The importance of considering competing risks in recurrence analysis of intracranial meningioma.

BACKGROUND: The risk of recurrence is overestimated by the Kaplan-Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of Kaplan-Meier that accounts for competing events. Meningiomas commonly occur in older individuals and have slow-growing properties, thereby warranting competing risk analysis. The extent to which competing events are considered in meningioma literature is unknown, and the consequences of using incorrect methodologies in meningioma recurrence risk analysis have not been investigated. METHODS: We surveyed articles indexed on PubMed since 2020 to assess the usage of competing risk analysis in recent meningioma literature. To compare recurrence risk estimates obtained through Kaplan-Meier and Aalen-Johansen methods, we applied our international database comprising ~ 8,000 patients with a primary meningioma collected from 42 institutions. RESULTS: Of 513 articles, 169 were eligible for full-text screening. There were 6,537 eligible cases from our PERNS database. The discrepancy between the results obtained by Kaplan-Meier and Aalen-Johansen was negligible among low-grade lesions and younger individuals. The discrepancy increased substantially in the patient groups associated with higher rates of competing events (older patients with high-grade lesions). CONCLUSION: The importance of considering competing events in recurrence risk analysis is poorly recognized as only 6% of the studies we surveyed employed Aalen-Johansen analyses. Consequently, most of the previous literature has overestimated the risk of recurrence. The overestimation was negligible for studies involving low-grade lesions in younger individuals; however, overestimation might have been substantial for studies on high-grade lesions.

Patients at Greatest Risk of Missing Initial 1-Year Follow-Up After Pituitary Adenoma Resection.

OBJECTIVE: Routine evaluation and surveillance imaging after pituitary adenoma (PA) endoscopic endonasal transsphenoidal resection (EETS) is a neurosurgical practice to identify tumor recurrence. This study aims to identify social and clinical factors that may contribute to patients missing their initial 1-year follow-up appointment and provide guidance for targeted education to improve patient adherence with postoperative treatment plans, ultimately reducing unknown adenoma recurrence. METHODS: The authors performed a single-center retrospective review of patients who underwent EETS for PAs from 2007 to 2023. Patients were analyzed for sociodemographic factors, presenting symptoms, time to surgery, surgical outcomes, and adherence to postoperative follow-up visits at 1 year after surgery. RESULTS: A total of 256 patients with PAs treated by EETS met inclusion criteria; 218 (85%) of these patients attended 1-year follow-up, and 38 (15%) missed this visit. Twenty-nine (76%) individuals who missed their 1-year follow up were men (P = 0.006). Divorced/widowed/separated patients were 2 times more likely to miss their follow-up compared with their married counterparts (P = 0.008). Additional significant risk factors included older age, as the mean age for patients who missed their 1-year appointment was 60.1 years compared with 54.7 years (P = 0.028). Patients with visual field deficits at initial presentation were also less likely to follow-up at 1 year (P = 0.03). CONCLUSIONS: Risk factors of missed 1-year follow-up appointments after PA resection include male sex, divorced/widowed/separated marital status, older age, and the presence of visual deficits at initial presentation. Increased education efforts can be selectively aimed at these at-risk patient cohorts to improve patient compliance and reduce consequences of undetected tumor recurrence.

Anti-aquaporin-4 immunoglobulin G/anti-myelin oligodendrocyte glycoprotein immunoglobulin G double-positive paraneoplastic neurological syndrome in a patient with triple-negative breast cancer.

We report a rare case of paraneoplastic neurological syndrome with dual seropositivity of anti-aquaporin-4 and myelin oligodendrocyte glycoprotein antibodies in a 40 year-old woman with metastatic triple-negative breast cancer. She received multiple lines of anti-neoplastic treatment, including immunotherapy with pembrolizumab, as well as cytotoxic chemotherapy. Paraneoplastic meningoencephalomyelitis developed 2 years after diagnosis of breast cancer and 1 year after discontinuation of immunotherapy with pembrolizumab. She first developed longitudinally extending transverse myelitis followed by left optic neuritis and meningoencephalitis with new enhancing lesions in the brain and spinal leptomeninges. Cerebrospinal fluid analysis during both episodes showed normal glucose and protein, and elevated white blood cell count. Cytology was negative for malignancy. Cerebrospinal fluid was positive for neuromyelitis optica immunoglobulin G antibody anti-aquaporin-4, and autoimmune myelopathy panel was positive for myelin oligodendrocyte glycoprotein antibody. The patient had significant clinical and radiographic improvement after completion of five cycles of plasmapheresis followed by intravenous immunoglobulin. She did not have recurrence of paraneoplastic syndrome with maintenance rituximab every 6 months and daily low-dose prednisone. She succumbed to progressive systemic metastatic disease 4.5 years after her breast cancer diagnosis. This case shows that these antibodies can occur concurrently and cause clinical features, such as both neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody disease, in a patient with a singular type of cancer. We highlight the importance of testing for paraneoplastic etiology in cancer patients with radiographic menigoencephalomyelitis or meningitis with atypical symptoms of meningeal carcinomatosis and/or cerebrospinal fluid profile negative for leptomeningeal carcinomatosis.

Single Center Neurosurgical Outcomes and Trends in Endoscopic Endonasal Resection of 297 Sellar/Suprasellar Tumors Stratified by Duration of Neurosurgical Career.

