Immunotherapy and transarterial embolization in patients with metastatic melanoma: a retrospective cohort study.

Aim: To investigate how the sequence of checkpoint immunotherapy (CPI) and transarterial embolization (TAE) affects overall survival (OS) of patients with metastatic melanoma.Materials & methods: This retrospective cohort study included 65 patients with metastatic melanoma who underwent both TAE and CPI between September 2011 and January 2022.Results: Significantly higher OS was seen in patients who received CPI before and after embolization (22 months, 95% CI 14-NR, p < 0.001) compared with only before embolization (4.5 months 95% CI, 14-NR). ≤3 hepatic metastasis (p < 0.01), more TAE procedures (p < 0.001) and CPI sequence (before and after embolization) (p < 0.001) were independent predictors of survival.Conclusion: Metastatic melanoma patients who underwent TAE have longer survival when CPI was sequenced both before and after embolization.

This study looked at how the order of two treatments, called checkpoint immunotherapy (CPI) and transarterial embolization (TAE), affects how long people with metastatic melanoma live. Sixty-five patients who had both treatments between September 2011 and January 2022 took part in the study. Patients with fewer than three liver metastases, cancer in just one part of the liver, and who had more TAE treatments tended to live longer. Patients who got CPI both before and after TAE lived longer compared with those who only got CPI before TAE.

Conversion Therapy to Transplant or Surgical Resection in Patients with Unresectable Hepatocellular Carcinoma Treated with Boosted Dose of Yttrium-90 Radiation Segmentectomy.

BACKGROUND/OBJECTIVES: The aim of this study was to assess the efficacy of boosted dose yttrium-90 radioembolization (TARE) as a modality for conversion therapy to transplant or surgical resection in patients with unresectable hepatocellular carcinoma (HCC). METHODS: In this single-center retrospective study, all patients with a diagnosis of HCC who were treated with boosted dose TARE (>190 Gy) between January 2013 and December 2023 were reviewed. Treatment response and decrease in tumor size were assessed with the RECIST v1.1 and mRECIST criteria. Milan and University of California, San Francisco (UCSF), criteria were used to determine transplant eligibility, and Barcelona Clinic Liver Cancer (BCLC) surgical resection recommendations were used to evaluate tumor resectability. RESULTS: Thirty-eight patients with primary HCC who were treated with boosted dose TARE were retrospectively analyzed. The majority of the patients were Child-Pugh A (n = 35; 92.1%), BCLC C (n = 17; 44.7%), and ECOG performance status 0 (n = 25; 65.8%). The mean sum of the target lesions was 6.0 cm (standard deviation; SD = 4.0). The objective response rate (ORR) was 31.6% by RECIST and 84.2% by mRECIST. The disease control rate (DCR) was 94.7% by both RECIST and mRECIST. Among patients outside of Milan or UCSF, 13/25 (52.0%, Milan) and 9/19 (47.4%, UCSF) patients were successfully converted to within transplant criteria. Of patients who were initially unresectable, conversion was successful in 7/26 (26.9%) patients. CONCLUSIONS: This study provides further real-world data demonstrating that boosted-dose TARE is an effective modality for conversion of patients with unresectable HCC to transplant or resection.

Intra-arterial locoregional therapies for intrahepatic cholangiocarcinoma.

INTRODUCTION: Intrahepatic cholangiocarcinoma (ICC) is the 2nd most common primary liver malignancy. For nonsurgical candidates, the primary treatment option is systemic chemotherapy, which can be combined with locoregional therapies to enhance local control. Common intra-arterial locoregional therapies include transarterial hepatic embolization, conventional transarterial chemoembolization, drug-eluting bead transarterial chemoembolization, transarterial radioembolization with Yttrium-90 microspheres, and hepatic artery infusion. This article aims to review the latest literature on intra-arterial locoregional therapies for treating ICC. AREAS COVERED: A literature search was conducted on PubMed using keywords: intrahepatic cholangiocarcinoma, intra-arterial locoregional therapy, embolization, chemoembolization, radioembolization, hepatic artery infusion, and immunotherapy. Articles from 2008 to 2024 were reviewed. Survival data from retrospective and prospective studies, meta-analyses, and clinical trials were evaluated. EXPERT OPINION: Although no level I evidence supports the superiority of any specific intra-arterial therapy, there has been a shift toward favoring radioembolization. In our expert opinion, radioembolization may offer superior outcomes when performed by skilled operators with meticulous planning and personalized dosimetry, particularly for radiation segmentectomy or treating lobar/bilobar disease in appropriate candidates.

