Use of Metformin and Survival in Patients with Hepatocellular Carcinoma (HCC) Undergoing Liver Directed Therapy: Analysis of a Nationwide Cancer Registry.

BACKGROUND: Examine the association of metformin use and overall survival (OS) in patients with HCC undergoing image-guided liver-directed therapy (LDT): ablation, transarterial chemoembolization (TACE), or Yttrium-90 radioembolization (Y90 RE). METHODS: Using National Cancer Institute Surveillance, Epidemiology, and End Results registry and Medicare claims databases between 2007 and 2016, we identified patients ≥ 66 years who underwent LDT within 30 days of HCC diagnosis. Patients with liver transplant, surgical resection, and other malignancies were excluded. Metformin use was identified by at least two prescription claims within 6 months before LDT. OS was measured by time between first LDT and death or last Medicare observation. Comparisons were performed between both all and diabetic patients on and not on metformin. RESULTS: Of 2746 Medicare beneficiaries with HCC undergoing LDT, 1315 (47.9%) had diabetes or diabetes-related complications. Among all and diabetic patients, 433(15.8%) and 402 (30.6%) were on metformin respectively. Median OS was greater for patients on metformin (19.6 months, 95% CI 17.1-23.0) vs those not (16.0 months, 15.0-16.9; p = 0.0238). Patients on metformin had lower risk of death undergoing ablation (HR 0.70; 0.51-0.95; p = 0.0239) and TACE (HR 0.76, 0.66-0.87; p = 0.0001), but not Y90 RE (HR1.22, 0.89-1.69; p = 0.2231). Among diabetics, OS was greater for those on metformin vs those not (HR 0.77, 0.68-0.88; p < 0.0001). Diabetic patients on metformin had longer OS undergoing TACE (HR 0.71, 0.61-0.83; p < 0.0001), but not ablation (HR 0.74, 0.52-1.04; p = 0.0886) or Y90 RE (HR 1.26, 0.87-1.85; p = 0.2217). CONCLUSION: Metformin use is associated with improved survival in HCC patients undergoing TACE and ablation.

Safety and feasibility of a novel bi-directional portal vein access kit during transjugular intrahepatic portosystemic shunt creation.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) creation remains as one of the more technically challenging endovascular procedures. Portal vein access from the hepatic vein often requires multiple needle passes, which increases procedure times, risk of complications, and radiation exposure. With its bi-directional maneuverability, the Scorpion X access kit may be a promising tool for easier portal vein access. However, the clinical safety and feasibility of this access kit has yet to be determined. MATERIALS AND METHODS: In this retrospective study, 17 patients (12 male, average age 56.6 ± 9.01) underwent TIPS procedure using Scorpion X portal vein access kits. The primary endpoint was time taken to access the portal vein from the hepatic vein. The most common indications for TIPS were refractory ascites (47.1%) and esophageal varices (17.6%). Radiation exposure, total number of needle passes, and intraoperative complications were recorded. Average MELD Score was 12.6 ± 3.39 (range: 8-20). RESULTS: Portal vein cannulation was successfully achieved in 100% of patients during intracardiac echocardiography-assisted TIPS creation. Total fluoroscopy time was 39.31 ± 17.97 min; average radiation dose was 1036.76 ± 644.15 mGy, while average contrast dose was 120.59 ± 56.87 mL. The average number of passes from the hepatic vein to the portal vein was 2 (range: 1-6). Average time to access the portal vein once the TIPS cannula was positioned in the hepatic vein was 30.65 ± 18.64 min. There were no intraoperative complications. CONCLUSIONS: Clinical utilization of the Scorpion X bi-directional portal vein access kit is both safe and feasible. Utilizing this bi-directional access kit resulted in successful portal vein access with minimal intraoperative complications. LEVEL OF EVIDENCE: Retrospective cohort.

Yttrium-90 Radiation Segmentectomy of Hepatocellular Carcinoma: A Comparative Study of the Effectiveness, Safety, and Dosimetry of Glass-Based versus Resin-Based Microspheres.

PURPOSE: To evaluate the differences in safety, effectiveness, and dosimetry between glass-based and resin-based ablative yttrium-90 (90Y) transarterial radioembolization (TARE) of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Using the modified Response Evaluation Criteria in Solid Tumors and Common Terminology Criteria for Adverse Events, both tumor response and adverse events (AEs) were assessed at 3 months after 90Y-TARE. Post procedure 90Y-bremsstrahlung single-photon emission computed tomography/computed tomography voxel-based dosimetry analysis was used to create tumor dose (TD) and normal tissue dose (NTD) volume histograms, and to calculate tumor particle loading and specific activity. The TD and NTD receiver operating characteristic curves evaluated the dose threshold able to predict objective (partial or complete) and complete tumor responses in addition to any-grade and grade ≥3 AE incidences. The chi-square test and Student t-test were used to assess variable differences where appropriate. RESULTS: Between 2019 and 2020, 81 patients with HCC (20 in the resin-based cohort and 61 in the glass-based cohort) underwent ablative 90Y-TARE. The resin-based cohort had more males (89% vs 65%, P = .03), lower tumor-to-normal ratio (1.81 ± 0.39 vs 2.22 ± 0.94, P = .03), higher tumor particle loading (40,172 particles/mL ± 28,039 vs 17,081 particles/mL ± 12,555, P = .0001), lower specific activity (158 Bq/particle ± 3 vs 1,058 Bq/particle ± 331, P = .001), and lower mean TD (308 Gy ± 210 vs 794 Gy ± 523, P = .0002) than the glass-based cohort. No significant differences in baseline characteristics or posttreatment AEs were noted. The overall objective and complete response rates were 85% (95% resin-based vs 82% glass-based; P = .1) and 65% (95% resin-based vs 56% glass-based; P = .003), respectively. The mean TD thresholds able to predict the objective and complete responses were 176 Gy and 247 Gy for resin-based radioembolization and 290 Gy and 481 Gy for glass-based radioembolization, respectively. A maximum NTD of 999 Gy predicted any-grade AEs in glass-based ablative 90Y-TARE. CONCLUSIONS: Compared with glass-based ablative 90Y-TARE, resin-based ablative 90Y-TARE can offer comparable safety and effectiveness profiles for patients with HCC. The impact of the significantly different tumor particle loading, particle specific activities, and delivered TDs on tumor response outcomes merits further investigation.

