Genomic profiling identifies somatic mutations predicting thromboembolic risk in patients with solid tumors.

Venous thromboembolism (VTE) associated with cancer (CAT) is a well-described complication of cancer and a leading cause of death in patients with cancer. The purpose of this study was to assess potential associations of molecular signatures with CAT, including tumor-specific mutations and the presence of clonal hematopoiesis. We analyzed deep-coverage targeted DNA-sequencing data of >14 000 solid tumor samples using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets platform to identify somatic alterations associated with VTE. End point was defined as the first instance of cancer-associated pulmonary embolism and/or proximal/distal lower extremity deep vein thrombosis. Cause-specific Cox proportional hazards regression was used, adjusting for pertinent clinical covariates. Of 11 695 evaluable individuals, 72% had metastatic disease at time of analysis. Tumor-specific mutations in KRAS (hazard ratio [HR], 1.34; 95% confidence interval (CI), 1.09-1.64; adjusted P = .08), STK11 (HR, 2.12; 95% CI, 1.55-2.89; adjusted P < .001), KEAP1 (HR, 1.84; 95% CI, 1.21-2.79; adjusted P = .07), CTNNB1 (HR, 1.73; 95% CI, 1.15-2.60; adjusted P = .09), CDKN2B (HR, 1.45; 95% CI, 1.13-1.85; adjusted P = .07), and MET (HR, 1.83; 95% CI, 1.15-2.92; adjusted P = .09) were associated with a significantly increased risk of CAT independent of tumor type. Mutations in SETD2 were associated with a decreased risk of CAT (HR, 0.35; 95% CI, 0.16-0.79; adjusted P = .09). The presence of clonal hematopoiesis was not associated with an increased VTE rate. This is the first large-scale analysis to elucidate tumor-specific genomic events associated with CAT. Somatic tumor mutations of STK11, KRAS, CTNNB1, KEAP1, CDKN2B, and MET were associated with an increased risk of VTE in patients with solid tumors. Further analysis is needed to validate these findings and identify additional molecular signatures unique to individual tumor types.

Antithrombotic Therapy After Venous Interventions: AJR Expert Panel Narrative Review.

Interventions for thrombotic and nonthrombotic venous disorders have increased with technical advances and more trained venous specialists. Antithrombotic therapy is essential to clinical and procedural success; however, postprocedural therapeutic regimens exhibit significant heterogeneity due to limited prospective randomized data and incomplete mechanistic understanding of the critical factors driving long-term patency. Postinterventional antithrombotic therapy for thrombotic venous disorders should adhere to existing venous thromboembolism management guidelines, which include 3-6 months of therapeutic anticoagulation at minimum and consideration of extended therapy in patients with higher risk of thrombosis because of procedural or patient factors. The added benefit of antiplatelet agents in the acute and intermediate period is unknown, having shown improved long-term stent patency in some retrospective studies. Dual- and/or triple-agent therapy should be limited based on individual risks of thrombosis and bleeding. The treatment of nonthrombotic disorders is more heterogeneous, though patients with limited flow, extensive stent material, or underlying prothrombotic states such as malignancy or chronic inflammation may benefit from single-agent or multiagent antithrombotic therapy. However, the agent, dose, and duration of therapy remain indeterminate. Future prospective studies are warranted to improve patient risk stratification and standardize postprocedural anti-thrombotic therapy in patients receiving venous interventions.

Endovascular Management of Venous Thromboembolic Disease in the Oncologic Patient Population.

PURPOSE OF REVIEW: Venous thromboembolic disease causes significant mortality and morbidity in the oncologic patient population. Recently, minimally invasive endovascular technologies have been developed as an adjunct to antithrombotic therapy for the management of DVT and PE. The current and potential roles for endovascular treatment of cancer-associated venous thromboembolism (VTE) will be reviewed in this article. RECENT FINDINGS: The recent NCCN guidelines recommend endovascular therapy in patients eligible for therapeutic anticoagulation who present with life-, organ-, or limb-threatening thrombosis. However, symptomatic non-life-threatening VTE can negatively affect QOL and physical function, both of which have prognostic implications in the cancer population. Endovascular therapies have been shown to improve physical function and QOL in prospective trials performed in a non-oncologic patient population as well as small retrospective studies in the cancer population. In addition to treating life- and limb-threatening thrombosis, endovascular therapy for VTE can improve QOL and physical function in comparison to anticoagulation alone. Prospective trials are warranted to assess the benefit of endovascular therapy for quality of life-years, performance status, and overall survival in the oncologic patient population.

