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Abstract Background High-grade gliomas (HGGs) have a rapid relapse and short survival. Studies have identified many clinical characteristics and biomarkers associated with progression-free survival (PFS) and over-survival (OS). However, there has not yet a comprehensive study on survival after the first progression (SAP). Methods From CGGA and TCGA, 319 and 308 HGGs were confirmed as the first progression. The data on clinical characteristics and biomarkers were analyzed in accordance with OS, PFS, and SAP. Results Analysis of 319 patients from CGGA, significant predictors of improved OS/PFS/SAP were WHO grade, MGMT promoter methylation, and Ki-67 expression in univariate analysis. Further multivariate analysis showed MGMT promoter methylation and Ki-67 expression were independent predictors. However, an analysis of 308 patients from TCGA found MGMT promoter methylation is the only prognostic marker. A longer SAP was observed in patients with methylated MGMT promoter after standard chemoradiotherapy. In our data, HGGs could be divided into low, intermediate, and high-risk groups for SAP by MGMT methylation and Ki-67 expression. Conclusions Patients with MGMT promoter methylation have a prolonger SAP after standard chemoradiotherapy. HGGs could be divided into low, intermediate, and high-risk groups for SAP according to MGMT status and Ki-67 expression.

Abstract Background PTPRZ1-MET fusion was reported to associate with glioma progression from low-grade to high-grade glioma, which was a target by a MET inhibitor vebreltinib. However, little is known about the further efficacy of vebreltinib among more glioma patients. This trial aims to evaluate the safety and efficacy of vebreltinib enteric-coated capsules in the treatment of sGBM/IDH mutant glioblastoma patients with the ZM fusion gene. Methods This multicentric, randomized, open-label, controlled trial plans to include 19 neurosurgical centers and recruit 84 sGBM or IDH mutant glioblastoma patients with the ZM fusion gene. This trial enrolls sGBM or IDH mutant glioblastoma patients with the inclusion criteria and without the exclusion criteria. It was registered with chinadrugtrials.org.cn (CTR20181664). The primary efficacy endpoint is overall survival (OS). The secondary endpoints are progression-free survival (PFS) and objective response rate (ORR). Discussion If proven effective, this targeted multifaceted intervention protocol will be extended for more glioma patients as a protocol to evaluate the safety and efficacy of MET inhibitors. Trial registration It was registered with chinadrugtrials.org.cn (CTR20181664).

Abstract Background Adjuvant temozolomide (TMZ) chemotherapy with standard regimen remarkably improves survival in patients with high-grade glioma (HGG). However, the influence of long-term TMZ chemotherapy on serum ions concentration is unclear. Methods One hundred and thirty-eight patients with HGG were included. Their blood samples were collected for blood biochemistry and routine test. The alteration in serum ions concentration, total protein, albumin, globin, and blood cells counts were used to identify the impact of long-term TMZ chemotherapy. Results Through the comparation of quantitative value of diverse parameters among different chemotherapy cycles, we identified that serum potassium concentration had a downward trend after TMZ administration (1st vs. 6th, p < 0.001; 1st vs. 12th, p < 0.001). Additionally, the correlation analysis showed that platelets was negatively correlated with chemotherapy cycles (r = − 0.649, p = 0.023). The hematological adverse events mainly centered on grade 1 to 2. Conclusion Long-term administration of TMZ may lead to serum ions disturbance. Besides the myelosuppression, we should pay attention to the alteration in serum ions concentration, and give patients proper symptomatic treatment when necessary.

Abstract Background Central nervous system germ cell tumors (CNS GCTs) represent a class of rare tumors that exhibit region-specific prevalence in some Asian areas (15.3%), higher than that in North America (3.6%), and age-specific prevalence in children and adolescents. According to the 2016 World Health Organization (WHO) classification, CNS GCTs can be categorized into germinomas and non-germinomatous GCTs (NGGCTs). Owing to the compression of the interventricular foramen by enlarged GCTs in the pineal gland, the resultant obstructive hydrocephalus may result in high intracranial pressure (HIP) at an alarming pace, which urgently requires a ventriculoperitoneal shunt for the relief of severe HIP. Although CNS GCT cells tend to migrate through the cerebrospinal fluid (CSF) starting from the subependymal lining, metastasis along the ventriculoperitoneal shunt tube is extremely rare. Case presentation In this study, we reported two cases of iGCTs with intraperitoneal metastasis. Both patients underwent ventriculoperitoneal shunt placement to alleviate HIP, and both received standard radiotherapy and chemotherapy, but they still developed abdominal metastasis, and all the abdominal masses were pathologically confirmed to be iGCTs. Conclusions We performed a literature study and found that from 1979 to 2020, a total of 18 cases of iGCTs were metastasized outside the nervous system. We also found a shift of the median of 13.5 months and that the most common primary site was the pineal region (83.3%); moreover, nearly half of the patients (44%) died within 1 year of metastasis, indicating a poor prognosis after celiac metastasis.

