Pancreatic ductal adenocarcinoma(PDAC)is an aggressive cancer with poor survival.Local control through surgical resection paired with radiotherapy and chemotherapy comprise the primary tenets of treatment.Debate exist...Pancreatic ductal adenocarcinoma(PDAC)is an aggressive cancer with poor survival.Local control through surgical resection paired with radiotherapy and chemotherapy comprise the primary tenets of treatment.Debate exists regarding the timing of treatment and ordering of systemic therapy and resection in the management of early stage disease.The goal of this study was to review the literature and describe the contemporary evidence basis for the role of neoadjuvant therapy(NAT)in the setting of upfront resectable(UP-R)PDAC.Five databases were searched in parallel to identify relevant original articles investigating neoadjuvant therapy where at least 1 study arm contained UP-R PDAC;studies with only borderline resectable or locally advanced disease were excluded.Due to the diversity in NAT regimens and study design between trials,qualitative analyses were performed to investigate patient selection,impact on perioperative and survival outcomes,safety,and cost effectiveness.Thirty-five studies met inclusion criteria,of which 24 unique trials are discussed here in detail.These studies included those trials using single agents as well as more recent trials comparing modern multiagent therapies,and several large database analyses.Overall the data suggest that NAT is safe,may confer survival benefit for appropriately selected patients,is cost effective,and is an appropriate approach for UP-R PDAC.Nevertheless,the risk for disease progression during upfront medical therapy,requires appropriate patient identification and close monitoring,and emphasizes the need for further discovery of more effective chemotherapeutics,useful biomarkers or molecular profiles,and additional prospective comparative studies.展开更多
BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a serious disease with a poor prognosis.Only a minority of patients undergo surgery due to the advanced stage of the disease,and patients with early-stage disease,wh...BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a serious disease with a poor prognosis.Only a minority of patients undergo surgery due to the advanced stage of the disease,and patients with early-stage disease,who are expected to have a better prognosis,often experience recurrence.Thus,it is important to identify the risk factors for early recurrence and to develop an adequate treatment plan.AIM To evaluate the predictive factors associated with the early recurrence of earlystage PDAC.METHODS This study enrolled 407 patients with stage I PDAC undergoing upfront surgical resection between January 2000 and April 2016.Early recurrence was defined as a diagnosis of recurrence within 6 mo of surgery.The optimal cutoff values were determined by receiver operating characteristic(ROC)analyses.Univariate and multivariate analyses were performed to identify the risk factors for early recurrence.RESULTS Of the 407 patients,98 patients(24.1%)experienced early disease recurrence:26(26.5%)local and 72(73.5%)distant sites.In total,253(62.2%)patients received adjuvant chemotherapy.On ROC curve analysis,the optimal cutoff values for early recurrence were 70 U/mL and 2.85 cm for carbohydrate antigen 19-9(CA 19-9)levels and tumor size,respectively.Of the 181 patients with CA 19-9 level>70 U/mL,59(32.6%)had early recurrence,compared to 39(17.4%)of 226 patients with CA 19-9 level≤70 U/mL(P<0.001).Multivariate analysis revealed that CA 19-9 level>70 U/mL(P=0.006),tumor size>2.85 cm(P=0.004),poor differentiation(P=0.008),and non-adjuvant chemotherapy(P=0.025)were significant risk factors for early recurrence in early-stage PDAC.CONCLUSION Elevated CA 19-9 level(cutoff value>70 U/mL)can be a reliable predictive factor for early recurrence in early-stage PDAC.As adjuvant chemotherapy can prevent early recurrence,it should be recommended for patients susceptible to early recurrence.展开更多
Background: Patients with endometrial cancer are mostly diagnosed at an early stage. But unfortunately 10% to 15% of endometrial cancer patients will present with advanced-stage disease, and hence poorer prognosis. Wh...Background: Patients with endometrial cancer are mostly diagnosed at an early stage. But unfortunately 10% to 15% of endometrial cancer patients will present with advanced-stage disease, and hence poorer prognosis. When disease is primarily intraperitoneal, cytoreduction to <2 cm has also been correlated with better survival, with the maximum benefit in patients who can be reduced to no visible disease remaining. Aim: Of the work is to detect the survival rate benefits of primary surgery in patients with advanced endometrial cancer at gynecologic oncology unit in El Shatby Maternity University Hospital. Methods and Materials: Retrospective study was conducted on 102 patients diagnosed to have advanced endometrial cancer FIGO (stage III/IV) in a duration of 4 years between 2016 and 2020 and had undergone cytoreductive surgery. The patients were further subdivided into two groups: group 1 who underwent optimal cytoreduction with residual disease less than or equal 1 cm visible lesion, and group 2 who had residual disease more than 1 cm visible lesion and they were followed to check the survival benefits. Results: The mean of disease free survival in group: 1) patients was 2 years which was significantly longer than those in group;2) those who had residual disease > 1 cm, p < 0.001. Also cases with type I endometrial cancer had significantly longer (DFS) than those diagnosed to have type II endometrial cancer, p = 0.046. Conclusion: Primary complete cytoreductive (upfront) surgery when possible has a favorable impact on overall survival in patients with advanced endometrial cancer.展开更多
