A. Tam

Use of Research Biopsies in Clinical Trials: Are Risks and Benefits Adequately Discussed?

PURPOSE Although the incorporation of research biopsies into clinical trials is increasing, limited information is available about how study protocols and informed consents integrate and describe their use. METHODS All therapeutic clinical trials in which image-guided research biopsies were performed from January 1, 2005, to October 1, 2010, were identified from an interventional radiology database. Data from study protocols and informed consents were extracted and analyzed. Procedural complications were recorded. RESULTS A total of 57 clinical trials were identified, of which 38 (67%) contained at least one mandatory biopsy. The analysis of the research biopsy tumor tissue was a study end point in 95% of trials. The primary indication for a research biopsy was for integral biomarker analysis in 32% and for correlative science in 68% of trials. A statistical analytic plan for the correlative science research biopsy tumor tissue was mentioned in 26%, described as exploratory in 51%, and not mentioned in 23% of trials. For studies with mandatory biopsies, biopsy was an eligibility criterion in 71% of trials, and a statistical justification for the research biopsy sample size was present in 50% of trials. A total of 745 research biopsies were performed on 576 patients. Overall and major complication rates were 5.2% (39 of 745 biopsies) and 0.8% (six of 745 biopsies), respectively. Complication rates for intrathoracic and abdominal/pelvic solid organ biopsies were 17.1% (36 of 211 biopsies) and 1.6% (three of 189 biopsies), respectively. Site-stratified research biopsy-related risks were discussed in five consents. CONCLUSION A better representation of the risks and benefits of research biopsies in study protocols and informed consents is needed.

Feasibility of Image-Guided Transthoracic Core-Needle Biopsy in the BATTLE Lung Trial

Background: As therapy for non–small-cell lung cancer (NSCLC) patients becomes more personalized, additional tissue in the form of core-needle biopsies (CNBs) for biomarker analysis is increasingly required for determining appropriate treatment and for enrollment into clinical trials. We report our experience with small-caliber percutaneous transthoracic (PT) CNBs for the evaluation of multiple molecular biomarkers in BATTLE (biomarker-integrated approaches of targeted therapy for lung cancer elimination), a personalized, targeted therapy NSCLC clinical trial. Methods: The medical records of patients who underwent PTCNB for consideration of enrollment in BATTLE were reviewed for diagnostic yield of 11 predetermined molecular markers and procedural complications. Univariate and multivariate analyses of factors related to patient and lesion characteristics were performed to determine possible influences on diagnostic yield. Results: One hundred and seventy PTCNBs were performed using 20-gauge biopsy needles in 151 NSCLC patients screened for the trial. The biopsy specimens of 82.9% of the patients were found to have adequate tumor tissue for analysis of the required biomarkers. On multivariate analysis, metastatic lesions were 5.4 times more likely to yield diagnostic tissue as compared with primary tumors (p = 0.0079). Pneumothorax and chest tube insertion rates were 15.3% and 9.4%, respectively. Conclusions: Image-guided 20-gauge PTCNB is safe and provides adequate tissue for analysis of multiple biomarkers in the majority of patients being considered for enrollment into a personalized, targeted therapy NSCLC clinical trial. Metastatic lesions are more likely to yield diagnostic tissue as compared with primary tumors.

Bronchial artery embolization for the management of hemoptysis in oncology patients: utility and prognostic factors.

PURPOSE To evaluate the utility of bronchial artery embolization (BAE) in the oncology population and determine prognostic factors. MATERIALS AND METHODS This is a retrospective review of 30 consecutive oncology patients (20 men, 10 women; mean age, 60 years) who were referred for BAE for the management of hemoptysis from 1992 to 2007. RESULTS The amount of hemoptysis at initial embolization was massive (frank blood >300 mL per 24 hours) in 13 patients (43%), moderate (frank blood <300 mL per 24 hours) in 15 (50%), and trivial (blood-tinged sputum) in two (7%). Eighteen patients (60%) had a primary intrathoracic malignancy, seven (23%) had pulmonary metastases, and five (17%) had no evidence of malignant disease in the lung. The technical success rate, defined as the ability to selectively embolize the abnormal vessel, was 86% (32 of 37 procedures). Clinical response categories and complications were defined according to the guidelines established by the SIR Standards of Practice Committee. The major complication rate was 3%, including one case of spinal cord infarction. BAE provided symptom palliation with an immediate decrease or resolution of bleeding in 24 out of 27 patients (89%). The 30-day mortality rate for this cohort was 30%, and the median survival was 5.5 months. Survival was significantly better in patients with non-tumor-related hemoptysis than in those with tumor-related bleeding (P = .004). There was no significant difference in median survival between patients with massive hemoptysis and those with moderate/mild hemoptysis (P = .81), between patients with an emergent procedure and those with a non-emergent procedure (P = .39), and between patients who had previously undergone radiation therapy and those who had not (P = .4). CONCLUSIONS BAE is safe and effective for the oncologic patient population. In patients with tumor-related hemoptysis, the prognosis remains poor; however, for the subset of oncology patients whose hemoptysis is not related to malignant disease in the lung, the survival is significantly better.