Abstract Background As molecular advances have deepened the knowledge on low-grade glioma (LGG), we investigated the effect of higher radiation dose on the survival of IDH-wildtype (IDHwt) LGG. Methods In the current study, 52 IDHwt LGG patients who received radiotherapy were enrolled from the Chinese Glioma Genome Atlas dataset. Radiation doses > 54 Gy were defined as high-dose, whereas doses ≤ 54 Gy were defined as low-dose. We performed univariate and multivariate survival analyses to examine the prognostic role of high-dose radiotherapy. Results In total, the radiation dose ranged from 48.6 Gy to 61.2 Gy, with a median of 55.8 Gy, and 31 patients were grouped into high-dose radiation. Univariate survival analysis indicated that high-dose radiotherapy (p = 0.015), tumors located in the frontal lobe (p = 0.009), and pathology of astrocytoma (p = 0.037) were significantly prognostic factors for overall survival. In multivariate survival analysis, high-dose radiotherapy (p = 0.028) and tumors located in the frontal lobe (p = 0.016) were independently associated with better overall survival. Conclusions In conclusion, high-dose radiotherapy independently improved the survival of IDHwt LGG. This can guide treatments for glioma with known molecular characteristics.

Abstract Background Surgical interventions including ventriculostomy and ventriculo-peritoneal shunt were usually administrated in pineal germ cell tumor patients with symptomatic hydrocephalus. Considering higher sensitivity of germinoma to anti-tumor therapy, we explored emergency irradiation as non-invasive measure in this situation. Methods Data of 35 germinoma patients with symptomatic hydrocephalus who received emergency irradiation of 3.4 Gy/2f were studied retrospectively. The maximum width of frontal horn and the minimum width of trunk of corpus callosum (TCC) were measured to evaluate hydrocephalus changing. Besides, mean deviation (MD) of Humphrey perimetry was employed to evaluate visual field defect. Correlations between hydrocephalus changing and clinical factors, including age, percentage of tumor regression, radiographic re-evaluation interval, and serum beta-human chorionic gonadotropin (β-HCG) level, were analyzed. Results The median maximum diameter and volume of pineal lesions was 27 mm (range 10–55 mm) and 6.5cm3 (range 0.4–74.1 cm3), respectively. At median 8 days after irradiation, the median percentage of tumor remission was 55% (range 10–100%). The median maximum width of FN and the median minimum width of TCC were 11.6 mm and 39.0 mm, and 8.0 mm and 31.4 mm, before and after irradiation, respectively. The improvement of both parameters reached significant level (p

Abstract Background Risk factors and treatments for brain metastasis (BM) in patients with adenocarcinoma have not been fully profiled in previous studies because of the enrolment of patients with tumours of mixed histology. Thus, we specifically addressed the issue in patients with adenocarcinoma. Methods Clinical data for 373 patients with pathologically confirmed adenocarcinoma were studied retrospectively. Factors including age (≤60 vs. > 60), gender (male vs. female), stage at diagnosis, T status (T1–2 vs. T3–4), N status (N0–1 vs. N2–3), epidermal growth factor receptor (EGFR) mutation status (wild-type vs. mutant) and smoking status (never vs. current) were analyzed. Results In multivariate analysis, age (P = 0.006) and N status (P = 0.041) were independent risk factors for BM. In patients with BM, adding systemic therapy to local therapy improved median post-brain-metastasis survival (mPBMS) (P = 0.02). However, if stratification was conducted according to the recursive partitioning analysis (RPA) classification or graded prognostic assessment (GPA) scoring, only patients in RPA class II (P = 0.020) or with GPA score 1.5-2.5 (P = 0.032) could benefit from local plus systemic therapy. Those who received both pemetrexed and tyrosine kinase inhibitors (TKIs) as systemic therapies had a longer mPBMS than those who received TKIs alone, regardless of whether local therapy was applied. In patients with EGFR-sensitive mutations, TKIs therapy led to a longer mPBMS than conventional chemotherapy (P = 0.002). Conclusions Adenocarcinoma patients who were younger than 60 years of age and those with N2–3 disease have a significantly higher risk of BM. The addition of systemic therapy to local therapy can significantly prolong mPBMS, but the survival benefit confined in certain populations. Patients with opportunity to receive both pemetrexed and TKIs had the longest mPBMS.

Abstract Background To explore risk factors and the efficacy of treatment strategies for brain metastasis (BM) in squamous cell carcinoma (SCC) of the lung. Methods The clinical data of 188 pathologically confirmed as squamous cell carcinoma or adenosquamous carcinoma patients were studied retrospectively. Factors including age (