Initial Chemoembolization Research Articles

Cone-Beam Computed Tomography-Hepatic Arteriography as a Diagnostic Tool for Small Hypervascular Hepatocellular Carcinomas: Method and Clinical Implications.

This study proposes a novel reference standard for hypervascular hepatocellular carcinomas (HCCs), established by cone-beam computed tomography-hepatic arteriography (CBCT-HA) and two-year imaging follow-up, and discusses its clinical implication on tumor staging and understanding the intrahepatic distant recurrence (IDR) in relation to dynamic computed tomography (CT). In this retrospective study, 99 patients were enrolled, who underwent CBCT-HA during initial chemoembolization for HCC suspected on CT. All patients underwent chemoembolization and regular clinical and imaging follow-up for two years. If IDR appeared on follow-up imaging, initial CBCT-HA images were reviewed to determine if a hypervascular focus pre-existed at the site of recurrence. Pre-existing hypervascular foci on CBCT-HA were regarded as HCCs in initial presentation. Initial HCCs were classified into three groups according to their mode of detection (Group I, detected on CT and CBCT-HA; Group II, additionally detected on CBCT-HA; Group III, confirmed by interval growth). We assessed the influence of CBCT-HA and two-year follow-up on initial tumor stage and calculated the proportion of IDR that pre-existed in initial CBCT-HA. A total of 405 nodules were confirmed as HCCs, and 297 nodules initially pre-existed. Of the initial 297 HCCs, 149 (50.2%) lesions were in Group I, 74 (24.9%) lesions were in Group II, and the remaining 74 (24.9%) lesions were in Group III. After applying CBCT-HA findings, 11 patients upstaged in T stage, and 4 patients had a change in Milan criteria. Our reference standard for HCC indicated that 120 of 148 (81.1%) one-year IDR and 148 of 256 (57.8%) two-year IDR existed on initial CBCT-HA. The proposed method enabled the confirmation of many sub-centimeter-sized, faintly vascularized HCC nodules that pre-existed initially but clinically manifested as IDR. Our reference standard for HCC helped in understanding the nature of IDR and the early development of HCC as well as the clinical impact of tumor staging and treatment decision.

Diagnostic accuracy of contrast-enhanced dynamic CT for small hypervascular hepatocellular carcinoma and assessment of dynamic enhancement patterns: Results of two-year follow-up using cone-beam CT hepatic arteriography.

ObjectiveTo evaluate the accuracy of CT for small, hypervascular hepatocellular carcinomas (HCCs) and assess the enhancement patterns on CT.Materials and methodsNinety-nine patients who underwent cone-beam CT hepatic arteriography (CBCT-HA) during initial chemoembolization for HCC suspected on CT were enrolled in this study. A total of 297 hypervascular HCCs (142 ≥ 1 cm, 155 < 1 cm) were confirmed as HCCs based on two-year follow-up CT and CBCT-HA images. During the two-year follow-up, pre-existing hypervascular foci on CBCT-HA were regarded as HCCs at the initial presentation. Two radiologists categorized HCCs according to the following enhancement patterns on CT: type I, arterial enhancement and washout; type II, arterial enhancement without washout; and type III, no arterial enhancement. Two blinded reviewers rated the possibility of HCC.ResultsFor the 297 HCCs, the enhancement patterns according to size were as follows: type I ≥1 cm in 114 HCCs; type I <1 cm in 40 HCCs; type II ≥1 cm in 16 HCCs; type II <1 cm in 37 HCCs; type III ≥1 cm in 12 HCCs; and type III <1 cm in 10 HCCs. The remaining 68 HCCs (22.9%) were not detected on CT. The detection rates of HCCs ≥ 1 cm were 83.1%, 76.8%, and 83.1% in the formal report for reviewer 1 and reviewer 2. In comparison, the detection rates of HCCs < 1 cm were 20.6%, 17.4%, and 17.4% in the formal report for reviewer 1 and reviewer 2.ConclusionMany subcentimeter sized hypervascular HCCs were frequently missed or not evident on CT at the initial diagnostic workup. CT has limitations for diagnosing HCCs that are <1 cm in size or have atypical enhancement patterns.

