[Clinical effect of surgery combined with chemotherapy and radiotherapy in children with central primitive neuroectodermal tumor and prognostic analysis].

OBJCTIVE: To study the clinical effect of surgery combined with chemotherapy and radiotherapy in children with central primitive neuroectodermal tumor (cPNET), as well as the risks factors for poor prognosis. METHODS: A retrospective analysis was performed for the clinical data of 42 children who were diagnosed with cPNET from June 2012 to September 2018. RESULTS: The 42 children had a median overall survival (OS) time of 2.0 years and a median event-free survival (EFS) time of 1.3 years; the 1-, 3-, and 5-year OS rates were 76.2%±6.6%, 41.4%±8.7%, 37.3%±8.8% respectively, and the 1-, 3-, and 5-year EFS rates were 64.3%±7.4%, 32.7%±8.0%, 28.0%±8.1% respectively. The univariate analysis showed that there were significant differences in the OS and EFS rates among the children with different patterns of surgical resection, chemotherapy cycles, and risk grades (P<0.05), and there was also a significant difference in the OS rate between the children receiving radiotherapy and those not receiving radiotherapy (P<0.05). The multivariate Cox regression analysis showed that chemotherapy cycles and risk grade were independent influencing factors for EFS and OS rates (P<0.05). The EFS and OS rates increased with the increase in chemotherapy cycles and the reduction in risk grade. CONCLUSIONS: Multimodality therapy with surgery, chemotherapy, and radiotherapy is an effective method for the treatment of cPNET in children. Early diagnosis and treatment and adherence to chemotherapy for as long as possible may improve EFS and OS rates.

LncRNA CDKN2BAS rs2157719 genetic variant contributes to medulloblastoma predisposition.

BACKGROUND: How germline single nucleotide polymorphisms are involved in the etiology of medulloblastoma remans poorly understood. We hypothesized that CCDKN2A/B rs1063192 and rs4977756 and also the long noncoding RNA (lncRNA) CDKN2BAS rs2157719 glioma susceptibility polymorphisms identified by genome-wide association studies may contribute to medulloblastoma predisposition. METHODS: To test this hypothesis, we genotyped these genetic variants among 160 medulloblastoma patients and 443 health controls in a Chinese population. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. RESULTS: We found that only the lncRNA CDKN2BAS rs2157719 T>C genetic polymorphism was significantly associated with an increased medulloblastoma risk (C allele: OR = 1.85, 95% CI = 1.32-2.58; p = 2.7 × 10-4 ). The stratified analyses showed an elevated risk of pediatric medulloblastoma associated with CDKN2BAS rs2157719 CC or TC genotype (both p < 0.05). Moreover, the association between the CDKN2BAS rs2157719 polymorphism and medulloblastoma risk is more pronounced in males (OR = 2.22, 95% CI = 1.36-3.62; p = 0.001). CONCLUSIONS: The findings of the present study provide important insights into the genetic complexities and predisposition of medulloblastoma in Chinese, especially at the lncRNA germline variation level.

RNA-seq of 272 gliomas revealed a novel, recurrent PTPRZ1-MET fusion transcript in secondary glioblastomas.

Studies of gene rearrangements and the consequent oncogenic fusion proteins have laid the foundation for targeted cancer therapy. To identify oncogenic fusions associated with glioma progression, we catalogued fusion transcripts by RNA-seq of 272 gliomas. Fusion transcripts were more frequently found in high-grade gliomas, in the classical subtype of gliomas, and in gliomas treated with radiation/temozolomide. Sixty-seven in-frame fusion transcripts were identified, including three recurrent fusion transcripts: FGFR3-TACC3, RNF213-SLC26A11, and PTPRZ1-MET (ZM). Interestingly, the ZM fusion was found only in grade III astrocytomas (1/13; 7.7%) or secondary GBMs (sGBMs, 3/20; 15.0%). In an independent cohort of sGBMs, the ZM fusion was found in three of 20 (15%) specimens. Genomic analysis revealed that the fusion arose from translocation events involving introns 3 or 8 of PTPRZ and intron 1 of MET. ZM fusion transcripts were found in GBMs irrespective of isocitrate dehydrogenase 1 (IDH1) mutation status. sGBMs harboring ZM fusion showed higher expression of genes required for PIK3CA signaling and lowered expression of genes that suppressed RB1 or TP53 function. Expression of the ZM fusion was mutually exclusive with EGFR overexpression in sGBMs. Exogenous expression of the ZM fusion in the U87MG glioblastoma line enhanced cell migration and invasion. Clinically, patients afflicted with ZM fusion harboring glioblastomas survived poorly relative to those afflicted with non-ZM-harboring sGBMs (P < 0.001). Our study profiles the shifting RNA landscape of gliomas during progression and reveled ZM as a novel, recurrent fusion transcript in sGBMs.

