The systematic treatment based on gemcitabine plus cisplatin is recommended as the current standard chemotherapy for unresectable or metastatic biliary tract cancers.However,the exact benefits from the recognized regi...The systematic treatment based on gemcitabine plus cisplatin is recommended as the current standard chemotherapy for unresectable or metastatic biliary tract cancers.However,the exact benefits from the recognized regime are still dismal.We thus elicit this study in an attempt to analyze whether targeted therapy coupled with various chemotherapy could produce improvement of survival benefits.The clinical trials were searched electronically from databases till July 2016 published in English and Chinese.Nine hundred and sixty-four patients from 7 trials were identified in our analysis.The overall analysis achieved a significantly higher overall response rate（ORR） among the patients treated with targeted drugs plus chemotherapy than chemotherapy alone（OR=1.87;95% CI：1.37–2.57;P=0.000）,but failed in the overall progression-free survival（PFS） [mean difference（MD）=0.63;95% CI：–0.45–1.72;P=0.26] and overall survival（OS）（MD=–0.67;95% CI：–2.54–1.20;P=0.49）.In the sub analysis,better ORR was obtained with the addition of EGFR（OR=1.75;95% CI：1.20–2.56;P=0.004） and VEGFR（OR=2.5;95% CI：1.28–4.87;P=0.007） targeted therapy.Furthermore,the sub analysis of EGFR target showed an significant improvement on PFS（MD=1.36;95% CI：0.29–2.43;P=0.01）.No significant differences were observed in the incidences of neutropenia（OR=1.37;95% CI：0.89–2.12）,thrombocytopenia（OR=1.40;95% CI：0.83–2.39）,anemia（OR=1.21;95% CI：0.62–2.38）,peripheral neuropathy（OR=1.52;95% CI：0.81–2.88）,increased AST/ALT（OR=1.40;95% CI：0.82–2.39） as well as fatigue（OR=1.65;95% CI：0.96–2.84） in either of the treatment groups.In conclusion,better ORR associated with chemotherapy combined with targeted therapy（both targeting EGFR and VEGF） is found in the present meta-analysis without the cost of increased unacceptable toxicities,but regretfully not for the OS.The sub-analysis of targeting EGFR instead of VEGF obtains a superior PFS.Otherwise,there is no statistically significant difference in the overall PFS between the combination regime and chemotherapy alone.Given the paucity of favorable data,we need further studies to characterize optimal targeted agents to confirm the potential value to biliary tract cancer.展开更多
BACKGROUND Targeted therapy(TT)has resulted in controversial efficacy as first-line treatment for biliary tract cancer(BTC).More efficacy comparisons are required to clarify the overall effects of chemotherapy(CT)comb...BACKGROUND Targeted therapy(TT)has resulted in controversial efficacy as first-line treatment for biliary tract cancer(BTC).More efficacy comparisons are required to clarify the overall effects of chemotherapy(CT)combined with TT and CT alone on advanced BTC.AIM To conduct a meta-analysis of the available evidence on the efficacy of CT combined with TT for advanced BTC.METHODS The PubMed,EMBASE,ClinicalTrials,Scopus and Cochrane Library databases were systematically searched for relevant studies published from inception to August 2022.Only randomized clinical trials(RCTs)including comparisons between the combination of gemcitabine-based CT with TT and CT alone as firstline treatment for advanced BTC were eligible(PROSPERO-CRD42022313001).The odds ratios(ORs)for the objective response rate(ORR)and hazard ratios(HRs)for both progression-free survival(PFS)and overall survival(OS)were calculated and analyzed.Subgroup analyses based on different targeted agents,CT regimens and tumor locations were prespecified.RESULTS Nine RCTs with a total of 1361 individuals were included and analyzed.The overall analysis showed a significant improvement in ORR in patients treated with CT+TT compared to those treated with CT alone(OR=1.43,95%CI:1.11-1.86,P=0.007)but no difference in PFS or OS.Similar trends were observed in the subgroup treated with agents targeting epidermal growth factor receptor(OR=1.67,95%CI:1.17-2.37,P=0.004)but not in the subgroups treated with agents targeting vascular endothelial growth factor receptor or mesenchymal-epithelial transition factor.Notably,patients who received a CT regimen of gemcitabine+oxaliplatin in the CT+TT arm had both a higher ORR(OR=1.75,95%CI:1.20-2.56,P=0.004)and longer PFS(HR=0.83,95%CI:0.70-0.99,P=0.03)than those in the CT-only arm.Moreover,patients with cholangiocarcinoma treated with CT+TT had significantly increased ORR and PFS(ORR,OR=2.06,95%CI:1.27-3.35,PFS,HR=0.79,95%CI:0.66-0.94).CONCLUSION CT+TT is a potential first-line treatment for advanced BTC that leads to improved tumor control and survival outcomes,and highlighting the importance of CT regimens and tumor types in the application of TT.展开更多
