment reductions and delays in treatment occurred due to especially hematological and neurotoxicity. Only one high-risk patient could complete all chemotherapy courses. 5-years progression-free survival (PFS) and overall survival (OS) for standard-risk patients appeared worse than for high-risk patients (PFS 69% vs. 90%, OS 81% vs. 90% respectively), although this wasn’t statistically significant. Conclusion: Combined chemo-radiotherapy is a toxic regimen for adult medulloblastoma patients that may result in improved survival.

KW - Adults

KW - Medulloblastoma

KW - Methylation array

KW - Toxicity

KW - Treatment

UR - https://www.scopus.com/pages/publications/85149958987

UR - https://www.ncbi.nlm.nih.gov/pubmed/36920679

U2 - 10.1007/s11060-023-04285-8

DO - 10.1007/s11060-023-04285-8

M3 - Article

C2 - 36920679

SN - 0167-594X

VL - 162

SP - 225

EP - 235

JO - Journal of neuro-oncology

JF - Journal of neuro-oncology

IS - 1

ER -

Medulloblastoma in adults: evaluation of the Dutch society for neuro-oncology treatment protocol

Abstract

UN SDGs

Keywords

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