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surgical management of metastatic neuroendocrine tumors:beyond the realm of evidence-based medicine

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Hepatobiliary Surgery and Nutrition 2024年第3期13卷 551-553页

作者： Jonathan R.Strosberg Taymeyah Al-Toubah department of Gastrointestinal oncology Moffitt Cancer Center&Research InstituteUniversity of South FloridaTampaFLUSA

How strong is the evidence supporting surgery for patients with metastatic neuroendocrine tumors(NETs)?This is the chief question from ***’comprehensive and balanced literature analysis on the surgical treatment of metastatic pancreatic NETs(1).No matter how many non-randomized studies demonstrate a survival advantage for patients undergoing cytoreductive hepatic surgery or resection of the primary pancreatic tumor,the methodological biases remain constant(2-9).Patients undergoing surgery tend to be younger and healthier,and their tumors tend to be lower grade,less aggressive,and fewer in number than patients undergoing other systemic or liver-directed *** other words,the survival advantage begins when the patient is selected as a surgical candidate and before the scalpel even touches the *** multivariate analyses can control for some confounding variables,it is impossible to control for *** a simple concept such as tumor burden is challenging to standardize:a patient with a few large tumors confined to a single hepatic lobe may have a vastly different prognosis than a patient with a similar burden of miliary tumors scattered throughout the liver(2).

关键词： Neuroendocrine tumor(NET) cytoreduction debulking surgery transplantation

Penpulimab,an anti-PD-1 antibody,for heavily pretreated metastatic nasopharyngeal carcinoma:a single-arm phase II study

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3056-3062页

作者： Xiaozhong Chen Wei Wang Qingfeng Zou Xiaodong Zhu Qin Lin Yi Jiang Yan Sun Liangfang Shen Lin Wang Guorong Zou Xiaoyan Lin Shaojun Lin Minying Li Ying Wang Ruilian Xu Rui Ao Rensheng Wang Haifeng Lin Shuang Huang Tingting Xu Wenting Li Mengying Xia Yu Xia Zhongmin Wang Baiyong Li Jingao Li Chaosu Hu department of Radiation oncology Cancer Hospital of the University of ChineseAcademy of Sciences(Zhejiang Cancer Hospital)HangzhouChina Gastroenterology and Urology department II Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangshaChina Clinical Research Center for Gastrointestinal cancer in Hunan Province ChangshaChina department of Medical oncology Affiliated Cancer Hospital&Institute of Guangzhou Medical UniversityGuangzhouChina department of Radiation oncology Guangxi Medical University Affiliated Tumor Hospital&Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor(Guangxi Medical University)Ministry of Education&Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency TumorGuangxi Medical UniversityNanningChina department of Radiation oncology Cancer CenterThe First Affiliated Hospital of Xiamen UniversityXiamenChina department of Medical oncology Cancer Hospital of Shantou University Medical CollegeShantouChina department of Radiation oncology Peking University Cancer Hospital&InstituteBeijingChina department of oncology Xiangya Hospital Central South UniversityChangshaChina department of Medical oncology Hainan General HospitalHainan Affiliated Hospital of Hainan Medical UniversityHaikouChina department of oncology The Affiliated Panyu Central Hospital of Guangzhou Medical UniversityGuangzhouChina department of Medical oncology Fujian Medical University Union HospitalFuzhouChina department of Radiation oncology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhouChina department of Radiation Therapy for Thoracic Tumors Zhongshan City People’s HospitalZhongshanChina Tumor Radiotherapy Center Chongqing University Cancer HospitalChongqing Cancer HospitalChongqing Cancer InstituteChongqingChina department of oncology Shenzhen People’s Hospital(The Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSo

Penpulimab is an anti-programmed cell death-1(PD-1)IgG1 antibody with no Fc gamma receptor(FcγR)binding activity,and thus theoretically reduced immune-related adverse events(irAEs)while maintaining *** single-arm,phase II trial conducted across 20 tertiary care centers in China enrolled adult patients with metastatic nasopharyngeal carcinoma(NPC)who had failed two or more lines of previous systemic *** received 200-mg penpulimab intravenously every 2 weeks(4 weeks per cycle)until disease progression or intolerable *** primary endpoint was objective response rate(ORR)per RECIST(version 1.1),as assessed by an independent radiological review *** secondary endpoints included progression-free survival(PFS)and overall survival(OS).One hundred thirty patients were enrolled and 125 were efficacy *** the data cutoff date(September 28,2022),1 patient achieved complete response and 34 patients attained partial *** ORR was 28.0%(95%CI 20.3–36.7%).The response was durable,with 66.8%still in response at 9 ***-three patients(26.4%)were still on *** median PFS and OS were 3.6 months(95%CI=1.9–7.3 months)and 22.8 months(95%CI=17.1 months to not reached),***(7.6%)patients experienced grade 3 or higher *** has promising anti-tumor activities and acceptable toxicities in heavily pretreated metastatic NPC patients,supporting further clinical development as third-line treatment of metastatic NPC.

