Background Risk stratification and radiotherapy optimization for medulloblastoma (MB) increasingly rely on molecular classification, yet large-scale, cross-regional, real-world evidence remains limited. Methods We assembled a global MB database (Chinese cohort: N = 729; international: N = 494). Overall survival (OS)/progression-free survival (PFS) and risk stratification were analyzed by integrating clinicopathological data with molecular subgroup-specific genetic events using Kaplan-Meier and Cox regression models. Findings While conventional clinical risk stratification effectively separated outcomes, metastatic stage alone, although a crucial factor, failed to adequately stratify survival across molecular subgroups. The average-risk group showed superior 5-year cumulative OS (84.4%) and PFS (77.5%), compared to the high-risk group (77.2% and 68.2%). Key genetic events, including TP53 mutation/17p loss (Sonic Hedgehog, SHH), MYC amplification (group_3), and CDK6 activation (group_4), were strongly associated with survival. Integrating genetic events with clinical features significantly facilitated prognostic discrimination. Importantly, radiotherapy dose-response effects were highly context dependent within defined molecular subgroups. No significant differences in OS or PFS were observed between craniospinal irradiation (CSI) doses of 30.6 and 36.0 Gy in high-risk patients with SHH, group_3, and group_4 receiving chemotherapy. In particular, 36.0 Gy CSI was warranted for aggressive MYC-amplified group_3 MB, even without dissemination. Conclusions Integrating subgroup-specific genetic events with clinical features facilitates MB risk stratification, informs context-dependent radiotherapy consideration, and provides actionable candidates for prospective validation. Funding This work was funded by the Natural Science Foundation of Beijing (JQ24040 and L2510021) and the National Natural Science Foundation of China (82273343 and 82573715).

The long‐term results confirmed that the OS and PFS benefits from the RT‐TMZ exceeded those of the RT alone in patients with IDH‐wt/pTERTmut gliomas with tolerable toxicity.

Background:Osteosarcoma (OS) is one of the most common primary malignant bone tumors. At present, research on the value of quantitative 99mTechnetium-methylene diphosphonate single photon emission computed tomography/computed tomography (99mTc-MDP SPECT/CT) for predicting neoadjuvant chemotherapy (NACT) efficacy in OS is limited. The purpose of this study was to assess the predictive value of quantitative 99mTc-MDP SPECT/CT in predicting NACT efficacy in OS. Methods:This retrospective study collected 99mTc-MDP bone scans and quantitative 99mTc-MDP SPECT/CT data of all OS patients from February 2019 to February 2025 at Beijing Jishuitan Hospital, Capital Medical University. The NACT efficacy was assessed based on postoperative pathology. The predictive value of maximum tumor/nontumor radioactive count (T/NTmax), and maximum standardized uptake value (SUVmax) before and after NACT were evaluated. The percentage change of T/NTmax [△T/NT, △T/NT = 100% × (Post-T/NTmax - Pre-T/NTmax)/Pre-T/NTmax] and SUVmax [△SUVmax, ΔSUVmax = 100% × (Post-SUVmax - Pre-SUVmax)/Pre-SUVmax] were also analyzed. Results:A total of 67 patients with OS were enrolled in this retrospective study, including 26 patients with good efficacy and 41 patients with poor efficacy. Post-SUVmax was significantly lower in the good efficacy group than that in the poor efficacy group [19.1 (7.4, 37.3) vs. 34.9 (21.6, 60.8), P=0.006]. The good efficacy group showed significantly greater reductions in ΔT/NTmax [-20.2% (-37.7%, 1.7%) vs. 24.3% (-18.9%, 77.1%), P=0.004] and ΔSUVmax [-32.5% (-60.3%, -13.3%) vs. 21.0% (-11.0%, 48.3%), P<0.001] compared to the poor efficacy group. ΔSUVmax showed a significantly higher area under the curve (AUC) than ΔT/NTmax (0.811 vs. 0.712, P=0.021), indicating higher predictive value. Conclusions:Quantitative 99mTc-MDP SPECT/CT is an efficient technique for predicting NACT efficacy in OS.

