Purpose To evaluate safety and efficacy of combined transarterial chemoembolization (TACE) with doxorubicin-eluting beads (DEB) and sorafenib in patients with advanced hepatocellular carcinoma (HCC). Patients and Methods A prospective single-center phase II study was undertaken involving patients with unresectable HCC. The protocol involved sorafenib 400 mg twice per day combined with DEB-TACE. Safety and response were assessed. Results DEB-TACE in combination with sorafenib was successfully administered in 35 patients: mean age, 63 years; Child’s A, 89%; Barcelona Clinic Liver Cancer stage C, 64%; Eastern Cooperative Oncology Group performance status of 0 and 1, 46% and 54%, respectively; and mean index tumor size, 7.7 cm (standard deviation, ± 4.2 cm). Patients underwent 128 cycles of therapy (sorafenib plus DEB-TACE, 60 cycles; sorafenib alone, 68 cycles). Median number of cycles per patient was two (range, one to five cycles); median number of days treated with sorafenib was 71 (range, 4 to 620 days). The most common toxicities during cycle one were fatigue (94%), anorexia (67%), alterations in liver enzymes (64%), and dermatologic adverse effects (48%). Although most patients experienced at least one grade 3 to 4 toxicity, most toxicities were minor (grade 1 to 2, 83% v grade 3 to 4, 17%). Toxicity during cycle two was decreased. Over the course of the study, there were 40 sorafenib dose interruptions and 25 sorafenib dose reductions. Sorafenib plus DEB-TACE was associated with a disease control rate of 95% (Response Evaluation Criteria in Solid Tumors Group)/100% (European Association for the Study of the Liver [EASL]), with an objective response of 58% (EASL). Conclusion The combination of sorafenib and DEB-TACE in patients with unresectable HCC is well tolerated and safe, with most toxicities related to sorafenib. Toxicity is manageable with dose adjustment of sorafenib. Preliminary efficacy data are promising.

Background Data on infiltrating hepatocellular carcinoma (HCC) are limited. We sought to define treatment and outcome of patients treated with infiltrating HCC compared with patients who had advanced multifocal HCC. Methods Between January 2000 and July 2011, a total of 147 patients with advanced HCC were identified from the Johns Hopkins Hospital database (infiltrative, n = 75; multifocal, n = 72). Clinicopathologic data were compared by HCC subtype. Results Patients with infiltrating HCC had higher alfafetoprotein levels (median infiltrative, 326.5 ng/mL vs. multifocal, 27.0 ng/mL) and larger tumors (median size, infiltrating, 9.2 cm vs. multifocal, 5.5 cm) (P < 0.05). Imaging failed to reveal a discrete lesion in 42.7 % of patients with infiltrating HCC. Most infiltrating HCC lesions presented as hypointense on T1-weighted images (55.7 %) and hyperintense on T2-weighted images (80.3 %). Among patients with infiltrating HCC, most (64.0 %) were treated with intra-arterial therapy (IAT), and periprocedural morality was 2.7 %. Patients treated with IAT had longer survival versus patients receiving best support care (median survival, IAT, 12 months vs. best supportive care, 3 months; P = 0.001). Survival after IAT was similar among patients treated with infiltrating HCC versus multifocal HCC (hazard ratio 1.29, 95 % confidence interval 0.82–2.03; P = 0.27). Among infiltrating HCC patients, pretreatment bilirubin >2 mg/dL and alfa-fetoprotein >400 ng/mL were associated with worse survival after IAT (P < 0.05). Patients with progressive disease after IAT had higher risk of death versus patients who had stable/responsive disease (hazard ratio 3.53, 95 % confidence interval 1.49–8.37; P = 0.004). Conclusions Patients with infiltrative HCC often present without a discrete lesion on imaging. IAT for infiltrative HCC was safe and was associated with survival comparable to IAT outcomes for patients with multifocal HCC. Infiltrative HCC morphology is not a contraindication to IAT therapy in select patients.