关键词： metastatic nasopharyngeal supporting

Monte Carlo method for evaluation of surface emission rate measurement uncertainty

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Nuclear Science and Techniques 2024年第7期35卷 126-136页

作者： Yuan-Qiao Li Min Lin Li-Jun Xu Rui Luo Yu-He Zhang Qian-Xi Ni Yun-Tao Liu China institute of Atomic Energy Beijing102413China National Key Laboratory for Metrology and Calibration Techniques Beijing102413China department of Radiation oncology Hunan Cancer HospitalChangsha410031China The Affiliated cancer Hospital of Xiangya School of Medicine Central South UniversityChangsha410031China

The aim of this study is to evaluate the uncertainty of 2πα and 2πβ surface emission rates using the windowless multiwire proportional counter *** study used the Monte Carlo method (MCM) to validate the conventional Guide to the Expression of Uncertainty in Measurement (GUM) method.A dead time measurement model for the two-source method was established based on the characteristics of a single-channel measurement system,and the voltage threshold correction factor measurement function was indirectly obtained by fitting the threshold correction *** uncertainty in the surface emission rate was calculated using the GUM method and the law of propagation of *** MCM provided clear definitions for each input quantity and its uncertainty distribution,and the simulation training was realized with a complete and complex mathematical *** results of the surface emission rate uncertainty evaluation for four radioactive plane sources using both methods showed the uncertainty’s consistency E_(n)<0.070 for the comparison of each source,and the uncertainty results of the GUM were all lower than those of the ***,the MCM has a more objective evaluation process and can serve as a validation tool for GUM results.

关键词： Surface emission rate Monte Carlo method Metrology Probability distribution function Dead time Low-energy loss correction Least-squares method

Phase Ib study of anti-EGFR antibody(SCT200)in combination with anti-PD-1 antibody(SCT-I10A)for patients with RAS/BRAF wild-type metastatic colorectal cancer

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cancer Biology & Medicine 2024年第7期21卷 636-650页

作者： Ming Bai Yao Lu Chunmei Shi Jianwei Yang Wei Li Xianli Yin Chenghui Huang Lin Shen Liangzhi Xie Yi Ba department of GI Medical oncology Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin's Clinical Research Center for CancerTianjin Key Laboratory of Digestive CancerTianjin 300060China Fujian Medical University Union Hospital Fuzhou 350001China Fujian Provincial cancer Hospital Fuzhou 350014China cancer Center The First Hospital of Jilin UniversityChangchun 130021China department of Medical oncology Gastroenterology and Urology Hunan Cancer HospitalAffiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha 410013China department of oncology The Third Xiangya HospitalCentral South UniversityChangsha 410013China department of Gastrointestinal oncology Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Bejing)Peking University Cancer Hospital and InstituteBeijing 100142China Beijing Engineering Research Center of Protein and Antibody Sinocelltech Ltd.Bejing 100176China department of cancer Center Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijing 100010China

Objective:This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor(EGFR)antibody(SCT200)and an anti-programmed cell death 1(PD-1)antibody(SCT-I10A)as third-line or subsequent therapies in patients with rat sarcoma viral oncogene(RAS)/v-raf murine sarcoma viral oncogene homolog B(BRAF)wild-type(wt)metastatic colorectal cancer(mCRC).Methods:We conducted a multicenter,open-label,phase Ib clinical *** with histologically confirmed RAS/BRAF wt m CRC with more than two lines of treatment were enrolled and treated with SCT-I10A and *** primary endpoints were the objective response rate(ORR)and *** secondary endpoints included disease control rate(DCR),progression-free survival(PFS),and overall survival(OS).Results:Twenty-one patients were enrolled in the study through January 28,*** ORR was 28.57%and the DCR was 85.71%(18/21).The median PFS and OS were 4.14 and 12.84 months,*** treatment-related adverse events(TRAEs)were ***,compared with the monotherapy cohort from our previous phase I study evaluating SCT200 for RAS/BRAF wt m CRC in a third-line setting,no significant improvements in PFS and OS were observed in the combination ***:SCT200 combined with SCT-I10A demonstrated promising efficacy in previously treated RAS/BRAF wt m CRC patients with an acceptable safety *** head-to-head studies with larger sample sizes are needed to validate whether the efficacy and safety of combined anti-EGFR and anti-PD-1 therapy are superior to anti-EGFR monotherapy in the third-line setting.(Registration ***04229537).

