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PURPOSE To study the impact of transarterial Yttrium-90 radioembolization (TARE) in combination with second-line systemic chemotherapy for colorectal liver metastases (CLM). METHODS In this international, multicenter, open-label phase III trial, patients with CLM who progressed on oxaliplatin- or irinotecan-based first-line therapy were randomly assigned 1:1 to receive second-line chemotherapy with or without TARE. The two primary end points were progression-free survival (PFS) and hepatic PFS (hPFS), assessed by blinded independent central review. Random assignment was performed using a web- or voice-based system stratified by unilobar or bilobar disease, oxaliplatin- or irinotecan-based first-line chemotherapy, and KRAS mutation status. RESULTS Four hundred twenty-eight patients from 95 centers in North America, Europe, and Asia were randomly assigned to chemotherapy with or without TARE; this represents the intention-to-treat population and included 215 patients in the TARE plus chemotherapy group and 213 patients in the chemotherapy alone group. The hazard ratio (HR) for PFS was 0.69 (95% CI, 0.54 to 0.88; 1-sided P = .0013), with a median PFS of 8.0 (95% CI, 7.2 to 9.2) and 7.2 (95% CI, 5.7 to 7.6) months, respectively. The HR for hPFS was 0.59 (95% CI, 0.46 to 0.77; 1-sided P < .0001), with a median hPFS of 9.1 (95% CI, 7.8 to 9.7) and 7.2 (95% CI, 5.7 to 7.6) months, respectively. Objective response rates were 34.0% (95% CI, 28.0 to 40.5) and 21.1% (95% CI, 16.2 to 27.1; 1-sided P = .0019) for the TARE and chemotherapy groups, respectively. Median overall survival was 14.0 (95% CI, 11.8 to 15.5) and 14.4 months (95% CI, 12.8 to 16.4; 1-sided P = .7229) with a HR of 1.07 (95% CI, 0.86 to 1.32) for TARE and chemotherapy groups, respectively. Grade 3 adverse events were reported more frequently with TARE (68.4% v 49.3%). Both groups received full chemotherapy dose intensity. CONCLUSION The addition of TARE to systemic therapy for second-line CLM led to longer PFS and hPFS. Further subset analyses are needed to better define the ideal patient population that would benefit from TARE.

Purpose To evaluate the safety and efficacy of 2 locoregional therapies (LRTs) including hepatic artery embolization (HAE) and transarterial radioembolization (TARE) in the treatment of patients with metastatic ovarian cancer to the liver. Material and Methods From October 2010 to May 2019, the data of 15 consecutive patients (median age, 54 years ± 9.8; range, 35–78 years) with hepatic metastatic ovarian cancer who were treated with either HAE (n = 6; 40%) or TARE (n = 9; 60%) were reviewed. The most common histopathologic type was epithelial ovarian carcinoma (80%). The most common chemotherapy regimens used prior to embolization included carboplatin, paclitaxel, cisplatin, and bevacizumab. Patients received a mean of 4 lines ± 3 (range, 1–9) of chemotherapy. All patients with serous carcinoma were resistant to platinum at the time of embolization. Indications for embolization were progression of disease to the liver while receiving chemotherapy in 14 (93.3%) patients and palliative pain control in 1 patient. Results The overall response rates at 1, 3, and 6 months were 92.4%, 85.6%, and 70%, respectively. Median overall survival from the time of LRT was 9 (95% confidence interval [CI], 4–14) months. Median local tumor progression was 6.4 months ± 5.03 (95% CI, 3.3–9.5). No grade 3–5 adverse events were detected in either group. Conclusions HAE and TARE were well tolerated in patients with metastatic ovarian cancer to the liver and possibly ensured prolonged disease control in heavily treated, predominantly in patients resistant to platinum. Larger numbers are needed to verify these data.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer focuses on systemic therapy options for the treatment of metastatic colorectal cancer (mCRC), because important updates have recently been made to this section. These updates include recommendations for first-line use of checkpoint inhibitors for mCRC, that is deficient mismatch repair/microsatellite instability-high, recommendations related to the use of biosimilars, and expanded recommendations for biomarker testing. The systemic therapy recommendations now include targeted therapy options for patients with mCRC that is HER2-amplified, or BRAF V600E mutation–positive. Treatment and management of nonmetastatic or resectable/ablatable metastatic disease are discussed in the complete version of the NCCN Guidelines for Colon Cancer available at NCCN.org. Additional topics covered in the complete version include risk assessment, staging, pathology, posttreatment surveillance, and survivorship.

PURPOSE: To evaluate safety and efficacy of radiation segmentectomy (RS) with (90)Y glass microspheres in patients with limited metastatic liver disease not amenable to resection or percutaneous ablation. METHODS: Patients with ≤3 tumors treated with RS from 6/2015–12/2017 were included. Target tumor radiation dose was > 190 Gy based on Medical Internal Radiation Dose (MIRD) dosimetry. Tumor response, local tumor progression (LTP), LTP-free survival (LTPFS) and disease progression rate in the treated segment were defined using Choi and RECIST 1.1 criteria. Toxicities were evaluated using modified SIR criteria. RESULTS: Ten patients with 14 tumors underwent 12 RS. Median tumor size was 3 cm (range, 1.4–5.6). Median follow-up was 17.8 months (range, 1.6–37.3). Response rates per Choi and RECIST 1.1 criteria were 8/8 (100%) and 4/9 (44%), respectively. Overall LTP rate was 3/14 (21%) during the study period. One-, two- and three -year LTPFS was 83%, 83% and 69%, respectively. Median LTPFS was not reached. Disease progression rate in the treated segment was 6/18 (33%). Median overal survival was 41.5 months (IQR, 16.7–41.5). Median delivered tumor radiation dose was 293 Gy (range, 163–1303). One major complication was recorded in a patient post-Whipple procedure who suffered anaphylactic reaction to prophylactic cefotetan and liver abscess in RS region 6.5 months post-RS. All patients were alive on last follow-up. CONCLUSION: RS of ≤ 3 hepatic segments can safely provide a two-year local tumor control rate of 83% in selected patients with limited metastatic liver disease and limited treatment options. Optimal dosimetry methodology requires further investigation.

The NCCN Guidelines for Rectal Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with rectal cancer. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines. These updates include clarifying the definition of rectum and differentiating the rectum from the sigmoid colon; the total neoadjuvant therapy approach for localized rectal cancer; and biomarker-targeted therapy for metastatic colorectal cancer, with a focus on new treatment options for patients with BRAF V600E– or HER2 amplification–positive disease.

Colorectal cancer (CRC) is the second most common cause of cancer death in the developed world and the third most common malignancy worldwide, with more than 1 million people affected. Approximately half of this population develops colorectal liver metastases (CLM) with a significant increase in morbidity and mortality, yet only a minority of these patients (10–15%) can undergo hepatectomy (1). Image-guided percutaneous thermal ablation (TA) destroys cancer cells by delivering heat directly into the tumor using radiofrequency (RFA) or microwave (MWA) energy, via special needles/electrodes.

