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BACKGROUND AND AIMS: Cholangiocarcinoma (CCA), a rare and aggressive hepatobiliary malignancy, presents significant clinical management challenges. Despite rising incidence and evolving treatment options, prognosis remains poor, motivating the exploration of real-world data for enhanced understanding and patient care. METHODS: This multicenter study analyzed data from 120 metastatic CCA patients at three institutions from 2016 to 2023. Kaplan-Meier curves assessed overall survival (OS), while univariate and multivariate analyses evaluated links between clinical variables (age, gender, tumor site, metastatic burden, ECOG performance status, response to first-line chemotherapy) and OS. Genetic profiling was conducted selectively. RESULTS: Enrolled patients had a median age of 68.5 years, with intrahepatic tumors predominant in 79 cases (65.8%). Among 85 patients treated with first-line chemotherapy, cisplatin and gemcitabine (41.1%) was the most common regimen. Notably, one-third received no systemic treatment. After a median 14-month follow-up, 81 CCA-related deaths occurred, with a median survival of 13.1 months. Two clinical variables independently predicted survival: response to first-line chemotherapy (disease control vs. no disease control; HR: 0.27; 95% CI: 0.14-0.50; p < 0.0001) and metastatic involvement (>1 site vs. 1 site; HR: 1.99; 95% CI: 1.04-3.80; p = 0.0366). The three most common genetic alterations involved the ARID1A, tp53, and CDKN2A genes. CONCLUSIONS: Advanced CCA displays aggressive clinical behavior, emphasizing the need for treatments beyond chemotherapy. Genetic diversity supports potential personalized therapies. Collaborative research and deeper CCA biology understanding are crucial to enhance patient outcomes in this challenging malignancy.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Anciano , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/genética , Conductos Biliares Intrahepáticos/patología , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/genética , Colangiocarcinoma/patología , Heterogeneidad Genética , PronósticoRESUMEN
The adoption of high-fidelity models in multidisciplinary design optimization (MDO) permits to enhance the identification of superior design configurations, but would prohibitively rise the demand for computational resources and time. Multifidelity Bayesian Optimization (MFBO) efficiently combines information from multiple models at different levels of fidelity to accelerate the MDO procedure. State-of-the-art MFBO methods currently meet two major limitations: (i) the sequential adaptive sampling precludes parallel computations of high-fidelity models, and (ii) the search scheme measures the utility of new design evaluations only at the immediate next iteration. This paper proposes a Non-Myopic Multipoint Multifidelity Bayesian Optimization (NM3-BO) algorithm to sensitively accelerate MDO overcoming the limitations of standard methods. NM3-BO selects a batch of promising design configurations to be evaluated in parallel, and quantifies the expected long-term improvement of these designs at future steps of the optimization. Our learning scheme leverages an original acquisition function based on the combination of a two-step lookahead policy and a local penalization strategy to measure the future utility achieved evaluating multiple design configurations simultaneously. We observe that the proposed framework permits to sensitively accelerate the MDO of a space vehicle and outperforms popular algorithms.
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Cholangiocarcinoma (CCA) is a rare cancer originating from the biliary epithelium and accounts for about 3% of all gastrointestinal malignancies. Unfortunately, the majority of patients are not eligible for surgical resection at the time of diagnosis, because of the locally advanced stage or metastatic disease. The overall survival time of unresectable CCA is generally less than 1 year, despite current chemotherapy regimens. Biliary drainage is often required as a palliative treatment for patients with unresectable CCA. Recurrent jaundice and cholangitis tend to occur because of reobstruction of the biliary stents. This not only jeopardizes the efficacy of chemotherapy, but also causes significant morbidity and mortality. Effective control of tumor growth is crucial for prolonging stent patency and consequently patient survival. Recently, endobiliary radiofrequency ablation (ERFA) has been experimented as a treatment modality to reduce tumor mass, and delay tumor growth, extending stent patency. Ablation is accomplished by means of high-frequency alternating current which is released from the active electrode of an endobiliary probe placed in a biliary stricture. It has been shown that tumor necrosis releases intracellular particles which are highly immunogenic and activate antigen-presenting cells, enhancing local immunity directed against the tumor. This immunogenic response could potentially enhance tumor suppression and be responsible for improved survival of patients with unresectable CCA who undergo ERFA. Several studies have demonstrated that ERFA is associated with an increased median survival of approximately 6 months in patients with unresectable CCA. Furthermore, recent data support the hypothesis that ERFA could ameliorate the efficacy of chemotherapy administered to patients with unresectable CCA, without increasing the risk of complications. This narrative review discusses the results of the studies published in recent years and focuses on the impact that ERFA could have on overall survival of patients with unresectable cholangiocarcinoma.
