Steven C. Rose

Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer

Oncolytic viruses and active immunotherapeutics have complementary mechanisms of action (MOA) that are both self amplifying in tumors, yet the impact of dose on subject outcome is unclear. JX-594 (Pexa-Vec) is an oncolytic and immunotherapeutic vaccinia virus. To determine the optimal JX-594 dose in subjects with advanced hepatocellular carcinoma (HCC), we conducted a randomized phase 2 dose-finding trial (n = 30). Radiologists infused low- or high-dose JX-594 into liver tumors (days 1, 15 and 29); infusions resulted in acute detectable intravascular JX-594 genomes. Objective intrahepatic Modified Response Evaluation Criteria in Solid Tumors (mRECIST) (15%) and Choi (62%) response rates and intrahepatic disease control (50%) were equivalent in injected and distant noninjected tumors at both doses. JX-594 replication and granulocyte-macrophage colony-stimulating factor (GM-CSF) expression preceded the induction of anticancer immunity. In contrast to tumor response rate and immune endpoints, subject survival duration was significantly related to dose (median survival of 14.1 months compared to 6.7 months on the high and low dose, respectively; hazard ratio 0.39; P = 0.020). JX-594 demonstrated oncolytic and immunotherapy MOA, tumor responses and dose-related survival in individuals with HCC.

Image-guided Tumor Ablation: Standardization of Terminology and Reporting Criteria—A 10-Year Update

Image-guided tumor ablation has become a well-established hallmark of local cancer therapy. The breadth of options available in this growing field increases the need for standardization of terminology and reporting criteria to facilitate effective communication of ideas and appropriate comparison among treatments that use different technologies, such as chemical (eg, ethanol or acetic acid) ablation, thermal therapies (eg, radiofrequency, laser, microwave, focused ultrasound, and cryoablation) and newer ablative modalities such as irreversible electroporation. This updated consensus document provides a framework that will facilitate the clearest communication among investigators regarding ablative technologies. An appropriate vehicle is proposed for reporting the various aspects of image-guided ablation therapy including classification of therapies, procedure terms, descriptors of imaging guidance, and terminology for imaging and pathologic findings. Methods are addressed for standardizing reporting of technique, follow-up, complications, and clinical results. As noted in the original document from 2003, adherence to the recommendations will improve the precision of communications in this field, leading to more accurate comparison of technologies and results, and ultimately to improved patient outcomes. Online supplemental material is available for this article .

Radioembolization for unresectable neuroendocrine hepatic metastases using resin 90Y-microspheres: Early results in 148 patients

Purpose:The use of 90Y-microspheres to treat unresectable liver metastases originating from a variety of neuroendocrine tumors was reviewed. Materials and Methods:This is a retrospective review from 10 institutions of patients given 90Y-microsphere therapy for neuroendocrine hepatic metastases. Physical, radiographic, biochemical, and clinical factors associated with treatment and response were examined. All patients were followed with laboratory and imaging studies at regular intervals until death, or censured whether other therapy was given after brachytherapy. Toxicities (acute and late) were recorded, and survival of the group determined. Results:A total of 148 patients were treated with 185 separate procedures. The median age was 58 years (26–95 years) at treatment with median performance status of Eastern Cooperative Oncology Group (0). The median activity delivered was 1.14 GBq (0.33–3.30 GBq) with a median of 99% of the planned activity able to be given (38.1%–147.4%). There were no acute or delayed toxicity of Common Terminology Criteria for Adverse Events v3.0 grade 3 in 67% of patients, with fatigue (6.5%) the most common side effect. Imaging response was stable in 22.7%, partial response in 60.5%, complete in 2.7% and progressive disease in 4.9%. No radiation liver failure occurred. The median survival is 70 months. Conclusion:Radioembolization with 90Y-microspheres to the whole liver, or lobe with single or multiple fractions are safe and produce high response rates, even with extensive tumor replacement of normal liver and/or heavy pretreatment. The acute and delayed toxicity was very low without a treatment related grade 4 acute event or radiation induced liver disease in this modest-sized cohort. The significant objective response suggests that further investigation of this approach is warranted.

