Superselective Chemoembolization of HCC: Comparison of Short-term Safety and Efficacy between Drug-eluting LC Beads, QuadraSpheres, and Conventional Ethiodized Oil Emulsion.

PURPOSE: To study the comparative short-term safety and efficacy of transcatheter arterial chemoembolization (TACE) with drug-eluting LC Beads loaded with doxorubicin (DEBDOX), doxorubicin-eluting QuadraSpheres (hqTACE), and conventional TACE using ethiodized oil for superselective C-arm computed tomography (CT)-guided treatment of hepatocellular carcinoma (HCC) after the onset of drug shortages. MATERIALS AND METHODS: From March 2010 to March 2011, 166 patients with HCC were treated with 232 superselective TACE procedures using C-arm cone-beam CT at one institution. Patients underwent treatment depending on the availability of materials after the onset of drug shortages. Conventional TACE with doxorubicin, cisplatin, and Ethiodol was performed for 159 procedures, DEBDOX TACE was performed for 47, and hqTACE was performed for 26. Toxicity and objective response were compared at 3 months after treatment. Data were stratified for the high-risk population (Child-Pugh class B, performance status 1, bilobar disease, and/or post-resection recurrence) and initial versus repeat treatment. Kruskal-Wallis H test, Mann-Whitney U test, and Fisher exact test were used to compare the groups, with Bonferroni correction where needed. RESULTS: Whole liver response rates trended higher for conventional TACE (conventional TACE, 65.4%; DEBDOX, 63.8%; hqTACE, 53.8%) (P = .085). Only minor trends for differences in toxicity were observed between the three groups. Low-risk patients had higher whole liver (P = .001) and treated lesion (P = .007) response rates when treated with conventional TACE, but no significant differences were seen for DEBDOX and hqTACE. Treatment-naive patients also had higher whole liver (P = .012) and treated lesion (P = .056) response rates. No advantages for drug-eluting microspheres were found. CONCLUSION: Within statistical power limitations, overall toxicity and efficacy were equivalent in patients treated with LC Beads, QuadraSpheres, or ethiodized oil emulsions, including in high-risk patients, when performed superselectively with cone-beam C-arm CT guidance.

Limitations of body surface area-based activity calculation for radioembolization of hepatic metastases in colorectal cancer.

PURPOSE: To calculate absorbed radiation doses in patients treated with resin microspheres prescribed by the body surface area (BSA) method and to analyze dose-response and toxicity relationships. MATERIALS AND METHODS: A retrospective review was performed of 45 patients with colorectal carcinoma metastases who received single-session whole-liver resin microsphere radioembolization. Prescribed treatment activity was calculated using the BSA method. Liver volumes and whole-liver absorbed doses (D(WL)) were calculated. D(WL) was correlated with toxicity and radiographic and biochemical response. RESULTS: The standard BSA-based administered activity (range, 0.85-2.58 GBq) did not correlate with D(WL) (mean, 50.4 Gy; range, 29.8-74.7 Gy; r = -0.037; P = .809) because liver weight was highly variable (mean, 1.89 kg; range, 0.94-3.42 kg) and strongly correlated with D(WL) (r = -0.724; P < .001) but was not accounted for in the BSA method. Patients with larger livers were relatively underdosed, and patients with smaller livers were relatively overdosed. Patients who received D(WL) > 50 Gy experienced more toxicity and adverse events (> grade 2 liver toxicity, 46% vs 17%; P < .05) but also responded better to the treatment than patients who received D(WL)< 50 Gy (disease control, 88% vs 24%; P < .01). CONCLUSIONS: Using the standard BSA formula, the administered activity did not correlate with D(WL). Based on this short-term follow-up after salvage therapy in patients with late stage metastatic colorectal carcinoma, dose-response and dose-toxicity relationships support using a protocol based on liver volume rather than BSA to prescribe the administered activity.

Safety of 90Y radioembolization in patients who have undergone previous external beam radiation therapy.

