Treatment barriers and clinical outcome of children with medulloblastoma in China: a report from the Chinese Children's Cancer Group (CCCG).

BACKGROUND: Medulloblastoma (MB) is the most common malignant central nervous system tumor of childhood. Management requires interdisciplinary care and is associated with unique challenges in developing regions. Here, we report the characteristics, clinical outcome and treatment barriers for Chinese children with MB based on a multi-institutional cohort from the Chinese Children's Cancer Group (CCCG). METHODS: Retrospective cohort study among 12 Chinese pediatric oncology units from the CCCG Brain Tumor Workgroup on patients aged <18 years diagnosed with MB from 2016 to 2019. RESULTS: 221 patients (male:female = 138:83) were included, 175 (79%) were ≥3 years of age, and 46 (21%) <3 years. 177 patients (80%) were completely staged, among which 50 (28%) had metastasis and 70 (40%) were considered to have high-risk (HR) disease. Gross/near-total resection was achieved in 203 patients (92%). In patients where molecular grouping could be assigned, 19 (16%), 35 (29%), and 65 (54%), respectively had WNT-activated, SHH-activated, and Group 3/4 MB. The median duration between resection and initiation of adjuvant therapy was 36 days. Respective 2-year PFS and OS rates were 76.0 ± 3.0% and 88.0 ± 2.3%. PFS was significantly associated with age, metastatic status and clinical risk grouping. Chemotherapy use during CSI or alkylator choice were not significant predictors for patient outcome. CONCLUSIONS: We reported the clinical profiles and outcome from the largest cohort of Chinese children with MB after multi-modal therapy. Strengths and limitations on the local provision of neuro-oncology service are identified.

Renal Denervation by Noninvasive Stereotactic Radiotherapy Induces Persistent Reduction of Sympathetic Activity in a Hypertensive Swine Model.

Background We have previously reported the feasibility of noninvasive stereotactic body radiotherapy (SBRT) as a novel approach for renal denervation. Methods and Results Herein, from a translational point of view, we assessed the antihypertensive effect and chronological evolution of SBRT-induced renal nerve injury within 6 months in a hypertensive swine model. Hypertension was induced in swine by subcutaneous implantation of deoxycorticosterone acetate pellets in combination with a high-salt diet. A single dose of 25 Gy with SBRT was delivered for renal denervation in 9 swine within 3.4±1.0 minutes. Blood pressure levels at baseline and 1 and 6 months post-SBRT were comparable to control (n=5), whereas renal norepinephrine was significantly lower at 6 months (P<0.05). Abdominal computed tomography, performed before euthanasia and renal function assessment, remained normal. Standard semiquantitative histological assessment showed that compared with control (1.4±0.4), renal nerve injury was greater at 1 month post-SBRT (2.3±0.3) and peaked at 6 months post-SBRT (3.2±0.8) (P<0.05), along with a higher proportion of active caspase-3-positive nerves (P<0.05). Moreover, SBRT resulted in continuous dysfunction of renal sympathetic nerves and low level of nerve regeneration in 6 months by immunohistochemistry analysis. Conclusions SBRT delivering 25 Gy for renal denervation was safe and related to sustained reduction of sympathetic activity by aggravating nerve damage and inhibiting nerve regeneration up to 6 months; however, its translation to clinical trial should be cautious because of the negative blood pressure response in the deoxycorticosterone acetate-salt hypertensive swine model.

RBM5-AS1 promotes radioresistance in medulloblastoma through stabilization of SIRT6 protein.

