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PURPOSE: To correlate irreversible electroporation (IRE) procedural resistance changes with survival outcomes and the IRE-induced systemic immune response in patients with locally advanced pancreatic cancer (LAPC). MATERIALS AND METHODS: Data on IRE procedural tissue resistance (R) features and survival outcomes were collected from patients with LAPC treated within the context of 2 prospective clinical trials in a single tertiary center. Preprocedural and postprocedural peripheral blood samples were prospectively collected for immune monitoring. The change (ie, decrease) in R during the first 10 test pulses (ΔR10p) and during the total procedure (ΔRtotal) were calculated. Patients were divided in 2 groups on the basis of the median change in R (large ΔR vs small ΔR) and compared for differences in overall survival (OS) and progression-free survival and immune cell subsets. RESULTS: A total of 54 patients were included; of these, 20 underwent immune monitoring. Linear regression modeling showed that the first 10 test pulses reflected the change in tissue resistance during the total procedure appropriately (P < .001; R2 = 0.91). A large change in tissue resistance significantly correlated with a better OS (P = .026) and longer time to disease progression (P = .045). Furthermore, a large change in tissue resistance was associated with CD8+ T cell activation through significant upregulation of Ki-67+ (P = .02) and PD-1+ (P = .047). Additionally, this subgroup demonstrated significantly increased expression of CD80 on conventional dendritic cells (cDC1; P = .027) and PD-L1 on immunosuppressive myeloid-derived suppressor cells (P = .039). CONCLUSIONS: IRE procedural resistance changes may serve as a biomarker for survival and IRE-induced systemic CD8+ T cell and cDC1 activation.
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Neoplasias Pancreáticas , Humanos , Estudios Prospectivos , Neoplasias Pancreáticas/terapia , Electroporación/métodos , Inmunidad Adaptativa , Biomarcadores , Neoplasias PancreáticasRESUMEN
OBJECTIVE: To evaluate the incidence, diagnostic management strategies and clinical outcomes of women with spontaneous haemoperitoneum in pregnancy (SHiP) and reassess the definition of SHiP. DESIGN: A population-based cohort study using the Netherlands Obstetric Surveillance System (NethOSS). SETTING: Nationwide, the Netherlands. POPULATION: All pregnant women between April 2016 and April 2018. METHODS: This is a case study of SHiP using the monthly registry reports of NethOSS. Complete anonymised case files were obtained. A newly introduced online Delphi audit system (DAS) was used to evaluate each case, to make recommendations on improving the management of SHiP and to propose a new definition of SHiP. MAIN OUTCOME MEASURES: Incidence and outcomes, lessons learned about clinical management and the critical appraisal of the current definition of SHiP. RESULTS: In total, 24 cases were reported. After a Delphi procedure, 14 cases were classified as SHiP. The nationwide incidence was 4.9 per 100 000 births. Endometriosis and conceiving after artificial reproductive techniques were identified as risk factors. No maternal and three perinatal deaths occurred. Based on the DAS, adequate imaging of free intra-abdominal fluid, and identifying and treating women with signs of hypovolemic shock could improve the early detection and management of SHiP. A revised definition of SHiP was proposed, excluding the need for surgical or radiological intervention. CONCLUSIONS: SHiP is a rare and easily misdiagnosed condition that is associated with high perinatal mortality. To improve care, better awareness among healthcare workers is needed. The DAS is a sufficient tool to audit maternal morbidity and mortality.
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Hemoperitoneo , Muerte Perinatal , Complicaciones del Embarazo , Femenino , Humanos , Embarazo , Estudios de Cohortes , Hemoperitoneo/diagnóstico , Hemoperitoneo/epidemiología , Hemoperitoneo/etiología , Parto , Mortalidad Perinatal , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/etiología , Recién NacidoRESUMEN
PURPOSE OF REVIEW: Based on good local control rates and an excellent safety profile, guidelines consider thermal ablation the gold standard to eliminate small unresectable colorectal liver metastases (CRLM). However, efficacy decreases exponentially with increasing tumour size. The preferred treatment for intermediate-size unresectable CRLM remains uncertain. This systematic review and meta-analysis compare safety and efficacy of local ablative treatments for unresectable intermediate-size CRLM (3-5 cm). RECENT FINDINGS: We systematically searched for publications reporting treatment outcomes of unresectable intermediate-size CRLM treated with thermal ablation, irreversible electroporation (IRE) or stereotactic ablative body-radiotherapy (SABR). No comparative studies or randomized trials were found. Literature to assess effectiveness was limited and there was substantial heterogeneity in outcomes and study populations. Per-patient local control ranged 22-90% for all techniques; 22-89% (8 series) for thermal ablation, 44% (1 series) for IRE, and 67-90% (1 series) for SABR depending on radiation dose. Focal ablative therapy is safe and can induce long-term disease control, even for intermediate-size CRLM. Although SABR and tumuor-bracketing techniques such as IRE are suggested to be less susceptible to size, evidence to support any claims of superiority of one technique over the other is unsubstantiated by the available evidence. Future prospective comparative studies should address local-tumour-progression-free-survival, local control rate, overall survival, adverse events, and quality-of-life.