PURPOSE: To validate an immuno-fluorescent assay (IFA) detecting residual viable tumor as intraprocedural thermal ablation (TA) zone assessment and demonstrate its prognostic value for local tumor progression after colorectal liver metastases (CLM) TA. MATERIALS AND METHODS: This prospective, IRB-approved study included 99 patients with 155 CLMs ablated between November 2009 and January 2019. Tissue samples from the ablation zone (AZ) center and minimal margin underwent immunofluorescent microscopic examination interrogating cellular morphology and mitochondrial viability (IFA) within 30 minutes after ablation. The same tissue samples were subsequently evaluated with standard morphological and immunohistochemical (IHC) methods. Sensitivity, specificity, and overall accuracy of IFA versus standard morphological and IHC examination were calculated. Local tumor progression (LTP)-free survival rates were evaluated for 12-month follow-up period. RESULTS: Of the 311 tissue samples stained, 304 (98%) were deemed evaluable. 27% (81/304) of specimens were considered positive for the presence of viable tumor. The accuracy of IFA was 94% (286/304). Sensitivity and specificity were 100% (63/63) and 93% (223/241), respectively. The 18 false-positive IFA assessments corresponded to samples that included viable cholangiocytes. The 12-month LTP-free survival was 59% vs 78% for IFA positive vs negative for viable tumor AZs, respectively (P

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.

To define positron emission tomography/computed tomography (PET/CT) imaging characteristics during follow-up of patients with metastatic breast cancer (MBC) treated with yttrium-90 (Y90) radioembolization (RE). From January 2011 to October 2017, 30 MBC patients underwent 38 Y90 glass or resin RE treatments. Pre-RE PET/CT was performed on average 51 days before RE. There were 68 PET/CTs performed after treatment. Response was assessed using modified PERCIST criteria focusing on the hepatic territory treated with RE, normalizing SUVpeak to the mean SUV of liver uninvolved by tumor. An objective response (OR) was defined as a decrease in SUVpeak by at least 30%. Of the 68 post-RE scans, 6 were performed at 0–30 days, 15 at 31–60 days, 9 at 61–90 days, 13 at 91–120 days, 14 scans at 121–180 days, and 11 scans at > 180 days after RE. Of the 30 patients, 25 (83%) achieved OR on at least one follow-up. Median survival was 15 months after the first RE administration. Highest response rates occurred at 30–90 days, with over 75% of cases demonstrating OR at that time. After 180 days, OR was seen in only 25%. There was a median TTP of 169 days among responders. In MBC, follow-up PET/CT after RE demonstrates optimal response rates at 30–90 days, with progression noted after 180 days. These results help to guide the timing of imaging and also to inform patients of expected outcomes after RE.

Colorectal cancer (CRC) is responsible for approximately 10% of cancer-related deaths in the Western world. Liver metastases are frequently seen at the time of diagnosis and throughout the course of the disease. Surgical resection is often considered as it provides long-term survival; however, few patients are candidates for resection. Percutaneous ablative therapies are also used in the management of this patient population. Different thermal ablation (TA) technologies are available including radiofrequency ablation, microwave ablation (MWA), laser, and cryoablation. There is growing evidence about the role of interventional oncology and image-guided percutaneous ablation in the management of metastatic colorectal liver disease. This article aims to outline the technical considerations, outcomes, and rational of TA in the management of patients with CRC liver metastases, focusing on the emerging role of MWA.

PET has become an essential tool for staging and response assessment in oncologic imaging. Over the past decade it has also evolved into a tool for image-guided interventions, specifically in the rapidly growing field of interventional oncology. PET-guided biopsies have greater sensitivity and diagnostic yield for fluorodeoxyglucose-avid lesions. Real-time PET imaging can also provide valuable image guidance during therapeutic minimally invasive procedures such as ablation of PET-avid tumors. The increasing use of PET in the assessment of therapeutic response results in earlier identification of disease that is amenable to image-guided therapies.

Small bowel adenocarcinoma (SBA) is a rare malignancy of the gastrointestinal tract that has increased in incidence across recent years. Often diagnosed at an advanced stage, outcomes for SBA are worse on average than for other related malignancies, including colorectal cancer. Due to the rarity of this disease, few studies have been done to direct optimal treatment, although recent data have shown that SBA responds to treatment differently than colorectal cancer, necessitating a separate approach to treatment. The NCCN Guidelines for Small Bowel Adenocarcinoma were created to establish an evidence-based standard of care for patients with SBA. These guidelines provide recommendations on the workup of suspected SBA, primary treatment options, adjuvant treatment, surveillance, and systemic therapy for metastatic disease. Additionally, principles of imaging and endoscopy, pathologic review, surgery, radiation therapy, and survivorship are described.

Estimate the incidence of nontarget embolization (NTE) as identified on immediate post-hepatic artery embolization CT. Two hundred hepatic embolizations performed with particles alone (bland embolization) in 147 patients between August 16, 2013 and August 26, 2014 with immediate post-procedure CT were retrospectively reviewed. Arterial anatomy, vessels treated, imaging findings of NTE, patient demographics, length of hospital stay following embolization, and procedure-related complications were recorded. The data were analyzed using two-sided t-tests and chi-squared tests. Evidence of NTE was seen on post-procedure CT in 64 of 200 cases (64/200, 32%). Six organs were affected, with 69 discrete sites in 64 patients. The majority (49/69, 71.0%) involved the gallbladder. The mean length of hospital stay (LOS) for patients with and without NTE was 2.9 ± 1.5 nights (range 1–7) and 2.9 ± 2.3 nights (range 0–21), respectively (P = 0.81). NTE was more common following embolization of replaced or accessory hepatic vessels. There were three complications in the NTE group (3/64, 4.7%) following the embolization procedure, one of which was cholecystitis directly related to NTE. The other two were one incidence each of contrast-induced nephropathy and pneumonia. In the group without NTE, seven complications occurred (7/136, 5.1%, P = 0.889), including one death resulting from hepatic failure, two gastrointestinal bleeds, two hepatic abscesses, flash pulmonary edema, and pancreatitis. Unanticipated NTE is not uncommon after bland hepatic artery embolization, particularly after treating accessory or replaced vessels, but does not increase complications or LOS. Level 2b, Retrospective Cohort.

This study aimed to evaluate whether rapid fluorescent tissue examination immediately after colorectal cancer liver metastasis (CLM) ablation correlates with standard pathologic and immunohistochemical (IHC) assessments. This prospective, National Institutes of Health-supported study enrolled 34 consecutive patients with 53 CLMs ablated between January 2011 and December 2014. Immediately after ablation, core needle sampling of the ablation zone was performed. Tissue samples were evaluated with fluorescent viability (MitoTracker Red) and nuclear (Hoechst) stains. Confocal microscope imaging was performed within 30 min after ablation. The same samples were subsequently fixed and stained with hematoxylin and eosin (H&E). Identified tumor cells underwent IHC staining for proliferation (Ki67) and viability (OxPhos). The study pathologist, blinded to the H&E and IHC assessment, evaluated the fluorescent images separately to detect viable tumor cells. Sensitivity, specificity, and overall concordance of the fluorescent versus H&E and IHC assessments were calculated. A total of 63 tissue samples were collected and processed. The overall concordance rate between the immediate fluorescent and the subsequent H&E and IHC assessments was 94% (59/63). The fluorescent assessment sensitivity and specificity for the identification of tumor cells were respectively 100% (18/18) and 91% (41/45). The study showed a high concordance rate between the immediate fluorescent assessment and the standard H&E and IHC assessment of the ablation zone. Given the documented prognostic value of ablation zone tissue characteristics for outcomes after ablation of CLM, the fluorescent assessment offers a potential intra-procedural biomarker of complete tumor ablation.

