Bronchial or Pulmonary Artery Chemoembolization for Unresectable and Unablatable Lung Metastases: A Phase I Clinical Trial.

Background Lung chemoembolization is an emerging treatment option for lung tumors, but the optimal embolic, drug, and technique are unknown. Purpose To determine the technical success rate and safety of bronchial or pulmonary artery chemoembolization of lung metastases using ethiodized oil, mitomycin, and microspheres. Materials and Methods Patients with unresectable and unablatable lung, endobronchial, or mediastinal metastases, who failed systemic chemotherapy, were enrolled in this prospective, single-center, single-arm, phase I clinical trial (December 2019-September 2020). Pulmonary and bronchial angiography was performed to determine the blood supply to the lung metastases. Based on the angiographic findings, bronchial or pulmonary artery chemoembolization was performed using an ethiodized oil and mitomycin emulsion, followed by microspheres. The primary objectives were technical success rate and safety, according to the National Cancer Institute Common Terminology Criteria for Adverse Events. CIs of proportions were estimated with the equal-tailed Jeffreys prior interval, and correlations were evaluated with the Spearman test. Results Ten participants (median age, 60 years; interquartile range, 52-70 years; six women) were evaluated. Nine of the 10 participants (90%) had lung metastases supplied by the bronchial artery, and one of the 10 participants (10%) had lung metastases supplied by the pulmonary artery. The technical success rate of intratumoral drug delivery was 10 of 10 (100%) (95% CI: 78, 100). There were no severe adverse events (95% CI: 0, 22). The response rate of treated tumors was one of 10 (10%) according to the Response Evaluation Criteria in Solid Tumors and four of 10 (40%) according to the PET Response Criteria in Solid Tumors. Ethiodized oil retention at 4-6 weeks was correlated with reduced tumor size (ρ = -0.83, P = .003) and metabolic activity (ρ = -0.71, P = .03). Pharmacokinetics showed that 45% of the mitomycin dose underwent burst release in 2 minutes, and 55% of the dose was retained intratumorally with a half-life of more than 5 hours. The initial tumor-to-plasma ratio of mitomycin concentration was 380. Conclusion Lung chemoembolization was technically successful for the treatment of lung, mediastinal, and endobronchial metastases, with no severe adverse events. Clinical trial registration no. NCT04200417 © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Georgiades et al in this issue.

Transarterial Embolization of Liver Cancer in a Transgenic Pig Model.

PURPOSE: To develop and characterize a porcine model of liver cancer that could be used to test new locoregional therapies. MATERIALS AND METHODS: Liver tumors were induced in 18 Oncopigs (transgenic pigs with Cre-inducible TP53R167H and KRASG12D mutations) by using an adenoviral vector encoding the Cre-recombinase gene. The resulting 60 tumors were characterized on multiphase contrast-enhanced CT, angiography, perfusion, micro-CT, and necropsy. Transarterial embolization was performed using 40-120 µm (4 pigs) or 100-300 µm (4 pigs) Embosphere microspheres. Response to embolization was evaluated on imaging. Complications were determined based on daily clinical evaluation, laboratory results, imaging, and necropsy. RESULTS: Liver tumors developed at 60/70 (86%) inoculated sites. Mean tumor size was 2.1 cm (range, 0.3-4 cm) at 1 week. Microscopically, all animals developed poorly differentiated to undifferentiated carcinomas accompanied by a major inflammatory component, which resembled undifferentiated carcinomas of the human pancreatobiliary tract. Cytokeratin and vimentin expression confirmed epithelioid and mesenchymal differentiation, respectively. Lymph node, lung, and peritoneal metastases were seen in some cases. On multiphase CT, all tumors had a hypovascular center, and 17/60 (28%) had a hypervascular rim. After transarterial embolization, noncontrast CT showed retained contrast medium in the tumors. Follow-up contrast-enhanced scan showed reduced size of tumors after embolization using either 40-120 µm or 100-300 µm Embosphere microspheres, while untreated tumors showed continued growth. CONCLUSIONS: Liver tumors can be induced in a transgenic pig and can be successfully treated using bland embolization.