Background Medulloblastoma (MB), a prevalent malignant pediatric brain tumor, typically necessitates a comprehensive treatment regimen. However, the standard treatment paradigm is often not viable for infants (< 3 years old) incomplete, which contraindicates traditional radiotherapy. This study retrospectively analyzed the efficacy of chemotherapy with deferred radiotherapy in infants. Methods The cohort consisted of 23 infants who receiving surgical resection of MB, which has been categorized into SHH, Group_3, and Group_4 subgroups and received postoperative chemotherapy. Molecular subgroups were identified using DNA methylation sequencing. This study analyzed the overall survival and recurrence rates based on molecular subgroup and evaluated the effects of treatment strategies. Results SHH accounted for 48%, Group_3 for 40%, and Group_4 for 12%. The follow-up period ranged from 1 to 131 months, with a median of 51 months. The overall survival rate was 60%, with survival rates for SHH, Group_3, and Group_4 at 66.7%, 50.0%, and 66.7%, respectively. The survival rates at 1, 3, 5, and 10 years were 92%, 80%, 48%, and 12%, respectively. Univariate and multivariate Cox regression analyses indicated that recurrence and treatment modalities significantly impacted survival times, with a hazard ratio of 10.28 for recurrence (95% CI: 1.99–53.03, p = 0.005) and 4.59 for chemotherapy alone (95% CI: 1.11–18.93, p = 0.035). The findings suggest that for infants with MB, a combined treatment approach of postoperative chemotherapy followed by delayed radiotherapy significantly improves overall survival compared to chemotherapy alone. Conclusion The findings suggest that infants with MB benefit substantially from postoperative chemotherapy followed by delayed radiotherapy.

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). 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. 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. 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.

In previous studies, patients with intracranial germ cell tumour (iGCT) with pure choriocarcinoma or mixed germ cell tumours with choriocarcinoma element showed similar dismal prognoses, with median overall survival (OS) of 22 months and 1-year survival rate of approximately 60

Abstract PURPOSE In 2016, we initiated a signal center prospective randomized trial to compare chemoradiotherapy (CRT) with temozolomide (TMZ) to radiotherapy (RT) alone in patients with IDH wild-type and TERT promoter mutation histological grade 2/3 gliomas. This study demonstrated patients who received CRT had a longer median OS than those who received RT alone and found no statistical difference in PFS between the two groups. Now, we recruited more patients in the CRT group to further explore whether there were differences in PFS between patients treated with CRT and RT. Besides, we explored the effect of MGMT promoter (MGMTp) methylation status on OS and PFS in patients receiving CRT therapy in the STUPP schedule. METHODS We expanded the scope by enrolling 21 participants in the CRT group and extending the follow-up period. OS and PFS were analyzed using the log-rank test, and high-risk factors were explored through Cox regression analysis. RESULTS Patients’ median follow-up is 21.9 months. CRT group has a longer median OS (25.3 vs 17.2 months; P = 0.029, HR = 0.443) and PFS (14.6 vs 8.3 months; P = 0.0008, HR = 0.387) than the RT group. Multivariate analysis identified CRT as a favorable prognostic variable for both OS (P = 0.003) and PFS (P = 0.002). The status of MGMTp methylation did not affect OS (P = 0.560, HR = 1.30) and PFS (P = 0.75, HR = 0.88) in patients with IDH-wt/TERTp-mut receiving TMZ chemotherapy. CRT with TMZ did not significantly increase grade 3 or higher toxicities. CONCLUSIONS The long-term results confirmed that the OS and PFS benefits of the RT plus TMZ regimen exceeded those of the RT alone group in patients with IDH-wt/TERTp-mut gliomas.

Introduction:Malignant gliomas are the most prevalent and fatal types of primary malignant brain tumors with poor prognosis. Protein phosphatase 3 catalytic subunit beta (PPP3CB) is a pivotal constituent of the Ca2+/calmodulin-dependent serine/threonine protein phosphatases and widely expressed in brain. We aimed at identifying whether PPP3CB has potential in being a novel biomarker of malignant gliomas, bringing new insights to clinical management and therapy.Methods:Transcriptomes and clinical data of Glioblastoma (GBM) and low-grade glioma (LGG) samples were downloaded from TCGA and CGGA. We first explored the expressional and survival features of tumor tissues. Then, PPP3CB-associated genes were identified and their functional pathways were explored through GSEA analyses. Western blotting was conducted to modify PPP3CB expression. Samples of glioma patients and healthy controls were collected and immunohistochemistry (IHC) staining was performed to detect protein level. Further, we carried out an immune infiltration analysis, explored the correlation between PPP3CB and immune checkpoint genes, as well as to assessed the tumor mutation burden (TMB) and tumor microenvironment score (TMEscore) of PPP3CB.Results:PPP3CB expression in malignant glioma tissues was significantly downregulated and was considered an independent prognostic factor. Several functional pathways were observed through functional pathway analyses. PPP3CB's expression was strongly related to the infiltration of various immune cells and expression of key immune checkpoint genes. PPP3CB expression in high-grade gliomas was significantly lower, affecting glioma cells' proliferation and apoptosis in vitro.Conclusion:PPP3CB was a potential biomarker for the diagnosis and prognosis of malignant gliomas.

