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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

Concurrent chemoradiotherapyof different radiation doses and different irradiation fields for locally advanced thoracic esophageal squamous cell carcinoma:A randomized,multicenter,phase Ⅲ clinical trial

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Cancer Communications 2024年第10期44卷 1173-1188页

作者： Jian Zhang Minghao Li Kaixian Zhang Anping Zheng Guang Li Wei Huang Shaoshui Chen Xiangming Chen Xiaomin Li Yanxing Sheng Xinchen Sun Liping Liu Xiaowei Liu Jie Li Jun Wang Hong Ge Shucheng Ye Qingsong Pang Xianwen Zhang Shengbin Dai Richard Yu Wendong Gu Mingming Dai Gaowa Siqin Yunwei Han Xiaolin Ge Xin Yuan Yongjing Yang Haiwen Zhu Juan Pu Lihua Dong Xiangdong Sun Jundong Zhou Weidong Mao Fei Gao Haiqun Lin Heyi Gong Tao Zhou Zhenjiang Li Hongsheng Li Zhongtang Wang Baosheng Li department of oncology Central Hospital Affiliated to Shandong First Medical UniversityJinanShandongP.R.China department of radiation oncology Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanShandongP.R.China department of oncology Tengzhou Central People’s HospitalTengzhouShandongP.R.China department of radiation oncology Anyang Tumor HospitalAnyangHenanP.R.China department of radiation oncology the First Hospital of China Medical UniversityShenyangLiaoningP.R.China department of oncology Binzhou Medical University HospitalBinzhouShandongP.R.China department of oncology Taian CentralHospitalTaianShandongP.R.China department of radiation oncology Shanxi Province Cancer HospitalTaiyuanShanxiP.R.China department of oncology Liaocheng People’s HospitalLiaochengShandongP.R.China department of radiation oncology the First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsuP.R.China department of oncology Jining First People′s HospitalJiningShandongP.R.China department of oncology the Affiliated Hospital of Jining Medical UniversityJiningShandongP.R.China department of radiation oncology the Fourth Hospital of Hebei Medical UniversityHebei Clinical Research Center for Radiation OncologyShijiazhuangHebeiP.R.China department of radiation oncology the Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhouHenanP.R.China department of radiation oncology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory ofCancer Prevention and TherapyTianjin’s ClinicalResearch Center for CancerTianjinP.R.China department of oncology Subei People’s Hospital of Jiangsu ProvinceYangzhouJiangsuP.R.China department of oncology Taizhou People’s Hospital of Jiangsu ProvinceTaizhouZhejiangP.R.China department of radiation oncology the Affiliated Hospital of Inner Mongolia Medical UniversityHohhotInner MongoliaP.R.China department of radiation O

Background:Concurrent chemoradiotherapy(CCRT)is the standard treatment for locally advanced esophageal squamous cell carcinoma(ESCC).However,the optimal radiotherapy regimen,particularly in terms of total dose and planned range of irradiation field,remains *** phase III clinical trial aimed to compare the survival benefits between different radiation doses and different target ***:This trial compared two aspects of radiation treatment,total dose and field,using a two-by-two factorial *** high-dose(HD)group received 59.4 Gy radiation,and the standard-dose(SD)group received 50.4 *** involved field irradiation(IFI)group and elective nodal irradiation(ENI)group adopted different irradiation *** participants were assigned to one of the four groups(HD+ENI,HD+IFI,SD+ENI and SD+IFI).The primary endpoint was overall survival(OS),and the secondary endpoints included progressionfree survival(PFS).The synergy indexwas used to measure the interaction effect between dose and ***:The interaction analysis did not reveal significant synergistic effects between the dose and irradiation *** comparison to the target field,patients in IFI or ENI showed similar OS(hazard ratio[HR]=0.99,95%CI:0.80-1.23,p=0.930)and PFS(HR=1.02,95%CI:0.82–1.25).TheHDtreatment did not show significantly prolonged OS compared with SD(HR=0.90,95%CI:0.72–1.11,p=0.318),but it suggested improved PFS(25.2 months to 18.0 months).Among the four groups,the HD+IFI group presented the best survival,while the SD+IFI group had the worst *** significant difference in the occurrence of severe adverse events was found in dose or field ***:IFI demonstrated similar treatment efficacy to ENI in CCRT of *** HD demonstrated improved PFS,but did not significantly improve *** dose escalation based on IFI(HD+IFI)showed better therapeutic efficacy than the current recommendation(SD+ENI)and is worth further validation.

