Journal of Neuro-Oncology最新文献

Purpose: This study evaluated prognostic factors and longitudinal outcomes associated with gamma knife radiosurgery (GKRS) in treating brain metastases from breast cancer, and assessed the efficacy of repeated GKRS in prolonging intracranial disease control.

Methods: In this retrospective study, we reviewed 159 breast cancer patients involving 640 brain metastases who underwent GKRS at a tertiary medical center. Overall survival (OS), local control (LC), and distant intracranial control were estimated using the Kaplan-Meier method. Prognostic factors were estimated using Cox regression models. The effect of repeat GKRS on intracranial disease control was also examined.

Results: The median OS was 19.2 months. In multivariate analysis, the Karnofsky Performance Scale (KPS), HER2 positivity, and ER/PR positivity were independently associated with longer survival. LC rates were 88.9% at 6 months and 83.0% at 12 months. Factors significantly associated with improved LC included a higher margin dose, HER2-negative status, smaller tumor volume, and absence of prior whole-brain radiotherapy (WBRT). Distant intracranial failure within 12 month occurred in 57.0% of patients. Median intracranial control among the 44 patients who underwent repeated GKRS (28.1 months) was significantly longer than those who received single GKRS (8.0 months; p < 0.001).

Conclusion: GKRS provides effective local tumor control and favorable survival outcomes for patients with breast cancer brain metastases. KPS score and receptor status (ER/PR and HER2) are significant predictors of overall survival. Repeat GKRS is a promising strategy for prolonging intracranial control and may reduce the need for WBRT or surgical intervention in selected patients.

Purpose: This study aimed to evaluate the prognostic significance of microvessel density (MVD), assessed by CD34 immunohistochemistry (IHC), and its correlation with radiological features and bevacizumab (BEV) treatment efficacy in newly diagnosed glioblastoma.

Methods: We retrospectively analyzed 41 patients with newly diagnosed glioblastoma. MVD was quantified using CD34 IHC, and patients were stratified into low and high MVD groups according to the cutoff value determined by receiver operating characteristic curve analysis (sensitivity, 76.5%; specificity, 75.0%; AUC, 0.725). Radiological characteristics-including relative cerebral blood flow (rCBF), peritumoral edema, and cystic components-were assessed. Survival outcomes were compared using Kaplan-Meier analysis. Treatment responses to temozolomide (TMZ) with or without BEV were evaluated in both MVD groups.

Results: Patients in the low MVD group exhibited significantly longer progression-free survival (PFS, p < 0.001) and overall survival (OS, p < 0.001) than those in the high MVD group. Low MVD was associated with significantly lower rCBF, less peritumoral edema, and a higher prevalence of cystic components. All six cystic-type cases were found in the low MVD group and showed favorable prognosis. The addition of BEV to TMZ significantly prolonged PFS in the high MVD group (p = 0.001) but not in the low MVD group, with no OS benefit observed in either group.

Conclusion: MVD serves as a prognostic biomarker and may help predict BEV treatment efficacy in glioblastoma. Combined with radiological features, MVD assessment could support more individualized therapeutic strategies. Further prospective studies using both CD34 protein and mRNA expression are warranted to validate these findings.

Background: Patients with WHO grade 2 and 3 isocitrate dehydrogenase mutation (IDHmt) gliomas commonly receive temozolomide (TMZ), with or without radiation therapy, as initial therapy. At progression, TMZ is sometimes reinstated despite a paucity of data on effectiveness.

Methods: We reviewed imaging outcomes of patients with WHO 2016 grade II/III IDHmt gliomas re-treated with TMZ at first progression between 2007 and 2019. Tumor growth rates were calculated over the year preceding re-treatment and throughout the re-treatment period, ranging from 3 to 41 months. RANO criteria were utilized to assess TMZ response rate.

Results: 15 subjects included six grade II, five grade III oligodendrogliomas, one grade II and three grade III astrocytomas. Median time between completion of the first TMZ course and initiation of re-treatment was 47 months. Median progression-free survival with TMZ re-treatment was 27.4 months and median overall survival was 47.8 months. Mean rate of tumor growth by bidimensional product increased from 0.29 cm² /month, in the year prior to first tumor progression, to 0.47 cm²/month during re-treatment, ranging from 3 to 41 months, with monotherapy TMZ. Volumetric mean rate of tumor growth was 1.12 cc/month in the year prior to first tumor progression versus 1.29 cc/month during TMZ re-treatment. Five patients experienced tumor growth rate reduction, of whom 3 patients experienced tumor shrinkage as measured by 2D; 2 of these 3 patients also experienced tumor shrinkage as measured by 3D. There was no radiographic response by RANO criteria.

Conclusion: These findings suggest previously treated, progressive IDHmt gliomas are generally resistant to TMZ, underscoring the need for alternative approaches.

