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Locoregional treatments (LRT) continue to advance for hepatocellular carcinoma (HCC). Selective internal radiation therapy (SIRT) or transarterial radioembolization (TARE) with radioactive 90 Yttrium (Y90) microspheres is currently widely accepted, and external beam and stereotactic body radiation (EBRT/SBRT) are increasingly used as LRT1-5. Assessment of treatment response after these radiation-based therapies can be challenging, given that the adjacent liver also undergoes treatment related changes, inflammatory changes occur, and there is a variable time for response to develop. In 2017, the liver imaging reporting and data system (LI-RADS) workgroup initially developed a single algorithm for the imaging assessment of treatment response encompassing all types of locoregional therapies, the LI-RADS treatment response (LR-TR) algorithm. Recognizing that response and imaging patterns differ between radiation and non-radiation based therapies, the LR-TR working group recently updated the algorithm to reflect the unique characteristics of tumor response for therapies involving radiation. This article aims to elucidate the changes in the new version of the LI-RADS TR, with a guide for algorithm utilization and illustration of expected and unexpected findings post liver directed therapies for HCC.
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BACKGROUND AND OBJECTIVES: Hepatic artery infusion pump (HAIP) therapy is an available option at highly specialized centers to treat unresectable liver tumors (e.g., colorectal liver metastases [CRLM]). This study describes the safety and outcomes of HAIP program implementation at an academic-based cancer center. METHODS: Patients who underwent HAIP placement (2021-2023) were included. Categorical and continuous variables were compared using Chi-square and Kruska-Wallis tests, respectively. Survival and variables associated with survival were calculated using the Kaplan-Meier method and Cox proportional hazards model, respectively. RESULTS: Of the 26 HAIP procedures for unresectable CRLM, four were done as adjuvant therapy. Median duration of HAIP therapy was 9.2 months and four patients subsequently underwent hepatectomy. Complication rate was 37.5%, with biliary complication rate of 23.1%. Median overall survival (OS) from date of diagnosis was 55.2 months. Concurrent primary tumor resection was associated with inferior OS (p = 0.030). Multivariable regression did not identify independent predictors of OS. Progression-free survival from time of HAIP placement was 7.8 months. CONCLUSIONS: HAIP placement was technically successful in most patients with an acceptable complication rate. Survival outcomes were comparable with those described in the literature for HAIP therapy in combination with systemic therapy. The significant difference in outcomes for those with concurrent colectomy warrants further investigation.
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Cholangiocarcinoma is a hepatobiliary malignancy which can manifest anywhere along the biliary tree. Intrahepatic cholangiocarcinoma occurs in the liver within or beyond the second order bile ducts. The prognosis for patients with intrahepatic cholangiocarcinoma is poor, even when successfully resected there is a very high rate of local recurrence. The available systemic therapies are currently limited and have high rates of toxicity. Percutaneous and transarterial liver-directed therapies can be used to treat intrahepatic cholangiocarcinoma with results comparable to current standard of care systemic therapies in some circumstances. This manuscript will review these the techniques and efficacy of percutaneous and transarterial liver-directed therapies for intrahepatic cholangiocarcinoma.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/terapia , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/terapia , Quimioembolização Terapêutica/métodosRESUMO
BACKGROUND: Liver-directed treatments - ablative therapy (AT), surgical resection (SR), liver transplantation (LT), and transarterial chemoembolization (TACE) - improve the overall survival of patients with early-stage hepatocellular carcinoma (HCC). Although racial and socioeconomic disparities affect access to liver-directed therapies, the temporal trends for the curative-intent treatment of HCC remain to be elucidated. METHODS: This study performed chi-square, logistic regression, and temporal trends analyses on data from the Nationwide Inpatient Sample from 2011 to 2019. The outcome of interest was the rate of AT, SR, LT (curative-intent treatments), and TACE utilization, and the primary predictors were racial/ethnic group and socioeconomic status (SES; insurance status). RESULTS: African American and Hispanic patients had lower odds of receiving AT (African American: odds ratio [OR], 0.78; P < .001; Hispanic: OR, 0.84; P = .005) and SR (African American: OR, 0.71; P < .001; Hispanics: OR, 0.64; P < .001) than White patients. Compared with White patients, the odds of LT was lower in African American patients (OR, 0.76; P < .001) but higher in Hispanic patients (OR, 1.25; P = .001). Low SES was associated with worse odds of AT (OR, 0.79; P = .001), SR (OR, 0.66; P < .001), and LT (OR, 0.84; P = .028) compared with high SES. Although curative-intent treatments showed significant upward temporal trends among White patients (10.6%-13.9%; P < .001) and Asian and Pacific Islander/other patients (14.4%-15.7%; P = .007), there were nonsignificant trends among African American patients (10.9%-10.1%; P = .825) or Hispanic patients (12.2%-13.7%; P = .056). CONCLUSION: Our study demonstrated concerning disparities in the utilization of curative-intent treatment for HCC based on race/ethnicity and SES. Moreover, racial/ethnic disparities have widened rather than improved over time.