Combined Cisplatin-Based Chemoembolization and Radiation Therapy for Hepatocellular Carcinoma Invading the Main Portal Vein

PurposeTo evaluate the safety and survival outcome of chemoembolization plus radiation therapy (RT) in patients with hepatocellular carcinoma (HCC) with main portal vein (PV) tumor thrombosis. Materials and MethodsThis retrospective study evaluated 151 patients with HCC and main PV involvement (101 with Child–Pugh class A liver function and 50 with Child–Pugh class B liver function) treated with combined cisplatin-based chemoembolization and RT. Medical records, imaging, and laboratory studies were reviewed, and complications, survival, and mortality rates were determined. ResultsAfter chemoembolization, major complications occurred in 19.9% of patients, with the rate of major complications significantly higher in Child–Pugh class B cases than in Child–Pugh class A cases (32% vs 13.9%; P = .016). The 30-day mortality rate was 0.7%. One hundred forty-seven patients received adjuvant RT an average of 17.4 days after chemoembolization for main PV tumor thrombosis. Adjuvant RT could not be performed in four patients because of intolerance of the initial chemoembolization. There were no major complications after RT. The objective tumor response at 6 months was 25.2%, with a median survival of 12 months (14 mo in Child–Pugh class A cases and 8 mo in Child–Pugh class B cases). Patients with Child–Pugh class B liver function with extrahepatic metastases, no tumor response, and absence of second-line sorafenib treatment had poor survival. ConclusionsChemoembolization combined with RT improves survival, with a median survival of 12 months in patients with HCC with main PV involvement.

The Safety and Clinical Outcomes of Chemoembolization in Child-Pugh Class C Patients with Hepatocellular Carcinomas.

ObjectiveTo evaluate the safety and clinical outcomes of chemoembolization in Child-Pugh class C patients with hepatocellular carcinomas (HCC).Materials and MethodsThe study comprised 55 patients with HCC who were classified as Child-Pugh class C and who underwent initial chemoembolization between January 2003 and December 2012. Selective chemoembolization was performed in all technically feasible cases to minimize procedure-related complications. All adverse events within 30 days were recorded using the Common Terminology Criteria for Adverse Events (CTCAE). The tumor response to chemoembolization was evaluated using the modified Response Evaluation Criteria In Solid Tumors.ResultsThirty (54.5%) patients were within the Milan criteria, and 25 (45.5%) were beyond. The mortality of study subjects at 30 days was 5.5%. Major complications were observed in five (9.1%) patients who were all beyond the Milan criteria: two hepatic failures, one hepatic encephalopathy, and two CTCAE grade 3 increases in aspartate aminotransferase/alanine aminotransferase abnormality. The mean length of hospitalization was 6.3 ± 8.3 days (standard deviation), and 18 (32.7%) patients were discharged on the next day after chemoembolization. The tumor responses of the patients who met the Milan criteria were significantly higher (p = 0.014) than those of the patients who did not. The overall median survival was 7.1 months (95% confidence interval: 4.4-9.8 months).ConclusionEven in patients with Child-Pugh class C, chemoembolization can be performed safely with a selective technique in selected cases with a small tumor burden.

Role of C-Arm CT in Identifying Caudate Arteries Supplying Hepatocellular Carcinoma

PurposeTo evaluate the role of C-arm computed tomography (CT) performed at the proper hepatic artery or equivalent in patients with caudate-lobe hepatocellular carcinoma (HCC) for the detection of tumor-feeding arteries during chemoembolization. Materials and MethodsFrom July 2009 to June 2012, 1,785 patients received initial chemoembolization at a single institution. Among them, 52 patients with caudate HCC underwent initial chemoembolization with the use of C-arm CT. C-arm CT images were obtained at the proper hepatic artery or equivalent. Two radiologists reviewed the C-arm CT scans and angiograms in consensus. The cumulative local recurrence rate was calculated by the Kaplan–Meier method. ResultsTumor-feeding arteries were single (n = 31), double (n = 12), triple (n = 6), and quadruple (n = 3). Seventy-nine tumor-feeding arteries and their origins in 48 patients were demonstrated on C-arm CT. In four patients (7.7%), five tumor-feeding arteries were not clearly indicated on C-arm CT because of poor image quality caused by failure of the patients to hold their breath. Selective chemoembolization via tumor-feeding arteries was successful in 45 patients (87%). The cumulative local recurrence rates at 6 months, 1 year, and 3 years were 19.4%, 32.8%, and 35.8%, respectively. Nonselective chemoembolization of tumor-feeding arteries of caudate-lobe HCC was a significantly important factor in higher cumulative local recurrence rates (hazard ratio, 3.916; 95% confidence interval, 1.367–11.216; P = .011). ConclusionC-arm CT obtained at the proper hepatic artery or equivalent level can demonstrate most tumor-feeding arteries supplying HCCs in the caudate lobe.

