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1.
Sci Rep ; 13(1): 22942, 2023 12 22.
Artículo en Inglés | MEDLINE | ID: mdl-38135704

RESUMEN

Gliomas with CDKN2A mutations are known to have worse prognosis but imaging features of these gliomas are unknown. Our goal is to identify CDKN2A specific qualitative imaging biomarkers in glioblastomas using a new informatics workflow that enables rapid analysis of qualitative imaging features with Visually AcceSAble Rembrandtr Images (VASARI) for large datasets in PACS. Sixty nine patients undergoing GBM resection with CDKN2A status determined by whole-exome sequencing were included. GBMs on magnetic resonance images were automatically 3D segmented using deep learning algorithms incorporated within PACS. VASARI features were assessed using FHIR forms integrated within PACS. GBMs without CDKN2A alterations were significantly larger (64 vs. 30%, p = 0.007) compared to tumors with homozygous deletion (HOMDEL) and heterozygous loss (HETLOSS). Lesions larger than 8 cm were four times more likely to have no CDKN2A alteration (OR: 4.3; 95% CI 1.5-12.1; p < 0.001). We developed a novel integrated PACS informatics platform for the assessment of GBM molecular subtypes and show that tumors with HOMDEL are more likely to have radiographic evidence of pial invasion and less likely to have deep white matter invasion or subependymal invasion. These imaging features may allow noninvasive identification of CDKN2A allele status.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Glioblastoma/diagnóstico por imagen , Glioblastoma/genética , Glioblastoma/patología , Homocigoto , Eliminación de Secuencia , Glioma/patología , Proteínas Inhibidoras de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Informática , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Mutación
2.
Cancers (Basel) ; 15(19)2023 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-37835516

RESUMEN

Stereotactic radiotherapy (SRT) is the standard of care treatment for brain metastases (METS) today. Nevertheless, there is limited understanding of how posttreatment lesional volumetric changes may assist prediction of lesional outcome. This is partly due to the paucity of volumetric segmentation tools. Edema alone can cause significant clinical symptoms and, therefore, needs independent study along with standard measurements of contrast-enhancing tumors. In this study, we aimed to compare volumetric changes of edema to RANO-BM-based measurements of contrast-enhancing lesion size. Patients with NSCLC METS ≥10 mm on post-contrast T1-weighted image and treated with SRT had measurements for up to seven follow-up scans using a PACS-integrated tool segmenting the peritumoral FLAIR hyperintense volume. Two-dimensional contrast-enhancing and volumetric edema changes were compared by creating treatment response curves. Fifty NSCLC METS were included in the study. The initial median peritumoral edema volume post-SRT relative to pre-SRT baseline was 37% (IQR 8-114%). Most of the lesions with edema volume reduction post-SRT experienced no increase in edema during the study. In over 50% of METS, the pattern of edema volume change was different than the pattern of contrast-enhancing lesion change at different timepoints, which was defined as incongruent. Lesions demonstrating incongruence at the first follow-up were more likely to progress subsequently. Therefore, edema assessment of METS post-SRT provides critical additional information to RANO-BM.

3.
Radiographics ; 43(9): e230040, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37590162

RESUMEN

According to the Centers for Disease Control and Prevention, trauma is the leading cause of fatal injuries for Americans aged 1-44 years old and the fourth leading overall cause of death. Accurate and early diagnosis, including grading of solid organ injuries after blunt abdominal trauma (BAT), is crucial to guide management and improve outcomes. The American Association for the Surgery of Trauma (AAST) Organ Injury Scale (OIS) is the most widely accepted BAT scoring system at CT both within the United States and internationally, and its uses include stratification of injury severity, thereby guiding management, and facilitation of clinical research, billing, and coding. Furthermore, this system also plays a role in the credentialing process for trauma centers in the United States. The newly revised 2018 OIS provides criteria for grading solid organ damage into three groups: imaging, operation, and pathology. The final grade is based on the highest of the three criteria. If multiple lower-grade (I or II) injuries are present in a single organ, one grade is advanced to grade III. The most substantial change in the revised 2018 AAST-OIS is incorporation of multidetector CT findings of vascular injury, including pseudoaneurysm and arteriovenous fistula. The authors outline the main revised aspects of grading organ injury using the AAST-OIS for the spleen, liver, and kidney after BAT, particularly the role of multidetector CT and alternative imaging in organ injury detection, the importance of vascular injuries in grade change, and the impact of these changes on patient management and in prediction of operative treatment success and in-hospital mortality. ©RSNA, 2023 Supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article. Quiz questions for this article are available through the Online Learning Center.


