Akbari H, Bakas S, Sako C, Fathi Kazerooni A, Villanueva-Meyer J, Garcia JA, Mamourian E, Liu F, Cao Q, Shinohara RT, Baid U, Getka A, Pati S, Singh A, Calabrese E, Chang S, Rudie J, Sotiras A, LaMontagne P, Marcus DS, Milchenko M, Nazeri A, Balana C, Capellades J, Puig J, Badve C, Barnholtz-Sloan JS, Sloan AE, Vadmal V, Waite K, Ak M, Colen RR, Park YW, Ahn SS, Chang JH, Choi YS, Lee SK, Alexander GS, Ali AS, Dicker AP, Flanders AE, Liem S, Lombardo J, Shi W, Shukla G, Griffith B, Poisson LM, Rogers LR, Kotrotsou A, Booth TC, Jain R, Lee M, Mahajan A, Chakravarti A, Palmer JD, DiCostanzo D, Fathallah-Shaykh H, Cepeda S, Santonocito OS, Di Stefano AL, Wiestler B, Melhem ER, Woodworth GF, Tiwari P, Valdes P, Matsumoto Y, Otani Y, Imoto R, Aboian M, Koizumi S, Kurozumi K, Kawakatsu T, Alexander K, Satgunaseelan L, Rulseh AM, Bagley SJ, Bilello M, Binder ZA, Brem S, Desai AS, Lustig RA, Maloney E, Prior T, Amankulor N, Nasrallah MP, O'Rourke DM, Mohan S, Davatzikos C
Glioblastoma (GBM) is the most aggressive adult primary brain cancer, characterized by significant heterogeneity, posing challenges for patient management, treatment planning, and clinical trial stratification. We developed a highly reproducible, personalized prognostication, and clinical subgrouping system using machine learning (ML) on routine clinical data, magnetic resonance imaging (MRI), and molecular measures from 2838 demographically diverse patients across 22 institutions and 3 continents. Patients were stratified into favorable, intermediate, and poor prognostic subgroups (I, II, and III) using Kaplan-Meier analysis (Cox proportional model and hazard ratios [HR]). The ML model stratified patients into distinct prognostic subgroups with HRs between subgroups I-II and I-III of 1.62 (95% CI: 1.43-1.84, P < .001) and 3.48 (95% CI: 2.94-4.11, P < .001), respectively. Analysis of imaging features revealed several tumor properties contributing unique prognostic value, supporting the feasibility of a generalizable prognostic classification system in a diverse cohort. Our ML model demonstrates extensive reproducibility and online accessibility, utilizing routine imaging data rather than complex imaging protocols. This platform offers a unique approach to personalized patient management and clinical trial stratification in GBM.