CNS Oncology最新文献

Aim: Understanding and supporting quality of life (QoL) and daily functioning in glioma patients is a clinical imperative. In this study, we examined the relationship between cognition, psychological factors, measures of health-related QoL and functioning in glioma survivors. Materials & methods: We examined neuropsychological, self-reported cognition, mood and QoL correlates of work and non-work-related daily functioning in 23 glioma survivors, and carried out linear models of the best predictors. Results & conclusion: A total of 13/23 participants were working at the time of enrollment. The best model for worse work-related functioning (R² = .83) included worse self-reported cognitive function, depression, loneliness and brain tumor symptoms. The best model for worse non-work-related functioning (R² = .61) included worse self-reported cognitive functioning, anxiety, sleep disturbance and physical functioning. Neuropsychological variables were not among the most highly correlated with function. Worse cognitive, particularly self-reported and psychosocial outcomes may compromise optimal functioning in glioma survivors.

Glioblastoma (GBM) accounts for over 50% of gliomas and carries the worst prognosis of all solid tumors. Owing to the limited local control afforded by surgery alone, efficacious adjuvant treatments such as radiotherapy (RT) and chemotherapy are fundamental in achieving durable disease control. The best clinical outcomes are achieved with tri-modality treatment consisting of surgery, RT and systemic therapy. While RT-chemotherapy combination regimens are well established in oncology, this approach was largely unsuccessful in GBM until the introduction of temozolomide. The success of this combination has stimulated the search for other candidate drugs for concomitant use with RT in GBM. This review seeks to collate the current evidence for these agents and synthesize possible future directions for the field.

Aim: To ascertain the maximum tolerated dose (MTD)/maximum feasible dose (MFD) of WP1066 and p-STAT3 target engagement within recurrent glioblastoma (GBM) patients. Patients & methods: In a first-in-human open-label, single-center, single-arm 3 + 3 design Phase I clinical trial, eight patients were treated with WP1066 until disease progression or unacceptable toxicities. Results: In the absence of significant toxicity, the MFD was identified to be 8 mg/kg. The most common adverse event was grade 1 nausea and diarrhea in 50% of patients. No treatment-related deaths occurred; 6 of 8 patients died from disease progression and one was lost to follow-up. Of 8 patients with radiographic follow-up, all had progressive disease. The longest response duration exceeded 3.25 months. The median progression-free survival (PFS) time was 2.3 months (95% CI: 1.7 months-NA months), and 6-month PFS (PFS6) rate was 0%. The median overall survival (OS) rate was 25 months (95% CI: 22.5 months-NA months), with an estimated 1-year OS rate of 100%. Pharmacokinetic (PK) data demonstrated that at 8 mg/kg, the T_1/2 was 2-3 h with a dose dependent increase in the C_max. Immune monitoring of the peripheral blood demonstrated that there was p-STAT3 suppression starting at a dose of 1 mg/kg. Conclusion: Immune analyses indicated that WP1066 inhibited systemic immune p-STAT3. WP1066 had an MFD identified at 8 mg/kg which is the target allometric dose based on prior preclinical modeling in combination with radiation therapy and a Phase II study is being planned for newly diagnosed MGMT promoter unmethylated glioblastoma patients.

Aim: Adult pilocytic astrocytoma is a rare tumor. We aim to contribute to understanding its clinical course and prognosis. Patients & methods: We searched our database for patients older than 18 years with pathology-proven pilocytic astrocytoma. Patients' clinical data were analyzed. Results: Fifteen patients were identified. The median age at diagnosis was 25 years (range: 18-56). Tumors were supratentorial in 47%. Gross-total and near-total resections were achieved in 40%, and sub-total resection in 47%. One (7%) recurrence and no mortality were encountered during a median follow-up of 11 months (range: 1-76). Conclusion: Pilocytic astrocytoma behaves differently in adults compared with pediatrics. It tends to arise in surgically challenging areas where the extent of resection may be limited. Total resection should be the main therapy whenever feasible. The survival rates are good, and recurrence is low.

