Publications by authors named "Xiaoguang Qiu"

35 Publications

The external metastasis of the central nerve system germ cell tumors: case report and review of the literature.

Chin Neurosurg J 2021 Jun 2;7(1):29. Epub 2021 Jun 2.

Department of Radiation Oncology, Beijing Tiantan Hospital, Capital Medical University, 119, South 4th Ring West Road, Fengtai District, Beijing, China.

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.
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http://dx.doi.org/10.1186/s41016-021-00246-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170731PMC
June 2021

Primary intracranial germ cell tumour originating from right brachium Pontis with hypertrophic Olivary degeneration: a case report.

BMC Neurol 2021 May 25;21(1):210. Epub 2021 May 25.

Department of Radiation Oncology, Beijing Tiantan Hospital, Capital Medical University, 119, South 4th Ring West Road, Fengtai District, Beijing, China.

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.
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http://dx.doi.org/10.1186/s12883-021-02238-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146987PMC
May 2021

Characteristics of growth disturbances in patients with intracranial germinomas of different origins.

Childs Nerv Syst 2021 May 24. Epub 2021 May 24.

Department of Radiation Oncology, Beijing Tiantan Hospital, Capital Medical University, No. 119, South 4th Ring West Road, Fengtai District, Beijing, 100070, China.

Purpose: To explore the characteristics of growth disturbance in patients with intracranial germinoma with different origins.

Methods: Clinical data of 151 patients with single-origin germinomas were studied retrospectively. Z-score of height (ZSOH) at both diagnosis and the last follow-up was calculated using the WHO AnthroPlus software. Linear regression was used to analyse the correlation between the absolute change in ZSOH (|ZSOH - ZSOH |) and clinical factors.

Results: The mean ZSOH decreased significantly in every origin subgroup at the last follow-up. In patients with sellar germinoma (n = 62), the mean ZSOH values at both diagnosis and the last follow-up were significantly lower than those in patients with pineal (n = 30) (p < 0.001) or basal ganglia germinomas (n = 59) (p < 0.001), respectively. In patients with basal ganglia germinoma, the mean absolute change in ZSOH decreased significantly compared to that in the patients with sellar (p = 0.006) or pineal germinomas (p = 0.04). Linear analysis revealed that sex (male vs female; p = 0.003) and age at diagnosis (≤10 years vs >10 years; p = 0.026) had negative correlations, while radiation dose at the hypothalamic-pituitary axis (HPA) (≤40 Gy vs >40 Gy; p = 0.085) had a marginally positive correlation, with absolute change in ZSOH.

Conclusions: Patients with germinoma experienced growth retardation after treatments. The growth disturbance was consistent and more severe in patients with germinoma of sellar origin, while the greatest aggravation was observed in patients with germinoma of basal ganglia origin. Decreasing radiation dose to the HPA may minimize the negative impact of radiotherapy on growth.
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http://dx.doi.org/10.1007/s00381-021-05189-6DOI Listing
May 2021

Changes in Peripheral Blood Regulatory T Cells and IL-6 and IL-10 Levels Predict Response of Pediatric Medulloblastoma and Germ Cell Tumors With Residual or Disseminated Disease to Craniospinal Irradiation.

Int J Radiat Oncol Biol Phys 2021 May 8. Epub 2021 May 8.

Department of Surgery, Duke University Medical Center, Durham, North Carolina. Electronic address:

Purpose: Radiation therapy (RT) modulates immune cells and cytokines, resulting in both clinically beneficial and detrimental effects. The changes in peripheral blood T lymphocyte subsets and cytokines during RT for pediatric brain tumors and the association of these changes with therapeutic outcomes have not been well described.

Methods And Materials: The study population consisted of children (n = 83, aged 3~18) with primary brain tumors (medulloblastoma, glioma, germ cell tumors (GCT), and central nervous system embryonal tumor-not otherwise specified), with or without residual or disseminated (R/D) diseases who were starting standard postoperative focal or craniospinal irradiation (CSI). Peripheral blood T lymphocyte subsets collected before and 4 weeks after RT were enumerated by flow cytometry. Plasma levels of interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-α, interferon-γ, and IL-17A were measured by cytometric bead array.

Results: Patients with R/D lesions receiving CSI (n = 32) had a post-RT increase in the frequency of CD3+T and CD8+T cells, a decrease in CD4+T cells, and an increase in regulatory T cells (Tregs) and CD8+CD28- suppressor cells, which was more predominantly seen in these patients than in other groups. In the CSI group with such R/D lesions, consisting of patients with medulloblastoma and germ cell tumors, 19 experienced a complete response (CR) and 13 experienced a partial response (PR) on imaging at 4 weeks after RT. The post/pre-RT ratio of Tregs (P = .0493), IL-6 (P = .0111), and IL-10 (P = .0070) was lower in the CR group than in the PR group. Multivariate analysis revealed that the post/pre-RT ratios of Treg, IL-6, and IL-10 were independent predictors of CR (P < .0001, P = .018, P < .0001, respectively). The areas under the receiver operating curves and confidence intervals were 0.7652 (0.5831-0.8964), 0.7794 (0.5980-0.9067), and 0.7085 (0.5223-0.8552) for IL-6, IL-10, and Treg, respectively. The sensitivities of IL-6, IL-10, and Treg to predict radiotherapeutic responses were 100%, 92.3%, and 61.5%, and specificity was 52.6%, 57.9%, and 84.2%, respectively.