A RAD52 genetic variant located in a miRNA binding site is associated with glioma risk in Han Chinese.

As a crucial homologous recombination repair gene, RAD52 participates in maintenance of genomic stability and prevention of tumorigenesis. Although several cancer susceptibility RAD52 single nucleotide polymorphisms (SNPs) have been identified previously, little was known on how the RAD52 SNPs are involved in glioma development in Han Chinese. Therefore, we examined the association between five RAD52 SNPs (rs1051669, rs10774474, rs11571378, rs7963551 and rs6489769) and glioma risk using a case-control design. Odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated by logistic regression. We found that only the RAD52 rs7963551 SNP was significantly associated with glioma risk, with the odds of having the rs7963551 AC or CC genotype in patients was 0.49 (95 % CI 0.37-0.65, P = 9.2 × 10(-6)) or 0.39 (95 % CI 0.18-0.81, P = 0.012) compared with the AA genotype. These data are consistent with functional relevance of allelic regulation of RAD52 expression by the rs7963551 SNP and miRNA let-7 in cancer cells. Stratified analyses elucidated that statistically significant association between glioma and rs7963551 SNP only existed in either astrocytic tumors (P = 6.3 × 10(-6)) or oligoastrocytic tumors (P = 0.002). In conclusion, our results support the hypothesis that genetic variants influencing miRNA-mediated regulation of tumor suppressor genes or oncogenes may contribute glioma susceptibility.

1p34.2 rs621559 and 14q21 rs398652 leukocyte telomere length-related genetic variants contribute to glioma susceptibility.

Recent genome-wide association studies have identified several leukocyte telomere length (LTL)-related single nucleotide polymorphisms (SNPs). Our previous data demonstrated that two SNPs (rs398652 on 14q21 and rs621559 on 1p34.2) were associated with LTL and risk of esophageal squamous cell carcinoma in Chinese. However, the role of these genetic variants on glioma risk is still unknown. Therefore, we examined if these genetic variants have impact on the genetic susceptibility of glioma in Chinese. On the basis of analyzing 404 glioma patients and frequency-matched 820 controls, we found that subjects having the 1p34.2 rs621559 AG or GG genotype had an OR of 1.82 (95 % CI = 1.07-3.09, P = 0.026) or 2.12 (95 % CI = 1.26-3.56, P = 0.005) for developing glioma, respectively, compared with subjects having the rs621559 AA genotype. Similarly, the 14q21 rs398652 AG or GG genotype was associated with increased glioma risk (OR = 1.39, 95 % CI = 1.07-1.80, P = 0.012; OR = 1.52, 95 % CI = 1.04-2.20, P = 0.029) compared to AA genotype. In all, our results highlight the possible role of telomere in carcinogenesis.

Functional FEN1 genetic variants and haplotypes are associated with glioma risk.

As a tumor suppressor, FEN1 plays an essential role in keeping genomic instability and preventing tumorigenesis. There are two functional genetic variants (-69G>A and 4150G>T) in the FEN1 gene, which have been associated with DNA damage levels in coke-oven workers as well as risks of lung cancer, hepatocellular carcinoma, esophageal cancer, gastric cancer and colorectal cancer in general populations. However, it is still unknown how these polymorphisms and their haplotypes are associated with glioma risk. Therefore, we investigated the role of these polymorphisms in glioma development using a case-control design in a Chinese population. The impact of the haplotypes constructed by these two polymorphisms on glioma risk was also examined. It was observed that the FEN1-69GG or 4150GG genotype were significantly associated to increased glioma risk compared with the -69AA or 4150TT genotype [Odds ratios (OR) = 1.87, 95 % confidence interval (CI) = 1.23-2.85, P = 0.003; or OR = 1.87, 95 % CI = 1.23-2.84, P = 0.003). The associations were more pronounced among female subjects (For -69AG or GG genotype: OR = 2.35, 95 % CI = 1.22-4.52; for 4150TG or GG genotype: OR = 2.33, 95 % CI = 1.21-4.48) and patients with grade 1 or 2 disease (For -69AG or GG genotype: OR = 2.21, 95 % CI = 1.20-4.05; for 4150TG or GG genotype: OR = 2.45, 95 % CI = 1.31-4.58). Additionally, the G(-69)G(4150) haplotype was also significantly associated with increased glioma risk compared with the A(-69)T(4150) haplotype. Our results suggest that FEN1 polymorphisms and haplotypes are associated with glioma risk.

