Study on Relapse Patterns of Intracranial Ependymoma

Background

Ependymoma (EPn) is a rare but highly heterogeneous central nervous system tumor, particularly common in children. Despite significant advances in the biology and molecular characteristics of ependymoma in recent years, its relapse patterns remain unclear. The timing and location of relapse vary significantly depending on the molecular subtype, which directly impacts patient treatment and follow-up strategies. Therefore, studying the relapse patterns of different molecular subtypes of ependymoma is crucial for optimizing treatment plans and improving patient outcomes.

This study aims to reveal the relapse patterns of different molecular subtypes of ependymoma and their impact on patient survival by analyzing clinical and molecular data from 269 patients with relapsed intracranial ependymoma. The research team hopes to provide a scientific basis for future clinical trials, treatment adjustments, and follow-up strategies through these data.

Source of the Study

The research was conducted by scholars from multiple internationally renowned institutions, including Denise Obrecht-Sturm, Melanie Schoof, Alicia Eckhardt, and others. The research team is affiliated with the University Medical Center Hamburg-Eppendorf in Germany, the National Cancer Institute in the United States, the Hospital for Sick Children in Canada, and other institutions. The paper was published online on August 22, 2024, in Neuro-Oncology, with the DOI 10.1093/neuonc/noae166.

Research Process and Results

1. Inclusion of Study Subjects and Data Collection

The research team collected clinical and molecular data from 269 patients with relapsed intracranial ependymoma from multiple cohorts in Europe and North America, including 233 pediatric patients and 36 adult patients. All patients were histopathologically confirmed and classified according to WHO criteria. The research team screened patients through the following steps: - Retrieving cases from the German HIT-MED and HIT-REZ databases from 2001 to 2021; - Searching local archives of the Institute of Neuropathology and Neurosurgery at the University Medical Center Hamburg-Eppendorf; - Contacting the Austrian research team (J. Gojo, N. Stepien) to obtain data from the Vienna cohort; - Including patient data from the study published by Ramaswamy et al. in 2016.

2. DNA Methylation Analysis and Molecular Subtyping

The research team performed DNA methylation analysis on tumor samples using the Illumina Human Methylation EPIC BeadChip to detect methylation patterns and analyzed copy number variations using the Conumee package. Tumors were classified into molecular subtypes based on the Heidelberg Brain Tumor Classifier (version 12.5). The study identified the following molecular subtypes: - PF-EPN-A (Posterior Fossa Ependymoma Type A): 177 cases; - ST-EPN-ZFTA (Supratentorial Ependymoma ZFTA Fusion Type): 45 cases; - PF-EPN-B (Posterior Fossa Ependymoma Type B): 31 cases; - PF-EPN-SE (Posterior Fossa Subependymoma): 12 cases; - ST-EPN-YAP (Supratentorial Ependymoma YAP Fusion Type): 4 cases.

3. Analysis of Relapse Patterns

The research team analyzed the timing and location of the first relapse for different molecular subtypes of ependymoma. The results showed: - The median time to first relapse for PF-EPN-A was 1.9 years, with relapses primarily at the primary tumor site (71.6%), but 30% involved the supratentorial region and 40% involved the spinal cord; - The median time to first relapse for PF-EPN-B was 4.3 years, with 35.5% of relapses being distant metastases, of which 72.7% involved the spinal cord; - The median time to first relapse for ST-EPN-ZFTA was 2.4 years, with 66.7% of relapses limited to the primary tumor site and 33.3% being distant metastases; - Relapses in ST-EPN-YAP and PF-EPN-SE were limited to the primary tumor site, with no distant metastases observed.

4. Post-Relapse Survival Analysis

The research team further analyzed the post-relapse survival (PRS) rates for different molecular subtypes: - The 5-year PRS for PF-EPN-A and ST-EPN-ZFTA was 44.5% and 47.8%, respectively, with a significant decline in 10-year PRS; - The 5-year PRS for PF-EPN-B and PF-EPN-SE was 89.5% and 90.0%, respectively, but the 10-year PRS for PF-EPN-B dropped to 45.8%; - ST-EPN-YAP and PF-EPN-SE had higher post-relapse survival rates, with no long-term deaths observed.

5. Relationship Between Treatment and Relapse Patterns

The research team also analyzed the impact of postoperative treatment on relapse patterns. The results showed no significant association between the radiation field (local radiotherapy vs. craniospinal irradiation) and relapse patterns or spinal cord involvement. Notably, all ST-EPN-YAP patients who received radiotherapy at relapse were successfully salvaged, while most PF-EPN-SE patients did not receive postoperative radiotherapy.

Conclusions and Significance

This study is the first to systematically reveal the relapse patterns of different molecular subtypes of ependymoma and their impact on patient survival. The results indicate that PF-EPN-A, PF-EPN-B, and ST-EPN-ZFTA are more prone to distant metastases, particularly involving the spinal cord, while relapses in ST-EPN-YAP and PF-EPN-SE are limited to the primary tumor site. These findings provide important evidence for future clinical trials and individualized treatment strategies.

Additionally, the study highlights the importance of long-term follow-up, especially for PF-EPN-B patients, whose relapse can occur up to 30 years after diagnosis. The research team recommends comprehensive spinal MRI at relapse to ensure accurate staging.

Highlights of the Study

1. First systematic analysis of relapse patterns in different molecular subtypes of ependymoma, revealing the high spinal metastasis rates in PF-EPN-B and PF-EPN-A;
2. Inclusion of long-term follow-up data, uncovering the risk of late relapse in PF-EPN-B patients;
3. Providing a scientific basis for individualized treatment and follow-up strategies, particularly for ST-EPN-YAP and PF-EPN-SE patients, where de-escalation of postoperative radiotherapy may be a viable option.

Research Value

This study not only deepens the understanding of the biological behavior of ependymoma but also provides important guidance for clinicians in treatment and follow-up. By combining molecular subtyping and relapse patterns, more precise treatment strategies can be developed in the future, thereby improving patient survival rates and quality of life.