Conclusions: CSI treatment to those with R/D lesions predominantly exerted an effect on antitumor immune response compared with both R/D lesion-free but exposed to focal or CSI RT and with R/D lesions and exposed to focal RT. Such CSI with R/D lesions group experiencing CR is more likely to have a decrease in immunoinhibitory molecules and cells than patients who only achieve PR. Measuring peripheral blood Treg, IL-6, and IL-10 levels could be valuable for predicting radiotherapeutic responses of pediatric brain tumors with R/D lesions to CSI for medulloblastoma and intracranial germ cell tumors.
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http://dx.doi.org/10.1016/j.ijrobp.2021.04.041DOI Listing
May 2021

High-dose radiation associated with improved survival in IDH-wildtype low-grade glioma.

Chin Neurosurg J 2021 Apr 1;7(1):22. Epub 2021 Apr 1.

Department of Radiation Oncology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.

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.
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http://dx.doi.org/10.1186/s41016-021-00239-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015052PMC
April 2021

Relapse pattern and quality of life in patients with localized basal ganglia germinoma receiving focal radiotherapy, whole-brain radiotherapy, or craniospinal irradiation.

Radiother Oncol 2021 05 19;158:90-96. Epub 2021 Feb 19.

Department of Radiation Oncology, Beijing Tiantan Hospital, Capital Medical University, China; Beijing Neurosurgery Institute, Capital Medical University, China.

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.
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http://dx.doi.org/10.1016/j.radonc.2021.02.009DOI Listing
May 2021

Electroless Formation of a Fluorinated Li/Na Hybrid Interphase for Robust Lithium Anodes.

J Am Chem Soc 2021 Feb 15;143(7):2829-2837. Epub 2021 Feb 15.

Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education), Research Center of High-Efficiency Energy Storage (Ministry of Education), College of Chemistry, Nankai University, Tianjin 300071, P. R. China.

Engineering a stable solid electrolyte interphase (SEI) is one of the critical maneuvers in improving the performance of a lithium anode for high-energy-density rechargeable lithium batteries. Herein, we build a fluorinated lithium/sodium hybrid interphase via a facile electroless electrolyte-soaking approach to stabilize the repeated plating/stripping of lithium metal. Jointed experimental and computational characterizations reveal that the fluorinated hybrid SEI mainly consisting of NaF, LiF, LiPOF, and organic components features a mosaic polycrystalline structure with enriched grain boundaries and superior interfacial properties toward Li. This LiF/NaF hybrid SEI exhibits improved ionic conductivity and mechanical strength in comparison to the SEI without NaF. Remarkably, the fluorinated hybrid SEI enables an extended dendrite-free cycling of metallic Li over 1300 h at a high areal capacity of 10 mAh cm in symmetrical cells. Furthermore, full cells based on the LiFePO cathode and hybrid SEI-protected Li anode sustain long-term stability and good capacity retention (96.70% after 200 cycles) at 0.5 C. This work could provide a new avenue for designing robust multifunctional SEI to upgrade the metallic lithium anode.
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http://dx.doi.org/10.1021/jacs.0c12051DOI Listing
February 2021

Growing Nanostructured CuO on Copper Foil via Chemical Etching to Upgrade Metallic Lithium Anode.

ACS Appl Mater Interfaces 2021 Feb 26;13(5):6367-6374. Epub 2021 Jan 26.

Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education), Engineering Research Center of High-efficiency Energy Storage (Ministry of Education), Renewable Energy Conversion and Storage Center, College of Chemistry, Nankai University, Tianjin 300071, China.

Metallic lithium is one of the most promising anode materials to build next generation electrochemical power sources such as Li-air, Li-sulfur, and solid-state lithium batteries. The implementation of rechargeable Li-based batteries is plagued by issues including dendrites, pulverization, and an unstable solid electrolyte interface (SEI). Herein, we report the use of nanostructured CuO grown on commercial copper foil ([email protected]) via chemical etching as a Li-reservoir substrate to stabilize SEI formation and Li stripping/plating. The lithiophilic interconnected CuO layer enhances electrolyte wettability. Besides, a mechanically stable LiO- and LiF-rich SEI is generated on [email protected] during initial discharge, which permits dense and uniform lithium deposition upon subsequent cycling. Compared with bare Cu, the [email protected] electrode exhibits superior performance in terms of Coulombic efficiency, discharge/charge overpotentials, and cyclability. By pairing with the [email protected] anodes, full cells with LiFePO and LiNiMnCoO cathodes sustain 300 cycles with 98.8% capacity retention at 1 C and deliver a specific capacity of 80 mAh g at 10 C, respectively. This work would shed light on the design of advanced current collectors with SEI modulation to upgrade lithium anodes.
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http://dx.doi.org/10.1021/acsami.0c22046DOI Listing
February 2021

Behavior Disorder and Social Function Impairment in Children with Basal Ganglia Germ Cell Tumors.

Neuropsychiatr Dis Treat 2021 14;17:91-98. Epub 2021 Jan 14.

Department of Radiation Oncology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, People's Republic of China.

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.
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http://dx.doi.org/10.2147/NDT.S287438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813642PMC
January 2021

Clinical practice guidelines for the management of adult diffuse gliomas.

Cancer Lett 2021 02 6;499:60-72. Epub 2020 Nov 6.

Department of Neurosurgery, The Fourth Medical Center of PLA General Hospital, Beijing, 100048, China.

