F. Edward Boas

Lung Adenocarcinoma: Predictive Value of KRAS Mutation Status in Assessing Local Recurrence in Patients Undergoing Image-guided Ablation

Purpose To establish the relationship between KRAS mutation status and local recurrence after image-guided ablation of lung adenocarcinoma. Materials and Methods This study consisted of a HIPAA-compliant institutional review board-approved retrospective review of 56 primary lung adenocarcinomas in 54 patients (24 men, 30 women; median age, 72 years; range, 54-87 years) treated with percutaneous image-guided ablation and with available genetic mutational analysis. KRAS mutation status and additional clinical and technical variables-Eastern Cooperative Oncology Group (ECOG) status, smoking history, stage at diagnosis, status (new primary or not), history of radiation, history of surgery, prior systemic treatment, modality of ablation, size of nodule, ablation margin, and presence of ground-glass appearance-were recorded and evaluated in relation to time to local recurrence, which was calculated from the time of ablation to the first radiographic evidence of recurrence. Predictors of outcome were identified by using a proportional hazards model for both univariate and multivariate analysis, with death as a competing risk. Results Technical success was 100%. Of the 56 ablated tumors, 37 (66%) were wild type for KRAS and 19 (34%) were KRAS mutants. The 1-year and 3-year cumulative incidences of recurrence were 20% and 35% for wild-type KRAS compared with 40% and 63% for KRAS mutant tumors. KRAS mutation status was a significant predictor of local recurrence at both univariate (P = .05; subdistribution hazard ratio [sHR], 2.32) and multivariate (P = .006; sHR, 3.75) analysis. At multivariate analysis, size (P = .026; sHR, 2.54) and ECOG status (P = .012; sHR, 2.23) were also independent significant predictors, whereas minimum margin (P = .066) was not. Conclusion The results of this study show that there is a relationship between KRAS mutation status and local recurrence after image-guided ablation of lung adenocarcinoma. Specifically, KRAS mutation status of the ablated lesion is a significant predictor of time to local recurrence, independent of size and margin.

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.

Therapeutic Application of Percutaneous Peritoneovenous (Denver) Shunt in Treating Chylous Ascites in Cancer Patients.

PURPOSE To evaluate the safety and efficacy of percutaneous peritoneovenous shunt (PPVS) placement in treating intractable chylous ascites (CA) in patients with cancer. MATERIALS AND METHODS Data from 28 patients with refractory CA treated with PPVS from April 2001 to June 2015 were reviewed. Demographic characteristics, technical success, efficacy, laboratory values, and complications were recorded. Univariate and multivariate logistic regression analysis was performed. RESULTS Technical success was 100%, and ascites resolved or symptoms were relieved in 92.3% (26 of 28) of patients. In 13 (46%) patients with urologic malignancies, whose ascites had resulted from retroperitoneal lymph node dissection, the ascites resolved, resulting in shunt removal within 128 days ± 84. The shunt provided palliation of symptoms in 13 of the remaining 15 patients (87%) for a mean duration of 198 days ± 214. Serum albumin levels increased significantly (21.4%) after PPVS placement from a mean of 2.98 g/dL ± 0.64 before the procedure to 3.62 g/dL ± 0.83 (P < .001). The complication rate was 37%, including shunt malfunction/occlusion (22%), venous thrombosis (7%), and subclinical disseminated intravascular coagulopathy (DIC) (7%). Smaller venous limb size (11.5 F) and the presence of peritoneal tumor were associated with a higher rate of shunt malfunction (P < .05). No patient developed overt DIC. CONCLUSIONS PPVS can safely and effectively treat CA in patients with cancer, resulting in significant improvement in serum albumin in addition to palliation of symptoms.

Comparison of biliary brush biopsy and fine needle biopsy in the diagnosis of biliary strictures

Abstract Purpose: The purpose of this study is to evaluate the accuracy of percutaneous fine needle biopsy (FNB) and brush biopsy (BB) at a cancer center. Material and methods: Retrospective analysis of all bile duct biopsies performed in Interventional Radiology between January 2000 and January 2015 was performed. FNB was performed under real-time cholangiographic guidance using a notched needle directed at the bile duct stricture. BB was performed by advancing a brush across the stricture and moving it back and forth to scrape the stricture. Biopsy results were categorized as true positive (TP), true negative (TN), false positive (FP) and false negative (FN) based on pathology reports and confirmed by surgical specimens or clinical follow-up of at least six months. Fisher’s exact test was used to compare the rate of TP in FNB and BB. Results: One-hundred and nineteen patients underwent FNB or BB. Fifteen were censored because of lack of follow-up. The remaining 104 patients underwent a total of 117 bile duct biopsies during the study period: 34 FNB and 83 BB. There were no complications in either group. In the FNB group 22/34 (64%) biopsies were TP, 4/34(12%) were TN and there were 8(24%) FN biopsies. In the BB group, 20/83 (24%) were TP, 38/83 (46%) TN and 25/83 (30%) FN biopsies. There were no FP biopsies in either group. The sensitivity of detecting malignancy by FNB was significantly higher than that by BB (73% vs 44%, p < .0005). There were no complications associated with FNB or BB. Conclusions: FNB of bile duct strictures is safe and has a higher sensitivity for detecting malignancy than BB.