Identification of a lactylation-related gene signature to characterize subtypes of hepatocellular carcinoma using bulk sequencing data.

Background: Prior studies indicate that lactylation regulates various biological mechanisms within cancer. However, lactylation-related genes (LRGs) have been found to have limited value in predicting the prognosis of hepatocellular carcinoma (HCC). The aim of this study was to review HCC LRGs using data from The Cancer Genome Atlas (TCGA). Methods: The RNA sequencing data and related clinical information of patients with HCC patients were collected from the TCGA database. A total of 20 LRGs were selected and bioinformatics analysis was performed. A consistency cluster analysis was conducted to classify the HCC tumors. Using a lactylation-related model of HCC, prognosis, immune cell infiltration, and immunotherapy was evaluated. Results: A total of 4,378 genes were associated with prognosis. Twenty LRGs (i.e., ACIN1, RAN, PPP1CB, ALDOB, SUMO2, THOC2, HDAC1, SF3A1, SF3B1, HNRNPM, PPP1CC, SRRM1, PRPF6, HDAC2, H2AFV, ALYREF, H2AFZ, H2AFX, HNRNPK, and MAGOH) were identified. The 20 LRGs were used to divide TCGA-HCC patients into low-risk (G1) and high-risk (G2) categories. The upregulated genes in the G1 group primarily participate in the p53 signaling pathway, focal adhesion, extracellular matrix (ECM)-receptor interaction, and cell cycle, while the downregulated genes primarily participate in the glycolysis/gluconeogenesis, carbon metabolism, and biosynthesis of amino acids. The box plots showed a significant difference in the immune cell populations, with a higher abundance of B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and myeloid dendritic cells in the G1 than the G2 HCC samples. Further, the box plots showed higher expression levels of seven of the eight immune checkpoint inhibitor (ICI)-related genes in the G1 HCC samples than the G2 samples. There was a significant disparity in the cancer stem cell (CSC) scores between the G1 and G2 TCGA-HCC patients. Additionally, the G1 TCGA-HCC patients had higher tumor immune dysfunction and exclusion (TIDE) scores than the G2 TCGA-HCC patients. The prognosis of the HCC patients was also predicted using a six-LRG model, comprising HDAC2, SRRM1, SF3B1, HDAC1, THOC2, and PPP1CB. Conclusions: Strong correlation between LRGs and tumor classification as well as immunity in patients with HCC was identified. LRG signatures serve as reliable prognostic markers for HCC.

Efficacy and safety of regorafenib as a first-line agent alone or in combination with an immune checkpoint inhibitor for advanced hepatocellular carcinoma: a retrospective cohort study.

Background: The RESORCE-III trial demonstrated that advanced hepatocellular carcinoma (HCC) patients who progressed on sorafenib and had second-line therapy with regorafenib improved overall survival compared with placebo. Later, immunotherapy with immune checkpoint inhibitors (ICIs) combined with antiangiogenetic antibodies has evolved as the preferred first-line treatment for fit patients. We aimed to explore the efficacy and safety of regorafenib as a first-line agent alone or in combination with ICIs in patients with advanced HCC. Methods: We identified 50 patients with advanced HCC treated with regorafenib as a first-line agent. Two patients were lost to follow-up and excluded. Baseline factors, dosing, concomitant use of ICIs, toxicity and outcome of treatment were recorded from electronic medical records. Results: Twenty-six patients received regorafenib as monotherapy and twenty-two received regorafenib + ICI in combination. In the total cohort, the median progression-free survival (mPFS) was 7.7 months and the median overall survival (mOS) was 16.7 months (P=0.02). Objective response rate (ORR) and disease control rate (DCR) assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 were 21% and 73%. In the regorafenib monotherapy group, mPFS was 5.9 months, and mOS was 13.9 months; in the combination group, mPFS was 7.8 months, and mOS was 23.6 months. ORR and DCR were 15% and 65% in the monotherapy group, and 27% and 82% in the combined treatment group, respectively. Conclusions: Regorafenib used in combination with ICIs had a mild safety profile and resulted in improved response and an almost doubling of mOS compared to monotherapy, warranting further prospective evaluation in a randomized study.

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.