Asunto(s)
Traumatismos Abdominales , Lesiones del Sistema Vascular , Heridas no Penetrantes , Humanos , Lactante , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Bazo/diagnóstico por imagen , Hígado/diagnóstico por imagen , Riñón/diagnóstico por imagen , Traumatismos Abdominales/diagnóstico por imagen , Heridas no Penetrantes/diagnóstico por imagen
4.
J Am Coll Radiol ; 20(4): 438-445, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36736547

RESUMEN

OBJECTIVE: This quality assurance study assessed the implementation of a combined artificial intelligence (AI) and natural language processing (NLP) program for pulmonary nodule detection in the emergency department setting. The program was designed to function outside of normal reading workflows to minimize radiologist interruption. MATERIALS AND METHODS: In all, 19,246 CT examinations including at least some portion of the lung anatomy performed in the emergent setting from October 1, 2021, to June 1, 2022, were processed by the combined AI-NLP program. The program used an AI algorithm trained on 6-mm to 30-mm pulmonary nodules to analyze CT images and an NLP to analyze radiological reports. Cases flagged as negative for pulmonary nodules by the NLP but positive by the AI algorithm were classified as suspected discrepancies. Discrepancies result in secondary review of examinations for possible addenda. RESULTS: Out of 19,246 CT examinations, 50 examinations (0.26%) resulted in secondary review, and 34 of 50 (68%) reviews resulted in addenda. Of the 34 addenda, 20 patients received instruction for new follow-up imaging. Median time to addendum was 11 hours. The majority of reviews and addenda resulted from missed pulmonary nodules on CT examinations of the abdomen and pelvis. CONCLUSION: A background quality assurance process using AI and NLP helped improve the detection of pulmonary nodules and resulted in increased numbers of patients receiving appropriate follow-up imaging recommendations. This was achieved without disrupting in-shift radiologist workflow or causing significant delays in patient follow for the diagnosed pulmonary nodule.


Asunto(s)
Neoplasias Pulmonares , Nódulos Pulmonares Múltiples , Humanos , Inteligencia Artificial , Procesamiento de Lenguaje Natural , Tomografía Computarizada por Rayos X/métodos , Neoplasias Pulmonares/diagnóstico por imagen , Servicio de Urgencia en Hospital
5.
Radiographics ; 42(5): 1377-1397, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35930473

RESUMEN

Although eating disorders are common, they tend to be underdiagnosed and undertreated because social stigma tends to make patients less likely to seek medical attention and less compliant with medical treatment. Diagnosis is crucial because these disorders can affect any organ system and are associated with the highest mortality rate of any psychiatric disorder. Because of this, imaging findings, when recognized, can be vital to the diagnosis and management of eating disorders and their related complications. The authors familiarize the radiologist with the pathophysiology and sequelae of eating disorders and provide an overview of the related imaging findings. Some imaging findings associated with eating disorders are nonspecific, and others are subtle. The presence of these findings should alert the radiologist to correlate them with the patient's medical history and laboratory results and the clinical team's findings at the physical examination. The combination of these findings may suggest a diagnosis that might otherwise be missed. Topics addressed include (a) the pathophysiology of eating disorders, (b) the clinical presentation of patients with eating disorders and their medical complications and sequelae, (c) the imaging features associated with common and uncommon sequelae of eating disorders, (d) an overview of management and treatment of eating disorders, and (e) conditions that can mimic eating disorders (eg, substance abuse, medically induced eating disorders, and malnourishment in patients with cancer). Online supplemental material is available for this article. ©RSNA, 2022.