Lack of Response after Initial Chemoembolization for Hepatocellular Carcinoma: Does It Predict Failure of Subsequent Treatment?

To (a) evaluate the response of hepatocellular carcinoma (HCC) to chemoembolization after initial nonresponse, as determined with European Association for the Study of the Liver (EASL) criteria and modified Response Evaluation Criteria in Solid Tumors (mRECIST), and (b) compare posttreatment survival of initial nonresponders versus that of initial responders. The institutional review board approved this retrospective study, which was compliant with HIPAA. A total of 116 consecutive patients (96 men, 20 women; mean age, 63 years) with unresectable HCC who underwent at least two chemoembolization procedures were included. The chemoembolization mixture consisted of 100 mg of cisplatin, 50 mg of doxorubicin, and 10 mg of mitomycin C mixed 1:1 with iodized oil. Tumor response at magnetic resonance imaging was evaluated after each chemoembolization procedure according to EASL criteria and mRECIST. The survival rate in each subgroup was calculated and correlated with response. The Wilcoxon test was used to test group comparability. Kaplan-Meier estimators were used to generate survival curves and compared by using the log-rank test. No response to initial chemoembolization was seen in 43% and 50% of patients according to EASL criteria and mRECIST, respectively. After a second chemoembolization procedure, 44% (EASL) and 47% (mRECIST) of initial nonresponders showed a significant response. With EASL criteria, the 1-, 2-, and 3-year survival rates (±standard error of the mean) after two chemoembolization procedures were 39%±10, 14%±7, and 0%, respectively, for nonresponders and 68%±10, 50%±11, and 37%±11 for responders (P=.036, P=.006, and P<.005 at 1, 2, and 3 years). With mRECIST, the 1-, 2-, and 3-year survival rates after two chemoembolization procedures were 49%±9, 20%±8, and 7%±6 for nonresponders and 67%±9, 44%±10, and 36%±9 for responders (P=.174, P=.046, and P=.011 at 1, 2, and 3 years). Patients who underwent chemoembolization for HCC showed a response (with both EASL criteria and mRECIST) and improved survival after the second chemoembolization treatment. At least two chemoembolization procedures should be performed in the same targeted lesions before further treatment is abandoned.

Society of Interventional Radiology Position Statement on Chemoembolization of Hepatic Malignancies

Society of Interventional Radiology Position Statement on Chemoembolization of Hepatic Malignancies

Hepatocellular Carcinoma Supplied by the Right Lumbar Artery

This study evaluated the clinical features of hepatocellular carcinoma (HCC) supplied by the right lumbar artery. Eleven patients with HCC supplied by the right lumbar artery were treated with chemoembolization. The patients' medical records were retrospectively analyzed. All patients underwent 6.7 +/- 3.7 (mean +/- SD) chemoembolization sessions, and the hepatic arterial branches were noted as being attenuated. The right inferior phrenic artery (IPA) was also embolized in 10 patients. The interval between initial chemoembolization and chemoembolization of the lumbar artery supply was 53.2 +/- 26.9 months. Mean tumor diameter was 3.1 +/- 2.4 cm and was located at the surface of S7 and S6. The feeding-branch arose proximal to the bifurcation of the dorsal ramus and muscular branches (n = 8) or from the muscular branches (n = 3) of the right first (n = 10) or second lumbar artery (n = 1). The anterior spinal artery originated from the tumor-feeding lumbar artery in one patient. All feeders were selected, and embolization was performed after injection of iodized oil and anticancer drugs (n = 10) or gelatin sponge alone in a patient with anterior spinal artery branching (n = 1). Eight patients died from tumor progression 10.1 +/- 4.6 months later, and two patients survived 2 and 26 months, respectively. The remaining patient died of bone metastases after 32 months despite liver transplantation 10 months after chemoembolization. The right lumbar artery supplies HCC located in the bare area of the liver, especially in patients who undergo repeated chemoembolization, including chemoembolization by way of the right IPA. Chemoembolization by way of the right lumbar artery may be safe when the feeder is well selected.

