Journal of Neuro-Oncology最新文献

Purpose: Immune checkpoint inhibitors (ICI) are increasingly being administered to cancer patients, including those with brain metastases (BMs). However, in a subset of cancer patients, ICI have shown to paradoxically accelerate tumor growth. This phenomenon is known as hyperprogressive disease (HPD). The aim of this study is to investigate the occurrence of HPD following initiation of ICI in BM patients.

Methods: We retrospectively reviewed the charts of 60 surgically treated patients with BMs from non-small cell lung cancer or melanoma who were administered ICI at the Brigham and Women's Hospital, Boston between July 2008 and July 2018. BM tumor volumes before and after initiation of ICI were collected. HPD was defined as a 'post-immunotherapy' tumor growth rate (TGR) > 2 times 'pre-immunotherapy' TGR within three months following initiation of ICI.

Results: Among the 25 included patients treated with ICI, five patients showed HPD with an increase of post-immunotherapy TGR ranging from 4.9 to 207.7 times the pre-immunotherapy TGR. The median survival after initiation of ICI was was 8.0 months in the HPD cases and 13 months in the non-HPD patients.

Conclusion: HPD occurred in about 20% of BM patients receiving ICI. More research is necessary to prospectively analyze the occurrence of HPD and identify predictive factors for HPD in BM patients.

Purpose: Caregivers of patients with brain tumors play an essential role in treatment and symptom relief; however, this responsibility often results in a substantial and prolonged burden, negatively impacting caregivers' health and quality of life. This study aimed to evaluate the mental health status of caregivers of patients with malignant brain tumors and identify factors influencing mental health outcomes.

Methods: We analyzed data from the National Survey on the Needs and Support of Brain Tumor Patients and Caregivers, conducted by the research group on the Needs and Support of Brain Tumor Patients and their Caregivers in 2023. The study protocol was approved by the Research Ethics Review Committee of the National Cancer Center (approval No.: 2022 - 430). A total of 115 caregivers (36 male and 79 female) participated in the study. Depression risk was assessed using the Distress and Impact Thermometer.

Results: Fifty caregivers (43.4%) were classified into the suspected depression group. Factors significantly associated with an increased risk of depression after multivariate adjustment included "being tired of caring for others" and "being diagnosed with a brain tumor within 2 years."

Conclusion: Caregivers of patients with brain tumors face considerable mental health challenges, with a notable proportion at risk of depression. Targeted interventions, particularly for those recently assuming caregiving roles and experiencing fatigue, are essential for improving their mental health and overall quality of life.

Purpose: This registry-based study aims to examine the variation in biopsy and resection indications for glioblastoma patients across Dutch hospitals and to identify patient- and hospital-related factors associated with the surgical treatment.

Methods: Data from all 7443 adults with first-time glioblastoma surgery at 12 hospitals were obtained from the prospective population-based Quality Registry Neurosurgery in the Netherlands between 2011 and 2021. Patients were stratified by either biopsy or resection. We analyzed variation in American Association of Anesthesiologist (ASA) classification, Karnofsky Performance Score (KPS), gender and age distribution between the different centers. Between-hospital variation in biopsy percentage was analyzed using a funnel plot. Logistic regression was used to identify associated patient- and hospital-related factors.

Results: In total, 32% of the newly diagnosed glioblastoma patients underwent a biopsy, with wide variations between the different centers (23-56%). Patients-related variables such as higher age or ASA classification and lower KPS were significantly associated with the indication for biopsy. After correction for these factors, between-hospital variation persisted, with two institutes performing more biopsies than expected and one less than expected. Median overall survival was 12.5 months (95% CI 12.2-12.9) in the resection group and 5.6 months (95% CI 5.1-6) in the biopsy group, with wide variations between the different centers.

Conclusion: A substantial between-hospital variation in biopsy percentages was found. Patient factors (age, ASA classification and KPS) but also hospital factors (such as academic setting) impact surgical decisions. Variation persisted also after correction for potential confounders, indicating that other factors play a role in decision-making.

Purpose: Methylation of the O⁶-methylguanine-DNA methyltransferase (MGMT) promoter is an important prognostic marker in glioblastoma (GBM); however, its implementation in clinical practice remains understudied. Here, we assessed the prevalence of MGMT methylation status among GBM patients in the United States. Additionally, we evaluated treatment practices and survival outcomes of GBM patients according to MGMT promoter methylation status.