关键词： clinical trial concurrent chemoradiotherapy elective nodal radiation esophageal squamous cell carcinoma high dose radiation involved field radiation overall survival standard dose radiation

STING agonist-conjugated metal-organic framework induces artificial leukocytoid structures and immune hotspots for systemic antitumor responses

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National Science Review 2024年第7期11卷 189-204页

作者： Taokun Luo Xiaomin Jiang Yingjie Fan Eric Yuan Jinhong Li Langston Tillman Wenbin Lin department of Chemistry University of Chicago department of radiation and Cellular oncology and the Ludwig Center for Metastasis Research University of Chicago

Radiotherapy is widely used for cancer treatment, but its clinical utility is limited by radioresistance and its inability to target metastases. Nanoscale metal-organic frameworks(MOFs) have shown promise as high-Z nanoradiosensitizers to enhance radiotherapy and induce immunostimulatory regulation of the tumor microenvironment. We hypothesized that MOFs could deliver small-molecule therapeutics to synergize with radiotherapy for enhanced antitumor efficacy. Herein, we develop a robust nanoradiosensitizer,GA-MOF, by conjugating a STING agonist, 2,3-cyclic guanosine monophosphate–adenosine monophosphate(GA), on MOFs for synergistic radiosensitization and STING activation. GA-MOF demonstrated strong anticancer efficacy by forming immune-cell-rich nodules(artificial leukocytoid structures) and transforming them into immunostimulatory hotspots with radiotherapy. Further combination with an immune checkpoint blockade suppressed distant tumors through systemic immune activation. Our work not only demonstrates the potent radiosensitization of GA-MOF, but also provides detailed mechanisms regarding MOF distribution, immune regulatory pathways and long-term immune effects.

关键词： metal-organic framework radiosensitization STING agonist artificial leukocytoid structures immune hotspots immunotherapy nanomedicine

Prediction of pathological complete response and prognosis in locally advanced rectal cancer

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World Journal of Gastrointestinal oncology 2024年第6期16卷 2520-2530页

作者： Yi-Jun Xu Dan Tao Song-Bing Qin Xiao-Yan Xu Kai-Wen Yang Zhong-Xu Xing Ju-Ying Zhou Yang Jiao Li-Li Wang department of radiation oncology The First Affiliated Hospital of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina department of radiation oncology The Fourth Affiliated Hospital of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina School of radiation Medicine and Protection Medical College of Soochow UniversitySuzhou 215123Jiangsu ProvinceChina

