The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1alpha.

SIRT6 is a member of a highly conserved family of NAD(+)-dependent deacetylases with various roles in metabolism, stress resistance, and life span. SIRT6-deficient mice develop normally but succumb to a lethal hypoglycemia early in life; however, the mechanism underlying this hypoglycemia remained unclear. Here, we demonstrate that SIRT6 functions as a histone H3K9 deacetylase to control the expression of multiple glycolytic genes. Specifically, SIRT6 appears to function as a corepressor of the transcription factor Hif1alpha, a critical regulator of nutrient stress responses. Consistent with this notion, SIRT6-deficient cells exhibit increased Hif1alpha activity and show increased glucose uptake with upregulation of glycolysis and diminished mitochondrial respiration. Our studies uncover a role for the chromatin factor SIRT6 as a master regulator of glucose homeostasis and may provide the basis for novel therapeutic approaches against metabolic diseases, such as diabetes and obesity.

Early post-treatment MRI predicts long-term hepatocellular carcinoma response to radiation segmentectomy.

OBJECTIVES: Radiation segmentectomy using yttrium-90 plays an emerging role in the management of early-stage HCC. However, the value of early post-treatment MRI for response assessment is uncertain. We assessed the value of response criteria obtained early after radiation segmentectomy in predicting long-term response in patients with HCC. MATERIALS AND METHODS: Patients with HCC who underwent contrast-enhanced MRI before, early, and 12 months after radiation segmentectomy were included in this retrospective single-center study. Three independent radiologists reviewed images at baseline and 1st follow-up after radiation segmentectomy and assessed lesion-based response according to mRECIST, LI-RADS treatment response algorithm (TRA), and image subtraction. The endpoint was response at 12 months based on consensus readout of two separate radiologists. Diagnostic accuracy for predicting complete response (CR) at 12 months based on the 1st post-treatment MRI was calculated. RESULTS: Eighty patients (M/F 60/20, mean age 67.7 years) with 80 HCCs were assessed (median size baseline, 1.8 cm [IQR, 1.4-2.9 cm]). At 12 months, 74 patients were classified as CR (92.5%), 5 as partial response (6.3%), and 1 as progressive disease (1.2%). Diagnostic accuracy for predicting CR was fair to good for all readers with excellent positive predictive value (PPV): mRECIST (range between 3 readers, accuracy: 0.763-0.825, PPV: 0.966-1), LI-RADS TRA (accuracy: 0.700-0.825, PPV: 0.983-1), and subtraction (accuracy: 0.775-0.825, PPV: 0.967-1), with no difference in accuracy between criteria (p range 0.053 to > 0.9). CONCLUSION: mRECIST, LI-RADS TRA, and subtraction obtained on early post-treatment MRI show similar performance for predicting long-term response in patients with HCC treated with radiation segmentectomy. CLINICAL RELEVANCE STATEMENT: Response assessment extracted from early post-treatment MRI after radiation segmentectomy predicts complete response in patients with HCC with high PPV (≥ 0.96). KEY POINTS: • Early post-treatment response assessment on MRI predicts response in patients with HCC treated with radiation segmentectomy with fair to good accuracy and excellent positive predictive value. • There was no difference in diagnostic accuracy between mRECIST, LI-RADS, and subtraction for predicting HCC response to radiation segmentectomy.

Comparison of a Patient-Mounted Needle-Driving Robotic System versus Single-Rotation CT Fluoroscopy to Perform CT-Guided Percutaneous Lung Biopsies.

