Case Report: Response to Regional Melphalan via Limb Infusion and Systemic PD1 Blockade in Recurrent Myxofibrosarcoma: A Report of 2 Cases.

Treatment options for patients with advanced sarcoma remain limited. Promising responses to checkpoint inhibition have been observed, but responses to single-agent PD-1 inhibition are rare. We report on two patients with multiply recurrent myxofibrosarcoma treated with the combination of regionally administered melphalan (via isolated limb infusion) and pembrolizumab. Both patients had recurrent disease after multiple surgical resections and radiation. Analysis of primary tumors demonstrated microsatellite stable tumors with few mutations. After combination treatment, one patient had a significant partial response of 6 months duration, the second patient had a complete response of 2 years duration. Post treatment biopsies demonstrated immune infiltration into the tumor. These promising responses in patients with multiply recurrent myxofibrosarcoma have prompted the development of an investigator-initiated clinical trial to formally study the combination of regional melphalan and pembrolizumab in a systematic fashion (NCT04332874).

Autologous Blood Patch Injection versus Hydrogel Plug in CT-guided Lung Biopsy: A Prospective Randomized Trial.

Purpose To compare the effect of autologous blood patch injection (ABPI) with that of a hydrogel plug on the rate of pneumothorax at CT-guided percutaneous lung biopsy. Materials and Methods In this prospective randomized controlled trial ( https://ClinicalTrials.gov , NCT02224924), a noninferiority design was used for ABPI, with a 10% noninferiority margin when compared with the hydrogel plug, with the primary outcome of pneumothorax rate within 2 hours of biopsy. A type I error rate of 0.05 and 90% power were specified with a target study population of 552 participants (276 in each arm). From October 2014 to February 2017, all potential study participants referred for CT-guided lung biopsy (n = 2052) were assessed for enrollment. Results The data safety monitoring board recommended the trial be closed to accrual after an interim analysis met prespecified criteria for early stopping based on noninferiority. The final study group consisted of 453 participants who were randomly assigned to the ABPI (n = 226) or hydrogel plug (n = 227) arms. Of these, 407 underwent lung biopsy. Pneumothorax rates within 2 hours of biopsy were 21% (42 of 199) and 29% (60 of 208); chest tube rates were 9% (18 of 199) and 13% (27 of 208); and delayed pneumothorax rates within 2 weeks after biopsy were 1.4% (three of 199) and 1.5% (three of 208) in the ABPI and hydrogel plug arms, respectively. Conclusion Autologous blood patch injection is noninferior to a hydrogel plug regarding the rate of pneumothorax after CT-guided percutaneous lung biopsy. © RSNA, 2018 Online supplemental material is available for this article.

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

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.

Outcomes after inferior vena cava filter placement in cancer patients diagnosed with pulmonary embolism: risk for recurrent venous thromboembolism.

Venous thromboembolism (VTE) is a common complication in cancer patients and anticoagulation (AC) remains the standard of care for treatment. Inferior vena cava (IVC) filters may also used to reduce the risk of pulmonary embolism, either alone or in addition to AC. Although widely used, data are limited on the safety and efficacy of IVC filters in cancer patients. We performed a retrospective review of outcomes after IVC filter insertion in a database of 1270 consecutive patients with cancer-associated pulmonary embolism (PE) at our institution between 2008 and 2009. Outcomes measured included rate of all recurrent VTE, recurrent PE, and overall survival within 12 months. 317 (25%) of the 1270 patients with PE had IVC filters placed within 30 days of the index PE event or prior to the index PE in the setting of prior DVT. Patients with IVC filters had markedly lower overall survival (7.3 months) than the non-IVC filter patients (13.2 months). Filter patients also had a lower rate of AC use at time of initial PE. There was a trend towards higher recurrent VTE in patients with IVC filters (11.9%) compared to non-filter patients (7.7%), but this was not significant (p = 0.086). The risk of recurrent PE was similar between the IVC filter cohort (3.5%) and non-filter group (3.5%, p = 0.99). Cancer patients receiving IVC filters had a similar risk of recurrent PE, but a trend towards more overall recurrent VTE. The filter patients had poorer overall survival, which may reflect a poorer cancer prognosis, and had greater contraindication to AC; therefore these patients likely had a higher inherent risk for recurrent VTE. A prospective study would be helpful for further clarification on the partial reduction in the recurrent PE risk by IVC filter placement in cancer patients.

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

UNLABELLED: The rationale of this study was to examine whether (18)F-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 (18)F-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.

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.

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.

UNLABELLED: 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 (18)F-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 (18)F-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 (18)F-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.

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.

Pattern of retained contrast on immediate postprocedure computed tomography (CT) after particle embolization of liver tumors predicts subsequent treatment response.

PURPOSE: To determine if the pattern of retained contrast on immediate postprocedure computed tomography (CT) after particle embolization of hepatic tumors predicts modified Response Evaluation Criteria in Solid Tumors (mRECIST) response. MATERIALS AND METHODS: This study was approved by the Institutional Review Board with a waiver of authorization. One hundred four liver tumors were embolized with spherical embolic agents (Embospheres, Bead Block, LC Bead) and polyvinyl alcohol. Noncontrast CT was performed immediately after embolization to assess contrast retention in the targeted tumors, and treatment response was assessed by mRECIST criteria on follow-up CT (average time 9.0 ± 7.7 weeks after embolization). Tumor contrast retention (TCR) was determined based on change in Hounsfield units (HUs) of the index tumors between the preprocedure and immediate postprocedure scans; vascular contrast retention (VCR) was rated; and defects in contrast retention (DCR) were also documented. The morphology of residual enhancing tumor on follow-up CT was described as partial, circumferential, or total. Association between TCR variables and tumor response were assessed using multivariate logistic regression. RESULTS: Of 104 hepatic tumors, 51 (49%) tumors had complete response (CR) by mRECIST criteria; 23 (22.1%) had partial response (PR); 21 (20.2%) had stable disease (SD); and 9 (8.7%) had progressive disease (PD). By multivariate analysis, TCR, VCR, and tumor size are independent predictors of CR (p = 0.02, 0.05, and 0.005 respectively). In 75 tumors, DCR was found to be an independent predictor of failure to achieve complete response (p < 0.0001) by imaging criteria. CONCLUSION: TCR, VCR, and DCR on immediate posttreatment CT are independent predictors of CR by mRECIST criteria.

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.

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

PURPOSE: 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). MATERIALS AND METHODS: Thirty-one patients who had undergone EVAR to repair an abdominal aortic aneurysm were evaluated with both TR-MRA and DSA to determine endoleak etiology. The patient population consisted of 26 men and 5 women with a mean age of 78.5 years (range, 55-93 years). The mean time interval between TR-MRA and DSA was 1.5 weeks (range, 1-8 weeks). Endoleaks were classified as type II when enhancement of the external iliac vessels was observed before the appearance of the endoleak; otherwise the endoleak was classified as type I or III. The results of TR-MRA classification were compared with the reference gold standard, DSA. RESULTS: Agreement between TR-MRA and DSA regarding endoleak classification occurred in 30 of 31 cases (97%). Discordant classification occurred in a case in which a Type II endoleak was misclassified as a Type III due to failure to visualize a lumbar vessel. CONCLUSION: TR-MRA is highly effective in classifying endoleaks following EVAR when compared with DSA.