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Neoplasias Colorrectales , Neoplasias Hepáticas , Ablación por Radiofrecuencia , Neoplasias Colorrectales/patología , Electroporación/métodos , Humanos , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Microondas , Ablación por Radiofrecuencia/métodosRESUMEN
OBJECTIVE: This study compared median OS after resection of LAPC after upfront FOLFIRINOX versus a propensity-score matched cohort of LAPC patients treated with FOLFIRINOX-only (ie, without resection). BACKGROUND: Because the introduction of FOLFIRINOX chemotherapy, increased resection rates in LAPC patients have been reported, with improved OS. Some studies have also reported promising OS with FOLFIRINOX-only treatment in LAPC. Multicenter studies assessing the survival benefit associated with resection of LAPC versus patients treated with FOLFIRINOX-only are lacking. METHODS: Patients with non-progressive LAPC after 4 cycles of FOLFIRINOX treatment, both with and without resection, were included from a prospective multicenter cohort in 16 centers (April 2015-December 2019). Cox regression analysis identified predictors for OS. One-to-one propensity score matching (PSM) was used to obtain a matched cohort of patients with and without resection. These patients were compared for OS. RESULTS: Overall, 293 patients with LAPC were included, of whom 89 underwent a resection. Resection was associated with improved OS (24 vs 15âmonths, P < 0.01), as compared to patients without resection. Before PSM, resection, Charlson Comorbidity Index, and Response Evaluation Criteria in Solid Tumors (RECIST) response were predictors for OS. After PSM, resection remained associated with improved OS [Hazard Ratio (HR) 0.344, 95% confidence interval (0.222-0.534), P < 0.01], with an OS of 24 versus 15âmonths, as compared to patients without resection. Resection of LAPC was associated with improved 3-year OS (31% vs 11%, P < 0.01). CONCLUSIONS: Resection of LAPC after FOLFIRINOX was associated with increased OS and 3-year survival, as compared to propensity-score matched patients treated with FOLFIRINOX-only.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estadificación de Neoplasias , Páncreas/patología , Pancreatectomía/métodos , Neoplasias Pancreáticas/mortalidad , Puntaje de Propensión , Antineoplásicos/uso terapéutico , Femenino , Fluorouracilo/uso terapéutico , Estudios de Seguimiento , Humanos , Irinotecán/uso terapéutico , Leucovorina/uso terapéutico , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Oxaliplatino/uso terapéutico , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Estudios Prospectivos , Tasa de Supervivencia/tendenciasRESUMEN
Background Irreversible electroporation (IRE), an ablative technique that uses high-voltage electrical pulses, has shown promise for eradicating tumors near critical structures, including blood vessels and bile ducts. Purpose To investigate the efficacy and safety of IRE for colorectal liver metastases (CRLMs) unsuitable for resection or thermal ablation because of proximity to critical structures and for further systemically administered treatments. Materials and Methods Between June 2014 and November 2018, participants with fluorine 18 (18F) fluorodeoxyglucose (FDG) PET-avid CRLMs measuring 5.0 cm or smaller, unsuitable for partial hepatectomy and thermal ablation, underwent percutaneous or open IRE (ClinicalTrials.gov identifier: NCT02082782). Follow-up included tumor marker assessment and 18F-FDG PET/CT imaging. For the primary end point to be met, at least 50% of treated participants had to be alive without local tumor progression (LTP) at 12 months, defined as LTP-free survival. Secondary aims were safety, technical success, local control allowing for repeat procedures, disease-free status, and overall survival. Results A total of 51 participants (median age, 67 years [interquartile range, 62-75 years]; 37 men) underwent IRE. Of these 51 participants, 50 with a total of 76 CRLMs (median tumor size, 2.2 cm; range, 0.5-5.4 cm) were successfully treated in 62 procedures; in one participant, treatment was stopped prematurely because of pulse-induced cardiac arrhythmia. With a per-participant 1-year LTP-free survival of 68% (95% CI: 59, 84) according to competing risk analysis, the primary end point was met. Local control following repeat procedures was achieved in 74% of participants (37 of 50). Median overall survival from first IRE was 2.7 years (95% CI: 1.6, 3.8). Twenty-three participants experienced a total of 34 adverse events in 25 of the 62 procedures (overall complication rate, 40%). One participant (2%), who had an infected biloma after IRE, died fewer than 90 days after the procedure (grade 5 adverse event). Conclusion Irreversible electroporation was effective and relatively safe for colorectal liver metastases 5.0 cm or smaller that were unsuitable for partial hepatectomy, thermal ablation, or further systemic treatment. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Goldberg in this issue.
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Neoplasias Colorrectales/patología , Electroporación/métodos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/terapia , Anciano , Femenino , Fluorodesoxiglucosa F18 , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , RadiofármacosRESUMEN
BACKGROUND AND OBJECTIVES: Patients with locally advanced pancreatic cancer (LAPC) are increasingly treated with FOLFIRINOX, resulting in improved survival and resection of tumors that were initially unresectable. It remains unclear, however, which specific patients benefit from FOLFIRINOX. Two nomograms were developed predicting overall survival (OS) and resection at the start of FOLFIRINOX for LAPC. METHODS: From our multicenter, prospective LAPC registry in 14 Dutch hospitals, LAPC patients starting first-line FOLFIRINOX (April 2015-December 2017) were included. Stepwise backward selection according to the Akaike Information Criterion was used to identify independent baseline predictors for OS and resection. Two prognostic nomograms were generated. RESULTS: A total of 252 patients were included, with a median OS of 14 months. Thirty-two patients (13%) underwent resection, with a median OS of 23 months. Older age, female sex, Charlson Comorbidity Index ≤1, and CA 19.9 < 274 were independent factors predicting a better OS (c-index: 0.61). WHO ps >1, involvement of the superior mesenteric artery, celiac trunk, and superior mesenteric vein ≥ 270° were independent factors decreasing the probability of resection (c-index: 0.79). CONCLUSIONS: Two nomograms were developed to predict OS and resection in patients with LAPC before starting treatment with FOLFIRINOX. These nomograms could be beneficial in the shared decision-making process and counseling of these patients.