PURPOSE: To compare the effectiveness of percutaneous lung biopsy using a patient-mounted needle-driving robotic system with that using a manual insertion of needles under computed tomography (CT) fluoroscopy guidance. MATERIALS AND METHODS: In this institutional review board approved study, the cohort consisted of a series of patients who underwent lung biopsies following the intention-to-treat protocol from September 2022 to September 2023 using robot (n = 15) or manual insertion under single-rotation CT fluoroscopy (n = 66). Patient and procedure characteristics were recorded as well as outcomes. RESULTS: Although age, body mass index, and skin-to-target distance were not statistically different, target size varied (median, 8 mm [interquartile range, 6.5-9.5 mm] for robot vs 12 mm [8-18 mm] for single-rotation CT fluoroscopy; P = .001). No statistical differences were observed in technical success (86.7% [13/15] vs 89.4% [59/66], P = .673), Grade 3 adverse event (AE) (6.7% [1/15] vs 12.1% [8/66], P = .298), procedural time (28 minutes [22-32 minutes] vs 19 minutes [14.3-30.5 minutes], P = .086), and patient radiation dose (3.9 mSv [3.2-5.6 mSv] vs 4.6 mSv [3.3-7.5 mSv], P = .398). In robot-assisted cases, the median angle out of gantry plane was 10° (6.5°-16°), although it was null (0°-5°) for single-rotation CT fluoroscopy (P = .001). CONCLUSIONS: Robot-assisted and single-rotation CT fluoroscopy-guided percutaneous lung biopsies were similar in terms of technical success, diagnostic yield, procedural time, AEs, and radiation dose, although robot allowed for out-of-gantry plane navigation along the needle axis.

Percutaneous Lung Biopsies With Robotic Systems: A Systematic Review of Available Clinical Solutions.

Objectives: This systematic review aims to assess existing research concerning the use of robotic systems to execute percutaneous lung biopsy. Methods: A systematic review was performed and identified 4 studies involving robotic systems used for lung biopsy. Outcomes assessed were operation time, radiation dose to patients and operators, technical success rate, diagnostic yield, and complication rate. Results: One hundred and thirteen robot-guided percutaneous lung biopsies were included. Technical success and diagnostic yield were close to 100%, comparable to manual procedures. Technical accuracy, illustrated by needle positioning, showed less frequent needle adjustments in robotic guidance than in manual guidance (P < .001): 2.7 ± 2.6 (range 1-4) versus 6 ± 4 (range 2-12). Procedure time ranged from comparable to reduced by 35% on average (20.1 ± 11.3 minutes vs 31.4 ± 10.2 minutes, P = .001) compared to manual procedures. Patient irradiation ranged from comparable to reduced by an average of 40% (324 ± 114.5 mGy vs 541.2 ± 446.8 mGy, P = .001). There was no significant difference in reported complications between manual biopsy and biopsies that utilized robotic guidance. Conclusion: Robotic systems demonstrate promising results for percutaneous lung biopsy. These devices provide adequate accuracy in probe placement and could both reduce procedural duration and mitigate radiation exposure to patients and practitioners. However, this review underscores the need for larger, controlled trials to validate and extend these findings.

Early Prediction of Response of Hepatocellular Carcinoma to Yttrium-90 Radiation Segmentectomy Using a Machine Learning MR Imaging Radiomic Approach.

PURPOSE: To assess the accuracy of a machine learning (ML) approach based on magnetic resonance (MR) imaging radiomic quantification obtained before treatment and early after treatment for prediction of early hepatocellular carcinoma (HCC) response to yttrium-90 transarterial radioembolization (TARE). MATERIALS AND METHODS: In this retrospective single-center study of 76 patients with HCC, baseline and early (1-2 months) post-TARE MR images were collected. Semiautomated tumor segmentation facilitated extraction of shape, first-order histogram, and custom signal intensity-based radiomic features, which were then trained (n = 46) using a ML XGBoost model and validated on a separate cohort (n = 30) not used in training to predict treatment response assessed at 4-6 months (based on modified Response and Evaluation Criteria in Solid Tumors criteria). Performance of this ML radiomic model was compared with those of models comprising clinical parameters and standard imaging characteristics using area under the receiver operating curve (AUROC) analysis for prediction of complete response (CR). RESULTS: Seventy-six tumors with a mean (±SD) diameter of 2.6 cm ± 1.6 were included. Sixty, 12, 1, and 3 patients were classified as having CR, partial response, stable disease, and progressive disease, respectively, at 4-6 months posttreatment on the basis of MR images. In the validation cohort, the radiomic model showed good performance (AUROC, 0.89) for prediction of CR, compared with models comprising clinical and standard imaging criteria (AUROC, 0.58 and 0.59, respectively). Baseline imaging features appeared to be more heavily weighted in the radiomic model. CONCLUSIONS: The use of ML modeling of radiomic data combining baseline and early follow-up MR imaging could predict HCC response to TARE. These models need to be investigated further in an independent cohort.

Safety and Feasibility of a Novel Externally Cooled Bronchoscopic Radiofrequency Ablation Catheter for Ablation of Peripheral Lung Tumours: A First-In-Human Dose Escalation Study.

