R.H. Siegelbaum

Percutaneous Radiofrequency Ablation of Colorectal Cancer Liver Metastases: Factors Affecting Outcomes—A 10-year Experience at a Single Center

PURPOSE To identify predictors of oncologic outcomes after percutaneous radiofrequency ablation (RFA) of colorectal cancer liver metastases (CLMs) and to describe and evaluate a modified clinical risk score (CRS) adapted for ablation as a patient stratification and prognostic tool. MATERIALS AND METHODS This study consisted of a HIPAA-compliant institutional review board-approved retrospective review of data in 162 patients with 233 CLMs treated with percutaneous RFA between December 2002 and December 2012. Contrast material-enhanced CT was used to assess technique effectiveness 4-8 weeks after RFA. Patients were followed up with contrast-enhanced CT every 2-4 months. Overall survival (OS) and local tumor progression-free survival (LTPFS) were calculated from the time of RFA by using the Kaplan-Meier method. Log-rank tests and Cox regression models were used for univariate and multivariate analysis to identify predictors of outcomes. RESULTS Technique effectiveness was 94% (218 of 233). Median LTPFS was 26 months. At univariate analysis, predictors of shorter LTPFS were tumor size greater than 3 cm (P < .001), ablation margin size of 5 mm or less (P < .001), high modified CRS (P = .009), male sex (P = .03), and no history of prior hepatectomy (P = .04) or hepatic arterial infusion chemotherapy (P = .01). At multivariate analysis, only tumor size greater than 3 cm (P = .01) and margin size of 5 mm or less (P < .001) were independent predictors of shorter LTPFS. Median and 5-year OS were 36 months and 31%. At univariate analysis, predictors of shorter OS were tumor size larger than 3 cm (P = .005), carcinoembryonic antigen level greater than 30 ng/mL (P = .003), high modified CRS (P = .02), and extrahepatic disease (EHD) (P < .001). At multivariate analysis, tumor size greater than 3 cm (P = .006) and more than one site of EHD (P < .001) were independent predictors of shorter OS. CONCLUSION Tumor size of less than 3 cm and ablation margins greater than 5 mm are essential for satisfactory local tumor control. Tumor size of more than 3 cm and the presence of more than one site of EHD are associated with shorter OS.

Split-Dose Technique for FDG PET/CT–guided Percutaneous Ablation: A Method to Facilitate Lesion Targeting and to Provide Immediate Assessment of Treatment Effectiveness

PURPOSE To describe a split-dose technique for fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT)-guided ablation that permits both target localization and evaluation of treatment effectiveness. MATERIALS AND METHODS Institutional review board approved the study with a waiver of consent. From July to December 2011, 23 patients (13 women, 10 men; mean age, 59 years; range, 35-87 years) with 29 FDG-avid tumors (median size, 1.4 cm; range, 0.6-4.4 cm) were targeted for ablation. The location of the lesion was the liver (n = 23), lung (n = 4), adrenal gland (n = 1), and thigh (n = 1). Radiofrequency ablation was performed in 17 lesions; microwave ablation, in six; irreversible electroporation, in five; and cryoablation, in one. The pathologic condition of the tumor was metastatic colorectal adenocarcinoma in 18 lesions, primary hepatocellular carcinoma in one lesion, and a variety of metastatic tumors in the remaining 10 lesions. A total of 4 mCi (148 MBq) of FDG was administered before the procedure for localization and imaging guidance. At completion of the ablation, an additional 8 mCi (296 MBq) of FDG was administered to assess ablation adequacy. Results of subsequent imaging follow-up were used to determine if postablation imaging after the second dose of FDG reliably helped predict complete tumor ablation. Descriptive statistics were used to summarize the results. RESULTS Twenty-eight of 29 (97%) ablated lesions showed no residual FDG activity after the second intraprocedural FDG dose. One patient with residual activity underwent immediate biopsy that revealed residual viable tumor and was immediately re-treated. Follow-up imaging at a median of 155 days (range, 92-257 days) after ablation showed local recurrences in two (7%) lesions that were originally negative at postablation PET. CONCLUSION Split-dose FDG PET/CT may be a useful tool to provide both guidance and endpoint evaluation, allowing an opportunity for repeat intervention if necessary. Further work is necessary to validate these concepts.