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Adenocarcinoma/mortalidad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Nomogramas , Pancreatectomía/mortalidad , Neoplasias Pancreáticas/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/terapia , Anciano , Terapia Combinada , Femenino , Fluorouracilo/uso terapéutico , Estudios de Seguimiento , Humanos , Irinotecán/uso terapéutico , Leucovorina/uso terapéutico , Masculino , Persona de Mediana Edad , Oxaliplatino/uso terapéutico , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/terapia , Pronóstico , Estudios Prospectivos , Tasa de SupervivenciaRESUMEN
PURPOSE OF REVIEW: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive neoplasms, bearing a terrible prognosis. Stage III tumors, also known as locally advanced pancreatic cancer (LAPC), are unresectable, and current palliative chemotherapy regimens have only modestly improved survival in these patients. At this stage of disease, interventional techniques may be of value and further prolong life. The aim of this review was to explore current literature on locoregional percutaneous management for LAPC. RECENT FINDINGS: Locoregional percutaneous interventional techniques such as ablation, brachytherapy, and intra-arterial chemotherapy possess cytoreductive abilities and have the potential to increase survival. In addition, recent research demonstrates the immunomodulatory capacities of these treatments. This immune response may be leveraged by combining the interventional techniques with intra-tumoral immunotherapy, possibly creating a durable anti-tumor effect. This multimodality treatment approach is currently being examined in several ongoing clinical trials. The use of certain interventional techniques appears to improve survival in LAPC patients and may work synergistically when combined with immunotherapy. However, definitive conclusions can only be made when large prospective (randomized controlled) trials confirm these results.
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Técnicas de Ablación/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Braquiterapia/métodos , Inmunoterapia/métodos , Neoplasias Pancreáticas/terapia , Terapia Combinada , Humanos , Infusiones IntraarterialesRESUMEN
Background Patients with locally advanced pancreatic cancer have a dismal prognosis, with a median overall survival (OS) of 12-14 months with systemic therapies. Irreversible electroporation (IRE), a nonthermal ablative technique, may prolong survival of patients with locally advanced pancreatic cancer. Purpose To investigate the safety and efficacy of percutaneous IRE for locally advanced pancreatic cancer and locally recurring pancreatic cancer in a prospective phase II trial. Materials and Methods Between December 2012 and September 2017, participants with locally advanced pancreatic cancer or postresection local recurrence were prospectively treated with percutaneous CT-guided IRE (ClinicalTrials.gov identifier: NCT01939665). The primary end point was median OS from diagnosis. The target median OS was 11.6 months for participants receiving no induction chemotherapy or gemcitabine-based induction chemotherapy and 14.9 months for those receiving induction 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX). Results Fifty participants (25 men and 25 women; median age, 61 years [interquartile range, 56-69 years]; 40 with locally advanced pancreatic cancer and 10 with local recurrence) were included. Median OS measured by using the Kaplan-Meier method was 17 months from diagnosis of locally advanced pancreatic cancer (95% confidence interval [CI]: 15 months, 19 months) and 10 months from IRE (95% CI: 8 months, 11 months). In the locally advanced pancreatic cancer group, 18 participants received no therapy or gemcitabine-based induction chemotherapy and 22 received FOLFIRINOX. The median OS from diagnosis was 17 months for both groups (95% CI: 7 months, 28 months and 15 months, 18 months, respectively; P = .26). For participants with postresection local recurrence, the median OS was 16 months from diagnosis of recurrence (95% CI: 11 months, 22 months) and 9 months from IRE (95% CI: 2 months, 16 months). After IRE, local recurrence developed in 23 of the 50 participants (46%). Tumor volume of 37 cm3 or greater (hazard ratio [HR], 2.9; P = .02), pre-IRE carbohydrate antigen 19-9 (CA 19-9) level of 2000 U/mL or greater (HR, 12.1; P = .001), and decrease in CA 19-9 level of 50% or less 3 months after IRE (HR, 3.1; P = .01) were predictors of worse survival. Fourteen minor and 21 major complications occurred in 29 of the 50 participants (58%). Two participants died less than 90 days after IRE; one of these deaths was likely related to IRE. Conclusion The target median overall survival with CT-guided percutaneous irreversible electroporation was exceeded in participants with locally advanced pancreatic cancer (17 months) and those with local recurrence (16 months). © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Goldberg in this issue.