To follow the revision of the fourth edition of WHO classification and the recent progress on the management of diffuse gliomas, the joint guideline committee of Chinese Glioma Cooperative Group (CGCG), Society for Neuro-Oncology of China (SNO-China) and Chinese Brain Cancer Association (CBCA) updated the clinical practice guideline. It provides recommendations for diagnostic and management decisions, and for limiting unnecessary treatments and cost. The recommendations focus on molecular and pathological diagnostics, and the main treatment modalities of surgery, radiotherapy, and chemotherapy. In this guideline, we also integrated the results of some clinical trials of immune therapies and target therapies, which we think are ongoing future directions. The guideline should serve as an application for all professionals involved in the management of patients with adult diffuse glioma and also a source of knowledge for insurance companies and other institutions involved in the cost regulation of cancer care in China and other countries.
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http://dx.doi.org/10.1016/j.canlet.2020.10.050DOI Listing
February 2021

Comparison between Craniospinal Irradiation and Limited-Field Radiation in Patients with Non-metastatic Bifocal Germinoma.

Cancer Res Treat 2020 Oct 9;52(4):1050-1058. Epub 2020 Jul 9.

Department of Radiation Oncology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Purpose: Whether craniospinal irradiation (CSI) could be replaced by limited-field radiation in non-metastatic bifocal germinoma remains controversial. We addressed the issue based on the data from our series and the literature.

Materials And Methods: Data from 49 patients diagnosed with non-metastatic bifocal germinoma at our hospital during the last 10 years were collected. The Pediatric Quality of Life Inventory 4.0 was used to evaluate health-related quality of life (HRQOL). Additionally, 81 patients identified from the literature were also analyzed independently.

Results: In our cohort, 34 patients had tumors in the sellar/suprasellar (S/SS) plus pineal gland (PG) regions and 15 in the S/SS plus basal ganglia/thalamus (BG/T) regions. The median follow-up period was 52 months (range, 10 to 134 months). Our survival analysis showed that patients treated with CSI (n=12) or whole-brain radiotherapy (WBRT; n=34) had comparable disease-free survival (DFS; p=0.540), but better DFS than those treated with focal radiotherapy (FR; n=3, p=0.016). All 81 patients from the literature had tumors in the S/SS+PG regions. Relapses were documented in 4/45 patients treated with FR, 2/17 treated with whole-ventricle irradiation, 0/4 treated with WBRT, and 1/15 treated with CSI. Survival analysis did not reveal DFS differences between the types of radiation field (p=0.785). HRQOL analysis (n=44) in our cohort found that, compared with S/SS+PG germinoma, patients with BG/T involvement had significantly lower scores in social and school domains. However, HRQOL difference between patients treated with CSI and those not treated with CSI was not significant.

Conclusion: In patients with non-metastatic bifocal germinoma, it is rational that CSI could be replaced by limited-field radiation. HRQOL in patients with BG/T involvement was poorer.
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http://dx.doi.org/10.4143/crt.2020.437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577802PMC
October 2020

Prognostic value of a nine-gene signature in glioma patients based on tumor-associated macrophages expression profiling.

Clin Immunol 2020 07 20;216:108430. Epub 2020 Apr 20.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, China; Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, China. Electronic address:

Tumor-associated macrophages (TAMs) are regarded as the most abundantly infiltrating immune cells around the tumor microenvironment in gliomas, which plays an important role in tumorgenesis and immunosuppression. A total of 216 patients diagnosed with primary glioma were obtained from the Chinese Glioma Genome Atlas of which the RNA sequencing data was used as training set. RNA sequencing from the Cancer Genome Atlas was applicated for validation. We found that mesenchymal subtype showed strong positive correlation with macrophage-related genes (MRGs) expression. Survival analysis showed that high expression level of MRG predicted poor prognosis. A TAM-based nine-gene signature was constructed, which divided the samples into high- and low-risk of unfavorable outcome. The result of Cox regression analysis showed that the risk score was an independent prognostic factor in gliomas. Hence, the expression of TAMs was correlated with patient survival. The nine-TAM-related gene signature can predict patient survival efficiently.
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http://dx.doi.org/10.1016/j.clim.2020.108430DOI Listing
July 2020

Intraoperative radiotherapy for glioblastoma: an international pooled analysis.

Radiother Oncol 2020 01 16;142:162-167. Epub 2019 Oct 16.

Department of Radiation Oncology, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. Electronic address:

Purpose: To report the results of the first international pooled analysis of patients with glioblastoma treated with intraoperative radiotherapy (IORT) in addition to standard of care therapy.

Methods: Data from 51 patients treated at five centers in Germany, China and Peru were analyzed. All patients underwent tumor resection followed by a single application of IORT (10-40 Gy, prescribed to the applicator surface) with low-energy X-rays. Thereafter, standard adjuvant radiochemotherapy and maintenance chemotherapy were applied. Factors of interest were overall survival (OS), progression-free survival (PFS), local PFS (L-PFS; defined as appearance of new lesions ≤1 cm to the cavity border) and distant PFS (D-PFS; lesions >1 cm). The same endpoints were estimated at 1-, 2- and 3-years using the Kaplan-Meier method. Additionally, rates and severity (as per Common Terminology Criteria for Adverse Events Version 5.0) of radionecrosis (RN) were analyzed.

Results: The median age was 55 years (range: 16-75) and the median Karnofsky Performance Status was 80 (20-100). At a median follow-up of 18.0 months (2-42.4), the median OS, PFS, L-PFS and D-PFS were 18.0 months (95% CI: 14.7-21.3), 11.4 months (95%CI: 7.58-15.22), 16 months (95%CI: 10.21-21.8) and 30.0 months (95%CI: 18.59 - 41.41), respectively. The estimated 1-, 2- and 3-year OS, PFS, L-PFS and D-PFS were 79.5%, 38.7% and 25.6%; 46.2%, 29.4%, and 5.9%; 60.9, 37.9%, and 12.6%; and 76.7%, 65.0%, and 39.0% respectively. First progression occurred locally in only 35.3% of cases. Grade 1 RN was detected in 7.8% and grade 3 in 17.6% of the patients. No grade 4 toxicity was reported and no treatment-related deaths occurred.