PurposeRadiosurgery requires precise lesion localization. Fiducial markers enable lesion tracking, but complications from insertion may occur. The purpose of this study was to describe complications of fiducial marker insertion into pulmonary lesions.Materials and MethodsClinical and imaging records of 28 consecutive patients with 32 lung nodules or masses who underwent insertion of a total of 59 fiducial markers before radiosurgery were retrospectively reviewed.ResultsEighteen patients (67%) developed a pneumothorax, and six patients (22%) required a chest tube. The rates of pneumothorax were 82% and 40%, respectively, when 18-gauge and 19-gauge needles were used for marker insertion (P = 0.01). Increased rate of pneumothorax was also associated with targeting smaller lesions (P = 0.03) and tumors not in contact with the pleural surface (P = 0.04). A total of 11 fiducials (19%) migrated after insertion into the pleural space (10 markers) or into the airway (1 marker). Migration was associated with shorter distances from pleura to the marker deposition site (P = 0.04) and with fiducial placement outside of the target lesion (P = 0.03).ConclusionFiducial marker placement into lung lesions is associated with a high risk of pneumothorax and a risk of fiducial migration.

Background Assessment of patient performance status is often subjective. Sarcopenia—measurement of muscle wasting—may be a more objective means to assess performance status and therefore mortality risk following intra-arterial therapy (IAT). Methods Total psoas area (TPA) was measured on cross-sectional imaging in 216 patients undergoing IATof hepatic malignancies between 2002 and 2012. Sarcopenia was defined as TPA in the lowest sex-specific quartile. Impact of sarcopenia was assessed relative to other clinicopathological factors. Results Indications for IAT included hepatocellular carcinoma (51 %), intrahepatic cholangiocarcinoma (13 %), colorectal liver metastasis (7 %), or other metastatic disease (30 %). Median TPA among men (568 mm2/m2) was greater than women (413 mm2/m2). IAT involved conventional chemoembolization (54 %), drug-eluting beads (40 %), or yttrium-90 (6 %). Median tumor size was 5.8 cm; most patients had multiple lesions (74 %). Ninety-day mortality was 9.3 %; 3-year survival was 39 %. Factors associated with risk of death were tumor size (HR=1.84) and Child's score (HR=2.15) (all P <0.05). On multivariate analysis, sarcopenia remained independently associated with increased risk of death (lowest vs. highest TPA quartile, HR=1.84; P =0.04). Sarcopenic patients had a 3-year survival of 28 vs. 44 % for non-sarcopenic patients. Conclusions Sarcopenia was an independent predictor of mortality following IAT with sarcopenic patients having a twofold increased risk of death. Sarcopenia is an objective measure of frailty that can help clinical decision-making regarding IAT for hepatic malignancies.

Purpose To demonstrate that hepatic tumor volume and enhancement pattern measurements can be obtained in a time efficient and reproducible manner on a voxel-by-voxel basis to provide a true 3D volumetric assessment. Materials and Methods Retrospective evaluation of MRI data obtained from 20 patients recruited for a single-institution prospective study. All patients carried a diagnosis of hepatocellular carcinoma (HCC) and underwent drug-eluting beads transcatheter arterial chemoembolization (DEB-TACE) for the first time. All patients had undergone contrast-enhanced MRI before and after DEB-TACE although poor image quality excluded 3 resulting in a final count of 17 patients. vRECIST and qEASL were measured and segmentation and processing times were recorded. Results Thirty-four scans were analyzed. The time for semi-automatic segmentation was 65±33 seconds with a range of 40–200 seconds. vRECIST and qEASL of each tumor were then computed less than one minute for each. Conclusion Semi-automatic quantitative tumor enhancement (qEASL) and volume (vRECIST) assessment is feasible in a workflow efficient time frame. Clinical correlation is necessary, but vRECIST and qEASL could become part of the assessment of intra-arterial therapy for interventional radiologists.

