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Sa1867 Endoscopically-Delivered Neoadjuvant Photodynamic Therapy and Radiofrequency Ablation in Patients With Unresectable Cholangiocarcinoma Awaiting Liver Transplantation: A Pilot Experience
Sa1866
Table 1. Clinical characteristics of patients with confirmed or suspected CCA who underwent ERCP-directed PDT and/or RFA for locoregional control prior to LT.
Background Whilst AFP is secreted by some HCCs, it is not recommended as a diagnostic test in current guidelines owing to its low sensitivity. AFP is felt to provide prognostic information. The cut off value for this purpose has been arbitrarily based on a previous "diagnostic cut off" of 400ng/mL. We aim to determine the optimal cut off value for AFP that could achieve prognostic utility. Method Consecutive HCC patients (n=469) with a valid AFP measurement diagnosed during 2005 to 2014 in the Liverpool region, UK were included. Area under the receiver operating characteristic curve (ROC) was constructed to define optimum cut off values to achieve high sensitivities by bootstrapping and likelihood ratio (LR) methods. 1000 iterations were involved in determining the value at fixed sensitivities and specificities with the best predictor used to assess overall survival (OS) for those above and below the cut off value. This process was repeated for LR. The cut off value with the optimum diagnostic accuracy was used to assess OS for recruited subjects; relative to treatment type [supportive care (BSC), systemic therapy, loco-regional therapy and curative therapy] using Kaplan Meier survival statistic. The performance of the new cut off was assessed by comparison of ROC of Hepatoma arterial-embolisation prognostic (HAP) score (using AFP>400ng/mL) versus the modified score (using new cut off) in patients treated with transarterial chemoembolization (TACE). Results The serum AFP cut off value by LR (>43ng/mL) predicted prognosis better (sensitivity 48% / specificity 78%) than the cut off of >400ng/mL (sensitivity 28% / specificity 89%). The median survival was 28 months (95% confidence interval: 21-33) in patients with AFP <43ng/mL compared to 7 months (95% CI: 5-8) with AFP >43ng/mL. This lower AFP cut off accurately predicted OS for HCC patients receiving loco-regional therapy (34 months vs. 14 months, p<0.0001), curative therapy (43 months vs. 15 months, p=0.001) and those on best supportive care (4 months vs. 2 months, p=0.04). ROC of HAP score-AFP>43 was higher than HAP score-AFP>400 (0.7 vs 0.6, p=0.17). Conclusion AFP value of 43 ng/mL was defined as a cut off to determine prognosis in this group of patients overall and specifically those receiving potentially curative or loco-regional therapy. These results require validation in a separate cohort of patients to determine whether the cut off of 43 can be used to influence decision making in clinical practice.
Abbreviations: CCA - cholangiocarcinoma, HD - hepatic duct, LT - liver transplantation, PSC - primary sclerosing cholangitis Table 2. Biliary PDT/RFA treatments, pre- and post- PDT/RFA outcomes, and post-LT staging and outcomes
Sa1867 Endoscopically-Delivered Neoadjuvant Photodynamic Therapy and Radiofrequency Ablation in Patients With Unresectable Cholangiocarcinoma Awaiting Liver Transplantation: A Pilot Experience Dushant S. Uppal, Patrick G. Northup, Curtis K. Argo, Shawn J. Pelletier, Daniel G. Maluf, Osama E. Rahma, Paul W. Read, Dawn G. Cox, Daniel S. Strand, Andrew Y. Wang Introduction: Cholangiocarcinoma (CCA) is a malignancy of biliary epithelium associated with high morbidity and mortality. Neoadjuvant chemoradiation followed by liver transplantation (LT) can offer curative therapy for selected patients with unresectable CCA. In some centers endoscopically-delivered brachytherapy is used in conjunction with chemoradiotherapy prior to LT. ERCP-directed photodynamic therapy (PDT) has been shown to offer a survival advantage in patients with unresectable CCA. ERCP-directed radiofrequency ablation (RFA) is another modality that offers the potential for local tumor control in patients with unresectable CCA. Aim: Our aim was to describe outcomes of patients with unresectable CCA who underwent ERCP-directed ablative therapy with PDT and/or RFA for locoregional tumor control as part of an institutional neoadjuvant treatment protocol prior to LT. Methods: Patients with suspicion of or pathologically-proven CCA, who were deemed unresectable, met criteria for protocol LT, and underwent neoadjuvant chemoradiation followed by ERCPdirected ablative therapy, were retrospectively