Venkatesh Krishnasamy

Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma

BACKGROUND & AIMS Tremelimumab is a fully human monoclonal antibody that binds to cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) on the surface of activated T lymphocytes. Ablative therapies induce a peripheral immune response which may enhance the effect of anti-CTLA4 treatment in patients with advanced hepatocellular carcinoma (HCC). This study aimed to demonstrate whether tremelimumab could be combined safely and feasibly with ablation. METHODS Thirty-two patients with HCC were enrolled: male:female: 28:4; median age: 62 (range 36-76). Patients were given tremelimumab at two dose levels (3.5 and 10mg/kg i.v.) every 4weeks for 6 doses, followed by 3-monthly infusions until off-treatment criteria were met. On day 36, patients underwent subtotal radiofrequency ablation or chemoablation. Staging was performed by contrast-enhanced CT or MRI scan every 8weeks. RESULTS No dose-limiting toxicities were encountered. The most common toxicity was pruritus. Of the 19 evaluable patients, five (26.3%; 95% CI: 9.1-51.2%) achieved a confirmed partial response. Twelve of 14 patients with quantifiable HCV experienced a marked reduction in viral load. Six-week tumor biopsies showed a clear increase in CD8+ T cells in patients showing a clinical benefit only. Six and 12-month probabilities of tumor progression free survival for this refractory HCC population were 57.1% and 33.1% respectively, with median time to tumor progression of 7.4months (95% CI 4.7 to 19.4months). Median overall survival was 12.3months (95% CI 9.3 to 15.4months). CONCLUSIONS Tremelimumab in combination with tumor ablation is a potential new treatment for patients with advanced HCC, and leads to the accumulation of intratumoral CD8+ T cells. Positive clinical activity was seen, with a possible surrogate reduction in HCV viral load. LAY SUMMARY Studies have shown that the killing of tumors by direct methods (known as ablation) can result in the immune system being activated or switched on. The immune system could potentially also recognize and kill the cancer that is left behind. There are new drugs available known as immune checkpoint inhibitors which could enhance this effect. Here, we test one of these drugs (tremelimumab) together with ablation. CLINICAL TRIAL NUMBER ClinicalTrials.gov: NCT01853618.

Characterization of a novel intrinsically radiopaque Drug-eluting Bead for image-guided therapy: DC Bead LUMI™

ABSTRACT We have developed a straightforward and efficient method of introducing radiopacity into Polyvinyl alcohol (PVA)‐2‐Acrylamido‐2‐methylpropane sulfonic acid (AMPS) hydrogel beads (DC Bead™) that are currently used in the clinic to treat liver malignancies. Coupling of 2,3,5‐triiodobenzaldehyde to the PVA backbone of pre‐formed beads yields a uniformly distributed level of iodine attached throughout the bead structure (˜ 150 mg/mL) which is sufficient to be imaged under standard fluoroscopy and computed tomography (CT) imaging modalities used in treatment procedures (DC Bead LUMI™). Despite the chemical modification increasing the density of the beads to ˜ 1.3 g/cm3 and the compressive modulus by two orders of magnitude, they remain easily suspended, handled and administered through standard microcatheters. As the core chemistry of DC Bead LUMI™ is the same as DC Bead™, it interacts with drugs using ion‐exchange between sulfonic acid groups on the polymer and the positively charged amine groups of the drugs. Both doxorubicin (Dox) and irinotecan (Iri) elution kinetics for all bead sizes evaluated were within the parameters already investigated within the clinic for DC Bead™. Drug loading did not affect the radiopacity and there was a direct relationship between bead attenuation and Dox concentration. The ability (Dox)‐loaded DC Bead LUMI™ to be visualized in vivo was demonstrated by the administration of into hepatic arteries of a VX2 tumor‐bearing rabbit under fluoroscopy, followed by subsequent CT imaging.