Cancer stem cells (CSCs) contribute to radioresistance in medulloblastoma. Thus, identification of key regulators of medulloblastoma stemness is critical for improving radiotherapy for medulloblastoma. In the present study, we profiled CSC-related long non-coding RNAs (lncRNAs) between radioresistant and parental medulloblastoma cells. The roles of the lncRNA RBM5-AS1 in the stemness and radiosensitivity of medulloblastoma cells were investigated. We found that RBM5-AS1, a novel inducer of medulloblastoma stemness, was significantly upregulated in radioresistant medulloblastoma cells compared to parental cells. Knockdown of RBM5-AS1 diminished the viability and clonogenic survival of both radioresistant and parental medulloblastoma cells after radiation. Silencing of RBM5-AS1 significantly enhanced radiation-induced apoptosis and DNA damage. In vivo studies confirmed that depletion of RBM5-AS1 inhibited tumor growth and increased radiosensitivity in a medulloblastoma xenograft model. In contrast, overexpression of RBM5-AS1 reduced radiation-induced apoptosis and DNA damage in medulloblastoma cells. Mechanistically, RBM5-AS1 interacted with and stabilized sirtuin 6 (SIRT6) protein. Silencing of SIRT6 reduced the stemness and reinforced radiation-induced DNA damage in medulloblastoma cells. Overexpression of SIRT6 rescued medulloblastoma cells from RBM5-AS1 depletion-induced radiosensitization and DNA damage. Overall, we identify RBM5-AS1 as an inducer of stemness and radioresistance in medulloblastoma. Targeting RBM5-AS1 may represent a potential strategy to overcome the resistance to radiotherapy in this malignancy.

Genetic variations in DNA repair gene NEIL1 associated with radiation pneumonitis risk in lung cancer patients.

BACKGROUND: Radiation pneumonitis (RP) is a common side effect in lung cancer patients who received radiotherapy. Our previous study found genetic variations in DNA repair gene NEIL1 may be a predictor of RP in patients with esophageal cancer. So, we hypothesis genetic variations in NEIL1 gene could affect the risk of RP in lung cancer patients following radiotherapy. METHODS: Genetic variations rs4462560 G>C and rs7402844 C>G in NEIL1 gene were genotyped in 174 lung cancer patients received radio(chemo)therapy. Luciferase assay, real-time PCR and Western blot were used to access the effect of the variants on NEIL1 in HELF and HEF cell lines which were transfected with plasmids containing rs4462560 G>C and rs7402844 C>G. RESULTS: Patients with rs4462560 CC genotype had a lower risk of RP grade ≥2 than GG genotype. Compared with the CC genotype, rs7402844 GG genotype was associated with an increased RP grade ≥2 risk. What is more, rs4462560 G decreased the relative luciferase activity of NEIL1 gene promoter compared with the negative control in vitro, while rs4462560 C can increase the relative luciferase activity. The mRNA and protein level of the NEIL1 gene in rs4462560 G were lower than rs4462560 C. CONCLUSIONS: Genetic variants of NEIL1 are associated with RP risk through regulation of NEIL1 expression and serve as independent biomarkers for prediction of RP in patients treated with thoracic radiotherapy.

SPARC regulates ferroptosis induced by sorafenib in human hepatocellular carcinoma.

BACKGROUND: Secreted protein acidic and rich in cysteine (SPARC) is implicated in cancer progression, but its role and associated molecular mechanism in the sorafenib sensitivity of hepatocellular carcinoma cells (HCC) remains elusive. METHODS: Human HCC cell lines Hep3B and HepG2 were treated with sorafenib alone or combined with activator or inhibitor of ferroptosis. Cell viability assay, reactive oxygen species (ROS) assay, lactate dehydrogenase (LDH) assay and western blot were used to study the regulatory mechanism of SPARC on HCC cells. RESULTS: Overexpression of SPARC enhanced the cytotoxic effect of sorafenib in Hep3B and HepG2 cells compared with parental cells. Depletion of SPARC decreased the cytotoxic effect of sorafenib in Hep3B and HepG2 cells compared with parental cells. Moreover, overexpression of SPARC significantly induced LDH release, whereas depletion of SPARC suppressed the release of LDH in Hep3B and HepG2 cells. Inhibition of ferroptosis exerted a clear inhibitory role against LDH release, whereas activation of ferroptosis promoted the release of LDH in HCC cells, as accompanied with deregulated expression of ferroptosis-related proteins. Furthermore, overexpression of SPARC induced oxidative stress, whereas depletion of SPARC suppressed the production of ROS. Deferoxamine (DFX)-induced inhibition of ferroptosis suppressed the production of ROS, while activation of ferroptosis promoted the contents of ROS in HCC cells exposed to sorafenib. CONCLUSION: Our findings give a better understanding of ferroptosis and its molecular mechanism in HCC cells that is regulated by SPARC in response to sorafenib.

