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BACKGROUND: Family caregivers of cancer patients are very involved in communication with healthcare teams; however, little is known about their experiences. Limited information is known about how the type of cancer patients have impact caregiving experiences. OBJECTIVES: This study seeks to compare the caregiving experience of caregivers of hospice lung cancer patients with hospice caregivers of patients with all other cancer types. METHOD: This study is based on a secondary analysis of data generated from a parent study evaluating a behavioral intervention with caregivers of hospice cancer patients. RESULTS: When comparing caregiving experiences by patient diagnosis, significant differences were found in caregivers of hospice lung cancer demographics and experiences with caregiver-centered communication. Specifically, caregivers of lung cancer patients have significantly more trouble with exchange of information, fostering relationships, and decision making with their hospice team. CONCLUSION: More research is needed to understand the impact of lung cancer on caregiver centered communication and the necessary interventions required to address these issues.
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Cuidados Paliativos al Final de la Vida , Hospitales para Enfermos Terminales , Neoplasias Pulmonares , Humanos , Cuidadores , Padres , FamiliaRESUMEN
PURPOSE: Shared decision making has been a long-standing practice in oncology and, despite a lack of research on the subject, is a central part of the philosophical foundation of hospice. This mixed methods study examined the perceptions of staff regarding shared decision making and their use of shared decision elements in hospice interdisciplinary team meetings. METHODS: The revised Leeds Attitude to Concordance scale (LatConII) was used to measure the attitudes of hospice staff toward shared decision making. Field notes and transcripts of hospice interdisciplinary team meetings that included family caregivers as participants were coded to identify 9 theory-driven shared decision making elements. The results were mixed in a matrix analysis comparing attitudes with practice. Three transcripts demonstrate the variance in the shared decision making process between hospice teams. RESULTS: Hospice staff reported overall positive views on shared decision making; however, these views differed depending on participants' age and position. The extent to which staff views were aligned with the observed use of shared decision making elements in hospice interdisciplinary team meetings varied. CONCLUSION: Policy and practice conditions can make shared decision making challenging during hospice interdisciplinary team meetings despite support for the process by staff. TRIAL REGISTRATION: This study is a sub-study of a parent study registered with clinicaltrials.gov (NCT02929108).
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Cuidados Paliativos al Final de la Vida , Hospitales para Enfermos Terminales , Cuidadores , Toma de Decisiones , Toma de Decisiones Conjunta , HumanosRESUMEN
We investigated characteristics of patients with colon cancer that predicted nonreceipt of posttreatment surveillance testing and the subsequent associations between surveillance status and survival outcomes. This was a retrospective cohort study of the Surveillance, Epidemiology, and End Results database combined with Medicare claims. Patients diagnosed between 2002 and 2009 with disease stages II and III and who were between 66 and 84 years of age were eligible. A minimum of 3 years' follow-up was required, and patients were categorized as having received any surveillance testing (any testing) versus none (no testing). Poisson regression was used to obtain risk ratios with 95% confidence intervals for the relative likelihood of No Testing. Cox models were used to obtain subdistribution hazard ratios with 95% confidence intervals for 5- and 10-year cancer-specific and noncancer deaths. There were 16,009 colon cancer cases analyzed. Patient characteristics that predicted No Testing included older age, Black race, stage III disease, and chemotherapy. Patients in the No Testing group had an increased rate of 10-year cancer death that was greater for patients with stage III disease (subdistribution hazard ratio = 1.79, 95% confidence interval: 1.48, 2.17) than those with stage II disease (subdistribution hazard ratio = 1.41, 95% confidence interval: 1.19, 1.66). Greater efforts are needed to ensure all patients receive the highest quality medical care after diagnosis of colon cancer.
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Neoplasias del Colon/patología , Neoplasias del Colon/terapia , Factores de Edad , Anciano , Anciano de 80 o más Años , Quimioterapia Adyuvante , Neoplasias del Colon/mortalidad , Comoras , Femenino , Humanos , Masculino , Medicare/estadística & datos numéricos , Persona de Mediana Edad , Estadificación de Neoplasias , Oportunidad Relativa , Pronóstico , Modelos de Riesgos Proporcionales , Calidad de la Atención de Salud , Grupos Raciales , Estudios Retrospectivos , Programa de VERF/estadística & datos numéricos , Factores Socioeconómicos , Estados UnidosRESUMEN
OBJECTIVE: Shared decision-making (SDM) occurs when physicians and patients jointly select treatment that aligns with patient care goals. Incorporating patient preferences into the decision-making process is integral to successful decision-making. This study explores factors influencing treatment selection in older patients with early-stage breast cancer (EBC). METHODS: This qualitative study included women age ≥65 years with EBC. To understand role preferences, patients completed the Control Preferences Scale. Semi-structured interviews were conducted to explore patients' treatment selection rationale. Interview transcripts were analyzed using a constant comparative method identifying major themes related to treatment selection. RESULTS: Of 33 patients, the majority (48%) desired shared responsibility in treatment decision-making. Interviews revealed that EBC treatment incorporated three domains: Intrinsic and extrinsic influences, clinical characteristics, and patient values. Patients considered 19 treatment selection themes, the most prioritized including physician trust and physical side effects. CONCLUSIONS: Because preferences and approach to treatment selection varied widely in this sample of older, EBC patients, more research is needed to determine best practices for preference incorporation to optimize SDM at the time of treatment decisions.