Factors Associated With Local Tumor Control and Complications After Thermal Ablation of Colorectal Cancer Liver Metastases: A 15-year Retrospective Cohort Study.

INTRODUCTION: The purpose of this study was to identify risk factors associated with local tumor progression-free survival (LTPFS) and complications after colorectal liver metastases (CLM) thermal ablation (TA). PATIENTS AND METHODS: This retrospective analysis included 286 patients with 415 CLM undergoing TA (radiofrequency and microwave ablation) in 378 procedures from January 2003 to July 2017. Prior hepatic artery infusion (HAI), bevacizumab, pre-existing biliary dilatation, ablation modality, minimal ablation margin (MM), prior hepatectomy, CLM number, and size were analyzed as factors influencing complications and LTPFS. Statistical analysis included the Kaplan-Meier method, Cox proportional hazards model, competing risk analysis, univariate/multivariate logistic/exact logistic regressions, and the Fisher exact test. Complications were reported according to modified Society of Interventional Radiology guidelines. RESULTS: The median follow-up was 31 months. There was no LTP for MM > 10 mm. Smaller tumor size, increased MM, and prior hepatectomy correlated with longer LTPFS. The major complications occurred following 28 (7%) of 378 procedures. There were no biliary complications in HAI-naive patients, versus 11% in HAI patients (P < .001), of which 7% were major. Biliary complications predictors in HAI patients included biliary dilatation, bevacizumab, and MM > 10 mm. In HAI patients, ablation with 6 to 10 mm and > 10 mm MM resulted in major biliary complication rates of 4% and 21% (P = .0011), with corresponding LTP rates of 24% and 0% (P = .0033). In HAI-naive patients, the LTP rates for 6 to 10 mm and > 10 mm MM were 27% and 0%, respectively. CONCLUSIONS: No LTP was seen for MM > 10 mm. Biliary complications occurred only in HAI patients, especially in those with biliary dilatation, bevacizumab, and MM > 10 mm. In HAI patients, MM of 6 to 10 mm resulted in 76% local tumor control and 4% major biliary complications incidence.

Re-Appraisal of Echocardiographic Assessment in Patients with Pulmonary Embolism: Prospective Blinded Long-Term Follow-Up.

BACKGROUND: Acute pulmonary embolism (PE) is considered to be one of the most common cardiovascular diseases with considerable mortality. Conflicting data imply possible role for echocardiography in assessing this disease. OBJECTIVES: To determine which of the echo parameters best predicts short-term and long-term mortality in patients with PE. METHODS: We prospectively enrolled 235 patients who underwent computed tomography of pulmonary arteries (CTPA) and transthoracic Echocardiography (TTE) within < 24 hours. TTE included a prospectively designed detailed evaluation of the right heart including right ventricular (RV) myocardial performance index (RIMP), RV end diastolic and end systolic area, RV fractional area change, acceleration time (AT) of pulmonary flow and visual estimation. Interpretation and performance of TTE were blinded to the CTPA results. RESULTS: Although multiple TTE parameters were associated with PE, all had low discriminative capacity (AUC < 0.7). Parameters associated with 30-day mortality in univariate analysis were acceleration time (AT) < 81 msec (P = 0.04), stroke volume < 44 cc (P = 0.005), and RIMP > 0.42 (P = 0.05). The only RV independent echo parameter associated with poor long-term prognosis (adjusted for significant clinical, and routine echo associates of mortality) was RIMP (hazard ratio 3.0, P = 0.04). The only independent RV echo parameters associated with mortality in PE patients were RIMP (P = 0.05) and AT (P = 0.05). Addition of RIMP to nested models eliminated the significance of all other parameters assessing RV function. CONCLUSIONS: Doppler-based parameters like pulmonary flow AT, RIMP, and stroke volume, have additive value in addition to visual RV estimation to assess prognosis in patients with PE.