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Some cancer patients display a less aggressive form of metastatic disease, characterized by a low tumor burden and involving a smaller number of sites, which is referred to as "oligometastatic disease" (OMD). This review discusses new biomarkers, as well as methodological challenges and perspectives characterizing OMD. Recent studies have revealed that specific microRNA profiles, chromosome patterns, driver gene mutations (ERBB2, PBRM1, SETD2, KRAS, PIK3CA, SMAD4), polymorphisms (TCF7L2), and levels of immune cell infiltration into metastases, depending on the tumor type, are associated with an oligometastatic behavior. This suggests that OMD could be a distinct disease with specific biological and molecular characteristics. Therefore, the heterogeneity of initial tumor burden and inclusion of OMD patients in clinical trials pose a crucial methodological question that requires responses in the near future. Additionally, a solid understanding of the molecular and biological features of OMD will be necessary to support and complete the clinical staging systems, enabling a better distinction of metastatic behavior and tailored treatments.
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Immunotherapy is acquiring a primary role in treating endometrial cancer (EC) with a relevant benefit for many patients. Regardless, patients progressing during immunotherapy or those who are resistant represent an unmet need. The mechanisms of immune resistance and escape need to be better investigated. Here, we review the major mechanisms of immune escape activated by the indolamine 2,3-dioxygenase 1 (IDO1) pathway in EC and focus on potential therapeutic strategies based on IDO1 signaling pathway control. IDO1 catalyzes the first rate-limiting step of the so-called "kynurenine (Kyn) pathway", which converts the essential amino acid l-tryptophan into the immunosuppressive metabolite l-kynurenine. Functionally, IDO1 has played a pivotal role in cancer immune escape by catalyzing the initial step of the Kyn pathway. The overexpression of IDO1 is also associated with poor prognosis in EC. These findings can lead to advantages in immunotherapy-based approaches as a rationale for overcoming the immune escape. Indeed, besides immune checkpoints, other mechanisms, including the IDO enzymes, contribute to the EC progression due to the immunosuppression induced by the tumor milieu. On the other hand, the IDO1 enzyme has recently emerged as both a promising therapeutic target and an unfavorable prognostic biomarker. This evidence provides the basis for translational strategies of immune combination, whereas IDO1 expression would serve as a potential prognostic biomarker in metastatic EC.
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Neoplasias Endometriales , Quinurenina , Biomarcadores , Neoplasias Endometriales/terapia , Femenino , Humanos , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Quinurenina/metabolismo , Triptófano/metabolismoRESUMEN
BACKGROUND: The clinical observation showed a potential additive effect of anti-PD-1 agents and cetirizine in patients with advanced melanoma. METHODS: Clinical outcomes of concomitant cetirizine/anti-PD-1 treatment of patients with stage IIIb-IV melanoma were retrospectively collected, and a transcriptomic analysis was performed on blood samples obtained at baseline and after 3 months of treatment. RESULTS: Patients treated with cetirizine concomitantly with an anti-PD-1 agent had significantly longer progression-free survival (PFS; mean PFS: 28 vs 15 months, HR 0.46, 95% CI: 0.28-0.76; p = 0.0023) and OS (mean OS was 36 vs 23 months, HR 0.48, 95% CI: 0.29-0.78; p = 0.0032) in comparison with those not receiving cetirizine. The concomitant treatment was significantly associated with ORR and DCR (p < 0.05). The expression of FCGR1A/CD64, a specific marker of macrophages, was increased after the treatment in comparison with baseline in blood samples from patients receiving cetirizine, but not in those receiving only the anti-PD1, and positively correlated with the expression of genes linked to the interferon pathway such as CCL8 (rho = 0.32; p = 0.0111), IFIT1 (rho = 0.29; p = 0.0229), IFIT3 (rho = 0.57; p < 0.0001), IFI27 (rho = 0.42; p = 0.008), MX1 (rho = 0.26; p = 0.0383) and RSAD2 (rho = 0.43; p = 0.0005). CONCLUSIONS: This retrospective study suggests that M1 macrophage polarization may be induced by cetirizine through the interferon-gamma pathway. This effect may synergize with the immunotherapy of advanced melanoma with anti-PD-1 agents.