PURPOSE: Previous external beam radiation therapy (EBRT) is theoretically contraindicated for yttrium-90 ((90)Y) radioembolization (RE) because the liver has a lifetime tolerance to radiation before becoming vulnerable to radiation-induced liver disease. We analyzed the safety of RE as salvage treatment in patients who had previously undergone EBRT. METHODS AND MATERIALS: Between June 2004 and December 2010, a total of 31 patients who had previously undergone EBRT were treated with RE. Three-dimensional treatment planning with dose-volume histogram (DVH) analysis of the liver was used to calculate the EBRT liver dose. Liver-related toxicities including RE-induced liver disease (REILD) were reviewed and classified according to Common Terminology Criteria for Adverse Events version 4.02. RESULTS: The mean EBRT and RE liver doses were 4.40 Gy (range, 0-23.13 Gy) and 57.9 Gy (range, 27.0-125.9 Gy), respectively. Patients who experienced hepatotoxicity (≥grade2; n=12) had higher EBRT mean liver doses (7.96 ± 8.55 Gy vs 1.62 ± 3.39 Gy; P=.037), the only independent predictor in multivariate analysis. DVH analysis showed that the fraction of liver exposed to ≥30 Gy (V30) was the strongest predictor of hepatotoxicity (10.14% ± 12.75% vs 0.84% ± 3.24%; P=.006). All patients with V30 >13% experienced hepatotoxicity. Fatal REILD (n=2) occurred at the 2 highest EBRT mean liver doses (20.9 Gy and 23.1 Gy) but also at the highest cumulative liver doses (91.8 Gy and 149 Gy). CONCLUSIONS: Prior exposure of the liver to EBRT may lead to increased liver toxicity after RE treatment, depending on fractional liver exposure and dose level. The V30 was the strongest predictor of toxicity. RE appears to be safe for the treatment of hepatic malignancies only in patients who have had limited hepatic exposure to prior EBRT.

Root cause analysis of gastroduodenal ulceration after yttrium-90 radioembolization.

INTRODUCTION: A root cause analysis was performed on the occurrence of gastroduodenal ulceration after hepatic radioembolization (RE). We aimed to identify the risk factors in the treated population and to determine the specific mechanism of nontarget RE in individual cases. METHODS: The records of 247 consecutive patients treated with yttrium-90 RE for primary (n = 90) or metastatic (n = 157) liver cancer using either resin (n = 181) or glass (n = 66) microspheres were reviewed. All patients who developed a biopsy-proven microsphere-induced gastroduodenal ulcer were identified. Univariate and multivariate analyses were performed on baseline parameters and procedural data to determine possible risk factors in the total population. Individual cases were analyzed to ascertain the specific cause, including identification of the culprit vessel(s) leading to extrahepatic deposition of the microspheres. RESULTS: Eight patients (3.2 %) developed a gastroduodenal ulcer. Stasis during injection was the strongest independent risk factor (p = 0.004), followed by distal origin of the gastroduodenal artery (p = 0.004), young age (p = 0.040), and proximal injection of the microspheres (p = 0.043). Prolonged administrations, pain during administration, whole liver treatment, and use of resin microspheres also showed interrelated trends in multivariate analysis. Retrospective review of intraprocedural and postprocedural imaging showed a probable or possible culprit vessel, each a tiny complex collateral vessel, in seven patients. CONCLUSION: Proximal administrations and those resulting in stasis of flow presented increased risk for gastroduodenal ulceration. Patients who had undergone bevacizumab therapy were at high risk for developing stasis.

Yttrium-90 radioembolization of renal cell carcinoma metastatic to the liver.

PURPOSE: To investigate the safety and efficacy of yttrium-90 ((90)Y) hepatic radioembolization treatment of patients with liver-dominant metastatic renal cell carcinoma (RCC) refractory to immunotherapy and targeted therapies. MATERIALS AND METHODS: Between March 2006 and December 2010, six patients with metastatic RCC underwent eight radioembolization treatments with (90)Y-labeled resin microspheres for unresectable liver-dominant metastases. All six patients had previous hepatic tumor progression despite targeted therapies or immunotherapies. All had bilobar disease and required whole-liver treatment. Clinical and biochemical toxicities were recorded, and tumor response was assessed every 2-3 months after treatment by cross-sectional imaging. RESULTS: The median dose delivered was 1.89 Gbq (range 0.41-2.03 Gbq). Grade 1 and 2 toxicities were noted in all patients, primarily fatigue. Follow-up imaging was available for five patients. In follow-up periods from 2-64 months (mean 25 months), three patients showed complete responses, and 1 patient showed a partial response by standard imaging criteria, and these patients are alive at 64 months, 55 months, 17 months, and 7 months after treatment. Two patients with rapid progression of disease died within 2 months of treatment, although hepatic malignancy or failure was not the cause of death in either patient. CONCLUSIONS: (90)Y radioembolization is a promising option for liver-dominant metastatic RCC with potential for providing long-term survival in patients refractory to or intolerant of targeted therapies.

