Boris Gorodetski

How I do it: a practical database management system to assist clinical research teams with data collection, organization, and reporting.

RATIONALE AND OBJECTIVES The objective of this study was to demonstrate that an intra-arterial liver therapy clinical research database system is a more workflow efficient and robust tool for clinical research than a spreadsheet storage system. The database system could be used to generate clinical research study populations easily with custom search and retrieval criteria. MATERIALS AND METHODS A questionnaire was designed and distributed to 21 board-certified radiologists to assess current data storage problems and clinician reception to a database management system. Based on the questionnaire findings, a customized database and user interface system were created to perform automatic calculations of clinical scores including staging systems such as the Child-Pugh and Barcelona Clinic Liver Cancer, and facilitates data input and output. RESULTS Questionnaire participants were favorable to a database system. The interface retrieved study-relevant data accurately and effectively. The database effectively produced easy-to-read study-specific patient populations with custom-defined inclusion/exclusion criteria. CONCLUSIONS The database management system is workflow efficient and robust in retrieving, storing, and analyzing data.

90Y Radioembolization of Colorectal Hepatic Metastases Using Glass Microspheres: Safety and Survival Outcomes from a 531-Patient Multicenter Study

Hepatic metastases of colorectal carcinoma are a leading cause of cancer-related mortality. Most colorectal liver metastases become refractory to chemotherapy and biologic agents, at which point the median overall survival declines to 4–5 mo. Radioembolization with 90Y has been used in the salvage setting with favorable outcomes. This study reports the survival and safety outcomes of 531 patients treated with glass-based 90Y microspheres at 8 institutions, making it the largest 90Y study for patients with colorectal liver metastases. Methods: Data were retrospectively compiled from 8 institutions for all 90Y glass microsphere treatments for colorectal liver metastases. Exposure to chemotherapeutic or biologic agents, prior liver therapies, biochemical parameters before and after treatment, radiation dosimetry, and complications were recorded. Uni- and multivariate analyses for predictors of survival were performed. Survival outcomes and clinical or biochemical adverse events were recorded. Results: In total, 531 patients received 90Y radioembolization for colorectal liver metastases. The most common clinical adverse events were fatigue (55%), abdominal pain (34%), and nausea (19%). Grade 3 or 4 hyperbilirubinemia occurred in 13% of patients at any time. The median overall survival from the first 90Y treatment was 10.6 mo (95% confidence interval, 8.8–12.4). Performance status, no more than 25% tumor burden, no extrahepatic metastases, albumin greater than 3 g/dL, and receipt of no more than 2 chemotherapeutic agents independently predicted better survival outcomes. Conclusion: This multiinstitutional review of a large cohort of patients with colorectal liver metastases treated with 90Y radioembolization using glass microspheres has demonstrated promising survival outcomes with low toxicity and low side effects. The outcomes were reproducible and consistent with prior reports of radioembolization.

Transarterial chemoembolization in soft-tissue sarcoma metastases to the liver – The use of imaging biomarkers as predictors of patient survival

BACKGROUND The clinical management of patients with metastatic soft-tissue sarcoma of the liver is complicated by the paucity of reliable clinical data. This study evaluated the safety profile, survival outcome as well as the role of imaging biomarkers of tumor response in metastatic soft-tissue sarcoma (mSTS) of the liver treated with conventional transarterial chemoembolization (cTACE). MATERIALS/METHODS This retrospective analysis included 30 patients with mSTS of the liver treated with cTACE. The safety profile, overall survival (OS) and progression-free survival (PFS) after the procedure were evaluated. Tumor response in each patient was assessed using RECIST, modified (m) RECIST and EASL guidelines. In addition, a 3D quantification of the enhancing tumor volume (quantitative [q] EASL) was performed. For each method, patients were classified as responders (R) and non-responders (NR), and evaluated using Kaplan-Meier and multivariate Cox proportional hazard ratio (HR) analysis. RESULTS No Grade III or IV toxicities were reported in a total of 77 procedures (mean, 2.6/patient). Median OS was 21.2 months (95% CI, 13.4-28.9) and PFS was 6.3 months (95% CI, 4.4-8.2). The enhancement-based techniques identified 11 (44%), 12 (48%) and 12 (48%) patients as R according to EASL, mRECIST and qEASL, respectively. No stratification was achieved with RECIST. Multivariate analysis identified tumor response according to mRECIST and qEASL as reliable predictors of improved patient survival (P=0.019; HR 0.3 [0.1-0.8] and P=0.006; HR 0.2 [0.1-0.6], respectively). CONCLUSION This study confirmed the role of cTACE as a safe salvage therapy option in patients with mSTS of the liver. The demonstrated advantages of enhancement-based tumor response assessment techniques over size-based criteria validate mRECIST and qEASL as preferable methods after intraarterial therapy.

