Treatment Strategies for Glioblastoma in the Elderly: What Should We Focus on Compared to Younger Patients.

(1) Background: Although the incidence of glioblastoma (GB) has a peak in patients aged 75-84 years, no standard treatment regimen for elderly patients has been established so far. The goal of this study was to analyze the outcome of GB patients ≥ 65 years to detect predictors with relevant impacts on overall survival (OS) and progression-free survival (PFS). (2) Methods: Medical records referred to our institution from 2006 to 2020 were analyzed. Adult GB patients with clinical data, postoperative MRI data, and ≥1 follow-up investigation after surgical resection were included. The complete cohort was divided into a younger (<65) and an elderly group (≥65 years). Multiple factors regarding OS and PFS were scanned using univariate and multivariable regression with p < 0.05. (3) Results: 1004 patients were included with 322 (61.0%) male individuals in the younger and 267 (56.1%) males in the older cohort. The most common tumor localization was frontal in both groups. Gross total resection (GTR) was the most common surgical procedure in both groups, followed by subtotal resection (STR) (145; 27.5%) in the younger group, and biopsy (156; 32.8%) in the elderly group. Multivariate analyses detected that in the younger cohort, MGMT promoter methylation and GTR were predictors for a longer OS, while MGMT methylation, GTR, and hypofractionated radiation were significantly associated with a longer OS in the elderly group. (4) Conclusions: Elderly patients benefit from surgical resection of GB when they show MGMT promoter methylation, undergo GTR, and receive hypofractionated radiation. Furthermore, MGMT methylation seems to be associated with a longer PFS in elderly patients. Further investigations are required to confirm these findings, especially within prospective radiation therapy studies and molecular examinations.

The influence of radiological tumor growth pattern on sino­nasal health in pituitary adenomas.

Pituitary adenomas are one of the most common mass lesions of the brain and are associated with a reduced quality of life. While transnasal and transsphenoidal endoscopic approaches are considered to deliver similar recovery rates for sino-nasal health (SNH), the impact of radiological tumor growth patterns on SNH has not been evaluated. In the present study, the influence of radiological tumor growth on SNH was examined before and after endoscopic transsphenoidal tumor resection. Patient data were prospectively collected between August 1, 2016 and August 31, 2022. The Knosp and Hardy classifications were used to dichotomize pituitary adenoma lesions into low- and high-graded lesions. SNH was assessed shortly before surgery and at follow-up examinations 3-6 months after operation using the Sino-Nasal Outcome Test for Neurosurgery (SNOT-NC) questionnaire. Fully completed SNOT-NC questionnaires were collected before and after surgery from a total of 101 patients. Independent t-tests showed significantly higher rates of deterioration after surgery in patients with Knosp low-graded lesions compared with those with high-graded tumors for the SNOT-NC total score P=0.048, nasal discomfort P=0.034, sleep problems P=0.024 and visual impairment P=0.042. Pre- and post-operative comparisons for the Knosp low-graded tumor cohort showed an increase of nasal discomfort (P=0.004), while the Knosp high-graded tumor cohort reported decreased visual impairment (P=0.016) after surgery. Assessing the Hardy classification, increased nasal discomfort was reported in patients with high-graded infrasellar tumors after surgery (P=0.046). Growth characteristics of pituitary adenomas based on Knosp and Hardy classifications may influence SNH. Patients with less invasive lesions were revealed to be more prone to experiencing a decrease in SNH, which went beyond the assumed deterioration of 1-3 months. These findings indicate the importance of detailed information regarding SNH as part of every pre-operative patient briefing.

Modifiable vascular risk factors in patients with cerebral and spinal cavernous malformations: a complete 10-year follow-up study.

BACKGROUND AND PURPOSE: The aim was to investigate the effect of modifiable vascular risk factors on the risk of first and recurrent bleeding for patients with a cavernous malformation (CM) of the central nervous system (CNS) over a 10-year period. METHODS: A retrospective review of our CM institutional database was performed spanning from 2003 to 2021. The inclusion criteria were non-missing serial magnetic resonance imaging studies and clinical baseline metrics such as vascular risk factors. The exclusion criteria were patients who underwent surgical CM removal and patients with less than a decade of follow-up. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative risk (10 years) of hemorrhage. RESULTS: Eighty-nine patients with a CM of the CNS were included. Our results showed a non-significant increased risk of hemorrhage during 10 years of follow-up in patients using nicotine (hazard ratio 2.11, 95% confidence interval 0.86-5.21) and in patients with diabetes (hazard ratio 3.25, 95% confidence interval 0.71-14.81). For the presence of modifiable vascular risk factors at study baseline different cumulative 10-year risks of bleeding were observed: arterial hypertension 42.9% (18.8%-70.4%); diabetes 66.7% (12.5%-98.2%); hyperlipidemia 30% (8.1%-64.6%); active nicotine abuse 50% (24.1%-76%); and obesity 22.2% (4%-59.8%). Overall cumulative (10-year) hemorrhage risk was 30.3% (21.3%-41.1%). CONCLUSIONS: The probability of hemorrhage in untreated CNS CM patients increases progressively within a decade of follow-up. None of the modifiable vascular risk factors showed strong indication for an influence on hemorrhage risk, but our findings may suggest a more aggressive course in patients with active nicotine abuse or suffering from diabetes.

