- Email: [email protected]
Sa1864 Factors Influencing Surveillance for Hepatocellular Carcinoma in Patients With Liver Cirrhosis
the angiogenesis-independent antitumor effects of apatinib in EBDC. Methods: Three EBDC cell lines FRH, TFK-1and EGI were examined for basal expression of VEGF, VEGFR1, and VEGFR2 by western blotting (WB). The cells were treated with recombinant human VEGF (rhVEGF), and VEGFR phosphorylation was examined by WB, and cell proliferation was evaluated by BrdU incorpation assay. Cells were then treated with 0, 60, or 120 nM of apatinib for 24 hour, and were assayed for VEGFR signaling and cell proliferation. Finally, FRH cells were inoculated into nude mice for further evaluation for apatinib treatment efficacy in vivo. Results: All three EBDC cell lines expressed VEGF and phosphorylated (p) VEGF receptor 1 (pVEGFR1) and 2 (pVEGFR2). By protein fractionalization, we found that VEGFR1 and VEGFR2 were both present on membrane of these three cells. The rhVEGF promoted phosphorylation of VEGFR1 and VEGFR2 at 30 min (FRH and EGI) or 15 min after treatment. The rhVEGF increased cell proliferation (+16.8%, +13.4% and +20.5% for FRH, TFK and EGI respectively) after 24 hr of treatment, which was prevented by preincubation with VEGFR1 or VEGFR2 neutralizing antibody. Apatinib treatment inhibited the phosphorylation of VEGFR1 and VEGFR2 and cell proliferation in all three cell lines in a dose-dependent fashion. Finally, the apatinib-treated FRH xenograft tumors displayed a substantial delayed growth after one week-treatment. The averages of final tumor volumes were significantly different between the vehicle and apatinib-treated groups after 4 weeks of treatment (P<0.05). Conclusion: VEGF directly activated VEGF receptors on EBDC cells and promoted cancer cell proliferation; apatinib inhibited VEGF signaling and suppressed cell proliferation in vitro and delayed xenograft tumor growth in vivo. These findings support a potential role for apatinib in the treatment of extrahepatic bile duct cancers.
control of HCC with comparable post LT complication indicating that randomized controlled trials in this patient population are warranted. Table 1
Post-Ablation Safety Margin of Radiofrequency Ablation of Hepatocellular Carcinoma: Precise Assessment With a Three Dimensionalreconstruction Technique Yanyan Zhang, Zhengpeng Peng, Weifeng Liu, Ming Kuang
Sa1863 Incidence and Risk Factors for Hepatocellular Cancer Among Patients With Chronic Hepatitis B in a Large Regional U.S. Integrated Health Care System Rasham Mittal, Bechien U. Wu
Purpose: To analyze the precise ablative margin produced by radiofrequency ablation (RFA) by the fusing three-dimensional (3-D) images of tumor zones and ablated zones with a reconstruction technique. Materials and Methods: From March 2011 to May 2013, 134 patients (21 female and 113 male) with 159 primary or recurrent hepatocellular carcinoma tumors less than 5 cm received RFA were enrolled. All tumors were treated by RFA with curative intention. 64-row Contrast-Enhanced Computer Tomography (CT) scan was performed before and 1 month after treatment. CT data were processed with 3-D reconstruction software. Three dimensional tumor and ablated zones were reconstructed and fused to show the ablation margins for accurate measurement retrospectively. Results: Follow-up was conducted on all patients for a median of 16 months (range, 2 to 44 months). The reconstructed ablated zone covers the original tumor zone completely each tumor, but the minimal ablative margin (AM) varied in all directions. The minimal AM ranged from 1 to 9.3 mm (mean, 4.3 ± 1.8 mm) on the fusion image. A 5-mm minimal AM was achieved in only 36.5% (58/159) tumors. During the follow-up, local tumor progression (LTP) was observed in 19 tumors, with cumulative LTP rates at 1, 2, and 3 years of 6.7%, 12.3%, and 28.0%, respectively. In the group analysis, an minimal AM of 3.3 ± 1.6 mm (ranged, 1-7.1mm) was found at where LTP happened, while the minimal AM of those without LTP was 4.5 ± 1.8 mm (range, 1.3 to 9.3 mm) (P=0.023). Multivariate analysis identified that only insufficient minimal AM was independent risk factor for local tumor progression after RFA (P = 0.044). Conclusion: Post-ablation evaluation of ablative margin with 3-D technique provides more information for local response of RFA. To achieve the best local efficacy, a post-ablation safety margin of at least 5 mm is necessary.