Embolization of parasitized extrahepatic arteries to reestablish intrahepatic arterial supply to tumors before yttrium-90 radioembolization.

PURPOSE: To perform embolization of parasitized extrahepatic arteries (EHAs) before radioembolization to reestablish intrahepatic arterial supply to large, peripheral tumors, and to evaluate the technical and clinical outcomes of this intervention. MATERIALS AND METHODS: Among 201 patients retrospectively analyzed, embolization of 73 parasitized EHAs in 35 patients was performed. Most embolization procedures were performed during preparatory angiography using large particles and coils. Digital subtraction angiography (DSA), C-arm computed tomography (CT), and technetium-99m macroaggregated albumin ((99m)TcMAA) scintigraphy were used to evaluate the immediate perfusion via intrahepatic collateral channels of target tumor areas previously supplied by parasitized EHAs. Follow-up imaging of differential regional tumor response was used to evaluate microsphere distribution and clinical outcome. RESULTS: After embolization, reestablishment of intrahepatic arterial supply was confirmed by both DSA and C-arm CT in 94% of territories and by scintigraphy in 96%. In 32% of patients, the differential response of treatment could not be evaluated because of uniform disease progression. However, symmetric regional tumor response in 94% of evaluable patients indicated successful delivery of microspheres to the territories previously supplied by parasitized EHAs. CONCLUSIONS: Reestablishment of intrahepatic arterial inflow to hepatic tumors by embolization of parasitized EHAs is safe and effective and results in successful delivery of yttrium-90 microspheres to tumors previously perfused by parasitized EHAs.

Consolidation of hepatic arterial inflow by embolization of variant hepatic arteries in preparation for yttrium-90 radioembolization.

PURPOSE: Before yttrium-90 ((90)Y) radioembolization administration, the authors consolidated arterial inflow by embolizing variant hepatic arteries (HAs) to make microsphere delivery simpler and safer. The present study reviews the technical and clinical success of these consolidation procedures. MATERIALS AND METHODS: Preparatory and treatment angiograms were retrospectively analyzed for 201 patients. Variant HAs were coil-embolized during preparatory angiography to simplify arterial anatomy. Collateral arterial perfusion of territories previously supplied by variant HAs was evaluated by digital subtraction angiography (DSA), C-arm computed tomography (CT), and technetium-99m ((99m)Tc)-macroaggregated albumin (MAA) scintigraphy, and by follow-up evaluation of regional tumor response. RESULTS: A total of 47 variant HAs were embolized in 43 patients. After embolization of variant HAs, cross-perfusion into the embolized territory was depicted by DSA and by C-arm CT in 100% of patients and by (99m)Tc-MAA scintigraphy in 92.7%. Uniform progressive disease prevented evaluation in 33% of patients, but regional tumor response in patients who responded supported successful delivery of microspheres to the embolized territories in 95.5% of evaluable patients. CONCLUSIONS: Embolization of variant HAs for consolidation of hepatic supply in preparation for (90)Y radioembolization promotes treatment of affected territories via intrahepatic collateral channels.

Imaging guidance with C-arm CT: prospective evaluation of its impact on patient radiation exposure during transhepatic arterial chemoembolization.