BACKGROUND: Radiofrequency ablation (RFA) is an established modality for percutaneous ablation of non-small cell lung cancer (NSCLC) in medically inoperable patients but is underutilized clinically due to side effects. We have developed a novel, completely endobronchial RFA catheter with an externally cooled electrode. OBJECTIVES: The objective of this study was to establish the safety and feasibility of bronchoscopic RFA using a novel, externally cooled catheter for ablation of peripheral NSCLC. METHODS: Patients with stage I biopsy-confirmed NSCLC underwent bronchoscopic RFA of tumour 7 days prior to lobectomy. The RFA catheter was delivered bronchoscopically to peripheral NSCLC lesions, guided by radial endobronchial ultrasound, with positioning confirmed using intra-procedural cone beam CT. Pre-operative CT chest and histologic examination of resected specimens were used to establish distribution/uniformity of ablation and efficacy of tumour ablation. RESULTS: RFA in the first patient was complicated by dispersal of heated saline due to cough, resulting in ICU admission. The patient recovered fully and underwent uncomplicated lobectomy. Subsequently, the protocol was altered to mandate neuromuscular blockade with a pre-determined dose escalation, with algorithm-restricted energy (kJ) and irrigated saline volume (mL) constraints. A further 10 patients consented and seven underwent successful bronchoscopic RFA of peripheral NSCLC. No significant adverse events were noted. Ablation zone included tumour in all cases (proportion of tumour ablated ranged 8-72%), with uniform necrosis of tissue within ablation zones observed at higher energy levels. Ablation zone diameter correlated with RFA energy delivered (R2 = 0.553), with maximum long axis diameter of ablation zone 3.1 cm (22.9 kJ). CONCLUSION: Bronchoscopic RFA using an externally cooled catheter is feasible, appears safe, and achieves uniform ablation within the treatment zone. Uncontrolled escape of heated saline poses a major safety risk but can be prevented procedurally through neuromuscular blockade and by limiting irrigation.

Fertility after Transcatheter Arterial Embolization for Obstetric Hemorrhage: An Urban Health Care System Observational Study.

OBJECTIVE: This study aimed to investigate pregnancy rate, pregnancy outcomes, and resumption of menses after transcatheter arterial embolization (TAE) for obstetric hemorrhage (OH). STUDY DESIGN: Sixty-seven patients who underwent TAE for OH from 2006 to 2020 within an urban, multihospital health care system were identified retrospectively. Selected patients were interviewed by phone to complete a survey with a primary outcome of self-reported pregnancy in those seeking pregnancy. Secondary outcomes included pregnancy outcomes and resumption of menses. Univariate testing of association of pregnancy and miscarriage rate with embolic agent was performed using Fisher's exact test. RESULTS: Thirty-three of 50 patients (66%) meeting the inclusion criteria completed the survey on fertility, a median of 47 (range, 13-123) months after TAE for OH. Of the 13 patients who attempted pregnancy, there was a pregnancy rate of 77% and miscarriage rate of 38%. Those who delivered live newborns conceived spontaneously, carried to term, and delivered a healthy newborn via cesarean section at a weight appropriate for gestational age. Thirty (91%) patients resumed menstruation, and the majority with unchanged frequency. Most patients underwent bilateral uterine artery embolization with radial artery access (54%). The most common embolic agents used were gelfoam only (30%) and glue only (24%). There was no statistically significant association between embolic agent and pregnancy or miscarriage rate. CONCLUSION: Spontaneous pregnancy with live birth and resumption of menses can occur in a majority of patients after TAE for OH. KEY POINTS: · Most patients who attempted pregnancy after TAE for OH achieved pregnancy.. · Most patients who became pregnant conceived spontaneously and delivered healthy newborns at term.. · Most patients resumed menstruation after TAE for OH.. · There was no significant association between type of embolic and pregnancy or miscarriage rate..

Angiotensin II drives the production of tumor-promoting macrophages.

