Chinese Tumor Patients Research Articles

The safety and short-term efficacy of selective internal radiation therapy combined with systemic treatment for unresectable malignant hepatic tumors in Chinese patients.

e16247 Background: There are many systemic treatment options for patients with unresectable malignant hepatic tumors. In China, selective internal radiation therapy (SIRT) with yttrium-90 (Y90) resin microspheres was approved until 2022. The aim of this retrospective study was to investigate the safety and short-term efficacy of SIRT with Y90 resin microspheres followed by systemic treatment in Chinese patients. Methods: The study analyzed patients who received SIRT with Y90 combined with systemic treatment at our center between June 2022 and October 2023. The study's primary endpoint was to determine the objective response rate (ORR), while safety was the secondary endpoint. Response was measured based on modified Response Evaluation Criteria in Solid Tumors criteria (mRECIST) up to 90 days after the initial therapy. Safety was evaluated using the Common Terminology Criteria for Adverse Events Version 5.0. Results: 21 patients wereincluded, of whom 22 times of SIRT were performed. 18 patients had HCC, and 3 had mCRC.The baseline characteristics of the patients are shown in Table. The median age was 54 years (IQR, 48-59 years) and 90.5% of patients were male. According to Eastern Cooperative Oncology Group performance status, grade 0 and grade 1 were 81% and 19%, respectively, whereas Child-Pugh A represented 90.5% of cases. The proportion of patients with hepatitis B virus infection was 95.2%. Thirteen (61.9%) patients received different treatments before SIRT. The median number of tumors was 2.5 (IQR, 1-4.3), whereas the median diameter of the largest lesion was 100.4 mm (IQR, 68.3-127.7 mm). PVTT was classified as follows: Vp1 (n = 3), Vp2 (n = 2), Vp3 (n = 2) and Vp4 (n = 1). Median AFP was 33.2 ng/mL (IQR, 5.9-401 ng/mL). The median total radiation activity administered was 1.4 GBq (IQR, 0.9-2.7 GBq) and the median target tissue dose was 205 Gy (IQR, 155-242 Gy). Nine (43%) patients were downstaged to surgery. Four (19%) patients had a complete response, fifteen (71.4%) had a partial response and two (9.5%) had a progressive disease. ORR and disease control rate were 90.5% and 90.5%, respectively. None of the patients experienced grade 3 and higher adverse events. The most common treatment-related adverse events were fever and abdominal pain, which required no special treatment. Conclusions: SIRT with Y90 resin microspheres combined with systemic treatment is safe and effective in patients with unresectable malignant hepatic tumors, which resulted in encouraging ORR (90.5%) and a downstaging rate (43%). Clinical trial information: ChiCTR2300077524. [Table: see text]

Mir-21-5p and Mir-455-5p as Markers for Diagnosis and Prognosis of Rectal Adenocarcinoma may Reduce Local CD4+ and CD8+ Lymphocyte Infiltration.

This study aimed to verify miRNAs and the molecular mechanisms of diagnostic and prognostic biomarkers for rectal adenocarcinoma. Two miRNA datasets of rectal adenocarcinoma were obtained from GEO and TCGA. GEO2R tool, Venn diagram, Kaplan-Meier survival analysis, KEGG pathway analyses, DIANA TOOLS, and Wilcoxon rank-sum test were used for biological information analysis. The diagnostic utility of miRNAs and immune infiltration of tumors in Chinese patients were validated by RTqPCR and immunofluorescence analysis. MiR-21-5P and miR-455-5p were both found to have a significant correlation with poor prognosis and higher expression in rectal adenocarcinoma. Besides, the ability to prognosis was independent of the clinicopathological stage. MiR-21-5P and miR-455-5p were enriched in the TGF-beta, Wnt, MAKP, and PI3K-AKT signaling pathways. Meanwhile, the high expression phenotype of miR-21-5P and miR-455-5p decreased CD4+ and CD8+ T cells. In summary, we found two significant diagnostic and prognostic miRNAs of rectal adenocarcinoma via integrated bioinformatics approach and clinical trials, which might decrease CD4+ and CD8+ T cells.