Treatment Parameters and Outcome in 680 Treatments of Internal Radiation With Resin 90Y-Microspheres for Unresectable Hepatic Tumors

PURPOSE Radioembolization (RE) using (90)Y-microspheres is an effective and safe treatment for patients with unresectable liver malignancies. Radiation-induced liver disease (RILD) is rare after RE; however, greater understanding of radiation-related factors leading to serious liver toxicity is needed. METHODS AND MATERIALS Retrospective review of radiation parameters was performed. All data pertaining to demographics, tumor, radiation, and outcomes were analyzed for significance and dependencies to develop a predictive model for RILD. Toxicity was scored using the National Cancer Institute Common Toxicity Criteria Adverse Events Version 3.0 scale. RESULTS A total of 515 patients (287 men; 228 women) from 14 US and 2 EU centers underwent 680 separate RE treatments with resin (90)Y-microspheres in 2003-2006. Multifactorial analyses identified factors related to toxicity, including activity (GBq) Selective Internal Radiation Therapy delivered (p < 0.0001), prescribed (GBq) activity (p < 0.0001), percentage of empiric activity (GBq) delivered (p < 0.0001), number of prior liver treatments (p < 0.0008), and medical center (p < 0.0001). The RILD was diagnosed in 28 of 680 treatments (4%), with 21 of 28 cases (75%) from one center, which used the empiric method. CONCLUSIONS There was an association between the empiric method, percentage of calculated activity delivered to the patient, and the most severe toxicity, RILD. A predictive model for RILD is not yet possible given the large variance in these data.

Image-guided tumor ablation: standardization of terminology and reporting criteria--a 10-year update.

Image-guided tumor ablation has become a well-established hallmark of local cancer therapy. The breadth of options available in this growing field increases the need for standardization of terminology and reporting criteria to facilitate effective communication of ideas and appropriate comparison among treatments that use different technologies, such as chemical (eg, ethanol or acetic acid) ablation, thermal therapies (eg, radiofrequency, laser, microwave, focused ultrasound, and cryoablation) and newer ablative modalities such as irreversible electroporation. This updated consensus document provides a framework that will facilitate the clearest communication among investigators regarding ablative technologies. An appropriate vehicle is proposed for reporting the various aspects of image-guided ablation therapy including classification of therapies, procedure terms, descriptors of imaging guidance, and terminology for imaging and pathologic findings. Methods are addressed for standardizing reporting of technique, follow-up, complications, and clinical results. As noted in the original document from 2003, adherence to the recommendations will improve the precision of communications in this field, leading to more accurate comparison of technologies and results, and ultimately to improved patient outcomes.

Revascularization for Chronic Mesenteric Ischemia: Comparison of Operative Arterial Bypass Grafting and Percutaneous Transluminal Angioplasty☆

PURPOSE To compare the relative safety and efficacy of the two primary techniques for treatment of chronic mesenteric ischemia (CMI): operative bypass grafting (OBG) and percutaneous transluminal angioplasty (PTA). PATIENTS AND METHODS Retrospective analysis of hospital charts and angiograms, and supplemental telephone follow-up were performed for 17 patients treated for CMI between January 1985 and September 1993. Nine patients underwent OBG; eight patients underwent PTA (one patient underwent two PTA procedures). RESULTS Technical success was 100% for OBG versus 30% according to angiographic criteria for PTA (although 80% had improved luminal diameter). Procedure-related mortality was 11% (one of nine patients) for OBG and 13% (one of eight) for PTA. The nonfatal major complication rate was 33% (three of nine) for OBG and 25% (two of eight) for PTA. Initial pain relief occurred in seven of nine (78%) successful OBGs and all of seven (100%) PTA procedures with lumen improvement. Long-term pain relief among OBG survivors was complete in seven of eight (88%) and four of six (67%) of PTA survivors with CMI (mean follow up, 34.5 and 9.2 months, respectively). CONCLUSIONS Due to the greater durability of results, OBG is indicated in patients with low operative risk and classic symptoms and angiographic findings of CMI ischemia. PTA is best reserved for patients with prohibitive operative risks, classic symptoms, and atherosclerotic stenoses.