关键词： Colorectal cancer SCT-I10A SCT200 epidermal growth factor receptor programmed cell death 1

Circular RNAs in breast cancer diagnosis,treatment and prognosis

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oncology Research 2024年第2期32卷 241-249页

作者： XIAOJIA HUANG CAILU SONG JINHUI ZHANG LEWEI ZHU HAILIN TANG department of Breast oncology Surgery Affiliated Cancer Hospital&Institute of Guangzhou Medical UniversityGuangzhou510095China State Key Laboratory of oncology in south China Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou510060China department of Breast Surgery The First People’s Hospital of FoshanFoshan528000China

Breast cancer has surpassed lung cancer to become the most common malignancy *** incidence rate and mortality rate of breast cancer continue to rise,which leads to a great burden on public *** RNAs(circRNAs),a new class of noncoding RNAs(ncRNAs),have been recognized as important oncogenes or suppressors in regulating cancer initiation and *** breast cancer,circRNAs have significant roles in tumorigenesis,recurrence and multidrug resistance that are mediated by various ***,circRNAs may serve as promising targets of therapeutic strategies for breast cancer *** study reviews the most recent studies about the biosynthesis and characteristics of circRNAs in diagnosis,treatment and prognosis evaluation,as well as the value of circRNAs in clinical applications as biomarkers or therapeutic targets in breast *** the mechanisms by which circRNAs function could help transform basic research into clinical applications and facilitate the development of novel circRNA-based therapeutic strategies for breast cancer treatment.

关键词： CircRNA Breast cancer Diagnosis Treatment Biomarker

Beyond clinical trials:CDK4/6 inhibitor efficacy predictors and nomogram model from real‐world evidence in metastatic breast cancer

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cancer Innovation 2024年第6期3卷 58-75页

作者： Binliang Liu Zhe‐Yu Hu Ning Xie Liping Liu Jing Li Xiaohong Yang Huawu Xiao Xuran Zhao Can Tian Hui Wu Jun Lu Jianxiang Gao Xuming Hu Min Cao Zhengrong Shui Yu Tang Quchang Ouyang department of Breast cancer Medical oncology Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangshaHunanChina department of Radiation oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina department of Gastroenterology The Third Xiangya Hospital of Central South UniversityChangshaHunanChina

Background:CDK4/6 inhibitors(CDK4/6i)have shown promising results in the treatment of hormone receptor‐positive(HR+)metastatic breast cancer(MBC)when combined with endocrine therapy(ET).It is crucial to evaluate the actual effectiveness and safety of CDK4/6i in clinical practice,as well as to analyze the factors that can predict their ***:Patients with HR+MBC who received CDK4/6i‐based therapy between May 2016 and May 2023 at Hunan cancer Hospital were evaluated for progression‐free survival(PFS).Adverse reactions were assessed based on the National cancer institute Common Toxicity Criteria(version 5.0).Results:This study included 344 patients,with a median PFS(mPFS)of 12.8 months(range:10.4–15.2 months).After adjustment,Cox multivariate regression analysis revealed that visceral metastasis(specifically liver and brain metastases),Eastern Cooperative oncology Group Performance Status(ECOG PS)≥1,estrogen receptor≤80%,progesterone receptor≤10%,Ki‐67>30%,and treatment in later stages were significant factors associated with reduced *** on this,we created a prognostic nomogram and validated its performance,obtaining a C‐index of 0.714(95%confidence interval:0.640–0.787)as well as reliable calibration and clinical *** mPFS of CDK4/6i rechallenge was 7.7 months;for patients who initially discontinued CDK4/6i for reasons other than disease progression,CDK4/6i rechallenge still provided a mPFS of 11.4 *** tolerability and safety of combining CDK4/6is with ET were *** events led to treatment discontinuation in 3.8%of ***(29.1%),leukopenia(13.7%),and anemia(4.1%)were the primary grade 3/4 adverse ***:This real‐world study highlights the ample efficacy and reasonable safety of combined CDK4/6i and ET in patients with HR+*** treatment decisions and ongoing safety monitoring are important to optimize the therapeutic benefit of CDK4/6i treatment.

