Survival outcomes and treatment experience of 124 patients with primary central nervous system lymphoma.

PURPOSE: Primary central nervous system lymphoma (PCNSL) is a rare malignancy of the central nervous system with high invasiveness. There is little consensus on the treatment of PCNSL. This study retrospectively studied data from PCNSL patients in a single center to summarize treatment experience and explore prognostic factors. METHODS: Survival curves were drawn using the Kaplan-Meier method and prognostic factors were analyzed using Cox's hazards model. RESULTS: In multivariate analysis, cerebrospinal fluid lactic acid dehydrogenase (CSF LDH; p = 0.005 and p = 0.002), neutrophil to lymphocyte ratio (NLR; p = 0.014 and p = 0.038), and completion of four cycles of induction therapy (p < 0.001and p < 0.001) were significant and independent predictors of overall survival (OS) and progression-free survival (PFS), respectively. CONCLUSION: On the basis of this study, we propose that PCNSL patients should receive early induction therapy with sufficient cycles. Subsequent consolidation therapy can prevent relapses and improve survival. In patients with PCNSL, the independent prognostic factors for OS and PFS were CSF LDH level, NLR, and full cycles of induction therapy.

Down-regulation of miR-675-5p contributes to tumor progression and development by targeting pro-tumorigenic GPR55 in non-small cell lung cancer.

BACKGROUND: microRNAs are small noncoding RNAs that modulate a variety of cellular processes by regulating multiple targets, which can promote or inhibit the development of malignant behaviors. Accumulating evidence suggests that miR-675-5p plays important roles in human carcinogenesis. However, its precise biological role remains largely elusive. This study examined the role of miR-675-5p in non- small cell lung cancer (NSCLC). METHODS: The expression of miR-675-5p was analyzed by real-time quantitative PCR (qRT-PCR). The effect of miR-675-5p on proliferation was evaluated through MTT and colony formation assays, and cell migration and invasion were evaluated through transwell assays. The expression of target proteins and downstream molecules was analyzed by western blotting and immunohistochemical staining. The luciferase reporter assay was used to assess the target genes of miR-675-5p in non-small cell lung cancer cells. RESULTS: The expression levels of miR-675-5p in NSCLC tissues were significantly reduced compared to those in adjacent non-cancerous tissues (P < 0.001). The expression of miR-675-5p in patients with non-small cell lung cancer had a negative correlation with lymph node metastasis (P < 0.01) and TNM stage (P < 0.05). Down-regulation of miR-675-5p promoted cell growth, proliferation, colony formation, invasion and migration, and promoted the tumorigenicity graft growth of nude mice in vivo (P < 0.01); whereas up-regulation of miR-675-5p had the contrary effects. The luciferase reporter assay showed that GPR55 was a direct target gene of miR-675-5p. Overexpression of miR-675-5p can lead to the down-regulation of GPR55 and its signaling pathway, whereas the effect can be reversed by down-regulation of miR-675-5p expression. CONCLUSIONS: miR-675-5p functions as a novel tumor suppressor in NSCLC and the anti-oncogenic activity may involve its inhibition of the target gene GPR55. These findings suggest the possibility for miR-675-5p as a therapeutic target in NSCLC.

SNARE proteins: Core engines of membrane fusion in cancer.

Vesicles are loaded with a variety of cargoes, including membrane proteins, secreted proteins, signaling molecules, and various enzymes, etc. Not surprisingly, vesicle transport is essential for proper cellular life activities including growth, division, movement and cellular communication. Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) mediate membrane fusion of vesicles with their target compartments that is fundamental for cargo delivery. Recent studies have shown that multiple SNARE family members are aberrantly expressed in human cancers and actively contribute to malignant proliferation, invasion, metastasis, immune evasion and treatment resistance. Here, the localization and function of SNARE proteins in eukaryotic cells are firstly mapped. Then we summarize the expression and regulation of SNAREs in cancer, and describe their contribution to cancer progression and mechanisms, and finally we propose engineering botulinum toxin as a strategy to target SNAREs for cancer treatment.

