RESUMEN
BACKGROUND: Patients with unresectable recurrent rectal cancer (RRC) or colorectal cancer (CRC) with liver metastases, refractory to at least two lines of traditional systemic therapy, may receive third line intraarterial chemotherapy (IC) and targeted therapy (TT) using drugs selected by chemosensitivity and tumor gene expression analyses of liquid biopsy-derived circulating tumor cells (CTCs). METHODS: In this retrospective study, 36 patients with refractory unresectable RRC or refractory unresectable CRC liver metastases were submitted for IC and TT with agents selected by precision oncotherapy chemosensitivity assays performed on liquid biopsy-derived CTCs, transiently cultured in vitro, and by tumor gene expression in the same CTC population, as a ratio to tumor gene expression in peripheral mononuclear blood cells (PMBCs) from the same individual. The endpoint was to evaluate the predictive accuracy of a specific liquid biopsy precision oncotherapy CTC purification and in vitro culture methodology for a positive RECIST 1.1 response to the therapy selected. RESULTS: Our analyses resulted in evaluations of 94.12% (95% CI 0.71-0.99) for sensitivity, 5.26% (95% CI 0.01-0.26) for specificity, a predictive value of 47.06% (95% CI 0.29-0.65) for a positive response, a predictive value of 50% (95% CI 0.01-0.98) for a negative response, with an overall calculated predictive accuracy of 47.22% (95% CI 0.30-0.64). CONCLUSIONS: This is the first reported estimation of predictive accuracy derived from combining chemosensitivity and tumor gene expression analyses on liquid biopsy-derived CTCs, transiently cultured in vitro which, despite limitations, represents a baseline and benchmark which we envisage will be improve upon by methodological and technological advances and future clinical trials.
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Neoplasias Colorrectales , Neoplasias Hepáticas , Células Neoplásicas Circulantes , Neoplasias del Recto , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Expresión Génica , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Células Neoplásicas Circulantes/patología , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/genética , Estudios RetrospectivosRESUMEN
The spread of Severe Acute Respiratory Syndrome Coronavirus 2 new variants increased the number of subjects in home isolation and quarantine. The aim of this study was to assess the compliance with coronavirus disease 2019 home isolation rules for 32 subjects in home care in Marche Region, Italy. The results showed that subjects in home isolation were better informed about isolation rules (P = 0.007) than those who were in quarantine. They had lower educational level (P < 0.001) and none/single income (P < 0.001) and higher rate of clinical manifestation. The education for a safe quarantine should be strengthened widely, especially among disadvantaged subjects.
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COVID-19 , Servicios de Atención de Salud a Domicilio , Humanos , Cuarentena/métodos , COVID-19/epidemiología , COVID-19/prevención & control , Aislamiento de Pacientes , SARS-CoV-2RESUMEN
Particulate matter (PM) may play a role in differential distribution and transmission rates of SARS-CoV-2. For public health surveillance, identification of factors affecting the transmission dynamics concerning the endemic (persistent sporadic) and epidemic (rapidly clustered) component of infection can help to implement intervention strategies to reduce the disease burden. The aim of this study is to assess the effect of long-term residential exposure to outdoor PM ≤ 10 µm (PM10) concentrations on SARS-CoV-2 incidence and on its spreading dynamics in Marche region (Central Italy) during the first wave of the COVID-19 pandemic (February to May 2020), using the endemic-epidemic spatio-temporal regression model for individual-level data. Environmental and climatic factors were estimated at 10 km2 grid cells. 10-years average exposure to PM10 was associated with an increased risk of new endemic (Rate Ratio for 10 µg/m3 increase 1.14, 95%CI 1.04-1.24) and epidemic (Rate Ratio 1.15, 95%CI 1.08-1.22) infection. Male gender, older age, living in Nursing Homes and Long-Term Care Facilities residence and socio-economic deprivation index increased Rate Ratio (RR) in epidemic component. Lockdown increased the risk of becoming positive to SARS-CoV-2 as concerning endemic component while it reduced virus spreading in epidemic one. Increased temperature was associated with a reduction of endemic and epidemic infection. Results showed an increment of RR for exposure to increased levels of PM10 both in endemic and epidemic components. Targeted interventions are necessary to improve air quality in most polluted areas, where deprived populations are more likely to live, to minimize the burden of endemic and epidemic COVID-19 disease and to reduce unequal distribution of health risk.