关键词： breast cancer CDK4/6 inhibitor efficacy predictive factors real‐word study

Suppression of ITPKB degradation by Trim25 confers TMZ resistance in glioblastoma through ROS homeostasis

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1637-1650页

作者： Yuanliang Yan Shangjun Zhou Xi Chen Qiaoli Yi Songshan Feng Zijin Zhao Yuanhong Liu Qiuju Liang Zhijie Xu Zhi Li Lunquan Sun department of Pharmacy Xiangya HospitalCentral South UniversityChangsha 410008China department of Neurosurgery Xiangya HospitalCentral South UniversityChangsha 410008China department of Pathology Xiangya HospitalCentral South UniversityChangsha 410008China Xiangya cancer Center Xiangya HospitalCentral South UniversityChangsha 410008China Key Laboratory of Molecular Radiation oncology Hunan Province Changsha 410008China institute of cancer Research National Clinical Research Center for Geriatric Disorders(Xiangya)Xiangya HospitalCentral South UniversityChangsha 410008China

Temozolomide(TMZ)represents a standard-of-care chemotherapeutic agent in glioblastoma(GBM).However,the development of drug resistance constitutes a significant hurdle in the treatment of malignant *** specific innovative approaches,such as immunotherapy,have shown favorable clinical outcomes,the inherent invasiveness of most gliomas continues to make them challenging to ***,there is an urgent need to identify effective therapeutic targets for gliomas to overcome chemoresistance and facilitate drug *** investigation used mass spectrometry to examine the proteomic profiles of six pairs of GBM patients who underwent standard-of-care treatment and surgery for both primary and recurrent tumors.A total of 648 proteins exhibiting significant differential expression were *** Set Enrichment Analysis(GSEA)unveiled notable alterations in pathways related to METABOLISM_OF_LIPIDS and BIOLOGICAL_OXIDATIONS between the primary and recurrent *** through glioma tissue arrays and the Xiangya cohort confirmed substantial upregulation of inositol 1,4,5-triphosphate(IP3)kinase B(ITPKB)in the recurrence group,correlating with poor survival in glioma *** TMZ-resistant cells,the depletion of ITPKB led to an increase in reactive oxygen species(ROS)related to NADPH oxidase(NOX)activity and restored cell sensitivity to ***,the decreased phosphorylation of the E3 ligase Trim25 at the S100 position in recurrent GBM samples accounted for the weakened ITPKB ***,in turn,elevated ITPKB stability and impaired ROS ***,ITPKB depletion or the ITPKB inhibitor GNF362 effectively overcome TMZ chemoresistance in a glioma xenograft mouse *** findings reveal a novel mechanism underlying TMZ resistance and propose ITPKB as a promising therapeutic target forTMZ-resistant GBM.

关键词： TMZ homeostasis impaired

Insights on liver-directed surgical innovations, targeted therapies, and immunotherapy for biliary tract cancer: navigating the new European Society for Medical oncology (ESMO) Clinical Practice Guidelines

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Hepatobiliary Surgery and Nutrition 2024年第3期13卷 516-519页

作者： Ajay V.Maker Division of surgical oncology Department of SurgeryUniversity of CaliforniaSan FranciscoCAUSA