Machine learning-based investigation of regulated cell death for predicting prognosis and immunotherapy response in glioma patients.

Glioblastoma is a highly aggressive and malignant type of brain cancer that originates from glial cells in the brain, with a median survival time of 15 months and a 5-year survival rate of less than 5%. Regulated cell death (RCD) is the autonomous and orderly cell death under genetic control, controlled by precise signaling pathways and molecularly defined effector mechanisms, modulated by pharmacological or genetic interventions, and plays a key role in maintaining homeostasis of the internal environment. The comprehensive and systemic landscape of the RCD in glioma is not fully investigated and explored. After collecting 18 RCD-related signatures from the opening literature, we comprehensively explored the RCD landscape, integrating the multi-omics data, including large-scale bulk data, single-cell level data, glioma cell lines, and proteome level data. We also provided a machine learning framework for screening the potentially therapeutic candidates. Here, based on bulk and single-cell sequencing samples, we explored RCD-related phenotypes, investigated the profile of the RCD, and developed an RCD gene pair scoring system, named RCD.GP signature, showing a reliable and robust performance in predicting the prognosis of glioblastoma. Using the machine learning framework consisting of Lasso, RSF, XgBoost, Enet, CoxBoost and Boruta, we identified seven RCD genes as potential therapeutic targets in glioma and verified that the SLC43A3 highly expressed in glioma grades and glioma cell lines through qRT-PCR. Our study provided comprehensive insights into the RCD roles in glioma, developed a robust RCD gene pair signature for predicting the prognosis of glioma patients, constructed a machine learning framework for screening the core candidates and identified the SLC43A3 as an oncogenic role and a prediction biomarker in glioblastoma.

[Clinical analysis of 45 patients with intracranial germinoma treated by radiotherapy].

OBJECTIVE: To report the prospective efficacy of 45 patients intracranial germinoma treated by radiotherapy and discuss its treatment. METHODS: From February 1998 to October 2007, a total of 45 intracranial germinoma patients were performed radiotherapy, including 15 combined chemotherapy in the Department of Oncology. Of them 23 were pathologically diagnosed while 22 cases were clinical diagnosed. Life table method showed the 5-year and 10-year survival rate. RESULTS: Forty patients were followed-up. Most symptoms of the patients were significantly reduced or disappeared completely. The 5-year and 10-year survival rate of all patients were 84% and 74%. CONCLUSION: Radiotherapy is the main treatment for intracranial germinoma. Craniospinal irradiation, whole brain irradiation and partial brain irradiation are the main treatments. Radiotherapy combined with chemotherapy, which can reduce the radiation range and dose will be the trend.

Prognostic analysis and nomogram construction for older patients with IDH-wild-type glioblastoma.

As many countries face an ageing population, the number of older patients with glioblastoma (GB) is increasing. Thus, there is an urgent need for prognostic models to aid in treatment decision-making and life planning. A total of 98 patients with isocitrate dehydrogenase (IDH)-wild-type GB aged ≥65 years were analysed from January 2012 to January 2020. Independent prognostic factors were identified by prognostic analysis. Using the independent prognostic factors for overall survival (OS), a nomogram was constructed by R software to predict the prognosis of older patients with IDH-wild-type GB. The concordance index (C-index) and receiver operating characteristic (ROC) curve were used to assess model discrimination, and the calibration curve was used to assess model calibration. Prognostic analysis showed that the extent of resection (EOR), adjusted Charlson comorbidity index (ACCI), O6-methylguanine-DNA methyltransferase (MGMT) methylation status, postoperative radiotherapy, and postoperative temozolomide (TMZ) chemotherapy were independent prognostic factors for OS. MGMT methylation status and subventricular zone (SVZ) involvement were independent prognostic factors for progression-free survival (PFS). A nomogram was constructed based on EOR, ACCI, MGMT methylation status, postoperative radiotherapy and postoperative TMZ chemotherapy to predict the 6-month, 12-month and 18-month OS of older patients with IDH-wild-type GB. The C-index of the nomogram was 0.72, and the ROC curves showed that the areas under the curve (AUCs) at 6, 12 and 18 months were 0.874, 0.739 and 0.779, respectively. The calibration plots showed that the nomogram was in good agreement with the actual observations in predicting the OS of older patients with IDH-wild-type GB. Older patients with IDH-wild-type GB can benefit from gross total resection (GTR), postoperative radiotherapy and postoperative TMZ chemotherapy. A high ACCI score and MGMT nonmethylation are poor prognostic factors. We constructed a nomogram including the ACCI to facilitate clinical decision-making and follow-up interval selection.