Background: To illustrate challenges of imaging interpretation in patients with oligodendroglioma seen at a referral center and evaluate interrater reliability. Methods: Two neuro-oncologists reviewed diagnostic preradiation MRIs of oligodendroglioma patients; interrater reliability was calculated with the kappa coefficient (k). A neuroradiologist measured presurgical apparent diffusion coefficient (ADC), if available. Results: Extensive enhancement was noted in four of 58 patients, k = 0.7; necrosis in seven of 58, k = 0.61; calcification in seven of 17, k = 1.0; diffusion restriction in two of 39 patients, k = 1.0 (all only in grade 3). ADC values with receiver operator characteristic analysis for area under the curve were 0.473, not significantly different from the null hypothesis (p = 0.14). Conclusions: Extensive enhancement, necrosis and calcification correlated with grade 3 oligodendroglioma in our sample. However, interrater variability is an important limitation when assessing radiographic features, supporting the need for standardization of imaging protocols and their interpretation.

Despite the improved understanding of the molecular and genetic heterogeneity of glioblastoma, there is still an unmet need for better therapeutics, as treatment approaches have remained unchanged in recent years. Research into the role of the immune microenvironment has generated enthusiasm for testing immunotherapy (specifically, immune checkpoint inhibitors). However, to date, trials of immunotherapy in glioblastoma have not demonstrated a survival advantage. Combination approaches aimed at optimally inducing response to immune checkpoint inhibitors with radiotherapy are currently being investigated. Herein, the authors describe their experience of the potential benefit and clinical outcomes of using combination pembrolizumab (an immune checkpoint inhibitor) and laser interstitial thermal therapy in a case series of patients with recurrent IDH-wild-type glioblastoma.

Avascular necrosis (AVN) is a rare but serious adverse event associated with the use of corticosteroids for long durations or at high doses. This case report describes a 47-year-old female patient with low-grade astrocytoma who was initiated on low-dose dexamethasone for symptom management. The patient developed joint pain 1 year after steroid exposure, then was found to have AVN of the hip followed by multiple other joints. This case report highlights the extent to which AVN can occur in patients with brain tumors following a short course of low-dose corticosteroids. Careful evaluation of and monitoring for the development of AVN should occur frequently in patients with brain tumors given the frequent use of corticosteroids for symptom management in this population.

Background: Primary intracranial germ cell tumors (ICGCT) are often diagnosed with tumor markers and imaging, which may avoid the need for a biopsy. An intracranial germ cell tumor with mild elevation of markers is seldom stratified as a distinct entity. Methods: Fifty-nine patients were stratified into three groups: pure germinoma (PG), secreting germinoma (SG) and non-germinomatous germ cell tumors (NGGCTs). Results: At 5 years, progression-free survival and overall survival of the three groups (PG vs SG vs NGGCT) were 91% versus 81% versus 59%, and 100% versus 82% versus 68%, respectively. There was no statistically significant difference in outcome among histologically and clinically diagnosed germinomas. Conclusion: A criterion for clinical diagnosis when a biopsy is not feasible is elucidated, and comparable outcomes were demonstrated with histologically diagnosed germinomas.

Aim: Investigate real-world outcomes and healthcare utilization of patients with glioblastoma multiforme (GBM) related to O⁶-methylguanine DNA methyltransferase (MGMT) promoter testing and methylation. Patients & methods: US Oncology Network data were analyzed for patients receiving first-line (1L) treatment for GBM. Results: Most patients received 1L radiation with temozolomide. Unadjusted median overall survival (OS) was higher in tested versus untested (median:18.1 vs 11.8 months) and in methylated versus unmethylated (median: 25.5 vs 12.4 months). Untested status, unmethylated MGMT and older age were associated with reduced OS and longer 1L treatment with increased OS. Similar findings were observed for progression-free survival. Utilization was similar between cohorts. Conclusion: In community oncology practices, MGMT methylation and testing were predictive of better survival in GBM.