BACKGROUND A well-recognized class effect of immune checkpoint inhibitors(ICI)is immune-related adverse events(IrAEs)ranging from low grade toxicities to life-threatening end organ damage requiring permanent discontin...BACKGROUND A well-recognized class effect of immune checkpoint inhibitors(ICI)is immune-related adverse events(IrAEs)ranging from low grade toxicities to life-threatening end organ damage requiring permanent discontinuation of ICI.Deaths are reported in<5%of patients treated with ICI.There are,however,no reliable markers to predict the onset and severity of IrAEs.We tested the association between neutrophil-lymphocyte ratio(NLR)and platelet-lymphocyte ratio(PLR)at baseline with development of clinically significant IrAEs(grade≥2)in hepatocellular carcinoma(HCC)patients treated with ICI.AIM To test the association between NLR and PLR at baseline with development of clinically significant IrAEs(grade≥2)in HCC patients treated with ICI.METHODS Data was extracted from an international database from a consortium of 11 tertiary-care referral centers.NLR=absolute neutrophil count/absolute lymphocyte count(ALC)and PLR=platelet count/ALC.Cutoff of 5 was used for NLR and 300 for PLR based on literature.We also tested the association between RESULTS Data was collected from 361 patients treated between 2016-2020 across the United States(67%),Asia(14%)and Europe(19%).Most patients received Nivolumab(n=255,71%).One hundred sixty-seven(46%)patients developed at least one IrAE,highest grade 1 in 80(48%),grade≥2 in 87(52%)patients.In a univariable regression model PLR>300 was significantly associated with a lower incidence of grade≥2 IrAEs(OR=0.40;P=0.044).Similarly,a trend was observed between NLR>5 and lower incidence of grade≥2 IrAEs(OR=0.58;P=0.097).Multivariate analyses confirmed PLR>300 as an independent predictive marker of grade≥2 IrAEs(OR=0.26;P=0.011),in addition to treatment with programmed cell death ligand 1(PD-1)/cytotoxic T lymphocyte-associated protein-4(OR=2.57;P=0.037)and PD-1/tyrosine kinase inhibitor(OR=3.39;P=0.01)combinations.Antibiotic use was not associated with IrAE incidence(OR=1.02;P=0.954).Patients treated with steroids had a>2-fold higher incidence of grade≥2 IrAEs(OR=2.74;P<0.001),although 74%were prescribed steroids for the treatment of IrAEs.CONCLUSION Given that high baseline NLR and PLR are associated with a decreased incidence of IrAEs,lower baseline NLR and PLR may be predictive biomarkers for the appearance of IrAEs in HCC treated with ICI.This finding is in keeping with several studies in solid tumors that have shown that baseline NLR and PLR appear predictive of IrAEs.展开更多
AIM To perform a systematic review and meta-analysis on clinical outcomes of photodynamic therapy(PDT) in non-resectable cholangiocarcinoma. METHODS Included studies compared outcomes with photodynamic therapy and bil...AIM To perform a systematic review and meta-analysis on clinical outcomes of photodynamic therapy(PDT) in non-resectable cholangiocarcinoma. METHODS Included studies compared outcomes with photodynamic therapy and biliary stenting(PDT group) vs biliary stenting only(BS group) in palliation of non-resectable cholangiocarcinoma. Articles were searched in MEDLINE, PubM ed, and EMBASE. Pooled proportions were calculated using fixed and random effects model. Heterogeneity among studies was assessed using the I2 statistic.RESULTS Ten studies(n = 402) that met inclusion criteria were included in this analysis. The P for χ2 heterogeneity for all the pooled accuracy estimates was > 0.10. Pooled odds ratio for successful biliary drainage(decrease in bilirubin level > 50% within 7days after stenting)in PDT vs BS group was 4.39(95%CI: 2.35-8.19).Survival period in PDT and BS groups were 413.04d(95%CI: 349.54-476.54) and 183.41(95%CI:136.81-230.02) respectively. The change in Karnofsky performance scores after intervention in PDT and BS groups were +6.99(95%CI: 4.15-9.82) and-3.93(95%CI:-8.63-0.77) respectively. Odds ratio for postintervention cholangitis in PDT vs BS group was 0.57(95%CI: 0.35-0.94). In PDT group, 10.51%(95%CI:6.94-14.72) had photosensitivity reactions that were self-limiting. Subgroup analysis of prospective studies showed similar results, except the incidence of cholangitis was comparable in both groups. CONCLUSION In palliation of unresectable cholangiocarcinoma, PDT seems to be significantly superior to BS alone. PDT should be used as an adjunct to biliary stenting in these patients.展开更多