Clinical Outcomes and Prognostic Analysis of 101 Patients of Central Neurocytoma: A 10-Year Treatment Experience at a Single Institution.

Objective: Central neurocytoma (CN) is a rare type of tumor that currently lacks an optimal treatment protocol. This study aimed to explore the clinical outcomes of CN in a cohort of 101 patients and identify prognostic factors associated with multiple treatment modalities. Methods: This monocentric study retrospectively analyzed the clinical data of 101 CN patients who underwent surgical resection. The patients were followed up, and their overall survival (OS) and progression-free survival (PFS) were calculated. Results: For the entire cohort, the 5- and 10-year OS rates were 88.7% and 82.8%, respectively, and the 5- and 10-year PFS rates were 86.5% and 64.9%, respectively. Of the 82 (81.19%) patients with CN who underwent gross total resection (GTR), 28 (28/82, 34.1%) also received radiotherapy (RT). Of the 19 (18.81%) patients with CN who underwent subtotal resection (STR), 11 (11/19, 57.9%) also received RT or stereotactic radiosurgery (SRS). Compared to STR, GTR significantly improved the 5-year OS (92.4% vs. 72.4%, P=0.011) and PFS (92.4% vs. 60.4%, P=0.009) rates. Radiotherapy did not affect OS in the GTR group (p=0.602), but it had a statistically significant effect on OS in the STR group (P<0.001). However, the OS (P=0.842) and PFS (P=0.915) in the STR plus radiotherapy group were comparable to those in the GTR alone group. Compared to STR alone, STR plus radiotherapy improved the 5-year PFS rate from 25% to 75% in patients with atypical CN (P=0.004). Cox regression models and a competing risk model showed that the removal degree and radiotherapy were independent prognostic factors for survival. With improvements in modern radiotherapy techniques, severe radiotherapy toxicity was not observed. Conclusion: Our findings support the use of GTR whenever possible. Radiotherapy can improve the prognosis of patients who undergo STR, especially in atypical CNs having a higher tendency to relapse. Close imaging follow-up is necessary. Our findings will help clinicians to select optimal, individualized treatment strategies to improve OS and PFS for patients with CN.

Study on the Appropriate Timing of Postoperative Adaptive Radiotherapy for High-Grade Glioma.