Functional BCL-2 rs2279115 Promoter Noncoding Variant Contributes to Glioma Predisposition, Especially in Males.

As a crucial oncogene, B cell lymphoma-2 (BCL-2) could promote cancer cell survival by inhibiting apoptosis via suppressing activation of proapoptotic proteins, such as BAX and BAK. There is a functional rs2279115 genetic polymorphism locating in BCL-2 promoter and deregulating BCL-2 expression. However, it is still largely undefined how BCL-2 rs2279115 promoter noncoding genetic variant is involved in glioma development. We examined the association between BCL-2 rs2279115 and glioma risk using a case-control approach. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression adjusted by age and sex. Our results demonstrated that BCL-2 rs2279115 was significantly associated with glioma risk. The odd of individuals harboring A allele (CA + AA genotype) was 0.50 (95% CI = 0.39-0.64, p = 1.0 × 10-7) compared with CC genotype carriers. Stratification analyses by sex elucidated that BCL-2 rs2279115 was significantly associated with glioma risk in males (OR = 0.41, 95% CI = 0.30-0.58, p = 1.0 × 10-7), but not in females (p > 0.05). In summary, our results indicate that the functional BCL-2 rs2279115 genetic variant contributes to glioma predisposition and suggest prevalent involvement of regulatory genetic variations in glioma development.

Emergency irradiation with 3.4 Gy/2f in sellar/suprasellar germinoma patients with rapid visual acuity decline.

BACKGROUND: Rapid visual acuity (VA) decline was a common complaint in patients with sellar/suprasellar germinoma. In our hospital, 3.4 Gy/2f of emergency irradiation was applied to save patient VA and enable subsequent chemoradiotherapy. This study aimed to investigate the efficacy of emergency irradiation with 3.4 Gy/2f in patients with sellar/suprasellar germinoma who had rapid VA decline. METHODS: From January 2014 to December 2017, 33 patients with sellar/suprasellar germinoma who complained of VA decline within 3 months received 3.4 Gy/2f of emergency irradiation in Beijing Tiantan Hospital. The best-corrected VA (BCVA) and mean deviation (MD) were measured. Correlations between visual function change and clinical factors, including age at diagnosis, duration of VA decline, extent of tumor regression, serum level of tumor markers, were analyzed. RESULTS: Among 33 patients with sellar/suprasellar germinoma, the median diameter and volume of sellar/suprasellar lesions were 32 mm (range: 5-55 mm) and 12.9 cm (range 0.6-58.5 cm), respectively. Data on pre- and post-emergency-irradiation BCVA were obtained in 32 patients. For the right eyes, BCVA was improved in 23 patients (71.9%), unchanged in 7 (21.9%), and worsened in 2 (6.2%); and for the left eyes, these numbers were 27 (84.4%), 4 (12.5%), and 1 (3.1%), respectively. In terms of the logarithm of the minimum angle of resolution (logarithm of the minimum angle of resolution = Log (1/BCVA) score, the improvement was significant in both eyes (P < 0.001). In terms of MD, six patients had paired data and the improvement was marginal in the right eyes (P = 0.068) and significant in the left eyes (P = 0.043). However, no clinical factor was found to have correlation with visual function improvement. CONCLUSION: In sellar/suprasellar germinoma patients with VA decline, 3.4 Gy/2f of emergency irradiation was effective in improving visual function.

Role of Recursive Partitioning Analysis and Graded Prognostic Assessment on Identifying Non-Small Cell Lung Cancer Patients with Brain Metastases Who May Benefit from Postradiation Systemic Therapy.