Correlation of Non-tumoral Liver Dose with Treatment-Related Adverse Events in Patients with Hepatocellular Carcinoma Treated with Glass-Based Yttrium-90 Radioembolization.

PURPOSE: To evaluate the relationship between non-tumor liver (NTL) dose and adverse events (AE) in patients with hepatocellular carcinoma (HCC) treated with glass-based Yttrium-90 radioembolization (Y90-RE). MATERIALS AND METHODS: A retrospective analysis of patients with HCC treated with Y90-RE between 2013 and 2018 was performed. Baseline characteristics including demographics and Y90-RE treatment approach were captured. Common Terminology Criteria for Adverse Events v5 was assessed at months 3 and 6 post-treatment. Using voxel-based dosimetry with MIM Software V. 6.9, dose-volume histograms of treated area of liver were created. Receiver operator characteristic curve was used to determine NTL dose threshold predicting AEs. Multivariate analysis was used to determine independent clinical factors of predicting severe AEs. Chi-square analysis was used to compare proportions. RESULTS: Two hundred and twenty-nine consecutive patients (115(50.2%) lobar and 114(49.8%) segmental) were included. At 3 months, there was a lower rate of any grade AE (55(46%) segmental and 36(31%) lobar, p = 0.009) and increased rate of severe AEs for lobar compared to segmental (2(2%) segmental and 9(8%) lobar, p = 0.029). At 6 months, severe AEs were greater for lobar than segmental (1(1%) segmental vs 10(9%) lobar, p = 0.005). For lobar Y90-RE, mean NTL dose of 112 Gy predicted severe AE (89% sensitivity and 91% specificity (AUC = 0.95, p = < 0.0001) at 3 and 6 months. For the segmental group, no significant association was found between NTL dose and severe treatment-related AE at 3 and 6 months. CONCLUSION: In patients with HCC undergoing glass-based lobar Y90-RE, NTL dose of > 112 Gy is associated with severe treatment-related AEs at 3-6 months.

Surgical resection, radiotherapy and percutaneous thermal ablation for treatment of stage 1 non-small cell lung cancer: protocol for a systematic review and network meta-analysis.

INTRODUCTION: Non-small cell lung cancer (NSCLC) makes up the majority of lung cancer cases. Currently, surgical resection is the gold standard of treatment. However, as patients are becoming medically more complex presenting with advanced disease, minimally invasive image-guided percutaneous ablations are gaining popularity. Therefore, comparison of surgical, ablative and second-line external beam therapies will help clinicians, as management of NSCLC changes. We will conduct a meta-analysis, reviewing literature investigating these therapies in adult patients diagnosed with stage 1 NSCLC, with neither hilar nor mediastinal nodal involvement, confirmed either through cytology or histology regardless of type. METHODS AND ANALYSIS: We will search electronic databases (MEDLINE, Embase, Web of Science, Scopus, ClinicalTrials.gov, Cochrane) from their inception to January 2021 to identify randomised controlled trials (RCTs), cluster RCTs and cohort studies comparing survival and clinical outcomes between any two interventions (lobectomy, wedge resection, video-assisted thoracoscopic surgery/robot-assisted thoracoscopic surgery, radiofrequency ablation, microwave ablation, cryoablation and consolidated radiation therapies (external beam radiation therapy, stereotactic body radiation therapy, and 3D conformal radiation therapy). The primary outcomes will include cancer-specific survival, lung disease-free survival, locoregional recurrence, death, toxicity and non-target organ injury. We will also search published and unpublished studies in trial registries and will review references of included studies for possible inclusion. Risk of bias will be assessed using tools developed by the Cochrane collaboration. Two reviewers will independently assess the eligibility of studies and conduct the corresponding risk of bias assessments. For each outcome, given enough studies, we will conduct a network meta-analysis. Finally, we will use the Confidence in Network Meta-Analysis tool to assess quality of the evidence for each of the primary outcomes. ETHICS AND DISSEMINATION: We aim to share our findings through high-impact peer review. As interventional techniques become more popular, it will be important for providers in multidisciplinary teams caring for these patients to receive continuing medical education related to these interventions. Data will be made available to readers. PROSPERO REGISTRATION NUMBER: CRD42021276629.

Successful sclerotherapy of a recurrent, benign parotid cyst.

Benign parotid lesions can grow to be a cosmetic deformation with psychological sequelae for a patient. Although surgical resection is the treatment of choice, cyst aspiration has also been attempted. This, however, has been shown to recur, requiring repeat intervention. An alternative therapeutic method not as widely recognized, but which has been reported to be both effective and less invasive than surgery for treating parotid cyst lesions, is sclerotherapy. Here we describe a report of a patient with a benign, localized, cystic neck mass refractory to 2 trials of fine needle aspiration. After the patient refused surgical resection, a trial of sterile ethanol sclerotherapy was performed. Our patient tolerated the procedure well with a significant reduction in the size of the lesion.