Prognostic significance of C-MYC dysregulation in esophageal squamous cell carcinoma: a meta-analysis.

Aim: The clinicopathological and prognostic significance of C-MYC dysregulation (amplification or overexpression) in esophageal squamous cell carcinoma (ESCC) remains controversial. Therefore, we performed this meta-analysis to elucidate this relationship. Materials & methods: Available studies were retrieved from PubMed, Web of Science, EMBASE and the Cochrane Library, and ten studies with a total of 1432 patients were included in this meta-analysis. Results: Pooled results showed that C-MYC dysregulation was significantly associated with poor overall survival (hazard ratio: 1.405 [95% CI: 1.170-1.639]; p < 0.001) and lymph node metastasis (odds ratio: 1.798 [95% CI: 1.125-2.873]; p = 0.014). Subgroup analysis confirmed the results and more prominent predictive effects were observed in the C-MYC amplification group. Conclusion: C-MYC dysregulation is a promising biomarker for ESCC prognosis.

Metabolic Fingerprinting on Synthetic Alloys for Medulloblastoma Diagnosis and Radiotherapy Evaluation.

Diagnostics is the key in screening and treatment of cancer. As an emerging tool in precision medicine, metabolic analysis detects end products of pathways, and thus is more distal than proteomic/genetic analysis. However, metabolic analysis is far from ideal in clinical diagnosis due to the sample complexity and metabolite abundance in patient specimens. A further challenge is real-time and accurate tracking of treatment effect, e.g., radiotherapy. Here, Pd-Au synthetic alloys are reported for mass-spectrometry-based metabolic fingerprinting and analysis, toward medulloblastoma diagnosis and radiotherapy evaluation. A core-shell structure is designed using magnetic core particles to support Pd-Au alloys on the surface. Optimized synthetic alloys enhance the laser desorption/ionization efficacy and achieve direct detection of 100 nL of biofluids in seconds. Medulloblastoma patients are differentiated from healthy controls with average diagnostic sensitivity of 94.0%, specificity of 85.7%, and accuracy of 89.9%, by machine learning of metabolic fingerprinting. Furthermore, the radiotherapy process of patients is monitored and a preliminary panel of serum metabolite biomarkers is identified with gradual changes. This work will lead to the application-driven development of novel materials with tailored structural design and establishment of new protocols for precision medicine in near future.

Comparison of Nodal Target Volume Definition in Breast Cancer Radiation Therapy According to RTOG Versus ESTRO Atlases: A Practical Review From the TransAtlantic Radiation Oncology Network (TRONE).

Regional nodal irradiation has gained interest in recent years with the publication of several important randomized trials and the availability of more conformal techniques. Target volume delineation represents a critical step in the radiation planning process. Adequate coverage of the microscopic tumor spread to regional lymph nodes must be weighed against exposure of critical structures such as the heart and lungs. Among available guidelines for delineating the clinical target volume for the breast/chest wall and regional nodes, the Radiation Therapy Oncology Group and European Society for Radiotherapy and Oncology guidelines are the most widely used internationally. These guidelines have been formulated based on anatomic boundaries of areas historically covered in 2-dimensional field-based radiation therapy but have not been validated by patterns-of-failure studies. In recent years, an important body of data has emerged from mapping studies documenting patterns of local and regional recurrence. We aim to review, discuss, and compare contouring guidelines for breast cancer radiation therapy in the context of contemporary data on locoregional relapse to improve their implementation in modern practice.

Scattered Dose to Ovary From Radiotherapy for Neuroblastoma in Female Children.