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Electroporación/métodos , Recurrencia Local de Neoplasia/terapia , Neoplasias Pancreáticas/terapia , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico por imagen , Páncreas/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico por imagen , Estudios Prospectivos , Radiografía Intervencional/métodos , Análisis de Supervivencia , Tomografía Computarizada por Rayos X/métodos , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate safety and efficacy of CT hepatic arteriography compared with conventional CT fluoroscopy guidance in percutaneous radiofrequency (RF) and microwave (MW) ablation to treat colorectal liver metastases (CRLM). MATERIALS AND METHODS: This single-center comparative, retrospective study analyzed data of 108 patients treated with 156 percutaneous ablation procedures (42 CT fluoroscopy guidance [25 RF ablation, 17 MW ablation]; 114 CT hepatic arteriography guidance [18 RF ablation, 96 MW ablation]) for 260 CRLM between January 2009 and May 2019. Local tumor progression-free survival (LTPFS) was assessed using univariate and multivariate Cox proportional hazard regression analyses. LTPFS and overall survival (OS) were estimated using the Kaplan-Meier method. RESULTS: There were no complications related to the transarterial catheter procedure. CT hepatic arteriography proved superior to CT fluoroscopy regarding 2-year LTPFS (18/202 [8.9%] vs 19/58 [32.8%]; P < .001, respectively). CT hepatic arteriography versus CT fluoroscopy (hazard ratio = 0.28; 95% confidence interval, 0.15-0.54; P < .001) and MW ablation versus RF ablation (hazard ratio = 0.52; 95% confidence interval, 0.24-1.12; P = .094) were positive predictors for longer LTPFS. Multivariate analysis revealed that CT hepatic arteriography versus CT fluoroscopy (hazard ratio = 0.41; 95% confidence interval, 0.19-0.90; P = .025) was associated with a significantly superior LTPFS. OS was similar between the 2 cohorts (P = .3). CONCLUSIONS: While adding procedure time and marginal patient burden, transcatheter CT hepatic arteriography-guided ablation was associated with increased local disease control and superior LTPFS compared with conventional CT fluoroscopy. CT hepatic arteriography represents a safe and valid alternative to CT fluoroscopy, as it reduces the number of repeat ablations required without adding risk or detrimental effect on survival.
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Técnicas de Ablación , Neoplasias Colorrectales/patología , Angiografía por Tomografía Computarizada , Neoplasias Hepáticas/cirugía , Radiografía Intervencional , Técnicas de Ablación/efectos adversos , Técnicas de Ablación/mortalidad , Anciano , Neoplasias Colorrectales/mortalidad , Angiografía por Tomografía Computarizada/efectos adversos , Angiografía por Tomografía Computarizada/mortalidad , Femenino , Fluoroscopía , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Países Bajos , Tempo Operativo , Supervivencia sin Progresión , Radiografía Intervencional/efectos adversos , Radiografía Intervencional/mortalidad , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Factores de TiempoRESUMEN
BACKGROUND: Radiofrequency ablation (RFA) and microwave ablation (MWA) are widely accepted techniques to eliminate small unresectable colorectal liver metastases (CRLM). Although previous studies labelled thermal ablation inferior to surgical resection, the apparent selection bias when comparing patients with unresectable disease to surgical candidates, the superior safety profile, and the competitive overall survival results for the more recent reports mandate the setup of a randomized controlled trial. The objective of the COLLISION trial is to prove non-inferiority of thermal ablation compared to hepatic resection in patients with at least one resectable and ablatable CRLM and no extrahepatic disease. METHODS: In this two-arm, single-blind multi-center phase-III clinical trial, six hundred and eighteen patients with at least one CRLM (≤3 cm) will be included to undergo either surgical resection or thermal ablation of appointed target lesion(s) (≤3 cm). Primary endpoint is OS (overall survival, intention-to-treat analysis). Main secondary endpoints are overall disease-free survival (DFS), time to progression (TTP), time to local progression (TTLP), primary and assisted technique efficacy (PTE, ATE), procedural morbidity and mortality, length of hospital stay, assessment of pain and quality of life (QoL), cost-effectiveness ratio (ICER) and quality-adjusted life years (QALY). DISCUSSION: If thermal ablation proves to be non-inferior in treating lesions ≤3 cm, a switch in treatment-method may lead to a reduction of the post-procedural morbidity and mortality, length of hospital stay and incremental costs without compromising oncological outcome for patients with CRLM. TRIAL REGISTRATION: NCT03088150 , January 11th 2017.
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Neoplasias Colorrectales/cirugía , Neoplasias Hepáticas/cirugía , Hígado/cirugía , Adulto , Anciano , Ablación por Catéter/efectos adversos , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Femenino , Hepatectomía/efectos adversos , Humanos , Hígado/patología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Años de Vida Ajustados por Calidad de Vida , Resultado del TratamientoRESUMEN
Liver tumour ablation nowadays represents a routine treatment option for patients with primary and secondary liver tumours. Radiofrequency ablation and microwave ablation are the most widely adopted methods, although novel techniques, such as irreversible electroporation, are quickly working their way up. The percutaneous approach is rapidly gaining popularity because of its minimally invasive character, low complication rate, good efficacy rate, and repeatability. However, matched to partial hepatectomy and open ablations, the issue of ablation site recurrences remains unresolved and necessitates further improvement. For percutaneous liver tumour ablation, several real-time imaging modalities are available to improve tumour visibility, detect surrounding critical structures, guide applicators, monitor treatment effect, and, if necessary, adapt or repeat energy delivery. Known predictors for success are tumour size, location, lesion conspicuity, tumour-free margin, and operator experience. The implementation of reliable endpoints to assess treatment efficacy allows for completion-procedures, either within the same session or within a couple of weeks after the procedure. Although the effect on overall survival may be trivial, (local) progression-free survival will indisputably improve with the implementation of reliable endpoints. This article reviews the available needle navigation techniques, evaluates potential treatment endpoints, and proposes an algorithm for quality control after the procedure.
