Martijn R. Meijerink

Irreversible Electroporation for Nonthermal Tumor Ablation in the Clinical Setting: A Systematic Review of Safety and Efficacy

PURPOSE To provide an overview of current clinical results of irreversible electroporation (IRE), a novel, nonthermal tumor ablation technique that uses electric pulses to induce cell death, while preserving structural integrity of bile ducts and vessels. METHODS All in-human literature on IRE reporting safety or efficacy or both was included. All adverse events were recorded. Tumor response on follow-up imaging from 3 months onward was evaluated. RESULTS In 16 studies, 221 patients had 325 tumors treated in liver (n = 129), pancreas (n = 69), kidney (n = 14), lung (n = 6), lesser pelvis (n = 1), and lymph node (n = 2). No major adverse events during IRE were reported. IRE caused only minor complications in the liver; however, three major complications were reported in the pancreas (bile leak [n = 2], portal vein thrombosis [n = 1]). Complete response at 3 months was 67%-100% for hepatic tumors (93%-100% for tumors o 3 cm). Pancreatic IRE combined with surgery led to prolonged survival compared with control patients (20 mo vs 13 mo) and significant pain reduction. CONCLUSIONS In cases where other techniques are unsuitable, IRE is a promising modality for the ablation of tumors near bile ducts and blood vessels. This articles gives an extensive overview of the available evidence, which is limited in terms of quality and quantity. With the limitations of the evidence in mind, IRE of central liver tumors seems relatively safe without major complications, whereas complications after pancreatic IRE appear more severe. The available limited results for tumor control are generally good. Overall, the future of IRE for difficult-to-reach tumors appears promising.

Sunitinib for Treatment of Advanced Renal Cell Cancer: Primary Tumor Response

Purpose: Nephrectomy before immunotherapy in patients with metastatic renal cell cancer (RCC) will improve patient outcome. In addition, the primary tumor is known to be refractory to cytokines. Sunitinib is now approved for treatment of advanced RCC, but its effect on the primary tumor has yet to be reported. Experimental Design: All patients treated with sunitinib for advanced RCC without prior nephrectomy were reviewed and sequential computed tomography scans were evaluated for response in the primary tumor as well as metastases according to Response Evaluation Criteria in Solid Tumors. Volumes of primary tumors and central necrotic areas were measured with the perimeter method. Results: Computed tomography scans were available for evaluation of response in 17 of 22 patients with a primary tumor in situ (1 patient with two primaries). According to Response Evaluation Criteria in Solid Tumors, 4 patients had a partial response, 12 had stable disease, and 1 had progressive disease. The one-dimensional longest diameter of the primary tumor correlated with the volumetric measurements both at baseline and at the time of evaluation of response. Excluding the patient with progressive disease, the median volume reduction was 31% associated with a median increase in the volume of necrosis of 39%. Three patients underwent nephrectomy and tumors showed extensive necrotic areas next to small fields of vital tumor cells. Conclusions: Sunitinib can induce a significant reduction in volume of primary renal cell tumors. Further trials need to address the role of nephrectomy in advanced RCC patients on sunitinib treatment.

Choi response criteria for early prediction of clinical outcome in patients with metastatic renal cell cancer treated with sunitinib

Background:Because sunitinib can induce extensive necrosis in metastatic renal cell cancer (mRCC), we examined whether criteria defined by Choi might be valuable to predict early sunitinib efficacy.Methods:Computed tomography was used for measurement of tumour lesions in mm and lesion attenuation in Hounsfield units (HUs). According to Choi criteria partial response (PR) was defined as ⩾10% decrease in size or ⩾15% decrease in attenuation.Results:A total of 55 mRCC patients treated with sunitinib were included. At first evaluation, according to the Response Evaluation Criteria in Solid Tumours (RECIST) 7 patients had PR, 38 stable disease (SD), and 10 progressive disease (PD), whereas according to Choi criteria 36 patients had PR, 6 SD and 13 PD. Median tumour attenuation decreased from 66 to 47 HUs (P⩽0.001). In patients with PR, Choi criteria had a significantly better predictive value for progression-free survival and overall survival (both Ps<0.001) than RECIST (P=0.685 and 0.191 respectively). The predictive value for RECIST increased (P=0.001 and <0.001 respectively), when best response during treatment was taken into account.Conclusion:Choi criteria could be helpful to define early mRCC patients who benefit from sunitinib, but the use of these criteria will not change the management of these patients.

