Navigating Post-Operative Outcomes: A Comprehensive Reframing of an Original Graded Prognostic Assessment in Patients with Brain Metastases.

BACKGROUND: Graded Prognostic Assessment (GPA) has been proposed for various brain metastases (BMs) tailored to the primary histology and molecular profiles. However, it does not consider whether patients have been operated on or not and does not include surgical outcomes as prognostic factors. The residual tumor burden (RTB) is a strong predictor of overall survival. We validated the GPA score and introduced "volumetric GPA" in the largest cohort of operated patients and further explored the role of RTB as an additional prognostic factor. METHODS: A total of 630 patients with BMs between 2007 and 2020 were included. The four GPA components were analyzed. The validity of the original score was assessed using Cox regression, and a modified index incorporating RTB was developed by comparing the accuracy, sensitivity, specificity, F1-score, and AUC parameters. RESULTS: GPA categories showed an association with survival: age (p < 0.001, hazard ratio (HR) 2.9, 95% confidence interval (CI) 2.5-3.3), Karnofsky performance status (KPS) (p < 0.001, HR 1.3, 95% CI 1.2-1.5), number of BMs (p = 0.019, HR 1.4, 95% CI 1.1-1.8), and the presence of extracranial manifestation (p < 0.001, HR 3, 95% CI 1.6-2.5). The median survival for GPA 0-1 was 4 months; for GPA 1.5-2, it was 12 months; for GPA 2.5-3, it was 21 months; and for GPA 3.5-4, it was 38 months (p < 0.001). RTB was identified as an independent prognostic factor. A cut-off of 2 cm3 was used for further analysis, which showed a median survival of 6 months (95% CI 4-8) vs. 13 months (95% CI 11-14, p < 0.001) for patients with RTB > 2 cm3 and <2 cm3, respectively. RTB was added as an additional component for a modified volumetric GPA score. The survival rates with the modified GPA score were: GPA 0-1: 4 months, GPA 1.5-2: 7 months, GPA 2.5-3: 18 months, and GPA 3.5-4: 34 months. Both scores showed good stratification, with the new score showed a trend towards better discrimination in patients with more favorable prognoses. CONCLUSION: The prognostic value of the original GPA was confirmed in our cohort of patients who underwent surgery for BM. The RTB was identified as a parameter of high prognostic significance and was incorporated into an updated "volumetric GPA". This score provides a novel tool for prognosis and clinical decision making in patients undergoing surgery. This method may be useful for stratification and patient selection for further treatment and in future clinical trials.

Comparison of anatomical-based vs. nTMS-based risk stratification model for predicting postoperative motor outcome and extent of resection in brain tumor surgery.

BACKGROUND: Two statistical models have been established to evaluate characteristics associated with postoperative motor outcome in patients with glioma associated to the motor cortex (M1) or the corticospinal tract (CST). One model is based on a clinicoradiological prognostic sum score (PrS) while the other one relies on navigated transcranial magnetic stimulation (nTMS) and diffusion-tensor-imaging (DTI) tractography. The objective was to compare the models regarding their prognostic value for postoperative motor outcome and extent of resection (EOR) with the aim of developing a combined, improved model. METHODS: We retrospectively analyzed a consecutive prospective cohort of patients who underwent resection for motor associated glioma between 2008 and 2020, and received a preoperative nTMS motor mapping with nTMS-based diffusion tensor imaging tractography. The primary outcomes were the EOR and the motor outcome (on the day of discharge and 3 months postoperatively according to the British Medical Research Council (BMRC) grading). For the nTMS model, the infiltration of M1, tumor-tract distance (TTD), resting motor threshold (RMT) and fractional anisotropy (FA) were assesed. For the PrS score (ranging from 1 to 8, lower scores indicating a higher risk), we assessed tumor margins, volume, presence of cysts, contrast agent enhancement, MRI index (grading white matter infiltration), preoperative seizures or sensorimotor deficits. RESULTS: Two hundred and three patients with a median age of 50 years (range: 20-81 years) were analyzed of whom 145 patients (71.4%) received a GTR. The rate of transient new motor deficits was 24.1% and of permanent new motor deficits 18.8%. The nTMS model demonstrated a good discrimination ability for the short-term motor outcome at day 7 of discharge (AUC = 0.79, 95 %CI: 0.72-0.86) and the long-term motor outcome after 3 months (AUC = 0.79, 95 %CI: 0.71-0.87). The PrS score was not capable to predict the postoperative motor outcome in this cohort but was moderately associated with the EOR (AUC = 0.64; CI 0.55-0.72). An improved, combined model was calculated to predict the EOR more accurately (AUC = 0.74, 95 %CI: 0.65-0.83). CONCLUSION: The nTMS model was superior to the clinicoradiological PrS model for potentially predicting the motor outcome. A combined, improved model was calculated to estimate the EOR. Thus, patient counseling and surgical planning in patients with motor-associated tumors should be performed using functional nTMS data combined with tractography.

MRI-Based Risk Assessment for Incomplete Resection of Brain Metastases.

Object: Recent studies demonstrated that gross total resection of brain metastases cannot always be achieved. Subtotal resection (STR) can result in an early recurrence and might affect patient survival. We initiated a prospective observational study to establish a MRI-based risk assessment for incomplete resection of brain metastases. Methods: All patients in whom ≥1 brain metastasis was resected were prospectively included in this study (DRKS ID: DRKS00021224; Nov 2020 - Nov 2021). An interdisciplinary board of neurosurgeons and neuroradiologists evaluated the pre- and postoperative MRI (≤48h after surgery) for residual tumor. Extensive neuroradiological analyses were performed to identify risk factors for an unintended STR which were integrated into a regression tree analysis to determine the patients' individual risk for a STR. Results: We included 150 patients (74 female; mean age: 61 years), in whom 165 brain metastases were resected. A STR was detected in 32 cases (19.4%) (median residual tumor volume: 1.36ml, median EORrel: 93.6%), of which 6 (3.6%) were intended STR (median residual tumor volume: 3.27ml, median EORrel: 67.3%) - mainly due to motor-eloquent location - and 26 (15.8%) were unintended STR (uSTR) (median residual tumor volume: 0.64ml, median EORrel: 94.7%). The following risk factors for an uSTR could be identified: subcortical metastasis ≥5mm distant from cortex, diffuse contrast agent enhancement, proximity to the ventricles, contact to falx/tentorium and non-transcortical approaches. Regression tree analysis revealed that the individual risk for an uSTR was mainly associated to the distance from the cortex (distance ≥5mm vs. <5mm: OR 8.0; 95%CI: 2.7 - 24.4) and the contrast agent patterns (diffuse vs. non-diffuse in those with distance ≥5mm: OR: 4.2; 95%CI: 1.3 - 13.7). The preoperative tumor volume was not substantially associated with the extent of resection. Conclusions: Subcortical metastases ≥5mm distant from cortex with diffuse contrast agent enhancement showed the highest incidence of uSTR. The proposed MRI-based assessment allows estimation of the individual risk for uSTR and can help indicating intraoperative imaging.