P18.54.B DEVELOPMENT AND VALIDATION OF A CLINICAL RISK SCORE FOR POSTOPERATIVE OUTCOME IN NEWLY DIAGNOSED GLIOBLASTOMA: A REPORT OF THE RANO RESECT GROUP
Authors: Karschnia P , Young J S , Youssef G C , Dono A , Häni L , Sciortino T , Bruno F , Juenger S T , Teske N , Dietrich J , Weller M , Vogelbaum M A , van den Bent M , Beck J , Thon N , Gerritsen J K , Hervey-Jumper S , Cahill D P , Chang S M , Rudà R , Bello L , Schnell O , Esquenazi Y , Ruge M I , Grau S J , Huang R Y , Wen P Y , Berger M S , Molinaro A M , Tonn J 
Published: October 2024

Abstract

BACKGROUND
Following resection or biopsy, patients with newly diagnosed glioblastoma frequently enter clinical trials. Nuanced risk assessment is warranted to reduce imbalances between study arms. Here, we aim to make use of our RANO classification for extent of resection to (I) analyze the interactive effects of residual tumor with clinical and molecular factors on outcome (II) to define a postoperative risk assessment tool.

MATERIAL AND METHODS
The RANO resect group retrospectively compiled an international, seven-center training cohort of newly diagnosed glioblastoma. The combined effects of residual tumor with molecular and clinical factors on survival were analyzed, and recursive partitioning analysis was performed for risk modelling. Terminal regression tree nodes were combined into risk classes guided by Kaplan-Meier survival analyses and log-rank tests. The resulting model was prognostically verified in a separate external validation cohort.

RESULTS
Our training cohort compromised 1003 patients with newly diagnosed IDH-wildtype glioblastoma, including 744 patients who underwent adjuvant radiochemotherapy per EORTC-NCIC (TMZ/RT→TMZ). Residual tumor, MGMT promotor methylation status, age (as continuous variable; optimal cutoff: ≤65 years), and KPS (as continuous variable; optimal cutoff: ≥80) were prognostic of overall survival and forwarded into regression tree analysis. By combining eleven terminal nodes and individually weighting the prognostic factors, an additive scale (range, 0-9 points) integrating these four variables distinguished patients with low (0-2 points), intermediate (3-5 points), and high risk (6-9 points) for poor postoperative outcome (median overall survival: 24 vs. 16 vs. 6 months; p &lt; 0.01). Adjustment of the regression tree for adjuvant therapy was applied, and the presence of the three risk groups was confirmed in the subgroups of patients treated with or without RT/TMZ→TMZ. The prognostic value of the risk score was verified in a external single-center validation cohort of newly diagnosed glioblastoma (n = 231, p &lt; 0.01). When we compared our risk score to previously postulated risk models, our score was superior in concordance between predicted with observed survival across the exploratory and validation cohorts (Harrell’s C-index; development cohort: 0.7, validation cohort: 0.6).

CONCLUSION
The novel RANO risk score integrates molecular and clinical factors to serve as an easy-to-use, yet highly prognostic tool to stratify patients after resection or biopsy of newly diagnosed glioblastoma. The score may therefore serve to guide patient management and reduce imbalances between study arms in prospective interventional trials.