Asunto(s)
Trastornos de Alimentación y de la Ingestión de Alimentos , Trastornos Relacionados con Sustancias , Diagnóstico Diferencial , Diagnóstico por Imagen , Progresión de la Enfermedad , Trastornos de Alimentación y de la Ingestión de Alimentos/diagnóstico por imagen , Humanos
6.
Cancers (Basel) ; 14(9)2022 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-35565233

RESUMEN

Triple-negative breast cancer (TNBC) has been considered for many years an orphan disease in terms of therapeutic options, with conventional chemotherapy (CT) still representing the mainstay of treatment in the majority of patients. Although breast cancer (BC) has been historically considered a "cold tumor", exciting progress in the genomic field leading to the characterization of the molecular portrait and the immune profile of TNBC has opened the door to novel therapeutic strategies, including Immune Checkpoint Inhibitors (ICIs), Poly ADP-Ribose Polymerase (PARP) inhibitors and Antibody Drug Conjugates (ADCs). In particular, compared to standard CT, the immune-based approach has been demonstrated to improve progression-free survival (PFS) and overall survival (OS) in metastatic PD-L1-positive TNBC and the pathological complete response rate in the early setting, regardless of PD-L1 expression. To date, PD-L1 has been widely used as a predictor of the response to ICIs; however, many patients do not benefit from the addition of immunotherapy. Therefore, PD-L1 is not a reliable predictive biomarker of the response, and its accuracy remains controversial due to the lack of a consensus about the assay, the antibody, and the scoring system to adopt, as well as the spatial and temporal heterogeneity of the PD-L1 status. In the precision medicine era, there is an urgent need to identify more sensitive biomarkers in the BC immune oncology field other than just PD-L1 expression. Through the characterization of the tumor microenvironment (TME), the analysis of peripheral blood and the evaluation of immune gene signatures, novel potential biomarkers have been explored, such as the Tumor Mutational Burden (TMB), Microsatellite Instability/Mismatch Repair Deficiency (MSI/dMMR) status, genomic and epigenomic alterations and tumor-infiltrating lymphocytes (TILs). This review aims to summarize the recent knowledge on BC immunograms and on the biomarkers proposed to support ICI-based therapy in TNBC, as well as to provide an overview of the potential strategies to enhance the immune response in order to overcome the mechanisms of resistance.

7.
Clin Breast Cancer ; 21(4): e332-e339, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33353853

RESUMEN

BACKGROUND: Metronomic chemotherapy can induce disease control in patients with metastatic breast cancer (MBC) and has better safety profiles than conventional chemotherapy. Evidence suggests that cytotoxics can be anti-angiogenic in pre-clinical models and may have synergistic effects when combined with anti-vascular endothelial growth factor therapies. PATIENTS AND METHODS: Patients pretreated with ≥ 1 prior line of therapy for MBC received oral cyclophosphamide 50 mg daily in combination with oral vinorelbine at escalating doses of 20 mg (V20), 30 mg (V30), and 40 mg (V40) 3 times per week, and intravenous bevacizumab 15 mg/kg every 3 weeks. Patients with human epidermal growth factor receptor 2-positive disease were given the same regimen plus standard trastuzumab. Doses were escalated when 3 patients completed 3 treatment cycles of V20 and V30, without experiencing dose-limiting toxicities. The recommended dose was then tested in a further 6 patients. Circulating tumour cells and circulating endothelial cells (CEC) were measured in 30 mL of whole blood samples at baseline, after cycle 1, and at the disease progression. RESULTS: Fifteen patients were recruited from June 2013 to October 2015. The median age was 61 years (range, 29-72 years); 80% had estrogen receptor-positive and 33% had human epidermal growth factor receptor 2-positive disease. At least 67% had visceral metastases, and 80% had received ≥ 2 lines of prior treatment. No dose-limiting toxicities were observed at the 3 dose-levels, making V40 the recommended dose. Overall 8 (53%) patients developed grade 2 adverse events (arthralgia, n = 3 [20%]; asthenia, n = 2 [13%]; diarrhea, n = 2 [13%]; leukopenia, n = 2 [13%]). Bevacizumab was associated with grade 3 hypertension (n = 3 [20%]). Stable disease as best response was observed in 11 (73.3%) patients. The clinical benefit rate was 66.6% (10/15 patients). The median time to progression was 6.9 months. At baseline, CECs were more commonly detectable than circulating tumor cells; however, no statistical correlation was found between CEC kinetics and response. CONCLUSION: A metronomic vinorelbine dose of 40 mg combined with cyclophosphamide and bevacizumab is a promising treatment regimen in pretreated patients with MBC.


