Real-world data for pediatric medulloblastoma: can we improve outcomes?

Abstract

Medulloblastoma (MB) is a malignant embryonal tumor that develops especially in childhood, with overall survival (OS) at 5 years of up to 70%. The objective of this study is to analyze treatment delivery variables in a retrospective cohort and evaluate the impact of these treatment quality parameters on survival. From 2000 to 2018, 40 pediatric patients with medulloblastoma, treated according to current international protocols, were retrospectively analyzed. Treatment delivery quality indicators were analyzed including the extent of surgery, radiotherapy (RT) parameters, and chemotherapy variables, related with time and dose-intensity deviations. With a median follow-up of 74 months (range, 6–195), OS at 5 years was 74 ± 7%, 81 ± 8% for standard-risk, and 55 ± 16% for high-risk patients (p = 0.090). Disease-free survival at 5 years was not significantly affected by extent of surgery (p = 0.428) and RT-related variables such as surgery-RT interval (p = 0.776) neither RT duration (p = 0.172) or maintenance chemotherapy compliance (p = 0.634). Multivariate analysis identified risk groups predictive of worse DFS (p = 0.032) and leptomeningeal dissemination associated with inferior OS (p = 0.029).

Conclusion: Treatment delivery optimization has improved survival rates of patients with MB. Despite this, in our study, we have not established a clear influence of the considered radiotherapy and chemotherapy treatment quality parameters on outcomes.

What is Known:
• Improvement in treatment modalities during the last decades has reached a 5-year OS of up to 70% in these patients.
• Extent of resection and radiotherapy parameters such as interval between surgery-radiotherapy and radiotherapy duration has been described as probable survival prognostic factors.
What is New:
• Differences in medulloblastoma survival rates between prospective studies and retrospective series.
• The impact on survival of the three main treatment variables, surgery, radiotherapy and chemotherapy, susceptible to improvement.

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Fig. 1

Availability of data and materials

The data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

CG:

Children’s Oncology Group

ChT:

Chemotherapy

CI:

Confidence interval

CNS:

Central nervous system

CSI:

Craniospinal irradiation

CT:

Computed tomography

CTCAE:

Common Terminology Criteria for Adverse Events

DFS:

Disease-free survival

Gy:

Gray

HR:

Hazard ratio

HTRT:

Hyperfractionated radiotherapy

IGRT:

Image-guided radiation therapy

MB:

Medulloblastoma

MRI:

Magnetic resonance imaging

NCDB:

National Cancer Database

OR:

Odds ratio

OS:

Overall survival

PF:

Posterior fossa

PNET:

Primitive neuroectodermal tumors

RT:

Radiotherapy

RTQA:

Radiation therapy quality assurance

SE:

Standard error

SHH:

Sonic hedgehog

SIOP:

International Society of Paediatric Oncology

SPSS:

Statistical Package for the Social Sciences

STRT:

Standard radiotherapy

VMAT:

Volumetric modulated arc therapy

WNT:

Wingless

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Authors

Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Paula Sedano, Carmen González-San Segundo, Lourdes De Ingunza, Pedro Cuesta-Alvaro, and Alvaro Lassaletta. The first draft of the manuscript was written by Paula Sedano, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Alvaro Lassaletta.

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Ethics approval

Ethical approval was waived by the local Ethics Committee of Hospital Universitario Niño Jesus linked to University Autonoma de Madrid. In view of the retrospective nature of the study, all the procedures being performed were part of the routine clinical care.

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The authors declare that they have no conflict of interest.

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Sedano, P., Segundo, C.GS., De Ingunza, L. et al. Real-world data for pediatric medulloblastoma: can we improve outcomes?. Eur J Pediatr 180, 127–136 (2021). https://doi.org/10.1007/s00431-020-03722-4

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Keywords

  • Medulloblastoma
  • Surgery
  • Radiotherapy
  • Survival
  • Treatment quality
  • Children