BACKGROUND Metastatic pancreatic ductal adenocarcinoma(PDAC)is a lethal malignancy with dispiriting survival data.Immunotherapy is a promising approach to many cancer types,but achieves poor outcomes in advanced PDAC ...BACKGROUND Metastatic pancreatic ductal adenocarcinoma(PDAC)is a lethal malignancy with dispiriting survival data.Immunotherapy is a promising approach to many cancer types,but achieves poor outcomes in advanced PDAC due to its immunosuppressive tumor microenvironment.We describe a case of metastatic PDAC effectively treated with pembrolizumab.CASE SUMMARY We report the case of a 67-year-old woman with unresectable locally advanced PDAC,treated with gemcitabine plus nab-paclitaxel followed by radiotherapy plus capecitabine.At nine months,pancreatic tumor progression was observed at the level of the hepatic hilum with the appearance of a new pulmonary nodule suggestive of a second primary,confirmed by left lung biopsy.Systemic immunotherapy was then initiated with pembrolizumab,an immune checkpoint inhibitor targeting programmed cell death protein-1 that covers the two tumor types.The patient showed a complete metabolic response that was maintained throughout the treatment.The patient continues to be disease-free at 5.6 years since the start of immunotherapy.CONCLUSION These results suggest that the administration of pembrolizumab after chemoradiotherapy has a beneficial effect in patients with metastatic PDAC.To our knowledge,this is the first reported case of a patient with metastatic PDAC and metastatic lung cancer showing such a long-lasting complete response after pembrolizumab treatment without curative surgery.Further studies are required to determine biomarkers that identify PDAC patients most likely to benefit from this immunotherapy.展开更多
Autoimmune pancreatitis(AIP),a chronic inflammation caused by the immune system attacking the pancreas,usually presents imaging and clinical features that overlap with those of pancreatic ductal adenocarcinoma(PDAC).S...Autoimmune pancreatitis(AIP),a chronic inflammation caused by the immune system attacking the pancreas,usually presents imaging and clinical features that overlap with those of pancreatic ductal adenocarcinoma(PDAC).Serum biomarkers,substances that quantitatively change in sera during disease development,are a promising non-invasive tool with high utility for differentiating between these diseases.In this way,the presence of AIP is currently suspected when serum concentrations of immunoglobulin G4(IgG4)antibody are elevated.However,this approach has some drawbacks.Notably,IgG4 antibody concentrations are also elevated in sera from some patients with PDAC.This review focuses on the most recent and relevant serum biomarkers proposed to differentiate between AIP and PDAC,evaluating the usefulness of immunoglobulins,autoantibodies,chemokines,and cytokines.The proposed serum biomarkers have proven useful,although most studies had a small sample size,did not examine their presence in patients with PDAC,or did not test them in humans.In addition,current evidence suggests that a single serum biomarker is unlikely to accurately differentiate these diseases and that a set of biomarkers will be needed to achieve adequate specificity and sensitivity,either alone or in combination with clinical data and/or radiological images.展开更多
Pancreatic cancer(PC)continues to pose a major clinical challenge.There has been little improvement in patient survival over the past few decades,and it is projected to become the second leading cause of cancer mortal...Pancreatic cancer(PC)continues to pose a major clinical challenge.There has been little improvement in patient survival over the past few decades,and it is projected to become the second leading cause of cancer mortality by 2030.The dismal 5-year survival rate of less than 10%after the diagnosis is attributable to the lack of early symptoms,the absence of specific biomarkers for an early diagnosis,and the inadequacy of available chemotherapies.Most patients are diagnosed when the disease has already metastasized and cannot be treated.Cancer interception is vital,actively intervening in the malignization process before the development of a full-blown advanced tumor.An early diagnosis of PC has a dramatic impact on the survival of patients,and improved techniques are urgently needed to detect and evaluate this disease at an early stage.It is difficult to obtain tissue biopsies from the pancreas due to its anatomical position;however,liquid biopsies are readily available and can provide useful information for the diagnosis,prognosis,stratification,and follow-up of patients with PC and for the design of individually tailored treatments.The aim of this review was to provide an update of the latest advances in knowledge on the application of carbohydrates,proteins,cell-free nucleic acids,circulating tumor cells,metabo-lome compounds,exosomes,and platelets in blood as potential biomarkers for PC,focusing on their clinical relevance and potential for improving patient outcomes.展开更多
In this editorial,we comment on pancreatic cancer(PC),one of the most aggressive and lethal cancers.Only minimal improvements in survival rates have been achieved over recent years.Available chemotherapeutic regimens ...In this editorial,we comment on pancreatic cancer(PC),one of the most aggressive and lethal cancers.Only minimal improvements in survival rates have been achieved over recent years.Available chemotherapeutic regimens have little impact,and surgical resection remains the only reliable curative approach.We address current treatment options for these patients,focusing on the usefulness of breast cancer(BRCA)gene mutation as a prognostic biomarker and predictor of response to chemotherapy.Superior survival outcomes have been reported in patients with PC and mutant BRCA gene treated with first-line platinum-based chemotherapy.Therefore,it appears appropriate to include BRCA gene status among clinical criteria used to select the chemotherapy regimen.In addition,maintenance treatment with poly(ADP-ribose)polymerase inhibitors has been found to improve progression-free survival in patients with PC and mutated BRCA whose disease does not progress after first-line platinum-based chemotherapy.This combination has therefore been proposed as the optimal treatment regimen for these patients.展开更多