Utilization of integrated angiography-CT interventional radiology suites at a tertiary cancer center.

BACKGROUND: Integrated Angiography-Computed Tomography (ACT) suites were initially designed in the 1990's to perform complex procedures requiring high-resolution cross-sectional imaging and fluoroscopy. Since then, there have been technology developments and changes in patient management. The purpose of this study was to review the current usage patterns of a single center's integrated ACT suites. METHODS: All procedures performed in 2017 in 3 ACT suites (InterACT Discovery RT, GE Healthcare) at a tertiary cancer center were reviewed retrospectively. Usage was classified as: Standard, in which the patient underwent a single procedure using either fluoroscopy, CT, or ultrasound (US); Combined, in which the patient underwent a single procedure utilizing both fluoroscopy and CT; or Staged, in which the patient underwent 2 separate but successive procedures using fluoroscopy and CT individually. The most frequently performed Combined and Staged procedures were further reviewed to determine how the different modalities were used. The duration of the most common Staged procedures was compared to analogous procedures' durations in single modality rooms over the period Jan 2016 to Sep 2019. RESULTS: A total of 3591 procedures were performed on 2678 patients in the 3 ACT Suites. 80% of patients underwent a Standard procedure using fluoroscopy (38%), CT (32%) or US (10%) and accounted for 70% of the room occupation time. Fourteen and three percent of the patients underwent Combined or Staged procedures, occupying 19 and 5% of the room time, respectively. The remaining procedures were classified as both Combined and Staged, representing 3% of the patients and 6% of the room occupation time. The most common Combined procedures were drainages, hepatic arterial embolizations or radioembolizations, arterial, and biliary interventions. The most common Staged procedures were multiple drainages and hepatic arterial embolizations followed by biopsies or ablations. The room occupation time for liver tumor embolization and ablation was significantly shorter (p < 0.01) when performed in a Staged fashion versus the analogous procedures in single modality room. CONCLUSION: An integrated ACT system provides the capability to perform complex Combined or Staged procedures as well as scheduling flexibility by allowing any type of case to be performed in the IR suite.

Induction and characterization of pancreatic cancer in a transgenic pig model.

BACKGROUND: Preclinical testing of new locoregional therapies for pancreatic cancer has been challenging, due to the lack of a suitable large animal model. PURPOSE: To develop and characterize a porcine model of pancreatic cancer. Unlike small animals, pigs have similar physiology, drug dosing, and immune response to humans. Locoregional therapy in pigs can be performed using the same size catheters and devices as in humans. METHODS: The Oncopig is a transgenic pig with Cre-inducible TP53R167H and KRASG12D mutations. In 12 Oncopigs, CT-guided core biopsy of the pancreas was performed. The core biopsy was incubated with an adenoviral vector carrying the Cre recombinase gene. The transformed core biopsy was injected back into the pancreas (head, tail, or both). The resulting tumors (n = 19) were characterized on multi-phase contrast-enhanced CT, and on pathology, including immunohistochemistry. Angiographic characterization of the tumors was performed in 3 pigs. RESULTS: Pancreatic tumors developed at 19 out of 22 sites (86%) that were inoculated. Average tumor size was 3.0 cm at 1 week (range: 0.5-5.1 cm). H&E and immunohistochemical stains revealed undifferentiated carcinomas, similar to those of the pancreatobiliary system in humans. Neoplastic cells were accompanied by a major inflammatory component. 1 of 12 pigs only had inflammatory nodules without evidence of neoplasia. On multiphase CT, tumors were hypovascular compared to the normal pancreas. There was no pancreatic duct dilation. In 3 pigs, angiography was performed, and in all 3 cases, the artery supplying the pancreatic tumor could be catheterized using a 2.4 F microcatheter. Selective angiography showed the pancreatic tumor, without extra-pancreatic perfusion. CONCLUSION: Pancreatic cancer can be induced in a transgenic pig. Intra-arterial procedures using catheters designed for human interventions were technically feasible in this large animal model.