Asunto(s)
Antineoplásicos/administración & dosificación , Bevacizumab/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma/tratamiento farmacológico , Ciclofosfamida/administración & dosificación , Vinorelbina/administración & dosificación , Administración Metronómica , Administración Oral , Adulto , Anciano , Neoplasias de la Mama/patología , Carcinoma/patología , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Células Endoteliales , Femenino , Humanos , Persona de Mediana Edad , Células Neoplásicas Circulantes , Proyectos Piloto , Estudios Prospectivos
8.
J Immunother Cancer ; 8(2)2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-33060148

RESUMEN

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has overwhelmed the health systems worldwide. Data regarding the impact of COVID-19 on cancer patients (CPs) undergoing or candidate for immune checkpoint inhibitors (ICIs) are lacking. We depicted the practice and adaptations in the management of patients with solid tumors eligible or receiving ICIs during the COVID-19 pandemic, with a special focus on Campania region. METHODS: This survey (25 questions), promoted by the young section of SCITO (Società Campana di ImmunoTerapia Oncologica) Group, was circulated among Italian young oncologists practicing in regions variously affected by the pandemic: high (group 1), medium (group 2) and low (group 3) prevalence of SARS-CoV-2-positive patients. For Campania region, the physician responders were split into those working in cancer centers (CC), university hospitals (UH) and general hospitals (GH). Percentages of agreement, among High (H) versus Medium (M) and versus Low (L) group for Italy and among CC, UH and GH for Campania region, were compared by using Fisher's exact tests for dichotomous answers and χ2 test for trends relative to the questions with 3 or more options. RESULTS: This is the first Italian study to investigate the COVID-19 impact on cancer immunotherapy, unique in its type and very clear in the results. The COVID-19 pandemic seemed not to affect the standard practice in the prescription and delivery of ICIs in Italy. Telemedicine was widely used. There was high consensus to interrupt immunotherapy in SARS-CoV-2-positive patients and to adopt ICIs with longer schedule interval. The majority of the responders tended not to delay the start of ICIs; there were no changes in supportive treatments, but some of the physicians opted for delaying surgeries (if part of patients' planned treatment approach). The results from responders in Campania did not differ significantly from the national ones. CONCLUSION: Our study highlights the efforts of Italian oncologists to maintain high standards of care for CPs treated with ICIs, regardless the regional prevalence of COVID-19, suggesting the adoption of similar solutions. Research on patients treated with ICIs and experiencing COVID-19 will clarify the safety profile to continue the treatments, thus informing on the most appropriate clinical conducts.


Asunto(s)
Antineoplásicos Inmunológicos/administración & dosificación , Betacoronavirus/inmunología , Infecciones por Coronavirus/epidemiología , Oncología Médica/estadística & datos numéricos , Neoplasias/tratamiento farmacológico , Neumonía Viral/epidemiología , Adulto , Antineoplásicos Inmunológicos/efectos adversos , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/inmunología , Betacoronavirus/patogenicidad , COVID-19 , Antígeno CTLA-4/antagonistas & inhibidores , Antígeno CTLA-4/inmunología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/transmisión , Prescripciones de Medicamentos/estadística & datos numéricos , Femenino , Geografía , Humanos , Control de Infecciones/normas , Italia/epidemiología , Masculino , Oncología Médica/normas , Neoplasias/inmunología , Oncólogos/estadística & datos numéricos , Pandemias/prevención & control , Neumonía Viral/inmunología , Neumonía Viral/prevención & control , Neumonía Viral/transmisión , Pautas de la Práctica en Medicina/normas , Pautas de la Práctica en Medicina/estadística & datos numéricos , Prevalencia , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología , SARS-CoV-2 , Encuestas y Cuestionarios/estadística & datos numéricos , Tiempo de Tratamiento
9.
Artículo en Inglés | MEDLINE | ID: mdl-32605086