Response assessment of HCC undergoing chemoembolization by necrosis-adjusted models

e15528 Background: Chemoembolization (CE) is an accepted therapy for unresectable HCC. As treated tumors may not shrink in size, response assessment via measurement of the enhancing tumor (EASL) has been proposed as an alternate to whole tumor (RECIST) measures. However, the reliability of this model has not been tested in clinical practice. Methods: We identified 29 HCC patients treated with CE with known overall survival (OS) in whom MRI before and after initial CE therapy was available for review. Three radiologists evaluated the imaging, measuring the largest liver lesion in three dimensions and the largest enhancing region in two dimensions. Readers also assessed percent tumor necrosis and overall tumor response qualitatively. Response models in 1-, 2-, or 3- dimensions, with or without necrosis adjustment, were created to assign patients to CR/PR/SD/PD classes, based on majority classification. Predictive value for OS was assessed for PD vs. other, and for PR/CR vs. SD/PD by the Students’ t-test. Inter-reader concordance was assessed by the Fleiss κ statistic. Results: For non-necrosis adjusted models, OS for progressors vs. non-progressors was statistically significant (p values: 0.0002–0.04), but could not identify early responders. Necrosis adjusted models failed to identify early progressors, but identified responders with improved OS (p values: 0.02–0.12). Inter-reader concordance was higher for necrosis adjusted models (κ range: 0.36–0.52) than for non-necrosis adjusted models (0.16–0.23). Viable tumor response by a two-dimensional product was superior to a one-dimensional diameter for predicting OS (p=0.04 vs. 0.74), and demonstrated higher inter-reader concordance (κ=0.46 vs. 0.30). Qualitative assessment of hepatic tumor could predict differences in OS for both PD vs. others (p=0.0001) and responders vs. non-responders (p=0.04), with acceptable inter-reader concordance (κ=0.34). Conclusions: Two- dimensional, but not one-dimensional, viable tumor measurement can identify response of HCC to chemoembolization and predict OS. Models which incorporate qualitative reader assessment of tumor necrosis may be more flexible than direct measures of viable tumor, and should be considered as alternatives for tumor assessment in chemoembolization. No significant financial relationships to disclose.

Sarcomas Metastatic to the Liver: Response and Survival after Cisplatin, Doxorubicin, Mitomycin-C, Ethiodol, and Polyvinyl Alcohol Chemoembolization

To evaluate the response to and survival after chemoembolization with cisplatin, doxorubicin, mitomycin-C, Ethiodol, and polyvinyl alcohol for patients with sarcomas metastatic to the liver that are surgically unresectable. Sixteen patients were treated. Primary tumors included 11 gastrointestinal leiomyosarcomas, two splenic angiosarcomas, one leiomyosarcoma of the broad ligament, one leiomyosarcoma of the inferior vena cava, and one malignant fibrous histiocytoma of the colon. Chemoembolization with cisplatin, doxorubicin, mitomycin-C, Ethiodol, and polyvinyl alcohol particles was performed 1-5 times at approximately monthly intervals (mean, 2.8). Pre- and posttreatment cross-sectional imaging was performed 1 month after completion of treatment and then every 3 months. Thirty-day response was graded according to World Health Organization/Eastern Cooperative Oncology Group criteria. Survival was calculated with use of Kaplan-Meier analysis. Two patients (13%) exhibited partial morphologic response, 11 patients (69%) were morphologically stable, and three (19%) demonstrated progression of disease 30 days after completion of treatment. Among the 13 responders, two underwent partial hepatectomy after initial treatment. Seven developed intrahepatic progression at a mean of 10 months and a median time of 8 months. The remaining four patients had no documented intrahepatic progression at the time of last imaging follow-up. Nine patients developed extrahepatic progression at a mean time of 6.3 months and a median time of 6 months, of whom four underwent additional surgical resection. Response to therapy was based on time of first intervention. Cumulative survival from time of diagnosis with use of Kaplan-Meier analysis was 81% at 1 year, 54% at 2 years, and 40% at 3 years. Median survival time was 20 months. Cumulative survival from initial chemoembolization was 67% at 1 year, 50% at 2 years, and 40% at 3 years, with a median survival time of 13 months. The thirty-day mortality rate was zero. Durable tumor response with chemoembolization is possible in this form of metastatic disease, which is highly resistant to systemic chemotherapy.