reviewed (Table 1). All patients underwent at least one round of treatment with PDT, RFA, or both ablative therapies and subsequently underwent LT. Results: 7 patients (median age: 46 years, 4 males) with suspected or pathologically-diagnosed CCA who met criteria for LT and received ERCP-directed PDT (n= 6) or RFA (n=2) were included. One patient underwent both PDT and RFA prior to LT. Median cancer-free follow-up was 32.9 months (range: 6.3 - 103.0 months) with an overall cancer-free survival rate of 57% (4 out of 7 patients) (Table 2). One patient died with recurrent metastatic CCA, while another patient with recurrent metastatic disease is still living and undergoing palliative chemotherapy. One patient, who received a dual liverkidney transplant, died due to renal complications but had no evidence of recurrent biliary dysplasia or CCA. All patients experienced chemotherapy and/or external beam radiation dose delays. Complications of ERCP-directed ablative therapy included cholangitis in 2 patients following PDT, hemobilia in one patient following RFA, and mild photosensitivity in two patients who received PDT. There was no PDT- or RFA-associated mortality. Conclusions: ERCP-directed PDT and/or RFA appear to be safe and potentially efficacious modalities for providing local tumor control as part of a larger neoadjuvant protocol prior to LT, in this small group of patients with unresectable CCA. Multicenter, prospective studies to further evaluate the safety and effectiveness of ERCP-directed PDT and/or RFA in this patient population are needed.
Abbreviations: PDT - photodynamic therapy, RFA - radiofrequency ablation, RHD - right hepatic duct, LTH - left hepatic duct, CHD - common hepatic duct, PTC - percutaneous transhepatic cholaniography drain, LT - liver transplantation, AdenoCA - adenocarcinoma Sa1868 Metformin Use Reduces Intrahepatic Cholangiocarcinoma Risk in Patients With Diabetes but Does Not Improve Survival of Cholangiocarcinoma Zhen Yang, Xiaodan Zhang, Lewis R. Roberts, Roongruedee Chaiteerakij Background: Epidemiologic studies have shown a protective effect of metformin against cancer development. We previously reported that metformin use was associated with a 60% reduction in risk of intrahepatic cholangiocarcinoma (CCA) in persons with diabetes. Aim and Methods: Here, we determined whether metformin use improved survival of CCA patients by retrospective analysis of 250 diabetic patients newly diagnosed with CCA between January 2001 and December 2012 at Mayo Clinic, Rochester, Minnesota. Survival of diabetic CCA patients on metformin versus that of patients not taking metformin was calculated using the Kaplan-Meier method and compared using the Log Rank test. The hazard ratio (HR) and 95% confidence interval (CI) were calculated using Cox Proportional Hazards analysis. We also investigated predictors of survival in CCA patients with diabetes mellitus (DM). Results: Of the 250 patients (65% male; mean age 68 years), the median survival was 9.5 months with a median follow-up of 24.7 months. Eighty-five patients (34%) used metformin prior to CCA diagnosis and 36 remained on metformin after CCA diagnosis. The 36 patients on metformin did not have a median survival different from that of those not on metformin (9.47 vs. 9.50 months; HR [95%CI] 0.91 [0.67-1.22], p=0.52). A history of metformin use prior to CCA diagnosis also did not affect survival. The results were consistent when categorized by CCA subtypes (114 intrahepatic, 105 perihilar, and 31 distal). ECOG >0, CA19-9 ≥1000 U/mL, tumor size and extrahepatic metastasis were significantly associated with survival, with HRs (95% CI) of 1.7 (1.3-2.3), 2.1 (1.5-3.0), 1.1 (1.0-1.1), and 1.5 (1.0-2.1); p<0.001, <0.0001, <0.005 and <0.05, respectively). Age, smoking, obesity, primary sclerosing cholangitis, nonalcoholic steatohepatitis, viral hepatitis B or C infection, cirrhosis, vascular encasement, intrahepatic metastasis and lymph node metastasis were not associated with survival. Conclusions: In summary, although metformin may reduce cancer risk, we were not able to show a demonstrable effect of metformin on survival of diabetic patients
S-1029
AASLD Abstracts
AASLD Abstracts
Alpha-Fetoprotein (AFP) in Hepatocellular Carcinoma (HCC): Determination of Optimal Cut Off for Prognosis Prediction Nimzing G. Ladep, Omar Noorullah, Elizabeth Boland, Wern Yew Ding, Tim Cross, Cyril Sieberhagen, Richard Sturgess, Nick Stern
Table 1. Clinical characteristics of patients with confirmed or suspected CCA who underwent ERCP-directed PDT and/or RFA for locoregional control prior to LT.