PURPOSE: To measure the scattered dose to ovary from radiotherapy for neuroblastoma in female children and to evaluate the relevant risks for radiation-induced ovarian damage. MATERIAL AND METHODS: Radiotherapy for child neuroblastoma was simulated on the water phantom. The scattered dose to ovary is measured by ionization chamber on the linear accelerator with 3-dimensional conformal radiation therapy and intensity-modulated radiation therapy treatment producing 6MV and 10MV X-rays. The treatment planning procedure was carried out on a computer system (TPS, Oncentra). Optimization of the number and orientation of beams were performed in order to minimize the ovarian dose. RESULTS: For the target dose of 21.6 Gy, the scattered dose to ovary was ranged from 1.3 to 46.8 cGy depending on the treatment method and the energy of the beams. The ovarian dose of intensity-modulated radiation therapy is 1.32 to 1.64 times higher than that of 3-dimensional conformal radiation therapy. The ovarian dose of 6MV beam's energy is 1.52 to 1.64 times higher than that of 10MV beam's energy. For the radiotherapy, the scattered dose of ovaries on phantom by ionization chamber was 1.40 to 2.32 times higher than that on TPS calculated. CONCLUSION: The dosimetric data suggest that pediatric radiotherapy is not associated with a risk for permanent damage to the ovaries in female children. Through choosing the beams' energy and treatment plan's method, the scattered dose of ovaries can be reduced. The risk for development of hereditary disorders in offspring conceived after exposure is low.

Noninvasive Stereotactic Radiotherapy for Renal Denervation in a Swine Model.

BACKGROUND: Catheter-based renal denervation (RDN) has achieved promising outcomes to treat hypertension in recent randomized controlled trials. OBJECTIVES: The purpose of this study was to assess the feasibility, efficacy, and safety of noninvasive stereotactic body radiotherapy (SBRT) as an approach for RDN. METHODS: SBRT was performed in 24 renal arteries from 12 normotensive swine at doses of 25, 35, and 45 Gy (n = 4 each), and an additional 4 swine served as controls. Blood pressure (BP), renal function, and serum norepinephrine (NE) values were obtained at baseline and at 7 days, 1 month, and 3 months after SBRT. Abdominal contrast-enhanced computed tomography (CT) was performed after 3 months before euthanasia. Renal NE concentration was determined, and histological analysis and immunohistochemistry against tyrosine hydroxylase were performed. RESULTS: SBRT procedure was successful in all 12 swine. BP was comparable among groups. Serum and renal NE levels at 3 months were significantly lower in treatment groups compared with control group. Furthermore, SBRT resulted in significantly greater nerve injury score and lower tyrosine hydroxylase score compared with control subjects, whereas there were no statistical differences between SBRT groups. Circumferential lesions created with 35 and 45 Gy were significantly greater than with 25 Gy. CT and histology analysis revealed that animals receiving 35 and 45 Gy experienced more collateral damage, which was minimal in the 25-Gy group. CONCLUSIONS: Noninvasive SBRT was feasible and effective for complete, circumferential RDN in a swine model, with dosage at 25 Gy providing the safest short-term profile.

Label-Free Electrochemical Sensor for CD44 by Ligand-Protein Interaction.

Detection of biomarkers in biosystems plays a key role in advanced biodiagnostics for research and clinical use. Design of new analytical platforms is challenging and in demand, addressing molecular capture and subsequent quantitation. Herein, we developed a label-free electrochemical sensor for CD44 by ligand-protein interaction. We assembled carbon nanotube composites on the electrode to enhance electronic conductivity by 6.2-fold and reduce overpotential with a shift of 77 mV. We conjugated hyaluronic acid (HA) to the surface of carbon nanotubes via electrostatic interaction between HA and poly(diallyldimethylammonium chloride) (PDDA). Consequently, we performed direct electrochemical sensing of CD44 with a dynamic range of 0.01-100 ng/mL and detection limit of 5.94 pg/mL without any postlabeling for amplification, comparable to the best current results. The sensor also displayed high selectivity, reproducibility with relative standard deviation (RSD, n = 5) of 2.57%, and long-term stability for 14 days. We demonstrated applications of the sensor in detection of human serum and cancer cells. Our work guides the development of more sensor types by ligand-protein interactions and contributes to design of interfaces in given biosystems for diagnosis.

Expression of γ-H2AX and patient prognosis in breast cancer cohort.

