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Title: WE-AB-BRA-05: PET-Guided Delivery Quality Evaluation of Yttrium-90 Microsphere Radioembolizaton for Hepatocellular Carcinoma Patients: The Optimal Sequence of Radioembolizaton and Chemoembolization Treatments

Abstract

Purpose: Selective-internal-radiation-therapy (SIRT) and transarterial-chemoembolization (TACE) are commonly used for treatment of liver tumors. The use of TACE, which is macroembolic, prior to SIRT may cause hemodynamic changes in tumor vasculature that impair yttrium-90 (90Y) microsphere delivery to the targeted lesions. This work aims to quantify dosimetric tumor coverage using 90Y positron emission tomography (PET) dosimetry after SIRT alone compared to TACE followed by SIRT. Methods: A total of 40 consecutive hepatocellular carcinoma (HCC) SIRT patients who had a post-SIRT 90Y PET/CT scan were evaluated. The patient-specific-3D-dose was reconstructed from the PET images. Patients were categorized into two groups: patients received TACE prior SIRT procedure (n=18) and patient received SIRT alone (n=22). The lesions and liver were delineated by a senior radiologist. We evaluated both the lesion-specific dose-volume-histogram (DVH) and the selectivity index (SI) defined as the ratio of the average dose inside the total lesion(s) and the average dose of the normal liver. The SI values of patients were compared based on whether TACE was previously used. Results: A wide spectrum was observed in the lesion-specific DVH-evaluation and SI appeared to be suitable of evaluating the quality of each SIRT infusion. The average SI of the entire patient groupmore » was 3.0, i.e. targeted lesion receiving three times higher dose than normal liver. The average SI was 1.8 for patients who had prior TACE and 3.9 for patients who did not have prior TACE (p=0.008). 85% of the patients with prior TACE demonstrated poor 90Y-microsphere delivery (SI <2) while none demonstrated excellent delivery (SI >4). On the other hand, the incidence SI >4 among patients with no prior TACE was 37%. Conclusion: 3D dose evaluation using post-SIRT PET suggests that 90Y microsphere delivery to liver tumors is impaired among patients who received prior TACE compared to those who receive SIRT alone.« less

Authors:
 [1];  [2]
  1. The University of Texas Southwestern Medical Ctr, Dallas, TX (United States)
  2. University of Maryland School of Medicine, Baltimore, MD (United States)
Publication Date:
OSTI Identifier:
22654095
Resource Type:
Journal Article
Resource Relation:
Journal Name: Medical Physics; Journal Volume: 43; Journal Issue: 6; Other Information: (c) 2016 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 61 RADIATION PROTECTION AND DOSIMETRY; DELIVERY; HEPATOMAS; IMAGE PROCESSING; LIVER; MICROSPHERES; PATIENTS; POSITRON COMPUTED TOMOGRAPHY; RADIATION DOSES; YTTRIUM 90