AIM:To analyze the pathogenetic role and potential clinical usefulness of the epidermal growth factor receptor(EGFR)and the human epidermal growth factor receptor 2(HER2)in patients with advanced biliary tract cancer(...AIM:To analyze the pathogenetic role and potential clinical usefulness of the epidermal growth factor receptor(EGFR)and the human epidermal growth factor receptor 2(HER2)in patients with advanced biliary tract cancer(BTC). METHODS:EGFR and HER2 expression was studied in biopsy samples from 124 patients(51%women; median age 64.8 years),with advanced BTC diagnosed between 1997 and 2004.Five micrometers sections of paraffin embedded tissue were examined by standard, FDA approved immunohistochemistry.Tumors with scores of 2+or 3+for HER2 expression on immunochemistry were additionally tested for HER2 gene amplification by fluorescence in situ hybridisation(FISH).RESULTS:34/124 patients(27.4%)had gallbladder cancer,47(37.9%)had intrahepatic BTC and 43(34.7%)had extrahepatic or perihilar BTC.EGFR expression was examined in a subset of 56 samples. EGFR expression was absent in 22/56 tumors(39.3%). Of the remaining samples expression was scored as 1+in 12(21.5%),2+in 13(23.2%)and 3+in 9(16%), respectively.HER2 expression was as follows:score 0 73/124(58.8%),score 1+27/124(21.8%),score 2+ 21/124(17%)and score 3+4/124(3.2%).HER2 gene amplification was present in 6/124,resulting in an overall amplification rate of 5%. CONCLUSION:Our data suggest that routine testing and therapeutic targeting of HER2 does not seem to be useful in patients with BTC,while targeting EGFR may be promising.展开更多
Cholangiocarcinoma(CCA) is a rare cancer arising from the biliary tree with a poor prognosis and limited therapeutic options. Recent large scale molecular characterisation studies have identified recurrent genetic alt...Cholangiocarcinoma(CCA) is a rare cancer arising from the biliary tree with a poor prognosis and limited therapeutic options. Recent large scale molecular characterisation studies have identified recurrent genetic alterations in CCA which may be amenable to therapeutic targeting. In this review we explore the genomic landscape of CCA and examine results from trials of molecularly targeted agents and immunotherapy in this disease. Challenges in CCA diagnosis, treatment and trial design are discussed and we reflect on future directions which may lead to improved outcomes for CCA patients.展开更多
BACKGROUND Outcomes for cholangiocarcinoma(CCA)are extremely poor owing to the complexities in diagnosing and managing a rare disease with heterogenous sub-types.Beyond curative surgery,which is only an option for a m...BACKGROUND Outcomes for cholangiocarcinoma(CCA)are extremely poor owing to the complexities in diagnosing and managing a rare disease with heterogenous sub-types.Beyond curative surgery,which is only an option for a minority of patients diagnosed at an early stage,few systemic therapy options are currently recommended to relieve symptoms and prolong life.Stent insertion to manage disease complications requires highly specialised expertise.Evidence is lacking as to how CCA patients are managed in a real-world setting and whether there is any variation in treatments received by CCA patients.AIM To assess geographic variation in treatments received amongst CCA patients in England.METHODS Data used in this cohort study were drawn from the National Cancer Registration Dataset(NCRD),Hospital Episode Statistics and the Systemic Anti-Cancer Therapy Dataset.A cohort of 8853 CCA patients diagnosed between 2014-2017 in the National Health Service in England was identified from the NCRD.Potentially curative surgery for all patients and systemic therapy and stent insertion for 7751 individuals who did not receive surgery were identified as three end-points of interest.Linear probability models assessed variation in each of the three treatment modalities according to Cancer Alliance of residence at