Background: In previous studies, patients with intracranial germ cell tumour (iGCT) with pure choriocarcinoma or mixed germ cell tumours with choriocarcinoma element showed similar dismal prognoses, with median overall survival (OS) of 22 months and 1-year survival rate of approximately 60%. However, these conclusions need to be updated because radiotherapy, which is the milestone for this disease, was not applied in a number of patients. Methods: Clinical data of patients with iGCTs with histologically confirmed choriocarcinoma element or beta-human chorionic gonadotropin (β-HCG) > 500 IU/L were collected from the archives of our institution and retrospectively studied. Results: A total of 76 patients were eligible for this study. In terms of the initial treatment, 11 patients underwent surgery, four patients received radiotherapy, and 61 patients received chemotherapy. Except for two early deaths, all patients received radiotherapy (craniospinal irradiation [CSI], n=23; non-CSI, n=51). The median follow-up duration for the entire series was 63 months (range, 6–188 months). The 5-year event-free survival (EFS) and OS rates were 81.5% and 84.1%, respectively. Among patients who did not have early death or progressive disease after induction chemotherapy, multivariate analysis revealed that chemotherapy cycles (>4 vs. ≤4) (hazard ratio [HR] for EFS 0.144, p=0.020; HR for OS 0.111, p=0.028) and β-HCG levels (>3000 IU/L vs. ≤3000 IU/L) (HR for EFS 4.342, p=0.059; HR for OS 6.614, p=0.033) were independent factors for survival. Radiation volume (non-CSI vs. CSI) was not proven to be a prognostic factor for either EFS or OS (HR for EFS 1.902, p=0.59; HR for OS 2.425, p=0.49). Conclusions: Patients with iGCTs with choriocarcinoma element or β-HCG >500 IU/L showed improved survival with radiotherapy-based treatments. Additional chemotherapy cycles could result in additional survival benefits. Patients with β-HCG level >3000 IU/L had poorer prognosis.

Background The radiation dose for patients with low-grade gliomas (LGGs) is controversial. The objective of this study was to investigate the impact of the radiation dose on survival for patients with LGGs and especially for molecularly defined subgroups. Methods Three hundred fifty-one patients with newly diagnosed LGGs from the multicenter Chinese Glioma Cooperative Group received postoperative radiotherapy (RT) in 2005-2018. The RT dose, as a continuous variable, was entered into a Cox regression model using penalized spline regression to allow for a nonlinear relationship between the RT dose and overall survival (OS) or progression-free survival (PFS). Inverse probability of treatment weighting (IPTW)-adjusted propensity scores were used to correct for potential confounders. Dose effects on survival within IDH mutation and 1p/19q codeletion defined subgroups were analyzed. Results The risk of mortality and disease progression decreased sharply until 54 Gy. High-dose RT (>= 54 Gy) was associated with significantly better 5-year OS (81.7% vs 64.0%; hazard ratio [HR], 0.33; P < .001) and PFS (77.4% vs 54.5%; HR, 0.46; P < .001) than low-dose RT (<54 Gy). IPTW correction confirmed the associations (HR for OS, 0.44; P = .001; HR for PFS, 0.48; P = .003). High-dose RT was associated with longer PFS (HR, 0.25; P = .002; HR, 0.21; P = .039) and OS (HR, 0.27; P = .006; HR, 0.07; P = .017) in IDH-mutant/1p/19q noncodeleted and IDH wild-type subgroups, respectively. No significant difference in survival was observed with high-dose RT in the IDH-mutant/1p/19q codeleted subgroup. Conclusions High-dose RT (>= 54 Gy) was effective in LGGs. Patients with an IDH mutation/1p/19q noncodeletion or IDH wild-type may need to be considered for high-dose RT. Lay Summary The radiotherapy dose-response was observed in patients with low-grade gliomas, and high-dose radiotherapy (>= 54 Gy) was associated with improved survival. Patients with an IDH mutation/1p/19q noncodeletion or wild-type IDH may have improved survival with the administration of high-dose radiotherapy.