MR Enteroclysis in the Diagnosis of Small-Bowel Neoplasms

PURPOSE To evaluate the diagnostic accuracy and interobserver variance of magnetic resonance (MR) enteroclysis in the diagnosis of small-bowel neoplasms, with small-bowel endoscopy, surgery, histopathologic analysis, and follow-up serving as standards of reference, and to identify MR enteroclysis characteristics capable of enabling discrimination between benign and malignant small-bowel neoplasms. MATERIALS AND METHODS This study was performed in accordance with the guidelines of the institutional review board, and the requirement for informed consent was waived. MR enteroclysis studies of 91 patients (43 women, 48 men; age range, 18-83 years) were retrospectively evaluated by two radiologists blinded to clinical details. Only studies explicitly performed to investigate or exclude the presence of small-bowel neoplasms were included. Radiologic findings were compared with findings of double-balloon endoscopy (n = 45), surgery (n = 18), esophagogastroduodenoscopy (n = 3), ileocolonoscopy (n = 2), autopsy (n = 2), and clinical follow-up for more than 18 months (n = 21). Efficacy parameters were calculated with 95% confidence intervals. Tumor characteristics were compared with the Student t test and the Fisher exact test. RESULTS Readers 1 and 2 interpreted 31 and 33 studies, respectively, as depicting a small-bowel neoplasm and 19 and 17 studies, respectively, as depicting small-bowel malignancy. In 32 patients, the presence of small-bowel neoplasm was confirmed. In 19 of these patients, the neoplasm was malignant. Sensitivity and specificity in the diagnosis of small-bowel neoplasms was 0.91 and 0.95, respectively, for reader 1 and 0.94 and 0.97, respectively, for reader 2; the kappa value was 0.95. Factors associated with malignancy were the presence of longer solitary nonpedunculated lesions, mesenteric fat infiltration, and enlarged mesenteric lymph nodes. CONCLUSION Eighty-six of 91 studies were correctly interpreted, resulting in an overall diagnostic accuracy of 0.95 for MR enteroclysis in the detection of small-bowel neoplasms. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.09090828/-/DC1.

Cardiac PET-CT: advanced hybrid imaging for the detection of coronary artery disease.

Hybrid imaging of positron emission tomography (PET) together with computed tomography (CT) is rapidly emerging. In cardiology, this new advanced hybrid imaging modality allows quantification of cardiac perfusion in combination with assessment of coronary anatomy within a single scanning session of less than 45 minutes. The near-simultaneous anatomical evaluation of coronary arteries using CT and corresponding functional status using PET provides a wealth of complementary information in patients who are being evaluated for (suspected) coronary artery disease, and could help guide clinical patient management in a novel manner. Clinical experience gained with this recently introduced advanced hybrid imaging tool, however, is still limited and its implementation into daily clinical practice remains largely unchartered territory. This review discusses principles of perfusion PET, its diagnostic accuracy, and potential clinical applications of cardiac PET-CT in patients with ischaemic heart disease. (Neth Heart J 2010;18:90–8.)

Phase I evaluation of cediranib, a selective VEGFR signalling inhibitor, in combination with gefitinib in patients with advanced tumours

AIM Cediranib is a highly potent inhibitor of vascular endothelial growth factor receptor (VEGFR) signalling. Preclinical and clinical data suggest that inhibition of the VEGFR and epidermal growth factor receptor (EGFR) pathways may be synergistic. Combination treatment with cediranib and gefitinib, an EGFR signalling inhibitor, was evaluated in patients with advanced solid tumours. PATIENTS AND METHODS Ninety patients received treatment in this four-part, open-label study (NCT00502060). The patients received once-daily oral doses of cediranib (20-45mg) and gefitinib 250mg (part A1; n=16) or 500mg (part B1; n=44). A cohort expansion phase investigated the potential pharmacokinetic interaction of cediranib 30mg with gefitinib 250mg (part A2; n=15) or 500mg (part B2; n=15). The primary objective was to assess the safety and tolerability of cediranib with gefitinib. Secondary assessments included pharmacokinetics, efficacy and pharmacodynamics. RESULTS Combination treatment was generally well tolerated; the protocol-defined maximum-tolerated dose of cediranib was 30mg/day with gefitinib 250mg/day (part A1) and cediranib 45mg/day was the maximum dose investigated with gefitinib 500mg/day (part B1). The most common adverse events were diarrhoea (84 [93%]), anorexia (63 [70%]) and fatigue (60 [67%]). Cediranib pharmacokinetic parameters were not substantially different when given alone or in combination with gefitinib. Gefitinib pharmacokinetic parameters were similar to those seen previously with gefitinib monotherapy. Efficacy results included eight (9%) confirmed partial responses (6 renal; 1 lung; 1 osteosarcoma) and 38 (42%) patients with stable disease. Pharmacodynamic assessments demonstrated changes in levels of VEGF and soluble VEGFR-2 following treatment. CONCLUSIONS Combination treatment was generally well tolerated and showed encouraging antitumour activity in patients with advanced solid tumours. These results merit further exploration.

