Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma.

BACKGROUND & AIMS: Chemoembolization is one of several standards of care treatment for hepatocellular carcinoma (HCC). Radioembolization with Yttrium-90 microspheres is a novel, transarterial approach to radiation therapy. We performed a comparative effectiveness analysis of these therapies in patients with HCC. METHODS: We collected data from 463 patients who were treated with transarterial locoregional therapies (chemoembolization or radioembolization) over a 9-year period. We excluded patients who were not appropriate for comparison and analyzed data from 245 (122 who received chemoembolization and 123 who received radioembolization). Patients were followed for signs of toxicity; all underwent imaging analysis at baseline and follow-up time points. Overall survival was the primary outcome measure. Secondary outcomes included safety, response rate, and time-to-progression. Uni- and multivariate analyses were performed. RESULTS: Abdominal pain and increased transaminase activity were more frequent following chemoembolization (P < .05). There was a trend that patients treated with radioembolization had a higher response rate than with chemoembolization (49% vs 36%, respectively, P = .104). Although time-to-progression was longer following radioembolization than chemoembolization (13.3 months vs 8.4 months, respectively, P = .046), median survival times were not statistically different (20.5 months vs 17.4 months, respectively, P = .232). Among patients with intermediate-stage disease, survival was similar between groups that received chemoembolization (17.5 months) and radioembolization (17.2 months, P = .42). CONCLUSIONS: Patients with HCC treated by chemoembolization or radioembolization with Yttrium-90 microspheres had similar survival times. Radioembolization resulted in longer time-to-progression and less toxicity than chemoembolization. Post hoc analyses of sample size indicated that a randomized study with > 1000 patients would be required to establish equivalence of survival times between patients treated with these two therapies.

Early assessment of the efficacy of digital infrared thermal imaging in pediatric extremity trauma.

Young children or those with intellectual disability with trauma to an extremity often undergo radiographs of the whole limb. The objective of the study was to assess the efficacy of digital infrared thermal images (DITI) in pediatric extremity trauma. We hypothesized fractures to be associated with local hyperthermia, detectable with DITI, which could direct focused radiographs. In this exploratory study, patients seen over a 2-month period in a pediatric emergency department for limb trauma were included if an extremity radiograph was taken on the same day. Patients had DITI of symptomatic and contralateral limbs. The warmest area of each image was compared to the site of pain and/or fracture on the radiograph. Fifty-one patients were enrolled. DITI matched 73% of pain sites. Fractures were seen in 11 patients. DITI matched 7 of 11 (64%) fracture sites. DITI performance in pinpointing the site of injury, although suboptimal, is encouraging for further evaluation.

Chemoembolization for hepatocellular carcinoma: comprehensive imaging and survival analysis in a 172-patient cohort.

PURPOSE: To determine comprehensive imaging and long-term survival outcome following chemoembolization for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: One hundred seventy-two patients with HCC treated with chemoembolization were studied retrospectively in an institutional review board approved protocol; this study was HIPAA compliant. Baseline laboratory and imaging characteristics were obtained. Clinical and laboratory toxicities following treatment were assessed. Imaging characteristics following chemoembolization were evaluated to determine response rates (size and necrosis) and time to progression (TTP). Survival from the time of first chemoembolization treatment was calculated. Subanalyses were performed by stratifying the population according to Child-Pugh, United Network for Organ Sharing, and Barcelona Clinic for Liver Cancer (BCLC) staging systems. RESULTS: Cirrhosis was present in 157 patients (91%); portal hypertension was present in 139 patients (81%). Eleven patients (6%) had metastases at baseline. Portal vein thrombosis was present in 11 patients (6%). Fifty-five percent of patients experienced some form of toxicity following treatment; 21% developed grade 3 or 4 bilirubin toxicity. Post-chemoembolization response was seen in 31% and 64% of patients according to size and necrosis criteria, respectively. Median TTP was 7.9 months (95% confidence interval: 7.1, 9.4) but varied widely by stage. Median survival was significantly different between patients with BCLC stages A, B, and C disease (stage A, 40.0 months; B, 17.4 months; C, 6.3 months; P < .0001). CONCLUSION: The determination of TTP and survival in patients with HCC is confounded by tumor biology and background cirrhosis; chemoembolization was shown to be a safe and effective therapy in patients with HCC.

Safety of yttrium-90 microsphere radioembolization in patients with biliary obstruction.