BACKGROUND Colorectal cancer is currently the third most common malignant tumor and the second leading cause of cancer-related death *** chemoradiotherapy(nCRT)is standard for locally advanced rectal cancer(LARC).Except for pathological examination after resection,it is not known exactly whether LARC patients have achieved pathological complete response(pCR)before *** date,there are no clear clinical indicators that can predict the efficacy of nCRT and patient *** To investigate the indicators that can predict pCR and long-term outcomes following nCRT in patients with *** Clinical data of 128 LARC patients admitted to our hospital between September 2013 and November 2022 were retrospectively *** were categorized into pCR and non-pCR *** analysis(using the χ^(2) test or Fisher’s exact test)and logistic multivariate regression analysis were used to study clinical predictors affecting *** 5-year disease-free survival(DFS)and overall survival(OS)rates were calculated using Kaplan-Meier analysis,and differences in survival curves were assessed with the log-rank *** Univariate analysis showed that pretreatment carcinoembryonic antigen(CEA)level,lymphocyte-monocyte ratio(LMR),time interval between neoadjuvant therapy completion and total mesorectal excision,and tumor size were correlated with *** results showed that CEA≤5 ng/mL(P=0.039),LMR>2.73(P=0.023),and time interval>10 wk(P=0.039)were independent predictors for *** analysis demonstrated that patients in the pCR group had significantly higher 5-year DFS rates(94.7%vs 59.7%,P=0.002)and 5-year OS rates(95.8%vs 80.1%,P=0.019)compared to the non-pCR *** deposits(TDs)were significantly correlated with shorter DFS(P=0.002)and OS(P<0.001).CONCLUSION Pretreatment CEA,LMR,and time interval contribute to predicting nCRT efficacy in LARC *** pCR demonstrates longer DFS and *** correlate with poor pr

关键词： Locally advanced rectal cancer Neoadjuvant chemoradiotherapy Pathological complete response Carcinoembryonic antigen Inflammation-related markers Tumor deposit Prognosis

Efficacy and safety of anlotinib combined with the STUPP regimen in patients with newly diagnosed glioblastoma: a multicenter, single-arm, phase Ⅱ trial

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Cancer Biology & Medicine 2024年第5期21卷 433-444页

作者： Shuzhen Lai Peijing Li Xiaohui Liu Guihong Liu Tieming Xie Xing Zhang Xiaoxuan Wang Jing Huang Yiqiang Tang Zhigang Liu Guoping Shen Chaoming Li Fangxiao Lu Lei Wang Fagui Jiang Caixing Sun Yuanyuan Chen Ming Chen department of radiation oncology The Second Affiliated Hospital of Soochow UniversitySuzhou 215000China department of radiation oncology Yuebei People’s Hospital Affiliated to the Medical College of Shantou UniversityShaoguan 512026China Chinese Academy of SciencesHangzhou 310022China department of radiation oncology The Second Clinical Medical College of Zhejiang Chinese Medical UniversityHangzhou 311403China department of radiation oncology The Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221004China Chinese Academy of SciencesHangzhou 310022China State Key Laboratory of Translational Medicine and Innovative Drug Development Jiangsu Simcere Diagnostics Co.LtdNanjing 210000China department of radiation oncology The Affiliated Huai’an First People’s Hospital of Nanjing Medical UniversityHuai’an 223399China department of radiation oncology Jiangxi Cancer Hospital of Nanchang UniversityNanchang 330029China department of Radiotherapy Dongguan Institute of Clinical Cancer ResearchDongguan Key Laboratory of Precision Diagnosis and Treatment for TumorsAffiliated Dongguan HospitalSouthern Medical UniversityDongguan 523059China The Cancer Center The Fifth Affiliated Hospital of Sun Yat-Sen UniversityZhuhai 519000China department of radiation oncology The First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510080China department of oncology Maoming People’s HospitalMaoming 525000China department of radiation oncology Kecheng District People’s HospitalQuzhou 324003China Chinese Academy of SciencesHangzhou 310022China department of radiation oncology State Key Laboratory of Oncology in South ChinaSun Yat-sen University Cancer CenterGuangzhou 510060China United Laboratory of Frontier Radiotherapy Technology of Sun Yat-sen university&Chinese Academy of Sciences Ion Medical Technology Co. LtdGuangzhou 510060China

