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prognostic model of survival outcomes in non-small cell lung cancer patients initiated on afatinib: pooled analysis of clinical trial data

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Cancer Biology & Medicine 2019年第2期16卷 341-349页

作者： Ashley M. Hopkins Adel Shahnam Sasha Zhang Chris S. Karapetis Andrew Rowland Michael J. Sorich Flinders Centre for Innovation in Cancer Department of Clinical Pharmacology College of Medicine and Public Health Flinders University Adelaide 5042 Australia The Canberra Hospital Garran 2605 Australia

Objective: Several predictors of survival have been identified in EGFR-positive non-small cell lung cancer(NSCLC) patients treated with first generation EGFR inhibitors. prognostic models of survival outcomes with afatinib have not been evaluated.Methods: A prognostic tool for overall survival(OS)/progression free survival(PFS) based on pre-treatment clinicopathological factors was developed for EGFR-positive advanced NSCLC patients treated with first-line afatinib using penalised regression of individual-participant data from LUX-Lung 3 and 6(n = 468). Favourable, intermediate and poor risk groups were identified and externally validated using LUX-Lung 1(n = 390) and LUX-Lung 2(n = 129) trials that initiated afatinib following previous chemotherapy or EGFR inhibitor treatment.Results: Discriminative performance was good in the development and validation cohorts. For patients treated with first-line afatinib, the median OS for the favourable, intermediate and poor risk groups were > 47.7, 29.3 and 16.4 months, respectively, and the median PFS were 17.3, 13.2 and 8.3 months, respectively. The improvement in median OS with afatinib use compared to chemotherapy was > 12.4 months for the favourable risk group, whereas no OS benefit was apparent for the poor risk group. The improvement in median PFS with afatinib use compared to chemotherapy was 10.2 months for the favourable risk group and 3.2 months for the poor risk group.Conclusions: A prognostic tool was developed and validated to identify favourable, intermediate and poor risk groups for OS/PFS in EGFR-positive advanced NSCLC patients treated with afatinib. The prognostic groups can inform the likely absolute OS/PFS benefit expected from afatinib compared to chemotherapy in first-line treatment.

关键词： Afatinib non-small cell lung cancer prognostic model

prognostic factors of refractory NSCLC patients receiving anlotinib hydrochloride as the third-or further-line treatment

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Cancer Biology & Medicine 2018年第4期15卷 443-451页

作者： Jing Wang Yizhuo Zhao Qiming Wang Li Zhang Jianhua Shi Zhehai Wang Ying Cheng Jianxing He Yuankai Shi Hao Yu Yang Zhao Weiqiang Chen Yi Luo Xiuwen Wang Kejun Nan Faguang Jin Jian Dong Baolan Li Zhujun Liu Baohui Han Kai Li Department of Pulmonary Oncology Tianjin Medical University Cancer Institute and Hospital Department of Respiratory Medicine Shanghai Chest Hospital Department of Medical Oncology Henan Province Tumor Hospital Department of Respiratory Medicine Peking Union Medical College Hospital Department of Medical Oncology Linyi Cancer Hospital Department of Internal Medicine Shandong Cancer Hospital Department of Thoracic Oncology Jilin Cancer Hospital Department of Thoracic Surgery The First Affiliated Hospital of Guangzhou Medical University Department of Medical Oncology Cancer Hospital Chinese Academy of Medical Sciences Department of Biostatistics School of Public Health Nanjing Medical University Department of Respiratory Medicine Lanzhou Military General Hospital Department of Head and Neck Oncology Hunan Cancer Hospital Department of Chemotherapy Qilu Hospital of Shandong University Department of Medical Oncology The First Affiliated Hospital of Xi'an Jiaotong University Department of Respiratory and Critical Diseases Tang Du Hospital Department of Oncology Yunnan Cancer Hospital General Department Capital Medical University Beijing Chest Hospital