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Disparidades em Assistência à Saúde , Hispânico ou Latino , Neoplasias Hepáticas , Transplante de Fígado , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Técnicas de Ablação/estatística & dados numéricos , Técnicas de Ablação/tendências , Negro ou Afro-Americano , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/etnologia , Quimioembolização Terapêutica/estatística & dados numéricos , Quimioembolização Terapêutica/tendências , Disparidades em Assistência à Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde/tendências , Hepatectomia/estatística & dados numéricos , Hepatectomia/tendências , Cobertura do Seguro/estatística & dados numéricos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/etnologia , Transplante de Fígado/estatística & dados numéricos , Transplante de Fígado/tendências , Estados Unidos , BrancosRESUMO
Transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) are common liver-directed therapies (LDTs) for unresectable HCC. While both deliver intra-arterial treatment directly to the site of the tumor, they differ in mechanisms of action and side effects. Several studies have compared their side effect profile, time to progression, and overall survival data, but often these lack practical considerations when choosing which treatment modality to use. Many factors can impact operator's choice for treatment, and the choice depends on treatment availability, cost, insurance coverage, operator's comfort level, patient-specific factors, tumor location, tumor biology, and disease stage. This review discusses survival data, time to progression data, as well as more practical patient and tumor characteristics for personalized LDT with TACE or TARE.
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Uveal melanoma is the most common primary intraocular tumor in adults. Approximately 50% of patients develop metastatic disease despite successful treatment of the primary eye tumor. The liver is the most common site of metastatic disease occurring in more than 90% of patients. Clinical prognosis is dependent on the ability to control the growth of liver tumors. Locoregional therapies play an important role in stabilizing liver metastases, prolonging survival for patients with metastatic uveal melanoma. As overall survival is prolonged, the development of extrahepatic disease becomes more common. Immunoembolization, a form of liver-directed therapy, not only focuses on treating hepatic metastases by stimulating the local immune system to suppress the growth of liver tumors, but it potentially generates a systemic immune response delaying the growth of extrahepatic metastases as well. The following article discusses immunoembolization for the treatment of metastatic uveal melanoma including the rationale, mechanism of action, indications, contraindications, outcomes, and associated toxicities.
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Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related deaths in the world. Patients with early-stage HCC are treated with liver-directed therapies to bridge or downstage for liver transplantation (LT). In this study, the impact of HCC care delay on HCC progression among early-stage patients was investigated. Early-stage HCC patients undergoing their first cycle of liver-directed therapy (LDT) for bridge/downstaging to LT between 04/2016 and 04/2022 were retrospectively analyzed. Baseline variables were analyzed for risk of disease progression and time to progression (TTP). HCC care delay was determined by the number of rescheduled appointments related to HCC care. The study cohort consisted of 316 patients who received first-cycle LDT. The HCC care no-show rate was associated with TTP (p = 0.004), while the overall no-show rate was not (p = 0.242). The HCC care no-show rate and HCC care delay were further expanded as no-show rates and rescheduled appointments for imaging, laboratory, and office visits, respectively. More than 60% of patients experienced HCC care delay for imaging and laboratory appointments compared to just 8% for office visits. Multivariate analysis revealed that HCC-specific no-show rates and HCC care delay for imaging (p < 0.001) were both independently associated with TTP, highlighting the importance of minimizing delays in early-stage HCC imaging surveillance to reduce disease progression risk.
