Refining M1 stage in medulloblastoma: criteria for cerebrospinal fluid cytology and implications for improved risk stratification from the HIT-2000 trial.


Journal

European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373

Informations de publication

Date de publication:
03 2022
Historique:
received: 26 10 2021
revised: 21 12 2021
accepted: 27 12 2021
pubmed: 13 2 2022
medline: 22 4 2022
entrez: 12 2 2022
Statut: ppublish

Résumé

Medulloblastoma is the most common malignant paediatric brain tumour, and cerebrospinal fluid (CSF) dissemination (M1 stage) is a high-risk prognostic factor. Criteria for CSF evaluation and for differentiating M0 from M1 stage are not clearly defined, and the prognostic significance of M1 stage in this context is unknown. CSF investigations from 405 patients with medulloblastoma of the prospective multicenter trial HIT-2000 (HIirnTumor-2000) were reviewed. Data from 213 patients aged ≥4 years were related to 5-year progression-free (5y-PFS) and overall survival. Patients with cytological tumour dissemination only (M1 stage only) aged ≥4 years (n = 18) and patients with radiologically detected metastases (M2/3, n = 85) showed a worse 5y-PFS than M0 patients (n = 110) without signs of metastatic disease (5y-PFS 61.1% and 59.6% vs 80.7%; p < 0.02 and p < 0.01, log rank). Patients with positive samples drawn early after surgery who turned negative within 14 days postoperatively (n = 9) and patients with atypical cells (n = 6) showed a 5y-PFS similar to M0 patients. No tumour cells were detected in samples containing <10 nucleated cells. Analysis of cytological criteria showed a better predictive value for tumour cell clusters than ≥2 individual tumour cells. Based on our results, we suggest that CSF medulloblastoma staging should be performed 14 days postoperatively by lumbar puncture, and specimens should contain at least 10 nucleated cells. Cytological tumour dissemination alone (M1 stage only) appears a high-risk prognostic factor associated with an outcome comparable to M2/M3 stage. Tumour cell clusters seem to have a greater impact on prognosis than single tumour cells. This should be validated further.

Sections du résumé

BACKGROUND
Medulloblastoma is the most common malignant paediatric brain tumour, and cerebrospinal fluid (CSF) dissemination (M1 stage) is a high-risk prognostic factor. Criteria for CSF evaluation and for differentiating M0 from M1 stage are not clearly defined, and the prognostic significance of M1 stage in this context is unknown.
PATIENTS AND METHODS
CSF investigations from 405 patients with medulloblastoma of the prospective multicenter trial HIT-2000 (HIirnTumor-2000) were reviewed. Data from 213 patients aged ≥4 years were related to 5-year progression-free (5y-PFS) and overall survival.
RESULTS
Patients with cytological tumour dissemination only (M1 stage only) aged ≥4 years (n = 18) and patients with radiologically detected metastases (M2/3, n = 85) showed a worse 5y-PFS than M0 patients (n = 110) without signs of metastatic disease (5y-PFS 61.1% and 59.6% vs 80.7%; p < 0.02 and p < 0.01, log rank). Patients with positive samples drawn early after surgery who turned negative within 14 days postoperatively (n = 9) and patients with atypical cells (n = 6) showed a 5y-PFS similar to M0 patients. No tumour cells were detected in samples containing <10 nucleated cells. Analysis of cytological criteria showed a better predictive value for tumour cell clusters than ≥2 individual tumour cells.
CONCLUSION
Based on our results, we suggest that CSF medulloblastoma staging should be performed 14 days postoperatively by lumbar puncture, and specimens should contain at least 10 nucleated cells. Cytological tumour dissemination alone (M1 stage only) appears a high-risk prognostic factor associated with an outcome comparable to M2/M3 stage. Tumour cell clusters seem to have a greater impact on prognosis than single tumour cells. This should be validated further.

Identifiants

pubmed: 35151105
pii: S0959-8049(22)00004-1
doi: 10.1016/j.ejca.2021.12.032
pii:
doi:

Types de publication

Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

30-38

Informations de copyright

Copyright © 2022 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest statement The authors declare that they have no conflict of interest.

Auteurs

Christian Hagel (C)

Institute of Neuropathology, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany. Electronic address: hagel@uke.de.

Veronika Sloman (V)

Department of Pediatric Hematology and Oncology, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany.

Martin Mynarek (M)

Department of Pediatric Hematology and Oncology, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany.

Katharina Petrasch (K)

Department of Pediatric Hematology and Oncology, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany.

Denise Obrecht (D)

Department of Pediatric Hematology and Oncology, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany.

Joachim Kühl (J)

Department of Pediatric Hematology and Oncology, University Children's Hospital Wuerzburg, Germany.

Frank Deinlein (F)

Department of Pediatric Hematology and Oncology, University Children's Hospital Wuerzburg, Germany.

Renate Schmid (R)

Department of Pediatric Hematology and Oncology, University Children's Hospital Wuerzburg, Germany.

André O von Bueren (AO)

Department of Pediatrics, Obstetrics and Gynecology, Division of Pediatric Hematology and Oncology, University Hospital of Geneva, Geneva, Switzerland.

Carsten Friedrich (C)

Department of General Pediatrics and Pediatric Hematology/Oncology, University Children's Hospital, Klinikum Oldenburg AöR, Oldenburg, Germany.

B Ole Juhnke (BO)

Department of Pediatric Hematology and Oncology, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany.

Nicolas U Gerber (NU)

Department of Oncology, University Children's Hospital Zurich, Zurich, Switzerland.

Robert Kwiecien (R)

Institut für Biometrie und Klinische Forschung, Universitätsklinikum Münster, Münster, Germany.

Hermann Girschick (H)

Kinder- und Jugendmedizin, Vivantes-Klinikum, Berlin Friedrichshain, Berlin, Germany.

Alexandra Höller (A)

Institute of Medical Biometry and Epidemiology, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany.

Antonia Zapf (A)

Institute of Medical Biometry and Epidemiology, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany.

Katja von Hoff (K)

Department of Pediatric Hematology and Oncology, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany; Department of Pediatric Oncology/Hematology, Charité-University Medicine Berlin, Germany.

Stefan Rutkowski (S)

Department of Pediatric Hematology and Oncology, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany.

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Classifications MeSH