BACKGROUND: The role of postradiation systemic therapy in non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) was controversial. Thus, we explored the role of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG-RPA) and graded prognostic assessment (GPA) in identifying population who may benefit from postradiation systemic therapy. METHODS: The clinical data of NSCLC patients with documented BM from August 2007 to April 2015 of two hospitals were studied retrospectively. Cox regression was used for multivariate analysis. Survival of patients with or without postradiation systemic therapy was compared in subgroups stratified according to RTOG-RPA or GPA. RESULTS: Of 216 included patients, 67.1% received stereotactic radiosurgery (SRS), 24.1% received whole-brain radiation therapy (WBRT), and 8.8% received both. After radiotherapy, systemic therapy was administered in 58.3% of patients. Multivariate analysis found that postradiation systemic therapy (yes vs. no) (hazard ratio [HR] = 0.361, 95% confidence interval [CI] = 0.202-0.648, P = 0.001), radiation technique (SRS vs. WBRT) (HR = 0.462, 95% CI = 0.238-0.849, P = 0.022), extracranial metastasis (yes vs. no) (HR = 3.970, 95% CI = 1.757-8.970, P = 0.001), and Karnofsky performance status (<70 vs. ≥70) (HR = 5.338, 95% CI = 2.829-10.072, P < 0.001) were independent factors for survival. Further analysis found that subsequent tyrosine kinase inhibitor (TKI) therapy could significantly reduce the risk of mortality of patients in RTOG-RPA Class II (HR = 0.411, 95% CI = 0.183-0.923, P = 0.031) or with a GPA score of 1.5-2.5 (HR = 0.420, 95% CI = 0.182-0.968, P = 0.042). However, none of the subgroups stratified according to RTOG-RPA or GPA benefited from the additional conventional chemotherapy. CONCLUSION: RTOG-RPA and GPA may be useful to identify beneficial populations in NSCLC patients with BM if TKIs were chosen as postradiation systemic therapy.

Systemic Therapy after Radiotherapy Significantly Reduces the Risk of Mortality of Patients with 1-3 Brain Metastases: A Retrospective Study of 250 Patients.

BACKGROUND: For patients with a brain metastasis (BM), systemic therapy is usually administered after the completion of radiotherapy, especially in cases of multiple BMs. However, the role of systemic therapy in patients with a limited number of BMs is not clear. Therefore, we conducted a retrospective study to explore this question. METHODS: Consecutive patients with a pathologically confirmed malignancy and 1-3 intracranial lesions that had been documented within the last decade were selected from the databases of three hospitals in China. RESULTS: A total of 250 patients were enrolled; of them, 135 received radiotherapy alone and 115 received radiotherapy plus systemic therapy. In patients receiving whole-brain radiation therapy (WBRT) as radiotherapy, 28 received WBRT alone and 35 patients received WBRT plus systemic therapy. Of the patients treated with stereotactic radiosurgery (SRS), 107 received SRS alone and 80 received SRS plus systemic therapy. Multivariate analysis revealed that systemic therapy significantly reduced the risk of mortality compared with radiotherapy alone (hazard ratio [HR] = 0.294, 95% confidence interval [CI] = 0.158-0.548). Further, when the analysis was conducted in subgroups of WBRT (HR = 0.230, 95% CI = 0.081-0.653) or SRS (HR = 0.305, 95% CI = 0.127-0.731), systemic therapy still showed the ability to reduce the risk of mortality in patients with BMs. CONCLUSION: Systemic therapy after either SRS or WBRT radiotherapy may significantly reduce the risk of mortality of patients with 1-3 BMs.

Low c-Met expression levels are prognostic for and predict the benefits of temozolomide chemotherapy in malignant gliomas.

Aberrant c-Met has been implicated in the development of many cancers. The objective of this study was to identify an unfavorable prognostic marker that might guide decisions regarding clinical treatment strategies for high-grade gliomas. C-Met expression was measured using immunohistochemistry in 783 gliomas, and we further analyzed c-Met mRNA levels using the Agilent Whole Genome mRNA Microarray in 286 frozen samples. In vitro, we performed cell migration and invasion assays. Cell sensitivity to temozolomide (TMZ) chemotherapy was determined using MTT assays. Both mRNA and protein levels of c-Met were significantly associated with tumor grade progression and inversely correlated with overall and progression-free survival in high-grade gliomas (all P < 0.0001). These findings were nearly consistent at the mRNA level across 3 independent cohorts. Multivariable analysis indicated that c-Met was an independent prognostic marker after adjusting for age, preoperative Karnofsky Performance Status (KPS) score, the extent of resection, radiotherapy, TMZ chemotherapy, and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. Further analysis in vitro revealed that downregulating the expression of c-Met dramatically inhibited cell migration and invasion capacities, enhanced sensitivity to TMZ chemotherapy in H4 and U87 glioma cells. Our results suggest that c-Met may serve as a potential predictive maker for clinical decision making.