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BACKGROUND: Since 2013, North American Neuroendocrine Tumor Society (NANETS) consensus-guidelines have endorsed consideration of surgical intervention for pancreatic- neuroendocrine tumors (PNET) with liver metastases. METHODS: Patients with non-functional PNET with liver only metastases from 2010 to 2019 were identified from the National Cancer Database. RESULTS: 34.7% underwent surgical intervention (13% PNET resection, 2.1% surgical management of liver metastases (SMLM), 19.5% PNET resection â+ âSMLM). In multivariable analysis, government insurance, year of diagnosis>2013, increasing primary tumor size were associated with lower rate of surgical intervention. Receiving treatment at an academic center (OR 3.59, 95%CI 1.81-7.11; P â< â0.001) or integrated cancer network (OR 3.21, 95%CI 1.57-6.54; P â= â0.001) was associated with a higher rate of surgical intervention. The overall rate of surgical intervention decreased from 45.7% in 2010 to 23.0% in 2019. CONCLUSION: Despite guideline recommendations and the suggested survival benefits, only one-third of patients underwent surgical intervention, potentially influenced by the rising utilization of systemic therapy in the past decade.
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Neoplasias Hepáticas , Tumores Neuroectodérmicos Primitivos , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/secundário , Pancreatectomia , Tumores Neuroectodérmicos Primitivos/cirurgia , Estudos RetrospectivosRESUMO
Hepatic arterial infusion (HAI) pumps are used to deliver liver-directed therapy by allowing the administration of selective chemotherapy to the liver via a catheter implanted most commonly into the gastroduodenal artery connected to a subcutaneous pump. This selective administration helps maximize the chemotherapeutic effect within the hepatic tumors while minimizing systemic toxicity. While HAI therapy has primarily been used to treat liver-only metastatic colorectal cancer, the indications have expanded to other malignancies, including intrahepatic cholangiocarcinoma. Radiologists play an important role in pre-operative planning, assessment of treatment response, and evaluation for potential complications using various imaging studies, including computed tomography angiography, magnetic resonance imaging, and perfusion scintigraphy. This article describes the radiologist's role as part of a multi-disciplinary oncology team to help maximize the success of HAI therapy and also helps radiologists familiarize themselves with various aspects of HAI pumps.
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Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Infusões Intra-Arteriais/métodos , Neoplasias do Colo/patologia , Artéria Hepática/diagnóstico por imagem , Artéria Hepática/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Radiologistas , Bombas de Infusão , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologiaRESUMO
Bone metastases from gastroenteropancreatic neuroendocrine neoplasms (GEPNENs) have been associated with poor prognosis, but it is unclear whether patients with concurrent bone metastases who receive liver-directed therapy (LDT) would derive survival benefit. The California Cancer Registry dataset, merged with data from the California Office of Statewide Health Planning and Development, was used to perform a retrospective study of GEPNENs metastatic to both liver and bone between 2000 and 2012. A total of 203 patients were identified. Of these, 14.8% underwent LDT after bone metastasis diagnosis, 22.1% received LDT prior to that diagnosis, and 63.1% never received LDT. The median overall survival from the time of bone metastasis diagnosis was significantly longer in those that received LDT after diagnosis when compared with those that never received LDT (p = 0.005) and was not significantly different from the median overall survival of those that had received LDT prior to diagnosis (p = 0.256). LDT may still be associated with improved survival even after a diagnosis of bone metastasis.
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Metastases of uveal melanoma (UM) spread predominantly to the liver. Due to low response rates to systemic therapies, liver-directed therapies (LDT) are commonly used for tumor control. The impact of LDT on the response to systemic treatment is unknown. A total of 182 patients with metastatic UM treated with immune checkpoint blockade (ICB) were included in this analysis. Patients were recruited from prospective skin cancer centers and the German national skin cancer registry (ADOReg) of the German Dermatologic Cooperative Oncology Group (DeCOG). Two cohorts were compared: patients with LDT (cohort A, n = 78) versus those without LDT (cohort B, n = 104). Data were analyzed for response to treatment, progression-free survival (PFS), and overall survival (OS). The median OS was significantly longer in cohort A than in cohort B (20.1 vs. 13.8 months; P = 0.0016) and a trend towards improved PFS was observed for cohort A (3.0 vs. 2.5 months; P = 0.054). The objective response rate to any ICB (16.7% vs. 3.8%, P = 0.0073) and combined ICB (14.1% vs. 4.5%, P = 0.017) was more favorable in cohort A. Our data suggest that the combination of LDT with ICB may be associated with a survival benefit and higher treatment response to ICB in patients with metastatic UM.