Percutaneous Image-guided Splenic Biopsy in the Oncology Patient: An Audit of 156 Consecutive Cases

PURPOSE To assess the safety and diagnostic accuracy of percutaneous image-guided splenic biopsy in patients known to have or suspected of having malignancy. MATERIALS AND METHODS Data from all image-guided splenic biopsies performed at a single institution from January 1992 to March 2007 were retrospectively reviewed. One hundred fifty-six splenic biopsies were performed in 147 patients (78 male and 69 female patients; mean age, 54.9 years; age range, 13-81 years). The most common indications for biopsy were suspected recurrent lymphoma (n = 101, 64.7%), suspected metastatic disease (n = 39, 25%), and unknown diagnosis (n = 16, 10.3%). All biopsies were performed with computed tomographic (n = 86), ultrasonographic (n = 68), or fluoroscopic (n = 2) guidance. Most biopsies (91%) were performed with 22-gauge needles, with a mean of 2.8 passes. The mean lesion size was 3.2 cm (range, 0.8-13 cm). Final diagnosis was confirmed with splenectomy (n = 39), histopathologic correlation with concurrent biopsy or surgical specimen (n = 52), or clinical or imaging follow-up ranging from 2 weeks to 14 years (n = 44). Complications were recorded. RESULTS Sufficient tissue for pathologic analysis was obtained in 144 of the 156 biopsies (diagnostic yield, 92.3%). The overall sensitivity, specificity, and diagnostic accuracy were 83.4%, 87.8%, and 84.7%, respectively. Complications occurred in 26 biopsies (16.7%), with a 1.9% (n = 3) major complication rate and a 14.7% (n = 23) minor complication rate. Splenectomy was necessary in two patients. CONCLUSIONS Splenic biopsy in the evaluation of new or recurrent neoplasm is a minimally invasive procedure with low complication rates and a high diagnostic yield.

C-arm Cone Beam Computed Tomographic Needle Path Overlay for Fluoroscopic-Guided Placement of Translumbar Central Venous Catheters

C-arm cone beam computed tomography is an advanced 3D imaging technology that is currently available on state-of-the-art flat-panel-based angiography systems. The overlay of cross-sectional imaging information can now be integrated with real-time fluoroscopy. This overlay technology was used to guide the placement of three percutaneous translumbar inferior vena cava catheters.

From Protocols to Publications: A Study in Selective Reporting of Outcomes in Randomized Trials in Oncology

PURPOSE The decision by journals to append protocols to published reports of randomized trials was a landmark event in clinical trial reporting. However, limited information is available on how this initiative effected transparency and selective reporting of clinical trial data. METHODS We analyzed 74 oncology-based randomized trials published in Journal of Clinical Oncology, the New England Journal of Medicine, and The Lancet in 2012. To ascertain integrity of reporting, we compared published reports with their respective appended protocols with regard to primary end points, nonprimary end points, unplanned end points, and unplanned analyses. RESULTS A total of 86 primary end points were reported in 74 randomized trials; nine trials had greater than one primary end point. Nine trials (12.2%) had some discrepancy between their planned and published primary end points. A total of 579 nonprimary end points (median, seven per trial) were planned, of which 373 (64.4%; median, five per trial) were reported. A significant positive correlation was found between the number of planned and nonreported nonprimary end points (Spearman r = 0.66; P < .001). Twenty-eight studies (37.8%) reported a total of 65 unplanned end points; 52 (80.0%) of which were not identified as unplanned. Thirty-one (41.9%) and 19 (25.7%) of 74 trials reported a total of 52 unplanned analyses involving primary end points and 33 unplanned analyses involving nonprimary end points, respectively. Studies reported positive unplanned end points and unplanned analyses more frequently than negative outcomes in abstracts (unplanned end points odds ratio, 6.8; P = .002; unplanned analyses odd ratio, 8.4; P = .007). CONCLUSION Despite public and reviewer access to protocols, selective outcome reporting persists and is a major concern in the reporting of randomized clinical trials. To foster credible evidence-based medicine, additional initiatives are needed to minimize selective reporting.