文摘BACKGROUND A well-recognized class effect of immune checkpoint inhibitors(ICI)is immune-related adverse events(IrAEs)ranging from low grade toxicities to life-threatening end organ damage requiring permanent discontinuation of ICI.Deaths are reported in<5%of patients treated with ICI.There are,however,no reliable markers to predict the onset and severity of IrAEs.We tested the association between neutrophil-lymphocyte ratio(NLR)and platelet-lymphocyte ratio(PLR)at baseline with development of clinically significant IrAEs(grade≥2)in hepatocellular carcinoma(HCC)patients treated with ICI.AIM To test the association between NLR and PLR at baseline with development of clinically significant IrAEs(grade≥2)in HCC patients treated with ICI.METHODS Data was extracted from an international database from a consortium of 11 tertiary-care referral centers.NLR=absolute neutrophil count/absolute lymphocyte count(ALC)and PLR=platelet count/ALC.Cutoff of 5 was used for NLR and 300 for PLR based on literature.We also tested the association between RESULTS Data was collected from 361 patients treated between 2016-2020 across the United States(67%),Asia(14%)and Europe(19%).Most patients received Nivolumab(n=255,71%).One hundred sixty-seven(46%)patients developed at least one IrAE,highest grade 1 in 80(48%),grade≥2 in 87(52%)patients.In a univariable regression model PLR>300 was significantly associated with a lower incidence of grade≥2 IrAEs(OR=0.40;P=0.044).Similarly,a trend was observed between NLR>5 and lower incidence of grade≥2 IrAEs(OR=0.58;P=0.097).Multivariate analyses confirmed PLR>300 as an independent predictive marker of grade≥2 IrAEs(OR=0.26;P=0.011),in addition to treatment with programmed cell death ligand 1(PD-1)/cytotoxic T lymphocyte-associated protein-4(OR=2.57;P=0.037)and PD-1/tyrosine kinase inhibitor(OR=3.39;P=0.01)combinations.Antibiotic use was not associated with IrAE incidence(OR=1.02;P=0.954).Patients treated with steroids had a>2-fold higher incidence of grade≥2 IrAEs(OR=2.74;P<0.001),although 74%were prescribed steroids for the treatment of IrAEs.CONCLUSION Given that high baseline NLR and PLR are associated with a decreased incidence of IrAEs,lower baseline NLR and PLR may be predictive biomarkers for the appearance of IrAEs in HCC treated with ICI.This finding is in keeping with several studies in solid tumors that have shown that baseline NLR and PLR appear predictive of IrAEs.
文摘AIM To perform a systematic review and meta-analysis on clinical outcomes of photodynamic therapy(PDT) in non-resectable cholangiocarcinoma. METHODS Included studies compared outcomes with photodynamic therapy and biliary stenting(PDT group) vs biliary stenting only(BS group) in palliation of non-resectable cholangiocarcinoma. Articles were searched in MEDLINE, PubM ed, and EMBASE. Pooled proportions were calculated using fixed and random effects model. Heterogeneity among studies was assessed using the I2 statistic.RESULTS Ten studies(n = 402) that met inclusion criteria were included in this analysis. The P for χ2 heterogeneity for all the pooled accuracy estimates was > 0.10. Pooled odds ratio for successful biliary drainage(decrease in bilirubin level > 50% within 7days after stenting)in PDT vs BS group was 4.39(95%CI: 2.35-8.19).Survival period in PDT and BS groups were 413.04d(95%CI: 349.54-476.54) and 183.41(95%CI:136.81-230.02) respectively. The change in Karnofsky performance scores after intervention in PDT and BS groups were +6.99(95%CI: 4.15-9.82) and-3.93(95%CI:-8.63-0.77) respectively. Odds ratio for postintervention cholangitis in PDT vs BS group was 0.57(95%CI: 0.35-0.94). In PDT group, 10.51%(95%CI:6.94-14.72) had photosensitivity reactions that were self-limiting. Subgroup analysis of prospective studies showed similar results, except the incidence of cholangitis was comparable in both groups. CONCLUSION In palliation of unresectable cholangiocarcinoma, PDT seems to be significantly superior to BS alone. PDT should be used as an adjunct to biliary stenting in these patients.
