Functional outcomes after retrosigmoid approach to the cerebellopontine angle: Observations from a single-center experience of over 13 years.

Introduction: Accessing the posterior base of the skull is complex because of the vital neurovascular structures in the area. However, the retrosigmoid approach (RSA) offers a solution to this challenge. Research question: To analyze surgical outcome of RSA. Material and methods: This study involved a retrospective review of patient charts from a single center, focusing on the surgical procedure and outcomes following the operation. Results: The study included 517 patients suffering from conditions like vestibular schwannomas (VS), metastatic cancers, and trigeminal neuralgia. The most frequent symptoms reported were balance disorders (42.7%), hearing loss (36.5%), walking difficulties (21.2%), headaches (18.9%), facial pain (17.1%), issues with trigeminal nerve function (14.1%), cerebellar dysfunction (13.5%), and facial nerve paralysis (10.2%). The rate of complications stood at 21.1%, with 11.3% of patients needing revision surgery. The median score on the Clavien-Dindo scale was 2, and the rate of mortality related to surgery was 1.0%. Permanent symptom improvement was seen in 72.1% of cases. Temporary new deficits occurred in 43.2% of patients, with facial nerve paralysis being the most common (14.1%). No significant correlation was found between the size of the craniotomy and the extent of tumor resection (p = 0.155), except in the case of VS (p = 0.041). Larger craniotomy sizes were associated with higher rates of complications (p = 0.016), especially CSF leaks (p = 0.006). Complications significantly affected the likelihood and number of new deficits (p < 0.001 for both), particularly postoperative bleeding (p = 0.019, p = 0.001), CSF leaks (p = 0.026, p = 0.039), and hydrocephalus (p = 0.050, p = 0.007). Conclusions: The potential for complications related to the surgical approach cannot be overlooked. The size of the tumor should not dictate larger surgical approaches due to the associated increase in postoperative complications; a tailored approach that considers the precise tumor location and pathology is crucial for optimizing postoperative outcomes.

The Role of Repeated Surgical Resections for Recurrent Brain Metastases in Older Population.

Background and Objectives: The impact of surgery for recurrent brain metastases in elderly patients has been the object of debate due to limited information in the literature. We analyzed clinical outcome and survival of elderly patients with recurrent brain metastases in order to assess potentially beneficial role of surgery. Materials and methods: In total, 219 patients with recurrent brain metastases between 2007 and 2022 were identified, of which 95 underwent re-resection; 83 patients aged 65 and older were analyzed. A survival analysis was performed, and clinical outcomes were evaluated. Results: The median survival time after surgery for recurrent brain metastases was 6 months (95CI 4-10) in older patients and 8 (95CI 7-9) in younger patients (p = 0.619). Out of all the older patients, 33 who underwent surgical resection showed prolonged survival compared with patients who did not receive surgical resection (median: 14, 95CI 8-19 vs. 4, 95CI 4-7, p = 0.011). All patients had preoperative Karnofsky performance scores of >70, which did not deteriorate after surgery (87.02 ± 5.76 vs. 85 ± 6.85; p = 0.055). In the univariate analysis, complete cytoreduction was a favorable prognostic factor. The tumor volume, the number of metastases, extracranial disease progression, adjuvant radiation, and systemic therapy did not affect survival in this cohort. Conclusions: Patients aged 65 and older benefit from neurosurgical resections of recurrent brain metastases. Survival did not differ from that in younger patients, which can be explained by a better preoperative functional status. Moreover, independent of the extent of resection, older patients who underwent surgery showed better survival than patients who did not receive surgical treatment. Complete cytoreduction was a favorable prognostic marker.

Navigating Brain Metastases: Unveiling the Potential of 3-Tesla Intraoperative Magnetic Resonance Imaging.