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Melanoma , Receptor de Muerte Celular Programada 1 , Cetirizina/farmacología , Cetirizina/uso terapéutico , Humanos , Interferón gamma/uso terapéutico , Macrófagos/metabolismo , Melanoma/genética , Estudios RetrospectivosRESUMEN
PURPOSE: To assess efficacy and safety of cone beam computed tomography (CBCT) in the radiofrequency ablation (RFA) of osteoid osteoma (OO) in children and adolescents, and to compare technical success, clinical success, radiation dose and procedure duration time of CBCT guidance to conventional computed tomography (CT) guidance. MATERIALS AND METHODS: Between 2015 and 2019, 53 consecutive percutaneous RFA were performed on pediatric patients with CBCT or conventional CT guidance, respectively, in 24 and 29 children and adolescents with 24-month follow-up. Dose area product (DAP) and dose length product (DLP) were recorded, respectively, for CBCT and conventional CT and converted to effective doses (ED). RESULTS: CBCT and conventional CT groups were similar in terms of patient age and weight, tumor size and tumor location. Technical success was achieved in all cases. Primary clinical success was 91.67% (22/24) for the CBCT group and 89.66% (26/29) for the conventional CT group. Mean DAP was 64.75Gycm2 (range 6.0-266.7). Mean DLP was 972.62mGycm (range 337-2344). ED was significantly lower in the CBCT group compared to the conventional CT group (0.34 mSv vs. 5.53 mSv, p = 0.0119). Procedure duration time was not significantly longer in the CBCT group (102.25 min vs. 92.34 min, p = 0.065). No major complication was registered. Minor complications were observed in 4 patients (2 in CBCT; 2 in conventional CT). CONCLUSIONS: Compared to conventional CT guidance, CBCT guidance for percutaneous OO ablation shows similar technical and clinical success rates, with reduced radiation dose and equivalent procedure duration time. This technique helps sparing dose exposure to pediatric patients.
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Tomografía Computarizada de Haz Cónico/métodos , Osteoma Osteoide/diagnóstico por imagen , Osteoma Osteoide/cirugía , Dosis de Radiación , Ablación por Radiofrecuencia/métodos , Radiografía Intervencional/métodos , Adolescente , Femenino , Humanos , Masculino , Resultado del TratamientoRESUMEN
Endometrial cancer (EC) is the most common gynecologic cancer in Europe and its prevalence is increasing. EC includes a biological and clinical heterogeneous group of tumors, usually classified as type I (endometrioid) or type II (non-endometrioid) based on the histopathological characteristics. In 2013, a new molecular classification was proposed by The Cancer Genome Atlas (TCGA) based on the comprehensive molecular profiling of EC. Several molecular somatic alterations have been described in development and progression of EC. Using these molecular features, EC was reclassified into four subgroups: POLE ultra-mutated, MSI hypermutated, copy-number low, and copy-number high that correlate with the prognosis. To this regard, it is widely reported that EC has more frequent mutations in the phosphatidylinositol 3-kinase (PI3K) pathway signaling than any other tumor. PIK3CA is the main significant mutated gene after PTEN alterations. Overall, over 90% of endometrioid tumors have activating PI3K molecular alterations that suggests its critical role in the EC pathogenesis. Thus, the dysregulation of PI3K pathway represents an attractive target in EC treatment. Herein, we report a radiological and clinically meaningful response to a selective PIK3 inhibitor in a patient with extensively pre-treated advanced endometrioid EC harboring a somatic activating PIK3CA hotspot mutation. These evidences provide the rational for translational strategies of the PI3K inhibition and could support the clinical usefulness of PIK3CA genotyping in advanced EC. To our knowledge, this is the first clinical case of PIK3CA-mutated EC successfully treated with alpelisib.