RESUMEN

Background: International research has shown that healthcare professionals (HCPs) and nonhealthcare professionals (NHCPs) are unaware of the goals and purposes of palliative care. This study evaluates the knowledge of palliative care among a sample of Portuguese adults and correlates their level of knowledge with age, gender, profession, and experience of family member's palliative care. Method: A cross-sectional online survey was carried out on a sample of 152 HCPs and 440 NHCPs who completed an anonymous questionnaire of sociodemographic, family, and professional data, and an instrument of 26 dichotomous (true or false) questions focusing on palliative care goals and purposes. Results: The 592 participants had a mean age of 31.3 ± 11.1 years, and most were female. Statistically significant differences between statements considered as correct by HCPs and NHCPs were found in 24 statements; HCPs had the highest percentage of correct answers. The terms most frequently associated with palliative care mentioned by NHCPs were chronic and progressive disease (n = 76), while HCPs mostly mentioned quality-of-life promotion (n = 29). Women, the elderly, and HCPs had a higher level of knowledge regarding palliative care (p < 0.001). Conclusions: Results clearly show gaps in knowledge of palliative care, especially among NHCPs. An integrated approach is needed to inform and clarify the philosophy and goals of palliative care in different settings in order to improve knowledge.


Asunto(s)
Personal de Salud , Cuidados Paliativos , Adulto , Anciano , Actitud del Personal de Salud , Estudios Transversales , Femenino , Humanos , Masculino , Portugal , Adulto Joven
10.
Clin Imaging ; 67: 95-100, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32531695

RESUMEN

Myofibroma is a benign, soft tissue neoplasm that predominantly affects infants and young children. Most occur in the skin or subcutaneous tissues, with a predilection for the head and neck regions. We describe the magnetic resonance (MR) imaging and histophathologic findings of a rare case of intramuscular myofibroma of the right deltoid in a healthy 30-year-old male. MR imaging revealed a well-circumscribed intramuscular mass, with isointense signal on T1-weighted images, hyperintense signal on T2-weighed images, and a "target-sign" with peripheral rim enhancement after gadolinium administration. The lesion was surgically excised with no complications, and the histopathologic analysis revealed the typical morphologic and histochemical markers of a myofibroma. We conclude that, although rare, myofibroma can be considered in the differential diagnosis of adults with lesions the above signal characteristics.


Asunto(s)
Imagen por Resonancia Magnética , Miofibroma/diagnóstico por imagen , Adulto , Diagnóstico Diferencial , Gadolinio , Cabeza/patología , Humanos , Leiomioma , Masculino , Miofibroma/patología , Miofibromatosis , Cuello/patología , Neoplasias de los Tejidos Blandos
11.
Mol Clin Oncol ; 12(5): 456-460, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32257203

RESUMEN

Palbociclib is a potent cyclin-dependent kinase (CDK)4/6 inhibitor that disrupts cell cycle progression and has been recently approved in combination with an aromatase inhibitor or fulvestrant as first- and second-line treatment in hormone receptor (HR)+, human epidermal growth factor receptor (HER)2- metastatic breast cancer. There is evidence that palbociclib may reverse endocrine therapy resistance and that it may also be added to ongoing endocrine therapy beyond progression to obtain clinical benefit. The aim of the present study was to explore this possibility in 5 patients who received palbociclib + fulvestrant following disease progression while under treatment with fulvestrant alone. The median progression-free survival was not reached during a median follow-up of 25 months, and the most frequent best response was stable disease. Three patients remained under treatment on the last re-evaluation. All patients had highly endocrine-sensitive disease and had previously received fulvestrant for ≥12 months. The hypothesis that a selected subpopulation of patients with HR+/HER2- metastatic breast cancer may benefit from the addition of palbociclib to ongoing endocrine therapy beyond disease progression merits further investigation.

