Overall survival prediction scale for patients with grade 4 brain astrocytoma

OBJECTIVE

To create a prognostic scale for overall survival in grade 4 astrocytomas based on molecular biological data.

MATERIAL AND METHODS

After morphological confirmation of WHO grade 4 astrocytoma (2021 WHO classification criteria), 175 patients were classified as GBM (grade 4) without IDH1 mutations; IDH1 mutation was detected in 25 patients (12.5%; G4 astrocytoma). Molecular biological analysis of IDH1 gene mutations and MGMT promoter methylation was performed in 194 (97%) patients.

RESULTS

To study concomitant significance of IDH1 mutation and MGMT promoter methylation in grade 4 gliomas, we created the IDH1/MGMT index(0 — IDH1+/MGMT+; 1 — IDH1/MGMT (+/–); 2 — IDH1-/MGMT-). This predictor was digitized in 194 patients who underwent molecular analysis. The most informative classification matrix according to overall survival was as follows: IDH1/MGMT index (OR=1.712; p=0.0004), REP (OR=1.971; p=0.0001), functional status before microsurgery at the lowest possible level (OR=1.797; p=0.001). Simple summation of numerical indicators for factors 1—3 in each patient allowed us to identify 5 prognostic classes: class 1 (0—1 points), class 2 (2 points), class 3 (3 points), class 4 (4 points), class 5 (5 points). Log-rank criterion for Kaplan-Meier survival curves revealed significant differences between classes (χ²=55.780; p<0.001). The median survival rates were 71.5, 42.3, 23.6, 17.4 and 8.1 months, respectively. Significant differences in survival were noted between almost all neighboring classes: classes 1—2 (χ²=3.21; p=0.073), classes 2—3 (χ²=5.77; p=0.016), classes 3—4 (χ²=6.03; p=0.014), classes 4—5 (χ²=11.97; p=0.0005). In “classes 1—3” in prognostic scale, median overall survival was 44.98 months (n=53; 95% CI: 20.5—69.4) for 3 Gy fractionation regimen and only 23.23 months (n=78; 95% CI: 17.3—29.1; χ²=9.28; p=0.002) for 2 Gy regimen. There were other results for classes 4—5. Median overall survival for 3 and 2 Gy fractionation regimens was low: 17.41 (n=28; 95% Cl: 13.8—21.0) and 15.83 months (n=41; 95% Cl: 11.7—20.0; –2=0.59; p=0.442), respectively.

CONCLUSION

The new prognostic scale for overall survival, based on molecular data, allows not only to predict further course of disease, but also to recommend irradiation 3 Gy for patients in classes 1—3 as an alternative to radiotherapy.