Background Whilst AFP is secreted by some HCCs, it is not recommended as a diagnostic test in current guidelines owing to its low sensitivity. AFP is felt to provide prognostic information. The cut off value for this purpose has been arbitrarily based on a previous "diagnostic cut off" of 400ng/mL. We aim to determine the optimal cut off value for AFP that could achieve prognostic utility. Method Consecutive HCC patients (n=469) with a valid AFP measurement diagnosed during 2005 to 2014 in the Liverpool region, UK were included. Area under the receiver operating characteristic curve (ROC) was constructed to define optimum cut off values to achieve high sensitivities by bootstrapping and likelihood ratio (LR) methods. 1000 iterations were involved in determining the value at fixed sensitivities and specificities with the best predictor used to assess overall survival (OS) for those above and below the cut off value. This process was repeated for LR. The cut off value with the optimum diagnostic accuracy was used to assess OS for recruited subjects; relative to treatment type [supportive care (BSC), systemic therapy, loco-regional therapy and curative therapy] using Kaplan Meier survival statistic. The performance of the new cut off was assessed by comparison of ROC of Hepatoma arterial-embolisation prognostic (HAP) score (using AFP>400ng/mL) versus the modified score (using new cut off) in patients treated with transarterial chemoembolization (TACE). Results The serum AFP cut off value by LR (>43ng/mL) predicted prognosis better (sensitivity 48% / specificity 78%) than the cut off of >400ng/mL (sensitivity 28% / specificity 89%). The median survival was 28 months (95% confidence interval: 21-33) in patients with AFP <43ng/mL compared to 7 months (95% CI: 5-8) with AFP >43ng/mL. This lower AFP cut off accurately predicted OS for HCC patients receiving loco-regional therapy (34 months vs. 14 months, p<0.0001), curative therapy (43 months vs. 15 months, p=0.001) and those on best supportive care (4 months vs. 2 months, p=0.04). ROC of HAP score-AFP>43 was higher than HAP score-AFP>400 (0.7 vs 0.6, p=0.17). Conclusion AFP value of 43 ng/mL was defined as a cut off to determine prognosis in this group of patients overall and specifically those receiving potentially curative or loco-regional therapy. These results require validation in a separate cohort of patients to determine whether the cut off of 43 can be used to influence decision making in clinical practice.
Abbreviations: CCA - cholangiocarcinoma, HD - hepatic duct, LT - liver transplantation, PSC - primary sclerosing cholangitis Table 2. Biliary PDT/RFA treatments, pre- and post- PDT/RFA outcomes, and post-LT staging and outcomes
Sa1867 Endoscopically-Delivered Neoadjuvant Photodynamic Therapy and Radiofrequency Ablation in Patients With Unresectable Cholangiocarcinoma Awaiting Liver Transplantation: A Pilot Experience Dushant S. Uppal, Patrick G. Northup, Curtis K. Argo, Shawn J. Pelletier, Daniel G. Maluf, Osama E. Rahma, Paul W. Read, Dawn G. Cox, Daniel S. Strand, Andrew Y. Wang Introduction: Cholangiocarcinoma (CCA) is a malignancy of biliary epithelium associated with high morbidity and mortality. Neoadjuvant chemoradiation followed by liver transplantation (LT) can offer curative therapy for selected patients with unresectable CCA. In some centers endoscopically-delivered brachytherapy is used in conjunction with chemoradiotherapy prior to LT. ERCP-directed photodynamic therapy (PDT) has been shown to offer a survival advantage in patients with unresectable CCA. ERCP-directed radiofrequency ablation (RFA) is another modality that offers the potential for local tumor control in patients with unresectable CCA. Aim: Our aim was to describe outcomes of patients with unresectable CCA who underwent ERCP-directed ablative therapy with PDT and/or RFA for locoregional tumor control as part of an institutional neoadjuvant treatment protocol prior to LT. Methods: Patients with suspicion of or pathologically-proven CCA, who were deemed unresectable, met criteria for protocol LT, and underwent neoadjuvant chemoradiation followed by ERCPdirected ablative therapy, were retrospectively reviewed (Table 1). All patients underwent at least one round of treatment with PDT, RFA, or both ablative therapies and