Objective:Anlotinib hydrochloride is a multitarget tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor,fibroblast growth factor receptor,platelet-derived growth factor receptor,c-Kit,and c-MET;therefore,it exhibits both antitumor and anti-angiogenetic activities.A phase III trial has shown that anlotinib improved progression-free survival(PFS)and overall survival(OS)in patients with advanced non-small cell lung cancer(NSCLC),who presented with progressive disease or intolerance after standard chemotherapy.This study aimed to analyze the characteristics of patients receiving anlotinib treatment to determine the dominant populations who are fit for the treatment.Methods:Data were collected from March 2015 to January 2017 from a randomized,double-blind,placebo-controlled,multicenter,phase III trial of anlotinib(ALTER0303).A total of 437 patients were enrolled and randomly allocated(2:1)to the anlotinib and placebo groups.Kaplan–Meier analysis and log-rank test were performed to compare PFS and OS.Cox proportional hazards model was adopted for multivariate prognostic analysis.Results:Multivariate analysis indicated that high post-therapeutic peripheral blood granulocyte/lymphocyte ratio and elevated alkaline phosphatase levels were independent risk factors for PFS.Meanwhile,elevated thyroid-stimulating hormone,blood glucose,and triglyceride levels;hypertension;and hand–foot syndrome were independent protective factors of PFS.High posttherapeutic peripheral blood granulocyte/lymphocyte ratio,an Eastern Cooperative Oncology Group(ECOG)score≥2,and the sum of the maximal target lesion length at baseline were independent risk factors of OS,and hypertriglyceridemia was an independent protective factor of OS.Conclusions:This study preliminarily explored the possible factors that affected PFS and OS after anlotinib treatment in patients with advanced refractory NSCLC,and the baseline characteristics of the therapeutically dominant populations were then identified.

关键词： Non-small cell lung cancer anlotinib third- or further-line therapy prognostic factor analysis

prognostic value of the long noncoding RNA AFAP1-AS1 in cancers

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Oncology and Translational Medicine 2023年第3期9卷 133-146页

作者： Lixiu Zhu Jiawen Yan Guoqiang Xu Qiaoli Wang Tianrui Xu Ruixue Cao Chuanzheng Sun Yan Xi Wei Xiong Department of Radiotherapy Yunnan Cancer HospitalThe Third Affiliated Hospital of Kunming Medical UniversityKunming 650000China Department of Radiotherapy People's Hospital of Yuxi CityThe Sixth Affiliated Hospital of Kunming Medical UniversityYuxi 653100China Department of Head and Neck Surgery Yunnan Cancer HospitalThe Third Affiliated Hospital of Kunming Medical UniversityKunming 650000China

Objective This meta-analysis explored whether the expression of actin filament-associated protein 1 antisense RNA 1(AFAP1-AS1)is related to the prognosis and clinicopathological features of patients with cancer.Methods PubMed,EMBASE,and Cochrane Library were systematically searched.Hazard ratios(HRs)with 95%confidence intervals(CIs)were used to assess the prognostic value based on overall survival(OS),disease-free survival(DFS),and progression-free survival(PFS).Odds ratios(ORs)with 95%CIs were used to determine the relationships between AFAP1-AS1 and clinicopathological features,such as large tumor size(LTS),high tumor stage(HTS),poor histological grade(PHG),lymph node metastasis(LNM),and distant metastasis(DM).Results Thirty-five eligible articles and 3433 cases were analyzed.High AFAP1-AS1 expression,compared to low AFAP1-AS1 expression,correlated with significantly shorter OS(HR=2.15,95%CI=1.97-2.34,Pprognostic and clinicopathological features,suggesting that AFAP1-AS1 is a prognostic biomarker for human cancers.

关键词： long noncoding RNA(lncRNA) actin filament-associated protein 1 antisense RNA 1(AFAP1-AS1) prognostic meta-analysis

prognostic factors in the surgical treatment of caudate lobe hepatocellular carcinoma

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World Journal of Gastroenterology 2010年第9期16卷 1123-1128页

作者： Peng Liu,Jia-Mei Yang,Wen-Yang Niu,Tong Kan,Feng Xie,Dian-Qi Li,Ye Wang,Yan-Ming Zhou,Department of Special Treatment and Liver Transplantation,Eastern Hepatobiliary Surgery Hospital,Second Military Medical University,Shanghai 200438,China Peng Liu,Department of Hepatobiliary Surgery,Navy General Hospital,Beijing 100037,China Department of Special Treatment and Liver Transplantation Eastern Hepatobiliary Surgery Hospital Second Military Medical University Shanghai 200438 China.