PURPOSE: To investigate the appropriate timing of adaptive radiotherapy (ART) for high-grade glioma. METHODS: Ten patients with high-grade gliomas were selected and underwent CT/MRI (CT1/MRI1, CT2/MRI2, CT3/MRI3, and CT4/MRI4) scans before RT and during 10-, 20- and 30-fraction RT, and the corresponding RT plans (plan1, plan2, plan3 and plan4) were made. The dose of the initial plan (plan1) was projected to CT2 and CT3 using the image registration technique to obtain the projection plans (plan1-2 and plan1-3) and by superimposing the doses to obtain the ART plans (plan10+20 and plan20+10), respectively. The dosimetric differences in the target volume and organs at risk (OARs) were compared between the projection and adaptive plans. The tumor control probability (TCP) for the planning target volume (PTV) and normal tissue complication probability (NTCP) for the OARs were compared between the two adaptive plans. RESULTS: Compared with the projection plan, the D2 to the PTV of ART decreased, the conformity index (CI) to the PTV increased, and the D2/Dmean to the brainstem, optic chiasm and pituitary, as well as the V20, V30, V40 and V50 to the normal brain decreased. The D2 to the pituitary and optic chiasm as well as the V20, V30, V40 and V50 to the normal brain in plan10+20 were lower than those in plan20+10, while the CI to the PTV was higher than that in plan20+10. The TCP of the PTV in plan10+20 was higher than that in plan20+10. CONCLUSION: ART can improve the precision of target volume irradiation and reduce the irradiation dose to the OARs in high-grade glioma. The time point after 10 fractions of RT is appropriate for ART.

[Expression of Ezrin and E-cadherin in nasopharyngeal carcinoma and its significance].

OBJECTIVE: To explore the association of Ezrin and E-cadherin expression with the invasion, metastasis and prognois of nasopharyngeal carcinoma. METHODS: Imunohistochemical SP staining was used to detect the expression of Ezrin and E-cadherin in 42 nasopharyngeal carcinoma and 10 chronic nasopharyngitis specimens. RESULTS: Ezrin protein expression in the nasopharyngeal carcinoma tissues was significantly higher than that in the chronic nasopharyngitis tissues (P<0.05). E-cadherin expression in the nasopharyngeal carcinoma tissues was significantly lower than that in the chronic nasopharyngitis tissues (P<0.05). Expressions of both Ezrin and E-cadherin of nasopharyngeal carcinoma were closely associated with T staging,the cervical lymph node metastases and clinical staging (P<0.05). A negative correlation was found between Ezrin and E-cadherin expression in the nasopharyngeal carcinoma tissues (r=-0.450, P<0.05). Survival analysis showed that the abnormal expression of Ezrin and E-cadhrin, clinical staging and the cervical lymph node metastases were associated with the survival rate of patients with nasopharyngeal carcinoma. CONCLUSION: A negative correlation is found between Ezrin and E-cadherin expression in the nasopharyngeal carcinoma tissues. Ezrin and E-cadherin are closely related to clinical staging and the cervical lymph node metastases of nasopharyngeal carcinoma,suggesting that they may be important tumor markers for nasopharyngeal carcinoma. Combined detection of the expressions of Ezrin and E-cadherin is helpful for clinical doctors to determine the prognosis of patients with nasopharyngeal carcinoma.

Human Endogenous Retroviruses in Clear Cell Renal Cell Carcinoma: Biological Functions and Clinical Values.

Human endogenous retroviruses (HERVs) form an important part of the human genome, commonly losing their coding ability and exhibiting only rare expression in healthy tissues to promote the stability of the genome. However, overexpression of HERVs has been observed in various malignant tumors, including clear cell renal cell carcinoma (ccRCC), and may be closely correlated with tumorigenesis and progression. HERVs may activate the interferon (IFN) signaling pathway by a viral mimicry process to enhance antitumor immune responses. There is increasing interest in the diagnostic and prognostic value of HERVs in cancers, and they may be candidate targets for tumor immunotherapy. The review will introduce the biological functions of HERVs in ccRCC and their clinical value, especially in regard to immunotherapy.

Comparison of Dosimetric Gains Provided by Intensity-Modulated Radiotherapy, Volume-Modulated Arc Therapy, and Helical Tomotherapy for High-Grade Glioma.