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Contaminación del Aire , COVID-19 , COVID-19/epidemiología , Control de Enfermedades Transmisibles , Humanos , Masculino , Pandemias , Material Particulado , SARS-CoV-2RESUMEN
BACKGROUND: Treatment strategies for advanced cutaneous melanoma (CM) patients, resistant or not treatable with novel target and immunotherapeutic drugs, remain a significant challenge, particularly for patients with unresectable stage IIIC/D disease localized to inferior limbs and pelvis, for whom specific outcomes are rarely considered. MATERIALS AND METHODS: This is a prospective study of multidisciplinary treatments, including locoregional melphalan chemotherapy, in 62 BRAF wild-type CM patients with locoregional metastases in the inferior limbs and pelvis, including inguinal regions. Patients were either in progression following or ineligible for, or not treatable with novel immunotherapy. For exclusively inferior limb-localised disease, patients received locoregional melphalan chemotherapy performed by hyperthermic isolated limb perfusion (n = 19) or isolated limb infusion (n = 19), and for synchronous lesions localised to inferior limbs and pelvis, received hypoxic pelvic and limb perfusion (n = 24). Additional multidisciplinary therapy included local, locoregional and systemic treatments and the primary endpoint was tumour response. RESULTS: The objective response rate following first cycle of locoregional chemotherapy was 37.1% at 3 mo and median progression-free survival was 4-mo, with 12.9% procedure-related complications, 30.6% low-grade haematological toxicity and 11.3% severe limb toxic tissue reactions. Multivariate logistic regression showed that the odds of response were significantly higher for patients ≤ 75 y of age and for patients with locoregional metastases exclusively located in the inferior limbs. CONCLUSION: In this subgroup of CM patients with BRAF wild-type status, locoregional metastases localized to inferior limbs and pelvis, in progression following or ineligible for immunotherapy, melphalan locoregional chemotherapy demonstrated a safe and effective profile. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01920516; date of trial registration: August 6, 2013.
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Melanoma , Neoplasias Cutáneas , Quimioterapia del Cáncer por Perfusión Regional , Extremidades/patología , Humanos , Infusiones Intraarteriales , Melanoma/tratamiento farmacológico , Melanoma/genética , Melanoma/patología , Melfalán/uso terapéutico , Estudios Prospectivos , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patologíaRESUMEN
INTRODUCTION: For energy production, cancer cells maintain a high rate of glycolysis instead of oxidative phosphorylation converting glucose into lactic acid. This metabolic shift is useful to survive in unfavorable microenvironments. We investigated whether a positive glycolytic profile (PGP) in gastric adenocarcinomas may be associated with unfavorable outcomes under an anticancer systemic therapy, including the anti-angiogenic ramucirumab. MATERIALS AND METHODS: Normal mucosa (NM) and primary tumor (PT) of 40 metastatic gastric adenocarcinomas patients who received second-line paclitaxel-ramucirumab (PR) were analyzed for mRNA expression of the following genes: HK-1, HK-2, PKM-2, LDH-A, and GLUT-1. Patients were categorized with PGP when at least a doubling of mRNA expression (PT vs. NM) in all glycolytic core enzymes (HK-1 or HK-2, PKM-2, LDH-A) was observed. PGP was also related to TP53 mutational status. RESULTS: Mean LDH-A, HK-2, PKM-2 mRNA expression levels were significantly higher in PT compared with NM. 18 patients were classified as PGP, which was associated with significantly worse progression-free and overall survival times. No significant association was observed between PGP and clinical-pathologic features, including TP53 positive mutational status, in 28 samples. CONCLUSIONS: Glycolytic proficiency may negatively affect survival outcomes of metastatic gastric cancer patients treated with PR systemic therapy. TP53 mutational status alone does not seem to explain such a metabolic shift.