AIM:To evaluate the short-and long-term outcomes of liver resection for caudate lobe hepatocellular carcinoma (HCC).METHODS:We retrospectively analyzed 114 consecutive patients with HCC,originating from the caudate lobe,who underwent resection between January 2001 and January 2007.Univariate and multivariate analyses were performed on several clinicopathologic variables to determine the factors affecting long-term outcome and intrahepatic recurrence.RESULTS:Overall mortality and morbidity were 0% and 18%,respectively.After a median follow-up of 31 mo (interquartile range,11-66 mo),tumor recurrence had occurred in 76 patients (66.7%).The 1-,3-,and 5-year disease-free survival rates were 65.7%,38.1%,and 18.4%,respectively.The 1-,3-,and 5-year overall survival rates were 76.1%,54.7%,and 31.8%,respectively.Univariate analysis showed that subsegmental location of the tumor (45.7% vs 16.2%,P=0.01),liver cirrhosis (12.3% vs 47.9%,P=0.03),surgical margin (18.5% vs 54.6%,P=0.04),vascular invasion (37.9% vs 23.2%,P=0.04) and extended caudate resection (42.1% vs 15.4%,P=0.04) were related to poorer long-term survival.Multivariate analysis showed that only subsegmental location of the tumor,liver cirrhosis and surgical margin were significant independent prognostic factors.CONCLUSION:Hepatectomy was an effective treatment for HCC in the caudate lobe.The subsegmental location of the tumor,liver cirrhosis and surgical margin affected long-term survival.

关键词： Hepatectomy Hepatocellular carcinoma Caudate lobe prognostic factors

Establishment and verification of a surgical prognostic model for cervical spinal cord injury without radiological abnormality

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Neural Regeneration Research 2019年第4期14卷 713-720页

作者： Jie Wang Shuai Guo Xuan Cai Jia-Wei Xu Hao-Peng Li Second Affiliated Hospital of Xi'an Jiaotong University Health Science Center Xi'an Jiaotong University

Some studies have suggested that early surgical treatment can effectively improve the prognosis of cervical spinal cord injury without radiological abnormality, but no research has focused on the development of a prognostic model of cervical spinal cord injury without radiological abnormality. This retrospective analysis included 43 patients with cervical spinal cord injury without radiological abnormality. Seven potential factors were assessed: age, sex, external force strength causing damage, duration of disease, degree of cervical spinal stenosis, Japanese Orthopaedic Association score, and physiological cervical curvature. A model was established using multiple binary logistic regression analysis. The model was evaluated by concordant profiling and the area under the receiver operating characteristic curve. Bootstrapping was used for internal validation. The prognostic model was as follows: logit(P) =-25.4545 + 21.2576 VALUE + 1.2160SCORE-3.4224 TIME, where VALUE refers to the Pavlov ratio indicating the extent of cervical spinal stenosis, SCORE refers to the Japanese Orthopaedic Association score(0–17) after the operation, and TIME refers to the disease duration(from injury to operation). The area under the receiver operating characteristic curve for all patients was 0.8941(95% confidence interval, 0.7930–0.9952). Three factors assessed in the predictive model were associated with patient outcomes: a great extent of cervical stenosis, a poor preoperative neurological status, and a long disease duration. These three factors could worsen patient outcomes. Moreover, the disease prognosis was considered good when logit(P) ≥-2.5105. Overall, the model displayed a certain clinical value. This study was approved by the Biomedical Ethics Committee of the Second Affiliated Hospital of Xi'an Jiaotong University, China(approval number: 2018063) on May 8, 2018.

关键词： nerve regeneration surgical prognostic model cervical spinal cord injury retrospective study multiple binary logistic regression analysis bootstrapping internal validation multiple imputations cervical spinal stenosis duration of disease Pavlov ratio neural regeneration

prognostic impact of at least 12 lymph nodes after neoadjuvant therapy in rectal cancer: A meta-analysis

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World Journal of Gastrointestinal Oncology 2020年第12期12卷 1443-1455页

作者： Ling Tan Zi-Lin Liu Zhou Ma Zhou He Lin-Han Tang Yi-Lei Liu Jiang-Wei Xiao Department of Gastrointestinal Surgery Clinical Medical College and The First Affiliated Hospital of Chengdu Medical CollegeChengdu 610500Sichuan ProvinceChina

