Combination and Optimal Sequencing of Systemic and Locoregional Therapies in Hepatocellular Carcinoma: Proceedings from the Society of Interventional Radiology Foundation Research Consensus Panel.

Hepatocellular carcinoma, historically, has had a poor prognosis with very few systemic options. Furthermore, most patients at diagnosis are not surgical candidates. Therefore, locoregional therapy (LRT) has been widely used, with strong data supporting its use. Over the last 15 years, there has been progress in the available systemic agents. This has led to the updated Barcelona Clinic Liver Cancer (BCLC) algorithm's inclusion of these new systemic agents, with advocacy of earlier usage in those who progress on LRT or have tumor characteristics that make them less likely to benefit from LRT. However, neither the adjunct of LRT nor the specific sequencing of combination therapies is addressed directly. This Research Consensus Panel sought to highlight research priorities pertaining to the combination and optimal sequencing of LRT and systemic therapy, assessing the greatest needs across BCLC stages.

Two Affordable, High-Fidelity Central Venous Models for Ultrasound-Guided Interventional Training.

INTRODUCTION: Ultrasound-guided vascular access is an increasingly popular technique due to its reduced complication and higher success rates. Commercially bought training phantoms allow providers to develop tactile skills in a low-risk setting, but are also expensive and poorly accessible. This study analyzes the efficacy of homemade, low-cost, gelatin-based central line vascular models to teach vascular anatomy and intravascular access techniques in training physicians. METHODS: A gelatin mold was created using a mixture of unflavored gelatin, hot water, psyllium husk powder, and rubbing alcohol. Latex tubing, balloons, precooked hot dog, and tofu were inserted to simulate arteries, veins, nerves, and the sternocleidomastoid muscle, respectively. Medical students from a single institution participated in a 90-minute workshop led by interventional radiology residents. Participants completed presurveys and postsurveys that assessed knowledge acquisition and confidence levels related to acquiring central access. All images were obtained using a USB-C Butterfly iQ probe. RESULTS: Twenty medical students were analyzed after the workshop. There was a statistically significant increase in self-reported confidence in basic ultrasound use (adjusting gain, depth, probe manipulation), localizing major anatomical structures, using ultrasound for vessel access, and reported ease in identifying muscle, nerves, and major blood vessels under ultrasound. There was also a significant increase in correctly identified anatomical landmarks after the workshop, including the sternocleidomastoid muscle, internal jugular vein, carotid artery, femoral nerve, femoral artery, and femoral vein. CONCLUSIONS: Our findings suggest that our homemade, low-cost, gelatin-based models were effective in teaching vascular anatomy and ultrasound-guided vascular access techniques to training physicians.

For Hepatocellular Carcinoma Treated with Yttrium-90 Microspheres, Dose Volumetrics on Post-Treatment Bremsstrahlung SPECT/CT Predict Clinical Outcomes.

In transarterial radioembolization (TARE) of hepatocellular carcinoma (HCC) with Yttrium-90 (Y-90) microspheres, recent studies correlate dosimetry from bremsstrahlung single photon emission tomography (SPECT/CT) with treatment outcomes; however, these studies focus on measures of central tendency rather than volumetric coverage metrics commonly used in radiation oncology. We hypothesized that three-dimensional (3D) isodose coverage of gross tumor volume (GTV) is the driving factor in HCC treatment response to TARE and is best assessed using advanced dosimetry techniques applied to nuclear imaging of actual Y-90 biodistribution. We reviewed 51 lobar TARE Y-90 treatments of 43 HCC patients. Dose prescriptions were 120 Gy for TheraSpheres and 85 Gy for SIR-Spheres. All patients underwent post-TARE Y-90 bremsstrahlung SPECT/CT imaging. Commercial software was used to contour gross tumor volume (GTV) and liver on post-TARE SPECT/CT. Y-90 dose distributions were calculated using the Local Deposition Model based on post-TARE SPECT/CT activity maps. Median gross tumor volume (GTV) dose; GTV receiving less than 100 Gy, 70 Gy and 50 Gy; minimum dose covering the hottest 70%, 95%, and 98% of the GTV (D70, D95, D98); mean dose to nontumorous liver, and disease burden (GTV/liver volume) were obtained. Clinical outcomes were collected for all patients by chart and imaging review. HCC treatment response was assessed according to the modified response criteria in solid tumors (mRECIST) guidelines. Kaplan-Meier (KM) survival estimates and multivariate regression analyses (MVA) were performed using STATA. Median survival was 22.5 months for patients achieving objective response (OR) in targeted lesions (complete response (CR) or partial response (PR) per mRECIST) vs. 7.6 months for non-responders (NR, stable disease or disease progression per mRECIST). On MVA, the volume of underdosed tumor (GTV receiving less than 100 Gy) was the only significant dosimetric predictor for CR (p = 0.0004) and overall survival (OS, p = 0.003). All targets with less than CR (n = 39) had more than 20 cc of underdosed tumor. D70 (p = 0.038) correlated with OR, with mean D70 of 95 Gy for responders and 60 Gy for non-responders (p = 0.042). On MVA, mean dose to nontumorous liver trended toward significant association with grade 3+ toxicity (p = 0.09) and correlated with delivered activity (p < 0.001) and burden of disease (p = 0.05). Dosimetric models supplied area under the curve estimates of > 0.80 predicting CR, OR, and ≥grade 3 acute toxicity. Dosimetric parameters derived from the retrospective analysis of post-TARE Y-90 bremsstrahlung SPECT/CT after lobar treatment of HCC suggest that volumetric coverage of GTV, not a high mean or median dose, is the driving factor in treatment response and that this is best assessed through the analysis of actual Y-90 biodistribution.

Pathologic validation of an yttrium-90 trans-arterial radioembolization dosimetry: a case report.

