Pigs as Clinically Relevant Models for Synergizing Interventional Oncology and Immunotherapy.

Traditionally, rodent cancer models have driven preclinical oncology research. However, they do not fully recapitulate characteristics of human cancers, and their size poses challenges when evaluating tools in the interventional oncologists' armamentarium. Pig models, however, have been the gold standard for validating surgical procedures. Their size enables the study of image-guided interventions using human ultrasound (US), computed tomography (CT), and magnetic resonance (MR) imaging platforms. Furthermore, pigs have immunologic features that are similar to those of humans, which can potentially be leveraged for studying immunotherapy. Novel pig models of cancer are being developed, but additional research is required to better understand both the pig immune system and malignancy to enhance the potential for pig models in interventional oncology research. This review aims to address the main advantages and disadvantages of using a pig model for interventional oncology and outline the specific characteristics of pig models that make them more suitable for investigation of locoregional therapies.

Computed Tomography Angiography and Conventional Angiography for the Diagnosis and Treatment of Non-variceal Gastrointestinal Bleeding at a Tertiary Cancer Center.

INTRODUCTION: To evaluate the diagnostic value of computed tomography angiography (CTA) and conventional angiography (CA) and the therapeutic value of transarterial embolization for acute gastrointestinal bleeding in patients with malignancy. METHODS: A retrospective review of 100 patients who underwent CTA and/or CA for gastrointestinal bleeding at a comprehensive cancer center between the years 2011-2021 was performed. Clinical and patient outcome data were collected and analyzed using Kruskal-Wallis tests for continuous variables and chi-square tests or Fisher's exact tests (whichever is appropriate) for categorical variables in univariate analysis. All tests were two-sided at a significance level of 0.05. Analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC). RESULTS: Fifty-two percent of our patients underwent CTA alone, 29% underwent CA alone, and 19% underwent both procedures. Overall, CTA was positive in 11.3% (8/71) of patients and CA was positive in 22.9% (11/38) of patients. Of patients who underwent both studies, 52.6% (10/19) were positive for both. ICU admission was associated with CTA and/or CA positivity (p=0.015). Of 48 patients with data for embolization, 50% of patients underwent transarterial embolization for bleeding, 11 patients had identifiable bleeding on CA, and 13 patients underwent prophylactic embolization at the site of suspected bleeding. Rebleeding following embolization was found in 33.3% (8/24) of patients, including six patients who underwent prophylactic embolization and two patients who were treated for visualized bleeding. CONCLUSION: CTA and CA are two critical studies for patients with GI bleeding and a history of malignancy. Neither alone can effectively exclude an identifiable source of bleeding. In patients with a history of malignancy, transarterial embolization may be an effective treatment of both angiographically visible and occult sources of GI bleeding.

Optimizing 90Y Particle Density Improves Outcomes After Radioembolization.

PURPOSE: To determine how particle density affects dose distribution and outcomes after lobar radioembolization. METHODS: Matched pairs of patients, treated with glass versus resin microspheres, were selected by propensity score matching (114 patients), in this single-institution retrospective study. For each patient, tumor and liver particle density (particles/cm3) and dose (Gy) were determined. Tumor-to-normal ratio was measured on both 99mTc-MAA SPECT/CT and post-90Y bremsstrahlung SPECT/CT. Microdosimetry simulations were used to calculate first percentile dose, which is the dose in the cold spots between microspheres. Local progression-free survival (LPFS) and overall survival were analyzed. RESULTS: As more particles were delivered, doses on 90Y SPECT/CT became more uniform throughout the treatment volume: tumor and liver doses became more similar (p = 0.04), and microscopic cold spots between particles disappeared. For hypervascular tumors (tumor-to-normal ratio ≥ 2.6 on MAA scan), delivering fewer particles (< 6000 particles/cm3 treatment volume) was associated with better LPFS (p = 0.03). For less vascular tumors (tumor-to-normal ratio < 2.6), delivering more particles (≥ 6000 particles/cm3) was associated with better LPFS (p = 0.02). In matched pairs of patients, using the optimal particle density resulted in improved overall survival (11.5 vs. 6.8 months, p = 0.047), compared to using suboptimal particle density. Microdosimetry resulted in better predictions of LPFS (p = 0.03), and overall survival (p = 0.02), compared to conventional dosimetry. CONCLUSION: The number of particles delivered can be chosen to maximize the tumor dose and minimize the liver dose, based on tumor vascularity. Optimizing the particle density resulted in improved LPFS and overall survival.