Quality Improvement Guidelines for Percutaneous Needle Biopsy

THE membership of the Society of Interventional Radiology (SIR) Standards of Practice Committee represents experts in a broad spectrum of interventional procedures from both the private and academic sectors of medicine. Generally Standards of Practice Committee members dedicate the vast majority of their professional time to performing interventional procedures; as such they represent a valid broad expert constituency of the subject matter under consideration for standards production.

Research Reporting Standards for Radioembolization of Hepatic Malignancies

Primary Liver Tumors Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver; its incidence is increasing worldwide. It ranks as the sixth most common tumor and third most common cause of cancer-related mortality (1,2). Primary liver tumors include HCC and intrahepatic cholangiocarcinoma. Surgical resection is preferred over transplantation and is considered potentially curative in patients with resectable HCC and normal liver function (3). Transplantation is considered the gold standard for patients with unresectable HCC and whose disease is within the Milan criteria (4). Resection and transplantation have limited roles, given advanced disease (chronic liver disease and/or tumor extent) at presentation and limited organ availability (5–7). Chemoembolization and radiofrequency ablation represent standard therapies in treating patients and serve as a bridge to transplantation in selected patients (8,9). Radioembolization has an emerging role in “bridging” patients within criteria by delaying tumor progression. It has also been shown to downstage disease beyond the Milan, to within, transplant criteria (10–12). A recent study has demonstrated that radioembolization leads to longer time-to-progression and better toxicity profile when compared with chemoembolization (13). Patients with macrovascular tumor involvement have also exhibited evidence of clinical benefit after radioembolization (14).

Clinical Practice Guidelines for Endovascular Abdominal Aortic Aneurysm Repair: Written by the Standards of Practice Committee for the Society of Interventional Radiology and Endorsed by the Cardiovascular and Interventional Radiological Society of Europe and the Canadian Interventional Radiology Association

From the Department of Radiology, Division of Vascular Imaging and Intervention (T.G.W., S.P.K., K.Y., S.W.), Massachusetts General Hospital, Boston, Massachusetts; Department of Medical Imaging (S.K.), Scarborough General Hospital, Toronto, Ontario, Canada; Department of Interventional Radiology (P.D.), West Allis Memorial Hospital, Milwaukee, Wisconsin; Department of Radiology, Division of Interventional Radiology (B.J.D.), University of Maryland Medical Center, Baltimore, Maryland; Department of Radiology (S.C.R.), University of California San Diego Medical Center, San Diego, California; and Department of Radiology (J.F.C.), Geisinger Health System, Danville, Pennsylvania. Received May 4, 2010; final revision received May 24, 2010; accepted July 11, 2010. Address corre-

Value of Three-dimensional US for Optimizing Guidance for Ablating Focal Liver Tumors

PURPOSE To determine if three-dimensional ultrasound (3D US), by nature of its ability to simultaneously evaluate structures in three orthogonal planes and to study relationships of devices to tumor(s) and surrounding anatomic structures from any desired orientation, adds significant additional information to real-time 2D US used for placement of devices for ablation of focal liver tumors. MATERIALS AND METHODS Sixteen patients underwent focal ablation of 23 liver tumors during two intraoperative cryoablation (CA) procedures, three intraoperative radiofrequency ablation (RFA) procedures, 11 percutaneous ethanol injections (PEI) procedures, and six percutaneous RFA procedures. After satisfactory placement of the ablative device(s) with 2D US guidance, 3D US was used to reevaluate adequacy to device position. Information added by 3D US and resultant alterations in device deployment were tabulated. RESULTS 3D US added information in 20 of 22 (91%) procedures and caused the operator to readjust the number or position of ablative devices in 10 of 22 (45%) of procedures. Specifically, 3D US improved visualization and confident localization of devices in 13 of 22 (59%) procedures, detected unacceptable device placement in 10 of 22 (45%), and determined that 2D US had incorrectly predicted device orientation to a tumor in three of 22 (14%). CONCLUSIONS Compared to conventional 2D US, 3D US provides additional relationship information for improved placement and optimal distribution of ablative agents for treatment of focal liver malignancy.