Response to First-Line Treatment of Persistent MRI Lesions in Pediatric Medulloblastoma as a Surrogate Marker for Predicting Risk of Disease Progression

Medulloblastoma is one of the most common malignant central nervous system tumors in children. Although the multimodal treatment concept has significantly improved the prognosis for patients, the outcome remains suboptimal for some patients. Currently, the impact of persistent residual lesions (i.e., local residual tumor, persistent metastatic lesions, or lesions of uncertain composition) on prognosis after completion of first-line treatment remains unclear. Therefore, this study aimed to evaluate the impact of persistent residual lesions on prognosis, analyze risk factors affecting the survival of these patients, and comprehensively assess subsequent diagnostic work and treatment plans.

Study Source

This study was conducted by Denise Obrecht-Sturm and authors from various institutions in Germany, Switzerland, and Austria and published in the journal Neuro-Oncology in 2023.

Study Methods

1. Case source: Included were 84 pediatric medulloblastoma patients aged ≥4 years with persistent residual lesions identified by central imaging review after initial surgical treatment between January 1, 2000, and December 31, 2019.

2. Treatment regimen: Patients received risk-stratified postoperative chemoradiotherapy according to the HIT2000 trial protocol or national guidelines.

3. Response evaluation: Central imaging review assessed the overall best response, classified as partial remission (PR) or stable disease (SD). Patients were further categorized based on the location of residual lesions as local residual (R+/M0), distant metastases (R0/M+), or both (R+/M+).

4. Follow-up: Median follow-up was 6 years, evaluating post-progression-free survival (pPTFS) and post-progression overall survival (pPTOS).

5. Molecular subtyping: DNA methylation subtyping was performed for 58 cases.

Key Findings

1. Overall response was associated with prognosis: Compared to the SD group, the PR group had better 5-year pPTFS (62.5% vs. 35.9%, P=0.03) and pPTOS (79.7% vs. 55.5%, P=0.04).

2. The extent of residual lesions was associated with prognosis: The R+/M+ group had significantly lower 5-year pPTFS (22.9%) than the R+/M0 group (72.4%, P=0.03).

3. The type of leptomeningeal metastases affected prognosis: Patients with spinal leptomeningeal metastases had a poorer prognosis (5-year pPTFS 39.0%, P=0.03; 5-year pPTOS 55.3%, P=0.04).

4. The association between molecular subtyping and prognosis was not significant (P=0.08).

5. Additional post-operative treatment did not provide a survival benefit (P>0.5).

Study Significance

This study demonstrated that the overall response to first-line treatment and the extent and type of residual lesions could serve as surrogate markers for predicting the prognosis of pediatric medulloblastoma patients. For patients with only local residual lesions, additional treatment appeared to be of no benefit. Therefore, when deciding whether to provide additional treatment, the treatment response, residual lesion status, and other diagnostic information should be comprehensively considered. These findings may help manage these patients more rationally, avoiding over- or under-treatment.