Vascular Closure Devices: Technical Tips, Complications, and Management

Vascular closure devices (VCDs) are used to obtain hemostasis at the vascular access site while limiting the need for manual compression. They have gained significant popularity since their introduction in the mid-1990s. In the past 20 years, there has been a multitude of different devices introduced with various mechanisms of action. Manual compression remains the gold standard but can be very time consuming and painful for the patient. VCDs are advantageous in that they can reduce time to hemostasis and patient recovery and improve patient comfort. However, a large number of catheter-based procedures are performed without these closure devices owing to lack of operator familiarity, risk of complications, and cost. Most VCDs are approved for arteriotomies between 5 and 8F, with 1 device approved for up to 21F. Major complications include infection and limb ischemia. This article provides an update on currently approved VCDs, a brief overview of the literature, and our institutional experience with these devices.

Hyponatremia Following High-Volume D5W Hydrodissection During Thermal Ablation

To the Editor, During percutaneous thermal ablation such as radiofrequency ablation (RFA) and microwave ablation (MWA), a variety of protective maneuvers that include patient repositioning, hydrodissection, gas insufflation, balloon interposition, and applicator torquing have been employed to separate the lesion of interest from surrounding organs. Hydrodissection, typically the instillation of 5 % dextrose in water (D5W) or another non-ionic fluid, has been shown to impart effective organ separation while permitting CT, ultrasound, and MRI guidance for ablation [1]. In clinical practice, high volumes of hydrodissection fluid are sometimes necessary to establish satisfactory interposition between the organs of interest secondary to tightly packed organs or fascial planes as well as free communication with the peritoneal cavity. Although D5W is isosmolar and is thought to be less likely to cause dilutional electrolyte abnormalities compared to sterile water [2], deleterious effects of very high-volume D5W instillation do occur. The present report describes a case in which profound electrolyte abnormalities were observed in a patient following hepatic MWA that employed high-volume D5W hydrodissection in order to protect the heart and stomach, which had been intimately touching the target liver lesion. A 64-year-old female with metastatic adrenocortical carcinoma underwent MWA of two large metastatic liver lesions (Fig. 1). During the procedure, 5 % dextrose in water was infused to separate the liver tumor from the heart and from the stomach (Figs. 2, 3). Of note, adequate protective distraction of the lesion and heart was not attained until a total of 6500 mL of D5W were instilled. Following successful ablation, 3700 mL of the hydrodissection fluid was aspirated, for a net fluid retention of ?2800 mL. Initial (30-min) post-procedural serum sodium concentration was 121 mEq/L compared to the pre-procedural concentration of 142 mEq/L. The patient subsequently received continuous normal saline (NS) infusion at 125 mL/h [2 mL/(kg h)]; her serum sodium concentration was corrected to 135 mEq/ L in approximately 11 h. During and following the normalization of the patient’s electrolytes, no neurologic deficits such as speech disturbance, motor impairment, and altered consciousness that may be precipitated by rapid serum sodium correction [3] were observed on this patient’s hospital stay or on follow-up 14 days after discharge. The hydrodissection technique, also known as artificial ascites, has been in practice for over a decade [4]. A nonionic, roughly isosmotic (252 mosmol/L) solution, D5W has been suggested as an ideal protective fluid for abdominal infusion prior to thermal ablation [2]. In contrast, the instillation of water, a hyposmotic fluid, is thought to be more prone than D5W to precipitate & Liwei Jiang jiangl.mail@gmail.com

Multimodality Image-Guided Cryoablation for Inoperable Tumor-Induced Osteomalacia

Tumor‐induced osteomalacia (TIO) is a debilitating paraneoplastic condition caused by small phosphaturic mesenchymal tumors (PMTs) that secrete large amounts of the phosphate‐regulating and vitamin D‐regulating hormone, FGF23. Tumor removal results in cure. However, because of high perioperative comorbidity, either from tumor location or host factors, surgery is sometimes not an option. Tumor destruction via cryoablation may be an effective option for inoperable PMTs. Three subjects with a confirmed diagnosis of TIO were studied. All three underwent cryoablation of suspected PMTs rather than surgery due to significant medical comorbidities or challenging anatomical location. Subject 3 had tumor embolization 24 hours prior to cryoablation because of the size and hypervascularity of the tumor. The success of the tumor cryoablation was defined by normalization of serum phosphate and FGF23. Cryoablation resulted in a rapid decrease in plasma intact FGF23 by 24 hours postprocedure in all three subjects (0, 2, and 9 pg/mL, respectively) with normalization of blood phosphate by postprocedure day 3. Three‐day renal tubular reabsorption of phosphate increased to 76%, 94%, and 95.2%, respectively; 1, 25(OH)2 vitamin D increased to 84, 138, and 196 pg/ml, respectively. All three had dramatic clinical improvement in pain and weakness. Two subjects tolerated the procedure well with no complications; one had significant prolonged procedure‐related localized pain. Although surgery remains the treatment of choice, cryoablation may be an effective, less invasive, and safe treatment for patients with difficult to remove tumors or who are poor surgical candidates.