Image-guided Thermal Ablation of Tumors Increases the Plasma Level of Interleukin-6 and Interleukin-10

PURPOSE To identify changes in plasma cytokine levels after image-guided thermal ablation of human tumors and to identify the factors that independently predict changes in plasma cytokine levels. MATERIALS AND METHODS Whole-blood samples were collected from 36 patients at three time points: before ablation, after ablation (within 48 hours), and at follow-up (1-5 weeks after ablation). Plasma levels of interleukin (IL)-1α, IL-2, IL-6, IL-10, and tumor necrosis factor (TNF)-α were measured using a multiplex immunoassay. Univariate and multivariate analyses were performed using cytokine level as the dependent variable and sample collection, time, age, sex, primary diagnosis, metastatic status, ablation site, and ablation type as the independent variables. RESULTS There was a significant increase in the plasma level of IL-6 after ablation compared with before ablation (9.6-fold ± 31-fold, P<.002). IL-10 also showed a significant increase after ablation (1.9-fold ± 2.8-fold, P<.02). Plasma levels of IL-1α, IL-2, and TNF-α were not significantly changed after ablation. Cryoablation resulted in the largest change in IL-6 level (>54-fold), whereas radiofrequency ablation and microwave ablation showed 3.6-fold and 3.4-fold changes, respectively. Ablation of melanomas showed the largest change in IL-6 48 hours after ablation (92×), followed by ablation of kidney (26×), liver (8×), and lung (6×) cancers. Multivariate analysis revealed that ablation type (P<.0003) and primary diagnosis (P<.03) were independent predictors of changes to IL-6 after ablation. Age was the only independent predictor of IL-10 levels after ablation (P< .019). CONCLUSIONS Image-guided thermal ablation of tumors increases plasma levels of IL-6 and IL-10, without increasing plasma levels of IL-1α, IL-2, or TNF-α.

Time-resolved MR angiography for the classification of endoleaks after endovascular aneurysm repair.

To evaluate the utility of time‐resolved MR angiography (TR‐MRA), compared with digital subtraction angiography (DSA), in the classification of endoleaks in patients who have undergone endovascular aneurysm repair (EVAR).

18F-FDG PET/CT Is an Immediate Imaging Biomarker of Treatment Success After Liver Metastasis Ablation

The rationale of this study was to examine whether 18F-FDG PET/CT and contrast-enhanced CT performed immediately after percutaneous ablation of liver metastases are predictors of local treatment failure at 1 y. Methods: This Health Insurance Portability and Accountability Act–compliant, Institutional Review Board–approved retrospective study reviewed 25 PET/CT-guided thermal ablations performed from September 2011 to March 2013 on 21 patients (11 women and 10 men; mean age, 56.8 y; range, 35–79 y) for the treatment of liver metastases (colorectal, n = 23; breast, n = 1; and sarcoma, n = 1). One to 3 tumors (mean size, 2.3 cm; range, 0.7–4.6 cm; mean SUVmax, 22.7; range, 9.5–77.1) were ablated using radiofrequency (n = 16) or microwave (n = 9) energy in a single session. Immediate-postablation enhanced CT and PET/CT scans were qualitatively evaluated by 2 reviewers independently, and the results were compared with clinical and imaging outcome at 1 y. The PET/CT scans were also analyzed to determine tissue radioactivity concentration (TRC) from 3-dimensional regions of interest in the ablation zone, the margin, and the surrounding normal liver to calculate a TRC ratio, which was then compared with outcome at 1 y. Receiver operating characteristics (ROC) were used, and the maximal-accuracy threshold in predicting recurrence was calculated. Results: Eleven (44%) of the 25 tumors recurred within 1 y. Enhanced CT did not significantly correlate with recurrence (P = 0.288). Accuracy was 64% (16/25), and the area under the ROC curve was 0.601 (95% confidence interval [95% CI], 0.387–0.789). The accuracy of the qualitative analysis of 18F-FDG PET was 92% (23/25) (P < 0.001), and the area under the ROC curve was 0.929 (95% CI, 0.740–0.990). The mean TRC ratio was 40.6 in the recurrence group (SD, 9.2; range, 29.3–53.9) and 15.9 in the group without recurrence (SD, 7.3; range, 3–27.3). A TRC ratio of 28.3 predicted recurrence at 1 y with 100% accuracy (25/25) (P < 0.001), and the area under the ROC curve was 1 (95% CI, 0.863–1). Conclusion: Immediate PET/CT accurately predicts the success of liver metastasis ablation at 1 y and is superior to immediate enhanced CT.