12.
Clin Cancer Res ; 26(9): 2131-2139, 2020 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-31937617

RESUMEN

PURPOSE: Thymidine kinase 1 (TK1) is downstream to the CDK4/6 pathway, and TK activity (TKa) measured in blood is a dynamic marker of outcome in patients with advanced breast cancer (ABC). This study explores TK1 as a biomarker of palbociclib response, both in vitro and in patients with ABC. EXPERIMENTAL DESIGN: Modulation of TK1 levels and activity by palbociclib were studied in seven estrogen receptor-positive breast cancer cell lines: sensitive (PDS) and with palbociclib acquired resistance (PDR). TKa was assayed in plasma obtained at baseline (T0), after one cycle (T1), and at disease progression on palbociclib (T2) in patients enrolled in the "To Reverse ENDocrine Resistance" (TREnd) trial (n = 46). RESULTS: Among E2F-dependent genes, TK1 was significantly downregulated after short-term palbociclib. Early TKa reduction by palbociclib occurred in PDS but not in PDR cells. In patients, median TKa (mTKa) at T0 was 75 DiviTum units per liter (Du/L), with baseline TKa not proving prognostic. At T1, mTKa decreased to 35 Du/L, with a minority of patients (n = 8) showing an increase-correlating with a worse outcome than those with decreased/stable TKa (n = 33; mPFS 3.0 vs 9.0 months; P = 0.002). At T2, mTKa was 251 Du/L; patients with TKa above the median had worse outcomes on post-study treatment compared with those with lower TKa (2.9 vs 8.7 months; P = 0.05). CONCLUSIONS: TK is a dynamic marker of resistance to palbociclib which may lead to early identification of patients in whom treatment escalation may be feasible. In addition, TKa may stratify prognosis in patients with acquired resistance to palbociclib.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/enzimología , Piperazinas/uso terapéutico , Piridinas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/sangre , Neoplasias de la Mama/patología , Línea Celular Tumoral , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 4 Dependiente de la Ciclina/sangre , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 6 Dependiente de la Ciclina/sangre , Resistencia a Antineoplásicos , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Inhibidores de Proteínas Quinasas/uso terapéutico , Receptores de Estrógenos/metabolismo , Tasa de Supervivencia , Timidina Quinasa/sangre , Cambio de Tratamiento
13.
Cancers (Basel) ; 11(12)2019 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-31795152

RESUMEN

Mutations in the hotspot ligand-binding domain of the estrogen receptor (ER) gene ESR1 have recently been recognized as mechanisms of endocrine resistance in endocrine receptor-positive metastatic breast cancer (MBC). Accumulating data suggest these mutations develop under the selective pressure of endocrine treatments, and are infrequent in untreated ER-positive breast cancers. In vitro studies show that these mutations confer ligand-independent activity, resistance to estrogen deprivation, and relative resistance to tamoxifen and fulvestrant. Post-hoc retrospective and prospective analyses of ESR1 mutations in patients with MBC have consistently found that these mutations are markers of poor prognosis and predict resistance to aromatase inhibitors (AIs). These results warrant further investigation and prospective validation in dedicated studies. Moreover, studies are ongoing to clarify the activity of novel drugs in the context of metastatic endocrine resistant luminal breast cancer harboring ESR1 mutations. In this review, we summarize the pre-clinical and clinical findings defining the characteristics of ESR1 mutant breast cancer, and highlight the potential clinical developments in this field.

14.
Front Oncol ; 9: 666, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31396487

RESUMEN

The recent arrival of CDK4/6 inhibitor agents, with an approximate doubling of progression-free survival (PFS) associated with their use in hormone receptor-positive, HER2-negative advanced breast cancer (BC), has radically changed the approach to managing this disease. However, resistance to CDK4/6 inhibitors is considered a near-inevitability in most patients. Mechanisms of resistance to these agents are multifactorial, and research in this field is still evolving. Biomarkers with the ability to identify early resistance, or to predict the likelihood of successful treatment using CDK4/6 inhibitors are yet to be identified, and represent an area of unmet clinical need. Here we present selected mechanisms of resistance to CDK4/6 inhibitors, largely focussing on roles of Rb, cyclin E1, and the PIK3CA pathway, with discussion of associated biomarkers which have been investigated and applied in recent pre-clinical and clinical studies. These biological drivers may furthermore influence clinical treatment strategies adopted beyond CDK4/6 resistance.

