Search

Background: Glioblastoma (GBM), a primary malignant brain tumor, has a poor prognosis, even with standard treatments such as radiotherapy and chemotherapy. In this study, we explored the anticancer effects of the synergistic combination of perphenazine (PER), a dopamine receptor D2/3 (DRD2/3) antagonist, and temozolomide (TMZ), a standard treatment for GBM, in patient-derived human GBM tumorspheres (TSs)., Methods: The biological effects of the combination of PER and TMZ in GBM TSs were assessed by measuring cell viability, ATP, stemness, invasiveness, and apoptosis. Changes in protein and mRNA expression were analyzed using western blotting and RNA sequencing. Co-administration of PER and TMZ was evaluated in vivo using a mouse orthotopic xenograft model., Results: The Severance dataset showed that DRD2 and DRD3 expression was higher in tumor tissues than in the tumor-free cortex of patients with GBM. DRD2/3 knockout by CRISPR/Cas9 in patient-derived human GBM TSs inhibited cell growth and ATP production. The combined treatment with PER and TMZ resulted in superior effects on cell viability and ATP assays compared to those in single treatment groups. Flow cytometry, western blotting, and RNA sequencing confirmed elevated apoptosis in GBM TSs following combination treatment. Additionally, the combination of PER and TMZ downregulated the expression of protein and mRNA associated with stemness and invasiveness. In vivo evaluation showed that combining PER and TMZ extended the survival period of the mouse orthotopic xenograft model., Conclusions: The synergistic combination of PER and TMZ has potential as a novel combination treatment strategy for GBM., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Purpose: To investigate the clinical factors associated with breast cancer (BRCA) dural metastases (DMs), their impact on prognosis compared to brain parenchymal metastases (BPMs) alone, and differences between DM subtypes, aiming to inform clinical decisions., Materials and Methods: We retrospectively analyzed 119 patients with BRCA with brain metastasis, including 91 patients with BPM alone and 28 patients with DM. Univariate and multivariate analyses were performed to compare the clinical characteristics between the two groups and within subtypes of DM. Overall survival after DM (OSDM) and the interval from DM to leptomeningeal carcinomatosis (LMC) were compared using Kaplan-Meier analysis., Results: DM was notably linked with extracranial metastasis, luminal-like BRCA subtype (p=0.033), and skull metastases (p<0.001). Multiple logistic regression revealed a strong association of DM with extracranial and skull metastases, but not with subtype or hormone receptor (HR) status. Patients with DM did not show survival differences compared with patients with BPM alone. In the subgroup analysis, nodular type DM correlated with HER2 status (p=0.044), whereas diffuse type DM was significantly associated with a higher prevalence of the luminal-like subtype (p=0.048) and the presence of skull metastasis (p=0.002). Patients with diffuse DM did not exhibit a significant difference in OSDM but had a notably shorter interval from DM to LMC compared to those with nodular DM (p=0.049)., Conclusion: While the impact of DM on the overall prognosis of patients with BRCA is minimal, our findings underscore distinct characteristics and prognostic outcomes within DM subgroups.

Objective: In glioblastoma (GBM) patients, controlling the microenvironment around the tumor using various treatment modalities, including surgical intervention, is essential in determining the outcome of treatment. This study was conducted to elucidate whether recurrence patterns differ according to the extent of resection (EOR) and whether this difference affects prognosis., Methods: This single-center study included 358 eligible patients with histologically confirmed isocitrate dehydrogenase (IDH)-wild-type GBM from November 1, 2005, to December 31, 2018. Patients were assigned to one of three separate groups according to EOR: supratotal resection (SupTR), gross-total resection (GTR), and subtotal resection (STR) groups. The patterns of recurrence were classified as local, marginal, and distant based on the range of radiation. The relationship between EOR and recurrence pattern was statistically analyzed., Results: Observed tumor recurrence rates for each group were as follows: SupTR group, 63.4%; GTR group, 75.3%; and STR group, 80.5% (p = 0.072). Statistically significant differences in patterns of recurrences among groups were observed with respect to local recurrence (SupTR, 57.7%; GTR, 76.0%; STR, 82.8%; p = 0.036) and distant recurrence (SupTR, 50.0%; GTR, 30.1%; STR, 23.2%; p = 0.028). Marginal recurrence showed no statistical difference between groups. Both overall survival and progression-free survival were significantly increased in the SupTR group compared with the STR and GTR groups (p < 0.0001)., Conclusions: In this study, the authors investigated the association between EOR and patterns of recurrence in patients with IDH-wild-type GBM. The findings not only show that recurrence patterns differ according to EOR but also provide clinical evidence supporting the hypothesized mechanism by which distant recurrence occurs.

