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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.
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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 andâ ≥â 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, andâ ≥â 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.
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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.
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Tomografía Computarizada de Haz Cónico , Embolización Terapéutica , Arteria Hepática , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/mortalidad , Tomografía Computarizada de Haz Cónico/métodos , Femenino , Masculino , Embolización Terapéutica/métodos , Persona de Mediana Edad , Anciano , Arteria Hepática/diagnóstico por imagen , Adulto , Resultado del Tratamiento , Anciano de 80 o más Años , Estudios RetrospectivosRESUMEN
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.
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Carcinoma Hepatocelular , Embolización Terapéutica , Neoplasias Hepáticas , Radioisótopos de Itrio , Humanos , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/terapia , Masculino , Femenino , Anciano , Embolización Terapéutica/métodos , Radioisótopos de Itrio/uso terapéutico , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Anciano de 80 o más AñosRESUMEN
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.
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Pancreaticoduodenectomía , Hemorragia Posoperatoria , Humanos , Pancreaticoduodenectomía/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Hemorragia Posoperatoria/etiología , Hemorragia Posoperatoria/epidemiología , Duodeno/irrigación sanguínea , IncidenciaRESUMEN
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.
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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.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/radioterapia , Quimioembolización Terapéutica/métodos , Procedimientos Quirúrgicos VascularesRESUMEN
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.
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Neoplasias , Derrame Pericárdico , Procedimientos Quirúrgicos Torácicos , Enfermedades Vasculares , Humanos , Derrame Pericárdico/etiología , Derrame Pericárdico/cirugía , Neoplasias/complicaciones , Enfermedades Vasculares/etiología , Drenaje/métodos , Estudios Retrospectivos , HemodinámicaRESUMEN
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.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Resultado del Tratamiento , Arteria Hepática/diagnóstico por imagen , Arteria Hepática/patología , Colangiocarcinoma/diagnóstico por imagen , Colangiocarcinoma/terapia , Conductos Biliares Intrahepáticos/diagnóstico por imagen , Conductos Biliares Intrahepáticos/patología , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Neoplasias de los Conductos Biliares/terapiaRESUMEN
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.
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Carcinoma Hepatocelular , Ácidos Nucleicos Libres de Células , ADN Tumoral Circulante , Neoplasias Hepáticas , Estados Unidos , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Proteína BRCA1 , Estudios Retrospectivos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , ADN Tumoral Circulante/genética , Proteína BRCA2 , Ácidos Nucleicos Libres de Células/genéticaRESUMEN
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.
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Carcinoma Hepatocelular , Embolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Embolización Terapéutica/métodos , GlucólisisRESUMEN
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.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Embolización Terapéutica , Masculino , Femenino , Humanos , Anciano , Embolización Terapéutica/métodos , Colangiocarcinoma/radioterapia , Conductos Biliares Intrahepáticos/patología , Neoplasias de los Conductos Biliares/radioterapiaRESUMEN
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.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Trasplante de Hígado , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Selección de PacienteRESUMEN
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.
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Neoplasias Pulmonares , Nódulos Pulmonares Múltiples , Animales , Humanos , Porcinos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patología , Modelos Animales de Enfermedad , Pulmón/patología , Mutación , Microambiente TumoralRESUMEN
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.
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Implantación de Prótesis Vascular , Neoplasias , Lesiones del Sistema Vascular , Humanos , Arteria Hepática/diagnóstico por imagen , Arteria Hepática/cirugía , Resultado del Tratamiento , Grado de Desobstrucción Vascular , Lesiones del Sistema Vascular/etiología , Stents/efectos adversos , Implantación de Prótesis Vascular/efectos adversos , Complicaciones Posoperatorias/etiología , Neoplasias/complicaciones , Estudios Retrospectivos , Oclusión de Injerto Vascular/etiología , Prótesis Vascular/efectos adversosRESUMEN
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.
