# Prospective international phase-III study to improve neurocognitive outcomes in young children with low-risk medulloblastoma (YCMB-LR)

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 2024 · $235,324

## Abstract

PROJECT SUMMARY / ABSTRACT
Cancer is the second most frequent cause of death in children under 15 years of age, and primary central
nervous system (CNS) tumors are the most frequent cause of cancer-related childhood deaths. Medulloblastoma
(MB) is the most frequent malignant childhood brain tumor (incidence of 5.5/million/year). About 40% of cases
occur in children <5 years old, which can be sub-divided by biological markers into two groups: low-risk group,
biologically defined by either Wingless/Integrated (WNT) or Sonic Hedgehog (SHH) activation TP53-wt, while
the high-risk group is defined by non-WNT/non-SHH biology. As WNT-activated MB is extremely rare in early
childhood, only young patients (<5 years of age) with low-risk (SHH-activated) MB are eligible and have an
excellent prognosis if treated with either of the two randomized arms in this research study. Craniospinal
irradiation (CSI) is an integral component in the treatment of MB; however, because of the devastating impact
upon the central nervous system (CNS) and neurocognitive outcomes, it must be avoided whenever possible
given the significant interference with educational and vocational attainment. Consequently, maintaining or
improving neurocognitive and QoL functioning is an essential opportunity for early childhood survivors who can
now be cured with treatment that does not include CSI. The Prospective International SIOPE/CONNECT
phase-III study to improve neurocognitive outcomes in young children with low-risk medulloblastoma
(YCMB-LR) is the first ever randomized study directly comparing two highly effective irradiation-sparing
treatment regimens, Head Start 4 and HIT-SKK, which will take place at pediatric oncology centers across
Europe and North America and is the first to include neuropsychological and QoL outcome as the primary
objective. Aim 1) Compare the overall intelligence and IQ subdomains as measured by the Wechsler Preschool
and Primary Scale of Intelligence administered 2.5 years after diagnosis between patients with newly diagnosed,
non-metastatic, SHH-activated, TP53-wt MB randomized to the interventional arms A (Head Start 4) or B (HIT-
SKK). Aim 2) Compare the trajectory between the two randomized groups at baseline and again at 2.5 years
post diagnosis for: a) overall intelligence and IQ subdomains, b) behavioral development and c) QoL, along with
analyses at 2.5 years post diagnosis for: d) fine motor dexterity and processing speed, e) visual-motor
integration, f) executive functioning, and g) social-emotional functioning. Aim 3) Several quantitative imaging
metrics with regard to brain volumes and white matter injury will serve as ancillary noninvasive biomarkers for
comparison of the two interventional arms in Aim 1, and will be statistically correlated with the neurocognitive,
QoL and behavioral outcomes in Aim 2. Impact: Our work will define the new “gold standard” of treatment in
early childhood low-risk MB that is associated with better neurocognitive ...

## Key facts

- **NIH application ID:** 10918340
- **Project number:** 5R01CA283045-02
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** STEPHEN Alan SANDS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $235,324
- **Award type:** 5
- **Project period:** 2023-09-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10918340

## Citation

> US National Institutes of Health, RePORTER application 10918340, Prospective international phase-III study to improve neurocognitive outcomes in young children with low-risk medulloblastoma (YCMB-LR) (5R01CA283045-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10918340. Licensed CC0.

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