15.
Breast J ; 25(6): 1310-1311, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31338934
16.
Eur Heart J Cardiovasc Imaging ; 20(12): 1345-1352, 2019 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-31326981

RESUMEN

AIMS: This study assessed the impact of the strain-guided therapeutic approach on cancer therapy-related cardiac dysfunction (CTRCD) and rate of cancer therapy (CT) interruption in breast cancer. METHODS AND RESULTS: We enrolled 116 consecutive female patients with HER2-positive breast cancer undergoing a standard protocol by EC (epirubicine + cyclophosphamide) followed by paclitaxel + trastuzumab (TRZ). Coronary artery, valvular and congenital heart disease, heart failure, primary cardiomyopathies, permanent or persistent atrial fibrillation, and inadequate echo-imaging were exclusion criteria. Patients underwent an echo-Doppler exam with determination of ejection fraction (EF) and global longitudinal strain (GLS) at baseline and every 3 months during CT. All patients developing subclinical (GLS drop >15%) or overt CTRCD (EF reduction <50%) initiated cardiac treatment (ramipril+ carvedilol). In the 99.1% (115/116) of patients successfully completing CT, GLS and EF were significantly reduced and E/e' ratio increased at therapy completion. Combined subclinical and overt CTRCD was diagnosed in 27 patients (23.3%), 8 at the end of EC and 19 during TRZ courses. Of these, 4 (3.4%) developed subsequent overt CTRCD and interrupted CT. By cardiac treatment, complete EF recovery was observed in two of these patients and partial recovery in one. These patients with EF recovery re-started and successfully completed CT. The remaining patient, not showing EF increase, permanently stopped CT. The other 23 patients with subclinical CTRCD continued and completed CT. CONCLUSION: These findings highlight the usefulness of 'strain oriented' approach in reducing the rate of overt CTRCD and CT interruption by a timely cardioprotective treatment initiation.


Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Cardiopatías , Disfunción Ventricular Izquierda , Antineoplásicos/efectos adversos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Ecocardiografía , Femenino , Humanos , Volumen Sistólico
17.
Clin Breast Cancer ; 19(6): 392-398, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31358432

RESUMEN

The landscape of therapeutic options for the treatment of hormone receptor (HR)-positive (HR+) HER2- breast cancer (BC) has been profoundly changed by the introduction of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors into the metastatic setting. Currently all CDK4/6 inhibitors are approved only in the metastatic setting by Food and Drug Administration (FDA) and European Medicine Agency (EMA), whereas their role in the neoadjuvant setting is still at an investigational stage. Exploitation of novel agents such as CDK4/6 inhibitors to improve the efficacy of neoadjuvant endocrine therapy (ET) or to overcome de novo resistance to ET is an area of research under active evaluation. We present a review of the currently available data and ongoing clinical trials that are evaluating the role of CDK4/6 inhibitors in neoadjuvant therapy of HR+ HER2- early BC, and also illustrate translational aspects, such as the potential biomarkers of response to these new therapeutic agents.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Terapia Molecular Dirigida , Terapia Neoadyuvante , Neoplasias Hormono-Dependientes/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Femenino , Humanos , Neoplasias Hormono-Dependientes/metabolismo , Neoplasias Hormono-Dependientes/patología , Pronóstico , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo
18.
Cancer Treat Rev ; 74: 29-34, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30708267

RESUMEN

Patients with luminal early breast cancer are at risk of relapse, even after five years of adjuvant endocrine therapy. To date, no biomarkers have been clinically validated to identify those patients at risk of late recurrence, who might benefit from extended adjuvant endocrine therapy. In recent decades, multiple clinical trials have tested the role of extending adjuvant endocrine therapies in patients with luminal disease. However, the data currently at our disposal are conflicting. This article reviews all the major trials concerning extended adjuvant endocrine regimens, and formulates some general conclusions and hypotheses of future study.