Macrophages frequently infiltrate tumors and can enhance cancer growth, yet the origins of the macrophage response are not well understood. Here we address molecular mechanisms of macrophage production in a conditional mouse model of lung adenocarcinoma. We report that overproduction of the peptide hormone Angiotensin II (AngII) in tumor-bearing mice amplifies self-renewing hematopoietic stem cells (HSCs) and macrophage progenitors. The process occurred in the spleen but not the bone marrow, and was independent of hemodynamic changes. The effects of AngII required direct hormone ligation on HSCs, depended on S1P(1) signaling, and allowed the extramedullary tissue to supply new tumor-associated macrophages throughout cancer progression. Conversely, blocking AngII production prevented cancer-induced HSC and macrophage progenitor amplification and thus restrained the macrophage response at its source. These findings indicate that AngII acts upstream of a potent macrophage amplification program and that tumors can remotely exploit the hormone's pathway to stimulate cancer-promoting immunity.

Contemporary Management of Acute Pulmonary Embolism: Evolution of Catheter-based Therapy.

Acute pulmonary embolism (PE) affects more than 100 000 people in the United States annually and is the third leading cardiovascular cause of death. The standard management for PE is systemic anticoagulation therapy. However, a subset of patients experience hemodynamic decompensation, despite conservative measures. Traditionally, these patients have been treated with systemic administration of thrombolytic agents or open cardiac surgery, although attempts at endovascular treatment have a long history that dates back to the 1960s. The technology for catheter-based therapy for acute PE is rapidly evolving, with multiple devices approved over the past decade. Currently available devices fall into two broad categories of treatment methods: catheter-directed thrombolysis and percutaneous suction thrombectomy. Catheter-directed thrombolysis is the infusion of thrombolytic agents directly into the occluded pulmonary arteries to increase local delivery and decrease the total dose. Suction thrombectomy involves the use of small- or large-bore catheters to mechanically aspirate a clot from the pulmonary arteries without the need for a thrombolytic agent. A thorough understanding of the various risk stratification schemes and the available evidence for each device is critical for optimal treatment of this complex entity. Multiple ongoing studies will improve our understanding of the role of catheter-based therapy for acute PE in the next 5-10 years. A multidisciplinary approach through PE response teams has become the management standard at most institutions. An invited commentary by Bulman and Weinstein is available online. Online supplemental material is available for this article. ©RSNA, 2022.

Safety and Efficacy of Locoregional Treatment during Immunotherapy with Nivolumab for Hepatocellular Carcinoma: A Retrospective Study of 41 Interventions in 29 Patients.

PURPOSE: To assess the safety of locoregional treatment (LRT) combined with nivolumab for intermediate and advanced hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A single-center retrospective review included 29 patients undergoing 41 LRTs-transarterial chemoembolization or yttrium-90 transarterial radioembolization-60 days before or concurrently with nivolumab. Demographic, clinical, and laboratory values and adverse events were reviewed before and after nivolumab initiation and after each LRT. Treatment response and time to progression were assessed using Modified Response Evaluation Criteria in Solid Tumors. Clinical events, including nivolumab termination, death, and time of last follow-up, were assessed. RESULTS: Over a median nivolumab course of 8.1 months (range, 1.0-30) with a median of 14.2 2-week cycles (range, 1-53), predominantly Child-Pugh A (22/29) patients-12 Barcelona Clinic Liver Cancer (BCLC) B and 17 BCLC C-underwent 20 transarterial chemoembolization and 21 transarterial radioembolization LRTs at a median of 67 days (range, 48-609) after nivolumab initiation. Ten patients underwent multiple LRTs. During a median follow-up of 11.5 months (range, 1.8-35.1), no grade III/IV adverse events attributable to nivolumab were observed. There were five instances of grade III/IV hypoalbuminemia or hyperbilirubinemia within 3 months after LRT. There were no nivolumab-related deaths, and 30-day mortality after LRT was 0%. CONCLUSIONS: LRTs performed concurrently with nivolumab immunotherapy demonstrate an acceptable safety profile in patients with intermediate and advanced HCC.

Synthesis and SAR studies of novel benzodiazepinedione-based inhibitors of Clostridium difficile (C. difficile) toxin B (TcdB).

Synthesis and structure-activity relationships (SAR) of a novel series of benzodiazepinedione-based inhibitors of Clostridium difficile toxin B (TcdB) are described. Compounds demonstrating low nanomolar affinity for TcdB, and which possess improved stability in mouse plasma vs. earlier compounds from this series, have been identified. Optimized compound 11d demonstrates a good pharmacokinetic (PK) profile in mouse and hamster and is efficacious in a hamster survival model of Clostridium difficile infection.