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Adenocarcinoma/metabolismo , Anticuerpos Monoclonales Humanizados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Glucólisis/genética , Paclitaxel/uso terapéutico , Terapia Recuperativa/mortalidad , Neoplasias Gástricas/metabolismo , Adenocarcinoma/mortalidad , Anciano , Femenino , Mucosa Gástrica/metabolismo , Humanos , Masculino , Mutación , ARN Mensajero/metabolismo , Estudios Retrospectivos , Neoplasias Gástricas/mortalidad , Resultado del Tratamiento , Proteína p53 Supresora de Tumor/genética , RamucirumabRESUMEN
Merkel cell carcinomas (MCCs) are rare, aggressive, cutaneous neuroendocrine tumours, approximately 80% of which are caused by the genomic integration of Merkel cell polyomavirus (MCPyV). MCPyV-positive MCCs carry poor prognosis in approximately 70% of cases, highlighting the need for greater understanding of the oncogenic mechanisms involved in pathogenesis, progression and post-therapeutic relapse, and translation into novel therapeutic strategies. In a previous pilot study, we reported a potential relationship between MCPyV gene expression and oncogenic alternative Δ exon 6-7 TrkAIII splicing in formalin-fixed paraffin-embedded (FFPE) MCC tissues from a 12-patient cohort of >90% MCPyV-positive MCCs, diagnosed at San Salvatore Hospital, L'Aquila, Italy, characterising a new MCC subgroup and unveiling a novel potential MCPyV oncogenic mechanism and therapeutic target. This, however, could not be fully verified due to poor RNA quality and difficulty in protein extraction from FFPE tissues. Here, therefore, we extend our previous observations to confirm the relationship between MCPyV and oncogenic alternative Δ exon 6-7 TrkAIII splicing in fresh, nonfixed, MCPyV-positive MCC metastasis by detecting sequence-verified RT-PCR products, including full-length Δ exon 6-7 TrkAIII, and by Western blot detection of a 100 kDa TrkA protein isoform of identical size to 100 kDa Δ exon 6-7 TrkAIII expressed by stable transfected SH-SY5Y cells. We also report that in three MCC patients submitted for multidisciplinary treatment, including locoregional chemotherapy, MCPyV large T-antigen mRNA expression, Δ exon 6-7 TrkAIII mRNA expression and intracellular indirect immunofluorescence (IF) TrkA and phosphorylation protein isoform(s) immunoreactivity in FFPE tissues were not reduced in postchemotherapeutic-relapsed MCCs compared to pretherapeutic MCCs, extending the possible roles of this novel potential MCPyV oncogenic mechanism from MCC pathogenesis to post-therapeutic relapse and progression. Detection of alternative Δ exon 6-7 TrkAIII splicing in MCC, therefore, not only characterises a new MCPyV-positive MCC subgroup and unveils a novel potential MCPyV oncogenic mechanism but also identifies patients who may benefit from inhibitors of MCPyV T-antigen and/or TrkAIII expression or clinically approved Trk kinase inhibitors such as larotrectinib or entrectinib, which are known to inhibit activated TrkA oncogenes and to elicit durable responses in TrkA-fusion oncogene-driven cancers, supporting the call for a large-scale multicentre clinical study.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma de Células de Merkel , Infecciones por Polyomavirus , Receptor trkA/genética , Neoplasias Cutáneas , Infecciones Tumorales por Virus , Anciano , Anciano de 80 o más Años , Empalme Alternativo/genética , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Carcinoma de Células de Merkel/diagnóstico , Carcinoma de Células de Merkel/genética , Carcinoma de Células de Merkel/mortalidad , Carcinoma de Células de Merkel/terapia , Transformación Celular Neoplásica/genética , Terapia Combinada , Vías de Administración de Medicamentos , Femenino , Humanos , Comunicación Interdisciplinaria , Italia/epidemiología , Masculino , Poliomavirus de Células de Merkel/aislamiento & purificación , Poliomavirus de Células de Merkel/fisiología , Persona de Mediana Edad , Técnicas de Diagnóstico Molecular , Mutación , Grupo de Atención al Paciente , Infecciones por Polyomavirus/diagnóstico , Infecciones por Polyomavirus/genética , Infecciones por Polyomavirus/mortalidad , Infecciones por Polyomavirus/terapia , Pronóstico , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/terapia , Análisis de Supervivencia , Infecciones Tumorales por Virus/diagnóstico , Infecciones Tumorales por Virus/genética , Infecciones Tumorales por Virus/mortalidad , Infecciones Tumorales por Virus/terapiaRESUMEN
Circulating tumour cells (CTCs) from liquid biopsies are under current investigation in several cancers, including epithelial ovarian cancer (EOC) but face significant drawbacks in terms of non-standardised methodology, low viable cell numbers and accuracy of CTC identification. In this pilot study, we report that chemosensitivity assays using liquid biopsy-derived metastatic EOC CTCs, from 10 patients, nine with stage IIIC and one with stage IV disease, in progression after systemic chemotherapy, submitted for hypoxic isolated abdominal perfusion (HAP), are both feasible and useful in predicting response to therapy. Viable metastatic EOC CTCs (>5 cells/mL for all 10 blood samples), enriched by transient culture and identified by reverse transcription polymerase chain reaction (RT-PCR) and indirect immunofluorescence (IF), were subjected to flow cytometry-based Annexin V-PE assays for chemosensitivity to several chemotherapeutic agents and by RT-PCR for tumour gene expression profiling. Using a cut-off value of >80% cell death, CTC chemosensitivity tests were predictive of patient RECIST 1.1 responses to HAP therapy associated with 100% sensitivity, 50% specificity, 33% positive predictive, 100% negative predictive and 60% accuracy values. We propose that the methodology employed in this study is feasible and has the potential to predict response to therapy, setting the stage for a larger study.