Identifying Staging Markers for Hepatocellular Carcinoma before Transarterial Chemoembolization: Comparison of Three-dimensional Quantitative versus Non-three-dimensional Imaging Markers.

Purpose To test and compare the association between radiologic measurements of lesion diameter, volume, and enhancement on baseline magnetic resonance (MR) images with overall survival and tumor response in patients with unresectable hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE). Materials and Methods This HIPAA-compliant retrospective, single-institution analysis was approved by the institutional review board, with waiver of informed consent. It included 79 patients with unresectable HCC who were treated with TACE. Baseline arterial phase contrast material-enhanced (CE) MR imaging was used to measure the overall and enhancing tumor diameters. A segmentation-based three-dimensional quantification of the overall and enhancing tumor volumes was performed in each patient. Numeric cutoff values (5 cm for diameters and 65 cm(3) for volumes) were used to stratify the patient cohort in two groups. Tumor response rates according to Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST (mRECIST), and European Association for the Study of the Liver (EASL) guidelines were recorded for all groups. Survival was evaluated by using Kaplan-Meier analysis and was compared by using Cox proportional hazard ratios (HRs) after univariate and multivariate analysis. Results Stratification according to overall and enhancing tumor diameters did not result in a significant separation of survival curves (HR, 1.4; 95% confidence interval [CI]: 0.7, 2.5; P = .234; and HR, 1.6; 95% CI: 0.9, 2.8; P = .08, respectively). The stratification according to overall and enhancing tumor volume achieved significance (HR, 1.8; 95% CI: 0.9, 3.4; P = .022; and HR, 1.8; 95% CI: 1.1, 3.1; P = .017, respectively). As for tumor response, higher response rates were observed in smaller lesions compared with larger lesions, when the 5-cm threshold (27% vs 15% for mRECIST and 45% vs 24% for EASL) was used. Conclusion As opposed to anatomic tumor diameter as the most commonly used staging marker, volumetric assessment of lesion size and enhancement on baseline CE MR images is strongly associated with survival of patients with HCC who were treated with TACE.

Preclinical Benefit of Hypoxia-Activated Intraarterial Therapy with Evofosfamide in Liver Cancer

Purpose: To evaluate safety and characterize anticancer efficacy of hepatic hypoxia-activated intra-arterial therapy (HAIAT) with evofosfamide in a rabbit model. Experimental Design: VX2-tumor-bearing rabbits were assigned to 4 intra-arterial therapy (IAT) groups (n = 7/group): (i) saline (control); (ii) evofosfamide (Evo); (iii) doxorubicin–lipiodol emulsion followed by embolization with 100–300 μm beads (conventional, cTACE); or (iv) cTACE and evofosfamide (cTACE + Evo). Blood samples were collected pre-IAT and 1, 2, 7, and 14 days post-IAT. A semiquantitative scoring system assessed hepatocellular damage. Tumor volumes were segmented on multidetector CT (baseline, 7/14 days post-IAT). Pathologic tumor necrosis was quantified using manual segmentation on whole-slide images. Hypoxic fraction (HF) and compartment (HC) were determined by pimonidazole staining. Tumor DNA damage, apoptosis, cell proliferation, endogenous hypoxia, and metabolism were quantified (γ-H2AX, Annexin V, caspase-3, Ki-67, HIF1α, VEGF, GAPDH, MCT4, and LDH). Results: cTACE + Evo showed a similar profile of liver enzymes elevation and pathologic scores compared with cTACE. Neither hematologic nor renal toxicity were observed. Animals treated with cTACE + Evo demonstrated smaller tumor volumes, lower tumor growth rates, and higher necrotic fractions compared with cTACE. cTACE + Evo resulted in a marked reduction in the HF and HC. Correlation was observed between decreases in HF or HC and tumor necrosis. cTACE + Evo promoted antitumor effects as evidenced by increased expression of γ-H2AX, apoptotic biomarkers, and decreased cell proliferation. Increased HIF1α/VEGF expression and tumor glycolysis supported HAIAT. Conclusions: HAIAT achieved a promising step towards the locoregional targeting of tumor hypoxia. The favorable toxicity profile and enhanced anticancer effects of evofosfamide in combination with cTACE pave the way towards clinical trials in patients with liver cancer. Clin Cancer Res; 23(2); 536–48. ©2016 AACR.