CT findings are highly predictive for perforation in patients with diffuse large B-cell lymphoma involving the intestines.

Patients with diffuse large B-cell lymphoma (DLBCL) presenting with intestinal involvement are prone to develop perforation. Identification of those who are at high risk for this complication would enable a rational-based decision regarding preemptive surgery. Although computed tomography (CT) is widely used at diagnosis, data regarding its ability to predict intestinal perforation are scanty. We performed a retrospective single-center study, including all consecutive DLBCL patients presented with intestinal involvement, assessing predictors for perforation with an emphasis on CT-related parameters. Forty-nine patients were included, 43 (88%) underwent CT scan at diagnosis. Ten patients (20%) developed intestinal perforation. A univariate regression analysis found increased risk among patients with a concentric, transmural lesion, and a longer involved intestinal segment. In conclusion, CT scan results can define patients with DLBCL and intestinal involvement who are at risk for perforation, suggesting that a preemptive surgical resection should be considered in these cases.

Automatic assessment of cardiac load due to acute pulmonary embolism: Saddle vs. central and peripheral emboli distribution.

BACKGROUND: Changes in cardiac chambers' volumes in relations to different distributions of pulmonary embolism (PE) have not been investigated. OBJECTIVES: To compare cardiac chambers' volumes of patients with saddle, central or peripheral PE. METHODS: Consecutive patients with PE on computed tomography pulmonary angiography (CTPA), 1/2007-12/2010, divided according to emboli distribution. Software automatically provided the volumes of each cardiac compartment. We measured the ability of each chamber's volume and ratios between the right and left ventricles (RV/LV) and right and left atria (RA/LA) to discriminate between emboli locations. RESULTS: Among the 636 patients, 325 (51%) had peripheral, 278 (44%) central and 33 (5%) had saddle emboli. The RV/LV and RA/LA volume ratios discriminated well between saddle and central PE (AUC ≥0.74) and saddle and peripheral PE (AUC ≥0.83), but not between central and peripheral PE (AUC ≤0.6). CONCLUSION: Automatic volumetric analysis of diagnostic CTPAs provides rapid tool which can discriminate between cardiac responses in saddle, central or peripheral PE.

Prediction of Mortality in Pulmonary Embolism Based on Left Atrial Volume Measured on CT Pulmonary Angiography.

BACKGROUND: Preliminary reports suggest that a small left atrium (LA) is associated with severe acute pulmonary embolism (PE). This study used data derived from volumetric analyses of computed tomographic pulmonary angiography (CTPA) to investigate whether a reduced LA volume can predict adverse outcome in a large series of patients with acute PE. METHODS: We retrospectively analyzed 756 consecutive patients who received a diagnosis of acute PE by nongated CTPA between January 2007 and December 2010. Each CTPA was investigated with volumetric analysis software that automatically provides the volumes of the LA, right atrium, right ventricle, and left ventricle. A classification tree divided the cardiac chamber volumes and ratios into categories according to mortality. Cox regression assessed the association between these categories and 30-day mortality after adjustment for age, sex, and clinical background. RESULTS: The final study group consisted of 636 patients who had successful volumetric segmentation and complete outcome data. Eighty-four patients (13.2%) died within 30 days of PE diagnosis. There was a higher mortality rate among patients with an LA volume ≤62 mL compared with those with an LA volume >62 mL (19.6% vs 8.9%, respectively; HR, 2.44; P < .001), a left ventricle volume ≤67 mL (16.4% vs 8.3%; HR, 1.8; P = .024) and a right atrium/LA volume ratio >1.2 (17% vs 9.4%; HR, 2.1; P = .002). A reduced LA volume was the best predictor of adverse outcome. CONCLUSIONS: Decreased LA volume is associated with higher mortality and is the first among the various cardiac compartments to predict mortality in patients with acute PE.