Clinicogenomic predictors of outcomes in patients with hepatocellular carcinoma treated with immunotherapy.

INTRODUCTION: Immune checkpoint inhibitor (ICI) combinations extend overall survival (OS) while anti-PD-1/L1 monotherapy is non-inferior to sorafenib in treatment-naïve, patients with advanced hepatocellular carcinoma (HCC). Clinicogenomic features are posited to influence patient outcomes. METHODS: The primary objective of this retrospective study was to define the clinical, pathologic, and genomic factors associated with outcomes to ICI therapy in patients with HCC. Patients with histologically confirmed advanced HCC treated with ICI at Memorial Sloan Kettering Cancer Center from 2012 to 2022 were included. Association between clinical, pathological, and genomic characteristics were assessed with univariable and multivariable Cox regression model for progression-free survival (PFS) and OS. RESULTS: Two-hundred and forty-two patients were treated with ICI-based therapy. Patients were predominantly male (82%) with virally mediated HCC (53%) and Child Pugh A score (70%). Median follow-up was 28 months (0.5-78.4). Median PFS for those treated in 1st line, 2nd line and ≥ 3rd line was 4.9 (range: 2.9-6.2), 3.1 (2.3-4.0), and 2.5 (2.1-4.0) months, respectively. Median OS for those treated in 1st line, 2nd line, and ≥ 3rd line was 16 (11-22), 7.5 (6.4-11), and 6.4 (4.6-26) months, respectively. Poor liver function and performance status associated with worse PFS and OS, while viral hepatitis C was associated with favorable outcome. Genetic alterations were not associated with outcomes. CONCLUSION: Clinicopathologic factors were the major determinates of outcomes for patients with advanced HCC treated with ICI. Molecular profiling did not aid in stratification of ICI outcomes. Future studies should explore alternative biomarkers such as the level of immune activation or the pretreatment composition of the immune tumor microenvironment.

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.

Hemorrhage Sites and Mitigation Strategies After Pancreaticoduodenectomy.

Importance: Postpancreatectomy hemorrhage is an uncommon but highly morbid complication of pancreaticoduodenectomy. Clinical evidence often draws suspicion to the gastroduodenal artery stump, even without a clear source. Objective: To determine the frequency of gastroduodenal artery bleeding compared to other sites and the results of mitigation strategies. Design, Setting, and Participants: This cohort study involved a retrospective analysis of data for consecutive patients who had pancreaticoduodenectomy from 2011 to 2021 at Memorial Sloan Kettering Cancer Center (MSK) and Thomas Jefferson University Hospital (TJUH). Exposures: Demographic, perioperative, and disease-related variables. Main Outcomes and Measures: The incidence, location, treatment, and outcomes of primary (initial) and secondary (recurrent) hemorrhage requiring invasive intervention were analyzed. Imaging studies were re-reviewed by interventional radiologists to confirm sites. Results: Inclusion criteria were met by 3040 patients (n = 1761 MSK, n = 1279 TJUH). Patients from both institutions were similar in age (median [IQR] age at MSK, 67 [59-74] years, and at TJUH, 68 [60-75] years) and sex (at MSK, 814 female [46.5%] and 947 male [53.8%], and at TJUH, 623 [48.7%] and 623 male [51.3%]). Primary hemorrhage occurred in 90 patients (3.0%), of which the gastroduodenal artery was the source in 15 (16.7%), unidentified sites in 24 (26.7%), and non-gastroduodenal artery sites in 51 (56.7%). Secondary hemorrhage occurred in 23 patients; in 4 (17.4%), the gastroduodenal artery was the source. Of all hemorrhage events (n = 117), the gastroduodenal artery was the source in 19 (16.2%, 0.63% incidence in all pancreaticoduodenectomies). Gastroduodenal artery hemorrhage was more often associated with soft gland texture (14 [93.3%] vs 41 [62.1%]; P = .02) and later presentation (median [IQR], 21 [15-26] vs 10 days [5-18]; P = .002). Twenty-three patients underwent empirical gastroduodenal artery embolization or stent placement, 7 (30.4%) of whom subsequently experienced secondary hemorrhage. Twenty percent of all gastroduodenal artery embolizations/stents (8/40 patients), including 13% (3/13 patients) of empirical treatments, were associated with significant morbidity (7 hepatic infarction, 4 biliary stricture), with a 90-day mortality rate of 38.5% (n = 5) for patients with these complications vs 7.8% without (n = 6; P = .008). Ninety-day mortality was 12.2% (n = 11) for patients with hemorrhage (3 patients [20%] with primary gastroduodenal vs 8 [10.7%] for all others; P = .38) compared with 2% (n = 59) for patients without hemorrhage. Conclusions and Relevance: In this study, postpancreatectomy hemorrhage was uncommon and the spectrum was broad, with the gastroduodenal artery responsible for a minority of bleeding events. Empirical gastroduodenal artery embolization/stent without obvious sequelae of recent hemorrhage was associated with significant morbidity and rebleeding and should not be routine practice. Successful treatment of postpancreatectomy hemorrhage requires careful assessment of all potential sources, even after gastroduodenal artery mitigation.