文摘BACKGROUND Metastatic pancreatic ductal adenocarcinoma(PDAC)is a lethal malignancy with dispiriting survival data.Immunotherapy is a promising approach to many cancer types,but achieves poor outcomes in advanced PDAC due to its immunosuppressive tumor microenvironment.We describe a case of metastatic PDAC effectively treated with pembrolizumab.CASE SUMMARY We report the case of a 67-year-old woman with unresectable locally advanced PDAC,treated with gemcitabine plus nab-paclitaxel followed by radiotherapy plus capecitabine.At nine months,pancreatic tumor progression was observed at the level of the hepatic hilum with the appearance of a new pulmonary nodule suggestive of a second primary,confirmed by left lung biopsy.Systemic immunotherapy was then initiated with pembrolizumab,an immune checkpoint inhibitor targeting programmed cell death protein-1 that covers the two tumor types.The patient showed a complete metabolic response that was maintained throughout the treatment.The patient continues to be disease-free at 5.6 years since the start of immunotherapy.CONCLUSION These results suggest that the administration of pembrolizumab after chemoradiotherapy has a beneficial effect in patients with metastatic PDAC.To our knowledge,this is the first reported case of a patient with metastatic PDAC and metastatic lung cancer showing such a long-lasting complete response after pembrolizumab treatment without curative surgery.Further studies are required to determine biomarkers that identify PDAC patients most likely to benefit from this immunotherapy.
文摘Autoimmune pancreatitis(AIP),a chronic inflammation caused by the immune system attacking the pancreas,usually presents imaging and clinical features that overlap with those of pancreatic ductal adenocarcinoma(PDAC).Serum biomarkers,substances that quantitatively change in sera during disease development,are a promising non-invasive tool with high utility for differentiating between these diseases.In this way,the presence of AIP is currently suspected when serum concentrations of immunoglobulin G4(IgG4)antibody are elevated.However,this approach has some drawbacks.Notably,IgG4 antibody concentrations are also elevated in sera from some patients with PDAC.This review focuses on the most recent and relevant serum biomarkers proposed to differentiate between AIP and PDAC,evaluating the usefulness of immunoglobulins,autoantibodies,chemokines,and cytokines.The proposed serum biomarkers have proven useful,although most studies had a small sample size,did not examine their presence in patients with PDAC,or did not test them in humans.In addition,current evidence suggests that a single serum biomarker is unlikely to accurately differentiate these diseases and that a set of biomarkers will be needed to achieve adequate specificity and sensitivity,either alone or in combination with clinical data and/or radiological images.
基金Junta de Andalucia,No.PC-0498-2017 and No.PC-0549-2017.
文摘Pancreatic cancer(PC)continues to pose a major clinical challenge.There has been little improvement in patient survival over the past few decades,and it is projected to become the second leading cause of cancer mortality by 2030.The dismal 5-year survival rate of less than 10%after the diagnosis is attributable to the lack of early symptoms,the absence of specific biomarkers for an early diagnosis,and the inadequacy of available chemotherapies.Most patients are diagnosed when the disease has already metastasized and cannot be treated.Cancer interception is vital,actively intervening in the malignization process before the development of a full-blown advanced tumor.An early diagnosis of PC has a dramatic impact on the survival of patients,and improved techniques are urgently needed to detect and evaluate this disease at an early stage.It is difficult to obtain tissue biopsies from the pancreas due to its anatomical position;however,liquid biopsies are readily available and can provide useful information for the diagnosis,prognosis,stratification,and follow-up of patients with PC and for the design of individually tailored treatments.The aim of this review was to provide an update of the latest advances in knowledge on the application of carbohydrates,proteins,cell-free nucleic acids,circulating tumor cells,metabo-lome compounds,exosomes,and platelets in blood as potential biomarkers for PC,focusing on their clinical relevance and potential for improving patient outcomes.
基金by Junta de Andalucía,No.PC-0498-2017 and No.PC-0549-2017.
文摘In this editorial,we comment on pancreatic cancer(PC),one of the most aggressive and lethal cancers.Only minimal improvements in survival rates have been achieved over recent years.Available chemotherapeutic regimens have little impact,and surgical resection remains the only reliable curative approach.We address current treatment options for these patients,focusing on the usefulness of breast cancer(BRCA)gene mutation as a prognostic biomarker and predictor of response to chemotherapy.Superior survival outcomes have been reported in patients with PC and mutant BRCA gene treated with first-line platinum-based chemotherapy.Therefore,it appears appropriate to include BRCA gene status among clinical criteria used to select the chemotherapy regimen.In addition,maintenance treatment with poly(ADP-ribose)polymerase inhibitors has been found to improve progression-free survival in patients with PC and mutated BRCA whose disease does not progress after first-line platinum-based chemotherapy.This combination has therefore been proposed as the optimal treatment regimen for these patients.