BACKGROUND The number of dissected lymph nodes(LNs)in rectal cancer after neoadjuvant therapy has a controversial effect on the prognosis.AIM To investigate the prognostic impact of the number of LN dissected in rectal cancer patients after neoadjuvant therapy.METHODS We performed a systematic review and searched Pub Med,Embase(Ovid),MEDLINE(Ovid),Web of Science,and Cochrane Library from January 1,2000 until January 1,2020.Two reviewers examined all the publications independently and extracted the relevant data.Articles were eligible for inclusion if they compared the number of LNs in rectal cancer specimens resected after neoadjuvant treatment(LNs≥12 vs LNs<12).The primary endpoints were the overall survival(OS)and disease-free survival(DFS).RESULTS Nine articles were included in the meta-analyses.Statistical analysis revealed a statistically significant difference in OS[hazard ratio(HR)=0.76,95%confidence interval(CI):0.66-0.88,I2=12.2%,P=0.336],DFS(HR=0.76,95%CI:0.63-0.92,I2=68.4%,P=0.013),and distant recurrence(DR)(HR=0.63,95%CI:0.48-0.93,I2=30.5%,P=0.237)between the LNs≥12 and LNs<12 groups,but local recurrence(HR=0.67,95%CI:0.38-1.16,I2=0%,P=0.348)showed no statistical difference.Moreover,subgroup analysis of LN negative patients revealed a statistically significant difference in DFS(HR=0.67,95%CI:0.52-0.88,I2=0%,P=0.565)between the LNs≥12 and LNs<12 groups.CONCLUSION Although neoadjuvant therapy reduces LN production in rectal cancer,our data indicate that dissecting at least 12 LNs after neoadjuvant therapy may improve the patients’OS,DFS,and DR.

关键词： Rectal cancer Neoadjuvant therapy Lymph node prognostic Overall survival Meta-analysis

Five-CpG-based prognostic signature for predicting survival in hepatocellular carcinoma patients

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Cancer Biology & Medicine 2018年第4期15卷 425-433页

作者： Feng Fang Xiaoqing Wang Tianqiang Song Department of Hepatobiliary Cancer Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and Therapy Tianjin Tianjin's Clinical Research Center for Cancer

Objective:Hepatocellular carcinoma(HCC)is a common malignancy associated with high morbidity and mortality rates worldwide.Early diagnosis plays an important role in the improvement of HCC prognosis.Methods:In this study,we conducted a comprehensive analysis of HCC DNA methylation and gene expression datasets in The Cancer Genome Atlas(TCGA),to identify a prognostic signature for HCC diagnosis and survival prediction.First,we identified differential methylation CpG(dmCpG)sites in HCC samples and compared them with those in adjacent normal liver tissues;this was followed by univariate analysis and Sure Independence Screening(SIS)in the training set.The robustness of the identified prognostic signature was evaluated using the testing set.To explore the biological processes involved in HCC progression,we also performed functional enrichment analysis for overlapping genes between genes containing dmCpG sites(DMGs)and differential expression genes(DEGs)in HCC patients,using data from the Database for Annotation,Visualization,and Integrated Discovery(DAVID).Results:As a result,we identified five CpG sites that were significantly associated with HCC survival through univariate analysis and SIS.Univariate analysis of clinical characteristics identified age and risk factors(including alcohol consumption and smoking)as independent factors that indicated HCC survival.Multivariate analysis indicated that the integrated prognostic signature(weighted combination of the five CpG sites)that took age and risk factors into consideration resulted in more accurate survival prediction.Conclusions:This study provides a novel signature for predicting HCC survival,and should be helpful for early HCC diagnosis and personalized treatment.