PURPOSE: Because of the poor prognosis for high-grade glioma (HGG) patients, it is important to increase the dose of the tumor to improve the efficacy while minimizing the dose of organs at risk (OARs). Thus, we evaluated the potential dosimetric gains of helical tomotherapy (HT) versus intensity-modulated radiotherapy (IMRT) or volume-modulated arc therapy (VMAT) for high-grade glioma (HGG). METHODS: A total of 42 HGG patients were retrospectively selected who had undergone helical tomotherapy; then, IMRT and VMAT plans were generated and optimized for comparison after contouring crucial neuronal structures for neurogenesis and neurocognitive function. IMRT and VMAT were optimized with the Eclipse treatment planning system (TPS) (Version 11.0.31) and HT using TomoTherapy Hi-Art Software (Version 2.0.7) (Accuray, Madison, WI, USA). All three techniques were optimized for simultaneously delivering 60 Gy to planning target volume (PTV) 1 and 50-54 Gy to PTV2. We also analyzed the homogeneity index (HI) and conformity index (CI) of PTVs and organ at risk (OAR) sparing. RESULTS: There was no significant difference in the PTV coverage among IMRT, VMAT, or HT. As for the HI, HT plans (PTV1 HI: 0.09 ± 0.03, PTV2 HI: 0.17 ± 0.05) had the best homogeneity when compared to IMRT plans (PTV1 HI: 0.10 ± 0.04, PTV2 HI: 0.18 ± 0.04) and VMAT plans (PTV1 HI: 0.11 ± 0.03, PTV2 HI: 0.20 ± 0.03). The CI value of HT (PTV1 CI: 0.98 ± 0.03, PTV2: 0.98 ± 0.05) was closest to the optimal value. Except for the IMRT and VMAT groups, there were statistically significant differences between the other two groups of the CI values in both PTV1 and PTV2. The other comparison values were statistically significant except for the optic nerve, and VMAT had the best sparing of the optic chiasm. The mean and max doses of OARs declined significantly in HT. CONCLUSIONS: For high-grade glioma patients, HT had superior outcomes in terms of PTV coverage and OAR sparing as compared with IMRT/VMAT.

Dosimetric comparisons of craniospinal axis irradiation using helical tomotherapy, volume-modulated arc therapy and intensity-modulated radiotherapy for medulloblastoma.

BACKGROUND: To evaluate the potential dosimetric gains of helical tomotherapy (HT) versus intensity-modulated radiotherapy (IMRT) and volume-modulated arc therapy (VMAT) for craniospinal axis irradiation (CSI) of medulloblastoma. METHODS: A total of 36 treatment plans were calculated retrospectively for 12 patients with medulloblastoma receiving CSI using HT with TomoTherapy Hi-Art Software (Version 2.0.7) (Accuray, Madison, WI, USA). For each case, the other two different delivery techniques were re-planned with IMRT/VMAT optimized with Eclipse treatment planning system (TPS) (Version 11.0.31). Homogeneity index (HI) and conformity index (CI) of the planning target volume (PTV) and organs at risk (OARs) sparing were analyzed. Differences in plans were evaluated using paired-samples t-test for various dosimetric parameters. RESULTS: HT yielded the highest CI in all PTV coverage including PTV of gross tumor volume (PGTV) (HT: 0.7163; VMAT: 0.6688; IMRT: 0.6096), PTVbrain (HT: 0.8490; VMAT: 0.8384; IMRT: 0.7815) and PTVspine (HT: 0.5904; VMAT: 0.5862; IMRT: 0.5797). Meanwhile, HT yielded better HI in PGTV (HT: 0.0543; VMAT: 0.0759; IMRT: 0.0736), PTVbrain (HT: 0.5525; VMAT: 0.5619; IMRT: 0.5554) and PTVspine (HT: 0.0700; VMAT: 0.0782; IMRT: 0.0877). As for OARs, HT demonstrated marked superiority in critical organs including maximal/mean doses of brainstem PRV, optical chiasm and optic nerves. CONCLUSIONS: For CSI of medulloblastoma, HT offers superior outcomes in terms of PTV conformity, PTV homogeneity and critical OAR sparing as compared with IMRT/VMAT.

Effect of radiochemotherapy on the cognitive function and diffusion tensor and perfusion weighted imaging for high-grade gliomas: A prospective study.