PURPOSE: There are few data on radioembolization in the setting of biliary obstruction. The present study was performed to assess the safety of yttrium-90 ((90)Y) radioembolization in the setting of tumor-related biliary obstruction and total bilirubin levels of 2 mg/dL or lower. MATERIALS AND METHODS: Twelve patients with liver tumors underwent 19 treatment sessions with (90)Y to the obstructed liver lobe or segment. Initial bilirubin level was 2 mg/dL or lower in all cases. Measured outcomes included pre- and posttreatment white blood cell (WBC) count, total bilirubin level, and alkaline phosphatase (ALP) level. Bilirubin toxicities and biliary complications were assessed according to Common Toxicity Criteria, version 3.0. RESULTS: Lobar or segmental (90)Y was successful in all cases. Pre- and posttreatment median WBC counts (5.3 vs 5.3; P = .490), bilirubin levels (1.0 vs 1.1; P = .460), and ALP levels (195 vs 146; P = .712) showed no differences. One case of grade 3 bilirubin toxicity was noted in a patient with liver hilar nodal progression and subsequent biliary obstruction requiring external drainage. Complete resolution of biliary obstruction was seen after (90)Y treatment in one case of metastatic colorectal carcinoma at 1 month follow-up. No biliary complications (infection, sepsis, biliary necrosis, biloma formation, abscess development, or biliary stricture) were encountered in this cohort during an overall median follow-up time of 22.9 months. CONCLUSIONS: The use of (90)Y glass microspheres demonstrated a good safety profile in the setting of tumor-related biliary obstruction in patients with normal or near-normal bilirubin levels in this series, without evidence of therapy-related progressive leukocytosis, bilirubin increase, or infectious or biliary complications after treatment.

Agreement between competing imaging measures of response of hepatocellular carcinoma to yttrium-90 radioembolization.

PURPOSE: There are currently at least six major competing criteria used to determine response to yttrium-90 and other liver-directed therapies, including: (i) Response Evaluation Criteria in Solid Tumors (RECIST); (ii) World Health Organization (WHO), (iii) volumetric, (iv) two-dimensional (2D) European Association for the Study of the Liver (EASL), and (v) three-dimensional (3D) EASL criteria; and (vi) functional diffusion-weighted (DW) magnetic resonance (MR) imaging. This study evaluated agreement among these competing tumor response classification schemes based on quantitative measurements of tumor size, necrosis, and changes in water mobility. MATERIALS AND METHODS: In this retrospective study, 20 patients with hepatocellular carcinoma (HCC) underwent (90)Y radioembolization. The patients' tumor burden before and 3-6 months after treatment was assessed with MR imaging. The percent change in size of tumors was used to classify patients into response categories. kappa and agreement statistics were used to compare concordance among the different criteria. RESULTS: Conventional size criteria (RECIST, WHO, and volumetric) all had a substantial level of agreement (kappa = 0.76-0.78) when classifying patients into response categories. However, the conventional size criteria in relation to 2D or 3D EASL had only slight to moderate concurrence, with kappa statistics as low as 0.06. Two-dimensional EASL criteria and functional DW MR imaging resulted in the highest response rates, 55% (n = 11) and 75% (n = 15), respectively, whereas conventional size criteria produced lower response rates. CONCLUSIONS: Classification of HCC response to (90)Y radioembolization is related to which of the competing criteria are used. It is recommended that anatomic imaging criteria be used as the primary method to determine response and functional imaging criteria be used as a complementary secondary method.

Radiation lobectomy: preliminary findings of hepatic volumetric response to lobar yttrium-90 radioembolization.

PURPOSE: To describe volumetric changes of "radiation lobectomy," a manifestation of hepatic parenchymal response to lobar (90)Y microsphere radioembolization. METHODS: Twenty patients exhibiting this phenomenon were identified. Pre- and posttreatment absolute right and left hepatic lobar volume (HLV), relative HLV (rHLV = HLV/total liver volume), and degree of lobar atrophy (DA) or hypertrophy (DH) (DA or DH = |posttreatment rHLV - pretreatment rHLV|) were determined. Laboratory toxicities, tumor response, and patient survival were also assessed. RESULTS: Twenty patients with primary (HCC, n = 17; peripheral cholangiocarcinoma, n = 3) liver malignancies demonstrated findings of radiation lobectomy. Initial absolute right and left HLV was 955 cm(3) (range 644-1,842 cm(3), rHLV = 57%) and 719 cm(3) (range 328-1,387 cm(3), rHLV = 43%), respectively. Following (90)Y, absolute right HLV decreased to 460 cm(3) (range 185-948 cm(3), 52% reduction, rHLV = 31%, DA = 26%, P < 0.0001), while absolute left HLV increased to 1,004 cm(3) (range 560-1,558 cm(3), 40% increase, rHLV = 69%, DH = 26%, P < 0.0001). No grade 3 or 4 bilirubin toxicities were encountered. Tumor response ranged from 55% to 70% by size criteria. Forty-six percent 5-year survival was achieved in HCC patients. CONCLUSIONS: Radiation lobectomy following (90)Y radioembolization of right lobe tumors manifests extensive contralateral lobar hypertrophy, high response rates, and prolonged survival. This phenomenon was noted in 6.4% (20/315) of the entire cohort and 19.8% (20/101) of patients with unilobar right lobe tumors. Further investigation is necessary to determine contributing factors that may predict this effect.