Asunto(s)
Antineoplásicos Hormonales/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Inhibidores de la Aromatasa/administración & dosificación , Esquema de Medicación , Hormona Liberadora de Gonadotropina/agonistas , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Tamoxifeno/administración & dosificación
19.
Acta Derm Venereol ; 99(6): 557-563, 2019 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-30723872

RESUMEN

Human papillomavirus (HPV) infection is highly prevalent in the sexually active population. This study estimates the prevalence of HPV DNA in anal and oral samples from a cohort of men and women with incident anogenital warts. Anal and/or oral samples from 541 patients with anogenital warts were tested for 35 HPV genotypes using a PCR assay. The overall prevalence of anal HPV and oral HPV DNA was 59.9% (n = 305/509; 95% confidence interval (CI) 55.6-64.1%) and 14.5% (n = 78/538; 95% CI 11.8-17.7%), respectively. Among patients with perianal warts, the anal HPV DNA prevalence was 92.3% (95% CI 87.0-95.5%). Anal HPV DNA prevalence in patients with genital warts but no perianal warts was 55.7% (95% CI 50.6-60.7%). Both anal and oral HPV infections were more common in men who have sex with men than in heterosexual men (90.4% versus 38.5% and 20.8% versus 11.8%, respectively). Anal high risk-HPV infection was more common in women (58.8%) and in men who have sex with men (67.7%). We found that anogenital warts represent a clinical marker for both anal and oral HPV infections, including anal high risk-HPV infections, particularly among women and men who have sex with men.


Asunto(s)
Enfermedades del Ano/epidemiología , Condiloma Acuminado/epidemiología , ADN Viral/análisis , Enfermedades de la Boca/epidemiología , Papillomaviridae , Adulto , Canal Anal/virología , Enfermedades del Ano/virología , Condiloma Acuminado/virología , Femenino , Genotipo , Heterosexualidad , Homosexualidad Masculina , Humanos , Masculino , Enfermedades de la Boca/virología , Mucosa Bucal/virología , Papillomaviridae/genética , Enfermedades del Pene/virología , Portugal/epidemiología , Prevalencia , Enfermedades de la Vulva/virología
20.
Menopause ; 25(6): 657-662, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29286986

RESUMEN

OBJECTIVE: Vulvovaginal atrophy (VVA) is a condition frequently observed in menopause. Its symptoms can significantly affect the quality of life of patients. Since VVA is related to estrogen deficiency, chemotherapy and hormone therapy for breast cancer (BC) might cause VVA by inducing menopause. Given the lack of effective treatment for VVA in BC survivors, we retrospectively evaluated the efficacy and tolerability of fractional microablative CO2 laser therapy in these patients. METHODS: We treated 82 BC survivors with three cycles of CO2 laser after failure of topical nonestrogenic therapy. The severity of symptoms was assessed with a visual analog scale (VAS) at baseline and after completion of laser therapy. Differences in mean VAS scores of each symptom before and after treatment were assessed with multiple t tests for pairwise comparisons. Multivariate analyses were used to adjust the final mean scores for the main confounding factors. RESULTS: Pre versus post-treatment differences in mean VAS scores were significant for sensitivity during sexual intercourse, vaginal dryness, itching/stinging, dyspareunia and dysuria (P < 0.001 for all), bleeding (P = 0.001), probe insertion (P = 0.001), and movement-related pain (P = 0.011). Multivariate analyses confirmed that results were significant, irrespective of patients' age and type of adjuvant therapy. CONCLUSION: This study shows that CO2 laser treatment is effective and safe in BC patients with iatrogenic menopause. However, the optimal number of cycles to administer and the need for retreatment remain to be defined. Prospective trials are needed to compare CO2 laser therapy with therapeutic alternatives.


Asunto(s)
Neoplasias de la Mama , Enfermedades Vaginales/cirugía , Adulto , Atrofia , Femenino , Humanos , Terapia por Láser , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Sobrevivientes , Resultado del Tratamiento , Vagina/patología , Enfermedades Vaginales/patología , Vulva/patología
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