Objectives: This study aims to identify the radiological features of brain metastases (BM) from ovarian cancer (OC) and correlate them to clinical and genetic data. Additionally, the impact of neurosurgery on patient survival is evaluated.

Materials and methods: A single-center, retrospective, observational study was conducted, involving 106 patients with BM from OC. Neuroradiological imaging was available for 66 patients. The data collected were analyzed using linear correlation and ANOVA tests and multivariable Cox proportional hazards regression for survival analysis. Survival was assessed using Kaplan-Meier curves.

Results: The most prevalent histological subtypes were high grade serous (90%) OC. The main neuroradiological feature was necrosis (79%). BM were multiple in 56% of cases, with a prevalent distribution in the cerebral hemispheres (80.30%). Additional neuroradiological features included a volume greater than 1000 mm³ (71%), hemosiderin deposits on SWI (67%), abundant perilesional edema (53%), and the presence of hemorrhage (15%). The mean apparent diffusion coefficient (ADC) value of BM was 781.5 × 10^-6 mm²/s, while relative cerebral volume (rCBV) was lower in patients with posterior fossa BM (p = 0.049). Neurological symptoms were present in 39% of cases, and a linear correlation was identified between neurological symptoms and both tumor volume (p = 0.0008) and the presence of necrosis (p = 0.04). The BRCAm was associated to longer survival (p = 0.04) and was associated with less perilesional edema (OR = 0.145, CI: 0.027-0.776). The Kaplan-Meier analysis showed an overall survival (OS) of 46 months in BRCAwt patients who underwent neurosurgery, vs. 37 months in patients who did not (p = 0.03). Cox analysis identified BRCAm status, performance status, post-BM chemotherapy, and CNS-only disease as independent predictors of better survival; surgery was not significant.

Conclusion: The current study supports the established protective value of the BRCA mutation and suggests that neurosurgical treatment of BM after a comprehensive evaluation may improve survival, even in BRCAwt patients.

Clinical relevance statement: The critical need for early detection of BMs that are appropriate for surgical intervention is highlighted, as timely action can greatly improve patient outcomes.

Purpose: Meningiomas are the second most common type of tumor associated with Neurofibromatosis Type 2 Schwannomatosis (NF2-SWN). While the characteristics of intracranial meningiomas have been extensively studied, data on the epidemiological and histological features of spinal meningiomas (SM) remain limited.

Methods: An observational, retrospective study was conducted on NF2-SWN patients who underwent surgical resection of SMs at three NF2-SWN reference centers. Data were compared to a cohort of patients operated on for sporadic SM at Pitié-Salpêtrière Hospital. To evaluate the prevalence of spinal meningiomas in NF2-SWN, we analyzed the craniospinal MRIs of NF2-SWN patients followed at the Pitié-Salpêtrière Hospital.

Results: Nineteen NF2-SWN patients who underwent surgery for 29 SMs between 1996 and 2024 were included (median age at surgery: 22 years; IQR:10-43). The most common location was the thoracic spine (22 cases, 76%). NF2-SWN patients were significantly younger than those with sporadic SMs (32 vs. 64 years; p < 0.001), and the female predominance was less pronounced (2:1 vs. 9:1; p = 0.01). Patients with sporadic tumors had a significantly shorter time to surgery (6.3 vs. 36.5 months; p < 0.001). No significant differences were observed between the two groups regarding tumor location, dural attachment, grade, histological subtype, rate of complete resection (85% vs. 89%; p = 0.5), or recurrence risk (8% vs. 9%; mean follow-up: 7.5 years; p = 0.9). Among the 115 NF2-SWN patients with at least one brain and spinal MRI, 39 (34%) had a SM. Patients with SM more frequently harbored intracranial meningiomas (95%) compared to NF2-SWN patients without SM (64%; p < 0.001).

Conclusion: Spinal meningiomas are common in NF2-SWN, mostly found in association with intracranial meningiomas and correlate with a higher tumor burden and more severe disease phenotype. However, these tumors progress slowly, rarely require surgical intervention, and do not demonstrate higher histopathological aggressiveness compared to sporadic spinal meningiomas.

Introduction: Hypertension, the most common adverse events associated with bevacizumab (BEV) treatment, has been proposed as a potential biomarker of treatment response in glioblastoma (GBM) patients. This study aimed to evaluate whether the timing of hypertension serves as a prognostic value in GBM patients.

Methods: This retrospective study consisting of 56 GBM patients treated with initial BEV between 2013 and 2024. Blood pressure was monitored peri-infusion of BEV (before and 60 min after). Patients were grouped into normotension, pre-existing hypertension (before first BEV infusion), and BEV-induced hypertension, further classified as early new-onset (≤ 3 cycles) or late-onset (> 3 cycles). Overall survival (OS) was assessed using the Kaplan-Meier method.