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Inibidores de Checkpoint Imunológico , Neoplasias Cutâneas , Humanos , Antígeno CTLA-4 , Inibidores de Checkpoint Imunológico/uso terapêutico , Fígado , Estudos ProspectivosRESUMO
BACKGROUND: Uveal melanoma is an orphan malignancy with very limited data on treatment options in metastatic setting. METHODS: In this single-center retrospective study, we describe real-world epidemiological and survival data on 121 metastatic uveal melanoma (MUM) patients registered in our institution. As a large tertiary referral center, almost 30% of all diagnoses in the Flemish region of Belgium were covered. Primarily, we determined whether introduction of immune checkpoint inhibitors (ICI) led to improved overall survival (OS) in MUM patients. Secondarily, response rates to ICI were assessed and we evaluated whether first-line ICI could be a valid alternative to liver-directed therapy (LDT) in liver-only disease. RESULTS: The initially perceived 10.8 months survival benefit from treatment with ICI disappeared after correction for immortality bias. By analyzing treatment type as time-varying covariate on OS, no significant benefit of ICI over other systemic therapies (HR = 0.771) or best supportive care (BSC) (HR = 0.780) was found. Also comparison of the pre-ICI versus ICI era showed no OS improvement after introduction of ICI in our center (p = 0.7994). Only liver-directed and local oligometastatic approaches were associated with a lower chance of mortality when compared to ICI (p = 0.0025), other systemic therapies (p = 0.0001) and BSC (p = 0.0003), yet without correction for selection bias. We reported overall response rates on ICI ranging from 8-15% and we found some support for neoadjuvant strategies with ICI resulting in remission or downsizing, allowing oligometastatic approaches later on. In first-line liver-only disease, median real-world progression-free survival and OS did not significantly differ between patients treated with LDT or ICI upfront (p = 0.2930 and p = 0.5461 respectively). CONCLUSION: Although we documented responses to ICI, our analyses do not demonstrate an OS benefit of ICI over alternative treatment strategies for MUM. However, local treatment options, whether liver-directed or for oligometastatic disease, may be beneficial and should be considered.
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Melanoma , Neoplasias Uveais , Humanos , Estudos Retrospectivos , Inibidores de Checkpoint Imunológico/uso terapêutico , Melanoma/patologia , Neoplasias Uveais/tratamento farmacológico , Neoplasias Uveais/patologiaRESUMO
BACKGROUND AND OBJECTIVE: Intrahepatic cholangiocarcinoma (ICC) is an aggressive primary hepatic malignancy, which has increased in incidence over the past decades. While surgical resection is the standard of care for patients with early-staged disease, many patients present with locally advanced and unresectable tumors. Given the importance of locoregional control and the potential for downstaging to resectability, knowledge of advances in the management of locally advanced ICC is critical for optimizing outcomes. METHODS: This is a narrative review providing an up-to-date summary of the current literature regarding contemporary management of locally advanced ICC including systemic and liver-directed therapies. KEY CONTENT AND FINDINGS: Along with systemic chemotherapy, several liver-directed therapies including transarterial chemoembolization, transarterial radioembolization, and hepatic artery infusion pumps, targeted therapies, and chemoradiation therapy have demonstrated promising results for improving local disease control and possibly extending survival. Unfortunately, successful downstaging to resection remains uncommon with no single treatment strategy established as standard of care. Although additional randomized controlled data are needed, multidisciplinary management using contemporary systemic and locoregional therapies improves outcomes for patients with locally advanced ICC. CONCLUSIONS: The optimal management of locally advanced ICC remains uncertain. Despite this, novel treatment options and ongoing clinical trials are currently contributing to more effective treatment and improved patient outcomes. Future advancements are likely to explore further novel therapies in addition to elucidating optimal patient selection and sequencing of multidisciplinary therapy.