Targeted therapies in renal cell cancer: recent developments in imaging

Targeted therapy has significantly improved the perspectives of patients with metastatic renal cell cancer (mRCC). Frequently, these new molecules cause disease stabilization rather than substantial tumor regression. As treatment options expand with the growing number of targeted agents, there is an increasing need for surrogate markers to early assess tumor response. Here, we review the currently available imaging techniques and response evaluation criteria for the assessment of tumor response in mRCC patients. For computed tomography (CT), different criteria are discussed including the Response Evaluation Criteria in Solid Tumors (RECIST), the Choi criteria, the modified Choi criteria, and the size and attenuation CT (SACT) criteria. Functional imaging modalities are discussed, such as dynamic contrast-enhanced CT (DCE-CT), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), dynamic contrast-enhanced ultrasonography (DCE-US), and positron emission tomography (PET).

Anaesthetic management during open and percutaneous irreversible electroporation

BACKGROUND Irreversible electroporation (IRE) is a novel tumour ablation technique involving repetitive application of electrical energy around a tumour. The use of pulsed electrical gradients carries a risk of cardiac arrhythmias, severe muscle contractions, and seizures. We aimed to identify IRE-related risks and the appropriate precautions for anaesthetic management. METHODS All patients who were treated with IRE were prospectively included. Exclusion criteria were arrhythmias, congestive heart failure, active coronary artery disease, and epilepsy. All procedures were performed under general anaesthesia with complete muscle relaxation during ECG-synchronized pulsing. Adverse events, cardiovascular effects, blood samples, cerebral activity, and post-procedural pain were analysed. RESULTS Twenty-eight patients underwent 30 IRE sessions for tumours in the liver, pancreas, kidney, and lesser pelvis. No major adverse events occurred during IRE. Median systolic and diastolic blood pressure increased by 44 mm Hg (range -7 to 108 mm Hg) and 19 mm Hg (range 1-50 mm Hg), respectively. Two transient minor cardiac arrhythmias without haemodynamic consequences were observed. Muscle contractions were mild and IRE caused no reactive brain activity on a simplified EEG. Pain in the first 24 h after percutaneous IRE was generally mild, but higher pain scores were reported after pancreatic treatment (mean VAS score 3; range 0-9). CONCLUSIONS Side-effects during IRE on tumours in the liver, pancreas, kidney, and lesser pelvis seem mild and manageable when current recommendations for anaesthesia management, including deep muscle relaxation and ECG synchronized pulsing, are followed. Electrical pulses do not seem to cause reactive cerebral activity and evidence for pre-existing atrial fibrillation as an absolute contra-indication for IRE is questionable.

Progression of a caval vein thrombus in two patients with primary renal cell carcinoma on pretreatment with sunitinib

1Department of Urology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands, 2Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands, 3Department of Medical Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands and 4Department of Radiology, VU University Medical Center, Amsterdam, The Netherlands

Early Detection of Local RFA Site Recurrence Using Total Liver Volume Perfusion CT: Initial Experience

RATIONALE AND OBJECTIVES The aim of this study was to prospectively evaluate the feasibility of a novel total liver volume perfusion computed tomographic technique in demonstrating treatment-site recurrence of liver metastases after radiofrequency ablation (RFA). MATERIALS AND METHODS Eleven patients considered to be at increased risk for local RFA-site tumor recurrence underwent both positron emission tomography (PET) and perfusion computed tomography (CTP): a 12-phase scan of the entire liver acquired before and 11 times after contrast injection. After coregistration, blood flow maps were created using the maximum slope method. RESULTS In all cases, the CTP-derived blood flow maps fully paralleled the PET images in showing either the absence (nine of 13 lesions) or presence (four of 13 lesions) of local RFA-site recurrence. Marginal lesions with high hepatic arterial perfusion (>50 mL/min/100 g) and low portal venous perfusion (<10 mL/min/100 g) represented recurring vital tumor tissue (P < .05). CONCLUSION Total liver volume CTP seems feasible for the detection and localization of treatment-site recurrence after RFA.