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Antineoplásicos/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Células Neoplásicas Circulantes/efectos de los fármacos , Células Neoplásicas Circulantes/patología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Adulto , Anciano , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Carcinoma Epitelial de Ovario/patología , Femenino , Expresión Génica/efectos de los fármacos , Expresión Génica/genética , Perfilación de la Expresión Génica/métodos , Humanos , Biopsia Líquida/métodos , Persona de Mediana Edad , Proyectos PilotoRESUMEN
Transarterial chemoembolization (TACE) is indicated in unresectable hepatocellular carcinoma and allows the delivery of embolics inside tumor vascularization to reduce blood supply and release gradually the drug. This lowers the systemic exposure to chemotherapeutics, while increasing their local concentration and tissue necrosis that is higher than conventional TACE. The technology of TACE has seen the introduction of several types of embolics that are made of different materials. Available embolics for TACE include: drug-eluting beads (DC beads), acrylic copolymer, tris-acrylic microspheres and polyethylene glycol (PEG) microspheres. Few studies are available on PEG embolics and their use for TACE. This review focuses on the efficacy and safety of TACE performed with PEG microspheres for the treatment of hepatocellular carcinoma and discusses future therapeutic advantages.
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Carcinoma Hepatocelular/terapia , Doxorrubicina/administración & dosificación , Sistemas de Liberación de Medicamentos , Neoplasias Hepáticas/terapia , Polietilenglicoles/administración & dosificación , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/efectos adversos , Antibióticos Antineoplásicos/química , Quimioembolización Terapéutica , Doxorrubicina/efectos adversos , Doxorrubicina/química , Evaluación de Medicamentos , Humanos , Microesferas , Tamaño de la Partícula , Polietilenglicoles/efectos adversos , Polietilenglicoles/química , Resultado del TratamientoRESUMEN
Transarterial chemoembolization is an effective, minimally invasive therapy that is widely used for treatment of unresectable colorectal cancer liver metastases (CRC-LM). However, chemoembolization induces a hypoxic microenvironment, which increases neoangiogenesis and may promote early progression. For this reason, transarterial chemoembolization efficacy may be improved by combining it with an angiogenesis inhibitor, such as bevacizumab. This report shows that transarterial chemoembolization with irinotecan-loaded polyethylene glycol embolics and bevacizumab therapy was effective and well tolerated by 6 patients with CRC-LM, resulting in a disease control rate of 83% and an overall improvement in quality of life.
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Inhibidores de la Angiogénesis/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/administración & dosificación , Camptotecina/análogos & derivados , Quimioembolización Terapéutica/métodos , Neoplasias Colorrectales/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Administración Intravenosa , Anciano , Inhibidores de la Angiogénesis/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/efectos adversos , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Quimioembolización Terapéutica/efectos adversos , Neoplasias Colorrectales/diagnóstico por imagen , Femenino , Humanos , Irinotecán , Italia , Neoplasias Hepáticas/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Datos Preliminares , Estudios Prospectivos , Calidad de Vida , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
AIM: The aim was to evaluate cost-effectiveness of yttrium-90 transarterial radioembolization (TARE) in comparison to sorafenib treatment. PATIENTS & METHODS: A single-center, retrospective, observational study was performed, 166 patients with intermediate-/advanced-stage hepatocellular carcinoma were treated with sorafenib and 19 with TARE. The patients out of the sorafenib group matching the inclusion criteria for TARE, were reassigned to a subgroup SOR3. RESULTS: Mean costs for SOR3 patients amounted to 27,992 per patient, instead for TARE treatment, mean expense per patient was 17,761 (p = 0.028). Overall survival was similar between the two groups, while midterm survival rates (p = 0.012) were significantly higher with TARE treatment. CONCLUSION: TARE causes significantly lower treatment costs than sorafenib with better outcome in midterm survival.