This study aimed to explore the effects of radiochemotherapy on the neurocognitive function of patients with high-grade gliomas (HGG). The mini-mental state examination (MMSE), Montreal Cognitive Assessment (MoCA), event-related potential P300 (ERP-P300), and specific MRI parameters were compared, and the associations between specific MRI parameters and different doses of radiation were determined for before and up to 12 months after radiotherapy. There were no significant differences in MMSE, MoCA, or ERP-P300 before and after radiotherapy. Compared with pre-radiochemotherapy, fractional anisotropy (FA) in the contralateral hippocampus decreased at 6 and 9 months after radiotherapy. FA in the ipsilateral hippocampus before radiochemotherapy decreased compared with 6 months after radiotherapy. Compared to the end of radiotherapy, as well as 3- and 6-months post-radiotherapy, the regional cerebral blood volume (rCBV) in the genu of the corpus was significantly lower at 12 months post-radiotherapy. Some MRI parameters in different regions of the brain were negatively correlated with the mean and maximum dose. There was no significant effect of radiochemotherapy on the neurocognitive functioning of patients with HGGs found before radiochemotherapy until 12 months after radiotherapy. The radiation-induced FA decrease in the bilateral hippocampus preceded cognitive dysfunction, and DTI of the hippocampus may provide a useful biomarker for predicting radiation-induced neurocognitive impairment in patients with HGGs.

[Clinical and prognostic analysis of nasopharyngeal carcinoma in 44 children and adolescents].

OBJECTIVE: To evaluate the clinical effect and prognostic factors of nasopharyngeal carcinoma in 44 children and adolescents. METHODS: From June 1987 to December 2003,44 children and adolescents with nasopharyngeal carcinoma were treated by radiotherapy, and some patients also received chemotherapy. Kaplan-Meier method was used for the survival rate and univariate analysis, and Cox proportional hazard model was used in multivariate analysis. RESULTS: The 3.5 year survival rate was 84.2% and 62.3%.In the univariate analysis, clinical stage, lymph node (N) stage, radiotherapy dose and chemotherapy were significant prognostic factors of survival.In the multivariate analysis, N stage and chemotherapy were the prognostic factors in the survival rate. CONCLUSION: Most nasopharyngeal carcinomas belong to the advanced degree. These patients are sensitive to radiotherapy and chemotherapy. Combined modality therapy can improve the clinical effect of nasopharyngeal carcinoma in children and adolescents.

Prognostic Factors as a Function of Disease-free Interval After Definitive (Chemo)radiation for Non-Small Cell Lung Cancer Using Conditional Survival Analysis.

PURPOSE: We analyzed overall and disease-free survival (OS and DFS) after definitive (chemo)radiation for stage III non-small cell lung cancer with 2 statistical methods: Kaplan-Meier (KM) analysis, with diagnosis as index date, and conditional survival (CS) analysis, with a variety of disease-free index dates, and determined whether prognostic factors varied based on the reference date. MATERIALS AND METHODS: All 651 patients analyzed received definitive (chemo)radiotherapy for stage III non-small cell lung cancer in November 1998 to December 2010 at a single institution; all had Karnofsky performance status scores ≥60 and received ≥60 Gy. OS and DFS were first calculated with the KM method, and then CS was used to calculate 2 outcomes: OS conditioned on DFS time (OS|DFS) and DFS conditioned on DFS time (DFS|DFS). Factors predicting OS and DFS conditioned on 1-, 2-, and 3-year DFS were sought in univariate and multivariate analyses. RESULTS: KM analysis produced 1-, 2-, and 3-year DFS rates of 48%, 30%, and 26%; OS rates were 64%, 41%, and 29%. By CS analysis, both OS|DFS and DFS|DFS showed an increase in 5-year OS after 6 months, and CS after 30 months approached 100%. On multivariate analyses, age and concurrent chemoradiation predicted OS|DFS; age, smoking history, tumor histology, disease stage, and radiation dose predicted DFS|DFS. CONCLUSIONS: CS analysis showed that the probability of long-term survival increases sharply after 6 months with no evidence of disease; factors predicting survival differed based on the method and endpoint used.