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Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Colangiocarcinoma , Neoplasias Hepáticas , Humanos , Colangiocarcinoma/terapia , Neoplasias dos Ductos Biliares/terapia , Ductos Biliares Intra-HepáticosRESUMO
In transarterial radioembolization (TARE) of hepatocellular carcinoma (HCC) with Yttrium-90 (Y-90) microspheres, recent studies correlate dosimetry from bremsstrahlung single photon emission tomography (SPECT/CT) with treatment outcomes; however, these studies focus on measures of central tendency rather than volumetric coverage metrics commonly used in radiation oncology. We hypothesized that three-dimensional (3D) isodose coverage of gross tumor volume (GTV) is the driving factor in HCC treatment response to TARE and is best assessed using advanced dosimetry techniques applied to nuclear imaging of actual Y-90 biodistribution. We reviewed 51 lobar TARE Y-90 treatments of 43 HCC patients. Dose prescriptions were 120 Gy for TheraSpheres and 85 Gy for SIR-Spheres. All patients underwent post-TARE Y-90 bremsstrahlung SPECT/CT imaging. Commercial software was used to contour gross tumor volume (GTV) and liver on post-TARE SPECT/CT. Y-90 dose distributions were calculated using the Local Deposition Model based on post-TARE SPECT/CT activity maps. Median gross tumor volume (GTV) dose; GTV receiving less than 100 Gy, 70 Gy and 50 Gy; minimum dose covering the hottest 70%, 95%, and 98% of the GTV (D70, D95, D98); mean dose to nontumorous liver, and disease burden (GTV/liver volume) were obtained. Clinical outcomes were collected for all patients by chart and imaging review. HCC treatment response was assessed according to the modified response criteria in solid tumors (mRECIST) guidelines. Kaplan-Meier (KM) survival estimates and multivariate regression analyses (MVA) were performed using STATA. Median survival was 22.5 months for patients achieving objective response (OR) in targeted lesions (complete response (CR) or partial response (PR) per mRECIST) vs. 7.6 months for non-responders (NR, stable disease or disease progression per mRECIST). On MVA, the volume of underdosed tumor (GTV receiving less than 100 Gy) was the only significant dosimetric predictor for CR (p = 0.0004) and overall survival (OS, p = 0.003). All targets with less than CR (n = 39) had more than 20 cc of underdosed tumor. D70 (p = 0.038) correlated with OR, with mean D70 of 95 Gy for responders and 60 Gy for non-responders (p = 0.042). On MVA, mean dose to nontumorous liver trended toward significant association with grade 3+ toxicity (p = 0.09) and correlated with delivered activity (p < 0.001) and burden of disease (p = 0.05). Dosimetric models supplied area under the curve estimates of > 0.80 predicting CR, OR, and ≥grade 3 acute toxicity. Dosimetric parameters derived from the retrospective analysis of post-TARE Y-90 bremsstrahlung SPECT/CT after lobar treatment of HCC suggest that volumetric coverage of GTV, not a high mean or median dose, is the driving factor in treatment response and that this is best assessed through the analysis of actual Y-90 biodistribution.
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The surgical management of primary and secondary liver tumors is constantly evolving. Patient selection, particularly with regard to determining resectability, is vital to the success of programs directed toward invasive treatments of liver tumors. Particular attention should be paid toward determining whether patients are best served with surgical resection or ablative therapies. A multidisciplinary approach is necessary to provide optimal care to patients with liver malignancy.
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Pancreatic neuroendocrine tumors (PNETs) are described by the World Health Organization (WHO) classification by grade (1-3) and degree of differentiation. Grade 1 and 2; well differentiated PNETs are often characterized as relatively "indolent" tumors for which locoregional therapies have been shown to be effective for palliation of symptom control and prolongation of survival even in the setting of advanced disease. The treatment of liver metastases includes surgical and non-surgical modalities with varying degrees of invasiveness; efficacy; and risk. Most of these modalities have not been prospectively compared. This paper reviews literature that has been published on treatment of pancreatic neuroendocrine liver metastases using surgery; liver directed embolization and peptide receptor radionuclide therapy (PRRT). Surgery is associated with the longest survival in patients with resectable disease burden. Liver-directed (hepatic artery) therapies can sometimes convert patients with borderline disease into candidates for surgery. Among the three embolization modalities; the preponderance of data suggests chemoembolization offers superior radiographic response compared to bland embolization and radioembolization; but all have similar survival. PRRT was initially approved as salvage therapy in patients with advanced disease that was not amenable to resection or embolization; though the role of PRRT is evolving rapidly.
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Cholangiocarcinomas (CCA) are a group of rare cancers with an incidence of about 1.26 per 100,000 people. The disease reflects one of three different subtypes: intrahepatic, perihilar or hilar and distal cholangiocarcinoma. The preferred modality of definitive therapy is surgical resection with or without adjuvant therapy, however the majority of patients with this disease do not present at an early stage. Some efforts to improve survival rates have come in the form of offering neoadjuvant therapy prior to surgical resection or liver transplantation. Some new protocols are in the process of development for neoadjuvant therapy. Despite advancements in locally advanced or borderline resectable lesions, most patient present at an advanced stage. The mainstay of treatment for advanced stage disease is chemotherapy regardless of location. The mainstay of treatment in fit patients is the combination of gemcitabine and cisplatin. The addition of nab-paclitaxel to this backbone is currently being evaluated in phase III trial. In addition, the role of targeted therapy is currently being studied extensively through multiple different mutational pathways including isocitrate dehydrogenase-1 (IDH1), fibroblast growth factor receptor (FGFR), epidermal growth factor receptor (EGFR) and ERBB2 (HER2/neu). CCA remains a significant challenge in medicine, however recent studies have shown that there is significant interest in advancing therapy in the form of neoadjuvant, adjuvant and palliative intent treatment.