A Spectrum of Nerve Injury after Thermal Ablation: A Report of Four Cases and Review of the Literature

Thermal ablation is an accepted alternative for the palliation of pain from bone metastases. Although rare, neurologic complications after thermal ablation have been reported. We present four cases, including two cases of rapid reversal of postcryoablation neurapraxia after the administration of steroid therapy, and review the literature.

Radiofrequency ablation of lung tumors.

Lung cancer is the commonest cause of cancer-related mortality throughout the world. Only 25% of patients are diagnosed early and are candidates for surgical resection with curative intent. Many early-stage patients are medically inoperable owing to comorbidities. For these patients, and for selected patients with pulmonary metastases, radiofrequency ablation is a minimally invasive therapeutic alternative. Radiofrequency ablation can be performed percutaneously, under conscious sedation, and as an outpatient or with a short hospital stay. Outcomes are similar or even superior to those obtained with more aggressive procedures, with lower complication rates. Human studies describing the feasibility, safety, and outcomes of radiofrequency ablation for the treatment of primary and secondary lung malignancies are the focus of this article.

Irreversible Electroporation of the Lumbar Vertebrae in a Porcine Model: Is There Clinical-Pathologic Evidence of Neural Toxicity?

PURPOSE To evaluate the effects of irreversible electroporation (IRE) in the porcine spine. MATERIALS AND METHODS This study was approved by the institutional animal care and use committee. Twenty computed tomographically guided IRE ablations in either a transpedicular location or directly over the posterior cortex were performed in the lumbar vertebrae of 10 pigs by a single operator. T1- and T2-weighted magnetic resonance (MR) imaging was performed with and without contrast material 2 or 7 days after ablation. Mathematical modeling was performed to estimate the extent of ablation. Clinical, radiologic, pathologic, and simulation findings were analyzed. The Miller low-bias back transformation was used to construct 95% confidence intervals for the mean absolute percentage difference between the maximum length and width of the ablation zone on MR images and pathologic measurements by using square-root-transformed data. RESULTS Bipolar IRE electrode placement and ablation were successful in all cases. The mean distances from the IRE electrode to the posterior wall of the vertebral body or the exiting nerve root were 2.93 mm ± 0.77 (standard deviation) and 7.87 mm ± 1.99, respectively. None of the animals had neurologic deficits. Well-delineated areas of necrosis of bone, bone marrow, and skeletal muscle adjacent to the vertebral body were present. Histopathologic changes showed outcomes that matched with simulation-estimated ablation zones. The percentage absolute differences in the ablation measurements between MR imaging and histopathologic examination showed the following average errors: 24.2% for length and 28.8% for width measurements on T2-weighted images, and 26.1% for length and 33.3% for width measurements on T1-weighted contrast material-enhanced images. CONCLUSION IRE ablation in the porcine spine is feasible and safe and produces localized necrosis with minimal neural toxicity. Signal intensity changes on images acquired with standard MR imaging sequences demonstrate the ablation zone to be larger than that at histopathologic examination.

Thermal Ablation of Painful Bone Metastases

Skeletal metastases are common in patients with advanced cancer. Although cancer pain can be complex, bone pain is one of the most common types of pain in oncology patients. Pain from skeletal metastases can be debilitating and result in significant morbidity and mortality. Although conventional therapies such as narcotic medication and radiation therapy remain the standard of care, many patients experience suboptimal and limited relief. Image-guided thermal ablation of bone metastases provides a minimally invasive alternative for pain palliation. This article reviews the use of radiofrequency ablation and cryoablation in the treatment of painful bone metastases.