Radioembolization of Colorectal Liver Metastases: Indications, Technique, and Outcomes

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 90Y 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 90Y 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 90Y 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.

Gene Signature Associated with Upregulation of the Wnt/β-Catenin Signaling Pathway Predicts Tumor Response to Transarterial Embolization

PURPOSE To identify gene mutations in tumors undergoing transarterial embolization and explore the relationship between gene mutations and tumor response to embolization. MATERIALS AND METHODS This was a retrospective review that included 17 patients with primary or metastatic liver tumors treated with embolization and had specimens analyzed for a 341-gene panel next-generation sequence assay. Pathologic conditions included hepatocellular, carcinoid, pancreatic neuroendocrine, melanoma, medullary thyroid, and liver acinar-cell carcinoma. Disease, procedure data, and tumor response data were collected. Dimensionality reduction was performed by using principal component analysis. A linear support vector machine was used to learn a prediction rule and identify the genes most predictive of objective tumor response (partial or complete) per modified Response Evaluation Criteria In Solid Tumors. Cross-validation was used to test the prediction on the holdout set. Permutation testing was used to determine statistical significance of prediction accuracy. Recursive feature elimination was used to identify the most predictive genes. RESULTS At 4 months after embolization, 9 tumors showed a response and 8 did not. Using the top two principal components, prediction accuracy of the gene mutation signature was 70% (±11%), which was statistically significant (P < .05). The most predictive genes were CTNNB1, MEN1, and NCOR1: three genes associated with the Wnt/β-catenin and hypoxia signaling pathways. CONCLUSIONS This study identifies gene mutations in tumors treated with transarterial embolization. A gene-mutation signature obtained from the mutation data suggests that upregulation of the Wnt/β-catenin signaling pathway may be associated with sensitivity to embolization.

Factors Affecting Oncologic Outcomes of 90Y Radioembolization of Heavily Pre-Treated Patients With Colon Cancer Liver Metastases

Introduction: The purpose of this study was 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 nomogram for OS. Materials and Methods: Metabolic, anatomic, laboratory, pathologic, genetic, primary disease, and procedure‐related factors, as well 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 associated with OS in MVA. These baseline parameters included number of extrahepatic disease sites (P < .001), carcinoembryonic antigen (P < .001), albumin (P = .005), alanine aminotransferase level (P < .001), tumor differentiation level (P < .001), and the sum of the 2 largest tumor diameters (P < .001). The 1‐year OS of patients with total points of < 25 versus > 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 maximum standardized uptake value was significant in MVA for LPFS prediction (P < .001; SHR = 1.06). Conclusion: The developed nomogram included 6 pre‐RAE parameters and provided good prediction of survival post‐RAE in heavily pretreated patients. Baseline maximum standardized uptake value was the single significant predictor of LPFS. Micro‐Abstract 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.

Role of Interventional Radiology in Managing Bile Duct Injuries

Biliary drainage can be used to treat postsurgical biliary injuries that are not accessible endoscopically. Small bile leaks can resolve spontaneously. If a biloma drain outputs more than 200 ml/day, biliary drainage can divert the bile away from the leak, allowing it to heal. Postsurgical biliary strictures can be treated with large bore biliary drains and cholangioplasty. Innovative percutaneous techniques for treating refractory bile duct injuries include covered biliary stents, bile duct embolization with glue, rendezvous procedures, and percutaneous hepaticojejunostomy and hepaticogastrostomy.

Targeted Transgastric Drainage of Isolated Pancreatic Duct Segments to Cure Persistent Pancreaticocutaneous Fistulas from Pancreatitis

Chronic pancreaticocutaneous fistulas can be difficult to treat. This article presents a snare-target technique for draining a nondilated pancreatic duct into the stomach, diverting pancreatic fluid away from the pancreaticocutaneous fistula to allow it to heal. Internal or internal/external transgastric pancreatic duct or fistula drains were placed in six patients. After an average of 4 months of drainage, all six patients experienced resolution of the cutaneous fistula. Two patients developed a pseudocyst but no recurrent fistula after drain removal, and the other four patients had no pseudocyst or fistula after an average 27-month follow-up (range, 6-74 mo).