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PURPOSE OF REVIEW: Oncological treatments are known to induce cardiac toxicity, but the impact of new-onset cancer in patients with pre-existing HF remains unknown. This review focuses on the epidemiology, pathophysiological mechanisms, and clinical implications of HF patients who develop malignancies. RECENT FINDINGS: Novel findings suggest that HF and cancer, beside common risk factors, are deeply linked by shared pathophysiological mechanisms. In particular, HF itself may enhance carcinogenesis by producing pro-inflammatory cytokines, and it has been suggested that neurohormonal activation, commonly associated with the failing heart, might play a pivotal role in promoting neoplastic transformation. The risk of malignancies seems to be higher in HF patients compared to the general population, probably due to shared risk factors and common pathophysiological pathways. Additionally, management of these patients represents a challenge for clinicians, considering that the co-existence of these diseases significantly worsens patients' prognosis and negatively affects therapeutic options for both diseases.
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Insuficiencia Cardíaca , Neoplasias , Cardiotoxicidad , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/terapia , Humanos , Neoplasias/epidemiología , Neoplasias/terapia , Pronóstico , Factores de RiesgoRESUMEN
PURPOSE: To assess efficacy and safety of imaging-guided radiofrequency ablation (RFA) of Osteoid Osteoma (OO) in both typical and atypical sites. METHODS AND MATERIALS: Between January 2014 and March 2019, 102 consecutive percutaneous RFA were performed and retrospectively reviewed. The procedures were performed using a RFA bipolar ablation system (Covidien, exposed tip of 0.7-1cm), under Computed Tomography (CT) guidance or using a navigation system (Masmec) under CT and Cone Beam CT (CBCT) guidance. Patients were followed up over 24 months. Clinical success and recurrences were considered on the base of established criteria. In patients with clinical failure and/or imaging evidence of relapse, retreatment was considered. RESULTS: Administered power per-procedure was ≤8 W (mean temperature, 90°C). The pre-procedure average value of visual analog scale (VAS) was 8.33+/-0.91. Primary and secondary success rate 96.08% (98/102) and100% (102/102), respectively. No major complication was described. Technical success was proved in every patient by CT scan acquisition after needle positioning. Relapse and tumour location were significantly correlated (p-value = 0.0165). The mean dose-length product was 751.55 mGycm2. Advanced bone healing was noted in 68 lesions after 1y-follow up and in 86 lesions after 2y-follow up. CONCLUSION: Imaging-guided percutaneous RFA is a highly effective technique for OO, both in typical and atypical sites. CT or CBCT guidance, navigation systems and operator experience grant the technical success, which is the most crucial parameter affecting outcome.
