Gastric cancer(GC)represents a leading cause of cancer related morbidity and mortality worldwide accounting for more than 1 million of newly diagnosed cases and thousands of deaths every year.In the last decade,the de...Gastric cancer(GC)represents a leading cause of cancer related morbidity and mortality worldwide accounting for more than 1 million of newly diagnosed cases and thousands of deaths every year.In the last decade,the development of targeted therapies and the optimization of already available chemotherapeutic drugs has expanded the available treatment options for advanced GC and granted better survival expectations to the patients.At the same time,global efforts have been undertaken to investigate in detail the genomic and epigenomic heterogeneity of this disease,resulting in the identification of new specific and sensitive predictive and prognostic biomarkers and in innovative molecular classifications based on gene expression profiling.Nonetheless,several randomized studies aimed at exploring new innovative agents,such as immune checkpoint inhibitors,failed to demonstrate clinically meaningful survival advantages.Therefore,it is essential to further improve the molecular characterization of GC subgroups in order to provide researchers and medical oncologists with new tools for patients’selection and stratification in future clinical development programs and subsequent trials.The aim of the present manuscript is to provide a global overview of the recent molecular classifications from The Cancer Genome Atlas and the Asian Cancer Research Group and to present key promising developments in the field of immunotherapy and targeted therapies in metastatic GC.展开更多
Tumor biopsies may help to reliably distinguish hepatocellular carcinoma(HCC) from other tumors, mostly cholangiocarcinoma as well as to identify the patient populations who most benefit from target-driven HCC treatme...Tumor biopsies may help to reliably distinguish hepatocellular carcinoma(HCC) from other tumors, mostly cholangiocarcinoma as well as to identify the patient populations who most benefit from target-driven HCC treatments, in order to improve the success rate of experimental therapies. Clarifying tumor biology may also lead to identify biomarkers with prognostic role and/or enabling to predict response or resistance to therapies. Recently, clinical trials have more efficiently included biomarker endpoints and increasingly collected tumor tissue from enrolled patients. Due to their frail status and sometimes fast-progressing disease, the performance status of patients with HCC progressing on first-line therapy can deteriorate quickly, preventing their enrollment in clinical trials. However, the challenge of identifying the proper patient at the proper time can be overcome by periodic inter-department meetings involving the key specialists taking care of HCC patients, and solid networks between research centers and referring institutions. An early planned biopsy would also facilitate timely inclusion of patients in biology-driven clinical trials. Ultimately, institution of multidisciplinary teams can optimize treatment choice, biopsy timing, and quick enrollment of patients in clinical trials, before their performance status deteriorates.展开更多
Aim:Gliomatosis cerebri(GC)is defined as a rare pattern of growth of diffuse gliomas involving three or more cerebral lobes.Given its rarity,it is difficult to define prognostic factors and standard of treatment.We re...Aim:Gliomatosis cerebri(GC)is defined as a rare pattern of growth of diffuse gliomas involving three or more cerebral lobes.Given its rarity,it is difficult to define prognostic factors and standard of treatment.We retrospectively analyzed patients(PT)with GC from a single institution with the aim of identifying the main prognostic factors and to assess optimal management.Methods:Medical records were reviewed of patients≥18 years with a histological and/or radiological diagnosis of GC(with no contrast enhancement)occurring between 2006 and 2017.Median progression free survival(PFS)and overall survival(OS)were calculated by the Kaplan-Meier method.Results:We analyzed 33 PT,22 males and 11 females;Eastern Cooperative Oncology Group(ECOG)performance status(PS)was 0-1 in 21 of the patients.Twenty-two PT underwent biopsy:16 were astrocytomas and 6 oligodendrogliomas.O6-methylguanin-DNA-methyltransferase(MGMT)was detected in 14 cases,and it was methylated in eight cases.Isocitrate dehydrogenase 1(IDH1)was analyzed in 16 PT,and it had mutated in 10 of them.Nine PT(27%)were treated with radiation therapy(RT)plus concurrent temozolomide(TMZ),22 PT(67%)received TMZ alone,and 2 PT(6%)underwent RT alone.We reported“complete response”in 1 patient(3%),partial response in 9 PT(27%),and stable disease in 15 PT(45%),while 8 PT(25%)had a progressive disease.For all PT,PFS and OS were 19.1 and 30.7 months,respectively.For ECOG PS 0-1 and≥2,PFS was 34.6 months vs.3.4 months(P<0.0001)and OS was 42 months vs.8.9 months(P<0.0001),respectively.Methylated MGMT was associated with longer PFS(41.6 months vs.8.9 months,P=0.05)and OS(52.7 months vs.14.6 months,P=0.009);PFS for IDH1 mutation and IDH wild-type was 52.7 months vs.8.9 months(P=0.006)and OS was 52.7 months vs.41.7 months(P=0.02),respectively.No significant difference was detected as regards treatments.With regard to histological subtype,OS was 42.0 months vs.52.7 months(P=0.8)and PFS was 41.6 months vs.28.6 months(P=0.7)for astrocytoma vs.oligodendroglioma,respectively.PT with treatment response showed a longer OS.PT receiving second-line treatment had a longer OS of 30.7 months vs.6.5 months(P=0.04).Conclusion:ECOG PS,MGMT methylation,and IDH1 mutational status seem to have an important prognostic significance,while the type of treatment does not seem to affect survival.Treatment response could be a surrogate marker for survival.展开更多
文摘Gastric cancer(GC)represents a leading cause of cancer related morbidity and mortality worldwide accounting for more than 1 million of newly diagnosed cases and thousands of deaths every year.In the last decade,the development of targeted therapies and the optimization of already available chemotherapeutic drugs has expanded the available treatment options for advanced GC and granted better survival expectations to the patients.At the same time,global efforts have been undertaken to investigate in detail the genomic and epigenomic heterogeneity of this disease,resulting in the identification of new specific and sensitive predictive and prognostic biomarkers and in innovative molecular classifications based on gene expression profiling.Nonetheless,several randomized studies aimed at exploring new innovative agents,such as immune checkpoint inhibitors,failed to demonstrate clinically meaningful survival advantages.Therefore,it is essential to further improve the molecular characterization of GC subgroups in order to provide researchers and medical oncologists with new tools for patients’selection and stratification in future clinical development programs and subsequent trials.The aim of the present manuscript is to provide a global overview of the recent molecular classifications from The Cancer Genome Atlas and the Asian Cancer Research Group and to present key promising developments in the field of immunotherapy and targeted therapies in metastatic GC.