Identification and initial optimization of inhibitors of Clostridium difficile (C. difficile) toxin B (TcdB).

The discovery, synthesis and preliminary structure-activity relationship (SAR) of a novel class of inhibitors of Clostridium difficile (C. difficile) toxin B (TcdB) is described. A high throughput screening (HTS) campaign resulted in the identification of moderately active screening hits 1-5 the most potent of which was compound 1 (IC50 = 0.77 µM). In silico docking of an early analog offered suggestions for structural modification which resulted in the design and synthesis of highly potent analogs 13j(IC50 = 1 nM) and 13 l(IC50 = 7 nM) which were chosen as leads for further optimization.

Reactive polymer enables efficient in vivo bioorthogonal chemistry.

There has been intense interest in the development of selective bioorthogonal reactions or "click" chemistry that can proceed in live animals. Until now however, most reactions still require vast surpluses of reactants because of steep temporal and spatial concentration gradients. Using computational modeling and design of pharmacokinetically optimized reactants, we have developed a predictable method for efficient in vivo click reactions. Specifically, we show that polymer modified tetrazines (PMT) are a key enabler for in vivo bioorthogonal chemistry based on the very fast and catalyst-free [4 + 2] tetrazine/trans-cyclooctene cycloaddition. Using fluorescent PMT for cellular resolution and (18)F labeled PMT for whole animal imaging, we show that cancer cell epitopes can be easily reacted in vivo. This generic strategy should help guide the design of future chemistries and find widespread use for different in vivo bioorthogonal applications, particularly in the biomedical sciences.

Origins of tumor-associated macrophages and neutrophils.

Tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs) can control cancer growth and exist in almost all solid neoplasms. The cells are known to descend from immature monocytic and granulocytic cells, respectively, which are produced in the bone marrow. However, the spleen is also a recently identified reservoir of monocytes, which can play a significant role in the inflammatory response that follows acute injury. Here, we evaluated the role of the splenic reservoir in a genetic mouse model of lung adenocarcinoma driven by activation of oncogenic Kras and inactivation of p53. We found that high numbers of TAM and TAN precursors physically relocated from the spleen to the tumor stroma, and that recruitment of tumor-promoting spleen-derived TAMs required signaling of the chemokine receptor CCR2. Also, removal of the spleen, either before or after tumor initiation, reduced TAM and TAN responses significantly and delayed tumor growth. The mechanism by which the spleen was able to maintain its reservoir capacity throughout tumor progression involved, in part, local accumulation in the splenic red pulp of typically rare extramedullary hematopoietic stem and progenitor cells, notably granulocyte and macrophage progenitors, which produced CD11b(+) Ly-6C(hi) monocytic and CD11b(+) Ly-6G(hi) granulocytic cells locally. Splenic granulocyte and macrophage progenitors and their descendants were likewise identified in clinical specimens. The present study sheds light on the origins of TAMs and TANs, and positions the spleen as an important extramedullary site, which can continuously supply growing tumors with these cells.

Adjusted Tumor Enhancement on Dual-Phase Cone-Beam CT: Predictor of Response and Overall Survival in Patients with Liver Malignancies Treated with Hepatic Artery Embolization.

The aim of this study was to examine the value of tumor enhancement parameters on dual-phase cone-beam CT (CBCT) in predicting initial response, local progression-free survival (L-PFS) and overall survival (OS) following hepatic artery embolization (HAE). Between Feb 2016 and Feb 2023, 13 patients with 29 hepatic tumors treated with HAE were analyzed. Pre- and post-embolization, subtracted CBCTs were performed, and tumor enhancement parameters were measured, resulting in three parameters: pre-embolization Adjusted Tumor Enhancement (pre-ATE), post-embolization ATE and the difference between pre- and post-ATE (∆ATE). Treatment response was evaluated using the mRECIST criteria at 1 month. Tumors were grouped into complete response (CR) and non-complete response (non-CR) groups. To account for the effect of multiple lesions per patient, a cluster data analytic method was employed. The Kaplan-Meier method was utilized for survival analysis using the lesion with the lowest ∆ATE value in each patient. Seventeen (59%) tumors showed CR and twelve (41%) showed non-CR. Pre-ATE was 38.5 ± 10.6% in the CR group and 30.4 ± 11.0% in the non-CR group (p = 0.023). ∆ATE in the CR group was 39 ± 12 percentage points following embolization, compared with 29 ± 11 in the non-CR group (p = 0.009). Patients with ∆ATE > 33 had a median L-PFS of 13.1 months compared to 5.7 in patients with ∆ATE ≤ 33 (95% CI = 0.038-0.21) (HR, 95% CI = 0.45, 0.20-0.9, p = 0.04). Patients with ∆ATE ≤ 33 had a median OS of 19.7 months (95% CI = 3.77-19.8), while in the ∆ATE > 33 group, median OS was not reached (95% CI = 20.3-NA) (HR, 95% CI = 0.15, 0.018-1.38, p = 0.04). CBCT-derived ATE parameters can predict treatment response, L-PFS and OS following HAE.