[The clinical features and treatment of intracranial tumors in infants].

OBJECTIVE: To explore the treatment plan of intracranial tumors in infants. METHODS: The clinical features and curative effect of 114 patients of intracranial tumors in infants who were admitted and performed microsurgery were analyzed retrospectively. The total removal of tumor was 72.0%, subtotal removal 17.5%, partial removal 10.5%. The patients of 3 years old or so were advised to perform radiotherapy after operation. Follow-up ranges from 13 months to 7 years. RESULTS: The tumor located at posterior fossa (37.7%), sella region (31.6%), hemisphere (19.3%) including in basal ganglia. The common symptoms included headache, vomiting, ataxia, and decrease of visual acuity. All the patients obtained good recovery except one patient dead after operation. Among 86 follow-up cases, 20 patients deceased and 66 patients survived. But 6 patients developed worse than the children of the same age. CONCLUSION: Good prognosis can not be obtained for embryonal tumors and ependymoma through operation only. Although radiotherapy is useful of inhibiting the growth of tumor, the dosage should be decreased for infants and the complications in long term also should be considered simultaneously. It is a trend towards performing chemotherapy after operation. It is not necessary to perform auxiliary therapy for astrocytoma, oligodendroglioma, and mixed glioma, because the prognosis is good after total removal of the tumor.

Long-term outcomes of adjuvant radiotherapy after surgical resection of central neurocytoma.

BACKGROUND AND PURPOSE: The role of adjuvant radiotherapy for central neurocytomas (CNs) is not clear. Therefore, we aimed to examine the clinical outcomes of treating histologically confirmed CNs with adjuvant RT after surgical resection. MATERIAL AND METHODS: Sixty-three CN patients were retrospectively evaluated: 24 patients underwent gross total resection (GTR); 28, subtotal resection (STR); 9, partial resection (PR), and 2, biopsy (Bx). They underwent adjuvant RT after surgery (median dose, 54 Gy). RESULTS: The median follow-up was 69 months (15-129 months). The 5-year overall survival (OS) and 5-year progression-free survival (PFS) were 94.4% and 95% after GTR + RT, 96.4% and 100% after STR + RT, and 100% and 90.9% after PR + RT. Only three patients had tumor recurrence: at the primary site at 30 and 24 months in two GTR + PR patients, and dissemination to the spinal cord at 75 months in one STR + RT patient. Thirty-eight (63.3%) patients experienced late neurotoxicity (28, grade 1; 7, grade 2; 3, grade 3). Short-term memory impairment was the most common toxicity. CONCLUSIONS: RT after incomplete resection (IR) led to OS and PFS comparable to those for GTR. Considering the excellent outcomes and limited late toxicity, adjuvant RT maybe a good option for CN patients who undergo IR.

Effect of intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy on clinical outcomes in patients with glioblastoma multiforme.

BACKGROUND: Few studies were reported on the comparison of clinical outcomes between intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) in the treatment of glioblastoma multiforme (GBM). This study aimed to determine whether IMRT improves clinical outcomes compared with 3D-CRT in patients with GBM. METHODS: The records of 54 patients with newly-diagnosed GBM from July 2009 to December 2010 were reviewed. The patients underwent postoperative IMRT or 3D-CRT with concurrent and adjuvant temozolomide. Kaplan-Meier method and log rank test were used to estimate differences of patients' survival. RESULTS: The median follow-up was 13 months. Of the 54 patients, fifty (92.6%) completed the combined modality treatment. The 1-year overall survival rate (OS) was 79.6%. The pattern of failure was predominantly local. A comparative analysis revealed that no statistical difference was observed between the IMRT group (n = 21) and the 3D-CRT group (n = 33) for 1-year OS (89.6% vs. 75.8%, P = 0.795), or 1-year progression-free survival (PFS) (61.0% vs. 45.5%, P = 0.867). In dosimetric comparison, IMRT seemed to allow better sparing of organs at risk than 3D-CRT did (P = 0.050, P = 0.055). However, there was no significant difference for toxicities of irradiation between the IMRT group and the 3D-CRT group. CONCLUSIONS: Our preliminary results suggested that delivering standard radiation doses by IMRT is unlikely to improve local control or overall survival for GBM compared with 3D-CRT. Given this lack of survival benefit and increased costs of IMRT, the utilization of IMRT treatment for GBM needs to be carefully rationalized.