文摘Tumor biopsies may help to reliably distinguish hepatocellular carcinoma(HCC) from other tumors, mostly cholangiocarcinoma as well as to identify the patient populations who most benefit from target-driven HCC treatments, in order to improve the success rate of experimental therapies. Clarifying tumor biology may also lead to identify biomarkers with prognostic role and/or enabling to predict response or resistance to therapies. Recently, clinical trials have more efficiently included biomarker endpoints and increasingly collected tumor tissue from enrolled patients. Due to their frail status and sometimes fast-progressing disease, the performance status of patients with HCC progressing on first-line therapy can deteriorate quickly, preventing their enrollment in clinical trials. However, the challenge of identifying the proper patient at the proper time can be overcome by periodic inter-department meetings involving the key specialists taking care of HCC patients, and solid networks between research centers and referring institutions. An early planned biopsy would also facilitate timely inclusion of patients in biology-driven clinical trials. Ultimately, institution of multidisciplinary teams can optimize treatment choice, biopsy timing, and quick enrollment of patients in clinical trials, before their performance status deteriorates.
文摘Aim:Gliomatosis cerebri(GC)is defined as a rare pattern of growth of diffuse gliomas involving three or more cerebral lobes.Given its rarity,it is difficult to define prognostic factors and standard of treatment.We retrospectively analyzed patients(PT)with GC from a single institution with the aim of identifying the main prognostic factors and to assess optimal management.Methods:Medical records were reviewed of patients≥18 years with a histological and/or radiological diagnosis of GC(with no contrast enhancement)occurring between 2006 and 2017.Median progression free survival(PFS)and overall survival(OS)were calculated by the Kaplan-Meier method.Results:We analyzed 33 PT,22 males and 11 females;Eastern Cooperative Oncology Group(ECOG)performance status(PS)was 0-1 in 21 of the patients.Twenty-two PT underwent biopsy:16 were astrocytomas and 6 oligodendrogliomas.O6-methylguanin-DNA-methyltransferase(MGMT)was detected in 14 cases,and it was methylated in eight cases.Isocitrate dehydrogenase 1(IDH1)was analyzed in 16 PT,and it had mutated in 10 of them.Nine PT(27%)were treated with radiation therapy(RT)plus concurrent temozolomide(TMZ),22 PT(67%)received TMZ alone,and 2 PT(6%)underwent RT alone.We reported“complete response”in 1 patient(3%),partial response in 9 PT(27%),and stable disease in 15 PT(45%),while 8 PT(25%)had a progressive disease.For all PT,PFS and OS were 19.1 and 30.7 months,respectively.For ECOG PS 0-1 and≥2,PFS was 34.6 months vs.3.4 months(P<0.0001)and OS was 42 months vs.8.9 months(P<0.0001),respectively.Methylated MGMT was associated with longer PFS(41.6 months vs.8.9 months,P=0.05)and OS(52.7 months vs.14.6 months,P=0.009);PFS for IDH1 mutation and IDH wild-type was 52.7 months vs.8.9 months(P=0.006)and OS was 52.7 months vs.41.7 months(P=0.02),respectively.No significant difference was detected as regards treatments.With regard to histological subtype,OS was 42.0 months vs.52.7 months(P=0.8)and PFS was 41.6 months vs.28.6 months(P=0.7)for astrocytoma vs.oligodendroglioma,respectively.PT with treatment response showed a longer OS.PT receiving second-line treatment had a longer OS of 30.7 months vs.6.5 months(P=0.04).Conclusion:ECOG PS,MGMT methylation,and IDH1 mutational status seem to have an important prognostic significance,while the type of treatment does not seem to affect survival.Treatment response could be a surrogate marker for survival.