During the past 10 years, performing real-time molecular imaging with positron emission tomography (PET) in combination with computed tomography (CT) during interventional procedures has undergone rapid development. Keeping in mind the interest of the nuclear medicine readers, an update is provided of the current workflows using real-time PET/CT in percutaneous biopsies and tumor ablations. The clinical utility of PET/CT guided biopsies in cancer patients with lung, liver, lymphoma, and bone tumors are reviewed. Several technological developments, including the introduction of new PET tracers and robotic arms as well as opportunities provided through acquiring radioactive biopsy specimens are briefly reviewed.

Approximately 50% of colorectal cancer patients will develop metastases during the course of the disease. Local or locoregional therapies for the treatment of liver metastases are used in the management of oligometastatic colorectal liver disease, especially in nonsurgical candidates. Thermal ablation (TA) is recommended in the treatment of limited liver metastases as free-standing therapy or in combination with surgery as long as all visible disease can be eradicated. Percutaneous TA has been proven as a safe and efficacious therapy offering sustained local tumor control and improved patient survival. Continuous technological advances in diagnostic imaging and guidance tools, the evolution of devices allowing for optimization of ablation parameters, as well as the ability to perform margin assessment have improved the efficacy of ablation. This allows resectable small volume diseases to be cured with percutaneous ablation. The ongoing detailed information and increasing understanding of tumor biology, genetics, and tissue biomarkers that impact oncologic outcomes as well as their implications on the results of ablation have further allowed for treatment customization and improved oncologic outcomes even in those with more aggressive tumor biology. The purpose of this review is to present the most common indications for image-guided percutaneous ablation in colorectal cancer liver metastases, to describe technical considerations, and to discuss relevant peer-reviewed evidence on this topic. The growing role of imaging and image-guidance as well as controversies regarding several devices are addressed.

PURPOSE: To determine the relationship of tumoral and nontumoral radiation dose to response and toxicity after transarterial radioembolization (TARE) of breast cancer liver metastasis. METHODS: This retrospective study evaluated all patients with breast cancer liver metastases treated with TARE (2/2011—6/2019). Extent of disease was measured as unilobar or bilobar on baseline PET/CT prior to TARE. Response was assessed for targeted regions with modified PERCIST criteria on first follow-up PET/CT. Tumoral and nontumoral liver dosimetry was evaluated by performing volumetric segmentation on post-TARE Bremsstrahlung SPECT/CT. ≥Grade 3 hepatotoxicity was defined as ≥grade 3 bilirubin/AST/ALT elevation or ascites requiring intervention. Fisher’s exact tests, Wilcoxon rank sum tests, and Kaplan-Meier survival analysis were performed. RESULTS: Among 64 women, 60 patients had pre- and post-TARE PET/CT, of whom 46/60 (77%) achieved objective response (OR). Responders received higher tumoral dose with a median (interquartile range) of 167 (96(—)217) vs. 54 (45(—)62) Gy (p79.5 Gy) was associated with OR, which was associated with longer survival. Pre-existing liver dysfunction was associated with hepatotoxicity, which was associated with decreased survival.

Background Intermediate stage hepatocellular carcinomas (HCCs) are treated by inducing ischemic cell death with transarterial embolization (TAE) or transarterial chemoembolization (TACE). A subset of HCCs harbor nuclear factor E2-related factor 2 (NRF2), a major regulator of the oxidative stress response implicated in cell survival after ischemia. NRF2-mutated HCC response to TAE and/or TACE is unknown. Purpose To test whether ischemia resistance is present in individuals with NRF2-mutated HCC and if this resistance can be overcome by means of NRF2 inhibition in HCC cell lines. Materials and Methods This was a combined retrospective review of an institutional database (from January 2011 to December 2018) and prospective study (from January 2014 to December 2018) of participants with HCC who underwent TAE and a laboratory investigation of HCC cell lines. Imaging follow-up included liver CT or MRI at 1 month after the procedure followed by 3-month interval scans. Tumor radiologic response was assessed on the basis of follow-up imaging. The time to local progression after TAE for individuals with and individuals without NRF2 pathway alterations was estimated by using competing risk analysis (Gray test). The in vitro response to ischemia in four HCC cell lines with and without NRF2 overexpression was evaluated, and the combination of ischemia with NRF2 knockdown by means of short hairpin RNA or an NRF2 inhibitor was tested. Doubling time estimates, dose response curve regression, and comparison analyses were performed. Results Sixty-five individuals (median age, 69 years [range, 19-84 years]; 53 men) were evaluated. HCCs with NRF2 pathway mutation had a shorter time to local progression after TAE compared to those without mutation (6-month cumulative incidence of local progression, 56% [range, 19%-91%] vs 22% [range, 12%-34%], respectively; P < .001) and confirmed ischemia resistance in NRF2-overexpressing HCC cell lines. However, ischemia and NRF2 knock-down worked synergistically to decrease proliferation of NRF2-overexpressing HCC cell lines. Dose response curves of ML385, an NRF2 inhibitor, showed that ischemia induces addiction to NRF2 in cells with NRF2 alterations. Conclusion Hepatocellular carcinoma with nuclear factor E2-related factor 2 (NRF2) alterations showed resistance to ischemia, but ischemia simultaneously induced sensitivity to NRF2 inhibition. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Weiss and Nezami in this issue.

BackgroundPreclinical testing of new locoregional therapies for pancreatic cancer has been challenging, due to the lack of a suitable large animal model.PurposeTo 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.MethodsThe 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.ResultsPancreatic 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.ConclusionPancreatic 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.