Epithelial membrane protein 3 regulates TGF-ß signaling activation in CD44-high glioblastoma.

Although epithelial membrane protein 3 (EMP3) has been implicated as a candidate tumor suppressor gene for low grade glioma, its biological function in glioblastoma multiforme (GBM) still remains poorly understood. Herein, we showed that EMP3 was highly expressed in CD44-high primary GBMs. Depletion of EMP3 expression suppressed cell proliferation, impaired in vitro tumorigenic potential and induced apoptosis in CD44-high GBM cell lines. We also identified TGF-ß/Smad2/3 signaling pathway as a potential target of EMP3. EMP3 interacts with TGF-ß receptor type 2 (TGFBR2) upon TGF-ß stimulation in GBM cells. Consequently, the EMP3-TGFBR2 interaction regulates TGF-ß/Smad2/3 signaling activation and positively impacts on TGF-ß-stimulated gene expression and cell proliferation in vitro and in vivo. Highly correlated protein expression of EMP3 and TGF-ß/Smad2/3 signaling pathway components was also observed in GBM specimens, confirming the clinical relevancy of activated EMP3/TGF-ß/Smad2/3 signaling in GBM. In conclusion, our findings revealed that EMP3 might be a potential target for CD44-high GBMs and highlight the essential functions of EMP3 in TGF-ß/Smad2/3 signaling activation and tumor progression.

Silencing platelet-derived growth factor receptor-ß enhances the radiosensitivity of C6 glioma cells in vitro and in vivo.

Platelet-derived growth factor receptor (PDGFR)-ß is an important tyrosine kinase and its downregulation has been reported to alter the radiosensitivity of glioma cells, although the underlying mechanism is unclear. In order to investigate the effect of PDGFR-ß on the radiosensitivity of glioblastoma, the present study transfected C6 glioma cells with a PDGFR-ß-specific small interfering (si)RNA expression plasmid, and downregulation of the expression of PDGFR-ß in C6 glioma cells was confirmed by western blotting and immunohistochemical analysis. Clone formation assays and xenograft growth curves demonstrated that PDGFR-ß-siRNA enhanced the radiosensitivity of C6 glioma cells in vitro and in vivo. Furthermore, MTT and xenograft growth curves demonstrated that PDGFR-ß-siRNA inhibited the proliferation of C6 glioma cells in vitro and in vivo, and terminal deoxynucleotidyl transferase dUTP nick end-labeling and immunohistochemical analyses demonstrated that PDGFR-ß-siRNA induced apoptosis and inhibited the expression of Ki-67, cyclin B1 and vascular endothelial growth factor in C6 glioma cell xenografts. Taken together, these results suggested that PDGFR-ß may be used as a target for the radiosensitization of glioblastoma.

Dosimetric comparison between intensity-modulated radiotherapy and RapidArc with single arc and dual arc for malignant glioma involving the parietal lobe.

