EP12.04 REAL-WORLD SURVIVAL OUTCOMES AFTER (CHEMO)RADIOTHERAPY FOR WHO 2021-CLASSIFIED GLIOMAS: A MULTICENTER ANALYSIS OF CLINICAL, TREATMENT-RELATED, DOSIMETRIC, AND HEMATOLOGIC PROGNOSTIC FACTORS

Abstract BACKGROUND The 2021 WHO classification of gliomas introduced molecular profiling into the diagnostic criteria, reshaping prognosis and therapeutic strategies. However, most existing outcomes data are based on previous classifications, creating a knowledge gap regarding survival outcomes for gliomas with contemporary molecular characterization. We aimed to provide new real-world evidence for survival outcomes in patients with WHO 2021-classified gliomas to evaluate the prognostic impact of radiation-induced leukopenia/lymphopenia (RIL) alongside clinical and dosimetric factors. MATERIAL AND METHODS Data from patients with intracranial WHO grade (G) 2-4 gliomas diagnosed according to the WHO 2021 criteria, treated with surgical resection followed by radio(chemo)therapy, were retrospectively collected across four centers in Poland and France. For patients diagnosed before the WHO 2021 classification, a molecular analysis of IDH1/2 and 1p19q codeletion was performed prospectively. Primary endpoints, overall survival (OS) and progression-free survival (PFS), were evaluated by clinical, treatment-related, dosimetric, and RIL parameters. Statistical analyses were performed using Python libraries scikit-learn and statsmodels. RESULTS A total of 179 patients (median age 53 years) were included. IDH1/2 mutations and 1p/19q codeletion were identified in 55.3% and 22.4% of cases, respectively. According to the WHO 2021 criteria, 45 tumors were G2, 51 G3, and 83 G4. Chemotherapy was administered in 74.9% of patients, and the median radiotherapy dose was 60 Gy (32.5-80 Gy). Patients with IDH1/2 mutations demonstrated significantly longer PFS (7.7 vs. 1.0 years; p<0.01) and OS (8.2 vs. 2.5 years; p<0.01). 1p/19q codeletion correlated with longer PFS (7.7 vs. 1.6 years; p<0.01) but not OS. In WHO G3 gliomas, the addition of chemotherapy significantly improved PFS (6.8 vs. 3.6 years; p<0.01) and OS (6.9 vs. 3.9 years; p<0.01). Lower grades of leukopenia (0-2) were associated with longer PFS (3.6 vs. 1.2 years; p=0.02) and OS (7.2 vs. 3.2 years; p=0.04) compared to severe leukopenia. Patients with an ALC ≤1×10³/mm³ had significantly inferior survival outcomes, with shorter OS (5.3 vs. 8.7 years; p=0.0043) and PFS (1.4 vs. 6.8 years; p<0.001). A clinical target volume (CTV) cut-off of 127 cm³ predicted OS in WHO G4 gliomas (1.7 vs. 3.2 years; p=0.012). Principal component analysis confirmed that glioma grade, molecular alterations, hematologic parameters, and steroid use were major factors associated with survival, while dosimetric parameters showed a moderate correlation with hematologic variables. CONCLUSION This multicenter study provides RWE that molecular, clinical, hematologic, and dosimetric factors significantly impact survival in WHO 2021-classified gliomas, emphasizing the need for their integration into personalized treatment strategies.