subsequently underwent LT. Results: 7 patients (median age: 46 years, 4 males) with suspected or pathologically-diagnosed CCA who met criteria for LT and received ERCP-directed PDT (n= 6) or RFA (n=2) were included. One patient underwent both PDT and RFA prior to LT. Median cancer-free follow-up was 32.9 months (range: 6.3 - 103.0 months) with an overall cancer-free survival rate of 57% (4 out of 7 patients) (Table 2). One patient died with recurrent metastatic CCA, while another patient with recurrent metastatic disease is still living and undergoing palliative chemotherapy. One patient, who received a dual liverkidney transplant, died due to renal complications but had no evidence of recurrent biliary dysplasia or CCA. All patients experienced chemotherapy and/or external beam radiation dose delays. Complications of ERCP-directed ablative therapy included cholangitis in 2 patients following PDT, hemobilia in one patient following RFA, and mild photosensitivity in two patients who received PDT. There was no PDT- or RFA-associated mortality. Conclusions: ERCP-directed PDT and/or RFA appear to be safe and potentially efficacious modalities for providing local tumor control as part of a larger neoadjuvant protocol prior to LT, in this small group of patients with unresectable CCA. Multicenter, prospective studies to further evaluate the safety and effectiveness of ERCP-directed PDT and/or RFA in this patient population are needed.
Abbreviations: PDT - photodynamic therapy, RFA - radiofrequency ablation, RHD - right hepatic duct, LTH - left hepatic duct, CHD - common hepatic duct, PTC - percutaneous transhepatic cholaniography drain, LT - liver transplantation, AdenoCA - adenocarcinoma Sa1868 Metformin Use Reduces Intrahepatic Cholangiocarcinoma Risk in Patients With Diabetes but Does Not Improve Survival of Cholangiocarcinoma Zhen Yang, Xiaodan Zhang, Lewis R. Roberts, Roongruedee Chaiteerakij Background: Epidemiologic studies have shown a protective effect of metformin against cancer development. We previously reported that metformin use was associated with a 60% reduction in risk of intrahepatic cholangiocarcinoma (CCA) in persons with diabetes. Aim and Methods: Here, we determined whether metformin use improved survival of CCA patients by retrospective analysis of 250 diabetic patients newly diagnosed with CCA between January 2001 and December 2012 at Mayo Clinic, Rochester, Minnesota. Survival of diabetic CCA patients on metformin versus that of patients not taking metformin was calculated using the Kaplan-Meier method and compared using the Log Rank test. The hazard ratio (HR) and 95% confidence interval (CI) were calculated using Cox Proportional Hazards analysis. We also investigated predictors of survival in CCA patients with diabetes mellitus (DM). Results: Of the 250 patients (65% male; mean age 68 years), the median survival was 9.5 months with a median follow-up of 24.7 months. Eighty-five patients (34%) used metformin prior to CCA diagnosis and 36 remained on metformin after CCA diagnosis. The 36 patients on metformin did not have a median survival different from that of those not on metformin (9.47 vs. 9.50 months; HR [95%CI] 0.91 [0.67-1.22], p=0.52). A history of metformin use prior to CCA diagnosis also did not affect survival. The results were consistent when categorized by CCA subtypes (114 intrahepatic, 105 perihilar, and 31 distal). ECOG >0, CA19-9 ≥1000 U/mL, tumor size and extrahepatic metastasis were significantly associated with survival, with HRs (95% CI) of 1.7 (1.3-2.3), 2.1 (1.5-3.0), 1.1 (1.0-1.1), and 1.5 (1.0-2.1); p<0.001, <0.0001, <0.005 and <0.05, respectively). Age, smoking, obesity, primary sclerosing cholangitis, nonalcoholic steatohepatitis, viral hepatitis B or C infection, cirrhosis, vascular encasement, intrahepatic metastasis and lymph node metastasis were not associated with survival. Conclusions: In summary, although metformin may reduce cancer risk, we were not able to show a demonstrable effect of metformin on survival of diabetic patients
S-1029
AASLD Abstracts
AASLD Abstracts
Alpha-Fetoprotein (AFP) in Hepatocellular Carcinoma (HCC): Determination of Optimal Cut Off for Prognosis Prediction Nimzing G. Ladep, Omar Noorullah, Elizabeth Boland, Wern Yew Ding, Tim Cross, Cyril Sieberhagen, Richard Sturgess, Nick Stern