Onco-functional outcome after resection for eloquent glioblastoma (GLIOFO): A propensity-score matched analysis of an international, multicentre, cohort study.
Authors: Gerritsen Jasper Kees Wim , Mekary Rania , Pisică Dana , Zwarthoed Rosa Hanne , Kilgallon John Laws , Nawabi Noah Lee , Jessurun Charissa Alissa Cassandra , Versyck Georges , Pruijn Koen Pepijn , Fisher Fleur Louise , Solie Lien , Kloet Alfred , Nandoe Tewarie Rishi , Schouten Joost Willem , Bos Eelke Marijn , Smith Timothy Richard , Dirven Clemens Maria Franciscus , Broekman Marike Lianne Daphne , Vincent Arnaud Jean Pierre Edouard , De Vleeschouwer Steven 
Published: July 2024

e14017

Background: Minimizing residual volume and preventing functional loss are the main goals in glioblastoma resections in eloquent areas. However, their combined impact on patient outcomes remains poorly understood. We therefore developed a novel onco-functional outcome (OFO) classification and evaluated its benefit in subgroups based on age, preoperative neurological morbidity (NIHSS), and Karnofsky Performance Score (KPS). Methods: Propensity-score matching was used to match OFO 1 (gross total resection, no functional loss) vs. OFO 2-3-4, OFO 2 (no gross total resection, no functional loss) vs. OFO 1-3-4, OFO 3 (gross total resection, functional loss) vs. OFO 1-2-4, and OFO 4 (no gross total resection, no functional loss) vs. OFO 1-2-3 for the overall cohort and subgroups. Cox proportional-hazard regressions and logistic regressions were performed to analyze the association between OFO class and postoperative outcomes, and the predictive value of perioperative factors on OFO class, respectively. Results: Between 2010 and 2020, 3919 patients were recruited, of whom 858 were included as the overall unmatched cohort. After propensity-score matching, the overall matched cohort comprised of 512 patients, of whom 256 had OFO 1 and 256 had OFO 2-3-4. Overall survival differed significantly between OFO groups: 21.0 months [19.0-25.0] (OFO 1) versus 14.0 months [13.0-16.0] (OFO 2) versus 12.0 [11.0-15.0] (OFO 3) versus 8.5 months [7.0-10.0] (OFO 4) (p<0.0001). In the overall matched cohort, OFO 1 versus OFO 2-3-4 resulted in fewer neurological deficits at 6 weeks (26 [10.2%] of 256 vs. 66 [25.8%] of 256, p <0.001), 3 months (30 [12.7%] of 237 vs. 69 [29.9%] of 231, p <0.001), and 6 months postoperatively (48 [21.0%] of 229 vs. 72 [35.1%] of 205, p = 0.0010), lower frequencies of KPS deterioration at 3 months (34 [14.2%] of 239 vs. 121 [52.4%] of 231, p <0.001), and 6 months postoperatively (61 [26.5%] of 230 vs. 110 [52.9%] of 208, p<0.001), longer overall survival (median 21.0 months [19.0-25.0] vs. 13.0 months [12.0-15.5], p<0.001), and longer progression-free survival (median 10.0 months [9.0-11.0] vs. 7.5 months [6.0-8.0], p<0.001). OFO 1 was associated with higher frequencies of receipt of adjuvant chemotherapy and radiotherapy, and longer overall survival and progression-free survival in all subgroups except the KPS 90-100 subgroup. Awake craniotomy more often led to OFO 1 compared to asleep resection (43.0% vs. 26.9%, p<0.001; OR 1.91, p = 0.0080). Conclusions: OFO 1 was associated with improved survival outcomes, neurological outcomes, and receipt of adjuvant therapy in all glioblastoma patients. Awake craniotomy was significantly associated with achieving this more often. Aggressive and safe resections (OFO 1) were superior to resections that were defensive but safe (OFO 2), aggressive but unsafe (OFO 3), or defensive but unsafe (OFO 4).