Yttrium-90 (Y-90) trans-arterial radioembolization (TARE) is used in the management of unresectable hepatocellular carcinoma (HCC). During the last 5 years, dosimetry software has been developed to allow for a more rigorous approach of dose prescription in Y-90 TARE. We present here a case study of a 77-year-old woman diagnosed with HCC, who underwent a Y-90 TARE as a bridge procedure to liver resection. This clinical scenario represents a unique opportunity to illustrate the predictive value of dosimetric findings correlating dosimetry with pathological findings. In this case, Y-90 TARE dosimetry was predictive of treatment response in which the tumor received a mean dose of 156 Gy and demonstrated a complete pathologic response.

Safety of Radioembolization in the Setting of Angiographically Apparent Arterioportal Shunting.

PURPOSE: To retrospectively analyze adverse events (AE) in patients with hepatocellular carcinoma (HCC) treated with yttrium-90 radioembolization in the setting of angiographically apparent arterioportal shunts (APSs). MATERIALS AND METHODS: Thirty-two patients with HCC underwent radioembolization with APSs from January 2011 to September 2016, totaling 34 administrations using resin (6) and glass (28) microspheres. APSs were graded angiographically as segmental (9), ipsilobar (15), contralobar (7), or main portal (2), according to portal perfusion. Tumors were categorized as solitary (9), multifocal (7), or infiltrative (16). Both unilobar (25) and bilobar (7) disease was treated. Child Pugh Score was A (22), B (10), or C (2), with a median Model for End-Stage Liver Disease (MELD)/Na-MELD of 8/8.5. Median procedure dose was 132.6 Gy. AEs were graded using Combined Terminology Criteria for Adverse Events (CTCAE) version 4.0. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST). RESULTS: CTCAE grade ≥3 AEs were observed in 22% of patients. Barcelona Clinic Liver Cancer (BCLC) C patients with nonsegmental shunts who received lobar administrations had a grade ≥3 AE rate of 38% compared with the remaining cohort, which was 12% (P = .076). No events were reported in patients with segmental shunts (P = .023). Imaging analysis revealed mRECIST complete response (17), partial response (13), stable disease (3), and progressive disease (1). Overall survival at 6 months and 12 months was 72% and 57%, respectively. CONCLUSIONS: Radioembolization in the setting of APS may have a higher AE profile than reported literature when BCLC-C patients with nonsegmental shunts receive lobar administrations. Segmental shunts are generally well tolerated.

Radiofrequency vs Microwave Ablation After Neoadjuvant Transarterial Bland and Drug-Eluting Microsphere Chembolization for the Treatment of Hepatocellular Carcinoma.

AIM: To retrospectively compare the initial response, local recurrence, and complication rates of radiofrequency ablation (RFA) vs microwave ablation (MWA) when combined with neoadjuvant bland transarterial embolization (TAE) or drug-eluting microsphere chemoembolization (TACE) for the treatment of hepatocellular carcinoma (HCC). METHODS: A total of 35 subjects with Barcelona Clinic Liver Cancer (BCLC) very early and early-stage HCC (range: 1.2-4.1cm) underwent TAE (23) or TACE (12) with RFA (15) or microwave ablation (MWA) (20) from January 2009 to June 2015 as either definitive therapy or a bridge to transplant. TAE and TACE were performed with 40-400µm particles and 30-100µm plus either doxorubicin- or epirubicin-eluting microspheres, respectively. Initial response and local progression were evaluated using modified response evaluation criteria in solid tumors. Complications were graded using common terminology criteria for adverse events version 5.0. RESULTS: Complete response rates were 80% (12/15) for RFA + TAE/TACE and 95% (19/20) for MWA + TAE/TACE (P = 0.29). Local recurrence rate was 30% (4/12) for RFA + TAE/TACE and 0% (0/19) for MWA + TAE/TACE. Durability of response, defined as local disease control for duration of the study, demonstrated a significant difference in favor of MWA (P = 0.0091). There was no statistical difference in complication rates (3 vs 2). CONCLUSIONS: MWA and RFA when combined with neoadjuvant TAE or TACE have similar safety and efficacy in the treatment of early-stage HCC. MWA provided more durable disease control in this study; however, prospective data remain necessary to evaluate superiority of either modality.

In vivo quantitative whole-brain T1 rho MRI of multiple sclerosis.

BACKGROUND: To apply quantitative whole-brain T1 -rho (T1ρ ) and T2 imaging to the detection and quantification of brain changes resulting from multiple sclerosis (MS). METHODS: Twenty-three MS patients with clinically isolated syndrome (10) and relapsing remitting MS (13) phenotypes, compared with 24 age-matched healthy controls were imaged at 3 Tesla. An axial T1ρ -weighted three-dimensional turbo spin echo sequence with a variable flip angle and fluid suppression was used. Spin-lock times of 0, 20, 40, 60, 80, and 100 ms were used. Corresponding T2 maps were also acquired. RESULTS: Whole brain white matter (WM) T1ρ maps were elevated compared with controls (P = 0.002). WM lesion T1ρ and T2 values were highly correlated (r = 0.83), but T1ρ demonstrated 25% better contrast to noise ratio (P < 0.001). WM lesion T1ρ correlated with disease duration. Gray matter T1ρ was negatively correlated with the Expanded Disability Status Scale, r = -0.45, P = 0.03. Normal appearing gray matter and cortical gray matter lesions were negatively correlated on T1ρ , but not on T2 (rT1ρ = -0.63, pT1ρ = 0.03; rT2 = -0.17, pT2 = 0.6). CONCLUSION: T1ρ MRI demonstrates enhanced lesion contrast compared with T2 , and in some cases may provide complementary information. T1ρ may provide a useful measure of demyelinating processes in MS.