H2AX phosphorylation is a novel marker of DNA double-stranded breaks. In the present study, we assessed the γ-H2AX expression, its association with other clinicopathologic characteristics, and the prognosis in a cohort of 97 patients with breast cancer. Ninety-seven specimens of tumor tissue and 77 adjacent normal tissues from patients with breast cancer were examined. All patients underwent modified radical mastectomy or local tumor resection without lymph node dissection. γ-H2AX expression was assessed by standard immunohistochemistry. Patients were followed after surgery for a mean duration of 70.1 ± 18.7 months (range, 6-93 months). The γ-H2AX staining was positive in 27 (27.8%) patients. The positive rates of H2AX were 26.0% and 2.6% in tumor tissue and adjacent normal tissues, respectively. γ-H2AX positive status was negatively associated with TNM staging, with 24 positive cases (32.4%) in TNM staging I-II, while no positive cases in TNM staging III-IV (P = 0.026). Sixteen patients (16.5%) died during the follow-up. No significant association between γ-H2AX expression and patient survival was detected. The unadjusted HR (hazard ratio) for γ-H2AX positive was 0.84 (95% CI: 0.27, 2.60). In TNM staging subgroup analysis, death only occurred in γ-H2AX negative patients. Our study is the first study to demonstrate that expression of γ-H2AX is associated with TNM staging. Due to the small sample and limited follow-up time, we did not observe a significant association between γ-H2AX and patient survival. γ-H2AX expression could be a potential biomarker for cancer diagnosis and prediction, and further studies are in need.

A Plasmonic Mass Spectrometry Approach for Detection of Small Nutrients and Toxins.

Nutriology relies on advanced analytical tools to study the molecular compositions of food and provide key information on sample quality/safety. Small nutrients detection is challenging due to the high diversity and broad dynamic range of molecules in food samples, and a further issue is to track low abundance toxins. Herein, we developed a novel plasmonic matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) approach to detect small nutrients and toxins in complex biological emulsion samples. Silver nanoshells (SiO2@Ag) with optimized structures were used as matrices and achieved direct analysis of ~ 6 nL of human breast milk without any enrichment or separation. We performed identification and quantitation of small nutrients and toxins with limit-of-detection down to 0.4 pmol (for melamine) and reaction time shortened to minutes, which is superior to the conventional biochemical method currently in use. The developed approach contributes to the near-future application of MALDI MS in a broad field and personalized design of plasmonic materials for real-case bio-analysis.

miR-339-5p Increases Radiosensitivity of Lung Cancer Cells by Targeting Phosphatases of Regenerating Liver-1 (PRL-1).

BACKGROUND Radiotherapy is the most effective non-surgical modality in lung cancer treatment, and microRNAs (miRNAs) have been suggested as key regulators in radiosensitization. Herein, we explored the specific function of miR-339-5p in the radiosensitivity of lung cancer cells. MATERIAL AND METHODS Radiosensitivity was assessed by cell viability (CCK-8 assay), cell apoptosis, and cell cycle changes (flow cytometry). qRT-PCR and subsequent Western blot assays were used to determine the expression of miR-339-5p and other related proteins. RESULTS We demonstrated that ionizing radiation (IR) exposure impaired lung cancer cell viability, and found that miR-339-5p is a novel IR-inducible miRNA. Overexpression of miR-339-5p enhanced radiosensitivity of A549 and H460 cells by inhibiting cell viability, increasing apoptosis, inducing cell cycle arrest, and suppressing cell proliferation. Further exploration validated that miR-339-5p can target phosphatases of regenerating liver-1  (PRL-1) in lung cancer cells. Restoration of PRL-1 partially reverses the enhanced radiosensitivity of lung cancer cells induced by miR-339-5p. CONCLUSIONS Our data support that miR-339-5p has potential therapeutic value by sensitizing lung cancer cells to radiation via targeting of PRL-1.

Analysis of Recurrent Sacrococcygeal Teratoma in Children: Clinical Features, Relapse Risks, and Anorectal Functional Sequelae.