Background Worldwide chronic hepatitis B (CHB) virus infection is a leading cause for hepatocellular cancer (HCC). In the United States, an estimated 1.4 million individuals have CHB. The epidemiology of HCC in the CHB population is largely unknown in the United States. Study Aims 1. To measure the incidence of HCC among patients with CHB in a diverse regional U.S. population 2. Determine risk factors for the development of HCC in this population. Methods We performed a retrospective cohort study (2006-2013) from an integrated health care system in Southern California. All CHB (age≥ 18 years) patients were identified using ICD codes. CHB status was further confirmed through reactive hepatitis B surface antigen (HBsAg) neutralization confirmatory antibody assay. HCC patients were identified using ICD code and cross referenced through a prospective internal cancer registry. Patients were censored based upon loss of membership, date of last clinic visit, or death due to causes other than HCC. Incidence was calculated as HCC cases per 100,000 person years follow up. Cox proportional hazard regression analysis was performed for risk factors including age, gender, race (Asian versus non-Asian), reactive hepatitis Be antigen (HBeAg) at time of HCC diagnosis, obesity (BMI≥30), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection. Results The study cohort included 9811 confirmed CHB patients [median age at CHB diagnosis was 46 years, IQR 36,55 years; 5351 (54.5%) male; 8372 (85.3%) Asians and 1386 (14.1%) obese]. Among CHB patients, 1644 (16.7%) developed liver cirrhosis; 443 (4.52%) and 433 (4.4%) were co-infected with HCV and HIV respectively. A total of 243 cases of HCC were detected during 44,367 years of follow up (incidence 547 per 100,000 person-years). In regression analysis, age (HR 1.05; 95% CI, 1.04-1.06; P<0.0001) reactive HBeAg (HR 1.86; 95% CI, 1.21-2.85; P=0.004) HCV coinfection (HR 1.53; 95% CI, 1.07-2.21; P=0.019) and cirrhosis (HR 5.69; 95% CI, 4.337.47; P<0.0001) were independently associated with increased risk of HCC. Asian race, HIV co-infection and obesity were not associated with increased risk of HCC. Female gender was associated with decreased risk (HR 0.32; 95% CI, 0.23-0.44; P<.0001) of HCC. Conclusion In this large U.S. cohort of CHB patients, we identified a high incidence of HCC. Established risk factors found in Asian population such as age, reactive HBeAg status, male gender, liver cirrhosis and HCV co-infection were also associated with increased risk of HCC in this U.S. cohort. Interestingly, co-infection with HIV was not associated with increased risk of HCC, potentially due to active anti-retroviral therapy.