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Radiología , Listas de Espera , Humanos , Simulación por Computador , Citas y Horarios , Método de Montecarlo , Vacaciones y FeriadosRESUMEN
Background: Despite the emergence of immune checkpoint inhibitors (ICIs) as first-line treatment for advanced hepatocellular carcinoma (HCC), there is an unmet need regarding subsequent treatments in patients that fail ICI. Regorafenib is a vascular endothelial growth factor receptor (VEGFR) inhibitor, which could increase programmed death-ligand 1 (PD-L1) expression in tumors and increase intra-tumoral CD8+ T-cell infiltration by normalizing the cancer vasculature and improving the efficacy of the programmed cell death protein 1 (PD-1) antibody. Thus, we evaluated the combination of regorafenib and a PD-1 inhibitor for advanced HCC patients that had failed combined tyrosine kinase inhibitors (TKIs) plus ICI. Methods: Data of patients with advanced HCC who had failed combined TKIs plus ICI treatment and were afterwards treated with combined regorafenib plus a PD-1 inhibitor were reviewed. All patients had received PD-1 inhibitors as part of the first-line treatment and regorafenib every 4 weeks until disease progression, intolerable toxicities, or physician/patient withdrawal. The clinical data, previous treatment strategies, follow-up imaging results, and adverse events (AEs) during follow-ups were recorded. Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0 was used to evaluate AEs and Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 was used to evaluate response. The primary endpoint was safety, and the secondary endpoints were the objective response rate (ORR), progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and duration of response (DOR). Results: From November 15, 2020, to January 31, 2022, data of 17 patients with advanced HCC that met the criteria were reviewed. The cohort included 16 men and 1 woman with a median age of 54 years (interquartile range, 46 to 63 years). Sixteen patients had Child-Pugh class A (n=16, 94.12%) and one with class B (n=1, 15.9%) liver disease. Thirteen patients received second-line treatment, and the remaining patients received third-line treatment. All patients received at least 1 dose of PD-1 inhibitors. The median follow-up duration was 7.62 months. Twelve recipients experienced treatment-related AEs. The most frequent AE (≥5%) included fatigue (17.64%), diarrhea (17.65%), proteinuria (5.88%), bleeding gums (11.76%), and hypertension (11.76%). No grade-4 AE or new safety signals were identified. The ORR and DCR were 41.2% and 64.7%, respectively, and the median PFS was 5.09 months. Conclusions: Regorafenib combined with PD-1 inhibitor is a promising regimen in treating patients with advanced HCC owing to its safety and effectiveness as well as low incidence of serious AEs with its use.
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PURPOSE: To determine how particle density affects dose distribution and outcomes after lobar radioembolization. METHODS: Matched pairs of patients, treated with glass versus resin microspheres, were selected by propensity score matching (114 patients), in this single-institution retrospective study. For each patient, tumor and liver particle density (particles/cm3) and dose (Gy) were determined. Tumor-to-normal ratio was measured on both 99mTc-MAA SPECT/CT and post-90Y bremsstrahlung SPECT/CT. Microdosimetry simulations were used to calculate first percentile dose, which is the dose in the cold spots between microspheres. Local progression-free survival (LPFS) and overall survival were analyzed. RESULTS: As more particles were delivered, doses on 90Y SPECT/CT became more uniform throughout the treatment volume: tumor and liver doses became more similar (p = 0.04), and microscopic cold spots between particles disappeared. For hypervascular tumors (tumor-to-normal ratio ≥ 2.6 on MAA scan), delivering fewer particles (< 6000 particles/cm3 treatment volume) was associated with better LPFS (p = 0.03). For less vascular tumors (tumor-to-normal ratio < 2.6), delivering more particles (≥ 6000 particles/cm3) was associated with better LPFS (p = 0.02). In matched pairs of patients, using the optimal particle density resulted in improved overall survival (11.5 vs. 6.8 months, p = 0.047), compared to using suboptimal particle density. Microdosimetry resulted in better predictions of LPFS (p = 0.03), and overall survival (p = 0.02), compared to conventional dosimetry. CONCLUSION: The number of particles delivered can be chosen to maximize the tumor dose and minimize the liver dose, based on tumor vascularity. Optimizing the particle density resulted in improved LPFS and overall survival.
Asunto(s)
Carcinoma Hepatocelular , Embolización Terapéutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/radioterapia , Embolización Terapéutica/métodos , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/radioterapia , Microesferas , Estudios Retrospectivos , Agregado de Albúmina Marcado con Tecnecio Tc 99m , Tomografía Computarizada de Emisión de Fotón Único , Radioisótopos de Itrio/uso terapéuticoRESUMEN
PURPOSE: To assess the accuracy, sensitivity, positive predictive value (PPV) and interobserver agreement of a virtual injection (VI) software that simulates selective arterial injection from nonselective cone-beam CT (CBCT) arteriography. METHODS: From March 2019 to May 2020, 20 consecutive patients in whom a nonselective injected CBCT and a selective CT angiography (CTA) were completed in the same procedure, were retrospectively included. The position of the microcatheter tip used for selective CTA injection was identified. The VI was simulated from the exact same point on the nonselective CBCT and the two volumes were merged. VI was compared to the real injection on the selective CTA. Three interventional radiologists evaluated the accuracy using a 6-point scale (Perfect; Good; Fair; Incorrect Origin; False Negative; Non existing). Sensitivity, PPV, and Fleiss' kappa were calculated. Numerical variables were presented as means ± standard deviations. RESULTS: Twenty procedures and 195 vessel segments were analyzed. Most vessels were 4th order (57/195; 29%) and 5th order (96/195; 49%). VI was classified as perfect to good in 96.8% ± 1.4 of 1st-3rd order arteries and in 83.4% ± 0.4 of 4th-5th order arteries. Interobserver agreement was substantial (Fleiss' kappa = 0.79; 95% confidence interval = 0.73-0.84, P < 0.01). False negatives were reported with a mean of 9.4% ± 0.3. Average sensitivity was 90.6% ± 0.3 and average PPV was 92.7% ± 0.02. Fourteen false positives were noted. CONCLUSION: CBCT-based VI software accurately simulated distal injections in the liver with high sensitivity and a substantial interobserver agreement.