Methods: The National Cancer Database was queried to identify all adult U.S. patients (≥ 18 years) diagnosed with IDH-wildtype GBM between 2018 and 2020. Treatment regimen was grouped into no chemotherapy and no radiotherapy, chemotherapy alone (without radiotherapy), radiotherapy alone (without chemotherapy), and chemoradiotherapy (chemotherapy and radiotherapy). Survival data were analyzed using Kaplan-Meier survival curves, log-rank tests, and multivariable Cox proportional hazard modeling.

Results: A total of 20,734 patients were included, of whom 6,404 (30.9%) had MGMT-methylated GBM, 9,065 (43.7%) had MGMT-unmethylated tumors, and 5,265 (25.4%) had unknown methylation status. The median and three-year overall survival were 12.4 months and 15.5%, respectively, for the entire cohort (16.4 months and 23.9% for MGMT-methylated patients and 11.8 months and 9.8% for MGMT-unmethylated patients, p < 0.001). Chemoradiotherapy was less commonly used for elderly (≥ 70 years, 58.5%) than non-elderly (< 70 years, 79.2%) patients. Among elderly patients, radiotherapy alone was more commonly administered than chemotherapy alone for patients with MGMT-unmethylated tumors (11.2% vs. 2.1%) and MGMT-methylated tumors (6.6% vs. 3.9%). However, chemotherapy alone was associated with a lower mortality risk (HR 0.71, 95% CI 0.51-0.99, p = 0.04) than radiotherapy alone for elderly patients with MGMT-methylated tumors, while chemotherapy alone was associated with a higher mortality risk (HR 1.63, 95% CI 1.09-2.44, p = 0.02) than radiotherapy alone for elderly patients with MGMT-unmethylated tumors. Patients who were elderly, uninsured, insured through Medicaid, lived in zip codes with lower median education levels, or received care at non-academic programs were less likely to undergo MGMT testing.

Conclusion: A high proportion of GBM patients in the United States undergo MGMT promoter testing, though significant sociodemographic disparities exist. While there was a decrease in chemoradiotherapy use with increasing age, radiotherapy alone was more commonly administered to elderly patients than chemotherapy alone irrespective of MGMT promoter methylation status.

Purpose: To evaluate the efficacy and safety of aumolertinib in treating non-small cell lung cancer (NSCLC) patients with leptomeningeal metastasis (LM) and epidermal growth factor receptor (EGFR) mutations.

Methods: We conducted a retrospective analysis of clinical data from 79 patients with EGFR-mutated advanced NSCLC treated with aumolertinib after being diagnosed with LM at Shandong Cancer Hospital and Institute between April 2020 and July 2023. We evaluated overall survival (OS), progression-free survival (PFS), LM-PFS, and safety. Patient prognosis was assessed using Kaplan-Meier and Cox regression analyses.

Results: The median follow-up duration was 19.8 months (95% CI: 16.2-23.4), and 16 (20.3%) patients had previously used third-generation EGFR-TKI. The median LM-PFS was 10.6 months (95% CI: 8.6-12.5). The overall response rate (ORR) for LM was 53.2%, while the disease control rate (DCR) reached 91.1%. Among the 67 (84.8%) patients presenting with symptoms attributable to LM, 60 reported improved or stable symptoms. The median OS was 17.7 months (95% CI: 13.7-21.7), while the median PFS was 9.7 months (95% CI: 7.5-11.9). The systemic ORR and DCR were 38.0% and 87.3%, respectively. Multivariate Cox regression analysis identified L858R mutations (hazard ratio [HR] = 2.22, P = 0.030), prior systemic therapy (HR = 3.89, P < 0.001), ECOG PS ≥ 2 (HR = 4.06, P < 0.001) and ≥ 3 extracranial organ metastases (HR = 2.20, P = 0.025) as independent negative predictors of OS. Creatine kinase elevation (HR = 0.41, P = 0.018) was an independent predictor of better OS. Treatment-related adverse events occurred in 61 patients (77.2%), predominantly as grade 1 or 2.

Conclusion: Aumolertinib showed potential in treating EGFR-mutated NSCLC patients with LM, with a tolerable safety profile.

Purpose: Sonodynamic therapy, which combines a tumor cell-selective sonosensitizer with ultrasound, is gaining attention as a promising new treatment approach for glioblastoma. The objective of this case study is to report on the first applications of 5-aminolevulinic acid (5-ALA) in combination with low-intensity, non-targeted ultrasound as neo-adjuvant treatment in therapy naïve glioblastoma.