Sa1862 A Retrospective Analysis of Pre Liver Transplant Use of Sorafenib Sushrut Trakroo, sirish sanaka, Randhir Jesudoss, Abdullah M. Al-Osaimi, Gary S. Cohen, Antonio Di Carlo, Mohammed Eyad Yaseen alsabbagh, Kamran Qureshi BACKGROUND AND AIM With long wait times, managing patients with hepatocellular carcinoma (HCC) on the liver transplant (LT) waitlist is challenging and is constantly evolving. The potential of multi-kinase inhibitor Sorafenib (SB), a cytostatic agent, in benefitting this patient population has been tempered by studies that have shown increased rates of post LT complications. In our study we compared patient survival, tumor recurrence and post LT complications in patients who received SB pre-LT with those who did not. METHODS We identified 37 consecutive patients who successfully underwent deceased donor LT for HCC at our center. 12 patients received SB prior to LT. We did a retrospective review comparing post LT outcomes between patients who received SB (group A) and those who did not (group B). RESULTS Eight of 12 patients received SB up to the day of LT. All received loco-regional therapy as per institutional protocol. There were no significant differences in demographic profile and etiologies between the two groups. Group A Patients had longer wait list time (p= 0.009). MELD at transplant was higher in group B although not statistically significant (p= 0.09). Nine (75%) in group A and 24(96%) in group B had viable tumor on explant. The total viable tumor burden on explant was similar although a higher number in group B had satellite lesions and multifocal HCC (16% in group A vs. 36% in Group B). Also, 83% in group A had T1 lesion or lower whereas 68% in group B had T2 lesions or higher. Four (33%) in group A and 7 (29%) in group B developed anastomotic strictures. All were managed endoscopically except one in group B who required surgical reconstruction. The 1, 3 and 5 year survival in Group A were 100% in patients who reached those timelines. The 1, 3 and 5 year survival in and Group B were 96%, 88% and 75% in patients who reached those timelines. No patients in group A had HCC recurrence at 5 years whereas 2/ 8 group B patients who reached 5 years of follow-up died of metastatic HCC. None of the patients in either group had surgical wound related complications. CONCLUSION In patients receiving SB pre-LT, we found that a greater number of SB naïve patients had multifocal HCC and higher tumor stage on explant pathology when compared to patients who received SB pre-LT. Also, a higher percentage of patients in group A had 1, 3 and 5 year survivals and a lower 5 year HCC recurrence compared to group B. There was no difference in the rates of post-LT complications between the two groups. Our study shows a better histologic
Sa1864 Factors Influencing Surveillance for Hepatocellular Carcinoma in Patients With Liver Cirrhosis Hager F. Ahmed Mohammed, Nasra H. Giama, Lewis R. Roberts Background: Hepatocellular carcinoma (HCC) is the sixth commonest cancer and the second most common cause of cancer related mortality. Liver cirrhosis is the major risk factor for HCC. We assessed the surveillance rate for HCC among Minnesota residents with cirrhosis seen at Mayo Clinic Rochester between 1/1/2007 and 12/31/2009. Methods: Using the medical record, we identified Minnesota residents with cirrhosis confirmed by histology, portal hypertension, imaging characteristics, or platelet count <120 x 10^9L in the setting of chronic liver disease between 1/1/2007 and 12/31/2009. Demographics, vital status, last follow-up, and abdominal images performed at Mayo Clinic (ultrasound, CT, or MRI) were abstracted. Images performed outside Mayo Clinic were not included due to the infeasibility of obtaining outside imaging data. Surveillance was calculated from 3 months after the date of cirrhosis diagnosis to the date of death, HCC diagnosis, liver transplant, or last followup date before 12/31/2013. The surveillance rate was calculated by dividing the actual surveillance frequency by the expected surveillance frequency. We classified surveillance rates into 6 levels: 0%, 1-24%, 25-49%, 50-74%, 75-99%, and 100%. Results: Between 1/ 1/2007 and 12/31/2009, 770 Minnesota residents with cirrhosis were seen at Mayo Clinic. 90 patients had insufficient data for analysis. The mean age of the 680 evaluable patients was 58.8 years (SD 12.7), and 58% were men. 100% surveillance was provided to 7.4% of the patients, 75-99% to 7%, 50-74% to 18.8%, 25-49% to 17.2%, and 1-24% to 17.7%.
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33% of the patients received at least annual surveillance at Mayo Clinic. 31.9% did not receive any imaging at Mayo Clinic. In an attempt to assess the proportion of patients who may have had additional outside imaging studies, we specifically reviewed the records of 25 patients who received 50-74% surveillance. For 23 (88%), the gastroenterologist specifically recommended semiannual screening. Conclusion: At a major tertiary center, HCC surveillance was recommended for almost all patients, however, patients frequently did not have surveillance performed at the referral center, but were recommended by specialists to have interval HCC surveillance coordinated by their primary physician. It will be of interest to determine whether the care transition between specialists and primary care physicians is one of the factors underlying the lack of adherence to recommended surveillance of patients with liver cirrhosis.