Feasibility of In Situ, High-Resolution Correlation of Tracer Uptake with Histopathology by Quantitative Autoradiography of Biopsy Specimens Obtained Under 18F-FDG PET/CT Guidance

Core biopsies obtained using PET/CT guidance contain bound radiotracer and therefore provide information about tracer uptake in situ. Our goal was to develop a method for quantitative autoradiography of biopsy specimens (QABS), to use this method to correlate 18F-FDG tracer uptake in situ with histopathology findings, and to briefly discuss its potential application. Methods: Twenty-seven patients referred for a PET/CT-guided biopsy of 18F-FDG–avid primary or metastatic lesions in different locations consented to participate in this institutional review board–approved study, which complied with the Health Insurance Portability and Accountability Act. Autoradiography of biopsy specimens obtained using 5 types of needles was performed immediately after extraction. The response of autoradiography imaging plates was calibrated using dummy specimens with known activity obtained using 2 core-biopsy needle sizes. The calibration curves were used to quantify the activity along biopsy specimens obtained with these 2 needles and to calculate the standardized uptake value, SUVARG. Autoradiography images were correlated with histopathologic findings and fused with PET/CT images demonstrating the position of the biopsy needle within the lesion. Logistic regression analysis was performed to search for an SUVARG threshold distinguishing benign from malignant tissue in liver biopsy specimens. Pearson correlation between SUVARG of the whole biopsy specimen and average SUVPET over the voxels intersected by the needle in the fused PET/CT image was calculated. Results: Activity concentrations were obtained using autoradiography for 20 specimens extracted with 18- and 20-gauge needles. The probability of finding malignancy in a specimen is greater than 50% (95% confidence) if SUVARG is greater than 7.3. For core specimens with preserved shape and orientation and in the absence of motion, one can achieve autoradiography, CT, and PET image registration with spatial accuracy better than 2 mm. The correlation coefficient between the mean specimen SUVARG and SUVPET was 0.66. Conclusion: Performing QABS on core-biopsy specimens obtained using PET/CT guidance enables in situ correlation of 18F-FDG tracer uptake and histopathology on a millimeter scale. QABS promises to provide useful information for guiding interventional radiology procedures and localized therapies and for in situ high-spatial-resolution validation of radiopharmaceutical uptake.

Safety and Efficacy of Percutaneous Cecostomy/Colostomy for Treatment of Large Bowel Obstruction in Adults with Cancer