Conclusion: Compared to historical data, this pooled analysis suggests improved efficacy and safety of IORT with low-energy X-rays for newly diagnosed glioblastoma. Prospective data is warranted to confirm these findings.
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http://dx.doi.org/10.1016/j.radonc.2019.09.023DOI Listing
January 2020

Emergency irradiation of 3.4Gy/2f in pineal gland germinoma patients with symptomatic hydrocephalus.

Chin Neurosurg J 2019 3;5:13. Epub 2019 Jun 3.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 South 4th Ring West Road, Fengtai District, Beijing, 100070 China.

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 6.5cm (range 0.4-74.1 cm), 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 ( < 0.001). However, none clinical factor was found to have correlation with their improvement. In 14 patients with paired data of pre- and post-irradiation MD, its change did not reach the significant level for both eyes. All patients successfully received subsequent chemoradiotherapy without surgical intervention.

Conclusions: Emergency irradiation of 3.4 Gy/2f was an effective non-invasive measure to relief hydrocephalus in pineal germinoma patients.
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http://dx.doi.org/10.1186/s41016-019-0160-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398300PMC
June 2019

Mutational Landscape of Secondary Glioblastoma Guides MET-Targeted Trial in Brain Tumor.

Cell 2018 11 18;175(6):1665-1678.e18. Epub 2018 Oct 18.

Department of Chemical and Biological Engineering, The Hong Kong University of Science and Technology, Hong Kong, China; Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China; Center of Systems Biology and Human Health, The Hong Kong University of Science and Technology, Hong Kong, China. Electronic address:

Low-grade gliomas almost invariably progress into secondary glioblastoma (sGBM) with limited therapeutic option and poorly understood mechanism. By studying the mutational landscape of 188 sGBMs, we find significant enrichment of TP53 mutations, somatic hypermutation, MET-exon-14-skipping (METex14), PTPRZ1-MET (ZM) fusions, and MET amplification. Strikingly, METex14 frequently co-occurs with ZM fusion and is present in ∼14% of cases with significantly worse prognosis. Subsequent studies show that METex14 promotes glioma progression by prolonging MET activity. Furthermore, we describe a MET kinase inhibitor, PLB-1001, that demonstrates remarkable potency in selectively inhibiting MET-altered tumor cells in preclinical models. Importantly, this compound also shows blood-brain barrier permeability and is subsequently applied in a phase I clinical trial that enrolls MET-altered chemo-resistant glioma patients. Encouragingly, PLB-1001 achieves partial response in at least two advanced sGBM patients with rarely significant side effects, underscoring the clinical potential for precisely treating gliomas using this therapy.
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http://dx.doi.org/10.1016/j.cell.2018.09.038DOI Listing
November 2018

MR imaging based fractal analysis for differentiating primary CNS lymphoma and glioblastoma.

Eur Radiol 2019 Mar 30;29(3):1348-1354. Epub 2018 Aug 30.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 6, Tiantan Xili, Dongcheng District, Beijing, 100050, China.

Objectives: The aim of this study was to differentiate primary central nervous system lymphoma (PCNSL) from glioblastomas (GBM) using the fractal analysis of conventional MRI data.

Materials And Methods: Sixty patients with PCNSL and 107 patients with GBM with MRI data available were enrolled. Fractal dimension (FD) and lacunarity values of the tumour region were calculated using fractal analysis. A predictive model combining fractal parameters and anatomical characteristics was built using logistic regression. The role of FD, lacunarity and the predictive model in differential diagnosis was evaluated using receiver-operating characteristic (ROC) curve analysis. The association between fractal parameters and anatomical characteristics of tumours was also investigated.

Results: PCNSL had lower FD values (p < 0.001) and higher lacunarity values (p < 0.001) than GBM. ROC curve analysis revealed that FD, lacunarity, and the predictive model could distinguish PCNSL from GBM (area under the curve: 0.895, 0.776, and 0.969, respectively). The following associations were observed between fractal parameters and anatomical characteristics: multiple lesions were significantly associated with higher lacunarity (p = 0.024), necrosis with higher FD (p = 0.027), corpus callosum involvement with higher lacunarity (p < 0.001) in PCNSL and subventricular zone involvement with higher FD (p < 0.001) in GBM.

Conclusions: The findings of the study indicate that fractal analysis on conventional MRI performs well in distinguishing PCNSL from GBM.

Key Points: • Fractal dimension and lacunarity were capable of differentiating PCNSL from GBM. • PCNSL and GBM exhibited different anatomical characteristics. • Fractal parameters were associated with some of these anatomical characteristics.
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http://dx.doi.org/10.1007/s00330-018-5658-xDOI Listing
March 2019

Identification of a DNA Repair-Related Multigene Signature as a Novel Prognostic Predictor of Glioblastoma.

World Neurosurg 2018 Sep 26;117:e34-e41. Epub 2018 May 26.

Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics, Beijing, China. Electronic address:

Background: Glioblastoma (GBM) is an extremely challenging malignancy to treat. Although temozolomide (TMZ) is a standard treatment regimen, many patients with GBM develop chemoresistance. The aim of this study was to identify a DNA repair-related gene signature to better stratify patients treated with TMZ.