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Técnicas de Ablación/métodos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Control de Calidad , Radiología Intervencionista/métodos , Humanos , Hígado/diagnóstico por imagen , Hígado/cirugía , Resultado del TratamientoRESUMEN
With the rapidly evolving field of image-guided tumor ablation, there is an increasing demand and need for tools to optimize treatment success. Known factors affecting the success of (non-)thermal liver ablation procedures are the ability to optimize tumor and surrounding critical structure visualization, ablation applicator targeting, and ablation zone confirmation. A recent study showed superior local tumor progression-free survival and local control outcomes when using transcatheter computed tomography hepatic angiography (CTHA) guidance in percutaneous liver ablation procedures. This pictorial review provides eight clinical cases from three institutions, MD Anderson (Houston, TX, USA), Gustave Roussy (Paris, France), and Amsterdam UMC (Amsterdam, The Netherlands), with the intent to demonstrate the added value of real-time CTHA guided tumor ablation for primary liver tumors and liver-only metastatic disease. The clinical illustrations highlight the ability to improve the detectability of the initial target liver tumor(s) and identify surrounding critical vascular structures, detect 'vanished' and/or additional tumors intraprocedurally, differentiate local tumor progression from non-enhancing scar tissue, and promptly detect and respond to iatrogenic hemorrhagic events. Although at the cost of adding a minor but safe intervention, CTHA-guided liver tumor ablation minimizes complications of the actual ablation procedure, reduces the number of repeat ablations, and improves the oncological outcome of patients with liver malignancies. Therefore, we recommend adopting CTHA as a potential quality-improving guiding method within the (inter)national standards of practice.
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BACKGROUND: Pancreatic ductal adenocarcinoma is an aggressive disease with a dismal prognosis. Stage III locally advanced pancreatic cancer is considered unresectable and current palliative chemotherapy regimens only modestly improve survival. Guidelines suggest chemoradiation or stereotactic ablative body radiotherapy (SABR) could be beneficial in certain circumstances. Other local treatments such as irreversible electroporation could enhance patient outcomes by extending survival while preserving quality of life. We aimed to compare the efficacy and safety of MRI-guided SABR versus CT-guided percutaneous irreversible electroporation following standard FOLFIRINOX chemotherapy. METHODS: CROSSFIRE was an open-label, randomised phase 2 superiority trial conducted at the Amsterdam University Medical Centre (Amsterdam, Netherlands). Eligible patients were aged 18 years or older with confirmed histological and radiological stage III locally advanced pancreatic cancer. The maximum tumour diameter was 5 cm and patients had to be pretreated with three to eight cycles of FOLFIRINOX. Patients were randomly assigned (1:1) to MRI-guided SABR (five fractions of 8 Gy delivered on non-consecutive days) or CT-guided percutaneous irreversible electroporation using a computer-generated variable block randomisation model. The primary endpoint was overall survival from randomisation, assessed in the intention-to-treat population. Safety was assessed in the per-protocol population. A prespecified interim futility analysis was done after inclusion of half the original sample size, with a conditional probability of less than 0·2 resulting in halting of the study. The trial was registered at ClinicalTrials.gov, NCT02791503. FINDINGS: Between May 1, 2016, and March 31, 2022, 68 patients were enrolled and randomly assigned to SABR (n=34) or irreversible electroporation (n=34), of whom 64 were treated according to protocol. Of the 68 participants, 36 (53%) were male and 32 (47%) were female, with a median age of 65 years (IQR 57-70). Median overall survival from randomisation was 16·1 months (95% CI 12·1-19·4) in the SABR group versus 12·5 months (10·9-17·0) in the irreversible electroporation group (hazard ratio [HR] 1·39 [95% CI 0·84-2·30]; p=0·21). The conditional probability to demonstrate superiority of either technique was 0·13; patient accrual was therefore stopped early for futility. 20 (63%) of 32 patients in the SABR group versus 19 (59%) of 32 patients in the irreversible electroporation group had adverse events (p=0·8) and five (16%) patients in the SABR group versus eight (25%) in the irreversible electroporation group had grade 3-5 adverse events (p=0·35). The most common grade 3-4 adverse events were cholangitis (two [6%] in the SABR group vs one [3%] in the irreversible electroporation group), abdominal pain (one [3%] vs two [6%]), and pancreatitis (none vs two [6%]). One (3%) patient in the SABR group and one (3%) in the irreversible electroporation group died from a treatment-related adverse event. INTERPRETATION: CROSSFIRE did not identify a difference in overall survival or incidence of adverse events between MRI-guided SABR and CT-guided percutaneous irreversible electroporation after FOLFIRINOX. Future studies should further assess the added value of local ablative treatment over chemotherapy alone. FUNDING: Adessium Foundation, AngioDynamics.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Pancreáticas , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Resultado del Tratamiento , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/radioterapia , Calidad de Vida , Electroporación , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Although microwave ablation (MWA) has a low complication rate and good efficacy for small-size (≤ 3 cm) colorectal liver metastases (CRLM), local control decreases with increasing size. Stereotactic body radiotherapy (SBRT) is gaining interest as a potential means to treat intermediate-size CRLM and might be less susceptible to increasing volume. The objective of this study is to compare the efficacy of MWA to SBRT in patients with unresectable, intermediate-size (3-5 cm) CRLM. METHODS: In this two-arm, multicentre phase II/ III randomized controlled trial, 68 patients with 1-3 unresectable, intermediate-size CRLM suitable for both MWA and SBRT, will be included. Patients will be treated with MWA or SBRT as randomised. The Primary endpoint is local tumour progression-free survival (LTPFS) at 1 year (intention-to-treat analysis). Main secondary endpoints are overall survival, overall and distant progression-free survival (DPFS), local control (LC) and procedural morbidity and mortality and assessment of pain and quality of life. DISCUSSION: Current guidelines lack clear recommendations for the local treatment of liver only intermediate-size, unresectable CRLM and studies comparing curative intent SBRT and thermal ablation are scarce. Although safety and feasibility to eradicate tumours ≤ 5 cm have been established, both techniques suffer from lower LTPFS and LC rates for larger-size tumours. For the treatment of unresectable intermediate-size CRLM clinical equipoise has been reached. We have designed a two-armed phase II/ III randomized controlled trial directly comparing SBRT to MWA for unresectable CRLM 3-5 cm. LEVEL OF EVIDENCE: Level 1, phase II/ III Randomized controlled trial. TRIAL REGISTRATION: NCT04081168, September 9th 2019.