PURPOSE To assess the safety and efficacy of image-guided percutaneous cecostomy/colostomy (PC) in the management of colonic obstruction in patients with cancer. MATERIALS AND METHODS Twenty-seven consecutive patients underwent image-guided PC to relieve large bowel obstruction at a single institution between 2000 and 2012. Colonic obstruction was the common indication. Patient demographics, diagnosis, procedural details, and outcomes including maximum colonic distension (MCD; ie, greatest transverse measurement of the colon on radiograph or scout computed tomography image) were recorded and retrospectively analyzed. RESULTS Following PC, no patient experienced colonic perforation; pain was relieved in 24 of 27 patients (89%). Catheters with tip position in luminal gas rather than mixed stool/gas or stool were associated with greater decrease in MCD (-40%, -12%, and -16%, respectively), with the difference reaching statistical significance (P = .002 and P = .013, respectively). Catheter size was not associated with change in MCD (P = .978). Catheters were successfully removed from six of nine patients (67%) with functional obstructions and two of 18 patients (11%) with mechanical obstructions. One patient underwent endoscopic stent placement after catheter removal. Three patients required diverting colostomy after PC, and their catheters were removed at the time of surgery. One major complication (3.7%; subcutaneous emphysema, pneumomediastinum, and sepsis) occurred 8 days after PC and was successfully treated with cecostomy exchange, soft-tissue drainage, and intravenous antibiotic therapy. CONCLUSIONS Image-guided PC is safe and effective for management of functional and mechanical bowel obstruction in patients with cancer. For optimal efficacy, catheters should terminate within luminal gas.

Emergent Embolization of Arterial Bleeding after Vacuum-Assisted Breast Biopsy

Vacuum-assisted core breast biopsy has become important in evaluating patients with suspicious breast lesions. It has proven to be a relatively safe procedure that in rare cases can result in vascular complications. These are the first reported cases of transcatheter embolization of uncontrolled breast hemorrhage after vacuum-assisted breast biopsy. With increased use of biopsy and larger-gauge devices, breast imaging groups may consider embolotherapy as a safe alternative for treatment of hemorrhage in a select group of patients.

Superselective internal radiation with yttrium-90 microspheres in the management of a chemorefractory testicular liver metastasis.

We treated a patient with biopsy-proven, chemotherapy-resistant testicular cancer liver metastasis using Y-90 selective internal radiation treatment. We chose yttrium-90 rather than surgery and ablation due to tumor location and size as well as the patient’s clinical history. The result was marked tumor response by positron emission tomography and computed tomography as well as significant improvement of the patient’s quality of life accompanied by a substantial decrease of his tumor markers.

Robust Antitumor Responses Result from Local Chemotherapy and CTLA-4 Blockade

Immunotherapy success depends on inflamed tumor microenvironments. In tumor models, inflammation induced by chemotherapy, combined with CTLA-4 blockade, improved survival rates. In a clinical trial, patients with melanoma showed a durable response to such combined therapy. Clinical responses to immunotherapy have been associated with augmentation of preexisting immune responses, manifested by heightened inflammation in the tumor microenvironment. However, many tumors have a noninflamed microenvironment, and response rates to immunotherapy in melanoma have been <50%. We approached this problem by utilizing immunotherapy (CTLA-4 blockade) combined with chemotherapy to induce local inflammation. In murine models of melanoma and prostate cancer, the combination of chemotherapy and CTLA-4 blockade induced a shift in the cellular composition of the tumor microenvironment, with infiltrating CD8+ and CD4+ T cells increasing the CD8/Foxp3 T-cell ratio. These changes were associated with improved survival of the mice. To translate these findings into a clinical setting, 26 patients with advanced melanoma were treated locally by isolated limb infusion with the nitrogen mustard alkylating agent melphalan followed by systemic administration of CTLA-4 blocking antibody (ipilimumab) in a phase II trial. This combination of local chemotherapy with systemic checkpoint blockade inhibitor resulted in a response rate of 85% at 3 months (62% complete and 23% partial response rate) and a 58% progression-free survival at 1 year. The clinical response was associated with increased T-cell infiltration, similar to that seen in the murine models. Together, our findings suggest that local chemotherapy combined with checkpoint blockade–based immunotherapy results in a durable response to cancer therapy. Cancer Immunol Res; 6(2); 189–200. ©2018 AACR.