Objective:Glioblastomas are highly vascularized malignant *** determined the efficacy and safety of the anti-angiogenic multi-kinase inhibitor,anlotinib,for a newly diagnosed ***:This multicenter,single-arm trial(NCT04119674)enrolled 33 treatment-naïve patients with histologically proven glioblastomas between March 2019 and November *** underwent treatment with the standard STUPP regimen[fractionated focal irradiation in daily fractions of 1.8-2 Gy given 5 d/w×6 w(total=54-60 Gy)]or radiotherapy plus continuous daily temozolomide(TMZ)(75 mg/m^(2)of body surface area/d,7 d/w from the first to the last day of radiotherapy),followed by 6 cycles of adjuvant TMZ(150-200 mg/m^(2)×5 d during each 28-d cycle)plus anlotinib(8 mg/d on d 1-14 of each 3-w cycle for 2 cycles during concomitant chemoradiotherapy,8 maximal cycles as adjuvant therapy,followed by maintenance at 8 mg/*** primary endpoint was progression-free survival(PFS).Secondary endpoints included overall survival(OS)and adverse events(AEs).Results:Thirty-three patients received the planned *** median PFS was 10.9 months(95%CI,9.9-18.7 months)and the 12-month PFS rate was 48.5%.The median OS was 17.4 months(95%CI,14.5-21.1 months)and the 12-month OS rate was 81.8%.The most common AEs included hypertriglyceridemia[58%(n=19)],hypoalbuminemia[46%(n=15)],and hypercholesterolemia[46%(n=15)]during concurrent chemoradiotherapy and leukopenia[73%(n=24)],hypertriglyceridemia[67%(n=22)],and neutropenia[52%(n=17)]during adjuvant *** patients discontinued treatment due to ***1(HR,5.6;95%CI,1.3-23.7;P=0.021)and RP1L1 alterations(HR,11.1;95%CI,2.2-57.2;P=0.004)were associated with a significantly shorter ***:Anlotinib plus the STUPP regimen has promising anti-tumor activity against glioblastoma and manageable ***1 and RP1L1 alterations might be novel predictive biomarkers of the response to anlotinib.

关键词： Glioblastoma anti-angiogenesis multi-kinase inhibitor anlotinib temozolomide progression-free survival

Prognosis prediction and immune microenvironment features of breast cancer indicated by a cuproptosis-associated long non-coding RNA signature

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Genes & Diseases 2024年第5期11卷 66-69页

作者： Siyi Liu Juanchan Huang Wei Zhao department of radiation oncology Guangxi Medical University Cancer HospitalNanningGuangxi 530000China Guangxi Medical university NanningGuangxi 530000China department of oncology Affiliated Wuming Hospital of Guangxi Medical UniversityNanningGuangxi 530000China

Cuproptosis is a newly discovered type of programmed cell death that involves the depletion of intracellular copper and is not influenced by other inhibitors of programmed cell *** modality was first identified and named by Tsvetkov et al in the previous year.1 To further explore the relationship between cuproptosis,the tumor microenvironment,immunotherapy,and prognosis for breast cancer(BC),the expression patterns of 19 cuproptosis-related long non-coding RNAs(lncRNAs)were determined using data from the Cancer Genome Atlas(TCGA).

关键词： breast cancer microenvironment

Association of previously irradiated stable brain metastases with outcomes of atezolizumab-treated non-small cell lung cancer: A pooled analysis of individual patient data from three randomized trials

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Cancer Communications 2024年第2期44卷 278-281页

作者： Tiantian Guo Yue Zhou Fei Liang Zezhou Wang Vincent Bourbonne Lukas Käsmann Nora Sundahl Abraham Jing-Ching Wu Jianjiao Ni Zhengfei Zhu department of radiation oncology Fudan University Shanghai Cancer CenterShanghaiP.R.China department of oncology Shanghai Medical CollegeFudan UniversityShanghaiP.R.China Shanghai Clinical Research Center for radiation oncology ShanghaiP.R.China Shanghai Key Laboratory of radiation oncology ShanghaiP.R.China department of Biostatistics Zhongshan HospitalFudan UniversityShanghaiP.R.China department of Cancer Prevention Fudan University Shanghai Cancer CenterShanghaiP.R.China radiation oncology department University HospitalBrestFrance department of radiation oncology University HospitalLMU MunichMunichGermany department of radiation oncology AZ GroeningeKortrijkBelgium department of radiation oncology Memorial Sloan Kettering Cancer CenterNew YorkNew YorkUSA Institute of Thoracic oncology Fudan UniversityShanghaiP.R.China