Background Deriving individual tumor genomic characteristics from patient imaging analysis is desirable. We explore the predictive value of 2-[18F]FDG uptake with regard to the KRAS mutational status of colorectal adenocarcinoma liver metastases (CLM). Methods 2-[18F]FDG PET/CT images, surgical pathology and molecular diagnostic reports of 37 patients who underwent PET/CT-guided biopsy of CLM were reviewed under an IRB-approved retrospective research protocol. Sixty CLM in 39 interventional PET scans of the 37 patients were segmented using two different auto-segmentation tools implemented in different commercially available software packages. PET standard uptake values (SUV) were corrected for: (1) partial volume effect (PVE) using cold wall-corrected contrast recovery coefficients derived from phantom spheres with variable diameter and (2) variability of arterial tracer supply and variability of uptake time after injection until start of PET scan derived from the tumor-to-blood standard uptake ratio (SUR) approach. The correlations between the KRAS mutational status and the mean, peak and maximum SUV were investigated using Student’s t test, Wilcoxon rank sum test with continuity correction, logistic regression and receiver operation characteristic (ROC) analysis. These correlation analyses were also performed for the ratios of the mean, peak and maximum tumor uptake to the mean blood activity concentration at the time of scan: SURMEAN, SURPEAK and SURMAX, respectively. Results Fifteen patients harbored KRAS missense mutations (KRAS+), while another 3 harbored KRAS gene amplification. For 31 lesions, the mutational status was derived from the PET/CT-guided biopsy. The Student’s t test p values for separating KRAS mutant cases decreased after applying PVE correction to all uptake metrics of each lesion and when applying correction for uptake time variability to the SUR metrics. The observed correlations were strongest when both corrections were applied to SURMAX and when the patients harboring gene amplification were grouped with the wild type: p ≤ 0.001; ROC area under the curve = 0.77 and 0.75 for the two different segmentations, respectively, with a mean specificity of 0.69 and sensitivity of 0.85. Conclusion The correlations observed after applying the described corrections show potential for assigning probabilities for the KRAS missense mutation status in CLM using 2-[18F]FDG PET images.

Thermal ablation of colorectal cancer liver metastases with minimum margin > 10 mm offers the best local tumor control. Biliary complications occurred only in patients that received hepatic artery infusion especially in the face of pre-existing biliary dilatation, exposure to bevacizumab, and ablation with minimum margin > 10 mm. For patients at risk, such as those in the hepatic artery infusion group, a margin of 6 to 10 mm offers 76% local tumor control rate and 4% major biliary complications incidence.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 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. (C) 2020 Published by Elsevier Inc.

Colorectal cancer affects more than 1 million people worldwide, and half of this population develops liver metastases. Image-guided thermal ablation is an acceptable local therapy for the management of oligometastatic colorectal cancer liver disease, in patients who are noneligible for surgery, or present with recurrence after hepatectomy. Continuous technological evolutions, understanding of tumor variability through disease biology and genetics, and optimization of ablation parameters with ablation margin assessment have allowed patients with resectable small-volume disease to be treated by thermal ablation with curative intent. The growing role of imaging and image guidance in thermal ablation for patient selection, procedure planning, tumor targeting, and assessment of technical success is discussed in this article.

Background Although snaring technique is a commonly used tool in the interventional radiologists’ armamentarium, there are no reports of its use in an extra-vascular space to achieve access across a pseudoaneurysm that was otherwise non-traversable. Case presentation We describe a case of an iliac-enteric fistula between a ruptured pseudoaneurysm of the external iliac artery and a surrounding contained colonic perforation, where access across the pseudoaneurysm was achieved only after snaring of the microwire from within the contained colonic perforation and back into the intra-vascular space, allowing the placement of a covered stent and control of the bleeding. Conclusions The described technique may be useful in situations where other, more conventional, endovascular techniques fail to achieve access across the bleeding pseudoaneurysm. While it was life-saving in this case, this technique should only be used in very limited scenarios, specifically in the palliative setting and when surgical management is not an option.

One way to enhance quality of life for patients with metastatic sarcoma is to maximize time off chemotherapy—a chemotherapy-free interval. While image-guided ablation of sarcoma metastases may reduce the need for chemotherapy, it remains unknown how long ablation could extend the chemotherapy-free interval. The purpose of our study was to determine the chemotherapy-free interval in comparison to overall survival and progression-free survival in sarcoma patients who undergo ablation procedures. An IRB-approved, single institution, HIPAA compliant database was queried for sarcoma patients who underwent image-guided ablation procedures between 2007 and 2018. Patient demographics, histologic subtype, and other clinical characteristics were recorded. Kaplan-Meier analysis was performed to compute median overall survival, median progression-free survival (local and distant), and the median chemotherapy-free interval (systemic and cytotoxic) after ablation. Univariate and multivariate analyses were performed using the log-rank test and Cox proportional-hazards model, respectively. A total of 100 sarcoma patients were included in the analysis. The most common histologic subtype was leiomyosarcoma (38%). Median overall survival after ablation of sarcoma metastases was 52.4 months (95% CI: 46.9–64.0 months). The median systemic chemotherapy-free interval following ablation of sarcoma metastases was 14.7 months (95% CI: 8.6–34.3 months). The median cytotoxic chemotherapy-free interval following ablation of sarcoma metastases was 81.3 months (95% CI: 34.3-median not reached). In conclusion, ablation of sarcoma metastases can provide an extended systemic chemotherapy-free interval of greater than 1 year. Ablation of sarcoma metastases may improve patient quality of life by extending the chemotherapy-free interval.

Transarterial embolization (TAE) can be used to treat unresectable and unablatable liver-dominant metastases from neuroendocrine tumor (NET) and sarcoma. TAE could also potentially be used to treat liver metastases from other primaries, but data on efficacy is limited outside of NET and sarcoma. For hepatocellular carcinoma, NET, and sarcoma, outcomes after TAE and transarterial chemoembolization are similar, suggesting that ischemia is the dominant mechanism causing tumor necrosis. For colorectal cancer liver metastases, transarterial chemoembolization using irinotecan-loaded drug-eluting beads improves overall survival. For NET liver metastases, arterial therapy is generally reserved for patients with progressive liver metastases who are either symptomatic or have a large tumor burden. Asymptomatic small-volume NET liver metastases can be followed and typically do not need to be embolized immediately. Generally, TAE (lobar or selective) is performed starting with 40–120-micron Embosphere microspheres (Merit Medical, South Jordan, UT) (up to five syringes), followed by 100–300-micron Embospheres. The endpoint for embolization is stasis.

The goal of this study was to develop and evaluate a volumetric three-dimensional (3D) approach to improve the accuracy of ablation margin assessment following thermal ablation of hepatic tumors. The 3D margin assessment technique was developed to generate the new 3D assessment metrics: volumes of insufficient coverage (VICs) measuring volume of tissue at risk post-ablation. VICs were computed for the tumor and tumor plus theoretical 5- and 10-mm margins. The diagnostic accuracy of the 3D assessment to predict 2-year local tumor progression (LTP) was compared to that of manual 2D assessment using retrospective analysis of a patient cohort that has previously been reported as a part of an outcome-centered study. Eighty-six consecutive patients with 108 colorectal cancer liver metastases treated with radiofrequency ablation (2002–2012) were used for evaluation. The 2-year LTP discrimination power was assessed using receiver operating characteristic area under the curve (AUC) analysis. A 3D assessment of margins was successfully completed for 93 out of 108 tumors. The minimum margin size measured using the 3D method had higher discrimination power compared with the 2D method, with an AUC value of 0.893 vs. 0.790 (p = 0.01). The new 5-mm VIC metric had the highest 2-year LTP discrimination power with an AUC value of 0.923 (p = 0.004). Volumetric semi-automated 3D assessment of the ablation zone in the liver is feasible and can improve accuracy of 2-year LTP prediction following thermal ablation of hepatic tumors. • More accurate prediction of local tumor progression risk using volumetric 3D ablation zone assessment can help improve the efficacy of image-guided percutaneous thermal ablation of hepatic tumors. • The accuracy of evaluation of ablation zone margins after thermal ablation of colorectal liver metastases can be improved using a volumetric 3D semi-automated assessment approach and the volume of insufficient coverage assessment metric. • The new 5-mm volume-of-insufficient-coverage metric, indicating the volume of tumor plus 5-mm margin that remained untreated, had the highest 2-year local tumor progression discrimination power.