Methods: We selected 89 cases of primary GBM (pGBM) from the Chinese Glioma Genome Atlas RNA-seq dataset as the training cohort, whereas The Cancer Genome Atlas RNA-seq and Gene Set Enrichment (GSE) 16011 mRNA array sets were used as validation cohorts. Regression analysis and linear risk score assessment were performed to build a DNA repair-related signature. We used Kaplan-Meier analysis to evaluate the predictive value of the signature for overall survival (OS) in the different groups. Multivariate Cox regression analysis was used to determine whether the 5-gene signature could independently predict OS.

Results: Using our 5-gene signature panel of APEX1, APRT, PARP2, PMS2L2, and POLR2L, we divided patients with pGBM into high- and low-risk groups. Patients with a low-risk score were predicted to have favorable survival and greater benefit from TMZ therapy compared with patients from the high-risk group (P < 0.05). Moreover, receiver operating characteristic curves showed that the multigene signature was the most sensitive and specific model for survival prediction (P < 0.05).

Conclusions: Among patients with pGBM, classification based on a risk score determined using a 5-gene panel indicated different OS and reaction to TMZ. The findings in this study demonstrate that this unique 5-gene signature could be a novel model to predict OS and provide accurate therapy for patients with pGBM.
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http://dx.doi.org/10.1016/j.wneu.2018.05.122DOI Listing
September 2018

Risk factors and treatments for brain metastasis in patients with adenocarcinoma of the lung: a retrospective analysis of 373 patients.

Chin Neurosurg J 2018 26;4. Epub 2018 Apr 26.

Department of Radiation Oncology, Beijing Tiantan Hospital affiliated to Capital Medical University, No. 6, Tiantan Xili, Dongcheng District, Beijing, 100050 China.

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 ( = 0.006) and N status ( = 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) ( = 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 ( = 0.020) or with GPA score 1.5-2.5 ( = 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 ( = 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.
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http://dx.doi.org/10.1186/s41016-018-0113-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398234PMC
April 2018

PD-1 related transcriptome profile and clinical outcome in diffuse gliomas.

Oncoimmunology 2018;7(2):e1382792. Epub 2017 Oct 25.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

PD-1 plays a critical part in control of immune response to malignancy. Anti-PD-1 treatment is a hopeful strategy to improve the dismal prognosis of gliomas. To characterize the role of PD-1 in diffuse gliomas, we investigated its related biological process at transcriptome level and its clinical prognostic value. Through Chinese Glioma Genome Atlas and TCGA datasets, we systematically reviewed a total of 994 cases with RNA-seq data and analyzed the functional annotation of PD-1 by Gene ontology (GO) analysis. Univariate and multivariate survival analysis were performed in 907 patients with survival data. We found PD-1 was significantly upregulated in glioblastoma and isocitrate dehydrogenase wild type tumors. According to TCGA transcriptional classification scheme, PD-1 expression was higher in tumors of mesenchymal subtype than other subtypes, and shown good predictive value to mesenchymal subtype. GO analysis revealed that genes significantly correlated with PD-1 were involved in essential functions associated with anti-tumor immune process. Through screening transcriptomic data, we found a strong correlation between PD-1 and immune cell populations especially for T cells. In addition, we investigated the association between PD-1 and genes related to its function, and found that PD-1 was significantly correlated with genes including TGFB1, IDO1, CD40, ICOS and SATB1, and other immune checkpoint molecules including CTLA4, LAG3, TIM3 and CD276. Survival analysis suggested that higher PD-1 expression was independently associated with worse prognosis of patients with diffuse gliomas. Our results indicated that PD-1 was involved in key steps of anti-tumor immune process and independently predicted worse prognosis in diffuse gliomas. These findings may expend our understanding of potential anti-PD-1 treatments.
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http://dx.doi.org/10.1080/2162402X.2017.1382792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749656PMC
October 2017

Relationship between necrotic patterns in glioblastoma and patient survival: fractal dimension and lacunarity analyses using magnetic resonance imaging.

Sci Rep 2017 08 16;7(1):8302. Epub 2017 Aug 16.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Necrosis is a hallmark feature of glioblastoma (GBM). This study investigated the prognostic role of necrotic patterns in GBM using fractal dimension (FD) and lacunarity analyses of magnetic resonance imaging (MRI) data and evaluated the role of lacunarity in the biological processes leading to necrosis. We retrospectively reviewed clinical and MRI data of 95 patients with GBM. FD and lacunarity of the necrosis on MRI were calculated by fractal analysis and subjected to survival analysis. We also performed gene ontology analysis in 32 patients with available RNA-seq data. Univariate analysis revealed that FD < 1.56 and lacunarity > 0.46 significantly correlated with poor progression-free survival (p = 0.006 and p = 0.012, respectively) and overall survival (p = 0.008 and p = 0.005, respectively). Multivariate analysis revealed that both parameters were independent factors for unfavorable progression-free survival (p = 0.001 and p = 0.015, respectively) and overall survival (p = 0.002 and p = 0.007, respectively). Gene ontology analysis revealed that genes positively correlated with lacunarity were involved in the suppression of apoptosis and necrosis-associated biological processes. We demonstrate that the fractal parameters of necrosis in GBM can predict patient survival and are associated with the biological processes of tumor necrosis.
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http://dx.doi.org/10.1038/s41598-017-08862-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5559591PMC
August 2017

A Retrospective Study of Progression-Free and Overall Survival in Pediatric Medulloblastoma Based on Molecular Subgroup Classification: A Single-Institution Experience.