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Background: Distant recurrence of esophageal cancer (EC), even after radical resection, is common, and the most frequent site of EC metastasis is the liver. However, a multidisciplinary treatment strategy for postoperative liver metastasis (LM) from EC has yet to be established; in particular, the role of liver-directed therapy (LDT) remains uncertain. We investigated the clinicopathological features and outcomes of patients undergoing post-esophagectomy LM with versus without LDT to explore its therapeutic implications. Methods: Among 624 consecutive patients undergoing R0/R1 esophagectomy for EC, 30 were identified in whom LM had developed as the initial recurrence. Their characteristics were retrospectively reviewed. Results: Six of the 30 subjects underwent LDT for metachronous LM. Five of those 6 also received systemic chemotherapy. A comparison between the 6 LDT and 24 non-LDT cases revealed no significant differences in major clinicopathological and operative factors, except for concurrent metastasis to extrahepatic organs (1/6 vs. 15/24, p=0.044). Twenty-nine of the 30 patients died during the study period, whereas 1 who had received multimodal treatment with LDT remained alive more than 200 months after multiple LM had been detected. Kaplan-Meier analysis for survival after LM demonstrated significantly prolonged survival in LDT cases compared to non-LDT cases treated with systemic chemotherapy alone (p=0.014). Even when the analysis was limited to patients without extrahepatic metastasis, this significant prognostic advantage of LDT was maintained (p=0.047). Conclusion: Multimodal treatment combined with LDT might be beneficial for patients with metachronous LM from EC and should therefore be considered a potential treatment option.
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Intermediate-stage hepatocellular carcinoma (HCC) consists of heterogeneous groups of patients in terms of tumor burden and organ function reserves. Although liver-directed therapy (LDT), including trans-catheter arterial chemoembolization, radiofrequency ablation or even surgical resection, is the recommended frontline treatment modality, intrahepatic and distant failures are common. The recent advances in systemic treatment, notably the introduction of immune checkpoint inhibitor (ICI)-based therapy, have significantly improved the objective tumor response rate, quality of response and overall survival in patients with recurrent and advanced HCC. Whether the combination of systemic treatment and LDT can further improve the outcome of patients with intermediate-stage HCC is currently being extensively evaluated. In this article, the recent clinical trials incorporating different ICI-based combinations with different LDT for intermediate-stage HCC were reviewed focusing on trial design issues, including patient selection, endpoint definition, and biomarker development. The strength and caveats of different combination strategies and novel biomarker development were discussed.
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BACKGROUND AND OBJECTIVES: Colorectal liver metastasis (CRLM) is a leading cause of morbidity and mortality in patients with colorectal cancer. Hepatic arterial infusion (HAI) chemotherapy has been demonstrated to improve survival in patients with resected CRLM and to facilitate conversion of technically unresectable disease. METHODS: Between 2016 and 2018, n = 22 HAI pumps were placed for CRLM. All patients received systemic chemotherapy concurrently with HAI floxuridine/dexamethasone. Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method. RESULTS: HAI pumps were placed in seven patients with completely resected CRLM and 15 patients with unresectable disease. Twenty-one patients received HAI floxuridine with a median of 5 total HAI cycles (interquartile range: 4-7). Biliary sclerosis was the most common HAI-related complication (n = 5, 24%). Of the 13 patients treated to convert unresectable CRLM, 3 (23%) underwent hepatic resection with curative intent after a median of 7 HAI cycles (range: 4-10). For all HAI patients, the mean OS was 26.7 months from CRLM diagnosis, while the median PFS and hepatic PFS from pump placement were 9 and 13 months, respectively. CONCLUSION: Concomitant HAI and systemic therapy can be utilized at multidisciplinary programs for patients with advanced CRLM, both in the adjuvant setting and to facilitate conversion of unresectable disease.