PURPOSE: To prospectively evaluate the impact of C-arm CT on radiation exposure to hepatocellular carcinoma (HCC) patients treated by chemoembolization. MATERIALS AND METHODS: Patients with HCC (N = 87) underwent digital subtraction angiography (DSA; control group) or combined C-arm CT/DSA (test group) for chemoembolization. Dose-area product (DAP) and cumulative dose (CD) were measured for guidance and treatment verification. Contrast agent volume and C-arm CT utility were also measured. RESULTS: The marginal DAP increase in the test group was offset by a substantial (50%) decrease in CD from DSA. Use of C-arm CT allowed reduction of DAP and CD from DSA imaging (P = .007 and P = .017). Experienced operators were more efficient in substituting C-arm CT for DSA, resulting in a negligible increase (7.5%) in total DAP for guidance, compared with an increase of 34% for all operators (P = .03). For treatment verification, DAP from C-arm CT exceeded that from DSA, approaching that of conventional CT. The test group used less contrast medium (P = .001), and C-arm CT provided critical or supplemental information in 20% and 17% of patients, respectively. CONCLUSIONS: Routine use of C-arm CT can increase stochastic risk (DAP) but decrease deterministic risk (CD) from DSA. However, the increase in DAP is operator-dependent, thus, with experience, it can be reduced to under 10%. C-arm CT provides information not provided by DSA in 33% of patients, while decreasing the use of iodinated contrast medium. As with all radiation-emitting modalities, C-arm CT should be used judiciously.

Development of new hepaticoenteric collateral pathways after hepatic arterial skeletonization in preparation for yttrium-90 radioembolization.

PURPOSE: Development of new hepaticoenteric anastomotic vessels may occur after endovascular skeletonization of the hepatic artery. Left untreated, they can serve as pathways for nontarget radioembolization. The authors reviewed the incidence, anatomy, management, and significance of collateral vessel formation in patients undergoing radioembolization. MATERIALS AND METHODS: One hundred thirty-eight treatments performed on 122 patients were reviewed. Each patient underwent a preparatory digital subtraction angiogram (DSA) and embolization of all hepaticoenteric vessels in preparation for yttrium-90 ((90)Y) administration. Successful skeletonization was verified by C-arm computed tomography (CACT) and technetium-99m macroaggregated albumin ((99m)TcMAA) scintigraphy. During the subsequent treatment session, DSA and CACT were repeated before administration of (90)Y, and the detection of extrahepatic perfusion prompted additional embolization. RESULTS: Forty-two patients (34.4%) undergoing 43 treatments (31.2%) required adjunctive embolization of hepaticoenteric vessels immediately before (90)Y administration. Previous scintigraphy findings showed extrahepatic perfusion in only three cases (7.1%). Vessels were identified by DSA in 54.1%, by CACT in 4.9%, or required both in 41.0%. The time interval between angiograms did not correlate with risk of requiring reembolization (P = .297). A total of 19.7% of vessels were new collateral vessels not visible during the initial angiography. Despite reembolization, three patients (7.1%) had gastric or duodenal ulceration, compared with 1.3% who never had visible collateral vessels, all of whom underwent whole-liver treatment with resin microspheres (P = .038). CONCLUSIONS: Development of collateral hepaticoenteric anastomoses occurs after endovascular skeletonization of the hepatic artery. Identified vessels may be managed by adjunctive embolization, but patients appear to remain at increased risk for gastrointestinal complications.

Alternatives to surgery for early stage non-small cell lung cancer-ready for prime time?

Surgery is the standard of care for early stage non-small cell lung cancer (NSCLC), with lobectomy being the most oncologically sound resection. Medically inoperable patients and high-risk surgical candidates require effective alternatives to surgery; even operable patients may opt for less invasive options if they are proven to achieve similar outcomes to surgery. Minimally invasive local treatment modalities including dose-intensified conformal radiation therapy, most notably stereotactic ablative radiotherapy (SABR; also known as stereotactic body radiation therapy), and thermal ablation methods such as radiofrequency ablation (RFA) and microwave ablation (MWA) are emerging as promising treatment options whose roles in the treatment of early stage lung cancer are being defined. Early clinical experience and a rapidly growing body of prospective clinical trials, primarily in medically inoperable patients, are demonstrating encouraging effectiveness and safety outcomes in some cases approaching historical results with surgery. Given the very poor prognosis of the medically inoperable patient population, these alternatives to surgery, particularly SABR, are starting to be considered appropriate first-line therapy in properly selected patients, and prospective cooperative group trials to evaluate and optimize RFA and SABR in specific patient subsets are being conducted. For operable patients, prospective multi-center and cooperative groups trials of SABR are ongoing or completed, and international randomized trials of SABR vs. surgery have been initiated. Thus, promising alternatives to surgery for early stage NSCLC are ready for prime time evaluation in the setting of clinical trials, and participation in ongoing trials for both operable and medically inoperable patients is strongly encouraged.