Intraoperative magnetic resonance imaging (iMRI) has witnessed significant growth in the field of neurosurgery, particularly in glioma surgery, enhancing image-guided neuronavigation and optimizing the extent of resection (EOR). Despite its extensive use in the treatment of gliomas, its utility in brain metastases (BMs) remains unexplored. This study examined the effect of iMRI on BM resection. This retrospective study was conducted at the neurosurgical center of the University Hospital of the Technical University of Munich and involved 25 patients with BM who underwent resection using 3-Tesla iMRI between 2018 and 2022. Volumetric measurements of the resected contrast-enhancing metastases were performed using preoperative, intraoperative, and postoperative MRI images. The Karnofsky Performance Score (KPS) and neurological status of the patients were assessed pre- and postoperatively. Local recurrence and in-brain progression were reported in patients who underwent follow-up MRI at 3 and 6 months postoperatively. In this cohort (n = 25, mean age 63.6 years), non-small-cell lung cancer (NSCLC) was the most common origin (28%). The mean surgical duration was 219.9 min, and that of iMRI was 61.7 min. Indications for iMRI were primarily associated with preoperative imaging, suggesting an unclear entity that is often suspicious for glioma. Gross total resection (GTR) was achieved in 21 patients (84%). Continued resection was pursued after iMRI in six cases (24%), resulting in an improved EOR of 100% in five cases and 97.6% in one case. Neurological status postoperatively remained stable in 60%, improved in 24%, and worsened in 16% of patients. No wound healing or postoperative complications were observed. Among the thirteen patients who underwent follow-up MRI 3 months postoperatively, one patient showed local recurrence at the site of resection, and seven patients showed in-brain progression. Of the eight patients who underwent a 6-month follow-up MRI, two showed local recurrence, while three exhibited in-brain progression. The observed favorable profiles of GTR, coupled with the notable absence of wound-healing problems and acute postoperative complications, affirm the safety and feasibility of incorporating iMRI into the neurosurgical workflow for resecting BM with specific indications. The real-time imaging capabilities of iMRI offer unparalleled precision, aiding meticulous tumor delineation and informed decision-making, ultimately contributing to improved patient outcomes. Although our experience suggests the potential benefits of iMRI as a safe tool for enhancing EOR, we acknowledge the need for larger prospective clinical trials. Comprehensive investigations on a broader scale are imperative to further elucidate the specific indications for iMRI in the context of BMs and to study its impact on survival. Rigorous prospective studies will refine our understanding of the clinical scenarios in which iMRI can maximize its impact, guiding neurosurgeons toward more informed and tailored decision-making.

New Breakthroughs in the Diagnosis of Leptomeningeal Carcinomatosis: A Review of Liquid Biopsies of Cerebrospinal Fluid.

Leptomeningeal carcinomatosis represents a terminal stage and is a devastating complication of cancer. Despite its high incidence, current diagnostic methods fail to accurately detect this condition in a timely manner. This failure to diagnose leads to the refusal of treatment and the absence of clinical trials, hampering the development of new therapy strategies. The use of liquid biopsy is revolutionizing the field of diagnostic oncology. The dynamic and non-invasive detection of tumor markers has enormous potential in cancer diagnostics and treatment. Leptomeningeal carcinomatosis is a condition where invasive tissue biopsy is not part of the routine diagnostic analysis, making liquid biopsy an essential diagnostic tool. Several elements in cerebrospinal fluid (CSF) have been investigated as potential targets of liquid biopsy, including free circulating tumor cells, free circulating nucleic acids, proteins, exosomes, and even non-tumor cells as part of the dynamic tumor microenvironment. This review aims to summarize current breakthroughs in the research on liquid biopsy, including the latest breakthroughs in the identification of tumor cells and nucleic acids, and give an overview of future directions in the diagnosis of leptomeningeal carcinomatosis.

Single brain metastases - prognostic factors and impact of residual tumor burden on overall survival.