Molecular genomic landscape of pediatric solid tumors in Chinese patients: implications for clinical significance.

Pediatric solid tumors are significantly different from adult tumors. Studies have revealed genomic aberrations in pediatric solid tumors, but these analyses were based on Western populations. Currently, it is not known to what extent the existing genomic findings represent differences in ethnic backgrounds. DESIGN: We retrospectively analyzed the basic clinical characteristics of the patients, including age, cancer type, and sex distribution, and further analyzed the somatic and germline mutations of cancer-related genes in a Chinese pediatric cohort. In addition, we investigated the clinical significance of genomic mutations on therapeutic, prognostic, diagnostic, and preventive actions. Our study enrolled 318 pediatric patients, including 234 patients with CNS tumors and 84 patients with non-CNS tumors. Somatic mutation analysis showed that there were significant differences in mutation types between CNS tumors and non-CNS tumors. P/LP germline variants were identified in 8.49% of patients. In total, 42.8% patients prompted diagnostic, 37.7% patients prompted prognostic, 58.2% patients prompted therapeutic, and 8.5% patients prompted tumor-predisposing and preventive, and we found that genomic findings might improve clinical management. Our study is the first large-scale study to analyze the landscape of genetic mutations in pediatric patients with solid tumors in China. Genomic findings in CNS and non-CNS solid pediatric tumors provide evidence for the clinical classification and individualized treatment of pediatric tumors, and they will facilitate improvement of clinical management. Data presented in this study should serve as a reference to guide the future design of clinical trials.

Pharmacokinetics and Comparative Bioavailability of Test or Reference Capecitabine and Discrepant Pharmacokinetics Among Various Tumors in Chinese Solid Cancer Patients.

The main objective of this study was to compare the pharmacokinetic (PK) bioequivalence of two capecitabine tablets and explore the different PK profiles of various tumors in Chinese patients with cancer. All 76 patients with a confirmed cancer diagnosis were included in this study. A single dose of 2000mg of test or reference capecitabine (Xeloda, Hoffmann-La Roche) was orally administered postprandially. After 24hours of washout, the patients were administered the test or the reference capecitabine alternately. PK samples were taken at the time of predose up to 6hours postdose. Bioequivalence evaluation was performed using the geometric mean ratios of peak concentration in plasma (Cmax) , area under the concentration-time curve from time 0 to 6 h (AUC0-t) , and area under the concentration-time curve from time 0 to infinity (AUC0-∞ ) for capecitabine and 5-fluorouracil (5-FU). In this study, 90% confidence intervals of test/reference mean ratios of Cmax , AUC0-t , AUC0-∞ of capecitabine and 5-FU were in the range of 80%-125%. Both the test and reference capecitabine regimens were well tolerated in this study. Furthermore, we found that patients with esophageal-gastrointestinal cancers had higher exposure to capecitabine and a shorter time to Cmax (Tmax) than those with breast cancer. In conclusion, a single oral dose of 2000mg of test capecitabine tablets after postprandial administration was bioequivalent to the reference drug.

Retrospective study of the clinicopathological characteristics and prognostic factors of gastrointestinal stromal tumors in Chinese patients