Front Neurol 2017 12;8:198. Epub 2017 May 12.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Background: Medulloblastoma (MB) has been classified into four core subgroups according to the transcriptional profile in recent years. However, some disagreement among researchers remains regarding the prognoses and most effective treatments of the different subgroups with different age distributions.

Objective: The objective of this study was to analyze MB prognosis in children population based on the classification of four molecular subgroups.

Methods: From January 2011 to January 2013, 84 consecutive MB patients aged underwent tumor removal at Beijing Tiantan Hospital. A total of 55 patients who ranged in age from 4 to 18 years underwent detailed follow-up. Molecular subgrouping was performed using RT-PCR.

Results: The 2-year progression-free survival (PFS) and overall survival (OS) rates for the entire cohort were 76.2 ± 5.8 and 81.8 ± 5.2%, respectively. Univariate analysis revealed that the Group 4 patients had a better survival (2-year OS, 90.6 ± 5.2%) than the SHH subgroup ( = 0.002) and Group 3 patients ( = 0.008). Only two of the 23 non-metastasized Group 4 patients relapsed, and chemotherapy did significantly affect these patients (PFS,  = 0.685). One out of five WNT patients had tumor relapse and died at last. Large cell/anaplastic (LC/A) histology and chemotherapy were independent risk factors in multivariate analysis.

Conclusion: In our study, the non-metastasized Group 4 patients had an excellent prognosis. The SHH subgroup and Group 3 patients had worst prognoses. LC/A histology had a dismal prognosis in our cohorts, which warrants intensive treatment.
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http://dx.doi.org/10.3389/fneur.2017.00198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5427081PMC
May 2017

Stratification according to recursive partitioning analysis predicts outcome in newly diagnosed glioblastomas.

Oncotarget 2017 Jun;8(26):42974-42982

Department of Molecular Pathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.

Glioblastoma accounts for more than half of diffuse gliomas. The prognosis of patients with glioblastoma remains poor despite comprehensive and intensive treatments. Furthermore, the clinical significance of molecular parameters and routinely available clinical variables for the prognosis prediction of glioblastomas remains limited. The authors describe a novel model may help in prognosis prediction and clinical management of glioblastoma patients. We performed a recursive partitioning analysis to generate three independent prognostic classes of 103 glioblastomas patients from TCGA dataset. Class I (MGMT promoter methylated, age <58), class II (MGMT promoter methylation, age ≥58; MGMT promoter unmethylation, age <54, KPS ≥70; MGMT promoter unmethylation, age >59, KPS ≥70), class III (MGMT promoter unmethylation, age 54-58, KPS ≥70; MGMT promoter unmethylation, KPS <70). Age, KPS and MGMT promoter methylation were the most significant prognostic factors for overall survival. The results were validated in CGGA dataset.This was the first study to combine various molecular parameters and clinical factors into recursive partitioning analysis to predict the prognosis of patients with glioblastomas. We included MGMT promoter methylation in our study, which could give better suggestion to patients for their chemotherapy. This clinical study will serve as the backbone for the future incorporation of molecular prognostic markers currently in development. Thus, our recursive partitioning analysis model for glioblastomas may aid in clinical prognosis evaluation.
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http://dx.doi.org/10.18632/oncotarget.17322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522120PMC
June 2017

Methotrexate-cytarabine-dexamethasone combination chemotherapy with or without rituximab in patients with primary central nervous system lymphoma.

Oncotarget 2017 Jul;8(30):49156-49164

Department of Hematology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Purpose: High-dose methotrexate based chemotherapy is the standard treatment for patients with newly diagnosed primary central nervous system lymphoma (PCNSL). The role of rituximab is controversial because of its large size, which limits its penetration of the blood-brain barrier. In this study, we investigated the efficacy and tolerability of adding rituximab to methotrexate-cytarabine-dexamethasone combination therapy (RMAD regimen).

Results: The patients treated with RMAD had a complete remission rate of 66.7% after induction chemotherapy; this rate was only 33.3% in patients treated with MAD alone (p = .011). The most common grade 1-3 adverse events were similar and included hematologic toxicity, increased aminotransferase levels, and gastrointestinal reactions. Multivariate analysis revealed that rituximab treatment was associated with longer progression-free survival (PFS, p = .005) but not overall survival (OS). Additionally, we observed that elevated serum lactate dehydrogenase was associated with shorter OS and PFS.

Materials And Methods: We retrospectively analyzed 60 immunocompetent patients with newly diagnosed PCNSL at Beijing Tiantan Hospital, Capital Medical University from January 2010 to June 2016. Twenty-four patients received 3-6 courses of 3.5 g/m2 methotrexate on day 1; 0.5-1 g/m2 cytarabine on day 2; and 5-10 mg dexamethasone on days 1, 2 and 3. Thirty-six patients received the same combination plus rituximab 375 mg/m2 on day 0. All patients repeated the treatment every 3 weeks.

Conclusions: High-dose methotrexate based chemotherapy with rituximab yields a higher complete remission rate and does not increase serious toxicities. PFS benefits from the addition of rituximab. OS has an increasing trend in patients treated with rituximab without statistical significance.
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http://dx.doi.org/10.18632/oncotarget.17101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564757PMC
July 2017

Radiation combined with temozolomide contraindicated for young adults diagnosed with anaplastic glioma.

Oncotarget 2016 Nov;7(48):80091-80100

Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.

Purpose: Age is a major prognostic factor for malignant gliomas. However, few studies have investigated the management of gliomas in young adults. We determined the role of survival and treatment in young adults with advanced gliomas in a large population from the Chinese Glioma Genome Atlas (CGGA).