diagnosis,and for socio-demographic and clinical characteristics at diagnosis.RESULTS Of 8853 CCA patients,1102(12.4%)received potentially curative surgery.The mean[95%confidence interval(CI)]percentage-point difference from the population average ranged from-3.96(-6.34 to-1.59)%to 3.77(0.54 to 6.99)%across Cancer Alliances in England after adjustment for patient sociodemographic and clinical characteristics,showing statistically significant variation.Amongst 7751 who did not receive surgery,1542(19.9%)received systemic therapy,with mean[95%CI]percentage-point difference from the population average between-3.84(-8.04 to 0.35)%to 9.28(1.76 to 16.80)%across Cancer Alliances after adjustment,again showing the presence of statistically significant variation for some regions.Stent insertion was received by 2156(27.8%),with mean[95%CI]percentage-point difference from the population average between-10.54(-12.88 to-8.20)%to 13.64(9.22 to 18.06)%across Cancer Alliances after adjustment,showing wide and statistically significant variation from the population average.Half of 8853 patients(n=4468)received no treatment with either surgery,systemic therapy or stent insertion.CONCLUSION Substantial regional variation in treatments received by CCA patients was observed in England.Such variation could be due to differences in case-mix,clinical practice or access to specialist expertise.展开更多
This article summarizes the drug therapy progress of advanced hepatocellularcarcinoma, biliary tract cancer, and pancreatic cancer in 2022, includingchemotherapy, molecular targeted therapy, and immunotherapy, to prov...This article summarizes the drug therapy progress of advanced hepatocellularcarcinoma, biliary tract cancer, and pancreatic cancer in 2022, includingchemotherapy, molecular targeted therapy, and immunotherapy, to providereference information for current clinical treatment and future clinicalresearch, and to better improve prognosis and quality of life in patients withhepatobiliary and pancreatic cancer.展开更多
基金supported by funds from Science and Technology Research Project of Hunan Province(No.2015SK2044)Health Department of Scientific Research of Hunan Province,China(No.B2014-090)
文摘The systematic treatment based on gemcitabine plus cisplatin is recommended as the current standard chemotherapy for unresectable or metastatic biliary tract cancers.However,the exact benefits from the recognized regime are still dismal.We thus elicit this study in an attempt to analyze whether targeted therapy coupled with various chemotherapy could produce improvement of survival benefits.The clinical trials were searched electronically from databases till July 2016 published in English and Chinese.Nine hundred and sixty-four patients from 7 trials were identified in our analysis.The overall analysis achieved a significantly higher overall response rate（ORR） among the patients treated with targeted drugs plus chemotherapy than chemotherapy alone（OR=1.87;95% CI：1.37–2.57;P=0.000）,but failed in the overall progression-free survival（PFS） [mean difference（MD）=0.63;95% CI：–0.45–1.72;P=0.26] and overall survival（OS）（MD=–0.67;95% CI：–2.54–1.20;P=0.49）.In the sub analysis,better ORR was obtained with the addition of EGFR（OR=1.75;95% CI：1.20–2.56;P=0.004） and VEGFR（OR=2.5;95% CI：1.28–4.87;P=0.007） targeted therapy.Furthermore,the sub analysis of EGFR target showed an significant improvement on PFS（MD=1.36;95% CI：0.29–2.43;P=0.01）.No significant differences were observed in the incidences of neutropenia（OR=1.37;95% CI：0.89–2.12）,thrombocytopenia（OR=1.40;95% CI：0.83–2.39）,anemia（OR=1.21;95% CI：0.62–2.38）,peripheral neuropathy（OR=1.52;95% CI：0.81–2.88）,increased AST/ALT（OR=1.40;95% CI：0.82–2.39） as well as fatigue（OR=1.65;95% CI：0.96–2.84） in either of the treatment groups.In conclusion,better ORR associated with chemotherapy combined with targeted therapy（both targeting EGFR and VEGF） is found in the present meta-analysis without the cost of increased unacceptable toxicities,but regretfully not for the OS.The sub-analysis of targeting EGFR instead of VEGF obtains a superior PFS.Otherwise,there is no statistically significant difference in the overall PFS between the combination regime and chemotherapy alone.Given the paucity of favorable data,we need further studies to characterize optimal targeted agents to confirm the potential value to biliary tract cancer.