The purpose of this study was to investigate the clinicopathological characteristics and prognostic factors of patients with gastrointestinal stromal tumors (GISTs) in mainland China. We retrospectively analyzed the clinicopathological characteristics and survival data of 149 patients with GISTs admitted to Shengjing Hospital of China Medical University from July 2011 to October 2017. The following details were collected from all patients: sex, age, symptoms, preoperative examination, pathology, surgical procedures, and follow-up data. Recurrence-free survival (RFS) and overall survival (OS) were used to assess survival outcomes. The Kaplan–Meier method was performed to draw survival curves and calculate the survival rate. The log-rank test was performed for univariate analysis, and the significant factors were included in multivariate analysis using a Cox proportional hazards model to determine prognostic factors. The 5-year RFS rate was 78.5 % and 5-year OS rate was 83.2 %. The univariate analysis showed that the following prognostic factors could significantly predict 5-year RFS and OS: tumor size, initial status, modified NIH classification, mitotic index, CD117 expression, Ki67 index, and surgical procedure (P < 0.05). The multivariate analysis showed that mitotic index, CD117, and Ki67 index were independent prognostic factors associated with 5-year RFS and 5-year OS. This study provides a reference for the clinicopathological characteristics and prognostic factors of patients with GISTs in mainland China, and the results suggest that focusing on immunohistochemical markers in clinical practice may be more reliable for the prediction of clinical outcomes.

Characteristics of TP53 germline variants and their correlations with Li-Fraumeni syndrome or Li-Fraumeni-like syndrome in Chinese tumor patients

Li-Fraumeni syndrome (LFS), a rare autosomal-dominant inheritance condition, is associated with a family cancer history as well as pathogenic/likely-pathogenic TP53 germline variants (P/LP TP53 GV). The current clinical methods for detecting LFS are limited. Here, we retrospectively investigate P/LP TP53 GV among Chinese cancer patients by next-generation sequencing and evaluate its relationship with a family cancer history. A total of 270 out of 19,226 cancer patients have TP53 GV, including 53 patients with P/LP TP53 GV. Patients with P/LP TP53 GV are mainly found in male with glioma, lung cancer or sarcoma. The median age of diagnosis for P/LP TP53 GV patients is significantly lower than that of non-P/LP TP53 GV patients (31-years vs. 53-years; P < 0.01). One LFS patient and 3 Li-Fraumeni-like syndrome (LFL) patients are among the 26 followed-up P/LP TP53 GV patients. Among 25 types of P/LP TP53 GV, the highest variant frequencies occurred at codon 175 and 248. p.M237I, p.R158H, p.C238Y and p.C275R, are firstly identified among the Chinese LFS/LFL patients. This study reports the (P/LP) TP53 GV characteristics of Chinese pan-cancer patients. These findings suggest analyzing the P/LP TP53 GV in cancer patients is an effective strategy for identifying cancer predisposition syndrome.

Retrospective Study of the Clinicopathological Characteristics and Prognostic Factors of Gastrointestinal Stromal Tumors in Chinese Patients

Retrospective Study of the Clinicopathological Characteristics and Prognostic Factors of Gastrointestinal Stromal Tumors in Chinese Patients

PET-CT for the diagnosis and treatment of primary musculoskeletal tumors in Chinese patients - experience from 255 patients in a single center.

The current study was carried out to assess the value of positron emission tomography (PET)/CT on the diagnosis and staging of primary musculoskeletal tumors. PET-CT test results and histopathological study reports of all the patients with primary musculoskeletal tumors in our department from January 2006 to July 2015 were retrospectively reviewed. Maximum standardized uptake value (SUVmax) in these PET-CT reports were recorded and analyzed respectively for each type of sarcoma. A total of 255 patients were included in the final analysis. Sensitivity of SUVmax based diagnosis was 96.6% for primary malignant osseous sarcomas and 91.2% for soft tissue sarcomas. SUVmax of high-grade osseous sarcomas (average 8.4 ± 5.5) was significantly higher (p < 0.001) than low-grade osseous sarcomas (average 3.9 ± 1.8); based on current case series, SUVmax of high-grade soft tissue sarcomas (7.5 ± 5.1) was not significantly different (p = 0.229) from that of low-grade soft tissue sarcomas (5.3 ± 3.7). Significant decrease of SUVmax value after chemotherapy was associated with favorable prognosis in patients with osteosarcoma. Results of the current study indicate that, the SUVmax based application of PET-CT can be a valuable supplementary method to histopathological tests regarding the diagnosis and staging of primary musculoskeletal sarcomas. SUVmax based application of PET-CT is a highly sensitive method in diagnosis of primary osseous and soft tissue sarcomas in Chinese patients.