Outcomes of Y90 Radioembolization for Hepatocellular Carcinoma in Patients Previously Treated with Transarterial Embolization.

The aim of this study was to evaluate outcomes of transarterial radioembolization (TARE) for hepatocellular carcinoma (HCC) in patients previously treated with transarterial embolization (TAE). In this retrospective study, all HCC patients who received TARE from 1/2012 to 12/2022 for treatment of residual or recurrent disease after TAE were identified. Overall survival (OS) was estimated using the Kaplan-Meier method. Univariate Cox regression was performed to determine significant predictors of OS after TARE. Twenty-one patients (median age 73.4 years, 18 male, 3 female) were included. Median dose to the perfused liver volume was 121 Gy (112-444, range), and 18/21 (85.7%) patients received 112-140 Gy. Median OS from time of HCC diagnosis was 32.9 months (19.4-61.4, 95% CI). Median OS after first TAE was 29.3 months (15.3-58.9, 95% CI). Median OS after first TARE was 10.6 months (6.8-27.0, 95% CI). ECOG performance status of 0 (p = 0.038), index tumor diameter < 4 cm (p = 0.022), and hepatic tumor burden < 25% (p = 0.018) were significant predictors of longer OS after TARE. TARE may provide a survival benefit for appropriately selected patients with HCC who have been previously treated with TAE.

Hybrid PET-optical imaging using targeted probes.

Fusion imaging of radionuclide-based molecular (PET) and structural data [x-ray computed tomography (CT)] has been firmly established. Here we show that optical measurements [fluorescence-mediated tomography (FMT)] show exquisite congruence to radionuclide measurements and that information can be seamlessly integrated and visualized. Using biocompatible nanoparticles as a generic platform (containing a (18)F isotope and a far red fluorochrome), we show good correlations between FMT and PET in probe concentration (r(2) > 0.99) and spatial signal distribution (r(2) > 0.85). Using a mouse model of cancer and different imaging probes to measure tumoral proteases, macrophage content and integrin expression simultaneously, we demonstrate the distinct tumoral locations of probes in multiple channels in vivo. The findings also suggest that FMT can serve as a surrogate modality for the screening and development of radionuclide-based imaging agents.

Image-guided percutaneous locoregional therapies for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the 3rd leading cause of cancer death worldwide. Treatment options include surgical resection, liver transplantation, image-guided percutaneous locoregional options, external beam radiation therapy (EBRT) and systemic therapies. Treatment choice depends on the stage of the disease and patient's characteristics including performance status and liver function. Barcelona Clinic Liver Cancer (BCLC) staging system, with its recent 2022 update, is one of the most widely endorsed staging system. Locoregional therapies (LRT) are recommended for very early stage (BCLC-0), early stage (BCLC-A), and the two first subgroups of intermediate stage (BCLC-B). Image-guided percutaneous locoregional therapies include ablation, mainly thermal ablation with radiofrequency (RFA), microwave ablations (MWA) and cryoablation, transarterial embolization (TAE, also known as bland embolization), transarterial chemoembolization (TACE), drug-eluding beads-transarterial chemoembolization (DEB-TACE), combination of ablation with embolization, transarterial radioembolization (TARE) also known as selective internal radioembolization therapy, and hepatic artery infusion (HAI). While ablation is recognized as a curative therapy, all intra-arterial therapies are considered non-curative options. There is growing evidence that TARE, through radiation segmentectomy, can be considered a curative intent treatment in appropriate selective patients. In this article, we will review indications, complications, and outcomes of locoregional therapies for HCC.