Background: Brain metastases (BM) are a common and challenging issue, with their incidence on the rise due to advancements in systemic therapies and increased patient survival. Most patients present with single BM, some of them without any further extracranial metastasis (i.e., solitary BM). The significance of postoperative intracranial tumor volume in the treatment of singular and solitary BM is still debated. Objective: This study aimed to determine the impact of resection and postoperative tumor burden on overall survival (OS) in patients with single BM. Methods: Patients with surgically treated single BM between 04/2007-01/2020 were retrospectively included. Residual tumor burden (RTB) was determined by manual segmentation of early postoperative brain MRI (72 h). Survival analyses were performed using Kaplan-Meier estimates for univariate analysis and Cox regression proportional hazards model for multivariate analysis, using preoperative Karnofsky performance status scale (KPSS), age, sex, RTB, incomplete resection and singular/solitary BM as covariates. Results: 340 patients were included, median age 64 years (54-71). 119 patients (35%) had solitary BM, 221 (65%) singular BM. Complete resection (RTB=0) was achieved in 73%, median preoperative tumor burden was 11.2 cm3 (5-25), and RTB 0 cm3 (0-0.2). Median OS of patients with singular BM was 13 months (4-33) vs 20 months (5-92) for solitary BM; p=0.062. Multivariate analysis revealed singular BM as independent risk factor for poorer OS: HR 1.840 (1.202-2.817), p=0.005. Complete vs. incomplete resection showed no significant OS difference (13 vs. 13 months, p=0.737). When focusing on solitary BM, complete resection led to a longer OS than incomplete resection (21 vs. 8 months), without statistical significance(p=0.250). Achieving RTB=0 resulted in higher OS for patients with solitary BM compared to singular BM (21 vs. 12 months, p=0.027). Patients who received postoperative radiotherapy (RT) had significantly longer OS compared to those without it (14 vs. 4 months, p<0.001), with favorable OS in those receiving stereotactic radiosurgery (SRS) (15 months (3-42), p<0.001) or hypofractionated stereotactic radiotherapy (HSRT). Conclusion: When complete intracranial tumor resection RTB=0 is achieved, patients with solitary BM have a favorable outcome compared to singular BM. Singular BM was confirmed as independent risk factor. There is a strong presumption that complete resection leads to an improved oncological prognosis. Patients with solitary BM tend to benefit with a favorable outcome following complete resection. Hence, surgical resection should be considered as a treatment option for patients presenting with either no or minimal extracranial disease. Furthermore, the highly favorable impact of postoperative RT on OS was demonstrated and confirmed, especially with SRS or HSRT.

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.

Fluorescein-stained confocal laser endomicroscopy versus conventional frozen section for intraoperative histopathological assessment of intracranial tumors.

BACKGROUND: The aim of this clinical trial was to compare Fluorescein-stained intraoperative confocal laser endomicroscopy (CLE) of intracranial lesions and evaluation by a neuropathologist with routine intraoperative frozen section (FS) assessment by neuropathology. METHODS: In this phase II noninferiority, prospective, multicenter, nonrandomized, off-label clinical trial (EudraCT: 2019-004512-58), patients above the age of 18 years with any intracranial lesion scheduled for elective resection were included. The diagnostic accuracies of both CLE and FS referenced with the final histopathological diagnosis were statistically compared in a noninferiority analysis, representing the primary endpoint. Secondary endpoints included the safety of the technique and time expedited for CLE and FS. RESULTS: A total of 210 patients were included by 3 participating sites between November 2020 and June 2022. Most common entities were high-grade gliomas (37.9%), metastases (24.1%), and meningiomas (22.7%). A total of 6 serious adverse events in 4 (2%) patients were recorded. For the primary endpoint, the diagnostic accuracy for CLE was inferior with 0.87 versus 0.91 for FS, resulting in a difference of 0.04 (95% confidence interval -0.10; 0.02; P = .367). The median time expedited until intraoperative diagnosis was 3 minutes for CLE and 27 minutes for FS, with a mean difference of 27.5 minutes (standard deviation 14.5; P < .001). CONCLUSIONS: CLE allowed for a safe and time-effective intraoperative histological diagnosis with a diagnostic accuracy of 87% across all intracranial entities included. The technique achieved histological assessments in real time with a 10-fold reduction of processing time compared to FS, which may invariably impact surgical strategy on the fly.