Programmed cell death protein-1 inhibitors in the treatment of digestive system tumors in Chinese population: an observational study of effectiveness and safety.

Tumor of the digestive system is a common malignancy with high morbidity and mortality. Although programmed cell death-1 (PD-1) inhibitors have become an effective treatment strategies for many kinds of tumors, there is still some uncertainty in digestive tumors, including: (I) therapeutic effects of PD-1 inhibitors are relatively limited; (II) responses of digestive system tumors to immunotherapies are highly heterogeneous. In the present study, we investigated the outcomes of PD-1 inhibitors for digestive system tumors in Chinese patients to analyze factors that may affect the effects of immunotherapies in digestive system tumors. Data were obtained from the Hospital Information System (HIS) of the Department of Digestive Oncology (Henan Cancer Hospital) between January 2019 and December 2019. Inclusion criteria included patients receiving the same PD-1 inhibitor continuously for advanced or recurrent/metastatic digestive system tumors. Indicators including age, sex, clinical diagnosis, height, weight, gene status, PD-1 inhibitors, treatment regimen, medication cycle, efficacy evaluation results, and adverse reactions were analyzed retrospectively. The clinical outcomes were progression-free survival (PFS) and safety. A total of 2,767 patients were discharged from HIS, of which 64 (37 male/27 female) were included in this study. Thirty-eight (59.4%) of the patients were aged <60 years. Tumors included esophageal, gastric, liver, colorectal, and pancreatic cancer. Up until 30 June 2020, 51 patients were followed up to median progression-free survival (PFS), which was 5 months; the longest PFS was 18.5 months. There was no statistical significance in grouping according to sex, age and body mass index. Nevertheless, the median PFS differed statistically between monotherapy (9.4 months) versus combined therapy (4.7 months), and Cox regression analysis suggested that patients might benefit more from monotherapy than combined therapy. The incidence of adverse reactions was 47.7%, with thyroid dysfunction the most common adverse reaction. The incidence of grade 3-4 adverse reactions was 9.2% and mainly included pulmonary infection, immune-associated hepatitis, and severe oral ulcers. In digestive tumors, especially for second-line treatment and beyond, PD-1 monotherapy might be more beneficial than combined therapy. However, this might be related to the patient's tolerance. Large-sample prospective studies are needed for confirmation.

Abstract 810: Enrichment and screening of LFS patients by analyzing TP53 germline mutations of a Chinese cancer cohort