Hemangiopericytomas in the spine: clinical features, classification, treatment, and long-term follow-up in 26 patients.

BACKGROUND: Intraspinal hemangiopericytoma (HPC) is a rare and malignant extra-axial tumor with a strong tendency to recur and metastasize. There is a paucity in the literature of large case series of patients with intraspinal HPCs. OBJECTIVE: We retrospectively analyzed the clinical radiological and histological features, classification, and treatment of 26 patients with HPCs in the spine. METHODS: Twenty-six patients with HPCs in the spine were treated at our institution between 1987 and 2010. Medical records were reviewed retrospectively to collect data on the clinical features, tumor morphology, surgical resection, recurrence, and follow-up. RESULTS: The 26 patients were predominantly male, and the mean age at diagnosis was 33.8 years. The intraspinal HPCs were divided into 3 types and 5 subtypes. Most of them involved the neighboring segments and/or caused bony erosion. All tumors were immunohistochemically positive for vimentin and negative for epithelial membrane antigen. All patients underwent at least 1 surgery, and most of them received postsurgical radiotherapy. The 5-year Kaplan-Meier rate of survival was 76%. The 5-year recurrence-free rate of survival was 29.4%. Only the tumor pathological grade was significantly associated with survival time and recurrence. CONCLUSION: High-grade tumors had a shorter survival time and recurred earlier than low-grade tumors. Surgical removal and postoperative radiotherapy are critical for the treatment of intraspinal HPCs. However, total resection may not necessary for these tumors. Stereotactic radiosurgery may be a good alternative to control the recurrent lesions.

MRI manifestions correlate with survival of glioblastoma multiforme patients.

OBJECTIVE: To identify the correlation between magnetic resonance manifestation and survival of patients with glioblastoma multiforme (GBM). METHODS: The magnetic resonance imaging (MRI) images of 30 glioblastoma patients were collected. Imaging features including degrees of contrasted area, edema surrounding the tumor, and intensity in T2-weighted imaging were selected to determine their correlation with patient survival. The relationship between imaging and survival time was studied using SPSS 19.0 software. Kaplan-Meier survival analysis and log-rank test were used to compare the survival curves. RESULTS: Patients with ≤5% contrasted enhancement area of tumor had longer overall survival (OS) than those with >5% contrasted enhancement area of tumor. Patients without edema surrounding the tumor had longer OS than those with edema. Patients with tumor of hyperintensity and/or isointensity in T2-weighted imaging had longer OS than those with hyperintensity and/or isointensity and hypointensity. CONCLUSIONS: Some MR imaging features including degrees of contrasted area, edema surrounding the tumor, and intensity in T2-weighted imaging are correlated with the survival of patients with GBM. These features can serve as prognostic indicators for GBM patients.

Endolymphatic sac papillary tumor: a case report.

Endolymphatic sac papillary tumor (ELST) is an extremely rare and aggressive tumor characterized by hearing loss and temporal bone destruction. A case with clinical, imaging, pathologic and treatment data is reported and relevant literature is reviewed. A 25-year-old woman, with ELST underwent craniotomy for tumor subtotal resection, and the diagnosis was confirmed by pathologic examination. Postoperative radiotherapy consisted of 50.4 Gy/28 f was given accordingly. The patient is currently alive with no signs of tumor recurrence locally and no radiation side-effects observed after one year follow-up. Complete resection is impossible in most cases, local resection, adjuvant radiotherapy may provide favored local control. A long-term follow-up is highly advocated in consideration of its slow development course.

Gene expression profiling reveals Ki-67 associated proliferation signature in human glioblastoma.