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Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Niacinamida/análogos & derivados , Compuestos de Fenilurea/administración & dosificación , Radioisótopos de Itrio/administración & dosificación , Anciano , Carcinoma Hepatocelular/economía , Carcinoma Hepatocelular/patología , Quimioembolización Terapéutica/economía , Quimioembolización Terapéutica/métodos , Análisis Costo-Beneficio/economía , Femenino , Humanos , Neoplasias Hepáticas/economía , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Niacinamida/administración & dosificación , Niacinamida/economía , Compuestos de Fenilurea/economía , Estudios Retrospectivos , Sorafenib , Radioisótopos de Itrio/economíaRESUMEN
OBJECTIVE: The purpose of this study is to determine the efficacy and tolerability of transarterial chemoembolization (TACE) using polyethylene glycol (PEG) drug-elutable microspheres loaded with doxorubicin for treatment of hepatocellular carcinoma (HCC). SUBJECTS AND METHODS: Forty-two patients with unresectable HCC, as determined by a tumor board, were assigned to undergo TACE and were treated with PEG drug-elutable embolics loaded with doxorubicin. Patients were prospectively enrolled and included 32 (76%) men and 10 (24%) women. Their median age was 65 years (range, 42-83 years). Patients were treated with 50 mg of doxorubicin loaded in 2 mL of PEG embolics (mean [± SD] diameter, 100 ± 25 µm) that were infused via a chemoembolization method. Data collected included previous cancer therapy, tumor size, number of lesions, history of TACE, tumor response (at 1, 3, and 6 months), type and intensity of adverse events, and quality of life (QOL) analysis. RESULTS: One month after TACE, the overall tumor response rate was 79% (50% complete response, 29% partial response, 17% stable disease, and 5% progressive disease). At 3 months, the rates were 48% for complete response, 24% for partial response, 24% for stable disease, and 3% for progressive disease. At 6 months, the rates were 43% for complete response, 19% for partial response, 29% for stable disease, and 10% for progressive disease. TACE was well tolerated by all patients, with no evidence of procedure-related complications or systemic drug-related adverse events. Fever (33%), increase in transaminase level (17%), and pain (33%) were the most frequent adverse events, and their intensity was mostly mild (grades 1 and 2). The QOL scores were 80 at 1 month, 81 at 3 months, and 82 at 6 months after TACE. CONCLUSION: These data suggest that PEG embolics are efficacious and safe for the treatment of HCC, as indicated by their good tolerability, QOL scores, and high tumor response.
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Antibióticos Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Doxorrubicina/administración & dosificación , Neoplasias Hepáticas/terapia , Polietilenglicoles/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Microesferas , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Resultado del TratamientoRESUMEN
AIM: Primary objectives of the study were to assess the safety of transarterial chemoembolization (TACE) using DC Bead LUMI™ for the treatment of hepatocellular carcinoma and beads distribution after TACE. PATIENTS/METHODS: This was a prospective observational cohort study. The study included 44 hepatocellular carcinoma patients who were treated with TACE using DC Bead LUMI. Beads distribution was monitored 1 h after TACE by CT scan. RESULTS: TACE had no intraprocedural complications. Observed side effects were of mild intensity and included pain in 5 (11%), fever in 4 (9%) and vomiting in 2 (5%) patients. Most patients (89%) reported no adverse event. Non-target distribution was observed in only two cases (5%). CONCLUSION: DC Bead LUMI allowed assessing in real time their distribution. This could prevent non-target infusion and reduce toxicity.