BACKGROUND Sacrococcygeal teratoma (SCT) is a relatively uncommon tumor. Recurrence with poor survival and anorectal dysfunction are the 2 leading problems for patients. Here, we would review the clinic features of patients with SCTs in our hospital to identify risk factors of recurrent SCTs and to analyze anorectal functional sequelae. MATERIAL AND METHODS A retrospective review of all patients with SCTs in our center between 2007 and 2013 was performed. We analyzed the recorded data on each patient and performed follow-up through phone calls. RESULTS Our study included 105 inpatients (78 girls and 27 boys); 104 cases underwent surgical resection, and 62.5% cases had a mature histopathology. The proportion of malignant teratomas rose with increasing age. Fifteen children developed recurrent SCTs with a median of 11.5 months, and most of them had an elevation of AFP levels. Four recurrent children experienced a second tumor relapse. We observed a statistically significant difference in survival rate through Kaplan-Meier method between relapsed (66.7%) and non-relapsed (94.4%) patients. In univariate analysis, incomplete primary resection and malignant histology were proven to increase recurrence risks. Nearly half of patients had at least 1 of the parameters reflecting abnormal bowel function (e.g., involuntary bowel movements, fecal incontinence, and constipation). For those recurrent SCTs patients, difficulty defecating was a major problem. CONCLUSIONS Tumor recurrence affected the prognosis of children with SCT. In our research, incomplete resection and malignant histology were considered risk factors. Constipation was the main problem in anorectal functional sequelae for children who had recurrence.

microRNA-539 suppresses tumor growth and tumorigenesis and overcomes arsenic trioxide resistance in hepatocellular carcinoma.

AIMS: Dysregulation of microRNAs (miRNAs) plays a critical role in tumor growth and progression. In this study, we sought to explore the expression and biological roles of miR-539 in hepatocellular carcinoma (HCC). MAIN METHODS: The expression of miR-539 in human HCC tissues and cell lines was examined. The effects of miR-539 overexpression on cell growth, tumorigenicity, arsenic trioxide resistance of HCC cells were determined. The signaling pathways involved in the action of miR-539 in HCC were also investigated. KEY FINDINGS: miR-539 was downregulated in HCC tissues and cells, relative to corresponding controls. Overexpression of miR-539 inhibited HCC cell viability and colony formation in vitro and impaired tumorigenesis of HCC cells in vivo. Transfection with miR-539 mimic significantly induced apoptosis in HepG2 cells, which was coupled with reduced expression of anti-apoptotic proteins Bcl-2 and Bcl-xL and decreased phosphorylation of Stat3. Overexpression of a constitutively active form of Stat3 partially blocked miR-539-mediated apoptosis. Enforced expression of miR-539 resensitized arsenic trioxide-resistant HCC cells to arsenic trioxide. Intratumoral delivery of miR-539 mimic significantly retarded the growth of xenograft tumors from arsenic trioxide-resistant HCC cells by about 35%, compared to delivery of control miRNA (P<0.05). In combination with arsenic trioxide, miR-539 mimic yielded about 80% decrease in tumor burden. SIGNIFICANCE: miR-539 functions as a tumor suppressor in HCC and reexpression of this miRNA offers a potential therapeutic strategy for this disease.

Chemokine CXCL1 may serve as a potential molecular target for hepatocellular carcinoma.

The purpose of this study was to screen for changes in chemokine and chemokine-related genes that are expressed in hepatocellular carcinoma (HCC) as potential markers of HCC progression. Total RNA was extracted from tumor and peritumor tissues from mice with HCC and analyzed using a PCR microarray comprising 98 genes. Changes in gene expression of threefold or more were screened and subsequently confirmed by immunohistochemical analyses and western blotting. Furthermore, whether chemokine knockdown by RNA interference (RNAi) could significantly suppress tumor growth in vivo was also evaluated. Finally, total serum samples were collected from HCC patients with HBV/cirrhosis (n = 16) or liver cirrhosis (n = 16) and from healthy controls (n = 16). The serum mRNA and protein expression levels of CXCL1 in primary liver cancer patients were detected by qRT-PCR and western blot analysis, respectively. Several genes were up-regulated in tumor tissues during the progression period, including CXCL1, CXCL2, CXCL3, and IL-1ß, while CXCR1 expression was down-regulated. CBRH-7919 cells carrying CXCL1 siRNA resulted in decreased tumor growth in nude mice. The differences in serum CXCL1 mRNA and protein levels among the HCC, hepatic sclerosis (HS), and control groups were significant (P < 0.001). The mRNA and protein levels of CXCL1 in the HCC group were up-regulated compared with the HS group or the control group (P < 0.001). Several chemokine genes were identified that might play important roles in the tumor microenvironment of HCC. These results provide new insights into human HCC and may ultimately facilitate early HCC diagnosis and lead to the discovery of innovative therapeutic approaches for HCC.