Citation Formats

Lin, M, and Saboury, B. WE-AB-BRA-05: PET-Guided Delivery Quality Evaluation of Yttrium-90 Microsphere Radioembolizaton for Hepatocellular Carcinoma Patients: The Optimal Sequence of Radioembolizaton and Chemoembolization Treatments. United States: N. p., 2016. Web. doi:10.1118/1.4957734.
Lin, M, & Saboury, B. WE-AB-BRA-05: PET-Guided Delivery Quality Evaluation of Yttrium-90 Microsphere Radioembolizaton for Hepatocellular Carcinoma Patients: The Optimal Sequence of Radioembolizaton and Chemoembolization Treatments. United States. doi:10.1118/1.4957734.
Lin, M, and Saboury, B. 2016. "WE-AB-BRA-05: PET-Guided Delivery Quality Evaluation of Yttrium-90 Microsphere Radioembolizaton for Hepatocellular Carcinoma Patients: The Optimal Sequence of Radioembolizaton and Chemoembolization Treatments". United States. doi:10.1118/1.4957734.
@article{osti_22654095,
title = {WE-AB-BRA-05: PET-Guided Delivery Quality Evaluation of Yttrium-90 Microsphere Radioembolizaton for Hepatocellular Carcinoma Patients: The Optimal Sequence of Radioembolizaton and Chemoembolization Treatments},
author = {Lin, M and Saboury, B},
abstractNote = {Purpose: Selective-internal-radiation-therapy (SIRT) and transarterial-chemoembolization (TACE) are commonly used for treatment of liver tumors. The use of TACE, which is macroembolic, prior to SIRT may cause hemodynamic changes in tumor vasculature that impair yttrium-90 (90Y) microsphere delivery to the targeted lesions. This work aims to quantify dosimetric tumor coverage using 90Y positron emission tomography (PET) dosimetry after SIRT alone compared to TACE followed by SIRT. Methods: A total of 40 consecutive hepatocellular carcinoma (HCC) SIRT patients who had a post-SIRT 90Y PET/CT scan were evaluated. The patient-specific-3D-dose was reconstructed from the PET images. Patients were categorized into two groups: patients received TACE prior SIRT procedure (n=18) and patient received SIRT alone (n=22). The lesions and liver were delineated by a senior radiologist. We evaluated both the lesion-specific dose-volume-histogram (DVH) and the selectivity index (SI) defined as the ratio of the average dose inside the total lesion(s) and the average dose of the normal liver. The SI values of patients were compared based on whether TACE was previously used. Results: A wide spectrum was observed in the lesion-specific DVH-evaluation and SI appeared to be suitable of evaluating the quality of each SIRT infusion. The average SI of the entire patient group was 3.0, i.e. targeted lesion receiving three times higher dose than normal liver. The average SI was 1.8 for patients who had prior TACE and 3.9 for patients who did not have prior TACE (p=0.008). 85% of the patients with prior TACE demonstrated poor 90Y-microsphere delivery (SI <2) while none demonstrated excellent delivery (SI >4). On the other hand, the incidence SI >4 among patients with no prior TACE was 37%. Conclusion: 3D dose evaluation using post-SIRT PET suggests that 90Y microsphere delivery to liver tumors is impaired among patients who received prior TACE compared to those who receive SIRT alone.},
doi = {10.1118/1.4957734},
journal = {Medical Physics},
number = 6,
volume = 43,
place = {United States},
year = 2016,
month = 6
}
  • Purpose. To elucidate the local therapeutic results of computed tomography (CT)-guided transcatheter arterial chemoembolization (TACE) as initial treatment for hepatocellular carcinoma (HCC), and to verify factors which affect local therapeutic results. Methods. From 1992 to 2002, 265 tumors of 79 HCC patients were treated by 139 sessions of CT-guided TACE as initial treatment. Among these 265 tumors, 182 constituted multiple new lesions, and the remaining 83 tumors were single new lesions. Local recurrence was retrospectively ascertained on follow-up CT images obtained after TACE. Results. The overall local recurrence-free rates (LR-FRs) after a single TACE session at 6, 12, and 36more » months were 67%, 49%, and 28%; those of the single new lesions were 80%, 66%, and 32%; and those of tumors with complete lipiodol accumulation were 82%, 68%, and 41%, respectively. LR-FRs of tumors of the single new lesions, and those of tumors with complete lipiodol accumulation, were significantly higher than the LR-FRs of multiple new lesions and tumors with incomplete lipiodol accumulation, respectively. For single new lesions {<=}4 cm and the tumors that were one of multiple new lesions, there were no significant differences in the LR-FRs regarding the number of TACE sessions on the basis of patient, tumor location, or tumor size. Conclusion. Local therapeutic results of single new lesions were better than those of multiple new lesions, and the local therapeutic effect of TACE was not affected by the number of treatments on the basis of patient, tumor location, or tumor size.« less
  • Purpose: To compare treatment response after transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) in patients with and without a transjugular intrahepatic portosystemic shunt (TIPS). Materials and Methods: A retrospective review of patients who underwent conventional TACE for HCC between January 2005 and December 2009 identified 10 patients with patent TIPS. From the same time period, 23 patients without TIPS were selected to control for comparable Model for End-Stage Liver Disease and Child-Pugh-Turcotte scores. The two groups showed similar distribution of Barcelona Clinic Liver Cancer and United Network of Organ Sharing stages. Target HCC lesions were evaluated according to the modifiedmore » response evaluation criteria in solid tumors (mRECIST) guidelines. Transplantation rate, time to tumor progression, and overall survival (OS) were documented. Results: After TACE, the rate of complete response was significantly greater in non-TIPS patients compared with TIPS patients (74 vs. 30 %, p = 0.03). Objective response rate (complete and partial response) trended greater in the non-TIPS group (83 vs. 50 %, p = 0.09). The liver transplantation rate was 80 and 74 % in the TIPS and non-TIPS groups, respectively (p = 1.0). Time to tumor progression was similar (p = 0.47) between the two groups. OS favored the non-TIPS group (p = 0.01) when censored for liver transplantation. Conclusion: TACE is less effective in achieving complete or partial response using mRECIST criteria in TIPS patients compared with those without a TIPS. Nevertheless, similar clinical outcomes may be achieved, particularly in TIPS patients who are liver-transplantation candidates.« less