关键词： Hepatocellular carcinoma methylation prognosis prognostic signature TCGA

A new tumor-associated antigen prognostic scoring system for spontaneous ruptured hepatocellular carcinoma after partial hepatectomy

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Cancer Biology & Medicine 2018年第4期15卷 415-424页

作者： Jingjing Wu Peng Zhu Zhanguo Zhang Bixiang Zhang Chang Shu Lin Chen Renjie Feng Abdoul aziz Mba'nbo koumpa Ganxun Li Qianyun Ge Department of Hepatic Surgery Center Tongji Hospital of Tongji Medical College of Huazhong University of Science and TechnologyWuhan 430030China Department of Neurology Tongji Hospital of Tongji Medical College of Huazhong University of Science and TechnologyWuhan 430030China

Objective:Spontaneous hepatocellular carcinoma(HCC)rupture can be fatal,and hepatic resection could achieve a favorable long-term survival among all strategies of tumor rupture.However,there is no available prognostic scoring system for patients with ruptured HCC who underwent partial hepatectomy.Methods:From January 2005 to May 2015,129 patients with spontaneous HCC rupture underwent partial hepatectomy.Preoperative clinical data were collected and analyzed.Independent risk factors affecting overall survival(OS)were used to develop the new scoring system.Harrell’s C statistics,Akaike information criterion(AIC),the relative likelihood,and the log likelihood ratio were calculated to measure the homogeneity and discriminatory ability of a prognostic system.Results:In the multivariable Cox regression analysis,three factors,including tumor size,preoperativeα-fetoprotein level,and alkaline phosphatase level,were chosen for the new tumor-associated antigen(TAA)prognostic scoring system.The 1-year OS rates were 88.1%,43.2%,and 30.2%for TAA scores of 0–5 points(low-risk group),6–9 points(moderate-risk group),and 10–13points(high-risk group),respectively.The TAA scoring system had superior homogeneity and discriminatory ability(Harrell’s C statistics,0.693 vs.0.627 and 0.634;AIC,794.79 vs.817.23 and 820.16;relative likelihood,bothprognostic scoring system is simple and effective in predicting both OS and DFS of patients with spontaneous ruptured HCC.

关键词： Spontaneous rupture prognostic scoring system homogeneity discriminatory ability overall survival disease-free survival hepatocellular carcinoma

Phosphoglucose isomerase gene expression as a prognostic biomarker of gastric cancer

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Chinese Journal of Cancer Research 2019年第5期31卷 771-784页

作者： Han-Chen Huang Xian-Zi Wen Hua Xue Run-Sheng Chen Jia-Fu Ji Lei Xu Key Laboratory of RNA Biology Institute of BiophysicsChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Division of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital&InstituteBeijing 100142China Guangdong Geneway Decoding Bio-Tech Co.Ltd Foshan 528316China Centre for Cognitive Machines and Computational Health(CMaCH) School of Electronic Information and Electrical EngineeringShanghai Jiao Tong UniversityShanghai 200240China Department of Computer Science and Engineering The Chinese University of Hong KongHong Kong 999077China

Objective: Tumor heterogeneity renders identification of suitable biomarkers of gastric cancer(GC)challenging. Here, we aimed to identify prognostic genes of GC using computational analysis.Methods: We first used microarray technology to profile gene expression of GC and paired nontumor tissues from 198 patients. Based on these profiles and patients’ clinical information, we next identified prognostic genes using novel computational approaches. Phosphoglucose isomerase, also known as glucose-6-phosphate isomerase(GPI), which ranked first among 27 candidate genes, was further investigated by a new analytical tool namely enviro-geno-pheno-state(E-GPS) analysis. Suitability of GPI as a prognostic marker, and its relationship with physiological processes such as metabolism, epithelial-mesenchymal transition(EMT), as well as drug sensitivity were evaluated using both our own and independent public datasets.Results: We found that higher expression of GPI in GC correlated with prolonged survival of patients.Particularly, a combination of CDH2 and GPI expression effectively stratified the outcomes of patients with TNM stage Ⅱ/Ⅲ. Down-regulation of GPI in tumor tissues correlated well with depressed glucose metabolism and fatty acid synthesis, as well as enhanced fatty acid oxidation and creatine metabolism, indicating that GPI represents a suitable marker for increased probability of EMT in GC cells.Conclusions: Our findings strongly suggest that GPI acts as a novel biomarker candidate for GC prognosis,allowing greatly enhanced clinical management of GC patients. The potential metabolic rewiring correlated with GPI also provides new insights into studying the relationship between cancer metabolism and patient survival.

关键词： Gastric cancer gene expression profile prognostic biomarker phosphoglucose isomerase tumor metabolism