Comparison of periprocedural and procedure room times between moderate sedation and monitored anesthesia care in interventional radiology.

Objectives: In recent years, there has been increased utilization of monitored anesthesia care (MAC) in interventional radiology (IR) departments. The purpose of this study was to compare pre-procedure bed, procedure room, and post-procedure bed times for IR procedures performed with either nurse-administered moderate sedation (MOSED) or MAC. Material and Methods: An institutional review board-approved single institution retrospective review of IR procedures between January 2010 and September 2022 was performed. Procedures performed with general anesthesia or local anesthetic only, missing time stamps, or where <50 cases were performed for both MAC and MOSED were excluded from the study. Pre-procedure bed, procedure room, post-procedure bed, and total IR encounter times were compared between MAC and MOSED using the t-test. The effect size was estimated using Cohen's d statistic. Results: 97,480 cases spanning 69 procedure codes were examined. Mean time in pre-procedure bed was 27 min longer for MAC procedures (69 vs. 42 min, P < 0.001, d = 0.95). Mean procedure room time was 11 min shorter for MAC (60 vs. 71 min, P < 0.001, d = 0.48), and mean time in post-procedure bed was 10 min longer for MAC (102 vs. 92 min, P < 0.001, d = 0.22). Total IR encounter times were on average 27 min longer for MAC cases (231 vs. 204 min, P < 0.001, d = 0.41). Conclusion: MAC improves the utilization of IR procedure rooms, but at the cost of increased patient time in the pre- and post-procedure areas.

Immune Effects of Intra-Arterial Liver-Directed Therapies.

Image-guided intra-arterial locoregional therapies (LRTs) such as transarterial embolization, transarterial chemoembolization, and transarterial radioembolization exhibit effects on the immune system. Understanding the humoral (cytokine, chemokine, and growth factor) and cellular (T cell, neutrophil, dendritic cell, and macrophage) mechanisms underlying the immune effects of LRT is crucial to designing rational and effective combinations of immunotherapy and interventional radiology procedures. This article aims to review the immune effects of intra-arterial LRTs and provide insight into strategies to combine LRTs with systemic immunotherapy.

Management of Pericardial Effusion in Patients With Solid Tumor: An Algorithmic, Multidisciplinary Approach Results in Reduced Mortality After Paradoxical Hemodynamic Instability.

OBJECTIVE: This study compared outcomes in patients with solid tumor treated for pericardial effusion with surgical drainage versus interventional radiology (IR) percutaneous drainage and compared incidence of paradoxical hemodynamic instability (PHI) between cohorts. BACKGROUND: Patients with advanced-stage solid malignancies may develop large pericardial effusions requiring intervention. PHI is a fatal and underreported complication that occurs following pericardial effusion drainage. METHODS: Clinical characteristics and outcomes were compared between patients with solid tumors who underwent s urgical drainage or IR percutaneous drainage for pericardial effusion from 2010 to 2020. RESULTS: Among 447 patients, 243 were treated with surgical drainage, of which 27 (11%) developed PHI, compared with 7 of 204 patients (3%) who were treated with IR percutaneous drainage ( P =0.002); overall incidence of PHI decreased during the study period. Rates of reintervention (30-day: 1% vs 4%; 90-day: 4% vs 6%, P =0.7) and mortality (30-day: 21% vs 17%, P =0.3; 90-day: 39% vs 37%, P =0.7) were not different between patients treated with surgical drainage and IR percutaneous drainage. For both interventions, OS was shorter among patients with PHI than among patients without PHI (surgical drainage, median [95% confidence interval] OS, 0.89 mo [0.33-2.1] vs 6.5 mo [5.0-8.9], P <0.001; IR percutaneous drainage, 3.7 mo [0.23-6.8] vs 5.0 mo [4.0-8.1], P =0.044). CONCLUSIONS: With a coordinated multidisciplinary approach focusing on prompt clinical and echocardiographic evaluation, triage with bias toward IR percutaneous drainage than surgical drainage and postintervention intensive care resulted in lower incidence of PHI and improved outcomes.