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Neoplasias Óseas/terapia , Dolor en Cáncer/terapia , Recurrencia Local de Neoplasia/epidemiología , Osteoma Osteoide/terapia , Ablación por Radiofrecuencia/métodos , Adolescente , Adulto , Neoplasias Óseas/complicaciones , Neoplasias Óseas/diagnóstico , Dolor en Cáncer/diagnóstico , Dolor en Cáncer/etiología , Tomografía Computarizada de Haz Cónico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/prevención & control , Osteoma Osteoide/complicaciones , Osteoma Osteoide/diagnóstico , Dimensión del Dolor/estadística & datos numéricos , Ablación por Radiofrecuencia/estadística & datos numéricos , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
COVID-19 pandemic following the outbreak in China and Western Europe, where it finally lost the momentum, is now devastating North and South America. It has not been identified the reason and the molecular mechanisms of the two different patterns of the pulmonary host responses to the virus from a minimal disease in young subjects to a severe distress syndrome (ARDS) in older subjects, particularly those with previous chronic diseases (including diabetes) and cancer. The Management of the Istituto Nazionale Tumori - IRCCS "Fondazione Pascale" in Naples (INT-Pascale), along with all Health professionals decided not to interrupt the treatment of those hospitalized and to continue, even if after a careful triage in order not to allow SARS-CoV-2 positive subjects to access, to take care of cancer patients with serious conditions. Although very few (n = 3) patients developed a symptomatic COVID-19 and required the transfer to a COVID-19 area of the Institute, no patients died during the hospitalization and completed their oncology treatment. Besides monitoring of the patients, all employees of the Institute (physicians, nurses, researchers, lawyers, accountants, gatekeepers, guardians, janitors) have been tested for a possible exposure. Personnel identified as positive, has been promptly subjected to home quarantine and subdued to health surveillance. One severe case of respiratory distress has been reported in a positive employees and one death of a family member. Further steps to home monitoring of COVID-19 clinical course have been taken with the development of remote Wi-Fi connected digital devices for the detection of early signs of respiratory distress, including heart rate and oxygen saturation.In conclusion cancer care has been performed and continued safely also during COVID-19 pandemic and further remote home strategies are in progress to ensure the appropriate monitoring of cancer patients.
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Solitary fibrous tumor (SFT) of the pleura is a rare neoplasm which is challenging for clinicians to treat and radiologists to diagnose. Herein, we report a case of recurrence of SFT of the pleura in a 77-year-old patient which was diagnosed and surgically treated on the first occasion in 2005. The patient had a recurrence in 2016 which was treated and then six months later, he again experienced chest pain and a further local recurrence was found. Taking into consideration the age and comorbidities of the patient, CT-guided percutaneous microwave-thermal ablation was preferrable to surgery and a safe and highly effective local ablative technique with few side-effects.
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Técnicas de Ablación/efectos adversos , Hipertermia Inducida/efectos adversos , Microondas/efectos adversos , Recurrencia Local de Neoplasia/etiología , Tumor Fibroso Solitario Pleural/cirugía , Técnicas de Ablación/instrumentación , Anciano , Humanos , Masculino , Recurrencia Local de Neoplasia/patología , Pronóstico , Tumor Fibroso Solitario Pleural/patologíaRESUMEN
PURPOSE: Portal vein thrombosis (PVT) is generally recognized as a prognostic factor in HCC. Our purpose is to assess and compare the survival of patients with PVT and without PVT, after Y-90 Trans-Arterial Radio-Embolization (TARE) of unresectable HCC, unresponsive to other loco-regional treatments. MATERIALS AND METHODS: Between November 2005 and November 2012, Y-90 resin-based TARE was performed in an IRB-approved prospective protocol, on 89 patients with unresectable HCC. 33/89 patients had PVT, the remaining 56 were resistant-to-cTACE or underwent TARE as a downstaging therapy. All patients were studied with Multi-Detector Computed Tomography (MDCT), angiography, 99mTc-MAA-scintigraphy and liver biopsy. Gastro-duodenal artery was embolized in most cases. Proton-Pump Inhibitors were administered to prevent gastritis and ulcers. χ2 test with Yates correction and log rank test were used to compare the two proportions and Kaplan-Meier survival curves, respectively. RESULTS: The average activity administered was 1.7 ± 0.4 GBq. After the treatment, CTCAE grade 2 adverse events occurred in 46% (41/89) patients: in particular, fever and abdominal pain were found in 25 and 16 patients, respectively. No major side-effect was observed. According to mRECIST criteria, partial response or complete response was found in 70% of patient three months after the treatment, and in 90.5% nine months after the treatment. No significant difference was found in survival of patients with PVT compared to those without PVT (p-value = 0.672). A complete regression of PVT was observed in almost half patients (13/27, 48.1%). CONCLUSIONS: Portal vein invasion does not affect survival in advanced stage HCC-patients undergoing TARE using Y-90 resin-based microspheres. Y90 procedure is associated with regression of portal vein tumor thrombus.