Cytoreduction of Residual Tumor Burden Is Decisive for Prolonged Survival in Patients with Recurrent Brain Metastases-Retrospective Analysis of 219 Patients.

BACKGROUND: Despite advances in treatment for brain metastases (BMs), the prognosis for recurrent BMs remains poor and requires further research to advance clinical management and improve patient outcomes. In particular, data addressing the impact of tumor volume and surgical resection with regard to survival remain scarce. METHODS: Adult patients with recurrent BMs between December 2007 and December 2022 were analyzed. A distinction was made between operated and non-operated patients, and the residual tumor burden (RTB) was determined by using (postoperative) MRI. Survival analysis was performed and RTB cutoff values were calculated using maximally selected log-rank statistics. In addition, further analyses on systemic tumor progression and (postoperative) tumor therapy were conducted. RESULTS: In total, 219 patients were included in the analysis. Median age was 60 years (IQR 52-69). Median preoperative tumor burden was 2.4 cm3 (IQR 0.8-8.3), and postoperative tumor burden was 0.5 cm3 (IQR 0.0-2.9). A total of 95 patients (43.4%) underwent surgery, and complete cytoreduction was achieved in 55 (25.1%) patients. Median overall survival was 6 months (IQR 2-10). Cutoff RTB in all patients was 0.12 cm3, showing a significant difference (p = 0.00029) in overall survival (OS). Multivariate analysis showed preoperative KPSS (HR 0.983, 95% CI, 0.967-0.997, p = 0.015), postoperative tumor burden (HR 1.03, 95% CI 1.008-1.053, p = 0.007), and complete vs. incomplete resection (HR 0.629, 95% CI 0.420-0.941, p = 0.024) as significant. Longer survival was significantly associated with surgery for recurrent BMs (p = 0.00097), and additional analysis demonstrated the significant effect of complete resection on survival (p = 0.0027). In the subgroup of patients with systemic progression, a cutoff RTB of 0.97 cm3 (p = 0.00068) was found; patients who had received surgery also showed prolonged OS (p = 0.036). Single systemic therapy (p = 0.048) and the combination of radiotherapy and systemic therapy had a significant influence on survival (p = 0.036). CONCLUSIONS: RTB is a strong prognostic factor for survival in patients with recurrent BMs. Operated patients with recurrent BMs showed longer survival independent of systemic progression. Maximal cytoreduction should be targeted to achieve better long-term outcomes.

Brain metastases in the elderly - Impact of residual tumor volume on overall survival.