Pancreatic ductal adenocarcinoma(PDAC),which is notorious for its aggressiveness and poor prognosis,remains an area of great unmet medical need,with a 5-year survival rate of 10%-the lowest of all solid tumours.At dia...Pancreatic ductal adenocarcinoma(PDAC),which is notorious for its aggressiveness and poor prognosis,remains an area of great unmet medical need,with a 5-year survival rate of 10%-the lowest of all solid tumours.At diagnosis,only 20%of patients have resectable pancreatic cancer(RPC)or borderline RPC(BRPC)disease,while 80%of patients have unresectable tumours that are locally advanced pancreatic cancer(LAPC)or have distant metastases.Nearly 60%of patients who undergo upfront surgery for RPC are unable to receive adequate adjuvant chemotherapy(CHT)because of postoperative complications and early cancer recurrence.An important paradigm shift to achieve better outcomes has been the sequence of therapy,with neoadjuvant CHT preceding surgery.Three surgical stages have emerged for the preoperative assessment of nonmetastatic pancreatic cancers:RPC,BRPC,and LAPC.The main goal of neoadjuvant treatment(NAT)is to improve postoperative outcomes through enhanced selection of candidates for curative-intent surgery by identifying patients with aggressive or metastatic disease during initial CHT,reducing tumour volume before surgery to improve the rate of margin-negative resection(R0 resection,a microscopic margin-negative resection),reducing the rate of positive lymph node occurrence at surgery,providing early treatment of occult micrometastatic disease,and assessing tumour chemosensitivity and tolerance to treatment as potential surgical criteria.In this editorial,we summarize evidence concerning NAT of PDAC,providing insights into future practice and study design.Future research is needed to establish predictive biomarkers,measures of therapeutic response,and multidisciplinary stra tegies to improve patient-centered outcomes.展开更多
This study examines an incentive of the credit rating agency(CRA)to exert effort to observe projects’signals and strategically disclose ratings when the upfront fee and performance-based fee scheme are imposed.Under ...This study examines an incentive of the credit rating agency(CRA)to exert effort to observe projects’signals and strategically disclose ratings when the upfront fee and performance-based fee scheme are imposed.Under the upfront fee scheme,the CRA obtains an upfront fee in exchange for its services but gains a performance-based fee only if its ratings accurately foresee the rated project’s outcome.In the setting,an issuer solicits a rating from the CRA,whose conduct of inflating and deflating ratings is considered.In addition,the CRA can endogenously exert effort to observe a project’s signal,which specifies the signal accuracy and how much operating costs the CRA incurs.After receiving the observed signal,the CRA can strategically decide to announce a rating corresponding to or contradicting the observed signal.The findings reveal that the performance-based fee scheme incentivizes the CRA to exert greater effort and truthfully disclose a more accurate rating.展开更多
文摘Pancreatic ductal adenocarcinoma(PDAC)is an aggressive cancer with poor survival.Local control through surgical resection paired with radiotherapy and chemotherapy comprise the primary tenets of treatment.Debate exists regarding the timing of treatment and ordering of systemic therapy and resection in the management of early stage disease.The goal of this study was to review the literature and describe the contemporary evidence basis for the role of neoadjuvant therapy(NAT)in the setting of upfront resectable(UP-R)PDAC.Five databases were searched in parallel to identify relevant original articles investigating neoadjuvant therapy where at least 1 study arm contained UP-R PDAC;studies with only borderline resectable or locally advanced disease were excluded.Due to the diversity in NAT regimens and study design between trials,qualitative analyses were performed to investigate patient selection,impact on perioperative and survival outcomes,safety,and cost effectiveness.Thirty-five studies met inclusion criteria,of which 24 unique trials are discussed here in detail.These studies included those trials using single agents as well as more recent trials comparing modern multiagent therapies,and several large database analyses.Overall the data suggest that NAT is safe,may confer survival benefit for appropriately selected patients,is cost effective,and is an appropriate approach for UP-R PDAC.Nevertheless,the risk for disease progression during upfront medical therapy,requires appropriate patient identification and close monitoring,and emphasizes the need for further discovery of more effective chemotherapeutics,useful biomarkers or molecular profiles,and additional prospective comparative studies.