To identify common gene mutations in patients with neuroendocrine liver metastases (NLM) undergoing transarterial embolization (TAE) and establish relationship between these mutations and response to TAE.Patients (n = 51; mean age 61 y; 29 men, 22 women) with NLMs who underwent TAE and had available mutation analysis were identified. Mutation status and clinical variables were recorded and evaluated in relation to hepatic progression-free survival (HPFS) (Cox proportional hazards) and time to hepatic progression (TTHP) (competing risk proportional hazards). Subgroup analysis of patients with pancreatic NLM was performed using Fisher exact test to identify correlation between mutation and event (hepatic progression or death) by 6 months. Changes in mutation status over time and across specimens in a subset of patients were recorded.Technical success of TAE was 100%. Common mutations identified were MEN1 (16/51; 31%) and DAXX (13/51; 25%). Median overall survival was 48.7 months. DAXX mutation status (hazard ratio = 6.21; 95% confidence interval [CI], 2.67-14.48; P .001) and tumor grade (hazard ratio = 3.05; 95% CI, 1.80-5.17; P.001) were associated with shorter HPFS and TTHP on univariate and multivariate analysis. Median HPFS was 3.6 months (95% CI, 1.7-5.3) for patients with DAXX mutation compared with 8.9 months (95% CI, 6.6-11.4) for patients with DAXX wild-type status. In patients with pancreatic NLMs, DAXX mutation status was associated with hepatic progression or death by 6 months (P = .024). DAXX mutation status was concordant between primary and metastatic sites.DAXX mutation is common in patients with pancreatic NLMs. DAXX mutation status is associated with shorter HPFS and TTHP after TAE.

OBJECTIVES: To assess safety and efficacy of (90)Y resin microspheres administration using undiluted non-ionic contrast material (UDCM) {100% 0mnipaque-300 (Io-hexol)} in both the “B” and “D” lines. MATERIALS AND METHODS: We reviewed all colorectal cancer liver metastases patients treated with (90)Y resin micro-spheres radioembolization (RAE) from 2009 to 2017. As of April 2013, two experienced operators started using UDCM (study group) instead of standard sandwich infusion (control group). Occurrence of myelosuppression (leukopenia, neutropenia, erythrocytopenia or/and thrombocytopenia), stasis, nontarget delivery (NTD), median fluoroscopy radiation dose (FRD), median infusion time (IT), liver progression-free (LPFS) and overall survivals (OS) was evaluated. Complications within 6 months post-RAE were reported according to CTCAE v3.0 criteria. RESULTS: Study and control groups comprised 23(28%) and 58(72%) patients, respectively. Median follow-up was 9.1 months. There was no statistically significant difference in myelosuppression incidence within 6 months post-RAE between groups. Median FRD and IT for study and control groups were 44.6 vs. 97.35 Gy/cm(2) (p = 0.048) and 31 vs. 39 min (p = 0.006), respectively. A 38% lower stasis incidence in study group was not significant (p = 0.34). NTD occurred in 1/27(4%) study vs. 5/73(7%) control group procedures (p =1). Grade 1–2 and grade 3–4 toxicities between study and control group patients were 36%(8/22) vs. 45%(26/58), p = 0.61 and 9%(2/22) vs. 16%(9/58), p = 0.72, respectively. There was no difference in LPFS and OS between groups. CONCLUSION: Administration of (90)Y resin microspheres using UDCM in both lines is safe and effective, resulting in lower fluoroscopy radiation dose and shorter infusion time, without evidence of myelosuppression or increased stasis incidence.

Rationale and Objectives There is lack of information on the learning curve and the effect of operator's experience on the quality outcomes of transarterial hepatic embolization (TAE). The aim of this study was to evaluate the effect of operator experience on outcomes of TAE of hepatocellular carcinoma. Materials and Methods Demographic characteristics and outcomes including overall survival (OS), time to local tumor progression (TLP), and post-procedure complications in patients with hepatocellular carcinoma treated with TAE were collected. Operators' experience was measured in years based on the years after completion of fellowship and the date of first embolization, and was divided into five groups: G1, less than 5 years of operator's experience (YOE) at the time of first embolization; G2, 5–10 YOE; G3, 10–15 YOE; G4, 15–20 YOE; and G5, more than 20 YOE. The effects of operator's experience and outcomes were assessed using linear regression. Results From January 2012 to January 2015, 93 patients (age range = 30–86 years) were treated. The number of patients treated by each group was as follows: G1 = 12; G2 = 8; G3 = 23; G4 = 5; and G5 = 45. All groups were similar in regard to degree of cirrhosis, Barcelona Clinic Liver Cancer staging, and Child-Pugh score (P > .05). Median TLP was 8.8 months. TLP was 7.0, 6.8, 19.2, 7.9, and 8.2 months in G1, G2, G3, G4, and G5, respectively (P = .56). OS for 1, 2, and 3 years was 75%, 56%, and 42% for G1; 87%, 54%, and 54% for G2; 91%, 71%, and 45% for G3, 100%, 50%, and 0 for G4; and 84%, 65%, and 40% for G5. Conclusion Among interventional radiology fellowship-trained operators in a tertiary cancer center, OS, TLP, and post-procedure complications of TAE were not affected by the years of post-fellowship experience.

The NCCN Guidelines for Colon Cancer provide recommendations regarding diagnosis, pathologic staging, surgical management, perioperative treatment, surveillance, management of recurrent and metastatic disease, and survivorship. These NCCN Guidelines Insights summarize the NCCN Colon Cancer Panel discussions for the 2018 update of the guidelines regarding risk stratification and adjuvant treatment for patients with stage III colon cancer, and treatment of BRAF V600E mutation-positive metastatic colorectal cancer with regimens containing vemurafenib.