Interventional Management of Portal Hypertension in Cancer Patients.

PURPOSE OF REVIEW: To provide an overview of the classifications and clinical hallmarks of common cancer-related conditions that contribute to the high incidence of portal hypertension in this population and provide an update on currently available interventional radiology therapeutic approaches. RECENT FINDINGS: In the last few decades, there have been significant advancements in understanding the pathophysiology of portal hypertension. This knowledge has led to the development of safer and more effective minimally invasive approaches. The main objective is to provide alternatives to prevent life-threatening complications from clinically significant portal hypertension and to allow the continuation of cancer treatment interventions that would otherwise be stopped. Clinicians involved in cancer care should be aware of risk factors, associated complications, and management of portal hypertension in cancer patients. Interventional radiology offers minimally invasive alternatives that play a central role in improving clinical outcomes and survival of these patients, allowing the continuation of cancer treatments.

Genicular Artery Embolization for Refractory Hemarthrosis following Total Knee Arthroplasty: Technique, Safety, Efficacy, and Patient-Reported Outcomes.

PURPOSE: To investigate the safety and efficacy of genicular artery embolization for treatment of refractory hemarthrosis following total knee arthroplasty. MATERIAL AND METHODS: Patients who underwent genicular artery embolization with spherical embolics between January 2010 and March 2020 at a single institution were included if they had undergone total knee arthroplasty and subsequently experienced recurrent hemarthrosis. Technical success was defined as the significant reduction or elimination of the hyperemic blush. Clinical success was defined as the absence of clinical evidence of further hemarthrosis. Clinical follow-up was performed 7-14 days after the procedure and at 3-month intervals thereafter via a telephone interview. A total of 117 embolizations, comprising 82 initial, 28 first repeat, and 7 second repeat, were performed. RESULTS: An average of 2.5 arteries was treated per procedure. The superior lateral genicular artery was the most frequently embolized. The most utilized embolic size was 100-300 µm. Follow-up was available for all patients, with a median duration of 21.5 months. 65.9%, 25.6%, and 8.5% of patients underwent 1, 2, and 3 treatments, respectively. Complications occurred following 12.8% of treatments, of which the most common was transient cutaneous ischemia. Technical success was achieved in all cases. Clinical success was achieved in 56%, 79%, and 85% of patients following the first, second, and third treatment, respectively. 83% of patients reported being either satisfied or very satisfied with the overall result. CONCLUSIONS: Targeted genicular artery embolization with spherical embolics is an effective treatment for recurrent hemarthrosis with infrequent serious complications. Repeat embolization should be considered in cases of recurrence following initial therapy.

Extrahepatic Clinical Application of Vessel Tracking Software and 3D Roadmapping Tools: Preliminary Experience.

This article demonstrates the use of a representative commercially available automated vessel-tracking software originally intended for liver-only application (Vessel Assist Flight Plan for Liver; GE) in 4 patients. Treatment settings included embolization of small bowel hemorrhage source, treatment of renal cell carcinoma, management of symptomatic benign prostate hypertrophy, and detection with subsequent closure of a mesenteric pseudoaneurysm. All patients were treated successfully.

Asthma status is associated with decreased risk of aggressive urothelial bladder cancer.