文摘BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a serious disease with a poor prognosis.Only a minority of patients undergo surgery due to the advanced stage of the disease,and patients with early-stage disease,who are expected to have a better prognosis,often experience recurrence.Thus,it is important to identify the risk factors for early recurrence and to develop an adequate treatment plan.AIM To evaluate the predictive factors associated with the early recurrence of earlystage PDAC.METHODS This study enrolled 407 patients with stage I PDAC undergoing upfront surgical resection between January 2000 and April 2016.Early recurrence was defined as a diagnosis of recurrence within 6 mo of surgery.The optimal cutoff values were determined by receiver operating characteristic(ROC)analyses.Univariate and multivariate analyses were performed to identify the risk factors for early recurrence.RESULTS Of the 407 patients,98 patients(24.1%)experienced early disease recurrence:26(26.5%)local and 72(73.5%)distant sites.In total,253(62.2%)patients received adjuvant chemotherapy.On ROC curve analysis,the optimal cutoff values for early recurrence were 70 U/mL and 2.85 cm for carbohydrate antigen 19-9(CA 19-9)levels and tumor size,respectively.Of the 181 patients with CA 19-9 level>70 U/mL,59(32.6%)had early recurrence,compared to 39(17.4%)of 226 patients with CA 19-9 level≤70 U/mL(P<0.001).Multivariate analysis revealed that CA 19-9 level>70 U/mL(P=0.006),tumor size>2.85 cm(P=0.004),poor differentiation(P=0.008),and non-adjuvant chemotherapy(P=0.025)were significant risk factors for early recurrence in early-stage PDAC.CONCLUSION Elevated CA 19-9 level(cutoff value>70 U/mL)can be a reliable predictive factor for early recurrence in early-stage PDAC.As adjuvant chemotherapy can prevent early recurrence,it should be recommended for patients susceptible to early recurrence.
文摘Background: Patients with endometrial cancer are mostly diagnosed at an early stage. But unfortunately 10% to 15% of endometrial cancer patients will present with advanced-stage disease, and hence poorer prognosis. When disease is primarily intraperitoneal, cytoreduction to <2 cm has also been correlated with better survival, with the maximum benefit in patients who can be reduced to no visible disease remaining. Aim: Of the work is to detect the survival rate benefits of primary surgery in patients with advanced endometrial cancer at gynecologic oncology unit in El Shatby Maternity University Hospital. Methods and Materials: Retrospective study was conducted on 102 patients diagnosed to have advanced endometrial cancer FIGO (stage III/IV) in a duration of 4 years between 2016 and 2020 and had undergone cytoreductive surgery. The patients were further subdivided into two groups: group 1 who underwent optimal cytoreduction with residual disease less than or equal 1 cm visible lesion, and group 2 who had residual disease more than 1 cm visible lesion and they were followed to check the survival benefits. Results: The mean of disease free survival in group: 1) patients was 2 years which was significantly longer than those in group;2) those who had residual disease > 1 cm, p < 0.001. Also cases with type I endometrial cancer had significantly longer (DFS) than those diagnosed to have type II endometrial cancer, p = 0.046. Conclusion: Primary complete cytoreductive (upfront) surgery when possible has a favorable impact on overall survival in patients with advanced endometrial cancer.
文摘Pancreatic ductal adenocarcinoma(PDAC),which is notorious for its aggressiveness and poor prognosis,remains an area of great unmet medical need,with a 5-year survival rate of 10%-the lowest of all solid tumours.At diagnosis,only 20%of patients have resectable pancreatic cancer(RPC)or borderline RPC(BRPC)disease,while 80%of patients have unresectable tumours that are locally advanced pancreatic cancer(LAPC)or have distant metastases.Nearly 60%of patients who undergo upfront surgery for RPC are unable to receive adequate adjuvant chemotherapy(CHT)because of postoperative complications and early cancer recurrence.An important paradigm shift to achieve better outcomes has been the sequence of therapy,with neoadjuvant CHT preceding surgery.Three surgical stages have emerged for the preoperative assessment of nonmetastatic pancreatic cancers:RPC,BRPC,and LAPC.The main goal of neoadjuvant treatment(NAT)is to improve postoperative outcomes through enhanced selection of candidates for curative-intent surgery by identifying patients with aggressive or metastatic disease during initial CHT,reducing tumour volume before surgery to improve the rate of margin-negative resection(R0 resection,a microscopic margin-negative resection),reducing the rate of positive lymph node occurrence at surgery,providing early treatment of occult micrometastatic disease,and assessing tumour chemosensitivity and tolerance to treatment as potential surgical criteria.In this editorial,we summarize evidence concerning NAT of PDAC,providing insights into future practice and study design.Future research is needed to establish predictive biomarkers,measures of therapeutic response,and multidisciplinary stra tegies to improve patient-centered outcomes.
文摘This study examines an incentive of the credit rating agency(CRA)to exert effort to observe projects’signals and strategically disclose ratings when the upfront fee and performance-based fee scheme are imposed.Under the upfront fee scheme,the CRA obtains an upfront fee in exchange for its services but gains a performance-based fee only if its ratings accurately foresee the rated project’s outcome.In the setting,an issuer solicits a rating from the CRA,whose conduct of inflating and deflating ratings is considered.In addition,the CRA can endogenously exert effort to observe a project’s signal,which specifies the signal accuracy and how much operating costs the CRA incurs.After receiving the observed signal,the CRA can strategically decide to announce a rating corresponding to or contradicting the observed signal.The findings reveal that the performance-based fee scheme incentivizes the CRA to exert greater effort and truthfully disclose a more accurate rating.