Tri-axial Biopsy Needle Cauterization During Splenic Biopsy

To the Editor, Image-guided splenic interventions are rarely performed due to concern for risk of hemorrhage leading to complications with risks often outweighing the benefits. The major complication rate for large-core (14G) splenic biopsy has been reported as high as 13% [1] likely due to the highly vascular nature of the organ. Smaller-gauge core needle biopsy decreases this rate of major complications to approximately\ 2% [2]. Although core needle biopsy has the highest tissue and diagnostic yield, fine needles (22G) have fewer bleeding complications [3]. Many cystic or solid splenic lesions cannot be characterized well with imaging alone. For these patients, biopsy may be very useful, especially in malignant diseases that can have diffuse or localized splenic involvement like Hodgkin and non-Hodgkin lymphoma [2]. A 38-year-old female with history of Li-Fraumeni syndrome developed an enlarging 3-cm splenic lesion with high signal intensity on T2-weighted MRI. RF ablation of the needle track was performed without an RFA probe, with a small-gauge active uninsulated 25G stylet (Covidien/Radionics) placed inside a 22G Chiba needle, and then placed inside the outer coaxial 19G cannula, with this all inside an insulating 18G Angiocath sheath (with the hub cut off). This RFA stylet is commonly used for neurolysis and is non-disposable and always used when contained within a larger needle. The tri-axial biopsy ablation system with a grounded thermochromic, tissue-mimicking

MP18-14 MULTIPLE RADIOFREQUENCY ABLATION ZONES ON KIDNEY FUNCTION

INTRODUCTION AND OBJECTIVES: Contrast Enhanced Computed Tomography (CECT) is the most common modality of imaging a renal mass. While metrics including pixel enhancement have been described for differentiation of various types of tumors, we describe an additional technique of texture analysis. METHODS: In this Institutional Review Board (IRB) approved, Health Insurance Portability and Accountability Act (HIPAA) compliant, retrospective study, we identified 136 patients with solid, non-lipid containing enhancing renal tumors based on post-surgical pathology examination (94 Malignant, 42 Benign). Here, we test the feasibility using textural biomarkers, to objectively quantify and differentiate the textural heterogeneity of malignant subtypes, here, clear cell renal carcinoma, papillary renal carcinoma, and chromophobe from, benign subtypes, here, oncocytoma and lipid poor angiomyolipoma, using standard-of-care contrast-enhanced computed tomography (CECT) images. RESULTS: Three sets of stepwise logistic regression were used to select the best predictor among all candidate predictors from 2D GLCM, 3D GLCM and spectral (Table 1). The discrimination power gain from spectral metrics in addition to 2D and 3D GLCM combined was assessed using a one-degree freedom chi square test when comparing the area under the curve between the full model and the model without spectral metrics. The full model with 2D, 3D GLCM and spectral predictors yielded an AUC of 0.92 (95% CI: 0.87-0.96), while the model with 2D and 3D only already reached almost the same AUC. The difference between the two model was less than 0.01 (p1⁄40.89) (Figure 1). CONCLUSIONS: CECT-based texture metrics can differentiate between malignantand benign-renal tumors, with 2D and 3D GLCM metrics providing the most information for segregating malignant from benign renal tumors. In combination with other metrics such as contrast enhancement, shape metrics etc., texture metrics, have the potential to improve patient management and help stratify renal tumors using prostate CECT. Source of Funding: This project has received funding from the Whittier Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Foundation.