Previous studies suggested an association between atopic conditions and specific cancers. The results on the association with urothelial bladder cancer (UBC) are scarce and inconsistent. To evaluate the association between asthma and risk of UBC, we considered 936 cases and 1,022 controls from the Spanish Bladder Cancer/EPICURO Study (86% males, mean age 65.4 years), a multicenter and hospital-based case-control study conducted during 1998-2001. Participants were asked whether they had asthma and detailed information about occupational exposures, smoking habits, dietary factors, medical conditions and history of medication was collected through face-to-face questionnaires performed by trained interviewers. Since asthma and UBC might share risk factors, association between patients' characteristics and asthma was studied in UBC controls. Association between UBC and asthma was assessed using logistic regression unadjusted and adjusted for potential confounders. The complex interrelationships, direct and mediating effect of asthma on UBC, were appraised using counterfactual mediation models. Asthma was associated with a reduced risk of UBC (odds ratio (OR) = 0.54, 95% confidence interval (CI) 0.37, 0.79) after adjusting for a wide range of confounders. No mediating effect was identified. The reduced risk associated with asthma was restricted to patients with high-risk non-muscle invasive (OR = 0.25, 95%CI 0.10, 0.62) and muscle invasive UBC (OR = 0.32, 95%CI 0.15, 0.69). Our results support that asthma is associated with a decreased risk of UBC, especially among aggressive tumors. Further work on the relationship between asthma and other atopic conditions and cancer risk should shed light on the relationship between immune response mechanisms and bladder carcinogenesis.

Treatment of Low-Flow Vascular Malformations of the Extremities Using MR-Guided High Intensity Focused Ultrasound: Preliminary Experience.

Five patients with painful vascular malformations of the extremities that were refractory to standard treatment and were confirmed as low-flow malformations on dynamic contrast-enhanced magnetic resonance (MR) imaging were treated with MR imaging-guided high intensity focused ultrasound. Daily maximum numeric rating scale scores for pain improved from 8.4 ± 1.5 to 1.6 ± 2.2 (P = .004) at a median follow-up of 9 months (range, 4-36 mo). The size of the vascular malformations decreased on follow-up MR imaging (median enhancing volume, 8.2 mL [0.7-10.1 mL] before treatment; 0 mL [0-2.3 mL] after treatment; P = .018) at a median follow-up of 5 months (range, 3-36 mo). No complications occurred.

Update on Embolization Therapies for Hepatocellular Carcinoma.

PURPOSE OF REVIEW: The purpose of the review is to summarize the latest applications for embolotherapy in the management of patients with HCC according to BCLC stage. RECENT FINDINGS: While traditionally reserved for patients with unresectable HCC and stage B disease, there is an important role for embolization therapies in earlier stage patients as an adjunct to ablation, bridging, or downstaging therapy, as a means to improve safety of resection, and potentially as an arterial ablative option in the case of radioembolization. Newer applications of radioembolization such as radiation segmentectomy have the potential to provide cure in localized unifocal disease, and transarterial chemoembolization-portal vein embolization and radiation lobectomy may provide a combination of treatment and future liver remnant hypertrophy for planned hepatic resection. There is also an increasing role for embolization in the treatment of stage C disease, and recent data suggest it can be used in combination with sorafenib with the potential for survival benefit over sorafenib alone, even in the case of portal vein tumor thrombus. Embolization therapies play an increasingly important role in patients with BCLC stage A-C hepatocellular carcinoma. While different therapies may be offered on a patient-specific basis, there are limited prospective RCT data to support superiority of one technique over another.

Quantitative Measurements of Enhancement on Preprocedure Triphasic CT Can Predict Response of Colorectal Liver Metastases to Radioembolization.

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: Response to radioembolization can be predicted using the AEF calculated from the preprocedure triphasic CT.

Pleural puncture that excludes the ablation zone decreases the risk of pneumothorax after percutaneous microwave ablation in porcine lung.