Safety and Efficacy of Hepatic Artery Embolization in Heavily Treated Patients with Intrahepatic Cholangiocarcinoma: Analysis of Clinicopathological and Radiographic Parameters Associated with Better Overall Survival.

The safety and efficacy of hepatic artery embolization (HAE) in treating intrahepatic cholangiocarcinoma (IHC) was evaluated. Initial treatment response, local tumor progression-free survival (L-PFS), and overall survival (OS) were evaluated in 34 IHC patients treated with HAE. A univariate survival analysis and a multivariate Cox proportional hazard analysis to identify independent factors were carried out. Objective response (OR) at 1-month was 79.4%. Median OS and L-PFS from the time of HAE was 13 (CI = 95%, 7.4-18.5) and 4 months (CI = 95%, 2.09-5.9), respectively. Tumor burden < 25% and increased tumor vascularity on preprocedure imaging and surgical resection prior to embolization were associated with longer OS (p < 0.05). Multivariate logistic regression analysis demonstrated that tumor burden < 25% and hypervascular tumors were independent risk factors. Mean post-HAE hospital stay was 4 days. Grade 3 complication rate was 8.5%. In heavily treated patients with IHC, after exhausting all chemotherapy and other locoregional options, HAE as a rescue treatment option appeared to be safe with a mean OS of 13 months. Tumor burden < 25%, increased target tumor vascularity on pre-procedure imaging, and OR on 1 month follow-up images were associated with better OS. Further studies with a control group are required to confirm the effectiveness of HAE in IHC.

Targeted Molecular Profiling of Circulating Cell-Free DNA in Patients With Advanced Hepatocellular Carcinoma.

PURPOSE: Next-generation sequencing (NGS) of tumor-derived, circulating cell-free DNA (cfDNA) may aid in diagnosis, prognostication, and treatment of patients with hepatocellular carcinoma (HCC). The operating characteristics of cfDNA mutational profiling must be determined before routine clinical implementation. METHODS: This was a single-center, retrospective study with the primary objective of defining genomic alterations in circulating cfDNA along with plasma-tissue genotype agreement between NGS of matched tumor samples in patients with advanced HCC. cfDNA was analyzed using a clinically validated 129-gene NGS assay; matched tissue-based NGS was analyzed with a US Food and Drug Administration-authorized NGS tumor assay. RESULTS: Fifty-three plasma samples from 51 patients with histologically confirmed HCC underwent NGS-based cfDNA analysis. Genomic alterations were detected in 92.2% of patients, with the most commonly mutated genes including TERT promoter (57%), TP53 (47%), CTNNB1 (37%), ARID1A (18%), and TSC2 (14%). In total, 37 (73%) patients underwent paired tumor NGS, and concordance was high for mutations observed in patient-matched plasma samples: TERT (83%), TP53 (94%), CTNNB1 (92%), ARID1A (100%), and TSC2 (71%). In 10 (27%) of 37 tumor-plasma samples, alterations were detected by cfDNA analysis that were not detected in the patient-matched tumors. Potentially actionable mutations were identified in 37% of all cases including oncogenic/likely oncogenic alterations in TSC1/2 (18%), BRCA1/2 (8%), and PIK3CA (8%). Higher average variant allele fraction was associated with elevated alpha-fetoprotein, increased tumor volume, and no previous systemic therapy, but did not correlate with overall survival in treatment-naïve patients. CONCLUSION: Tumor mutation profiling of cfDNA in HCC represents an alternative to tissue-based genomic profiling, given the high degree of tumor-plasma NGS concordance; however, genotyping of both blood and tumor may be required to detect all clinically actionable genomic alterations.

Anti-Glycolytic Drugs in the Treatment of Hepatocellular Carcinoma: Systemic and Locoregional Options.