Table 1. Baseline Characteristics and Staging
Sa1865 Efficacy and Predictors of Survival Using Yttrium 90 (y90) Therasphere Treatment for Hepatocellular Carcinoma Maheen Sheikh, Richard Gerkin, Anil B. Seetharam, David Wood Introduction: Locoregional therapies for Hepatocellular Carcinoma (HCC) are increasingly employed in downstaging protocols for those qualifying for liver transplant (LT) and as "destination" therapy in those with small lesions who are poor surgical candidates. Targeted radioembolization with yttrium-90 (y90) intra-arterially provides tumoricidal doses of radiation with minimal systemic toxicity. Further studies are needed to characterize outcomes with y90 therapy and identify predictors of response. Aims: To evaluate toxicity, response rate, time to progression (TTP) and survival in patients treated for HCC with y90. Methods: A retrospective case series identifying consecutive patients with a diagnosis of HCC of any size or number of lesions treated with y90 between August, 2006 and December, 2009 and pre-treatment total bilirubin <3.0 mg/dL. Baseline clinical and tumor characteristics were tabulated including Child's-Pugh Class, Barcelona Clinic Liver Cancer (BCLC) Stage and Tumor, Node, Metastases (T,N,M) stage [Table 1]. Toxicities were recorded using the Common Terminology Criteria version 4.0. Response rate and TTP were determined using standard World Health Organization (WHO) and European Association for the Study of the Liver (EASL) guidelines. Survival by stage was assessed. Univariate and multivariate analyses were performed to identify predictors of survival. Results: 116 patients underwent 169 y90 treatment sessions (median 118 Gy/treatment) over a median follow up of 13.2 months. There were no gastrointestinal ulcerations and 1 patient developed radiation pneumonitis at 149 days. 30 day mortality was 0.8%. Response rates were 43% (median time to response: 4.2 months) and 58% (median time to response: 3.6 months) based on WHO and EASL criteria, respectively. Overall TTP was 14 months (95% confidence interval, 8.2-19.8) with no significant difference when stratified by Child's Pugh Stage (p=0.952). Median survival was 22.5 months (95% CI 18.7-26.3). When survival was stratified by Child-Pugh stage, there was a significant difference between stages (p = 0.029), with significance representing Stage A compared with C. For Child-Pugh stages A and B, median survival was 746 days compared with 579 days, respectively (p = 0.095). Baseline performance status, unilobar tumor involvement, and EASL/WHO response predicted survival (p<0.05) [Table 2]. Conclusions: Y90 embolization is an effective adjunct or destination therapy in patients with Child's Class A cirrhosis and HCC, particularly those with good baseline functional status and unilobar tumor involvement. Further studies are needed to identify demographic and tumor characteristics that may predict favorable response to y90 in those with more advanced liver dysfunction.