Abstract Background: Li-Fraumeni syndrome (LFS) is a rare autosomal dominant inherited cancer syndrome; clinical diagnosis of it is mainly based on familial and personal history of cancer. Currently, most clinicians are lack of knowledge and experience of this rare disease, resulting in a difficulty to identify it. Consider that this is a rare tumor-type syndrome and 60-80% of the patients have germline variants of TP53, herein, we analyzed germline pathogenic/likely pathogenic (P/LP) TP53 variants in a Chinese tumor cohort with unknown familial history, and successfully established an analysis process to better screen for LFS patients. Methods: We retrospectively analyzed the germline TP53 mutations of a total of 19,226 Chinese tumor patients with unknown familial history. The screening process of LFS patients was as follows: 1) Germline P/LP TP53 variants must satisfy P/LP in any of the three databases: UMD_TP53, ClinVar or HGMD. It also must be defined as “non-functional” mutations in IARC database which includes all TP53 germline mutations of clinically determined LFS patients; 2) Follow up the familial and personal histories of patients with germline P/LP TP53 variants. Results: After screening, 26 germline P/LP TP53 variants were obtained, which involved 54 patients, mainly in brain cancer (34 pts) and lung cancer (9 pts). The median age of these 34 brain cancer patients was younger than that of 5,845 brain cancer patients in the cohort (28 vs. 44 year-old). Yet no such phenomenon was observed in lung cancer. It is necessary for young brain cancer patients to detect germline TP53 mutations. We then analyzed the relationship between germline P/LP TP53 variants and LFS in the 54 patients. According to the Chompret criterion of LFS, two patients who respectively had adrenocortical carcinoma (R175H of TP53) and choroid plexus carcinoma (G245S) were both LFS patients regardless of whether they had a familial history. We finally obtained follow-up information of 17 patients. Among them, four brain cancer patients (R248Q/R158H/C238Y/M237I), one lung cancer patient (R175H) and one leiomyosarcoma patient (R213Q) had family members who had cancers before 46-year-old. Another brain cancer patient (G245S; 1/17) had more than one cancer before 46-years-old. Hence, these seven patients (7/17; 41.18%) were also defined as LFS patients by the Chompret criterion. In total, 9 patients had LFS. It shows a high positive detection rate in our cohort by our analysis process. Conclusions: We have established an analysis process based on germline P/LP TP53 variants, which can efficiently screen for LFS patients in clinic. Citation Format: Changyu Lu, Yu Fang, Fachen Zhou, Yuntong Liu, Hongchuan Niu, Kai Li, Tonghui Ma, Xiaoyan Zhang. Enrichment and screening of LFS patients by analyzing TP53 germline mutations of a Chinese cancer cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 810.

Abstract 4283: Assessment of the tumor mutational burden in a large cohort of Chinese advanced pan-cancer patients

Abstract Background: Immunotherapy have led to a paradigm shift in cancer treatment, while only a small subset of patients can benefit from the treatment. Recent studies have revealed that tumor mutational burden (TMB) is positively correlated with immunotherapy, however, by far, limited data are available for Chinese tumor patients. Methods: We retrospectively assessed the TMB value with a validated 381-cancer-gene panel across 7,822 patients with advanced cancers, including gastric cancer (n= 457), gallbladder cancer (n=608), colorectal cancer (n=785), breast cancer (n=263), Hepatocellular carcinoma (n=904) and lung cancer (n=2135), Renal cell carcinoma (n=346), Liver cancer (904), NSCLC (2135), Melanoma (110), Ovarian cancer (177), Pancreatic cancer (363), Gastric carcinoma (457), Urinary tract cancer (166) and others. Results: A highest 20% of TMB in each histology was selected as the cut-point. Based on our analysis, the highest and the lowest TMB level was observed in endometrial cancer and RCC, respectively. More specifically, the TMB cut-point was 10.5 for biliary tumor, 9.7 for breast cancer, 15.2 for endometrial cancer, 12.1 for CRC, 49.8 for endometrial cancer, 12.1 for oesophageal cancer, 11.1 for head and neck carcinoma, 7.3 for RCC, 10.1 for HCC, 14.5 for NSCLC, 8.9 for melanoma, 8.1 for ovarian cancer, 7.4 for pancreatic cancer, 11.3 for GC, and 20.1 for urinary tract cancer. Consistent results were observed when the median TMB was applied in the analysis. Conclusion: This is the first study focusing on the distribution of TMB value in a large cohort of Chinese cancer patients. The results showed the varying distributions of TMB across histology and suggested that a high TMB status may not assigned by one universal cut-point across different cancer types. Our findings have provide clues to guide the treatment strategy in clinical practice and shed lights on the future trial design. Citation Format: Ping Liu, Longgang Cui, Shangli Cai. Assessment of the tumor mutational burden in a large cohort of Chinese advanced pan-cancer patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4283.