Background: Basal ganglia germ cell tumors (BGGCTs) are rare intracranial germ cell tumors (iGCTs) that often presents with cognitive impairment. Objective: To assess structural brain plasticity in the presence of unilateral basal ganglia germ cell tumors (BGGCTs), and the correlation between gray matter volume (GMV) changes and cognitive tests. Materials and methods: We applied voxel-based morphometry (VBM) to structural magnetic resonance imaging (MRI) scans to compare a sample of 41 patients with BGGCTs in the left (n = 22) or right (n = 19) and a sample of 16 patients as control group using a two-sample t-test, correcting for family-wise-errors. A battery of cognitive tests was administered to all BGGCTs patients prior to MRI. We used Pearson correlation analysis to assess the correlation between cognitive test scores and GMV changes. Results: In patients with left BGGCTs, whole-brain VBM analysis revealed a large cluster of voxels reflecting an increase in GMV in the left parahippocampal region (k = 529 voxels, T = 4.18, p < 0.01), right middle cingulate cortex (k = 172 voxels, T = 3.96, p < 0.01), and a decrease in volume in the left thalamus (k = 527 voxels, T = -4.88, p < 0.01), right inferior frontal gyrus (k = 495 voxels, T = -4.29, p < 0.01). Pearson correlation analysis showed that the GMV were significantly correlated with the Integrated Visual and Auditory continuous performance test (IVA-CPT) scale (r = 0.637, P = 0.002), abstract reasoning (r = 0.597, P = 0.011), Self-rating Depression Scale (SAS) scale (r = -0.623, P = 0.004) and memory recall (r = 0.648, P = 0.003). Conclusion: These results demonstrate that slow growing but destructive BGGCTs markedly and asymmetrically effect the GMV in left parahippocampal, left thalamus, right middle cingulate cortex, right inferior frontal gyrus and GMV changes were significantly associated with cognitive test.

BACKGROUND:Little is known about depression and anxiety among paediatric intracranial germ cell tumour (iGCT) survivors. We aimed to evaluate the risk factors associated with depression, anxiety and health-related quality of life (HRQoL) in paediatric iGCT survivors.METHODS:We recruited 200 iGCT patients (and their parents) from Beijing Tiantan Hospital and assessed their HRQoL using the Paediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales. The Children's Depression Inventory, Screen for Child Anxiety Related Emotional Disorders, and Symptom Checklist 90 were used to evaluate depression and anxiety. The results were analysed based on disease recurrence, tumour location and treatment strategies.RESULTS:Survivors with recurrent tumours had worse HRQoL scores than those with non-recurrent tumours. Patients with tumours involving both the suprasellar and basal ganglia regions had the worst HRQoL scores. A large proportion of survivors had depression or anxiety. Both depression and anxiety scores were highly correlated with the HRQoL emotional functioning scores. The parent proxy-reports (PPR) and child self-reports were highly correlated in all domains.CONCLUSIONS:This study demonstrated the clinical factors affecting paediatric iGCT survivors' depression, anxiety, and HRQoL. Therefore, psychological interventions should be implemented. It also suggests that the PedsQL PPR would be helpful for routine screening.

Background and purpose: The optimal target volume in localized basal ganglia (BG) germinoma is still undetermined. Thus, based on the relapse pattern and health-related quality of life (HRQOL), we evaluated three target volumes. Material and methods: The clinical data of 161 patients with localized BG germinoma were included in this retrospective study. Relapse status and relapse sites after treatment were explored. HRQOL was evaluated using the Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0) (<= 15 years) and Short Form-36 (SF-36) (> 15 years) questionnaires based on the patients' age at last follow-up. Results: After a median follow-up duration of 83 months (range, 20-214 months), 19 patients experienced relapse, including 15, 4, and 0 patients in the focal radiotherapy (FR) (n = 35), whole-brain radiotherapy (WBRT) plus boost (n = 109), and craniospinal irradiation (CSI) plus boost (n = 17) groups, respectively. The 5-year disease-free survival rates were 74.3%, 97.2%, and 100%, respectively (p < 0.001). Among the 15 patients who relapsed after FR, 14 had positive radiological findings, including seven (50.0%) with lesions in the periventricular area and seven (50.0%) with frontal lobe lesions. Relapse in both these areas were significantly reduced by WBRT or CSI. HRQOL data were available for 69 patients, who generally scored low. Among 38 patients evaluated by SF-36, those receiving CSI had significantly lower mental component scores than those receiving WBRT (p = 0.027) or FR (p = 0.011). Conclusions: Considering both disease control and HRQOL, WBRT is the optimal target volume in our series. The relapse pattern identified in patients receiving FR is informative for further treatment volume optimization. (c) 2021 The Authors. Published by Elsevier B.V. Radiotherapy and Oncology 158 (2021) 90-96 This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