AASLD Abstracts
Univariate and Multivariate Predictors of Response to Y90 Therapy
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control of HCC with comparable post LT complication indicating that randomized controlled trials in this patient population are warranted. Table 1
Post-Ablation Safety Margin of Radiofrequency Ablation of Hepatocellular Carcinoma: Precise Assessment With a Three Dimensionalreconstruction Technique Yanyan Zhang, Zhengpeng Peng, Weifeng Liu, Ming Kuang
Sa1863 Incidence and Risk Factors for Hepatocellular Cancer Among Patients With Chronic Hepatitis B in a Large Regional U.S. Integrated Health Care System Rasham Mittal, Bechien U. Wu
Purpose: To analyze the precise ablative margin produced by radiofrequency ablation (RFA) by the fusing three-dimensional (3-D) images of tumor zones and ablated zones with a reconstruction technique. Materials and Methods: From March 2011 to May 2013, 134 patients (21 female and 113 male) with 159 primary or recurrent hepatocellular carcinoma tumors less than 5 cm received RFA were enrolled. All tumors were treated by RFA with curative intention. 64-row Contrast-Enhanced Computer Tomography (CT) scan was performed before and 1 month after treatment. CT data were processed with 3-D reconstruction software. Three dimensional tumor and ablated zones were reconstructed and fused to show the ablation margins for accurate measurement retrospectively. Results: Follow-up was conducted on all patients for a median of 16 months (range, 2 to 44 months). The reconstructed ablated zone covers the original tumor zone completely each tumor, but the minimal ablative margin (AM) varied in all directions. The minimal AM ranged from 1 to 9.3 mm (mean, 4.3 ± 1.8 mm) on the fusion image. A 5-mm minimal AM was achieved in only 36.5% (58/159) tumors. During the follow-up, local tumor progression (LTP) was observed in 19 tumors, with cumulative LTP rates at 1, 2, and 3 years of 6.7%, 12.3%, and 28.0%, respectively. In the group analysis, an minimal AM of 3.3 ± 1.6 mm (ranged, 1-7.1mm) was found at where LTP happened, while the minimal AM of those without LTP was 4.5 ± 1.8 mm (range, 1.3 to 9.3 mm) (P=0.023). Multivariate analysis identified that only insufficient minimal AM was independent risk factor for local tumor progression after RFA (P = 0.044). Conclusion: Post-ablation evaluation of ablative margin with 3-D technique provides more information for local response of RFA. To achieve the best local efficacy, a post-ablation safety margin of at least 5 mm is necessary.
Background Worldwide chronic hepatitis B (CHB) virus infection is a leading cause for hepatocellular cancer (HCC). In the United States, an estimated 1.4 million individuals have CHB. The epidemiology of HCC in the CHB population is largely unknown in the United States. Study Aims 1. To measure the incidence of HCC among patients with CHB in a diverse regional U.S. population 2. Determine risk factors for the development of HCC in this population. Methods We performed a retrospective cohort study (2006-2013) from an integrated health care system in Southern California. All CHB (age≥ 18 years) patients were identified using ICD codes. CHB status was further confirmed through reactive hepatitis B surface antigen (HBsAg) neutralization confirmatory antibody assay. HCC patients were identified using ICD code and cross referenced through a prospective internal cancer registry. Patients were censored based upon loss of membership, date of last clinic visit, or death due to causes other than HCC. Incidence was calculated as HCC cases per 100,000 person years follow up. Cox proportional hazard regression analysis was performed for risk factors including age, gender, race (Asian versus non-Asian), reactive hepatitis Be antigen (HBeAg) at time of HCC diagnosis, obesity (BMI≥30), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection. Results The study cohort included 9811 confirmed CHB patients [median age at CHB diagnosis was 46 years, IQR 36,55 years; 5351 (54.5%) male; 8372 (85.3%) Asians and 1386 (14.1%) obese]. Among CHB patients, 1644 (16.7%) developed liver cirrhosis; 443 (4.52%) and 433 (4.4%) were co-infected with HCV and HIV respectively. A total of 243 cases of HCC were detected during 44,367 years of follow up (incidence 547 per 100,000 person-years). In regression analysis, age (HR 1.05; 95% CI, 1.04-1.06; P<0.0001) reactive HBeAg (HR 1.86; 95% CI, 1.21-2.85; P=0.004) HCV coinfection (HR 1.53; 95% CI, 1.07-2.21; P=0.019) and cirrhosis (HR 5.69; 95% CI, 4.337.47; P<0.0001) were independently associated with increased risk of HCC. Asian race, HIV co-infection and obesity were not associated with increased risk of HCC. Female gender was associated with decreased risk (HR 0.32; 95% CI, 0.23-0.44; P<.0001) of HCC. Conclusion In this large U.S. cohort of CHB patients, we identified a high incidence of HCC. Established risk factors found in Asian population such as age, reactive HBeAg status, male gender, liver cirrhosis and HCV co-infection were also associated with increased risk of HCC in this U.S. cohort. Interestingly, co-infection with HIV was not associated with increased risk of HCC, potentially due to active anti-retroviral therapy.