Atypical teratoid/rhabdoid tumours: clinicopathological characteristics, prognostic factors and outcomes of 22 children from 2010 to 2015 in China.

Atypical teratoid/rhabdoid tumours (AT/RTs) are rare, highly malignant tumours of the central nervous system (CNS) with poor prognosis that usually affect young children. The aim of this study was to assess the clinicopathological features and prognostic factors of AT/RTs. Here, we describe the clinicopathological and immunohistochemical characteristics, along with the treatments and outcomes, of 22 patients with AT/RTs treated in our hospital from 2010 to 2015. Morphologically, cytoplasmic vacuoles, the most common characteristic in our cases, were observed in 68% of the cases. Similarly, vesicular nuclei were detected in 68% of the cases. However, rhabdoid cells were found in only 59.1% of the cases and were not observed in 40.9% of the cases. Immunohistochemical analysis revealed loss of nuclear INI1 expression in all 22 cases. Age, surgical resection and adjuvant therapy, but not tumour location, were associated with AT/RTs patient prognosis. Our results showed that cells with cytoplasmic vacuoles or with vesicular nuclei are more common than rhabdoid cells in patients with AT/RTs and that a lack of INI1 protein expression is the most useful marker for the differential diagnosis of AT/RTs. Young age is a negative prognostic factor, whereas gross total surgical resection and adjuvant therapy are positive prognostic factors for AT/RT patients.

Clinical characteristics and abandonment and outcome of treatment in 67 Chinese children with medulloblastoma.

OBJECT The purpose of this study was to explore the clinical features and outcome of medulloblastoma in Chinese children. The authors analyze the reasons that treatment is abandoned and attempt to provide evidence-based recommendations for improving the prognosis of medulloblastoma in this population. METHODS A total of 67 pediatric cases of newly diagnosed medulloblastoma were included in this study. All of the children were treated at Xinhua Hospital between January 2007 and June 2013. The authors retrospectively analyzed the clinical data, treatment modalities, and outcome. The male-to-female ratio was 2:1, and the patients' median age at diagnosis was 51.96 months (range 3.96-168.24 months). The median duration of follow-up was 32 months (range 3-70 months). RESULTS At the most recent follow-up date, 31 patients (46%) were alive, 30 (45%) had died, and 6 (9%) had been lost to follow-up. The estimated 3-year overall survival and progression-free survival, based on Kaplan-Meier analysis, were 55.1% ± 6.4% and 45.6% ± 6.7%, respectively. Univariate analysis showed that standard-risk group (p = 0.009), postoperative radiotherapy (RT) combined with chemotherapy (p < 0.001), older age (≥ 3 years) at diagnosis (p = 0.010), gross-total resection (p = 0.012), annual family income higher than $3000 (p = 0.033), and living in urban areas (p = 0.008) were favorable prognostic factors. Multivariate analysis revealed that postoperative RT combined with chemotherapy was an independent prognostic factor (p < 0.001). The treatment abandonment rate in this cohort was 31% (21 of 67 cases). CONCLUSIONS There was a large gap between the outcome of medulloblastoma in Chinese children and the outcome in Western children. Based on our data, treatment abandonment was the major cause of therapeutic failure. Parents' misunderstanding of medulloblastoma played a major role in abandonment, followed by financial and transportation difficulties. Establishment of multidisciplinary treatment teams could improve the prognosis of medulloblastoma in Chinese children.

A new lead-free radiation shielding material for radiotherapy.

Lead has recently been recognised as a source of environmental pollution, including the lead used for radiation shielding in radiotherapy. The bremsstrahlung radiation caused by the interaction between the electron beam and lead may reduce the accuracy of radiotherapy. To avoid the use of lead, a new material composed of tungsten and hydrogenated styrene-butadiene-styrene copolymer is studied with the Monte Carlo (MC) method and experiment in this paper. The component of the material is chosen after simulation with the MC method and the practical measurement is taken to validate the shielding ability of the material. The result shows that the shielding ability of the new material is good enough to fulfill the requirement for application in radiotherapy. Compared with lead alloy, the present new material is so flexible that can be easily customized into arbitrary shapes. Moreover, the material is environmentally friendly and can be recycled conveniently. Therefore, the material can be used as an effective lead substitute for shielding against electron beams in radiotherapy.