Radiologic findings following Y90 radioembolization for primary liver malignancies.

A therapy gaining rapid clinical adoption involves radioembolization with the use of Yttrium-90 (90Y) microspheres. The 20-60 microm-sized microspheres are injected trans-arterially and flow to hepatic tumors given their preferential blood supply from the hepatic artery. Once they lodge in the arterioles, they impart a very intense local radiotherapeutic effect. Given the combined radiation and embolic effect, the imaging findings imparted by this mode of action differ significantly from other treatments. This work represents a comprehensive review of the imaging findings following radioembolization in patients with primary liver tumors. The report discusses imaging response, benign secondary effects, and complications. This should help educate the radiologist on imaging findings that should be expected following radioembolization and therefore aid in the proper image interpretation.

Radioembolization for the treatment of unresectable hepatocellular carcinoma: a clinical review.

Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world. The majority of patients with HCC present with unresectable disease. These patients have historically had limited treatment options secondary to HCC demonstrating chemoresistance to the currently available systemic therapies. Additionally, normal liver parenchyma has shown intolerance to tumoricidal radiation doses, limiting the use of external beam radiation. Because of these limitations, novel percutaneous liver-directed therapies have emerged. The targeted infusion of radioactive microspheres (radioembolization) represents one such therapy. Radioembolization is a minimally invasive transcatheter therapy through which radioactive microspheres are infused into the hepatic arteries that supply tumor. Once infused, these microspheres traverse the hepatic vascular plexus and selectively implant within the tumor arterioles. Embedded within the arterioles, the 90Y impregnated microspheres emit high energy and low penetrating radiation doses selectively to the tumor. Radioembolization has recently shown promise for the treatment of patients with unresectable HCC. The objective of this review article is to highlight two currently available radioembolic devices (90Y, 188Rh) and provide the reader with a recent review of the literature.

Incidental hyperdensities within the reticuloendothelial system.

This is a case report of a 79-year-old woman who was found to have numerous hyperdense nodular lesions in the upper abdomen, which were incidentally discovered during routine follow-up of a lung nodule. These hyperdense lesions included a lace-like reticular distribution within the liver, multiple extremely dense lymph nodes, and a shrunken hyperdense spleen. We discuss differential considerations for such a constellation of findings and explain why we believe the findings in this case are consistent with prior thorium dioxide exposure. We conclude with a discussion of the pathophysiology and important complications of thorium dioxide exposure and the best imaging modalities for its detection. We believe that this is an important entity that all physicians should be aware of because even though it is seldom seen today, it has characteristic imaging findings and the correct diagnosis is critical given the increased risk of malignancy for which such patients should be screened for.

Treating and downstaging hepatocellular carcinoma in the caudate lobe with yttrium-90 radioembolization.

PURPOSE: This study was designed to determine the technical feasibility, safety, efficacy, and potential to downstage patients to within transplantation criteria when treating patients with hepatocellular carcinoma (HCC) of the caudate lobe using Y90 radioembolization. METHODS: During a 4-year period, 8 of 291 patients treated with radioembolization for unresectable HCC had disease involving the caudate lobe. All patients were followed for treatment-related clinical/biochemical toxicities, serum tumor marker response, and treatment response. Imaging response was assessed with the World Health Organization (WHO) and European Association for the Study of the Liver (EASL) classification schemes. Pathologic response was reported as percent necrosis at explantation. RESULTS: Caudate lobe radioembolization was successfully performed in all eight patients. All patients presented with both cirrhosis and portal hypertension. Half were United Network for Organ Sharing (UNOS) stage T3 (n = 4, 50%). Fatigue was reported in half of the patients (n = 4, 50%). One (13%) grade 3/4 bilirubin toxicity was reported. One patient (13%) showed complete tumor response by WHO criteria, and three patients (38%) showed complete response using EASL guidelines. Serum AFP decreased by more than 50% in most patients (n = 6, 75%). Four patients (50%) were UNOS downstaged from T3 to T2, three of who underwent transplantation. One specimen showed histopathologic evidence of 100% complete necrosis, and two specimens demonstrated greater than 50% necrosis. CONCLUSIONS: Radioembolization with yttrium-90 appears to be a feasible, safe, and effective treatment option for patients with unresectable caudate lobe HCC. It has the potential to downstage patients to transplantation.