Methods: This study included 726 adults (age ≥ 18) with histologically proven anaplastic glioma or glioblastoma multiforme (GBM). The overall and progression-free survival was determined in young (age < 50) and older groups (age ≥ 50).

Results: The study included an older group (OP) of 264 patients and a younger group (YP) of 462patients. In the OP group with GBM and anaplastic glioma, patients treated with RT combined with temozolomide (TMZ) manifested significantly longer OS and PFS compared with patients assigned to RT alone (P < 0.05). In contrast, the YP group diagnosed with anaplastic glioma failed to show any survival advantage with RT plus TMZ compared with RT alone.

Conclusions: We observed no survival benefit in young adults (age < 50) with anaplastic glioma when treated with TMZ combined with RT. Our findings warrant further investigation of younger patients diagnosed with anaplastic glioma treated with radiotherapy plus TMZ chemotherapy.
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http://dx.doi.org/10.18632/oncotarget.11756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346774PMC
November 2016

Evaluation on efficacy and safety of the addition of X-knife therapy to gefitinib in NSCLC patients with symptomatic brain metastases.

Oncotarget 2017 Aug 6;8(34):57470-57476. Epub 2016 Jul 6.

Department of oncology, Guangdong 999 Brain Hospital, Guangzhou, China.

Background: Stereotactic radiosurgery (SRS) is a widely used therapy for brain metastases(BMs) in Non-small cell lung cancer(NSCLC). However, its role in symptomatic patients with EGFR mutation remains unclear. We have retrospectively reviewed the clinical data of patients with symptomatic BMs whom received SRS as a salvage approach and concurrent gifitinib therapy.

Methods: Seven patients with primary NSCLC, symptomatic BMs, and EGFR mutation were identified in a retrospective review of patients treated with SRS using X-knife at Guangdong 999 Brain Hospital between 1 January 2012 and 31 August 2014. The median follow-up of these patients was 16 months. Image fusion technique was used to determine cumulative doses to targeted lesions, whole brain, and critical brain structures. Toxicities and complications were identified by clinical records.

Results: SRS(X-knife) was selected to be performed on seven patients (two males and five females) diagnosed with NSCLC and EGFR mutation due to the presence of encephaledema, compression of ventricles, or other complications. Neurological symptoms (such as paresis, aphasia, sensory and visual disturbances) were not present in any patients before or after SRS treatment, and the postoperative Karnofsky performance status(KPS) was improved in all patients. Median overall survival(OS) was 16 months and median progression free survival(PFS) was 10 months.

Conclusions: The improvement of KPS and survival were reliable by SRS(X-knife) with concurrent gifitinib therapy in NSCLC patients with symptomatic BMs, and EGFR mutation. Given the small sample size, further prospective studies with a greater number of patients are warranted to confirm our results.
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http://dx.doi.org/10.18632/oncotarget.10420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593658PMC
August 2017

CGCG clinical practice guidelines for the management of adult diffuse gliomas.

Cancer Lett 2016 Jun 7;375(2):263-273. Epub 2016 Mar 7.

Department of Neurosurgery, Medical College of Soochow University, Suzhou 215123, China.

The Chinese Glioma Cooperative Group (CGCG) Guideline Panel for adult diffuse gliomas provided recommendations for diagnostic and therapeutic procedures. The Panel covered all fields of expertise in neuro-oncology, i.e. neurosurgeons, neurologists, neuropathologists, neuroradiologists, radiation and medical oncologists and clinical trial experts. The task made clearer and more transparent choices about outcomes considered most relevant through searching the references considered most relevant and evaluating their value. The scientific evidence of papers collected from the literature was evaluated and graded based on the Oxford Centre for Evidence-based Medicine Levels of Evidence and recommendations were given accordingly. The recommendations will provide a framework and assurance for the strategy of diagnostic and therapeutic measures to reduce complications from unnecessary treatment and cost. The guideline should serve as an application for all professionals involved in the management of patients with adult diffuse glioma and also as a source of knowledge for insurance companies and other institutions involved in the cost regulation of cancer care in China.
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http://dx.doi.org/10.1016/j.canlet.2016.01.024DOI Listing
June 2016

Classification based on mutations of TERT promoter and IDH characterizes subtypes in grade II/III gliomas.

Neuro Oncol 2016 08 7;18(8):1099-108. Epub 2016 Mar 7.

Beijing Neurosurgical Institute, Capital Medical University, Beijing, China (P.Y., W.Z., Y.W., X.Q., T.J.); Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (P.Y., W.Z., Y.W., B.C., T.J.); Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China (J.C., C.J.); Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China (W.Y., Y.Y.); Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (G.L.); Department of Neurosurgery, Beijing Sanbo Brain Hospital, Capital Medical University, Beijing, China (S.L., C.W.); Department of Pathology, Beijing Sanbo Brain Hospital, Capital Medical University, Beijing, China (K.Y.); Department of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China (W.L.); Department of Epidemiology and Biostatistics, School of Public Health and Family Medicine, Capital Medical University (X.P.); Department of Neurosurgery, Chinese PLA General Hospital, Beijing, China (L.C.); Department of Radiation Therapy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (X.Q.); China National Clinical Research Center for Neurological Diseases (T.J.).

Background: Grade II and III gliomas have variable clinical behaviors, showing the distinct molecular genetic alterations from glioblastoma (GBM), many of which eventually transform into more aggressive tumors. Since the classifications of grade II/III gliomas based on the genetic alterations have been recently emerging, it is now a trend to include molecular data into the standard diagnostic algorithm of glioma.