PURPOSE: To test the hypothesis that the geometry of probe placement with respect to the pleural puncture site affects the risk of pneumothorax after microwave (MW) ablation in the lung. MATERIALS AND METHODS: Computed tomography-guided MW ablation of the lung was performed in 8 swine under general anesthesia and mechanical ventilation. The orientation of the 17-gauge probe was either perpendicular (90°) or parallel (< 30°) with respect to the pleural puncture site, and the ablation power was 30 W or 65 W for 5 minutes. After MW ablation, swine were euthanized, and histopathologic changes were assessed. Frequency and factors affecting pneumothorax were evaluated by multivariate analysis. RESULTS: Among 62 lung MW ablations, 13 (21%) pneumothoraces occurred. No statistically significant difference was noted in the rate of pneumothorax between the perpendicular and the parallel orientations of the probe (31% vs 14%; odds ratio [OR], 2.8; P = .11). The pneumothorax rate was equal for 65-W and 30-W ablation powers (21% and 21%; OR, 1.0; P = .94). Under multivariate analysis, 2 factors were independent positive predictors of pneumothorax: ablation zone inclusive of pleural insertion point (OR, 7.7; P = .02) and time since intubation (hours) (OR, 2.7; P = .02). CONCLUSIONS: Geometries where the pleural puncture site excluded the ablation zone decreased pneumothorax in swine undergoing MW ablation in the lung. Treatment planning to ensure that the pleural puncture site excludes the subsequent ablation zone may reduce the rate of pneumothorax in patients undergoing MW ablation in the lung.

Combined genicular artery embolization and genicular nerve block to treat chronic pain following total knee arthroplasty.

BACKGROUND: Chronic knee pain after total knee arthroplasty (TKA) is a common complication that is difficult to treat. This report aims to highlight the benefit of combining embolotherapy and neurolysis intervention for symptomatic relief of post-TKA pain in a patient with long-standing pain refractory to conservative management. CASE PRESENTATION: A 77-year-old man who had previously undergone left knee arthroplasty has been grappling with worsening knee effusion and debilitating pain, resulting in limited mobility and progressive musculature deconditioning over a 20-year period. Diagnostic arteriography showed marked diffuse periarticular hyperemia around the medial and lateral joint spaces of the left knee, along with capsular distention. The patient initially underwent microsphere embolization to selectively target multiple branches of the genicular arteries, achieving a 50% reduction in pain at the one-month follow-up. Subsequently, the patient underwent image-guided genicular nerve neurolysis, targeting multiple branches of the genicular nerves, which led to further pain reduction (80% compared to the initial presentation or 60% compared to post-embolization) at the one-month follow-up. This improvement facilitated weight-bearing and enabled participation in physical therapy, with sustained pain relief over the 10-month follow-up period. CONCLUSION: The combination of genicular artery embolization and genicular nerve block may be a technically safe and effective option for alleviating chronic pain after total knee arthroplasty.

Frequent Amplification and Overexpression of PSMA in Basallike Breast Cancer from Analysis of The Cancer Genome Atlas.

Prostate-specific membrane antigen (PSMA) is frequently overexpressed in nonprostate malignancies. This preclinical study investigated the molecular basis of the application of PMSA-targeting radiopharmaceuticals in breast cancer subtypes. Methods: The somatic copy number status and the transcriptomic and protein expressions of FOLH1 (gene name of PSMA) were analyzed across breast cancer subtypes in 998 patients from The Cancer Genome Atlas dataset. Results: FOLH1 was frequently amplified in basallike breast cancer (BLBC) (32%) compared with luminal and human epidermal growth factor receptor 2-positive subtypes (16% and 17%, respectively; P < 0.01). FOLH1 expression was higher in BLBC (P < 0.001) and was negatively correlated with estrogen-receptor and progesterone-receptor expressions. Consistently, the PSMA protein level was higher in BLBC (P < 0.05). Interestingly, FOLH1 expression was associated with relapse-free and distant metastasis-free survival in patients with BLBC. Conclusion: The BLBC subtype exhibited frequent amplification and overexpression of PSMA, supporting the exploration of PSMA-targeting radiopharmaceuticals in this aggressive breast cancer subtype.

Iliocaval and iliofemoral venous stenting for obstruction secondary to tumor compression.