Radioembolization of colorectal hepatic metastases using yttrium-90 microspheres.

BACKGROUND: : The objective of the current study was to determine the safety and efficacy of Yttrium-90 (Y90) microsphere treatment in patients with liver-dominant colorectal metastases. METHODS: : Seventy-two patients with unresectable hepatic colorectal metastases were treated at a targeted absorbed dose of 120 Gray (Gy). Safety and toxicity were assessed using version 3 of the National Cancer Institute Common Terminology Criteria. Response was assessed by anatomic imaging and positron emission tomography (PET). Survival from the diagnosis of hepatic metastases and first treatment were estimated using the Kaplan-Meier method. Substratification analyses were performed. RESULTS: : The median dose delivered was 118 Gy. Treatment-related toxicities included fatigue (61%), nausea (21%), and abdominal pain (25%). Grade 3 and 4 bilirubin toxicities were observed in 9 of 72 patients (12.6%). The tumor response rate was 40.3%. The median time to hepatic progression was 15.4 months, and the median response duration was 15 months. The PET response rate was 77%. Overall survival from the first Y90 treatment was 14.5 months. Tumor replacement (< or =25% vs >25%) was associated with significantly greater median survival (18.7 months vs 5.2 months). The presence of extrahepatic disease was associated negatively with overall survival (7.9 months vs 21 months). Overall survival from the date of initial hepatic metastases was 34.6 months. A subset analysis of patients who had an Eastern Cooperative Oncology Group performance status of 0 demonstrated a median survival of 42.8 months and 23.5 months from the time of hepatic metastases and Y90 treatment, respectively. CONCLUSIONS: : Y90 liver therapy appears to provide sustained disease stabilization with acceptable toxicity. Asymptomatic patients with preserved liver function at the time of Y90 appeared to benefit most from treatment. Cancer 2009. (c) 2009 American Cancer Society.

Alpha-fetoprotein response after locoregional therapy for hepatocellular carcinoma: oncologic marker of radiologic response, progression, and survival.

PURPOSE: Alpha-fetoprotein (AFP) is considered to be an indicator of tumor activity in hepatocellular carcinoma (HCC). We present a novel correlation of AFP response to radiologic response, time-to-progression (TTP), progression-free survival (PFS), and overall survival (OS) in patients treated with locoregional therapies. PATIENTS AND METHODS: Four hundred sixty-three patients with HCC were treated with chemoembolization or radioembolization at our institution. One hundred twenty-five patients with baseline AFP higher than 200 ng/mL were studied for this analysis. AFP response was defined as more than 50% decrease from baseline. One hundred nineteen patients with follow-up imaging were studied for the AFP imaging correlation analysis. AFP response was correlated to radiologic response, TTP, PFS, and OS. Multivariate analyses were performed. RESULTS: Eighty-one patients (65%) showed AFP response. AFP response was seen in 26 (55%) of 47 and 55 (70%) of 78 of patients treated with chemoembolization and radioembolization, respectively (P = .12). WHO response was seen in 41 (53%) of 77 and 10 (24%) of 42 of AFP responders and nonresponders, respectively (P = .002). The hazard ratio (HR) for TTP in AFP nonresponders compared with responders was 2.8 (95% CI, 1.5 to 5.1). The HR for PFS was 4.2 (95% CI, 2.4 to 7.2) in AFP nonresponders compared with responders. The HR for OS in AFP nonresponders compared with responders was 5.5 (95% CI, 3.1 to 9.9) and 2.7 (95% CI, 1.6 to 4.6) on univariate and multivariate analyses, respectively. CONCLUSION: The data presented support the use of AFP response seen after locoregional therapy as an ancillary method of assessing tumor response and survival, as well as an early objective screening tool for progression by imaging.

Burned ear: the use of a staged Nagata technique for ear reconstruction.