  • Purpose: The short- and long-term effects of {sup 90}Yttrium microspheres therapy for hepatocellular carcinoma (HCC) on peripheral blood lymphocytes are unknown and were therefore examined. Methods and Materials: Ninety-two HCC patients were enrolled in a {sup 90}Yttrium therapy study and routine blood counts were examined as part of standard clinical monitoring. Results: We found an early, profound, and prolonged lymphopenia. In a subsequent cohort of 25 additional HCC patients, prospective flow cytometric immune-monitoring analysis was performed to identify specific changes on distinct lymphocyte subsets (i.e., CD3, CD4, CD8 T, and CD19 B lymphocytes) and NK cells absolute numbers, in additionmore » to the granulocytes and platelets subsets. We found that the pretreatment lymphocyte subset absolute numbers (with the exception of NK cells) had a tendency to be lower compared with healthy control values, but no significant differences were detected between groups. Posttherapy follow-up revealed that overall, all lymphocyte subsets, except for NK cells, were significantly (>50% from pretherapy values), promptly (as early as 24 h) and persistently (up to 30 months) depleted post-{sup 90}Yttrium microspheres therapy. In contrast, granulocytes increased rapidly (24 h) to compensate for lymphocyte depletion, and remained increased at 1-year after therapy. We further stratified patients into two groups, according to survival at 1 year. We found that lack of recovery of CD19, CD3, CD8, and especially CD4 T cells was linked to poor patient survival. No fungal or bacterial infections were noted during the 30-month follow-up period. Conclusions: The results show that lymphocytes (and not granulocytes, platelets, or NK cells) are sensitive to hepatic arterial {sup 90}Yttrium without associated clinical toxicity, and lack of lymphocyte recovery (possibly leading to dysregulation of adaptive cellular immunity) posttherapy indicates poor survival.« less
  • The purpose of this study was to assess the safety and efficacy of doxorubicin-loaded beads (DC Beads) delivered by transarterial embolization for the treatment of unresectable hepatocellular carcinoma (HCC). This open-label, single-center, single-arm study included 62 cirrhotic patients with documented single unresectable HCC. Mean tumor diameter was 5.6 cm (range, 3-9 cm) classified as Okuda stages 1 (n = 53) and 2 (n = 9). Patients received repeat embolizations with doxorubicin-loaded beads every 3 months (maximum of three). The maximum doxorubicin dose was 150 mg per embolization, loaded in DC Beads of 100-300 or 300-500 {mu}m. Regarding efficacy, overall, anmore » objective response according to the European Association for the Study of the Liver criteria was observed in 59.6%, 81.8%, and 70.8% across three treatments. A complete response was observed in 4.8% after the first procedure and 3.6% and 8.3% after the second and third procedures, respectively. At 9 months a complete response was seen in 12.2%, an objective response in 80.7%, progressive disease in 6.8%, and 12.2% showed stable disease. Mean tumor necrosis ranged from 77.4% to 83.9% (range, 28.6%-100%) across three treatments. {alpha}-Fetoprotein levels showed a mean decrease of 1123 ng/ml (95% CI = 846-1399; p = 3 x 10{sup -11}) after the first session and remained stable after the second and third embolizations (42 and 70 ng/ml decrease, respectively). Regarding safety, bilirubin, {gamma}-glutamyl transferase, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase showed only transient increases during the study period. Severe procedure-related complications were seen in 3.2% (cholecystitis, n 1; liver abscess, n = 1). Postembolization syndrome was observed in all patients. We conclude that hemoembolization using doxorubicin-loaded DC Beads is a safe and effective treatment of HCC as demonstrated by the low complication rate, increased tumor response, and sustained reduction of {alpha}-fetoprotein levels.« less
  • Our purpose was to compare the recurrence rate and survival in patients with hepatocellular carcinoma (HCC) who had elective transarterial chemoembolization (TACE), immediate preoperative TACE, or no treatment prior to orthotopic liver transplantation (OLT). A total of 132 patients with HCC had TACE prior to OLT. Eighteen patients had no TACE before OLT and functioned as a control group. The urgent group included 35 patients embolized less than 24 h before OLT and the elective group included 97 patients embolized greater than 1 day before transplantation. These groups were compared with regard to tumor staging, hepatic synthetic function, and post-TACEmore » tumor necrosis and survival and recurrence rates.Patients were followed for a mean of 780 days post OLT (1-2912 days). The tumor staging was similar between groups but the Childs-Pugh score in the urgent and untreated group was significantly higher than that of the other groups. The degree of necrosis at explant was also significantly different between the two treated groups, with an average 35% necrosis in the patients embolized less than 24 h before OLT vs 77% in the elective group (p < 0.002). Recurrence rate in the urgent group was 8 of 35 (23%) in a median of 580 days, 20 of 97 (21%) in a median of 539 days in the elective group, and 2 of 18 (11%) in a median of 331 days in the no-TACE group. Survival at 1, 3, and 5 years was 91%, 80%, and 72% in the elective group, 79%, 58%, and 39% in the urgent group, and 69%, 61%, and 41% in the no-TACE group, respectively. The urgent and no-TACE groups had significantly worse survival compared with the other groups; however, the tumor recurrence rates were statistically the same among all three groups. TACE within 24 h of OLT causes an average of 35% necrosis and elective TACE increases necrosis further to 77%. Despite this difference, the tumor recurrence rate in the three groups is equivalent and no different from that in the group that received no treatment before OLT. The decreased survival in the immediate and no-TACE groups was due to non-cancer-related deaths.« less