Comprehensive profiling of MDM2/TP53 genomic aberration in Chinese patients with diverse malignancies.

e13508 Background: Murine double minute-2 (MDM2) has increasing clinic relevance as preclinical and early clinical evidences have showed that the MDM2 inhibitors are promising alternative treatments for patients with MDM2-amplified (-amp) and TP53-wild-type (-WT) tumors by preventing TP53 protein degradation. However, exploration into genomic landscape of MDM2/TP53 across various solid tumors in Chinese patients is still limited. Methods: Formalin-fixed, paraffin-embedded (FFPE) tumor samples were collected from 10010 Chinese patients with solid tumors and subjected to a clinical-grade next-generation sequencing (NGS)-based 450 gene panel testing carried out by a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Genomic alterations (GAs) including single base substitutions, short and long insertion/deletions (Indels), copy number variations, gene fusions, and rearrangements were analyzed. Tumor mutational burden (TMB) was measured by a NGS algorithm. Results: Amplification of MDM2 occurred in 3.3% of Chinese patients. MDM2-amp was detected most frequently in soft tissue sarcoma (STS, 11.4 %), melanoma (10.3 %) and osteosarcoma (6.3 %). Notably, MDM2-amp was revealed to be mutually exclusive with TP53-mut in most tumor types other than esophageal carcinoma (93.9 %), head and neck carcinoma (68.4%) and ovarian carcinoma (50 %). Tumors with highest frequencies of MDM2-amp/ TP53-WT were melanoma (100%), osteosarcoma (100%) and urothelial carcinoma (100 %). The most common co-altered genes accompanied with MDM2-amp were FRS2 (84%), CDK4 (38%), EGFR (26%), TP53 (17%) and GLI1 (14%). 82.8% patients who had one or more co-alterations potentially targetable with either FDA-approved or investigational agent. Moreover, TMB of MDM2-amp tumors were significantly lower than that of MDM2-WT and MDM2-mutation (-mut) tumors (median TMB: 3.1 vs. 4.6 vs. 10.8, p &lt; 0.001 respectively). Conclusions: MDM2 amplification was found in 3.3% of 10010 Chinese cancer patients, 83.4% of whom harbored wild-type TP53 that were potentially responsive to MDM2 inhibitors. In addition, 82.8% of the patients with MDM2-amp harbored genomic co-alterations and were potentially therapy targetable. This study provided insights into identifying patients who might potentially benefit from anti-MDM2 therapies.

The clinical characteristics and outcomes of carotid body tumors in Chinese patients: A STROBE-compliant observational study.

This study aims to investigate the clinical characteristics and outcomes of carotid body tumors in Chinese patients in the last decade. A systematic search was conducted without limits and included studies published between January 2006 and December 2016 according to PubMed, the Chinese Science Citation Database, the China Science Periodical Database and the China National Knowledge Infrastructure. Relevant synonyms for the search terms “paraganglioma” and “carotid body tumor” were applied, and the clinical data were evaluated and analyzed. There were 1810 cases of CBTs reported in the last decade, of which females accounted for 60.22%, and the mean age was 40.60 years, with most cases being sporadic (98.51%). Surgical resection was performed in 1791 cases: vessel repair occurred in 38.88% of the cases, carotid ligation occurred in 1.42% of the cases, and 1.05% of the patients refused treatment. Some patients underwent selective embolization, and the results showed that embolization could decrease procedure time and blood loss (P < .01). Stroke and death occurred in 1.95% and 0.39% of patients, respectively. Malignant CBTs accounted for 4.30% of cases, and the metastatic sites involved were local metastasis (46.88%), lung (31.25%), bone (21.88%), liver (12.50%), and brain (9.38%). The overall survival rate was 98.87% 36 months after the procedure, and the survival rate of metastatic cases was 56.25% 6 months after recurrence; however, only 21.88% of metastatic cases received radiotherapy. The CBTs of Chinese patients showed some clinical features that were different from those of Western patients.