BACKGROUND: Cancer patients with pelviabdominal masses can suffer from lower extremity symptoms due to venous compression. The effectiveness of venous stenting has been established in extrinsic venous compression in benign conditions like May-Thurner syndrome. In this retrospective study we evaluate the efficacy and safety of caval, iliocaval and iliofemoral venous stenting for cases of extrinsic venous compression caused by malignant masses in cancer patients. METHODS: IRB-approved retrospective review of patients who underwent iliofemoral venography with venoplasty and stenting between January 2018 and February 2022 was performed. Patients with extrinsic venous compression caused by malignant masses were included. Data on patient demographics, pre-procedure symptoms, procedural technique, stent characteristics, outcomes and follow-up were collected. Descriptive statistics were used to assess technical success, clinical success, primary stent patency and adverse events of the procedure. RESULTS: Thirty-seven patients (19 males, 18 females) who underwent 45 procedures were included. Deep venous thrombosis (DVT) was present in 21 (57%) patients. Twenty-nine patients (78%, 95% CI 62-90%) reported clinical improvement of the presenting symptoms. The median overall survival after the procedure was 4.7 months (95% CI 3.58-5.99). Eight (22%) patients were alive at last follow up with median follow up of 10.33 months (Range 2-25 months). Twenty-six patients had patent stents on their last follow up imaging (70%, 95% CI 61%-91%). Two patients had a small access site hematoma which resolved spontaneously. Two patients developed moderate, and 1 patient developed severe adverse events related to post procedure therapeutic anticoagulation. CONCLUSION: Venous stenting is a safe procedure and should be considered as part of the palliative care for patients with debilitating lower extremity symptoms related to iliocaval and iliofemoral venous compression.

Iliocaval and Iliofemoral Venous Stenting for Obstruction Secondary to Tumor Compression: Single Center Experience.

Background: Cancer patients with pelviabdominal masses can suffer from lower extremity symptoms due to venous compression. The effectiveness of venous stenting has been established in extrinsic venous compression in benign conditions like May-Thurner syndrome. In this retrospective study we evaluate the efficacy and safety of caval, iliocaval and iliofemoral venous stenting for cases of extrinsic venous compression caused by malignant masses in cancer patients. Methods: IRB-approved retrospective review of patients who underwent iliofemoral venography with venoplasty and stenting between January 2018 and February 2022 was performed. Patients with extrinsic venous compression caused by malignant masses were included. Data on patient demographics, pre-procedure symptoms, procedural technique, stent characteristics, outcomes and follow-up were collected. Descriptive statistics were used to assess technical success, clinical success, primary stent patency and adverse events of the procedure. Results: Thirty-seven patients (19 males, 18 females) who underwent 45 procedures were included. Deep venous thrombosis (DVT) was present in 21 (57%) patients. Twenty-nine patients (78%, 95% CI 62-90%) reported clinical improvement of the presenting symptoms. The median overall survival after the procedure was 4.7 months (95% CI 3.58-5.99). Eight (22%) patients were alive at last follow up with median follow up of 10.33 months (Range 2-25 months). Twenty-six patients had patent stents on their last follow up imaging (70%, 95% CI 61%-91%). Two patients had a small access site hematoma which resolved spontaneously. Two patients developed moderate, and 1 patient developed severe adverse events related to post procedure therapeutic anticoagulation. Conclusion: Venous stenting is a safe procedure and should be considered as part of the palliative care for patients with debilitating lower extremity symptoms related to iliocaval and iliofemoral venous compression.

Perfusion-CT assessment of blood-brain barrier permeability in patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND: The goal of this study was to determine which clinical and radiographic variables in patients with subarachnoid hemorrhage (SAH) are associated with in vivo blood-brain barrier permeability (BBBP) assessments obtained using perfusion-CT (PCT) technology. METHODS: SAH patients with confirmed aneurysm etiology and with PCT and angiogram within 24 hours of each other were included, and relationships between clinical and imaging variables were analyzed using random-effects generalized linear models. RESULTS: One thousand one hundred and sixty two vascular territories from 83 patients were evaluated in this study. The mean BBBP increased by severity of vasospasm on DSA, however, in multivariate analysis, only mean transit time (MTT), cerebral blood volume (CBV), and severity of hydrocephalus were significantly associated with BBBP. Increased BBBP was not associated with angiographic vasospasm severity in multivariate analysis. CONCLUSION: Perfusion-CT assessment of BBBP may serve as a unique and useful biomarker in conjunction with angiography, additional perfusion-CT parameters, and clinical assessments, especially in characterizing microvascular dysfunction, or even in targeting treatments. However, future prospective studies will be required to definitively establish its clinical utility in the care of SAH patients.

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.