Hepatocellular cancer (HCC) is the most common primary liver cancer and the third leading cause of cancer-related death. Locoregional therapies, including transarterial embolization (TAE: bland embolization), chemoembolization (TACE), and radioembolization, have demonstrated survival benefits when treating patients with unresectable HCC. TAE and TACE occlude the tumor's arterial supply, causing hypoxia and nutritional deprivation and ultimately resulting in tumor necrosis. Embolization blocks the aerobic metabolic pathway. However, tumors, including HCC, use the "Warburg effect" and survive hypoxia from embolization. An adaptation to hypoxia through the Warburg effect, which was first described in 1956, is when the cancer cells switch to glycolysis even in the presence of oxygen. Hence, this is also known as aerobic glycolysis. In this article, the adaptation mechanisms of HCC, including glycolysis, are discussed, and anti-glycolytic treatments, including systemic and locoregional options that have been previously reported or have the potential to be utilized in the treatment of HCC, are reviewed.

Factors affecting outcomes of Yttrium-90 radioembolization in heavily pretreated patients with intrahepatic cholangiocarcinoma.

PURPOSE: Transarterial radioembolization (TARE) is a liver-directed treatment for unresectable intrahepatic cholangiocarcinoma (ICC). The aim of this study is to evaluate factors affecting outcomes of TARE in heavily pretreated ICC patients. METHODS: We evaluated pretreated ICC patients who received TARE from January 2013 to December 2021. Prior treatments included systemic therapy, hepatic resection, and liver-directed therapies, including hepatic arterial infusion chemotherapy, external beam radiation, transarterial embolization, and thermal ablation. Patients were classified based on history of hepatic resection and genomic status based on next-generation sequencing (NGS). The primary endpoint was overall survival (OS) after TARE. RESULTS: Fourteen patients with median age 66.1 years (range, 52.4-87.5), 11 females and 3 males, were included. Prior therapies included systemic in 13/14 patients (93%), liver resection in 6/14 (43%), and liver-directed therapy in 6/14 (43%). Median OS was 11.9 months (range, 2.8-81.0). Resected patients had significantly longer median OS compared to unresected patients (16.6 versus 7.9 months; p = 0.038). Prior liver-directed therapy (p = 0.043), largest tumor diameter > 4 cm (p = 0.014), and > 2 hepatic segments involvement (p = 0.001) were associated with worse OS. Nine patients underwent NGS; 3/9 (33.3%) and had a high-risk gene signature (HRGS), defined as alterations in TP53, KRAS, or CDKN2A. Patients with a HRGS had worse median OS (10.0 versus 17.8 months; p = 0.024). CONCLUSIONS: TARE may be used as salvage therapy in heavily treated ICC patients. Presence of a HRGS may predict worse OS after TARE. Further investigation with more patients is recommended to validate these results.

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.

Induction and preliminary characterization of neoplastic pulmonary nodules in a transgenic pig model.

OBJECTIVES: Lung cancer models in large animals are lacking. Oncopigs are transgenic pigs that carry both KRASG12D and TP53R167H Cre-inducible mutations. This study aimed to develop and histologically characterize a swine model of lung cancer that could serve for preclinical studies evaluating locoregional therapies. MATERIALS AND METHODS: In two Oncopigs, an adenoviral vector encoding the Cre-recombinase gene (AdCre) was injected endovascularly through the pulmonary arteries or inferior vena cava. In two other Oncopigs, a lung biopsy was performed and incubated with AdCre, before reinjecting the mixture into the lungs percutaneously. Animals were clinically and biologically (complete blood count, liver enzymes and lipasemia) monitored. Obtained tumors were characterized on computed tomography (CT) and on pathology and immunohistochemistry (IHC). RESULTS: Neoplastic lung nodules developed following 1 (1/10, 10%) endovascular inoculation, and 2 (2/6, 33%) percutaneous inoculations. All lung tumors were visible at the 1-week CT, and appeared as well-circumscribed solid nodules, with a median longest diameter of 14 mm (range: 5-27 mm). Only one complication occurred: an extravasation of the mixture into the thoracic wall during a percutaneous injection that resulted in a thoracic wall tumor. Pigs remained clinically healthy during the entire follow-up (14-21 days). On histology, tumors consisted of inflammatory undifferentiated neoplasms composed of atypical spindle and epithelioid cells and/or a fibrovascular stroma and abundant mixed leukocytic infiltrate. On IHC, atypical cells diffusely displayed expression of vimentin and some showed expression of CK WSS and CK 8/18. The tumor microenvironment contained abundant IBA1 + macrophages and giant cells, CD3 + T cells, and CD31 + blood vessels. CONCLUSION: Tumors induced in the lungs of Oncopigs are fast growing poorly differentiated neoplasms associated with a marked inflammatory reaction that can be easily and safely induced at site specific locations. This large animal model might be suitable for interventional and surgical therapies of lung cancer.