The Clinical Characteristics and Outcomes of Carotid Body Tumors in Chinese Patients: A 2006-2016 Population-based Study

The Clinical Characteristics and Outcomes of Carotid Body Tumors in Chinese Patients: A 2006-2016 Population-based Study

Major challenges in accurate mutation detection of multifocal lung adenocarcinoma by next-generation sequencing

ABSTRACTBackground: Many patients with advanced non-small cell lung cancer manifested with metastasis, and molecular heterogeneity may exhibit between primary and metastatic tumors. We sought to investigate the clinical detection strategy of primary and metastatic tumors in Chinese patients with NSCLC.Methods: Here, 77 paired tumors of Chinese patients with lung adenocarcinoma were analyzed, and 1836 mutation in hotspot regions of 22 genes were identified by next-generation sequencing. The expression of ALK in these paired tumors was also detected by immunohistochemistry.Results: The results showed that the concordance rate in multiple pulmonary nodules, primary-LN metastasis pairs and primary-distant metastasis pairs was 67.7%, 94.1% and 86.7%, respectively. In multiple pulmonary nodules, the concordance rate was 100% when the pathologic diagnosis was intrapulmonary metastasis, whereas the concordance rate was 23.1% when the pathologic diagnosis was multiple primary tumors. TP53 and CTNNB1 mutations were detected as the recurrent alterations in LN metastasis. Moreover, the concordance of ALK status was observed in these pairs.Conclusions: Our data suggested that hotspot mutations and ALK status in the primary-metastasis pairs had a high concordance in lung adenocarcinoma. Clinical detection of one lesion may be enough to identify the key alterations except that patients are diagnosed with multiple primary tumors or have disease progression after benefiting from target therapy.

Clinical significance of the histological and molecular characteristics of ependymal tumors: a single institution case series from China

BackgroundEpendymal tumors are pathologically defined intrinsic neoplasms originating in the intracranial compartments or the spinal cord that affect both children and adults. The recently integrated classification of ependymomas based on both histological and molecular characteristics is capable of subgrouping patients with various prognoses. However, the application of histological and molecular markers in Chinese patients with ependymomas has rarely been reported. We aimed to demonstrate the significance of histological characteristics, the v-relavian reticuloendotheliosis viral oncogene homolog A (RELA) fusions and other molecular features in ependymal tumors.MethodsWe reviewed the histological characteristics of ependymal tumors using conventional pathological slides and investigate the RELA fusions and Cylclin D1 (CCND1) amplification by Fluorescence in situ hybridization (FISH) and trimethylation of histone 3 lysine 27 (H3K27me3) expression by immunohistochemistry (IHC) methods. SPSS software was used to analyze the data.ResultsWe demonstrated that hypercellularity, atypia, microvascular proliferation, necrosis, mitosis, and an elevated Ki-67 index, were tightly associated with an advanced tumor grade. Tumor location, necrosis, mitosis and the Ki-67 index were related to the survival of the ependymomas, but Ki67 was the only independent prognostic factor. Additionally, RELA fusions, mostly presented in pediatric grade III intracranial ependymomas, indicated decreased survival times of patients, and closely related to the patients’ age, tumor grade, cellularity, cellular atypia, necrosis and Ki67 index in the intracranial ependymal tumors, whereas reduction of H3K27me3 predicted the worse prognosis in ependymal tumors.ConclusionsHistological and molecular features facilitate tumor grading and prognostic predictions for ependymal tumors in Chinese patients.