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Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/terapia , Trombosis de la Vena/terapia , Radioisótopos de Itrio/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Angiografía , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/mortalidad , Quimioembolización Terapéutica/mortalidad , Estudios de Cohortes , Femenino , Humanos , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/mortalidad , Masculino , Microesferas , Persona de Mediana Edad , Tomografía Computarizada Multidetector , Estadificación de Neoplasias , Vena Porta/diagnóstico por imagen , Vena Porta/patología , Vena Porta/efectos de la radiación , Pronóstico , Cintigrafía , Análisis de Supervivencia , Trombosis de la Vena/complicaciones , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/mortalidadRESUMEN
BACKGROUND: Following recent epidemiological studies, which showed tissue reactions from ionizing radiation at significantly lower doses, the 2013/59 EURATOM Directive of 5th December 2013 lowered the limit on the equivalent dose to the eye lens from 150 mSv to 20 mSv per year. Therefore, as a precautionary measure, it is considered appropriate to perform a timely dose monitoring by using specific dosimeters. OBJECTIVES: Analysis of the current state of the eye lens exposures during interventional procedures. The survey aimed at assessing the degree of information available to the exposed workers as regards lowering the dose limit in Interventional Radiology departments of some hospitals in Campania (Southern Italy). METHODS: The equivalent dose was assessed, over a period of 90 days, using specific Hp dosimeters(3), placed sideways with regard to prescription eye glasses. The level of awareness of the new dose limit among operators was assessed using a questionnaire. RESULTS: The values of the equivalent dose to the lens of the eye for the I and II Operators were found to be <150 mSv/year but for the I Operator a value of 54 mSv/year was obtained, ie higher than 20 mSv/year, that is the new limit of the equivalent dose according to 2013/59 EURATOM. The initial results of the questionnaire from 52 exposed workers, of which 46 (88%) were from exposure category A and 6 (12%) from category B, showed a low level of information (19%). CONCLUSIONS: The results highlight not only the importance of using specific devices for individual protection but also the importance of the level of training and information the exposed medical staff are given concerning the new regulations.
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Cristalino , Exposición Profesional , Exposición a la Radiación , Protección Radiológica , Humanos , Cristalino/efectos de la radiación , Dosis de Radiación , Radiología IntervencionistaRESUMEN
PURPOSE: Radioembolisation is part of the multimodal treatment of hepatocellular carcinoma (HCC) at specialist liver centres. This study analysed the impact of prior treatment on tolerability and survival following radioembolisation. METHODS: This was a retrospective analysis of 325 consecutive patients with a confirmed diagnosis of HCC, who received radioembolisation with yttrium-90 resin microspheres at eight European centres between September 2003 and December 2009. The decision to treat was based on the clinical judgement of multidisciplinary teams. Patients were followed from the date of radioembolisation to last contact or death and the nature and severity of all adverse events (AEs) recorded from medical records. RESULTS: Most radioembolisation candidates were Child-Pugh class A (82.5%) with multinodular HCC (75.9%) invading both lobes (53.1%); 56.3% were advanced stage. Radioembolisation was used first-line in 57.5% of patients and second-line in 34.2%. Common prior procedures were transarterial (chemo)embolisation therapies (27.1%), surgical resection/transplantation (17.2%) and ablation (8.6%). There was no difference in AE incidence and severity between prior treatment subgroups. Median (95% confidence interval [CI]) survival following radioembolisation was similar between procedure-naive and prior treatment groups for Barcelona Clinic Liver Cancer (BCLC) stage A: 22.1 months (15.1-45.9) versus 30.9 months (19.6-46.8); p = 0.243); stage B: 18.4 months (11.2-19.4) versus 22.8 months (10.9-34.2); p = 0.815; and stage C: 8.8 months (7.1-10.8) versus 10.8 months (7.7-12.6); p = 0.976. CONCLUSIONS: Radioembolisation is a valuable treatment option for patients who relapse following surgical, ablative or vascular procedures and remain suitable candidates for this treatment.