Background: Due to demographic changes and an increased incidence of cancer with age, the number of patients with brain metastases (BMs) constantly increases, especially among the elderly. Novel systemic therapies, such as immunotherapy, have led to improved survival in recent years, but intracranial tumor progression may occur independently of a systemically effective therapy. Despite the growing number of geriatric patients, they are often overlooked in clinical trials, and there is no consensus on the impact of BM resection on survival. Objectives: The aim of this study was to analyze the impact of resection and residual tumor volume on clinical outcome and overall survival (OS) in elderly patients suffering from BM. Methods: Patients ≥ 75 years who had surgery for BM between April 2007 and January 2020 were retrospectively included. Residual tumor burden (RTB) was determined by segmentation of early postoperative brain MRI (72 h). Contrast-enhancing tumor subvolumes were segmented manually. "Postoperative tumor volume" refers to the targeted BMs. Impact of preoperative Karnofsky performance status scale (KPSS), age, sex and RTB on OS was analyzed. Survival analyses were performed using Kaplan-Meier estimates for the univariate analysis and the Cox regression proportional hazards model for the multivariate analysis. Results: One hundred and one patients were included. Median age at surgery was 78 years (IQR 76-81). Sixty-two patients (61%) had a single BM; 16 patients (16%) had two BMs; 13 patients (13%) had three BMs; and 10 patients (10%) had more than three BMs. Median preoperative tumor burden was 10.3 cm3 (IQR 5-25 cm3), and postoperative tumor burden was 0 cm3 (IQR 0-1.1 cm3). Complete cytoreduction (RTB = 0) was achieved in 52 patients (52%). Complete resection of the targeted metastases was achieved in 78 patients (78%). Median OS was 7 months (IQR 2-11). In univariate analysis, high preoperative KPSS (HR 0.986, 95% CI 0.973-0.998, p = 0.026) and small postoperative tumor burden (HR 1.025, 95% CI 1.002-1.047, p = 0.029) were significantly associated with prolonged OS. Patients with RTB = 0 survived significantly longer than those with residual tumor did (12 [IQR 5-19] vs. 5 [IQR 3-7] months, p = 0.007). Furthermore, prolongation of survival was significantly associated with surgery in patients with favorable KPSS, with an adjusted HR of 0.986 (p = 0.026). However, there were no significances regarding age. Conclusions: RTB is a strong predictor for prolonged OS, regardless of age or cancer type. Postoperative MRI should confirm the extent of resection, as intraoperative estimates do not warrant a complete resection. It is crucial to aim for maximal cytoreduction to achieve the best long-term outcomes for these patients, despite the fact the patients are advanced in age.

Enhancing outcomes: neurosurgical resection in brain metastasis patients with poor Karnofsky performance score - a comprehensive survival analysis.

Background: A reduced Karnofsky performance score (KPS) often leads to the discontinuation of surgical and adjuvant therapy, owing to a lack of evidence of survival and quality of life benefits. This study aimed to examine the clinical and treatment outcomes of patients with KPS < 70 after neurosurgical resection and identify prognostic factors associated with better survival. Methods: Patients with a preoperative KPS < 70 who underwent surgical resection for newly diagnosed brain metastases (BM) between 2007 and 2020 were retrospectively analyzed. The KPS, age, sex, tumor localization, cumulative tumor volume, number of lesions, extent of resection, prognostic assessment scores, adjuvant radiotherapy and systemic therapy, and presence of disease progression were analyzed. Univariate and multivariate logistic regression analyses were performed to determine the factors associated with better survival. Survival > 3 months was considered favorable and ≤ 3 months as poor. Results: A total of 140 patients were identified. Median overall survival was 5.6 months (range 0-58). There was no difference in the preoperative KPS between the groups of > 3 and ≤ 3 months (50; range, 20-60 vs. 50; range, 10-60, p = 0.077). There was a significant improvement in KPS after surgery in patients with a preoperative KPS of 20% (20 vs 40 ± 20, p = 0.048). In the other groups, no significant changes in KPS were observed. Adjuvant radiotherapy was associated with better survival (44 [84.6%] vs. 32 [36.4%]; hazard ratio [HR], 0.0363; confidence interval [CI], 0.197-0.670, p = 0.00199). Adjuvant chemotherapy and immunotherapy resulted in prolonged survival (24 [46.2%] vs. 12 [13.6%]; HR 0.474, CI 0.263-0.854, p = 0.013]. Systemic disease progression was associated with poor survival (36 [50%] vs. 71 [80.7%]; HR 5.975, CI 2.610-13.677, p < 0.001]. Conclusion: Neurosurgical resection is an appropriate treatment modality for patients with low KPS. Surgery may improve functional status and facilitate further tumor-specific treatment. Combined treatment with adjuvant radiotherapy and systemic therapy was associated with improved survival in this cohort of patients. Systemic tumor progression has been identified as an independent factor for a poor prognosis. There is almost no information regarding surgical and adjuvant treatment in patients with low KPS. Our paper provides novel data on clinical outcome and survival analysis of patients with BM who underwent surgical treatment.