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

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

Transarterial Embolization of Liver Cancer in a Transgenic Pig Model.

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

Relationship of radiation dose to efficacy of radioembolization of liver metastasis from breast cancer.

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 (p < 0.001). ≥Grade 3 hepatotoxicity occurred in 8/64 (12.5 %) and was associated with higher pre-treatment bilirubin levels of 0.9 (0.9-1.1) vs. 0.5 (0.4-0.7) mg/dL (p = 0.013). Median overall survival (OS) was 11 (95 % CI 10-19) months. Bilobar disease (Hazard Ratio [HR]: 2.77, 95 % CI 1.11-6.89, p = 0.028) and elevated pre-TARE AST (HR 1.02, 95 % CI 1.01-1.03, p < 0.001) were independently associated with shorter survival. ≥Grade 3 hepatotoxicity was associated with reduced survival (p < 0.001). OR was associated with longer OS of 17 months, compared with 10 months (p = 0.027). CONCLUSION: In TARE for breast cancer liver metastasis, higher tumoral radiation dose (>79.5 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.

Anticoagulation reduces iliocaval and iliofemoral stent thrombosis in patients with cancer stented for nonthrombotic venous obstruction.

OBJECTIVE: To identify factors associated with venous stent thrombosis in patients with cancer treated for nonthrombotic iliocaval or iliofemoral venous obstruction. METHODS: We performed a retrospective review of relevant imaging and medical records from 30 consecutive patients with cancer treated at a single center who underwent venous stent placement for nonthrombotic iliocaval or iliofemoral venous obstruction between 2008 and 2018. Follow-up imaging was used to assess stent patency. Variables examined included patient demographics, cancer type, stent characteristics, anticoagulant, and antiplatelet medications and complications of treatment. RESULTS: Overall primary stent patency was 83% (25/30). The median follow-up period was 44 days (range, 3-365 days). Ten percent of patients occluded owing to in-stent thrombosis and 7% owing to tumor compression of the stent without thrombosis. Therapeutic poststent anticoagulation with enoxaparin, warfarin, or a factor Xa inhibitor was initiated in 87% of the patients. Stent thrombosis occurred in one patient in the anticoagulation group (4%) at 50 days. Stent thrombosis occurred in two patients in the nonanticoagulation group (50%), one at 9 days and the other at 91 days. Anticoagulation was found to be protective against stent thrombosis in this population (hazard ratio, 0.015; P = .011). No statistically significant associations were found among the remaining variables. One patient in the anticoagulation group experienced major bleeding (1/26 [4%]). CONCLUSIONS: Iliocaval and iliofemoral stent placement for nonthrombotic malignant venous obstruction is safe with favorable primary patency rates. Therapeutic anticoagulation is associated with less stent thrombosis in patients with cancer stented for nonthrombotic iliocaval and iliofemoral venous obstruction.

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

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

Development and comprehensive characterization of porcine hepatocellular carcinoma for translational liver cancer investigation.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. New animal models that faithfully recapitulate human HCC phenotypes are required to address unmet clinical needs and advance standard-of-care therapeutics. This study utilized the Oncopig Cancer Model to develop a translational porcine HCC model which can serve as a bridge between murine studies and human clinical practice. Reliable development of Oncopig HCC cell lines was demonstrated through hepatocyte isolation and Cre recombinase exposure across 15 Oncopigs. Oncopig and human HCC cell lines displayed similar cell cycle lengths, alpha-fetoprotein production, arginase-1 staining, chemosusceptibility, and drug metabolizing enzyme expression. The ability of Oncopig HCC cells to consistently produce tumors in vivo was confirmed via subcutaneous (SQ) injection into immunodeficient mice and Oncopigs. Reproducible development of intrahepatic tumors in an alcohol-induced fibrotic microenvironment was achieved via engraftment of SQ tumors into fibrotic Oncopig livers. Whole-genome sequencing demontrated intrahepatic tumor tissue resembled human HCC at the genomic level. Finally, Oncopig HCC cells are amenable to gene editing for development of personalized HCC tumors. This study provides a novel, clinically-relevant porcine HCC model which holds great promise for improving HCC outcomes through testing of novel therapeutic approaches to accelerate and enhance clinical trials.