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Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Medios de Contraste , Doxorrubicina/administración & dosificación , Neoplasias Hepáticas/terapia , Microesferas , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Quimioembolización Terapéutica/efectos adversos , Quimioembolización Terapéutica/métodos , Terapia Combinada , Doxorrubicina/efectos adversos , Doxorrubicina/farmacocinética , Femenino , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Retratamiento , Distribución Tisular , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Carga TumoralRESUMEN
Pelvic Melanoma relapse occurs in 15% of patients with loco regional metastases, and 25% of cases do not respond to new target-therapy and/or immunotherapy. Melphalan hypoxic pelvic perfusion may, therefore, be an option for these non-responsive patients. Overall median survival time (MST), stratified for variables, including BRAF V600E mutation and eligibility for treatments with new immunotherapy drugs, was retrospectively assessed in 41 patients with pelvic melanoma loco regional metastases. They had received a total of 175 treatments with Melphalan hypoxic perfusion and cytoreductive excision. Among the 41 patients, 22 (53.7%) patients exhibited a wild-type BRAF genotype, 11 of which were not eligible for immunotherapy. The first treatment resulted in a 97.5% response-rate in the full cohort and a 100% response-rate in the 22 wild-type BRAF patients. MST was 18 months in the full sample, 20 months for the 22 wild-type BRAF patients and 21 months for the 11 wild-type BRAF patients not eligible for immunotherapy. Melphalan hypoxic perfusion is a potentially effective treatment for patients with pelvic melanoma loco regional metastases that requires confirmation in a larger multicenter study.
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Antineoplásicos Alquilantes/uso terapéutico , Quimioterapia del Cáncer por Perfusión Regional/métodos , Melanoma/tratamiento farmacológico , Melfalán/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Pélvicas/tratamiento farmacológico , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Melanoma/patología , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Neoplasias Pélvicas/patología , Pelvis/patología , Proteínas Proto-Oncogénicas B-raf/genética , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
BACKGROUND: Contamination and transmission of different Listeria monocytogenes strains along food chain are a serious threat to public health and food safety. Understanding the distribution of diseases in time and space-time is fundamental in the epidemiological study and in preventive medicine programs. The aim of this study is to estimate listeriosis incidence along 10-years period and to perform space-time cluster analysis of listeriosis cases in Marche Region, Italy. METHODS: The number of observed listeriosis cases/year was derived from regional data of surveillance of notifiable diseases and hospital discharge form. The capture and recapture method (C-R method) was applied to estimate the real incidence of listeriosis cases in Marche Region and the space-time scan statistics analysis was performed to detect clusters of space-time of listeriosis cases and add precision to the conventional epidemiological analysis. RESULTS: The C-R method estimation of listeriosis cases was 119 in the 10- year period (2010-2019), with an average of 31.93 % of unobserved cases (lost cases). The estimated mean annual incidence of listeriosis was 0.77 per 100,000 inhabitants (95 %CI 0.65-0.92), accounting for 6.07 % of additional listeriosis cases per year than observed cases. Using the scan statistic, the two most likely clusters were identified, one of these was statistically significant (p < 0.05). The underdiagnosis and under-reporting in addition to listeriosis incidence variability suggested that the surveillance system of Marche Region should be improved. CONCLUSIONS: This study provides evidence of the ability of space-time cluster analysis to complement traditional surveillance of food-borne diseases and to understand the local risk factors by implementing timely targeted interventions.
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Enfermedades Transmitidas por los Alimentos , Listeria monocytogenes , Listeriosis , Humanos , Incidencia , Listeriosis/epidemiología , Enfermedades Transmitidas por los Alimentos/epidemiología , Italia/epidemiología , Microbiología de AlimentosRESUMEN
BACKGROUND: Glioblastoma is one of the most difficult to treat and most aggressive brain tumors, having a poor survival rate. The use of non-invasive modulated electro-hyperthermia (mEHT) and Tumor Treating Fields (TTF) devices has been introduced in the last few decades, both of which having proven anti-tumor effects. METHODS: A meta-analysis of randomized and observational studies about mEHT and TTF was conducted. RESULTS: A total of seven and fourteen studies about mEHT and TTF were included, with a total number of 450 and 1309 cases, respectively. A 42% [95% confidence interval (95% CI): 25-59%] 1-year survival rate was found for mEHT, which was raised to 61% (95% CI: 32-89%) if only the studies conducted after 2008 were investigated. In the case of TTF, 1-year survival was 67% (95% CI: 53-81%). Subgroup analyses revealed that newly diagnosed patients might get extra benefits from the early introduction of the devices (mEHT all studies: 73% vs. 37%, p = 0.0021; mEHT studies after 2008: 73% vs. 54%, p = 0.4214; TTF studies: 83% vs. 52%, p = 0.0083), compared with recurrent glioblastoma. CONCLUSIONS: Our meta-analysis showed that both mEHT and TTF can improve glioblastoma survival, and the most benefit may be achieved in newly diagnosed cases.