Clinicopathological characteristics and prognostic factors of gastrointestinal stromal tumors in Chinese patients.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms in the gastrointestinal tract, exhibiting wide variability in their biological behavior. The aim of the present study was to investigate the clinicopathological characteristics and prognostic factors of GISTs in Chinese patients. All GIST cases (n=182) retrieved from the pathology database and the archived files in Shanghai Changzheng Hospital between January 2011 and December 2014 were reviewed. The clinical symptoms, preoperative investigations, treatments, pathological characteristics and follow-up data of these patients were reviewed, and univariate and multivariate survival analyses were performed. A total of 73.1% of the GISTs were located in the stomach, and the most common three symptoms included abdominal pain (30.2%), dyspepsia (23.1%) and gastrointestinal bleeding (21.4%). Univariate analysis revealed that larger tumor size (P<0.001), higher mitotic rate (P<0.001), aggressive behavior (P<0.001), negative smooth muscle actin expression (P=0.009) and palliative resection (P<0.001) contributed toward poor overall survival (OS). In addition, non-gastric disease location (P<0.001), larger tumor size (P<0.001), higher mitotic rate (P=0.004), aggressive behavior (P<0.001) and palliative resection (P<0.001) were associated with poor relapse-free survival (RFS). Multivariate analysis indicated that mitotic rate [hazard ratio (HR=3.761, P=0.015)] and aggressive behavior (HR=3.916, P=0.010) were independent risk factors for OS, while non-gastric location (HR=4.740, P=0.002) and aggressive behavior (HR=4.009, P=0.004) were independent risk factors for RFS. The present study provided information on the clinicopathological characteristics and epidemiology of GISTs in the Chinese population. Non-gastric disease location, higher mitotic rate and tumor metastasis or local invasion prior to treatment were identified as predictors of a poor prognosis.

Retraction Note to: A randomized phase II study of everolimus for advanced pancreatic neuroendocrine tumors in Chinese patients

Everolimus, an oral inhibitor of mammalian target of mTOR, has been recently shown to have antitumor effect in a phase III, double-blind, randomized trial (RADIANT-3) of 410 patients with advanced pancreatic neuroendocrine tumors (PNETs). The purpose of this study was to investigate the specific efficacy and safety of everolimus in the Chinese patient with PNETs. In this randomized phase II study, the analysis on Chinese patients was performed comparing efficacy and safety between everolimus 10 mg/day orally (n = 44) and matching placebo (n = 35). The primary endpoint was progression-free survival (PFS). Adverse events were also examined. The median PFS was 15.47 months with everolimus [95 % confidence interval (CI) 10.52–26.37], as compared to 4.29 months with placebo (95 % CI 2.22–10.75), representing a 72 % reduction in the risk of progression or death (hazard ratio 0.27; 95 % CI 0.13–0.59; P < 0.001). Drug-associated adverse events (AEs) were mostly grade 1 or 2, observed in all 44 (100 %) patients receiving everolimus and in 29 (83 %) patients receiving placebo. The most common AEs (grade 1–4) associated with everolimus were rash (n = 38; 86 %), stomatitis (n = 30; 68 %), infections (n = 33; 75 %), epistaxis (n = 32; 73 %), pneumonitis (n = 27; 61 %) and anemia (n = 22; 50 %). Everolimus when compared with placebo is effectively in improving PFS in Chinese patients with PNETs.

Detection of BRAF mutation in Chinese tumor patients using a highly sensitive antibody immunohistochemistry assay.

BRAF mutations can be found in various solid tumors. But accurate and reliable screening for BRAF mutation that is compatible for clinical application is not yet available. In this study, we used an automated immunohistochemistry (IHC) staining coupled with mouse monoclonal anti-BRAF V600E (VE1) primary antibody to screen the BRAF V600E mutation in 779 tumor cases, including 611 colorectal carcinomas (CRC), 127 papillary thyroid carcinomas (PTC) and 41 malignant melanomas. Among the 779 cases, 150 cases were positive for BRAF (V600E) staining, including 38 (of 611, 6%) CRCs, 102 (of 127, 80%) PTCs and 10 (of 41, 24%) malignant melanomas. Sanger sequencing and real-time PCR confirmed the sensitivity and specificity of IHC staining for the V600E mutation are 100% and 99%, respectively. Therefore, our study demonstrates that the fully automated IHC is a reliable tool to determine BRAF mutation status in CRC, PTC and melanoma and can be used for routine clinical screen.

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