Results: Fifteen (36.6%) patients had pre-existing hypertension, while 26 (63.4%) were normotensive at baseline. Among the normotensive patients, twelve (46.1%) developed early new-onset hypertension, and 13 (50%) developed late-onset hypertension. Patients with pre-existing hypertension demonstrated significantly longer median OS compared to normotensive patients (32 vs. 22 months, p = 0.043). Early new-onset hypertension was also associated with improved OS compared to patients who remained normotensive after three cycles (25 vs. 16 months, p = 0.003). Additionally, patients with pre-existing and early new-onset hypertension showed longer OS compared to those with late-onset hypertension (25 vs. 14 months, p = 0.002).

Conclusion: Monitoring blood pressure during peri-infusion of BEV could be useful in predicting treatment response for GBM patients. Pre-existing or early new-onset hypertension is associated with improved survival, suggesting that timing of hypertension has a potential role as a biomarker for BEV efficacy.

Purpose: Selumetinib is a MEK inhibitor indicated for pediatric patients with neurofibromatosis type 1 (NF1) and symptomatic inoperable plexiform neurofibromas (PNs).

Methods: This retrospective study collected data from 70 patients (aged 3 - 18 years) with NF1 and symptomatic inoperable PNs treated with selumetinib as part of compassionate use at 11 Italian centers between October 2018 and October 2024. Assessments included the clinical benefit rate (CBR) after 24 months and at the last observation. Major response (MR) was defined as a ≥ 50% reduction from baseline in tumor volume. Adverse events (AEs), patient-reported pain and quality of life (QoL), and Eastern Cooperative Oncology Group performance status (ECOG PS), were also evaluated.

Results: Of 45/70 patients with available natural history data at C0, 33/45 (73.3%) had progressive disease (PD). Radiological evaluation at C6 in 17/33 patients showed 16 (94.1%) had stable disease (SD) or partial response (PR). 52/58 patients (91.5%) had SD or PR/MR at C12; final response at last radiological follow-up was PD (7.7%), SD (42.3%), PR (30.8%) and MR (19.2%). CBR was 83.3% (24/70) at C24 and 91.5% (43/47) at last radiological follow-up. Selumetinib significantly reduced pain perception and improved QoL and ECOG PS. The type of response at C6 seems to predict response at C12 and at last observation. Adverse events were generally mild (78% grade ≤ 2).

Conclusion: Our findings suggest that the response after 6 and 12 selumetinib cycles may predict long-term outcomes, providing clinicians with an early indicator for therapeutic decision-making.

Trial registration number: Not applicable.

Introduction and objectives: Leptomeningeal disease (LMD) involves disseminating cancer cells to the leptomeninges and cerebrospinal fluid. The impact of intracranial parenchymal brain metastases and extracranial disease burden at LMD diagnosis remains unclear. This study evaluates these factors alongside local and systemic therapies before and after LMD diagnosis.

Methods: A retrospective analysis was conducted on 188 patients diagnosed with LMD between 2011 and 2024. Data on demographics, imaging findings, and treatments were collected. Kaplan-Meier estimates were used for survival analysis, and independent prognostic factors were identified using a backward-stepwise Cox regression model.

Results: Primary cancers included breast cancer (34.0%), non-small cell lung cancer (22.3%), and melanoma (14.4%). LMD was diagnosed via MRI in 56.4% of cases, cerebrospinal fluid (CSF) cytology in 2.7%, and both in 41.0%. Median overall survival was 2.8 months [95% CI: 2.4 - 3.7]. Independent prognostic factors for improved survival included male sex (HR: 0.61 [95% CI: 0.40 - 0.93], p = 0.020), absence of hydrocephalus at LMD diagnosis (HR: 0.42 [95% CI: 0.22 - 0.79], p = 0.007), and targeted therapy post-diagnosis (HR: 0.33 [95% CI: 0.20 - 0.55], p < 0.001). Two or more lines of systemic therapy before LMD diagnosis increased mortality risk (HR: 1.73 [95% CI: 1.16 - 2.59], p = 0.007). Lack of CNS parenchymal disease at LMD diagnosis also increased risk (HR: 0.51 [95% CI: 0.30 - 0.89], p = 0.017). Pre-diagnosis radiation therapy showed no survival benefit, while post-diagnosis radiation improved outcomes (HR: 0.47 [95% CI: 0.32 - 0.70], p < 0.001).

Conclusion: Absence of hydrocephalus and use of targeted therapy post-diagnosis are favorable prognostic factors, while extensive prior systemic therapy and CNS parenchymal disease worsen outcomes. Tailored therapies addressing intracranial disease are crucial for improving survival in LMD patients.