RESUMEN
KRAS is involved in the stability and expression of PD-L1. We investigated the expression of circulating mRNA (cmRNA) of KRAS4A and KRAS4B and the possible impact on progression-free survival (PFS) of patients with metastatic lung adenocarcinoma treated with immunotherapy. Patients without driver mutations undergoing Pembrolizumab (P) or P plus chemotherapy (PC) were prospectively accrued for liquid biopsy analysis of KRAS4A, KRAS4B, and PD-L1 cmRNA. Both KRAS isoforms were also studied for association with PD-L1 cmRNA. Of 56 patients, 28 received P and 28 PC. Patients with high levels of both KRAS isoforms showed significantly better PFS. The median PFS for KRAS4A was 29 months (95% CI 22-29 months) and KRAS4B 24 months (95% CI 13-29 months), respectively. The median PFS of patients with low levels of both isoforms was 12 months (95% CI 6-15 months for KRAS4A and 95% CI 5-20 months for KRAS4B). High KRAS4A retained a significant positive association with PFS in the multivariate model. An exploratory analysis in treatment subgroups found a positive association between high KRAS4A and KRAS4B with PFS in patients treated with P. PD-L1 cmRNA was significantly higher in patients with high KRAS isoforms levels and this effect was pronounced for high KRAS4A carriers. KRAS4A deserves further investigation as a potential marker for defining patients who may benefit the most from immune checkpoint inhibitors therapy and improving personalized cancer immunotherapeutic strategies.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Antígeno B7-H1/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Biopsia Líquida , Isoformas de Proteínas/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
BACKGROUND: Several studies report the useful therapeutic results of regional hyperthermia in association with chemotherapy (CHT) and radiotherapy for the treatment of pancreatic cancer. Modulated electro-hyperthermia (mEHT) is a new hyperthermia technique that induces immunogenic death or apoptosis of pancreatic cancer cells in laboratory experiments and increases tumor response rate and survival in pancreatic cancer patients, offering beneficial therapeutic effects against this severe type of cancer. AIM: To assess survival, tumor response and toxicity of mEHT alone or combined with CHT compared with CHT for the treatment of locally advanced or metastatic pancreatic cancer. METHODS: This was a retrospective data collection on patients affected by locally advanced or metastatic pancreatic cancer (stage III and IV) performed in 9 Italian centers, members of International Clinical Hyperthermia Society-Italian Network. This study included 217 patients, 128 (59%) of them were treated with CHT (no-mEHT) and 89 (41%) patients received mEHT alone or in association with CHT. mEHT treatments were performed applying a power of 60-150 watts for 40-90 min, simultaneously or within 72 h of administration of CHT. RESULTS: Median patients' age was 67 years (range 31-92 years). mEHT group had a median overall survival greater than non-mEHT group (20 mo, range 1.6-24, vs 9 mo, range 0.4-56.25, P < 0.001). mEHT group showed a higher number of partial responses (45% vs 24%, P = 0.0018) and a lower number of progressions (4% vs 31%, P < 0.001) than the no-mEHT group, at the three months follow-up. Adverse events were observed as mild skin burns in 2.6% of mEHT sessions. CONCLUSION: mEHT seems safe and has beneficial effects on survival and tumor response of stage III-IV pancreatic tumor treatment. Further randomized studies are warranted to confirm or not these results.