Dear Editor:Brain metastasis(BM)has long been recognized as a prognostic factor associated with poor prognosis for non-small cell lung cancer(NSCLC)in the era of con-ventional chemotherapy and targeted therapy[1].In the era of immunotherapy,controversial findings have been reported regarding the prognostic significance of BM in patients with NSCLC treated with programmed death-1/programmed death-ligand 1(PD-1/PD-L1)inhibitors.

关键词： chemotherapy NSCLC metastasis death

^(18)F-FDG PET/CT findings of paratesticular alveolar rhabdomyosarcoma

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Cancer Innovation 2024年第2期3卷 68-71页

作者： Xueqi Chen Jiayin Shou Shanshi Li Yan Fan Jianhua Zhang department of Nuclear Medicine Peking University First HospitalBeijingChina department of radiation oncology Peking University First HospitalBeijingChina

Rhabdomyosarcoma(RMS)originates from primitive mesenchymal cells and is the most common soft tissue tumor in childhood.^(18)F-fluoro-deoxyglucose(^(18)F-FDG)positron emission tomography(PET)/computed tomography(CT)has been reported to be valuable in RMS staging and risk *** RMS is a relatively uncommon form of RMS,most of which are of the embryonal histologic *** alveolar RMS is associated with aggressive behavior,high metastatic potential,and poor *** the best of our knowledge,^(18)F-FDG PET/CT imaging findings of paratesticular alveolar RMS have never been ***,we report on a 16-year-old boy's rare paratesticular alveolar RMS with multiple metastases and its findings on^(18)F-FDG PET/*** case also demonstrates the potential value of^(18)F-FDG PET/CT in RMS staging and treatment decisions,and may aid in the differential diagnosis.

关键词： ^(18)F-FDG paratesticular alveolar rhabdomyosarcoma PET/CT

Nicotinamide adenine dinucleotide phosphate oxidase in pancreatic diseases:Mechanisms and future perspectives

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World Journal of Gastroenterology 2024年第5期30卷 429-439页

作者： Ya-Wei Bi Long-Song Li Nan Ru Bo Zhang Xiao Lei department of Gastroenterology The First Medical Center of Chinese PLA General HospitalBeijing 100853China department of radiation oncology Chinese PLA General HospitalBeijing 100853China

Pancreatitis and pancreatic cancer(PC)stand as the most worrisome ailments affecting the *** have dedicated efforts to unraveling the mechanisms underlying these diseases,yet their true nature continues to elude their *** this realm,oxidative stress is often believed to play a causal and contributory role in the development of pancreatitis and *** accumulation of reactive oxygen species(ROS)can cause oxidative stress,and the key enzyme responsible for inducing ROS production in cells is nicotinamide adenine dinucleotide phosphate hydrogen oxides(NOX).NOX contribute to pancreatic fibrosis and inflammation by generating ROS that injure acinar cells,activate pancreatic stellate cells,and mediate macrophage *** ROS production occurs during malignant transformation and pancreatic carcinogenesis,creating an oxidative microenvironment that can cause abnormal apoptosis,epithelial to mesenchymal transition and genomic ***,understanding the role of NOX in pancreatic diseases contributes to a more in-depth exploration of the exact pathogenesis of these *** this review,we aim to summarize the potential roles of NOX and its mechanism in pancreatic disorders,aiming to provide novel insights into understanding the mechanisms underlying these diseases.

关键词： Nicotinamide adenine dinucleotide phosphate hydrogen oxides Pancreatitis Pancreatic cancer Reactive oxygen species Mechanism