Objective: Following resection of glioblastoma (GBM), microscopic remnants of the GBM tumor remaining in nearby tissue cause tumor recurrence more often than for other types of tumors, even after gross-total resection (GTR). Although surgical oncologists traditionally resect some of the surrounding normal tissue, whether further removal of nearby tissue may improve survival in GBM patients is unknown. In this single-center retrospective study, the authors assessed whether lobectomy confers a survival benefit over GTR without lobectomy when treating GBMs in the noneloquent area., Methods: The authors selected 40 patients who had undergone GTR of a histopathologically diagnosed isocitrate dehydrogenase (IDH)-wild type GBM in the right frontal or temporal lobe and divided the patients into 2 groups according to whether GTR of the tumor involved lobectomy, defined as a supratotal resection (SupTR group, n = 20) or did not (GTR group, n = 20). Progression-free survival (PFS), overall survival (OS), and Karnofsky Performance Status (KPS) scores were compared between groups (p ≤ 0.05 for statistically significant differences)., Results: The median postoperative PFS times for each group were as follows: GTR group, 11.5 months (95% CI 8.8-14.2) and SupTR group, 30.7 months (95% CI 4.3-57.1; p = 0.007). The median postoperative OS times for each group were as follows: GTR group, 18.7 months (95% CI 14.3-23.1) and SupTR group, 44.1 months (95% CI 25.1-63.1; p = 0.040). The mean postoperative KPS scores (GTR, 76.5; SupTR, 77.5; p = 0.904) were not significantly different. In multivariate analysis, survival for the SupTR group was significantly longer than that for the GTR group in terms of both PFS (HR 0.230; 95% CI 0.090-0.583; p = 0.002) and OS (HR 0.247; 95% CI 0.086-0.704; p = 0.009)., Conclusions: In cases of completely resectable, noneloquent-area GBMs, SupTR provides superior PFS and OS without negatively impacting patient performance.

Background: During transsphenoidal surgery for pituitary adenomas with large suprasellar extension, cerebrospinal fluid (CSF) leakage commonly develops from a defect at the arachnoid recess between the resected dura margin and the anterior edge of a normal pituitary gland (type 1 CSF leakage)., Objective: To evaluate the usefulness of a direct suture technique of the normal gland edge on the incised dural margin to repair intraoperative CSF leakage from the arachnoid recess., Methods: Between November 2005 and December 2012, 861 patients with pituitary adenomas were operated on with transsphenoidal surgery, and intraoperative CSF leakage was encountered in 432 patients. Type 1 CSF leakage developed in a total of 122 patients, and their defects were repaired with the direct suture technique in 51 patients, whereas a fleece-coated fibrin glue patch alone was applied onto the defect in the other 71 patients. This direct suture technique required an additional 5 to 20 minutes in most cases., Results: We experienced no case of postoperative CSF rhinorrhea in the 51 patients whose defects were repaired by the direct suture technique and only 1 case of CSF rhinorrhea in 71 patients whose defects were repaired with a fleece-coated fibrin glue patch alone. There was no statistical difference in the outcome between 2 groups. Postoperative lumbar CSF drainage was not performed in any case., Conclusion: Our 2 different repair techniques for arachnoid recess tears are very reliable methods for managing this type of CSF leakage. The direct suture technique may be more appropriate for type 1 CSF leakage with a wider gap and more prominent CSF leakage.