基金Supported by China Academy of Medical Science Innovation Fund for Medical Sciences,CIFMS,No.2021-I2M-1-022-2021-S4.
文摘BACKGROUND Targeted therapy(TT)has resulted in controversial efficacy as first-line treatment for biliary tract cancer(BTC).More efficacy comparisons are required to clarify the overall effects of chemotherapy(CT)combined with TT and CT alone on advanced BTC.AIM To conduct a meta-analysis of the available evidence on the efficacy of CT combined with TT for advanced BTC.METHODS The PubMed,EMBASE,ClinicalTrials,Scopus and Cochrane Library databases were systematically searched for relevant studies published from inception to August 2022.Only randomized clinical trials(RCTs)including comparisons between the combination of gemcitabine-based CT with TT and CT alone as firstline treatment for advanced BTC were eligible(PROSPERO-CRD42022313001).The odds ratios(ORs)for the objective response rate(ORR)and hazard ratios(HRs)for both progression-free survival(PFS)and overall survival(OS)were calculated and analyzed.Subgroup analyses based on different targeted agents,CT regimens and tumor locations were prespecified.RESULTS Nine RCTs with a total of 1361 individuals were included and analyzed.The overall analysis showed a significant improvement in ORR in patients treated with CT+TT compared to those treated with CT alone(OR=1.43,95%CI:1.11-1.86,P=0.007)but no difference in PFS or OS.Similar trends were observed in the subgroup treated with agents targeting epidermal growth factor receptor(OR=1.67,95%CI:1.17-2.37,P=0.004)but not in the subgroups treated with agents targeting vascular endothelial growth factor receptor or mesenchymal-epithelial transition factor.Notably,patients who received a CT regimen of gemcitabine+oxaliplatin in the CT+TT arm had both a higher ORR(OR=1.75,95%CI:1.20-2.56,P=0.004)and longer PFS(HR=0.83,95%CI:0.70-0.99,P=0.03)than those in the CT-only arm.Moreover,patients with cholangiocarcinoma treated with CT+TT had significantly increased ORR and PFS(ORR,OR=2.06,95%CI:1.27-3.35,PFS,HR=0.79,95%CI:0.66-0.94).CONCLUSION CT+TT is a potential first-line treatment for advanced BTC that leads to improved tumor control and survival outcomes,and highlighting the importance of CT regimens and tumor types in the application of TT.
文摘AIM:To analyze the pathogenetic role and potential clinical usefulness of the epidermal growth factor receptor(EGFR)and the human epidermal growth factor receptor 2(HER2)in patients with advanced biliary tract cancer(BTC). METHODS:EGFR and HER2 expression was studied in biopsy samples from 124 patients(51%women; median age 64.8 years),with advanced BTC diagnosed between 1997 and 2004.Five micrometers sections of paraffin embedded tissue were examined by standard, FDA approved immunohistochemistry.Tumors with scores of 2+or 3+for HER2 expression on immunochemistry were additionally tested for HER2 gene amplification by fluorescence in situ hybridisation(FISH).RESULTS:34/124 patients(27.4%)had gallbladder cancer,47(37.9%)had intrahepatic BTC and 43(34.7%)had extrahepatic or perihilar BTC.EGFR expression was examined in a subset of 56 samples. EGFR expression was absent in 22/56 tumors(39.3%). Of the remaining samples expression was scored as 1+in 12(21.5%),2+in 13(23.2%)and 3+in 9(16%), respectively.HER2 expression was as follows:score 0 73/124(58.8%),score 1+27/124(21.8%),score 2+ 21/124(17%)and score 3+4/124(3.2%).HER2 gene amplification was present in 6/124,resulting in an overall amplification rate of 5%. CONCLUSION:Our data suggest that routine testing and therapeutic targeting of HER2 does not seem to be useful in patients with BTC,while targeting EGFR may be promising.