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Neoplasias Colorrectales , Neoplasias Hepáticas , Radiocirugia , Humanos , Ensayos Clínicos Fase II como Asunto , Neoplasias Colorrectales/patología , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/secundario , Microondas/uso terapéutico , Estudios Multicéntricos como Asunto , Calidad de Vida , Radiocirugia/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Ensayos Clínicos Fase III como AsuntoRESUMEN
PURPOSE: This study assessed the diagnostic value of CT hepatic arteriography (CTHA) for the intraprocedural detection of previously unknown colorectal liver metastases (CRLM) and the impact on the definitive treatment plan. MATERIALS AND METHODS: All patients treated with CTHA-guided percutaneous ablation for CRLM between January 2012 and March 2022 were identified from the Amsterdam Colorectal Liver Met Registry (AmCORE). Radiology reports of the ablative procedure and follow-up imaging were reviewed to see if (a) previously unknown CRLM were detected intra-procedurally and if (b) new CRLM, potentially missed on CTHA, appeared within 6 months following the procedure; three abdominal radiologists re-reviewed the baseline CTHA scans of these patients with early recurrence. To ratify immediate ablations of concomitantly detected CRLM, the upper limit of false positives was predefined at 10%. RESULTS: One hundred and fifty-two patients were included. With CTHA, a total of 17 additional tumours in 15 patients were diagnosed and treated immediately, two representing disappeared tumours following systemic chemotherapy. Compared to the conventional contrast-enhanced (ce)CT, ceMRI and 18F-FDG PET-CT, adding CTHA was superior for the detection of CRLM (P < .001). Within 12 months of follow-up 121, new CRLM appeared in 49/152 patients (32.2%); retrospective blinded assessment revealed 56 to already be visible on the baseline CTHA scan (46%); four lesions without substrate on follow-up scans were considered false positives (n = 4/60; 7%). Arterial ring enhancement was the most frequently reported imaging characteristic (n = 45/60; 75%). CONCLUSION: The subsequent use of CTHA has added value for the detection of previously unknown and vanished CRLM. Taking into account the low number of false positives (7%) and the favourable safety profile of percutaneous ablation, we believe that immediate ablation of typical ring-enhancing supplementary tumours is justified and sufficiently validated. LEVEL OF EVIDENCE: Level 3; individual cross-sectional study with consistently applied reference standard and blinding.
Asunto(s)
Ablación por Catéter , Neoplasias Colorrectales , Neoplasias Hepáticas , Humanos , Estudios Retrospectivos , Estudios Transversales , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias Colorrectales/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Angiografía , Tomografía Computarizada por Rayos X/métodos , Ablación por Catéter/métodosRESUMEN
BACKGROUND: Atherosclerotic renal artery stenosis (ARAS) is common in cardiovascular diseases and associated with hypertension, renal dysfunction and/or heart failure. There is a paucity of data about the prevalence and the role of ARAS in the pathophysiology of combined chronic heart failure (CHF) and chronic kidney disease (CKD). We investigated the prevalence in patients with combined CHF/CKD and its association with renal function, cardiac dysfunction and the presence and extent of myocardial fibrosis. METHODS: The EPOCARES study (ClinTrialsNCT00356733) investigates the role of erythropoietin in anaemic patients with combined CHF/CKD. Eligible subjects underwent combined cardiac magnetic resonance imaging (cMRI), including late gadolinium enhancement, with magnetic resonance angiography of the renal arteries (MRA). RESULTS: MR study was performed in 37 patients (median age 74 years, eGFR 37.4 ± 15.6 ml/min, left ventricular ejection fraction (LVEF) 43.3 ± 11.2%), of which 21 (56.8%) had ARAS (defined as stenosis >50%). Of these 21 subjects, 8 (21.6%) had more severe ARAS >70% and 8 (21.6%) had a bilateral ARAS >50% (or previous bilateral PTA). There were no differences in age, NT-proBNP levels and medication profile between patients with ARAS versus those without. Renal function declined with the severity of ARAS (p = 0.03), although this was not significantly different between patients with ARAS versus those without. Diabetes mellitus was more prevalent in patients without ARAS (56.3%) against those with ARAS (23.8%) (p = 0.04). The presence and extent of late gadolinium enhancement, depicting myocardial fibrosis, did not differ (p = 0.80), nor did end diastolic volume (p = 0.60), left ventricular mass index (p = 0.11) or LVEF (p = 0.15). Neither was there a difference in the presence of an ischemic pattern of late enhancement in patients with ARAS versus those without. CONCLUSIONS: ARAS is prevalent in combined CHF/CKD and its severity is associated with a decline in renal function. However, its presence does not correlate with a worse LVEF, a higher left ventricular mass or with the presence and extent of myocardial fibrosis. Further research is required for the role of ARAS in the pathophysiology of combined chronic heart and renal failure.