The aim of this study was to determine whether intraprocedural 18F-FDG PET/CT can be used as a predictor of local tumor progression after percutaneous ablation of colorectal liver metastases. Methods: In this institutional review board–approved prospective study, 39 patients (19 men and 20 women; median age, 56 y) underwent split-dose 18F-FDG PET/CT-guided ablation followed by immediate biopsy and contrast-enhanced CT imaging of the ablation zone. Binary categorization of biopsy tissues was performed on the basis of the presence of only nonviable coagulation necrosis or viable tumor cells. Minimum ablation margin measurements from contrast-enhanced CT imaging were categorized as 0 mm, 1–4 mm, 5–9 mm, or greater than or equal to 10 mm. SUVs were obtained from PET/CT imaging, and SUV ratios were calculated from 3-dimensional regions of interest located in the ablation zone and surrounding normal liver. All predictive variables (biopsy, minimum margin distance, and SUV ratio) were evaluated as predictors of time to local tumor progression identified on imaging using competing-risks regression models (uni- and multivariate analyses). Results: A total of 62 consecutive ablations were evaluated. The mean SUV ratio was significantly higher for viable tumor–positive immediate postablation biopsies (n = 10) than for tumor-negative biopsies (n = 52) (85.8 ± 92.2 vs. 42.3 ± 45.5) (P = 0.03) and for a minimum margin size of less than 5 mm (n = 15) than for a minimum margin size of greater than or equal to 5 mm (n = 47) (78.5 ± 99.1 vs. 38.3 ± 78.5) (P = 0.01). After a median follow-up period of 22.5 (range, 7–52) months, 23 of 62 ablated tumors showed local tumor progression (37.1%). The local tumor progression rate was significantly higher for viable tumor–positive biopsies (8/10) than for negative biopsies (15/52) (80% vs. 29%) (P = 0.001) and for a minimum margin size of less than 5 mm (9/15) than for a minimum margin size of greater than or equal to 10 mm (2/15) (60% vs. 13%) (P = 0.02) but not 5–9 mm (37.5%; 12/32) (P = 0.5). In a competing-risks analysis, biopsy results (P = 0.07) and the minimum margin size (P = 0.08) were borderline significant, but the SUV ratio was not (P = 0.22). However, for negative biopsy ablations, the minimum margin size and SUV ratio were predictive imaging factors for local tumor progression; subdistribution hazard ratios were 0.564 (0.325–0.978) (P = 0.04) and 1.005 (1.001–1.009) (P = 0.005), respectively. Conclusion: The SUV ratio and minimum margin size can independently predict colorectal metastasis local tumor progression after liver ablation when there are no viable tumor cells on immediate postablation biopsies.

Liver metastases are a major cause of death from colorectal cancer. Intraarterial therapy options for colorectal liver metastases include chemoinfusion via a hepatic arterial pump or port, irinotecan-loaded drug-eluting beads, and radioembolization using (90)Y microspheres. Intraarterial therapy allows the delivery of a high dose of chemotherapy or radiation into liver tumors while minimizing the impact on liver parenchyma and avoiding systemic effects. Specificity in intraarterial therapy can be achieved both through preferential arterial flow to the tumor and through selective catheter positioning. In this review, we discuss indications, contraindications, preprocedure evaluation, activity prescription, follow-up, outcomes, and complications of radioembolization of colorectal liver metastases. Methods for preventing off-target embolization, increasing the specificity of microsphere delivery, and reducing the lung-shunt fraction are discussed. There are 2 types of (90)Y microspheres: resin and glass. Because glass microspheres have a higher activity per particle, they can deliver a particular radiation dose with fewer particles, likely reducing embolic effects. Glass microspheres thus may be more suitable when early stasis or reflux is a concern, in the setting of hepatocellular carcinoma with portal vein invasion, and for radiation segmentectomy. Because resin microspheres have a lower activity per particle, more particles are needed to deliver a particular radiation dose. Resin microspheres thus may be preferable for larger tumors and those with high arterial flow. In addition, resin microspheres have been approved by the U.S. Food and Drug Administration for colorectal liver metastases, whereas institutional review board approval is required before glass microspheres can be used under a compassionate-use or research protocol. Finally, radiation segmentectomy involves delivering a calculated lobar activity of (90)Y microspheres selectively to treat a tumor involving 1 or 2 liver segments. This technique administers a very high radiation dose and effectively causes the ablation of tumors that are too large or are in a location considered unsafe for thermal ablation. The selective delivery spares surrounding normal liver, reducing the risk of liver failure.

PURPOSE: To evaluate the changes in T-cell balance in peripheral blood following percutaneous tumor ablation. MATERIAL AND METHODS: Patients underwent thermal ablation including radiofrequency (n = 9) and microwave ablation (n = 5), or cryoablation (n = 5). Target tumors were located in the lung (n = 7), soft tissue (n = 5), liver (n = 4), and bone (n = 3). Patient peripheral blood samples were collected before and within 14 days after ablation. Peripheral blood populations of cytotoxic T-cells (CTL), type-1 (T(h)1) and type-2 helper T-cells (T(h)2), and regulatory T-cells (T(reg)) were measured using flow cytometry. Changes in CTL/T(reg) and T(h)1/T(h)2 ratios before and after ablation therapy were compared using paired t-tests. RESULTS: Peripheral blood CTL population (27.5 ± 2.1% to 30.2 ± 2.5%, p < .03) and CTL/T(reg) ratios (18.8 ± 3.7% to 21.6 ± 3.6%, p < .05) increased significantly after ablation. Although a significant increase in CTL/T(reg) ratios was found after heat-based ablation (18.0 ± 4.4% to 21.6 ± 4.7%, p < .02), it remained unchanged after cryoablation (21.0 ± 7.0% to 21.5 ± 4.3%, p = .92). T(h)1/T(h)2 ratio (13.7 ± 3.0% to 17.2 ± 3.5%, p = .12) remained unchanged after ablation. CONCLUSION: Ablation therapy alters the T-cell balance by increasing the systemic CTL/T(reg,) ratio. Heat-based ablation might be a more effective approach than cryoablation to enhance systemic anti-tumor immunity.

Background: Surgical resection of limited colorectal liver disease improves long-term survival and can be curative in a subset of selected cases. Image-guided percutaneous ablation therapies have emerged as safe and effective alternative options for selected patients with unresectable colorectal liver metastases (CLM) that can be ablated with margins. Ablation causes focal destruction of tissue and has increasingly been shown to provide durable eradication of tumors. Methods: A selective review of literature was conducted in PubMed, focusing on recent studies reporting on the safety, efficacy, and long-term outcomes of percutaneous ablation modalities in the treatment of CLM. The present work gives an overview of the different ablation techniques, their current clinical indications, and reported outcomes from most recently published studies. The ‘test of time' concept for using ablation as a first local therapy is also described. Results: There are several thermal ablative tools currently available, including radiofrequency ablation (RFA), microwave ablation, and cryoablation. Most data to date originated from the application of RFA. Adjuvant thermal ablation in the treatment of oligometastatic colon cancer liver disease offers improved oncologic outcomes. The ideal CLM amenable to percutaneous ablation is a solitary tumor with the largest diameter up to 3 cm that can be completely ablated with a sufficient margin. 5-year overall survival rates up to 70% after ablation of unresectable CLM have been reported. Pathologic confirmation of complete tumor necrosis with margins over 5 mm provides best long-term local tumor control by thermal ablation. Conclusion: Current evidence suggests that percutaneous ablation as adjuvant to chemotherapy improves oncologic outcomes of patients with CLM. For small tumors that can be ablated completely with clear margins, percutaneous ablation may offer outcomes similar to those of surgery.

