Analysis of Risk Factors Related to Specific Domain Neurocognitive Outcomes in Pediatric Survivors of Posterior Fossa Brain Tumors – HIT 2000 Trial Results

Research Background

Brain tumors are the most common solid tumors in childhood, particularly central nervous system (CNS) tumors. Studies have shown that patients who receive craniospinal irradiation (CSI) treatment experience significant long-term neuropsychological outcomes. Glial tumors and medulloblastomas in the posterior fossa area are treated comprehensively through surgery, radiation therapy, and chemotherapy. However, radiation therapy, particularly extensive CSI, may lead to significant neurotoxicity, especially in cases with larger target volumes or higher dose treatments. As the number of pediatric brain tumor survivors increases, treatment-related toxicity and long-term quality of life, particularly neurocognitive function, are receiving growing attention.

Research Source

This paper was completed by Martin Mynarek and several researchers from various institutions such as the Department of Pediatric Hematology and Oncology at the University Medical Center Hamburg-Eppendorf, the University Hospital Rostock’s Pediatrics, and the University Children’s Hospital Würzburg, among others. This study was published in the journal “Neuro-Oncology” on June 7, 2024.

Subjects and Methods

The study selected 279 non-recurrent survivors from the HIT 2000 trial who underwent treatments like radiotherapy, chemotherapy, and surgery. The specific methods are introduced as follows:

1. Subjects: Included 241 medulloblastoma and 38 Ependymoma of the lower cranial fossa patients, who were over 4 years old at diagnosis and without recurrence or disease progression at the time of neuropsychological assessment.
2. Treatment Process: Medulloblastoma patients received combined chemotherapy and CSI, with different doses of CSI applied based on clinical risk factors.
3. Neuropsychological Assessment: Used a psychological basic diagnostic tool (NBD) based on the Cattell-Horn-Carroll intelligence model to assess cognitive outcomes in multiple subdomains.
4. Data Analysis: Employed various statistical analysis methods, such as independent sample t-tests, variance analysis, Pearson correlation analysis, etc., to explore various factors affecting neuropsychological outcomes.

Main Results

1. Neurocognitive Decline: All subtests were significantly lower than normal levels, with processing speed and psychomotor ability being the most severely impaired.
2. CSI Dose Relevance: CSI dose was strongly correlated with most subtests, particularly in areas such as fluid intelligence, short-term memory, and visual processing.
3. PCMS and Surgical Impact: PCMS was strongly associated with psychomotor ability and processing speed, and postoperative hydrocephalus was associated with crystallized intelligence and short-term memory.
4. Multivariate Analysis: High-dose CSI was associated with poorer neurocognitive outcomes, indicating that surgery and its complications play an important role in influencing neurocognitive outcomes.

Conclusion

The study confirmed the significant negative impact of CSI doses on neuropsychological outcomes, while emphasizing the strong and specific domain effects of the tumor itself, its surgical resection, and related complications on neurocognitive consequences. This provides important evidence for future research and improvement in treatment methods. Future studies should focus on reducing the toxicity of CSI doses and other treatment methods, as well as discovering better protective, rehabilitation, and intervention measures to improve outcomes in these areas.

Scientific Significance and Application Value

This study not only established a clear link between CSI doses and neurocognitive outcomes but also highlighted the importance of surgical techniques and complications in affecting long-term neurocognitive function. These findings are of great guiding significance for formulating more refined treatment plans, reducing treatment-related toxicity, and improving the quality of life of pediatric brain tumor survivors. Specifically, future studies should focus on measures to protect, recover, and improve in critical areas such as reduced processing speed.

Through this study, strong evidence is provided to the scientific community, directing future research on neurotoxicity, and offering valuable recommendations for various interventions in the clinical treatment of posterior fossa tumors.