Pulmonary Hypertension: A Nomogram Based on CT Pulmonary Angiographic Data for Prediction in Patients without Pulmonary Embolism.

PURPOSE: To use cardiovascular data from computerized tomographic (CT) pulmonary angiography for facilitating the identification of pulmonary hypertension (PH) in patients without acute pulmonary embolism. MATERIALS AND METHODS: The institutional human research committee approved this retrospective study; informed consent was waived. Patients without pulmonary embolism who underwent CT pulmonary angiography and echocardiography within 24 hours of each other between December 2008 and October 2012 were retrospectively identified. The diameters of the pulmonary artery, aorta, and right and left ventricles and the severity of reflux of contrast material were assessed. The volumes of each cardiac compartment were calculated. Doppler echocardiography served as a reference standard for PH. A prediction model for PH was built by using backward logistic regression and was presented on a nomogram. The prediction model was evaluated with 10-fold cross-validation, and a test group of patients was studied between November 2012 and June 2014. RESULTS: The final study group included 182 patients, of whom 98 (54%) were given a diagnosis of PH on the basis echocardiographic results. Age of 67 years or older (odds ratio [OR] = 4.46), reflux grade of 3 or higher (OR = 2.63), right atrial volume of greater than or equal to 106 cm(3) (OR = 3.59), pulmonary artery diameter greater than or equal to 28 mm (OR = 2.52) and pulmonary artery diameter to aorta diameter ratio of greater than or equal to 0.86 (OR = 2.17) were independently associated with PH. The logistic model showed good discrimination ability (area under the curve = 0.844, discrimination slope = 0.359). Tenfold cross-validation showed 85.7% sensitivity, 60.7% specificity, 71.3% positive predictive value, and 76.1% negative predictive value for identification of PH, while the test group showed similar results (84.1%, 60.5%, 71.2%, and 76.7%, respectively). CONCLUSION: Cardiovascular data derived from CT pulmonary angiography are associated with PH, and a nomogram can be created that may facilitate identification of PH after exclusion of acute pulmonary embolism.

Magnetic resonance-guided focused ultrasound surgery of breast cancer: reliability and effectiveness.

BACKGROUND: Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is a noninvasive technique that has been shown to coagulate benign and malignant tumors. The purpose of this study was to evaluate MRgFUS safety and effectiveness for the ablation of breast carcinomas. STUDY DESIGN: Thirty women with biopsy-proved breast cancer underwent MRgFUS treatment. Gadolinium-enhanced MR images were used for treatment planning and posttreatment radiologic assessment of treated tissue, and temperature-sensitive MR images provided real-time treatment monitoring. After MRgFUS, all 30 women underwent wide excision or mastectomy. The extent of thermal ablation was assessed with tumor histology. RESULTS: Treatment was well tolerated, with a minimum of adverse effects, especially when performed under local anesthesia. On pathologic examination, mean (+/-SD) necrosis of the targeted breast tumors was 96.9 +/- 4% (median 100%, range 78% to 100%) of tumor volume. Fifteen (53.5%) of 28 evaluable patients had 100% necrosis of the ablated tumor; only 3 patients (10.7%) had less than 95% necrosis. In 28 (93.3%) patients, 100% of the malignancy was within the treatment field, and 98% and 95% of tumor lay within the treatment field in 2 remaining patients. Retrospective analysis in two patients with residual tumor showed treatment was not delivered to the full recommended area, reaffirming the need for precise localization and the value of contrast-enhanced images for treatment planning. CONCLUSIONS: MRgFUS has great potential to become a viable noninvasive replacement for lumpectomy. Additional studies focusing on posttreatment image-based evaluation are needed.