Purpose To describe ablation of bone, liver, lung, and soft tissue tumors from oligometastatic breast cancer and to define predictors of local progression and progression-free survival (PFS). Materials and Methods A total of 33 women (mean age 52 ± 12 years old; range, 28–69 years), underwent 46 thermal ablations of liver (n = 35), lung (n = 7), and bone/soft tissue (n = 4) metastases. Mean tumor diameter was 18 ± 15 mm (range, 6–50 mm). Ablations were performed to eradicate all evident sites of disease (n = 24) or to control growing sites in the setting of other stable or responding sites of disease (n = 22). Patient characteristics, ablation margins, imaging responses, and cases of PFS were assessed. Follow-up imaging was performed using contrast-enhanced computed tomography (CT), magnetic resonance (MR) imaging, or positron-emission tomography/ CT. Results Median PFS was 10 months (95% confidence interval [CI], 6.2 –14.5 months), and time to local progression was 11 months (95% CI, 5–16 months). Eight patients (24%) maintained no evidence of disease during a median follow-up period of 39 months. Ablation margin ≥5 mm was associated with no local tumor progression. Longer PFS was noted in estrogen receptor-positive patients (12 vs 4 months; P = .037) and younger patients (12 vs 4 months; P = .039) treated to eradicate all sites of disease (13 vs 5 months; P = .05). Eighteen patients (55%) developed new metastases during study follow-up. Conclusions Thermal ablation of oligometastatic pulmonary, hepatic, bone, and soft tissue tumors can eliminate local tumor progression if margins are ≥5 mm. Longer PFS was observed in patients who were estrogen receptor-positive and patients who were younger and in whom all sites of disease were eradicated.

This study aimed to evaluate whether rapid fluorescent tissue examination immediately after colorectal cancer liver metastasis (CLM) ablation correlates with standard pathologic and immunohistochemical (IHC) assessments.This prospective, National Institutes of Health-supported study enrolled 34 consecutive patients with 53 CLMs ablated between January 2011 and December 2014. Immediately after ablation, core needle sampling of the ablation zone was performed. Tissue samples were evaluated with fluorescent viability (MitoTracker Red) and nuclear (Hoechst) stains. Confocal microscope imaging was performed within 30 min after ablation. The same samples were subsequently fixed and stained with hematoxylin and eosin (HE). Identified tumor cells underwent IHC staining for proliferation (Ki67) and viability (OxPhos). The study pathologist, blinded to the HE and IHC assessment, evaluated the fluorescent images separately to detect viable tumor cells. Sensitivity, specificity, and overall concordance of the fluorescent versus HE and IHC assessments were calculated.A total of 63 tissue samples were collected and processed. The overall concordance rate between the immediate fluorescent and the subsequent HE and IHC assessments was 94% (59/63). The fluorescent assessment sensitivity and specificity for the identification of tumor cells were respectively 100% (18/18) and 91% (41/45).The study showed a high concordance rate between the immediate fluorescent assessment and the standard HE and IHC assessment of the ablation zone. Given the documented prognostic value of ablation zone tissue characteristics for outcomes after ablation of CLM, the fluorescent assessment offers a potential intra-procedural biomarker of complete tumor ablation.

OBJECTIVE. The purpose of this study was to assess the mechanism by which aspirin therapy improves survival when combined with transarterial chemoembolization or transarterial embolization (TAE) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS. A retrospective review included 304 patients with HCC who were treated with TAE. The patients were divided into two groups on the basis of whether the patient took aspirin (n = 42) or did not take aspirin (n = 262) at the time of initial TAE. For each patient, response of embolized tumors, time to progression, initial site of progression, survival time, and liver function test results before and after embolization were evaluated. RESULTS. Patients taking aspirin and those not taking aspirin at the time of initial TAE for HCC had no difference in initial response rate (88% vs 90% complete response or partial response, p = 0.59), median time to progression (6.2 vs 5.2 months, p = 0.42), initial site of progression (p = 0.77), or fraction of patients dying with disease progression (88% vs 89%, p = 1.00). Before embolization, there was no difference in mean bilirubin level (0.8 vs 0.9 mg/dL, p = 0.11) for patients taking versus not taking aspirin. Among patients taking aspirin, bilirubin level was significantly lower 1 day (0.9 vs 1.3, p < 0.001), 1 month (0.9 vs 1.2, p = 0.048), and 1 year (0.8 vs 1.0, p = 0.021) after embolization. The median overall survival period after initial embolization was longer for patients taking aspirin (57 vs 23 months, p = 0.008). CONCLUSION. Aspirin use is associated with improved liver function test results and survival after TAE for HCC. It is not associated with differences in response or time to progression.

International audience; Comparison of Stereotactic Body Radiation Therapy and Radiofrequency Ablation in the Treatment of Intrahepatic Metastases” by Jackson et al is a thought-provoking addition to the literature concerning treatment of colorectal cancer metastasis (CLM). The benefits of hepatic CLM resection are well established; however, most patients are not candidates for resection. Local tumor ablation is a safe and effective alternative treatment for select patients. Considerable research has evaluated percutaneous ablation as treatment of CLM, including retrospective reviews with long-term follow-up and prospective randomized trials showing prolongation of progression-free and patient survival compared with chemotherapy alone.1, 2, 3 The National Comprehensive Cancer Network guidelines recommend ablation for patients with CLMs with or without surgery as long as all tumors can be effectively treated. Conversely, the evidence for stereotactic body radiation therapy (SBRT) in the treatment of any size of CLM is sparse; the National Comprehensive Cancer Network recommends that SBRT not be used indiscriminately when other treatment options are available.

One-year overall survival prediction nomogram included 6 easy-to-obtain pre Yttrium-90 radioembolization parameters and provided good prediction of overall survival post Yttrium-90 radioembolization. This can be useful for pretreatment patient stratification and counseling of heavily pretreated patients with colorectal cancer liver metastases. Baseline maximum standardized uptake value predicted liver progression-free survival.Introduction: The purpose of this studywas to identify predictors of overall (OS) and liver progression-free survival (LPFS) following Yttrium-90 radioembolization (RAE) of heavily pretreated patients with colorectal cancer liver metastases (CLM), as well as to create and validate a predictive nomogramfor OS. Materials and Methods: Metabolic, anatomic, laboratory, pathologic, genetic, primary disease, and procedure-related factors, aswell as pre- and post-RAE therapies in 103 patients with CLM treated with RAE from September 15, 2009 to March 21, 2017 were analyzed. LPFS was defined by Response Evaluation Criteria In Solid Tumors 1.1 and European Organization for Research and Treatment of Cancer criteria. Prognosticators of OS and LPFS were selected using univariate Cox regression, adjusted for clustering and competing risk analysis (for LPFS), and subsequently tested in multivariate analysis (MVA). The nomogram was built using R statistical software and internally validated using bootstrap resampling. Results: Patients received RAE at a median of 30.9 months (range, 3.4-161.7 months) after detection of CLM. The median OS and LPFS were 11.3 months (95% confidence interval, 7.9-15.1 months) and 4 months (95% confidence interval, 3.3-4.8 months), respectively. Of the 40 parameters tested, 6 were independently associatedwithOS inMVA. These baseline parameters included number of extrahepatic disease sites (P 80 was 90% and 10%, respectively. Bootstrap resampling showed good discrimination (optimism corrected c-index = 0.745) and calibration (mean absolute prediction error = 0.299) of the nomogram. Only baseline maximumstandardized uptake value was significant in MVA for LPFS prediction (P