Central nervous system cavernous malformations: cross-sectional study assessing rebleeding risk after a second haemorrhage.

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the 5-year risk of a third bleeding event in cavernous malformations (CMs) of the central nervous system. METHODS: Patients with cerebral or spinal CMs treated between 2003 and 2021 were screened using our institutional database. Patients with a complete magnetic resonance imaging dataset, clinical baseline characteristics, and history of two bleeding events were included. Patients who underwent surgical CM removal were excluded. Neurological functional status was obtained using the modified Rankin Scale score at the second and third bleeding. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative 5-year risk for a third haemorrhage. RESULTS: Forty-two patients were included. Cox regression analysis adjusted for age and sex did not identify risk factors for a third haemorrhage. 37% of patients experienced neurological deterioration after the third haemorrhage (p = 0.019). The cumulative 5-year risk of a third bleeding was 66.7% (95% confidence interval [CI] 50.4%-80%) for the whole cohort, 65.9% (95% CI 49.3%-79.5%) for patients with bleeding at initial diagnosis, 72.7% (95% CI 39.3%-92.7%) for patients with a developmental venous anomaly, 76.9% (95% CI 55.9%-90.3%) for patients with CM localization to the brainstem and 75% (95% CI 50.6%-90.4%) for patients suffering from familial CM disease. CONCLUSIONS: During an untreated 5-year follow-up after a second haemorrhage, a significantly increased risk of a third haemorrhage compared to the known risk of a first and second bleeding event was identified. The third bleeding was significantly associated with neurological deterioration. These findings may justify a surgical treatment after a second bleeding event.

Spinal Meningioma Surgery through the Ages-Single-Center Experience over Three Decades.

Background and Objectives: Spinal meningiomas, which are well characterized and are most frequently intradural extramedullary tumors, represent 25% of all intradural spinal tumors. The goal of this study was to compare the outcomes of surgically treated patients with spinal meningiomas in two time intervals with special emphasis on postoperative functional outcomes. Methods: Patients with spinal meningiomas admitted to our department between 1990 and 2020 were enrolled and divided into a historic cohort (HC; treated 1990−2007) and a current cohort (CC; treated 2008−2020). Patients' clinical data and surgical and radiological reports were retrospectively analyzed up to 5 years. Preoperative and postoperative neurological function were assessed using the modified McCormick Scale (mMCS). The Charlson Comorbidity Index (CCI) was used to evaluate the effect of comorbidities on the preoperative status and postoperative outcome. Results: We included 300 patients. Participants in the CC (n = 144) were significantly younger compared to those in the HC (n = 156), with twice as many patients <50 years of age (p < 0.001). The most common tumor location was the thoracic spine (n = 204). The median follow-up was 38.1 months (±30.3 standard deviation). A symptom duration until surgery <12 months was significantly associated with an earlier improvement in the mMCS (p = 0.045). In the CC, this duration was shorter and patients' neurological function at the first and last follow-ups was significantly better than for those in the HC (p < 0.001 for both). Conclusions: Our study results suggested that the impact of surgical management and postoperative rehabilitation on spinal meningioma patients' long-term neurological outcome has reached important milestones over the last decades. An earlier diagnosis led to earlier surgical treatment and improved patients' postoperative neurological recovery. Our results exposed that surgical therapy for spinal meningioma should be performed within 12 months after appearance of symptoms to achieve a better recovery.

Medication intake and hemorrhage risk in patients with familial cerebral cavernous malformations.