Methods: Here we sequenced TERT promoter mutational status (TERTp-mut) in the DNA of 377 grade II/III gliomas and analyzed the clinical factors, molecular aberrations, and transcriptome profiles.

Results: We found that TERTp-mut occurred in 145 of 377 grade II and III gliomas (38.5%), mutually exclusive with a TP53 mutation (TP53-mut; P < .001) and coincident with a 1p/19q co-deletion (P = .002). TERTp-mut was an independent predictive factor of a good prognosis in all patients (P = .048). It has been an independent factor associated with a good outcome in the IDH mutation (IDH-mut) subgroup (P = .018), but it has also been associated with a poor outcome in the IDH wild-type (IDH-wt) subgroup (P = .049). Combining TERTp-mut and IDH-mut allowed the grade II/III malignancies to be reclassified into IDH-mut/TERTp-mut, IDH-mut only, TERTp-mut only, and IDH-wt/TERTp-wt. 1p/19q co-deletion, TP53-muts, Ki-67 expression differences, and p-MET expression differences characterized IDH-mut/TERTp-mut, IDH-mut only, TERTp-mut only, and IDH-wt/TERTp-wt subtypes, respectively.

Conclusions: Our results showed that TERTp-mut combined with IDH-mut allowed simple classification of grade II/III gliomas for stratifying patients and clarifying diagnostic accuracy by supplementing standard histopathological criteria.
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http://dx.doi.org/10.1093/neuonc/now021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4933482PMC
August 2016

Clinicopathological factors predictive of postoperative seizures in patients with gliomas.

Seizure 2016 Feb 31;35:93-9. Epub 2015 Dec 31.

Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China; Chinese Glioma Cooperative Group (CGCG), China. Electronic address:

Purpose: Epilepsy is one of the most common manifestations in gliomas and has a severe effect on the life expectancy and quality of life of patients. The aim of our study was to assess the potential connections between clinicopathological factors and postoperative seizure.

Method: We retrospectively investigated a group of 147 Chinese high-grade glioma (HGG) patients with preoperative seizure to examine the correlation between postoperative seizure and clinicopathological factors and prognosis. Univariate analyses and multivariate logistic regression analyses were performed to identify factors associated with postoperative seizures. Survival function curves were calculated using the Kaplan-Meier method.

Results: 53 patients (36%) were completely seizure-free (Engel class I), and 94 (64%) experienced a postoperative seizure (Engel classes II, III, and IV). A Chi-squared analysis showed that anaplastic oligodendroglioma/anaplastic oligoastrocytoma (AO/AOA) (P=0.05), epidermal growth factor receptor (EGFR) expression (P=0.0004), O(6)-methylguanine DNA methyltransferase (MGMT) expression (P=0.011), and phosphatase and tensin homolog (PTEN) expression (P=0.045) were all significantly different. A logistic regression analysis showed that MGMT expression (P=0.05), EGFR expression (P=0.001), and AO/AOA (P=0.038) are independent factors of postoperative seizure. Patients with lower MGMT and EGFR expression and AO/AOA showed more frequent instances of postoperative seizure. Postoperative seizure showed no statistical significance on overall survival (OS) and progression-free survival (PFS).

Conclusion: Our study identified clinicopathological factors related to postoperative seizure in HGGs and found two predictive biomarkers of postoperative seizure: MGMT and EGFR. These findings provided insight treatment strategies aimed at prolonging survival and improving quality of life.
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http://dx.doi.org/10.1016/j.seizure.2015.12.013DOI Listing
February 2016

IDH mutation and MGMT promoter methylation in glioblastoma: results of a prospective registry.

Oncotarget 2015 Dec;6(38):40896-906

Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.

Background: The relative contribution of isocitrate dehydrogenase mutations (mIDH) and O6-methylguanine-DNA methyltransferase promoter methylation (methMGMT) as biomarkers in glioblastoma remain poorly understood.

Methods: We investigated the association between methMGMT and mIDH with progression free survival and overall survival in a prospectively collected molecular registry of 274 glioblastoma patients.

Results: For glioblastoma patients who underwent Temozolomide and Radiation Therapy, OS and PFS was most favorable for those with tumors harboring both mIDH and methMGMT (median OS: 35.8 mo, median PFS: 27.5 mo); patients afflicted glioblastomas with either mIDH or methMGMT exhibited intermediate OS and PFS (mOS: 36 and 17.1 mo; mPFS: 12.2 mo and 9.9 mo, respectively); poorest OS and PFS was observed in wild type IDH1 (wtIDH1) glioblastomas that were MGMT promoter unmethylated (mOS: 15 mo, mPFS: 9.7 mo). For patients with wtIDH glioblastomas, TMZ+RT was associated with improved OS and PFS relative to patients treated with RT (OS: 15.4 mo v 9.6 mo, p < 0.001; PFS: 9.9 mo v 6.5 mo, p < 0.001). While TMZ+RT and RT treated mIDH patients exhibited improved overall survival relative to those with wtIDH, there were no differences between the TMZ+RT or RT group. These results suggest that mIDH1 conferred resistance to TMZ. Supporting this hypothesis, exogenous expression of mIDH1 in independent astrocytoma/glioblastoma lines resulted in a 3-10 fold increase in TMZ resistance after long-term passage.

Conclusions: Our study demonstrates IDH mutation and MGMT promoter methylation status independently associate with favorable outcome in TMZ+RT treated glioblastoma patients. However, these biomarkers differentially impact clinical TMZ response.
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http://dx.doi.org/10.18632/oncotarget.5683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747376PMC
December 2015