3602 Background: Lung chemoembolization (via the bronchial or pulmonary artery) is a new treatment option for unresectable and unablatable lung metastases. Methods: 10 patients with unresectable and unablatable lung, endobronchial, or mediastinal metastases, who failed systemic chemotherapy, were enrolled in this single center, single arm, phase I trial. Pulmonary and bronchial angiography was performed in all patients, to determine the blood supply to the lung metastases. Based on the angiographic findings, bronchial or pulmonary artery chemoembolization was performed, using a lipiodol / mitomycin emulsion, followed by spherical particles. Technical success, safety, efficacy, and pharmacokinetics were evaluated. Wilcoxon signed-rank test was used to compare change in size of treated versus untreated tumors. Results: On angiography, all patients had lung metastases that were hypervascular compared to normal lung. 90% of patients had lung metastases supplied by the bronchial artery, and 10% were supplied by the pulmonary artery. Technical success rate of intra-tumoral drug delivery was 100% (95% CI: 76-100%). There were no severe adverse events, and all patients met criteria for discharge 4 hours post procedure. Response rate of treated lesions was 10% by RECIST and 40% by PERCIST. Treated tumors were mostly stable to decreased in size after chemoembolization (median change in size: 0%; IQR: -11% to 2%; mean: -4%), and untreated tumors were mostly increased in size (median change in size: 10%; IQR: 0% to 17%; mean 9%; p= 0.02). Intra-tumoral lipiodol retention at 4-6 weeks was correlated with decreased tumor size and metabolic activity. 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 > 5 hours. Initial tumor-to-plasma ratio of mitomycin concentration was 380. Half-life of intratumoral lipiodol retention was 16 days. In vitro experiments showed 50% emulsion separation in 6.2 days, and 50% drug release in 7.1 hours. Conclusions: Lung chemoembolization can safely treat lung, mediastinal, and endobronchial metastases, with minimal systemic toxicity. High intratumoral drug concentrations after chemoembolization can overcome chemoresistance. Clinical trial information: NCT04200417.

Colorectal liver metastases (CLM) have a variable response to radioembolization. This may be due at least partly to differences in tumor arterial perfusion. The present study examines whether quantitative measurements of enhancement on preprocedure triphasic CT can be used to predict the response of CLM to radioembolization.We retrospectively reviewed patients with CLM treated with radioembolization who underwent pretreatment PET/CT and triphasic CT examinations and posttreatment PET/CT examinations. A total of 31 consecutive patients with 60 target tumors were included in the present study. For each tumor, we calculated the hepatic artery coefficient (HAC), portal vein coefficient (PVC), and arterial enhancement fraction (AEF) based on enhancement measurements on pretreatment triphasic CT. HAC and PVC are estimates of the hepatic artery and portal vein blood supply. AEF, which is the arterial phase enhancement divided by the portal phase enhancement, provides an estimate of the hepatic artery blood supply as a fraction of the total blood supply. For each tumor, the metabolic response to radioembolization was based on findings from the initial follow-up PET/CT scan obtained at 4-8 weeks after treatment.A total of 55% of CLM had a complete or partial metabolic response. Arterial phase enhancement, the HAC, and the PVC did not predict which tumors responded to radioembolization. However, the AEF was statistically significantly greater in tumors with a complete or partial metabolic response than in tumors with no metabolic response (i.e., those with stable disease or disease progression) (p = 0.038). An AEF of less than 0.4 was associated with a 40% response rate, whereas an AEF greater than 0.75 was associated with a 78% response rate.Response to radioembolization can be predicted using the AEF calculated from the preprocedure triphasic CT.

Purpose To establish the prognostic value of biopsy of the central and marginal ablation zones for time to local tumor progression (LTP) after radiofrequency (RF) ablation of colorectal cancer liver metastasis (CLM). Materials and Methods A total of 47 patients with 67 CLMs were enrolled in this prospective institutional review board-approved and HIPAA-compliant study between November 2009 and August 2012. Mean tumor size was 2.1 cm (range, 0.6-4.3 cm). Biopsy of the center and margin of the ablation zone was performed immediately after RF ablation (mean number of biopsy samples per ablation zone, 1.9) and was evaluated for the presence of viable tumor cells. Samples containing tumor cells at morphologic evaluation were further interrogated with immunohistochemistry and were classified as either positive, viable tumor (V) or negative, necrotic (N). Minimal ablation margin size was evaluated in the first postablation CT study performed 4-8 weeks after ablation. Variables were evaluated as predictors of time to LTP with the competing-risks model (uni- and multivariate analyses). Results Technical effectiveness was evident in 66 of 67 (98%) ablated lesions on the first contrast material-enhanced CT images at 4-8-week follow-up. The cumulative incidence of LTP at 12-month follow-up was 22% (95% confidence interval [CI]: 12, 32). Samples from 16 (24%) of 67 ablation zones were classified as viable tumor. At univariate analysis, tumor size, minimal margin size, and biopsy results were significant in predicting LTP. When these variables were subsequently entered in a multivariate model, margin size of less than 5 mm (P < .001; hazard ratio [HR], 6.7) and positive biopsy results (P = .008; HR, 3.4) were significant. LTP within 12 months after RF ablation was noted in 3% (95% CI: 0, 9) of necrotic CLMs with margins of at least 5 mm. Conclusion Biopsy proof of complete tumor ablation and minimal ablation margins of at least 5 mm are independent predictors of LTP and yield the best oncologic outcomes. (©) RSNA, 2016.

Objectives: To test the feasibility of modified biopsy needles as probes for irreversible electroporation ablation and periprocedural biopsy. Methods: Core biopsy needles of 16-G/9-cm were customized to serve as experimental ablation probes. Computed tomography-guided percutaneous irreversible electroporation was performed in in vivo porcine kidneys with pairs of experimental (n = 10) or standard probes (n = 10) using a single parameter set (1667 V/cm, ninety 100 µs pulses). Two biopsy samples were taken immediately following ablation using the experimental probes (n = 20). Ablation outcomes were compared using computed tomography, simulation, and histology. Biopsy and necropsy histology were compared. Results: Simulation-suggested ablations with experimental probes were smaller than that with standard electrodes (455.23 vs 543.16 mm2), although both exhibited similar shape. Computed tomography (standard: 556 ± 61 mm2, experimental: 515 ± 67 mm2; P = .25) and histology (standard: 313 ± 77 mm2, experimental: 275 ± 75 mm2; P = .29) indicated ablations with experimental probes were not significantly different from the standard. Histopathology indicated similar morphological changes in both groups. Biopsies from the ablation zone yielded at least 1 core with sufficient tissue for analysis (11 of the 20). Conclusions: A combined probe for irreversible electroporation ablation and periprocedural tissue sampling from the ablation zone is feasible. Ablation outcomes are comparable to those of standard electrodes.