Reappraisal of Prognostic Factors in CNS WHO Grade 3 Oligodendrogliomas: Insights from the French POLA Cohort

Academic Background

Oligodendroglioma is a relatively rare primary brain tumor in the central nervous system (CNS), characterized by IDH gene mutations and 1p/19q co-deletion. According to the World Health Organization (WHO) classification of tumors, oligodendrogliomas are categorized into different grades, with grade 3 oligodendrogliomas considered to be highly malignant. Although advances in molecular diagnostic techniques have provided new tools for the classification and prognostic assessment of oligodendrogliomas, the discussion on prognostic factors remains controversial. In particular, how to further stratify patient prognosis based on pathological features and imaging findings remains an unresolved issue.

This study aims to reassess the prognostic factors of CNS WHO grade 3 oligodendrogliomas (IDH-mutant and 1p/19q co-deleted) using data from the French POLA cohort, with a focus on the impact of pathological features and imaging findings on patient survival. The study hopes to provide more accurate guidance for clinical treatment decisions through more detailed subgrouping and long-term follow-up data.

Source of the Paper

This study was conducted by Dominique Figarella-Branger and a team of researchers from several renowned medical institutions in France, including Aix-Marseille University, Sorbonne University, and Toulouse University Hospital. The paper was published in March 2025 in the journal Neuro-Oncology, titled “Reappraisal of prognostic factors in CNS WHO grade 3 oligodendrogliomas IDH-mutant and 1p/19q co-deleted: lessons from the French POLA cohort.”

Research Process

Study Subjects and Data Collection

The study included 494 patients from the French POLA cohort, all of whom were centrally reviewed and confirmed to have newly diagnosed CNS WHO grade 3 oligodendrogliomas (IDH-mutant and 1p/19q co-deleted). All patients provided written informed consent for the collection of clinical data and genetic analysis. The study database included clinical information such as age, gender, type of surgery, adjuvant therapy, and survival, as well as pathological and molecular data, including mitotic count, the presence of microvascular proliferation (MVP) and necrosis, IDH1/2 mutation status, 1p/19q co-deletion status, and CDKN2A homozygous deletion (HD) status in a subset of patients.

Pathological Grouping and Imaging Evaluation

Based on previous research, the patients were divided into three pathological groups:
1. Group 1: High mitotic count only;
2. Group 2: Presence of microvascular proliferation (MVP) but no necrosis;
3. Group 3: Presence of both microvascular proliferation and necrosis.

Additionally, the researchers paid special attention to the imaging findings of Group 1 patients, particularly the presence of contrast enhancement (CE) on MRI. The presence of CE was considered to be related to tumor angiogenesis and could potentially affect patient prognosis.

Survival Analysis

The researchers used the Kaplan-Meier method to plot overall survival (OS) and progression-free survival (PFS) curves for the patients and compared survival differences between groups using the log-rank test. Furthermore, the researchers evaluated the impact of other clinical factors (such as age, extent of surgery, postoperative treatment, etc.) and CDKN2A homozygous deletion on prognosis. Multivariate analysis further adjusted for variables such as age, extent of surgery, and postoperative treatment to determine the independent prognostic value of the pathological groups.

Key Findings

Pathological Grouping and Survival

Survival analysis showed that pathological grouping was significantly associated with both progression-free survival (PFS) and overall survival (OS). The 5-year OS for Group 1 patients was 91%, significantly higher than that of Group 2 (85%) and Group 3 (77%). However, at 10 years, the difference in OS between Group 1 and Group 2 was no longer significant. Similarly, the PFS of Group 1 patients was significantly better than that of Group 2 and Group 3.

Prognostic Value of Contrast Enhancement

Among Group 1 patients, those with contrast enhancement (CE) had a worse prognosis, with significantly lower OS and PFS compared to those without CE. Further dividing Group 1 patients into CE+ and CE- subgroups revealed that CE- patients had a significantly better prognosis than CE+ patients, even comparable to Group 2 patients.

Other Prognostic Factors

Multivariate analysis showed that patients younger than 50 years, those with a greater extent of surgical resection, higher postoperative Karnofsky Performance Status (KPS), those who received postoperative radiotherapy combined with PCV chemotherapy, and those without CDKN2A homozygous deletion had significantly longer OS and PFS. In particular, CDKN2A homozygous deletion was identified as a significant negative prognostic factor.

Conclusions and Significance

This study, using long-term follow-up data from the French POLA cohort, confirmed the prognostic value of pathological grouping in CNS WHO grade 3 oligodendrogliomas and, for the first time, proposed the stratification role of contrast enhancement (CE) in Group 1 patients. The findings indicate that necrosis and CDKN2A homozygous deletion are negative prognostic factors in CNS WHO grade 3 oligodendrogliomas, while contrast enhancement is an important prognostic marker for Group 1 patients.

This discovery provides clinicians with a more refined tool for prognostic assessment, particularly for patients with only a high mitotic count but no contrast enhancement, who may not require overly aggressive treatment. Additionally, the study suggested the possibility of incorporating CDKN2A homozygous deletion and necrosis into the grading of oligodendrogliomas, offering new insights for future WHO classification standards.

Research Highlights

1. Long-term Follow-up Data: The median follow-up time of 96 months in this study provides reliable data support for the prognostic assessment of oligodendrogliomas.
   
2. Stratification Role of Contrast Enhancement: The study is the first to propose the prognostic value of contrast enhancement in patients with only a high mitotic count, providing new guidance for clinical treatment decisions.
   
3. Multivariate Analysis: By adjusting for variables such as age, extent of surgery, and postoperative treatment, the study determined the independent prognostic value of pathological groups.
   
4. Prognostic Significance of CDKN2A Homozygous Deletion: The study found that CDKN2A homozygous deletion is a negative prognostic factor in CNS WHO grade 3 oligodendrogliomas, offering a new direction for future molecular diagnostics and grading.

Other Valuable Information

The researchers also suggested that future studies should further explore the biological mechanisms of contrast enhancement in oligodendrogliomas and the relationship between CDKN2A homozygous deletion and tumor progression. Additionally, the study called for the establishment of larger multicenter cohorts to validate and generalize the findings.

This study provides important scientific evidence for the prognostic assessment and treatment decision-making of CNS WHO grade 3 oligodendrogliomas, with significant clinical and research value.