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BACKGROUND: Breast cancer (BC) is the most common invasive cancer in women, and exercise can significantly improve the outcomes of BC survivors. MoviS (Movement and Health Beyond Care) is a randomized controlled trial aimed to evaluate the potential health benefits of exercise and proper nutritional habits. This study aims to assess the efficacy of aerobic exercise training in improving quality of life (QoL) and health-related factors in high-risk BC. METHODS: One hundred seventy-two BC survivor women, aged 30-70 years, non-metastatic, stage 0-III, non-physically active, 6-12 months post-surgery, and post chemo- or radiotherapy, will be recruited in this study. Women will be randomly allocated to the intervention arm (lifestyle recommendations and MoviS Training) or control arm (lifestyle recommendations). The MoviS training consists of 12 weeks of aerobic exercise training (2 days/week of supervised and 1 day/week of unsupervised exercise) with a progressive increase in exercise intensity (40-70% of heart rate reserve) and duration (20-60 min). Both arms will receive counseling on healthy lifestyle habits (nutrition and exercise) based on the World Cancer Research Fund International (WCRF) 2018 guidelines. The primary outcome is the improvement of the QoL. The secondary outcomes are improvement of health-related parameters such as Mediterranean diet adherence, physical activity level, flexibility, muscular fitness, fatigue, cardiorespiratory fitness (estimated maximal oxygen uptake), echocardiographic parameters, heart rate variability (average of the standard deviations of all 5 min normal to normal intervals (ASDNN/5 min) and 24 h very low and low frequency), and metabolic, endocrine, and inflammatory serum biomarkers (glycemia, insulin resistance, progesterone, testosterone, and high-sensitivity C-reactive protein). DISCUSSION: This trial aims to evaluate if supervised exercise may improve QoL and health-related factors of BC survivors with a high risk of recurrence. Findings from this project could provide knowledge improvement in the field of exercise oncology through the participation of a multidisciplinary team that will provide a coordinated program of cancer care to improve healthcare quality, improve prognosis, increase survival times and QoL, and reduce the risk of BC recurrence. TRIAL REGISTRATION: ClinicalTrials.gov NCT04818359 . Retrospectively registered on March 26, 2021.
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Neoplasias de la Mama , Supervivientes de Cáncer , Femenino , Humanos , Calidad de Vida , Neoplasias de la Mama/patología , Recurrencia Local de Neoplasia , Ejercicio Físico/fisiología , Sobrevivientes , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Peritoneal Carcinomatosis (PC) is considered as a terminal disease with short survival. It is treated with palliative therapies, consisting of repeated drainages and sometimes instillation of chemotherapy. Since the nineties, surgery has been combined with more effective systemic chemotherapy, intraperitoneal chemotherapy and hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of PC. This combination therapy significantly increases the overall survival of selected PC patients. The understanding of how intraperitoneal chemotherapy and HIPEC can cure patients is still unclear. Experts hypothesized that the efficacy is obtained by the ability of high peritoneal drug exposure and hyperthermia to directly kill cancer cells. Several studies indicate that cancer cells death directly influences the response of the immune system. For this reason, the protective effect of intraperitoneal chemotherapy and HIPEC could be mediated by its ability to kill cancer cells in an immuno-genic way, causing an efficient anticancer immune response. In this review, we investigate the role of the innate peritoneal or locoregional therapy-induced immune response in PC therapy.
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Hipertermia Inducida , Neoplasias Peritoneales , Terapia Combinada , Humanos , Inmunidad , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/cirugíaRESUMEN
INTRODUCTION: Standardised nutritional screening methods improve the rate of recognising older patients with undernutrition, which is strongly encouraged in hospitals and residential settings. Therefore, our study compared the rates of identifying undernutrition before and after introducing the Mini Nutritional Assessment (MNA®) in a community hospital. METHODS: This was a single-centre, retrospective, observational before-after study. Participants were subjects aged 65 years or older, admitted to a community hospital from May 2018 to December 2020. The nursing assessment at admission included the MNA® from January 2020. The prevalence of undernutrition gathered by nursing diagnoses from 2018 to 2019 was compared with data obtained using the MNA® in 2020. Then, a confirmatory analysis was conducted to compare the prevalence of undernutrition in 2020 when both nursing diagnoses and the MNA® were used. RESULTS: We analysed data of approximately 316 patients (238 before and 78 after introducing the MNA®). Overall, results showed that 47.1% (n = 149) of the patients were undernourished. As observed, the prevalence of undernutrition was 38.6% (n = 92) in 2018-2019 and 73.1% (n = 57) in 2020 (p < 0.001). In 2020, however, 38.5% of patients (n = 30) were identified as undernourished using the MNA® but not using nursing diagnoses. Therefore, the correlation between these two methods was poor (Pearson's correlation 0.169, p = 0.14). CONCLUSION: Identifying elderly patients with undernutrition significantly increased after introducing the MNA®. Undernutrition is a common condition that should be systematically screened using a validated tool to activate personalised nutritional interventions promptly.