Stent Graft Placement for the Treatment of Hepatic Artery Injury in Patients with Cancer: Primary Patency and Clinical Outcomes.

PURPOSE: To evaluate the safety, primary patency, and clinical outcomes of hepatic artery stent graft (SG) placement for vascular injuries. MATERIALS AND METHODS: Patients treated with hepatic arterial SG placement for vascular injuries between September 2018 and September 2021 were reviewed. Data on demographic characteristics, indication, stent graft characteristics, antiplatelet/anticoagulant use, clinical success rate, complications, and type of follow-up imaging were collected. Follow-up images were reviewed by 2 independent reviewers to assess primary patency. A time-to-event analysis was performed. The median duration of stent graft patency was estimated using Kaplan-Meier curves. A Cox proportional hazard model was used to evaluate factors related to stent graft patency. RESULTS: Thirty-five patients were treated with hepatic arterial SG placement, 11 for postoperative bleeds and 24 for hepatic artery infusion pump catheter-related complications. Clinical success was achieved in 32 (91%) patients (95% CI, 77-98). The median primary patency was 87 days (95% CI, 73-293). Stent grafts of ≥6-mm diameter retained patency for a longer duration than that with stent grafts of smaller diameters (6 mm vs 5 mm; hazard ratio, 0.35; 95% CI, 0.14-0.88; P = .026; and 7+ mm vs 5 mm; hazard ratio, 0.27; 95% CI, 0.09-0.83; P = .023). Anticoagulation/antiplatelet regimen was not associated with increased stent graft patency duration (P > .05). Only minor complications were reported in 2 (5.7%) patients. CONCLUSIONS: Stent grafts can be used safely and effectively to treat injuries of the hepatic artery. Stent graft diameters of ≥6 mm seem to provide more durable patency.

Reducing Wait Times for Radiology Exams Around Holiday Periods: A Monte Carlo Simulation.

Reducing patient wait times is a key operational goal and impacts patient outcomes. The purpose of this study is to explore the effects of different radiology scheduling strategies on exam wait times before and after holiday periods at an outpatient imaging facility using computer simulation. An idealized Monte Carlo simulation of exam scheduling at an outpatient imaging facility was developed based on the actual distribution of scheduled exams at outpatient radiology sites at a tertiary care medical center. Using this simulation, we examined three scheduling strategies: (1) no scheduling modifications, (2) increase imaging capacity before or after the holiday (i.e. increase facility hours), and (3) use a novel rolling release scheduling paradigm. In the third scenario, a fraction of exam slots are blocked to long-term follow-up exams and made available only closer to the exam date, thereby preventing long-term follow-up exams from filling the schedule and ensuring slots are available for non-follow-up exams. We examined the effect of these three scenarios on utilization and wait times, which we defined as the time from order placement to exam completion, during and after the holiday period. The baseline mean wait time for non-follow-up exams was 5.4 days in our simulation. When no scheduling modifications were made, there was a significant increase in wait times in the week preceding the holiday when compared to baseline (10.0 days vs 5.4 days, p < 0.01). Wait times remained elevated for 4 weeks following the holiday. Increasing imaging capacity during the holiday and post-holiday period by 20% reduced wait times by only 6.2% (9.38 days vs 10.0 days, p < 0.01). Increasing capacity by 50% resulted in a 7.1% reduction in wait times (9.28 days, p < 0.01), and increasing capacity by 100% resulted in a 13% reduction in wait times (8.75 days, p < 0.01). In comparison, using a rolling release model produced a reduction in peak wait times equivalent to doubling capacity (8.76 days, p < 0.01) when 45% of slots were reserved. Improvements in wait times persisted even when rolling release was limited to the 3 weeks preceding or 1 week following the holiday period. Releasing slots on a rolling basis did not significantly decrease utilization or increase wait times for long-term follow-up exams except in extreme scenarios where 80% or more of slots were reserved for non-follow-up exams. A rolling release scheduling paradigm can significantly reduce wait time fluctuations around holiday periods without requiring additional capacity or impacting utilization.