OBJECTIVE: The objective of this study was to analyze the impact of medication intake on hemorrhage risk in patients with familial cerebral cavernous malformation (FCCM). METHODS: The authors' institutional database was screened for patients with FCCM who had been admitted to their department between 2003 and 2020. Patients with a complete magnetic resonance imaging (MRI) data set, evidence of multiple CCMs, clinical baseline characteristics, and follow-up (FU) examination were included in the study. The authors assessed the influence of medication intake on first or recurrent intracerebral hemorrhage (ICH) using univariate and multivariate logistic regression adjusted for age and sex. The longitudinal cumulative 5-year risk of hemorrhage was calculated by applying Kaplan-Meier and Cox regression analyses adjusted for age and sex. RESULTS: Two hundred five patients with FCCMs were included in the study. Multivariate Cox regression analysis revealed ICH as a predictor for recurrent hemorrhage during the 5-year FU. The authors also noted a tendency toward a decreased association with ICH during FU in patients on statin medication (HR 0.22, 95% CI 0.03-1.68, p = 0.143), although the relationship was not statistically significant. No bleeding events were observed in patients on antithrombotic therapy. Kaplan-Meier analysis and log-rank test showed a tendency toward a low risk of ICH during FU in patients on antithrombotic therapy (p = 0.085), as well as those on statin therapy (p = 0.193). The cumulative 5-year risk of bleeding was 22.82% (95% CI 17.33%-29.38%) for the entire cohort, 31.41% (95% CI 23.26%-40.83%) for patients with a history of ICH, 26.54% (95% CI 11.13%-49.7%) for individuals on beta-blocker medication, 6.25% (95% CI 0.33%-32.29%) for patients on statin medication, and 0% (95% CI 0%-30.13%) for patients on antithrombotic medication. CONCLUSIONS: ICH at diagnosis was identified as a risk factor for recurrent hemorrhage. Although the relationships were not statistically significant, statin and antithrombotic medication tended to be associated with decreased bleeding events.

Multiple cerebral cavernous malformations: Clinical course of confirmed, assumed and non-familial disease.

BACKGROUND AND PURPOSE: Analyze and compare the natural course of confirmed familial cerebral cavernous malformation (FCCM), assumed FCCM and non-familial multiple cerebral cavernous malformation (CCM) disease over a 5-year period. METHODS: Our institutional database was screened for patients with CCM admitted between 2003 and 2020. Patients with complete magnetic resonance imaging dataset, evidence of multiple CCM, clinical baseline characteristics, and follow-up examination were included. Patients were separated into confirmed familial cases, assumed familial cases or non-familial multiple cavernous malformations. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative 5-year risk for hemorrhage and recurrent hemorrhage. RESULTS: A total of 238 patients with multiple CCM were analyzed; 90 individuals had a confirmed FCCM disease, 115 an assumed FCCM, and 33 were allocated to the non-FCCM group. Univariate Cox regression analysis identified intracerebral hemorrhage (ICH) as mode of presentation (p = 0.001) as a predictor for occurrence of recurrent hemorrhage during the 5-year follow-up (FU). The cumulative 5-year risk of (re)bleeding was 21.6% for the entire cohort, 30.7% for patients with ICH at diagnosis, 22.1% for those patients with a confirmed diagnosis of FCCM, 23.5% for those with an assumed FCCM, and 21% for the non-FCCM cases. CONCLUSIONS: FCCM patients with ICH at diagnosis are prone to develop rebleeding. During untreated 5-year FU, FCCM patients and patients with sporadic multiple CCM reveal an almost equal susceptibility for (re)hemorrhage. Moreover, confirmed, assumed and non-FCCM patients showed an equal cumulative 5-year risk of symptomatic ICH. The probability of hemorrhage tends to increase over time, particularly in cases with ICH at presentation.

Ciprofloxacin enhances phototoxicity of 5-aminolevulinic acid mediated photodynamic treatment for chordoma cell lines.

BACKGROUND: Chordoma are uncommon aggressive tumors of the skeleton. Surgical resection is often subtotal and adjuvant treatment possibilities are limited as chordomas are highly chemo- and radioresistant. In the present study we examined the impact of 5-ALA PDT on different human chordoma cell lines. Furthermore, we investigated the variation of two parameters: (1.) 5-ALA incubation time and (2.) supplemental use of ciprofloxacin as iron chelator. METHODS: Experiments were realized in vitro with three different human chordoma cell lines: U-CH2, U-CH2B and U-CH14. After pre-incubation for 24 h with various concentrations of ciprofloxacin (1.5 - 5.0 µg/ml), different amounts of 5-ALA (15 - 50 µg/ml) were applied to the cells either for a brief (4 h) or a long (6 h) incubation time. Subsequently cells were exposed to photodynamic radiation. Cell viability was exploited by WST-1 assay. Thus, for each of the three cell lines, two drug combinations (ciprofloxacin plus 5-ALA and 5-ALA only) and two incubation times (short, 4 h and long, 6 h) were tested. Negative control groups were also examined. RESULTS: Supplemental use of ciprofloxacin led to increased cell death in each of the cell lines. Different 5-ALA incubation times (4 h vs. 6 h) showed no significant differences in cell viability except for U-CH2. CONCLUSION: Ciprofloxacin as an ordinary applied antibiotic, enhanced the effect of 5-ALA PDT on different human chordoma cell lines in vitro. The impact was dependent on the dose of ciprofloxacin-5-ALA. There were no notable differences for the tested 5-ALA incubation times. In human chordoma cell lines 5-ALA PDT may effectively be amended by ciprofloxacin.