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Carcinoma Hepatocelular/radioterapia , Embolización Terapéutica , Neoplasias Hepáticas/radioterapia , Hígado/efectos de la radiación , Adulto , Anciano , Anciano de 80 o más Años , Embolización Terapéutica/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Seguridad , Análisis de Supervivencia , Adulto JovenRESUMEN
Despite major advances in the molecular definition of the disease, screening and therapy, non-small cell lung cancer (NSCLC) is still characterized by a disappointing overall survival, depending on subtype and tumor stage. To address this challenge, in the last years the therapeutic algorithm of NSCLC has become much more complex and articulated, with different kinds of drugs, including chemotherapy, targeted-based agents, angiogenesis inhibitors and immunotherapy, and multiple lines of treatments, for patients with squamous and non-squamous hystology, EGFR mutation and ALK rearrangement. This short viewpoint describes the emerging strategies for the management of NSCLC, indicating how a personalized approach, characterized by a specific multidisciplinary involvement, implies a process that starts with early detection and includes surgery and systemic therapy.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Medicina de Precisión/métodos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/terapia , Detección Precoz del Cáncer , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapiaRESUMEN
MOTIVATION: Vaccines represent the most effective and cost-efficient weapons against a wide range of diseases. Nowadays new generation vaccines based on subunit antigens reduce adverse effects in high risk individuals. However, vaccine antigens are often poor immunogens when administered alone. Adjuvants represent a good strategy to overcome such hurdles, indeed they are able to: enhance the immune response; allow antigens sparing; accelerate the specific immune response; and increase vaccine efficacy in vulnerable groups such as newborns, elderly or immuno-compromised people. However, due to safety concerns and adverse reactions, there are only a few adjuvants approved for use in humans. Moreover, in practice current adjuvants sometimes fail to confer adequate stimulation. Hence, there is an imperative need to develop novel adjuvants that overcome the limitations of the currently available licensed adjuvants. RESULTS: We developed a computational framework that provides a complete pipeline capable of predicting the best citrus-derived adjuvants for enhancing the immune system response using, as a target disease model, influenza A infection. In silico simulations suggested a good immune efficacy of specific citrus-derived adjuvant (Beta Sitosterol) that was then confirmed in vivoAvailability: The model is available visiting the following URL: http://vaima.dmi.unict.it/AdjSim CONTACT: francesco.pappalardo@unict.it; fp@francescopappalardo.net.
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Adyuvantes Inmunológicos , Citrus , Sistema Inmunológico , Vacunas contra la Influenza , Anciano , Antígenos , Predicción , Humanos , Huésped Inmunocomprometido , Recién Nacido , Modelación Específica para el PacienteRESUMEN
PURPOSE: To evaluate safety and efficacy of Trans-Arterial Ethanol-Lipiodol Embolization (TAELE) compared with conventional Trans-Arterial Chemo-Embolization (cTACE) in the treatment of small intermediate-HCC (BCLC-Stage B). MATERIALS AND METHODS: A random sample of 87 patients (37.93% male; 62.07% female; age range, 36-86 years) with documented small intermediate-HCC and treated with TAELE (mixture 1:1 of Ethanol and Lipiodol) or cTACE (mixture of 50mg-Epirubicin and 5cc-Lipiodol) were retrospectively studied in an institutional review board approved protocol. The two procedures were compared with χ2-test, χ2-test with Yates correction, McNemar's exact test, ANOVA test and log-rank test. RESULTS: TAELE and cTACE therapies were performed in 45 and 42 patients, respectively. Thirty days after the procedure, a Multi-Detector Computed Tomography (MDCT) showed no significant difference in the number of patients with partial and complete response between the two groups (p-value = 0.958), according to mRECIST. Contrary, significant differences were found in tumor-devascularization, lesion-reduction and post-embolization syndrome occurrence (p-value = 0.0004, p-value = 0.0003 and p-value = 0.009, respectively). Similar survival was observed during 36-month follow-up (p-value = 0.884). CONCLUSION: Compared to cTACE, TAELE showed a better toxicity profile with similar 36-month survival and similar one-month anti-tumor effects, which makes it better tolerated by patients, especially in case of more than one treatment.