BACKGROUND/OBJECTIVE: Endoscopic endonasal transsphenoidal surgery (EETS) is a common treatment for sellar and suprasellar tumors. While endoscopic training has improved over the years and formal fellowship training is now broadly available, the operative nuances of EETS conjectures the existence a learning curve as a neurosurgeon matures with experience. We aim to evaluate operative outcomes of 3 different experience levels of neurosurgeons over time at a single institution. METHODS: We reviewed all adult patients who underwent EETS at Loyola University Medical Center by 3 early career, 1 midcareer, and 2 late career neurosurgeons from 2007 to 2023. A comparative assessment of patient demographics, tumor features, and surgical outcomes was done using metrics such as length of surgery, rates of gross total resection (GTR) and symptomatic improvement, new postoperative steroid dependence, and development of diabetes insipidus (DI). T-tests and χ2 were used to statistically evaluate the study cohorts. RESULTS: A total of 297 patients underwent EETS. One hundred three (35%) were operated on by an early career, 122 (41%) by a mid-career, and 72 (24%) by a late career neurosurgeon. Late-career surgeons had shorter operation times (144 vs. 180 minutes with early and mid-career, P = 0.029) and increased GTR rates (P = 0.008). There were no significant differences between the symptomatic improvement rates amongst various surgeon experience levels. Although not statistically significant, early-career neurosurgeons had lower rates of new postoperative steroid dependence. Patients of early career surgeons experienced significantly less DI (15% vs. 40%, P = 0.004). CONCLUSIONS: Late-career neurosurgeons had shorter operation lengths, achieved higher rates of GTR, and their patients experienced significantly higher rates of DI. Overall outcomes remained stable throughout the course of 16 years between different surgeon experience levels.

Cerebral arterial vasospasm complicating supratentorial meningioma resection: illustrative cases.

BACKGROUND: Cerebral arterial vasospasm is a rare complication after supratentorial meningioma resection. The pathophysiology of this condition may be similar to vasospasm after aneurysmal subarachnoid hemorrhage, and treatment options may be similar. OBSERVATIONS: The authors present two cases of cerebral vasospasm after supratentorial meningioma resection and perform a systematic literature review of similar cases. LESSONS: Cerebral arterial vasospasm after supratentorial meningioma resection may be associated with significant morbidity due to cerebral ischemia if not addressed in a timely manner. Treatment paradigms may be adopted from the management of arterial vasospasm associated with subarachnoid hemorrhage.

National Trends and Factors Associated with Voluntary Refusal of Glioblastoma Treatment: A Retrospective Review of the National Cancer Database.

OBJECTIVE: Adherence to combinatorial treatments are important predictors of improved long-term outcomes for patients with glioblastoma (GB); however, factors associated with refusal of surgery, chemotherapy, or radiotherapy (RT) by patients with GB have not been studied. METHODS: The National Cancer Database was queried from 2004 to 2018 to identify patients with a primary diagnosis of GB who underwent surgical resection alone or followed by either RT or chemotherapy. Adult patients who voluntarily rejected a physician's recommendations for 1 or more treatment were selected. Multivariable regression was used to identify factors associated with rejection of surgical resection, chemotherapy, and RT. Patients receiving treatment were 3:1 propensity score matched to those rejecting treatment and median overall survival (OS) was compared. RESULTS: 58,788 patients were included in the analysis. Factors associated with voluntary refusal of GB treatment included: old age, nonprivate insurance, female sex, Black race, comorbidities, treatment at a nonacademic facility, and living 55+ miles away from a treatment facility (P < 0.05). On propensity matched analysis, refusal of surgery conferred a 4 month decrease in OS (P < 0.001), RT an 8 month decrease in OS (P < 0.001), and chemotherapy a 7 month decrease in OS (P < 0.001). CONCLUSIONS: In patients with GB, age, sex, race, nonprivate insurance, medical comorbidities, distance from treatment facility, and geographic location were associated with refusal of surgery, postsurgical RT, and chemotherapy. In addition, treatment refusal had a significant impact on OS length.

Age-stratified comorbid and pharmacologic analysis of patients with glioblastoma.

Background: Increased age is a strong and unfavorable prognostic factor for patients with glioblastoma (GBM). However, the relationships between stratified patient age, comorbidities, and medications have yet to be explored in GBM patient survival analyses. Objective: To evaluate co-morbid conditions, tumor-related symptoms, medication prescriptions, and subject age for patients with GBM and to establish potential targets for prospective studies. Methods: Electronic health records for 565 patients with IDHwt GBM were evaluated at a single center between January 1, 2000 and August 9, 2021 were retrospectively assessed. Data were stratified by MGMT promoter methylation status when available and were used to construct multivariable time-dependent cox models and intra-cohort hazards. Results: Younger (<65 years of age) but not older (≥65 years) GBM patients demonstrated a worse prognosis with movement related disabilities (P < 0.0001), gait/balance difficulty (P = 0.04) and weakness (P = 0.007), as well as psychiatric conditions, mental health disorders (P = 0.002) and anxiety (P = 0.001). In contrast, older but not younger GBM patients demonstrated a worse prognosis with epilepsy (P = 0.039). Both groups had worse survival with confusion/altered mental status (P = 0.023 vs < 0.000) and an improved survival with a Temozolomide prescription. Older but not younger GBM patients experienced an improved hazard with a prescription of ace-inhibitor medications (P = 0.048). Conclusion: Age-dependent novel associations between clinical symptoms and medications prescribed for co-morbid conditions were demonstrated in patients with GBM. The results of the current work support future mechanistic studies that investigate the negative relationship(s) between increased age, comorbidities, and drug therapies for differential clinical decision-making across the lifespan of patients with GBM.