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Aterosclerosis/epidemiología , Síndrome Cardiorrenal/epidemiología , Insuficiencia Cardíaca/epidemiología , Imagen por Resonancia Magnética , Miocardio/patología , Obstrucción de la Arteria Renal/epidemiología , Insuficiencia Renal Crónica/epidemiología , Función Ventricular Izquierda , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/patología , Aterosclerosis/fisiopatología , Síndrome Cardiorrenal/tratamiento farmacológico , Síndrome Cardiorrenal/patología , Síndrome Cardiorrenal/fisiopatología , Distribución de Chi-Cuadrado , Medios de Contraste , Eritropoyetina/uso terapéutico , Femenino , Fibrosis , Tasa de Filtración Glomerular , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/patología , Insuficiencia Cardíaca/fisiopatología , Hematínicos/uso terapéutico , Humanos , Angiografía por Resonancia Magnética , Masculino , Meglumina , Persona de Mediana Edad , Países Bajos/epidemiología , Compuestos Organometálicos , Valor Predictivo de las Pruebas , Prevalencia , Pronóstico , Arteria Renal/patología , Obstrucción de la Arteria Renal/tratamiento farmacológico , Obstrucción de la Arteria Renal/patología , Obstrucción de la Arteria Renal/fisiopatología , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/patología , Insuficiencia Renal Crónica/fisiopatología , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Volumen SistólicoRESUMEN
BACKGROUND: To analyze long-term oncological outcomes of open and percutaneous thermal ablation in the treatment of patients with colorectal liver metastases (CRLM). METHODS: This assessment from a prospective, longitudinal tumor registry included 329 patients who underwent 541 procedures for 1350 CRLM from January 2010 to February 2021. Three cohorts were formed: 2010-2013 (129 procedures [53 percutaneous]), 2014-2017 (206 procedures [121 percutaneous]) and 2018-2021 (206 procedures [135 percutaneous]). Local tumor progression-free survival (LTPFS) and overall survival (OS) data were estimated using the Kaplan-Meier method. Potential confounding factors were analyzed with uni- and multivariable Cox regression analyses. RESULTS: LTPFS improved significantly over time for percutaneous ablations (2-year LTPFS 37.7% vs. 69.0% vs. 86.3%, respectively, P < .0001), while LTPFS for open ablations remained reasonably stable (2-year LTPFS 87.1% [2010-2013], vs. 92.7% [2014-2017] vs. 90.2% [2018-2021], P = .12). In the latter cohort (2018-2021), the open approach was no longer superior regarding LTPFS (P = .125). No differences between the three cohorts were found regarding OS (P = .088), length of hospital stay (open approach, P = .065; percutaneous approach, P = .054), and rate and severity of complications (P = .404). The rate and severity of complications favored the percutaneous approach in all three cohorts (P = .002). CONCLUSION: Over the last 10 years efficacy of percutaneous ablations has improved remarkably for the treatment of CRLM. Oncological outcomes seem to have reached results following open ablation. Given its minimal invasive character and shorter length of hospital stay, whenever feasible, percutaneous procedures may be favored over an open approach.
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Ablación por Catéter , Neoplasias Colorrectales , Neoplasias Hepáticas , Ablación por Catéter/métodos , Neoplasias Colorrectales/patología , Humanos , Neoplasias Hepáticas/secundario , Estudios Prospectivos , Sistema de Registros , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The prognosis of metastatic pancreatic ductal adenocarcinoma (mPDAC) remains universally poor, requiring new and innovative treatment approaches. In a subset of oligometastatic PDAC patients, locoregional therapy, in addition to systemic chemotherapy, may improve survival. The aim of this systematic review was to explore and evaluate the current evidence on locoregional treatments for mPDAC. A systematic literature search was conducted on locoregional techniques, including resection, ablation and embolization, for mPDAC with a focus on hepatic and pulmonary metastases. A total of 59 studies were identified, including 63,453 patients. Although subject to significant bias, radical-intent local therapy for both the primary and metastatic sites was associated with a superior median overall survival from metastatic diagnosis or treatment (hepatic mPDAC 7.8-19 months; pulmonary mPDAC 22.8-47 months) compared to control groups receiving chemotherapy or best supportive care (hepatic mPDAC 4.3-7.6 months; pulmonary mPDAC 11.8 months). To recruit patients that may benefit from these local treatments, selection appears essential. Most significant is the upfront possibility of local radical pancreatic and metastatic treatment. In addition, a patient's response to neoadjuvant systemic chemotherapy, performance status, metastatic disease load and, to a lesser degree, histological differentiation grade and tumor marker CA19-9 serum levels, are powerful prognostic factors that help identify eligible subjects. Although the exact additive value of locoregional treatments for mPDAC patients cannot be distillated from the results, locoregional primary pancreatic and metastatic treatment seems beneficial for a highly selected group of oligometastatic PDAC patients. For definite recommendations, well-designed prospective randomized controlled trials with strict in- and exclusion criteria are needed to validate these results.