Methods: Three patients with therapy naïve newly diagnosed glioblastoma were treated once before cytoreductive surgery with 5-ALA in combination with hemispheric, low-intensity, non-targeted ultrasound, assuming cell death to be triggered by non-ablative activation of 5-ALA-induced, tumor selective porphyrins.

Results: No adverse effects were noted. Post-procedural MRI indicated a decrease in apparent diffusion coefficient values in tumors, suggesting cytotoxic effects. Relative cerebral blood volumes and leakage were increased for two patients with available perfusion imaging. Tissue obtained during surgery suggested increased cleaved-caspase III expression, a marker of apoptosis.

Conclusion: We saw an immediate marked imaging response indicating cytotoxic edema and indications of a histopathology response from just a single treatment. Correlation to clinical outcomes and extension of overall survival remains to be seen. A Phase 1 safety study has been submitted for regulatory approval.

Purpose: Opting for first-line surgery in carefully selected patients with microprolactinomas provides the advantage of avoiding long-term dopamine agonist (DA) medication and potential associated side effects. However, the lack of comprehensive long-term data poses a challenge in identifying those patients who would benefit the most from upfront surgery. To improve guidance in the selection process for microprolactinoma patients in clinical practice, we aimed to establish simple clinical and biochemical parameters predicting non-dependence on DAs.

Methodology: Retrospective analysis of a prospectively maintained database, focusing on patients with microprolactinomas who underwent upfront surgery. We assessed clinical and biochemical risk factors for the patients' reliance on DAs at their latest follow-up using regression analysis. We next proceeded to conduct Receiver Operating Characteristic (ROC) analysis to determine the optimal threshold cutoff prolactin (PRL) level for practical application in clinical settings that best differentiates between surgical long-term remission status and long-term dependence on DAs.

Results: A microadenoma was observed in 46 patients, of whom 12 (26%) exhibited long-term dependence on DAs at a median follow-up of 78 months. Baseline PRL values were significantly higher in patients with long-term DA dependence compared to those without (p = 0.05). High baseline PRL values (HR 23.9, 95% CI 1.0-593.7, p = 0.05), but not the presence of headache or male gender, were identified as independent predictors of long-term dependence on DAs. PRL thresholds for discriminating long-term DA dependence were estimated to be 290 µg/L (AUROC = 0.73, 95% CI 0.55-0.92, p = 0.03; sensitivity = 90%, specificity = 80%).

Conclusions: In patients with microprolactinomas, first-line surgery presents a favorable prospect for reducing reliance on DAs. However, for those with high PRL levels ≥ 290 µg/L at diagnosis, first-line surgery is not recommended, as the majority of them require adjuvant DA therapy in the long term.

Purpose: Social media platforms, particularly Twitter (X), play an important role in healthcare communication by sharing information and personal disease experiences. We investigated glioblastoma multiforme (GBM) posting behaviors on Twitter by comparing patient and informal caregiver tweets to healthcare professional tweets.

Methods: Using Keyhole, a third-party analytics tool, we analyzed 1,639 tweets containing the keyword "#glioblastoma" from January 1 to December 31, 2023. Users were categorized as patients, informal caregivers, or healthcare professionals. We employed Generalized Estimating Equation models and multinomial distributions to compare sentiment, thematic, and frequency engagement patterns across stakeholder groups.

Results: Informal caregivers produced the slight majority of tweets (51.6%), followed by healthcare professionals (39.0%). Informal caregivers expressed significantly more negative sentiments (relative to neutral ones) than healthcare professionals (p < 0.001). Thematic analysis revealed that patients (p < 0.001) and informal caregivers (p < 0.001) engaged in more emotional support than healthcare professionals. Healthcare professionals were more likely than patients (p < 0.001) and informal caregivers (p < 0.001) to self-promote. Patients (p < 0.001) and informal caregivers (p < 0.001) tweeted more on survival/mortality than healthcare professionals. Additionally, patients (p < 0.001) and informal caregivers (p < 0.001) had a higher average posting frequency per user than healthcare professionals.

Conclusion: Our findings indicate that GBM patients and informal caregivers were more likely to discuss emotional aspects of GBM care, while healthcare professionals had more informational and professional motives. Healthcare professionals who address these emotional, social, and financial communication disconnects can make their social media engagement more meaningful to patients who are often at least one of the primary targets of these accounts.