Role of microsurgical tumor burden reduction in patients with breast cancer brain metastases considering molecular subtypes: a two-center volumetric survival analysis.

BACKGROUND: Advancements in metastatic breast cancer (BC) treatment have enhanced overall survival (OS), leading to increased rates of brain metastases (BM). This study analyzes the association between microsurgical tumor reduction and OS in patients with BCBM, considering tumor molecular subtypes and perioperative treatment approaches. METHODS: Retrospective analysis of surgically treated patients with BCBM from two tertiary brain tumor Swiss centers. The association of extent of resection (EOR), gross-total resection (GTR) achievement, and postoperative residual tumor volume (RV) with OS and intracranial progression-free survival (IC-PFS) was evaluated using Cox proportional hazard model. RESULTS: 101 patients were included in the final analysis, most patients (38%) exhibited HER2-/HR + BC molecular subtype, followed by HER2 + /HR + (25%), HER2-/HR- (21%), and HER2 + /HR- subtypes (13%). The majority received postoperative systemic treatment (75%) and radiotherapy (84%). Median OS and intracranial PFS were 22 and 8 months, respectively. The mean pre-surgery intracranial tumor volume was 26 cm3, reduced to 3 cm3 post-surgery. EOR, GTR achievement and RV were not significantly associated with OS or IC-PFS, but higher EOR and lower RV correlated with extended OS in patients without extracranial metastases. HER2-positive tumor status was associated with longer OS, extracranial metastases at BM diagnosis and symptomatic lesions with shorter OS and IC-PFS. CONCLUSIONS: Our study found that BC molecular subtypes, extracranial disease status, and BM-related symptoms were associated with OS in surgically treated patients with BCBM. Additionally, while extensive resection to minimize residual tumor volume did not significantly affect OS across the entire cohort, it appeared beneficial for patients without extracranial metastases.

Data-driven characterization of walking after a spinal cord injury using inertial sensors.

BACKGROUND: An incomplete spinal cord injury (SCI) refers to remaining sensorimotor function below the injury with the possibility for the patient to regain walking abilities. However, these patients often suffer from diverse gait deficits, which are not objectively assessed in the current clinical routine. Wearable inertial sensors are a promising tool to capture gait patterns objectively and started to gain ground for other neurological disorders such as stroke, multiple sclerosis, and Parkinson's disease. In this work, we present a data-driven approach to assess walking for SCI patients based on sensor-derived outcome measures. We aimed to (i) characterize their walking pattern in more depth by identifying groups with similar walking characteristics and (ii) use sensor-derived gait parameters as predictors for future walking capacity. METHODS: The dataset analyzed consisted of 66 SCI patients and 20 healthy controls performing a standardized gait test, namely the 6-min walking test (6MWT), while wearing a sparse sensor setup of one sensor attached to each ankle. A data-driven approach has been followed using statistical methods and machine learning models to identify relevant and non-redundant gait parameters. RESULTS: Clustering resulted in 4 groups of patients that were compared to each other and to the healthy controls. The clusters did differ in terms of their average walking speed but also in terms of more qualitative gait parameters such as variability or parameters indicating compensatory movements. Further, using longitudinal data from a subset of patients that performed the 6MWT several times during their rehabilitation, a prediction model has been trained to estimate whether the patient's walking speed will improve significantly in the future. Including sensor-derived gait parameters as inputs for the prediction model resulted in an accuracy of 80%, which is a considerable improvement of 10% compared to using only the days since injury, the present 6MWT distance, and the days until the next 6MWT as predictors. CONCLUSIONS: In summary, the work presented proves that sensor-derived gait parameters provide additional information on walking characteristics and thus are beneficial to complement clinical walking assessments of SCI patients. This work is a step towards a more deficit-oriented therapy and paves the way for better rehabilitation outcome predictions.

Maximal surgical tumour load reduction in immune-checkpoint inhibitor naïve patients with melanoma brain metastases correlates with prolonged survival.

BACKGROUND: Recent therapeutic advances in metastatic melanoma have led to improved overall survival (OS) rates, with consequently an increased incidence of brain metastases (BM). The role of BM resection in the era of targeted and immunotherapy should be reassessed. In the current study we analysed the role of residual intracranial tumour load in a cohort of melanoma BM patients. METHODS: Retrospective single-centre analysis of a prospective registry of resected melanoma BM from 2013 to 2021. Correlations of residual tumour volume and outcome were determined with respect to patient, tumour and treatment regimens characteristics. RESULTS: 121 individual patients (66% male, mean age 59.9 years) were identified and included in the study. Pre- and postoperative systemic treatments included BRAF/MEK inhibitors, as well as combination or monotherapy of immune-checkpoint inhibitors (ICIs). Median OS of the entire cohort was 20 months. Cox proportional-hazard analysis revealed postoperative anti-CTLA4+anti-PD-1 therapy (HR 0.07, p = .01) and postoperative residual intracranial tumour burden (HR 1.4, p = .027) as significant predictors for OS. Further analysis revealed that ICI-naïve patients with residual tumour volume ≤3.5 cm3 and postoperative ICI showed significantly prolonged OS compared to patients with residual volume >3.5 cm3 (p < .0001). Subgroup analysis of ICI-naïve patients showed steroid intake postoperatively to be negatively associated with OS, however residual tumour volume ≤3.5 cm3 remained independently correlated with superior OS (HR 0.14, p < .001). CONCLUSION: Besides known predictive factors like postoperative ICI, a maximal intracranial tumour burden reduction seems to be beneficial, especially in ICI-naïve patients. This highlights the importance of local CNS control and the need to further investigating the role of initial surgical tumour load reduction in randomised clinical trials.