Sa1862 A Retrospective Analysis of Pre Liver Transplant Use of Sorafenib Sushrut Trakroo, sirish sanaka, Randhir Jesudoss, Abdullah M. Al-Osaimi, Gary S. Cohen, Antonio Di Carlo, Mohammed Eyad Yaseen alsabbagh, Kamran Qureshi BACKGROUND AND AIM With long wait times, managing patients with hepatocellular carcinoma (HCC) on the liver transplant (LT) waitlist is challenging and is constantly evolving. The potential of multi-kinase inhibitor Sorafenib (SB), a cytostatic agent, in benefitting this patient population has been tempered by studies that have shown increased rates of post LT complications. In our study we compared patient survival, tumor recurrence and post LT complications in patients who received SB pre-LT with those who did not. METHODS We identified 37 consecutive patients who successfully underwent deceased donor LT for HCC at our center. 12 patients received SB prior to LT. We did a retrospective review comparing post LT outcomes between patients who received SB (group A) and those who did not (group B). RESULTS Eight of 12 patients received SB up to the day of LT. All received loco-regional therapy as per institutional protocol. There were no significant differences in demographic profile and etiologies between the two groups. Group A Patients had longer wait list time (p= 0.009). MELD at transplant was higher in group B although not statistically significant (p= 0.09). Nine (75%) in group A and 24(96%) in group B had viable tumor on explant. The total viable tumor burden on explant was similar although a higher number in group B had satellite lesions and multifocal HCC (16% in group A vs. 36% in Group B). Also, 83% in group A had T1 lesion or lower whereas 68% in group B had T2 lesions or higher. Four (33%) in group A and 7 (29%) in group B developed anastomotic strictures. All were managed endoscopically except one in group B who required surgical reconstruction. The 1, 3 and 5 year survival in Group A were 100% in patients who reached those timelines. The 1, 3 and 5 year survival in and Group B were 96%, 88% and 75% in patients who reached those timelines. No patients in group A had HCC recurrence at 5 years whereas 2/ 8 group B patients who reached 5 years of follow-up died of metastatic HCC. None of the patients in either group had surgical wound related complications. CONCLUSION In patients receiving SB pre-LT, we found that a greater number of SB naïve patients had multifocal HCC and higher tumor stage on explant pathology when compared to patients who received SB pre-LT. Also, a higher percentage of patients in group A had 1, 3 and 5 year survivals and a lower 5 year HCC recurrence compared to group B. There was no difference in the rates of post-LT complications between the two groups. Our study shows a better histologic
Sa1864 Factors Influencing Surveillance for Hepatocellular Carcinoma in Patients With Liver Cirrhosis Hager F. Ahmed Mohammed, Nasra H. Giama, Lewis R. Roberts Background: Hepatocellular carcinoma (HCC) is the sixth commonest cancer and the second most common cause of cancer related mortality. Liver cirrhosis is the major risk factor for HCC. We assessed the surveillance rate for HCC among Minnesota residents with cirrhosis seen at Mayo Clinic Rochester between 1/1/2007 and 12/31/2009. Methods: Using the medical record, we identified Minnesota residents with cirrhosis confirmed by histology, portal hypertension, imaging characteristics, or platelet count <120 x 10^9L in the setting of chronic liver disease between 1/1/2007 and 12/31/2009. Demographics, vital status, last follow-up, and abdominal images performed at Mayo Clinic (ultrasound, CT, or MRI) were abstracted. Images performed outside Mayo Clinic were not included due to the infeasibility of obtaining outside imaging data. Surveillance was calculated from 3 months after the date of cirrhosis diagnosis to the date of death, HCC diagnosis, liver transplant, or last followup date before 12/31/2013. The surveillance rate was calculated by dividing the actual surveillance frequency by the expected surveillance frequency. We classified surveillance rates into 6 levels: 0%, 1-24%, 25-49%, 50-74%, 75-99%, and 100%. Results: Between 1/ 1/2007 and 12/31/2009, 770 Minnesota residents with cirrhosis were seen at Mayo Clinic. 90 patients had insufficient data for analysis. The mean age of the 680 evaluable patients was 58.8 years (SD 12.7), and 58% were men. 100% surveillance was provided to 7.4% of the patients, 75-99% to 7%, 50-74% to 18.8%, 25-49% to 17.2%, and 1-24% to 17.7%.