NRF2 Dysregulation in Hepatocellular Carcinoma and Ischemia: A Cohort Study and Laboratory Investigation.

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.

PET/CT Imaging Characteristics After Radioembolization of Hepatic Metastasis from Breast Cancer.

PURPOSE: 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). MATERIALS AND METHODS: 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%. RESULTS: 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. CONCLUSION: 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.

Aspirin Is Associated With Improved Liver Function After Embolization of Hepatocellular Carcinoma.

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.

Outcomes After Transarterial Embolization of Neuroendocrine Tumor Liver Metastases Using Spherical Particles of Different Sizes.

PURPOSE: To evaluate initial response and overall survival of neuroendocrine tumor (NET) liver metastases initially treated with transarterial embolization (TAE) using spherical particles of different sizes. METHODS: A single-institution retrospective review was performed of 160 patients with NET liver metastases initially treated with TAE using < 100 µm (n = 77) or only ≥ 100 µm (n = 83) spherical particles. For each patient, we evaluated: initial response by mRECIST, time to progression, overall survival, complications, primary site, tumor grade and degree of differentiation, volume of liver disease, extrahepatic disease, NET-related symptoms, comorbidities, Child-Pugh score, performance status, lobar versus selective embolization, and arteriovenous shunting. RESULTS: Initial response was higher for TAE using particles < 100 versus TAE using only particles ≥ 100 µm (64 vs 42%, p = 0.007). Multivariate logistic regression showed that use of particles < 100 µm and liver < 50% replaced with tumor were independent predictors of a better initial response rate. There was no difference in major or minor complications between the two particle size groups. Median overall survival after TAE was 55 months for well- to moderately differentiated NET and 13 months for poorly differentiated or undifferentiated NET. There was no significant difference in survival between TAE patients treated with < 100 versus only ≥ 100-µm particles. CONCLUSION: NET patients treated with TAE using particles < 100 µm had better initial response, but the same overall survival, compared to TAE using only particles ≥ 100 µm.

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.

DAXX Mutation Status of Embolization-Treated Neuroendocrine Tumors Predicts Shorter Time to Hepatic Progression.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: DAXX mutation is common in patients with pancreatic NLMs. DAXX mutation status is associated with shorter HPFS and TTHP after TAE.

Association of PI3K Pathway Mutations with Early Positron-Emission Tomography/CT Imaging Response after Radioembolization for Breast Cancer Liver Metastases: Results of a Single-Center Retrospective Pilot Study.

PURPOSE: To describe imaging response and survival after radioembolization for metastatic breast cancer and to delineate genetic predictors of imaging responses and outcomes. MATERIALS AND METHODS: This retrospective study included 31 women (average age, 52 y) with liver metastasis from invasive ductal carcinoma who underwent resin and glass radioembolization (average cumulative dose, 2.0 GBq ± 1.8) between January 2011 and September 2017 after receiving ≥ 3 lines of chemotherapy. Twenty-four underwent genetic profiling with MSK-IMPACT or Sequenom; 26 had positron-emission tomography (PET)/CT imaging before and after treatment. Survival after the first radioembolization and 2-4-month PET/CT imaging response were assessed. Laboratory and imaging features were assessed to determine variables predictive of outcomes. Unpaired Student t tests and Fisher exact tests were used to compare responders and nonresponders categorized by changes in fluorodeoxyglucose avidity. Kaplan-Meier survival analysis was used to determine the impact of predictors on survival after radioembolization. RESULTS: Median survival after radioembolization was 11 months (range, 1-49 mo). Most patients (18 of 26; 69%) had complete or partial response based on changes in fluorodeoxyglucose avidity. Imaging response was associated with longer survival (P = .005). Whereas 100% of patients with PI3K pathway mutations showed an imaging response, only 45% of wild-type patients showed a response (P = .01). Median survival did not differ between PI3K pathway wild-type (10.9 mo) and mutant (undefined) patients (P = .50). CONCLUSIONS: These preliminary data suggest that genomic profiling may predict which patients with metastatic breast cancer benefit most from radioembolization. PI3K pathway mutations are associated with improved imaging response, which is associated with longer survival.