文摘Cholangiocarcinoma(CCA) is a rare cancer arising from the biliary tree with a poor prognosis and limited therapeutic options. Recent large scale molecular characterisation studies have identified recurrent genetic alterations in CCA which may be amenable to therapeutic targeting. In this review we explore the genomic landscape of CCA and examine results from trials of molecularly targeted agents and immunotherapy in this disease. Challenges in CCA diagnosis, treatment and trial design are discussed and we reflect on future directions which may lead to improved outcomes for CCA patients.
基金Supported by AMMFNational Disease Registration Service,National Health Service England.
文摘BACKGROUND Outcomes for cholangiocarcinoma(CCA)are extremely poor owing to the complexities in diagnosing and managing a rare disease with heterogenous sub-types.Beyond curative surgery,which is only an option for a minority of patients diagnosed at an early stage,few systemic therapy options are currently recommended to relieve symptoms and prolong life.Stent insertion to manage disease complications requires highly specialised expertise.Evidence is lacking as to how CCA patients are managed in a real-world setting and whether there is any variation in treatments received by CCA patients.AIM To assess geographic variation in treatments received amongst CCA patients in England.METHODS Data used in this cohort study were drawn from the National Cancer Registration Dataset(NCRD),Hospital Episode Statistics and the Systemic Anti-Cancer Therapy Dataset.A cohort of 8853 CCA patients diagnosed between 2014-2017 in the National Health Service in England was identified from the NCRD.Potentially curative surgery for all patients and systemic therapy and stent insertion for 7751 individuals who did not receive surgery were identified as three end-points of interest.Linear probability models assessed variation in each of the three treatment modalities according to Cancer Alliance of residence at diagnosis,and for socio-demographic and clinical characteristics at diagnosis.RESULTS Of 8853 CCA patients,1102(12.4%)received potentially curative surgery.The mean[95%confidence interval(CI)]percentage-point difference from the population average ranged from-3.96(-6.34 to-1.59)%to 3.77(0.54 to 6.99)%across Cancer Alliances in England after adjustment for patient sociodemographic and clinical characteristics,showing statistically significant variation.Amongst 7751 who did not receive surgery,1542(19.9%)received systemic therapy,with mean[95%CI]percentage-point difference from the population average between-3.84(-8.04 to 0.35)%to 9.28(1.76 to 16.80)%across Cancer Alliances after adjustment,again showing the presence of statistically significant variation for some regions.Stent insertion was received by 2156(27.8%),with mean[95%CI]percentage-point difference from the population average between-10.54(-12.88 to-8.20)%to 13.64(9.22 to 18.06)%across Cancer Alliances after adjustment,showing wide and statistically significant variation from the population average.Half of 8853 patients(n=4468)received no treatment with either surgery,systemic therapy or stent insertion.CONCLUSION Substantial regional variation in treatments received by CCA patients was observed in England.Such variation could be due to differences in case-mix,clinical practice or access to specialist expertise.
基金National Natural Science Foundation of China,Grant/Award Number:82072664。
文摘This article summarizes the drug therapy progress of advanced hepatocellularcarcinoma, biliary tract cancer, and pancreatic cancer in 2022, includingchemotherapy, molecular targeted therapy, and immunotherapy, to providereference information for current clinical treatment and future clinicalresearch, and to better improve prognosis and quality of life in patients withhepatobiliary and pancreatic cancer.