Four features, manifested in various combinations, characterise deformity in the burned ear: (i) the presence of scarred skin at the site of and surrounding the ear, with dramatic loss of skin elasticity; (ii) the presence of longitudinal scars of the pinna due to previous drainage of the perichondritis as an initial trial for saving the ear; (iii) absence of different components of the framework of the ear, mostly the helix/antihelix complex (the cartilage-containing part) with or without the ear lobule; (iv) scarred chest wall due to associated burns of the skin of the chest. In the face of these deformities, the surgical goals for auricular reconstruction include the following: (i) removal of the remaining cartilage of the burned ear, part or the whole of it in severe cases, because it may be a source of infection; (ii) wide exposure of the cartilage of the ribs through sufficient chest wall incision to overcome the severe fibrosis of the burned chest wall skin; (iii) creation of delicate smooth cartilage framework, free of sharp edges; (iv) creation of a skin pocket of sufficient size. Eight patients with a unilateral or bilateral deformity of the ear following burns were operated on during the period from May 2006 to July 2007, with a median age of 23.25 years. There was a good colour match between the reconstructed auricle and the surrounding skin. Patient satisfaction was high and the results were well accepted.

Treatment of unresectable cholangiocarcinoma using yttrium-90 microspheres: results from a pilot study.

BACKGROUND: The objective of this report was to present data from an open-label cohort study in which patients with intrahepatic cholangiocarcinoma (ICC) underwent radioembolization with yttrium-90 ((90)Y) microspheres. METHODS: Twenty-four patients with histologically proven ICC were treated. The planned target dose was 120 Gray. Patients were stratified according to Eastern Cooperation Oncology Group (ECOG) performance status, tumor morphology (infiltrative vs peripheral), tumor distribution (solitary vs multifocal), and the presence or absence of portal vein thrombosis (PVT). Before and after the procedure, the following variables were assessed: 1) biochemical and clinical toxicity, 2) imaging (computed tomography/magnetic resonance imaging) response according to World Health Organization and European Association for the Study of Liver Disease (EASL) criteria, and 3) median survival after the first treatment using Kaplan-Meier methodology. RESULTS: In total, 48 (90)Y treatments were administered to hepatic segments or lobes. Fatigue and transient abdominal pain were reported in 18 patients (75%) and 10 patients (42%), respectively. One patient (4%) developed grade 3 bilirubin toxicity. One patient (4%) developed a treatment-related gastroduodenal ulcer. On imaging follow-up of 22 patients, tumors demonstrated a partial response in 6 patients (27%), stable disease in 15 patients (68%), and progressive disease in 1 patient (5%). By using EASL guidelines, 17 patients (77%) showed >50% tumor necrosis on imaging follow-up. Two patients (9%) demonstrated 100% tumor necrosis. The median overall survival for the entire cohort (n = 24) was 14.9 months. The median survival for patients with an ECOG performance status of 0, 1, and 2 was 31.8 months, 6.1 months, and 1 month, respectively (P < .0001); the median survival for patients without and with PVT was 31.8 months and 5.7 months, respectively (P = .0003); and the median survival for patients with peripheral versus periductal-infiltrative tumors was 31.8 months and 5.7 months, respectively (P = .0005). CONCLUSIONS: Radioembolization with (90)Y may be a therapeutic option for the treatment of unresectable ICC. Cancer 2008.

Radiographic response to yttrium-90 radioembolization in anterior versus posterior liver segments.

The purpose of our study was to determine if preferential radiographic tumor response occurs in tumors located in posterior versus anterior liver segments following radioembolization with yttrium-90 glass microspheres. One hundred thirty-seven patients with chemorefractory liver metastases of various primaries were treated with yttrium-90 glass microspheres. Of these, a subset analysis was performed on 89 patients who underwent 101 whole-right-lobe infusions to liver segments V, VI, VII, and VIII. Pre- and posttreatment imaging included either triphasic contrast material-enhanced CT or gadolinium-enhanced MRI. Responses to treatment were compared in anterior versus posterior right lobe lesions using both RECIST and WHO criteria. Statistical comparative studies were conducted in 42 patients with both anterior and posterior segment lesions using the paired-sample t-test. Pearson correlation was used to determine the relationship between pretreatment tumor size and posttreatment tumor response. Median administered activity, delivered radiation dose, and treatment volume were 2.3 GBq, 118.2 Gy, and 1,072 cm(3), respectively. Differences between the pretreatment tumor size of anterior and posterior liver segments were not statistically significant (p = 0.7981). Differences in tumor response between anterior and posterior liver segments were not statistically significant using WHO criteria (p = 0.8557). A statistically significant correlation did not exist between pretreatment tumor size and posttreatment tumor response (r = 0.0554, p = 0.4434). On imaging follow-up using WHO criteria, for anterior and posterior regions of the liver, (1) response rates were 50% (PR = 50%) and 45% (CR = 9%, PR = 36%), and (2) mean changes in tumor size were -41% and -40%. In conclusion, this study did not find evidence of preferential radiographic tumor response in posterior versus anterior liver segments treated with yttrium-90 glass microspheres.