BACKGROUND:Choroid plexus carcinomas (CPCs) are rare pediatric tumors commonly associated with Li-Fraumeni syndrome (LFS), which involves a germline mutation of the tumor suppressor gene TP53. MATERIALS AND METHODS:We retrospectively analyzed the corresponding information of 12 cases, including the effects of surgery and radiotherapy and TP53 germline mutations, to analyse the management strategies. Kaplan-Meier curves and the log-rank test were used to evaluate the progression-free survival (PFS). RESULTS:Twelve CPC patients were included, of which TP53 germline mutations were found in eight cases. All patients underwent surgical resection, and six patients received radiotherapy following with operation after initial diagnosis, one patient received radiotherapy following relapse. It was significantly different (P=0.012 and 0.028) that patients with TP53 germline mutation receiving the gross total resection (GTR) without radiotherapy showed survival advantages. Without TP53 germline mutations also showed survival advantages, but there is no statistical significance (P=0.063). CONCLUSIONS:These findings provide evidence for the therapeutic strategy that radiotherapy should not be considered for patients with TP53 germline mutations.

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.

BACKGROUND:Primary right brachium pontis germinoma with hypertrophic olivary degeneration (HOD) is extremely rare. A preoperative diagnosis is challenging due to the absence of characterized clinical and neuroimaging features, and biopsy should be considered.CASE PRESENTATION:A 20-year-old male patient presented with a case of primary intracranial germinoma originating from right brachium pontis with HOD manifesting as ocular myoclonus, nystagmus in both eyes, ataxic gait and incoordination of the limbs. Magnetic resonance imaging (MRI) revealed an irregular patchy lesion with hyperintensity on T2-weighted images (T2WI) and T2 fluid-attenuated inversion recovery (FLAIR) without enhancement by gadolinium (Gd). Furthermore, a focal hyperintense nodule on T2WI in the left inferior olive nucleus (ION) of the medulla oblongata was considered hypertrophic olivary degeneration (HOD) based on the patient's symptoms and neuroimaging findings. Due to suspected demyelinating disease and low-grade glioma (LGG), a biopsy was planned. The pathological diagnosis was germinoma. Subsequently, he received chemoradiation therapy, resulting in the improvement of neurological deficits and the disappearance of the lesion on MRI.CONCLUSION:A case of "Primary right brachium pontis germinoma with HOD" is reported for the first time. A preoperative diagnosis is challenging due to the fact of absence of clinical signs and symptoms and neuroimaging characteristics. However, patients can have favourable prognoses with appropriate evaluation and treatment.

Purpose: Basal ganglia intracranial germ cell tumors (iGCTs) can specifically destroy the basal ganglia network, leading to several cognitive, learning, behavioral, and social impairments. This study aimed to investigate the behavior and social disorders of patients with basal ganglia iGCTs . Patients and Methods: We recruited 30 newly diagnosed iGCTs patients (and their parents) for the current study. The Child Behavior Checklist/6-18 was used to evaluate emotional and behavioral problems. The Conner's Parent Rating Scales was used to assess symptoms of hyperactivity/impulsivity and conduct problems. The health-related quality of life (HRQoL) was assessed using the Pediatric Quality of Life Inventory 4.0 Generic Core Scale. Performance status was assessed using the Lansky play-performance scale and Karnofsky performance scale. The effects of basal ganglia lesions on these scores were examined. Results: Patients with basal ganglia iGCTs (n = 10) had more behavioral problems (attention problems, aggressive behavior, learning problems, hyperactivity index), social function impairment, anxiety/depression, and poorer HRQoL compared to patients with non-basal ganglia iGCTs (n = 20). There was no significant difference in the Lansky play-performance /Karnofsky performance scale scores. Conclusion: This study demonstrates the effects of basal ganglia lesions on behavioral and emotional outcomes, social functions, and HRQoL of patients with iGCTs. The results may help to understand the function of basal ganglia and provide evidence for the benefit of early psychological intervention to improve the treatment for this rare disease.