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The aim of this study was to assess primary tumor sidedness of colorectal cancer (CRC), rat sarcoma viral oncogene homolog (RAS) and v-raf murine sarcoma viral oncogene homolog B (BRAF) mutations and microsatellite instability (MSI) status as prognostic factors predicting complications, survival outcomes, and local tumor progression (LTP) following surgery and thermal ablation in patients with colorectal liver metastases (CRLM). This Amsterdam Colorectal Liver Met Registry (AmCORE) based study included 520 patients, 774 procedures, and 2101 tumors undergoing local treatment (resection and/or thermal ablation) from 2000 to 2021. Outcomes following local treatment were analyzed for primary tumor sidedness of CRC, RAS, and BRAF mutations and MSI status. The Kaplan-Meier method was used to estimate local tumor progression-free survival (LTPFS), local control (LC), distant progression-free survival (DPFS), and overall survival (OS). Uni- and multivariable analyses were performed based on Cox proportional hazards model. The chi-square test was used to analyze complications. Complications (p = 0.485), OS (p = 0.252), LTPFS (p = 0.939), and LC (p = 0.423) was not associated with tumor-sidedness. Compared to right-sided colon cancer (CC) (reference HR 1.000), DPFS was superior for left-sided CC and rectal cancer (p = 0.018) with an HR for left-sided CC of 0.742 (95% CI, 0.596-0.923) and for RC of 0.760 (95% CI, 0.597-0.966). Regarding RAS mutations, no significant difference was found in OS (p = 0.116). DPFS (p = 0.001), LTPFS (p = 0.039), and LC (p = 0.025) were significantly lower in the RAS mutation group. Though no difference in LTPFS was found between RAS wildtype and RAS mutated CRLM following resection (p = 0.532), LTPFS was worse for RAS mutated tumors compared to RAS wildtype following thermal ablation (p = 0.037). OS was significantly lower in the BRAF mutation group (p < 0.001) and in the MSI group (p < 0.001) following local treatment, while both did not affect DPFS, LTPFS, and LC. This AmCORE based study suggests the necessity of wider margins to reduce LTP rates in patients with RAS mutated CRLM, especially for thermal ablation. Upfront knowledge regarding molecular biomarkers may contribute to improved oncological outcomes.
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This cohort study aimed to evaluate efficacy, safety, and survival outcomes of neoadjuvant chemotherapy (NAC) followed by repeat local treatment compared to upfront repeat local treatment of recurrent colorectal liver metastases (CRLM). A total of 152 patients with 267 tumors from the prospective Amsterdam Colorectal Liver Met Registry (AmCORE) met the inclusion criteria. Two cohorts of patients with recurrent CRLM were compared: patients who received chemotherapy prior to repeat local treatment (32 patients) versus upfront repeat local treatment (120 patients). Data from May 2002 to December 2020 were collected. Results on the primary endpoint overall survival (OS) and secondary endpoints local tumor progression-free survival (LTPFS) and distant progression-free survival (DPFS) were reviewed using the Kaplan-Meier method. Subsequently, uni- and multivariable Cox proportional hazard regression models, accounting for potential confounders, were estimated. Additionally, subgroup analyses, according to patient, initial and repeat local treatment characteristics, were conducted. Procedure-related complications and length of hospital stay were compared using chi-square test and Fisher's exact test. The 1-, 3-, and 5-year OS from date of diagnosis of recurrent disease was 98.6%, 72.5%, and 47.7% for both cohorts combined. The crude survival analysis did not reveal a significant difference in OS between the two cohorts (p = 0.834), with 1-, 3-, and 5-year OS of 100.0%, 73.2%, and 57.5% for the NAC group and 98.2%, 72.3%, and 45.3% for the upfront repeat local treatment group, respectively. After adjusting for two confounders, comorbidities (p = 0.010) and primary tumor location (p = 0.023), the corrected HR in multivariable analysis was 0.839 (95% CI, 0.416-1.691; p = 0.624). No differences between the two cohorts were found with regards to LTPFS (HR = 0.662; 95% CI, 0.249-1.756; p = 0.407) and DPFS (HR = 0.798; 95% CI, 0.483-1.318; p = 0.378). No heterogeneous treatment effects were detected in subgroup analyses according to patient, disease, and treatment characteristics. No significant difference was found in periprocedural complications (p = 0.843) and median length of hospital stay (p = 0.600) between the two cohorts. Chemotherapy-related toxicity was reported in 46.7% of patients. Adding NAC prior to repeat local treatment did not improve OS, LTPFS, or DPFS, nor did it affect periprocedural morbidity or length of hospital stay. The results of this comparative assessment do not substantiate the routine use of NAC prior to repeat local treatment of CRLM. Because the exact role of NAC (in different subgroups) remains inconclusive, we are currently designing a phase III randomized controlled trial (RCT), COLLISION RELAPSE trial, directly comparing upfront repeat local treatment (control) to neoadjuvant systemic therapy followed by repeat local treatment (intervention).