BACKGROUND: Everlasting cellular proliferation is the fundamental feature during gliomagenesis and Ki-67 is one of the classical proliferation markers in human glioblastoma multiforme (GBM). However, the driver genes or core pathways for cellular proliferation in GBM have not been elucidated systematically. METHODS: We evaluated by immunohistochemistry the prognostic value of Ki-67 expression in the clinical outcome of 156 Chinese patients with GBM and a total of 64 GBM samples were selected for further Agilent genome-wide microarray analysis. On the basis of the microarray data from Tiantan (n = 64) and The Cancer Genome Atlas (TCGA) (n = 202) database, differentially expressed genes between the GBM subgroups with high or low level of Ki-67 expression were identified using Significance Analysis of Microarrays (SAM). Gene Ontology (GO) and KEGG Pathway analyses were then undertaken for the Ki-67 associated genes to identify the most significant biological processes and signaling pathways. RESULTS: We confirmed that Ki-67 was an independent prognostic indicator in the largest Chinese patient cohort of 156 GBM samples via immunohistochemical staining. Survival analysis of Ki-67 over-expression revealed a highly significant association with a worse clinical outcome (P = 0.010 for progression-free survival; P = 0.007 for overall survival). Comparative and integrated analysis between Tiantan and TCGA database identified a 247-gene "proliferation signature" (205 up-regulated and 42 down-regulated genes) that distinguished Ki-67 expression phenotypes. GO and KEGG Pathway analyses further indicated that Ki-67 expression phenotype was associated with distinct changes in gene expression associated with the regulation of cellular growth and proliferation. CONCLUSIONS: Proliferation marker Ki-67 is an independent prognostic indicator in Chinese GBM patients. And Ki-67 associated proliferation signature identified through genome-wide microarray analysis may provide potential targets for anti-proliferation therapy in GBM.

Increase of plasma IgE during treatment correlates with better outcome of patients with glioblastoma.

BACKGROUND: Previous studies have shown that glioma patients have lower blood IgE levels than controls. To evaluate its potential as a surrogate biomarker for glioma, we measured plasma IgE levels in glioma patients and healthy controls, and correlated them with clinicopathological factors and the patients' outcome. METHODS: We used enzyme-linked immunosorbant assay (ELISA) to determine the plasma IgE levels of 25 normal subjects and 252 glioma patients (85 patients with grade II glioma, 46 patients with grade III glioma, and 121 patients with glioblastoma). We also collected longitudinal plasma samples from glioblastoma patients and compared the plasma IgE levels before operation, one week after operation, in the middle of radiotherapy, after two cycles of chemotherapy, and after recurrence. The correlations between plasma IgE levels and the outcomes of the patients were determined. RESULTS: Plasma IgE levels were significantly lower in glioma patients (P = 0.004); patients with low-grade glioma have lower IgE levels than patients with high-grade glioma do (P = 0.029). In 24 patients with both preoperative plasma and two-cycle chemotherapy plasma samples, IgE levels increased after successful removal of the tumor (P = 0.021), and the increase correlated with the patients' survival (increase > 100 ng/ml vs. ≤ 100 ng/ml, 127.5 weeks vs. 62.3 weeks. P = 0.012, log-rank). Plasma IgE level increase of > 100 ng/ml has a specificity of 80% and a sensitivity of 78% to predict the patients' long survival (> 18 months). CONCLUSIONS: Our results suggest that plasma IgE level correlates with clinical and pathological factors in glioma patients. It has the potential to be a biomarker for glioma patients.

Prognostic factors influencing clinical outcomes of glioblastoma multiforme.

BACKGROUND: Glioblastoma multiforme (GBM) is the most malignant kind of astrocytic tumors and is associated with a poor prognosis. In this retrospective study, we assessed the clinical, radiological, genetic molecular and treatment factors that influence clinical outcomes of patients with GBM. METHODS: A total of 116 patients with GBM who received surgery and radiation between January 2006 and December 2007 were included in this study. Kaplan-Meier survival analysis and Cox regression analysis were used to find the factors independently influencing patients' progression free survival (PFS) time and overall survival (OS) time. RESULTS: Age, preoperative Karnofsky Performance Scale (KPS) score, KPS score change at 2 weeks after operation, neurological deficit symptoms, tumor resection extent, maximal tumor diameter, involvement of eloquent cortex or deep structure, involvement of brain lobe, Ki-67 expression level and adjuvant chemotherapy were statistically significant factors (P < 0.05) for both PFS and OS in the univariate analysis. Cox proportional hazards modeling revealed that age or= 80, KPS score change after operation >or= 0, involvement of single frontal lobe, non-eloquent area or deep structure involvement, low Ki-67 expression and adjuvant chemotherapy were independent favorable factors (P < 0.05) for patients' clinical outcomes. CONCLUSIONS: Age at diagnosis, preoperative KPS score, KPS score change at 2 weeks postoperation, involvement of brain lobe, involvement of eloquent cortex or deep structure, Ki-67 expression level and adjuvant chemotherapy correlate significantly with the prognosis of patients with GBM.