The aim of the present study was to evaluate the difference in treatment plan quality, monitor units (MUs) per fraction and dosimetric parameters between IMRT (intensity-modulated radiotherapy) and RapidArc with single arc (RA1) and dual arc (RA2) for malignant glioma involving the parietal lobe. Treatment plans for IMRT and RA1 and RA2 were prepared for 10 patients with malignant gliomas involving the parietal lobe. The Wilcoxon matched-pair signed-rank test was used to compare the plan quality, monitor units and dosimetric parameters between IMRT and RA1 and RA2 through dose-volume histograms. Dnear-max (D2%) to the left lens, right lens and left optical nerve in RA1 were less compared with those in IMRT; D2% to the right lens and right optic nerve in RA2 were less compared with those in IMRT. D2% to the optic chiasma in RA2 was small compared with that in RA1. The median dose (D50%) to the right lens and right optic nerve in RA1 and RA2 was less compared with the identical parameters in IMRT, and D50% to the brain stem in RA2 was less compared with that in RA1. The volume receiving at least 45 Gy (V45) or V50 in normal brain tissue (whole brain minus the planning target volume 2; B-P) in RA1 was less compared with that in IMRT. V30, V35, V40, V45, or V50 in B-P in RA2 was less compared with that in IMRT. The MUs per fraction in RA1 and RA2 were significantly less compared with those in IMRT. All differences with a P-value<0.05 were considered to be significantly different. In conclusion, RA1 and RA2 markedly reduced the MUs per fraction, and spared partial organs at risk and B-P compared with IMRT.

Intensity-modulated radiotherapy for gliomas:dosimetric effects of changes in gross tumor volume on organs at risk and healthy brain tissue.

AIM: The aim of this study was to explore the effects of changes in the gross tumor volume (GTV) on dose distribution in organs at risk (OARs) and healthy brain tissue in patients with gliomas. METHODS: Eleven patients suffering from gliomas with intensity-modulated radiotherapy (IMRT) plans treated with a simultaneous integrated boost technique planned before therapy (initial plans) were prospectively enrolled. At the end of radiotherapy, patients underwent repeat computed tomography and magnetic resonance imaging, and IMRT was replanned. The GTV and dosimetric parameters between the initial and replanned IMRT were compared using the Wilcoxon two-related-sample test, and correlations between the initial GTV and the replanned target volumes were assessed using the bivariate correlation test. RESULTS: The volume of the residual tumor did not change significantly (P>0.05), the volume of the surgical cavity decreased significantly (P<0.05), and the GTV and target volumes decreased significantly at the end of IMRT (all P<0.05). The near-maximum dose to OARs and volumes of healthy brain tissue receiving total doses of 10-50 Gy were lower in the replanned IMRT than in the initial IMRT (all P<0.05). The GTV in the initial plan was significantly positively correlated with the changes in the GTV and planning target volume 1 that occurred during IMRT (all P<0.05). CONCLUSION: The reduction in the GTV in patients with gliomas resulted from shrinkage of the surgical cavity during IMRT, leading to decreased doses to the OARs and healthy brain tissue. Such changes appeared to be most meaningful in patients with large initial GTV values.

Different setup errors assessed by weekly cone-beam computed tomography on different registration in nasopharyngeal carcinoma treated with intensity-modulated radiation therapy.

The study aimed to investigate the difference of setup errors on different registration in the treatment of nasopharyngeal carcinoma based on weekly cone-beam computed tomography (CBCT). Thirty nasopharyngeal cancer patients scheduled to undergo intensity-modulated radiotherapy (IMRT) were prospectively enrolled in the study. Each patient had a weekly CBCT before radiation therapy. In the entire study, 201 CBCT scans were obtained. The scans were registered to the planning CT to determine the difference of setup errors on different registration sites. Different registration sites were represented by bony landmarks. Nasal septum and pterygoid process represent head, cervical vertebrae 1-3 represent upper neck, and cervical vertebrae 4-6 represent lower neck. Patient positioning errors were recorded in the right-left (RL), superior-inferior (SI), and anterior-posterior (AP) directions over the course of radiotherapy. Planning target volume margins were calculated from the systematic and random errors. In this study, we can make a conclusion that there are setup errors in RL, SI, and AP directions of nasopharyngeal carcinoma patients undergoing IMRT. In addition, the head and neck setup error has the difference, with statistical significance, while patient setup error of neck is greater than that of head during the course of radiotherapy. In our institution, we recommend a planning target volume margin of 3.0 mm in RL direction, 1.3 mm in SI direction, and 2.6 mm in AP direction for nasopharyngeal cancer patients undergoing IMRT with weekly CBCT scans.