cancers of the bile duct,including gallbladder cancer,extrahepatic cholangiocarcinoma,hilar and intrahepatic cholangiocarcinoma,present a significant treatment *** by their notorious difficulty to diagnose or biopsy,intricate anatomical locations and diverse clinical presentations,these malignancies collectively contribute to a significant burden on global *** epidemiology of bile duct cancers reveals worldwide variations in incidence,prevalence,and mortality rates,emphasizing the need for a nuanced understanding of each subtype and the local environmental *** in early diagnosis further compound the complexity of managing these cancers,often leading to advanced stage at the time of detection and treatment *** remains the cornerstone of curative-intent treatment of bile duct cancers,yet the rate of recurrence and metastases underscores the importance of comprehensive multidisciplinary therapeutic *** randomized clinical trials have been performed;however,they have been challenged by the lack of active agents,a limited number of accrued patients,and a grouping of all patients together regardless of where in the biliary tract the tumor *** has resulted in variations in treatment strategies and multiple treatment options that range from immunotherapy to radiation to hepatic artery infusion therapy(more on this later).A greater understanding of the mutational landscape of biliary tract cancers has resulted in optimism around appropriately targeted agents and combination ***,many of these regimens await robust outcomes data,and it is questionable if they significantly move the needle forward to improve overall *** now,more than ever,there is a need for updated treatment guidelines.

关键词： Gallbladder cancer cholangiocarcinoma guidelines bile duct cancer hepatic artery infusion pump

The Chinese Society of Clinical oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer, 2023

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cancer Communications 2024年第1期44卷 127-172页

作者： Feng-Hua Wang Xiao-Tian Zhang Lei Tang Qi Wu Mu-Yan Cai Yuan-Fang Li Xiu-Juan Qu Hong Qiu Yu-Jing Zhang Jie-Er Ying Jun Zhang Ling-Yu Sun Rong-Bo Lin Chang Wang Hao Liu Miao-Zhen Qiu Wen-Long Guan Sheng-Xiang Rao Jia-Fu Ji Yan Xin Wei-Qi Sheng Hui-Mian Xu Zhi-Wei Zhou Ai-Ping Zhou Jing Jin Xiang-Lin Yuan Feng Bi Tian-Shu Liu Han Liang Yan-Qiao Zhang Guo-Xin Li Jun Liang Bao-Rui Liu Lin Shen Jin Li Rui-Hua Xu department of Medical oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdongP.R.China department of Gastrointestinal oncology Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education)Peking University Cancer HospitalBeijingP.R.China department of Radiology Peking University Cancer HospitalBeijingP.R.China department of Endoscopy Center Peking University Cancer HospitalBeijingP.R.China department of Pathology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center of Cancer MedicineGuangzhouGuangdongP.R.China department of Gastric Surgery Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdongP.R.China department of Medical oncology The First Hospital of China Medical UniversityShenyangLiaoningP.R.China department of Medical oncology Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and TechnologyWuhanHubeiP.R.China department of Radiotherapy Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdongP.R.China department of Medical oncology Zhejiang Cancer HospitalHangzhouZhejiangP.R.China department of Medical oncology Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiP.R.China department of surgical oncology The Fourth Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjiangP.R.China department of Medical oncology Fujian Cancer HospitalFuzhouFujianP.R.China Tumor Center The First Hospital of Jilin UniversityChangchunJilinP.R.China department of General Surgery Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdongP.R.China department of Radiology Zhongshan HospitalFudan UniversityShanghaiP.R.China department of

The 2023 update of the Chinese Society of Clinical oncology(CSCO)Clini-cal Guidelines for Gastric cancer focuses on standardizing cancer diagnosis and treatment in China,reflecting the latest advancements in evidence-based medicine,healthcare resource availability,and precision *** updates address the differences in epidemiological characteristics,clinicopatho-logical features,tumor biology,treatment patterns,and drug selections between Eastern and Western gastric cancer *** revisions include a structured template for imaging diagnosis reports,updated standards for molecular marker testing in pathological diagnosis,and an elevated recommendation for neoadju-vant chemotherapy in stage III gastric *** advanced metastatic gastric cancer,the guidelines introduce new recommendations for immunotherapy,anti-angiogenic therapy and targeted drugs,along with updated management strategies for human epidermal growth factor receptor 2(HER2)-positive and deficient DNA mismatch repair(dMMR)/microsatellite instability-high(MSI-H)***,the guidelines offer detailed screening recommendations for hereditary gastric cancer and an appendix listing drug treatment regimens for various stages of gastric *** 2023 CSCO Clinical Guidelines for Gastric cancer updates are based on both Chinese and international clinical research and expert consensus to enhance their applicability and relevance in clinical practice,particularly in the heterogeneous healthcare landscape of China,while maintaining a commitment to scientific rigor,impartiality,and timely revisions.

关键词： Chinese Society of Clinical oncology(CSCO) gastric cancer diagnosis surgery neoadjuvant adjuvant radiotherapy chemotherapy targeted therapy immunotherapy