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33% of the patients received at least annual surveillance at Mayo Clinic. 31.9% did not receive any imaging at Mayo Clinic. In an attempt to assess the proportion of patients who may have had additional outside imaging studies, we specifically reviewed the records of 25 patients who received 50-74% surveillance. For 23 (88%), the gastroenterologist specifically recommended semiannual screening. Conclusion: At a major tertiary center, HCC surveillance was recommended for almost all patients, however, patients frequently did not have surveillance performed at the referral center, but were recommended by specialists to have interval HCC surveillance coordinated by their primary physician. It will be of interest to determine whether the care transition between specialists and primary care physicians is one of the factors underlying the lack of adherence to recommended surveillance of patients with liver cirrhosis.
Table 1. Baseline Characteristics and Staging
Sa1865 Efficacy and Predictors of Survival Using Yttrium 90 (y90) Therasphere Treatment for Hepatocellular Carcinoma Maheen Sheikh, Richard Gerkin, Anil B. Seetharam, David Wood Introduction: Locoregional therapies for Hepatocellular Carcinoma (HCC) are increasingly employed in downstaging protocols for those qualifying for liver transplant (LT) and as "destination" therapy in those with small lesions who are poor surgical candidates. Targeted radioembolization with yttrium-90 (y90) intra-arterially provides tumoricidal doses of radiation with minimal systemic toxicity. Further studies are needed to characterize outcomes with y90 therapy and identify predictors of response. Aims: To evaluate toxicity, response rate, time to progression (TTP) and survival in patients treated for HCC with y90. Methods: A retrospective case series identifying consecutive patients with a diagnosis of HCC of any size or number of lesions treated with y90 between August, 2006 and December, 2009 and pre-treatment total bilirubin <3.0 mg/dL. Baseline clinical and tumor characteristics were tabulated including Child's-Pugh Class, Barcelona Clinic Liver Cancer (BCLC) Stage and Tumor, Node, Metastases (T,N,M) stage [Table 1]. Toxicities were recorded using the Common Terminology Criteria version 4.0. Response rate and TTP were determined using standard World Health Organization (WHO) and European Association for the Study of the Liver (EASL) guidelines. Survival by stage was assessed. Univariate and multivariate analyses were performed to identify predictors of survival. Results: 116 patients underwent 169 y90 treatment sessions (median 118 Gy/treatment) over a median follow up of 13.2 months. There were no gastrointestinal ulcerations and 1 patient developed radiation pneumonitis at 149 days. 30 day mortality was 0.8%. Response rates were 43% (median time to response: 4.2 months) and 58% (median time to response: 3.6 months) based on WHO and EASL criteria, respectively. Overall TTP was 14 months (95% confidence interval, 8.2-19.8) with no significant difference when stratified by Child's Pugh Stage (p=0.952). Median survival was 22.5 months (95% CI 18.7-26.3). When survival was stratified by Child-Pugh stage, there was a significant difference between stages (p = 0.029), with significance representing Stage A compared with C. For Child-Pugh stages A and B, median survival was 746 days compared with 579 days, respectively (p = 0.095). Baseline performance status, unilobar tumor involvement, and EASL/WHO response predicted survival (p<0.05) [Table 2]. Conclusions: Y90 embolization is an effective adjunct or destination therapy in patients with Child's Class A cirrhosis and HCC, particularly those with good baseline functional status and unilobar tumor involvement. Further studies are needed to identify demographic and tumor characteristics that may predict favorable response to y90 in those with more advanced liver dysfunction.
AASLD Abstracts
Univariate and Multivariate Predictors of Response to Y90 Therapy
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