Intraprocedural C-arm dual-phase cone-beam CT can be used immediately after TACE with doxorubicin-eluting beads to predict HCC tumor response at 1-month MR imaging follow-up.

Purpose To evaluate safety in an interim analysis of transarterial chemoembolization (TACE) with doxorubicin-eluting beads (DEB) in 13 patients with hepatic metastases from neuroendocrine tumors (NETs) as part of a phase II trial. Methods Institutional Review Board approval and informed consent were obtained. Thirteen patients completed preliminary safety analysis. Their mean age was 65 years, Eastern Cooperative Oncology Group status was 0/1, tumor burden range was 4–75 %, and mean targeted tumor size was 5.9 cm. Up to four DEB-TACE sessions (100–300 μm beads loaded with ≤100 mg doxorubicin) within 6 months were allowed. Tumor response was assessed by magnetic resonance imaging 1 month after treatment using contrast-enhancement [European Association for the Study of the Liver (EASL) and size Response Evaluation Criteria in Solid Tumors (RECIST)] criteria. Safety was assessed by National Cancer Institute Common Terminology Criteria. Results DEB-TACE was successfully performed in all 13 patients. At 1 month follow-up, there was a mean 12 % decrease in tumor size (p <0.0003) and a 56 % decrease in tumor enhancement (p <0.0001). By EASL criteria, the targeted lesion objective response rate was 78 %. Grade 3 to 4 toxicities were fatigue (23 %), increased alanine amino transferase (15 %), hyperglycemia (15 %), and abdominal pain (8 %). Seven patients developed bilomas (54 %); all of these patients had multiple small (<4 cm) lesions. Subsequently, four underwent percutaneous drainage, three for abscess formation and one for symptoms related to mass effect. Conclusions Although biloma and liver abscess are known risks after TACE, the high incidence in our study population was unexpected and forced interruption of the trial. Although this occurred in a small group of patients, we have changed our technique and patient selection as a result of these findings, thus allowing resumption of the trial.

Purpose To determine if volumetric changes of diffusion-weighted and contrast material–enhanced magnetic resonance (MR) imaging can help assess early tumor response to intraarterial therapy (IAT) in neuroendocrine liver metastasis (NELM). Materials and Methods This retrospective single-center comprehensive imaging analysis was performed in compliance with HIPAA and was institutional review board approved. Informed patient consent was waived. Seventy-one patients (39 men; mean age, 62.3 years) with NELM treated with IAT were analyzed retrospectively. MR studies were performed before and 3–4 weeks after therapy. The index lesion was segmented to provide volumetric functional analysis of apparent diffusion coefficient (ADC) and contrast-enhanced MR imaging in the hepatic arterial phase (HAP) and portal venous phase (PVP). Tumor response was defined as increase in volumetric ADC of 15% or greater and decrease in volumetric enhancement of 25% or greater during the HAP or of 50% or greater during the PVP. Patient overall survival was the primary end point after therapy initiation. Univariate analysis included Kaplan-Meier survival curves. The Cox proportional hazards regression model was used to detect interactions between volumetric ADC and contrast-enhanced MR imaging and to calculate the hazard ratio. Results There was significant increase in mean volumetric ADC (27%, P < .0001) and significant decrease in mean volumetric enhancement during the HAP (−25.3%, P < .0001) and the PVP (−22.4%, P < .0001) in all patients. Patients who had 15% or greater volumetric ADC increase (n = 49) after therapy had better prognosis than those who had less than 15% increase in volumetric ADC (n = 22) (log-rank test, P < .002). Patients who had 25% or greater decrease in volumetric arterial enhancement (n = 40) or 50% or greater decrease in venous enhancement (n = 18) had better prognosis than those who had less than 25% decrease in volumetric arterial enhancement (n = 31) or less than 50% decrease in venous enhancement (n = 53) (log-rank test, P < .02). Conclusion Volumetric functional MR imaging criteria may act as biomarkers of early response, indicating that these criteria may be important to incorporate in future NELM clinical trials.