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Neoplasias de la Mama/terapia , Toma de Decisiones Conjunta , Prioridad del Paciente/psicología , Relaciones Médico-Paciente , Anciano , Neoplasias de la Mama/patología , Femenino , Humanos , Estadificación de Neoplasias , Planificación de Atención al Paciente , Investigación CualitativaRESUMEN
BACKGROUND: Little data exist on perceptions of guideline-based care in oncology. This qualitative analysis describes patients' and oncologists' views on the value of guideline-based care as well as discussing guidelines when making metastatic breast cancer (MBC) treatment decisions. PATIENTS AND METHODS: In-person interviews completed with MBC patients and community oncologists and focus groups with academic oncologists were audio-recorded and transcribed. Two coders utilized a content analysis approach to analyze transcripts independently using NVivo. Major themes and exemplary quotes were extracted. RESULTS: Participants included 20 MBC patients, 6 community oncologists, and 5 academic oncologists. Most patients were unfamiliar with the term "guidelines." All patients desired to know if they were receiving guideline-discordant treatment but were often willing to accept this treatment. Five themes emerged explaining this including trusting the oncologist, relying on the oncologist's experiences, being informed of rationale for deviation, personalized treatment, and openness to novel therapies. Physician discussions regarding the importance of guidelines revealed three themes: consistency with scientific evidence, insurance coverage, and limiting unusual practices. Oncologists identified three major limitations in using guidelines: lack of consensus, inability to "think outside the box" to personalize treatment, and lack of guideline timeliness. Although some oncologists discussed guidelines, it was often not considered a priority. CONCLUSIONS: Patients expressed a desire to know whether they were receiving guideline-based care but were amenable to guideline-discordant treatment if the rationale was made clear. Providers' preference to limit discussions of guidelines is discordant with patients' desire for this information and may limit shared decision-making.
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Neoplasias de la Mama , Neoplasias , Oncólogos , Neoplasias de la Mama/terapia , Toma de Decisiones , Toma de Decisiones Conjunta , Femenino , Humanos , Oncología Médica , Relaciones Médico-PacienteRESUMEN
An ideal model for decision making in cancer is shared decision-making (SDM). Primary facilitators in this model are information-seeking about treatment options and patient-physician trust. Previous studies have investigated the role of each of these parameters individually. However, little is known about their convergent role in treatment decision-making. Therefore, we explored perspectives of metastatic breast cancer (MBC) patients and healthcare professionals about the influence of health information-seeking and physician trust in the SDM process. Qualitative interviews with 20 MBC patients and 6 community oncologists, as well as 3 separate focus groups involving lay navigators, nurses, and academic oncologists, were conducted, recorded, and transcribed. Qualitative data analysis employed a content analysis approach, which included a constant comparative method to generate themes from the transcribed textual data. Five emergent themes were identified (1) physicians considered themselves as the patients' primary source of treatment information; (2) patients trusted their physician's treatment recommendations; (3) patients varied in their approach to seeking further health information regarding the discussed treatment options (e.g., internet websites, family and friends, support groups); (4) other healthcare professionals were cognizant of their fundamental role in facilitating further information-seeking; and (5) patient and physician discordant perspectives on shared decision making were present. Patient procurement of treatment information and the capacity to use it effectively in conjunction with patient trust in physicians play an important role in the shared decision-making process.
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Actitud del Personal de Salud , Neoplasias de la Mama/terapia , Toma de Decisiones Conjunta , Técnicas de Apoyo para la Decisión , Oncólogos/psicología , Participación del Paciente , Relaciones Médico-Paciente , Adulto , Anciano , Medicina Basada en la Evidencia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Investigación Cualitativa , Encuestas y CuestionariosRESUMEN
BACKGROUND: Metastatic breast cancer (MBC) is an ideal environment for shared decision-making because of the large number of guideline-based treatment options with similar efficacy but different toxicity profiles. This qualitative analysis describes patient and provider factors that influence decision-making in treatment of MBC. MATERIALS AND METHODS: Patients and community oncologists completed in-person interviews. Academic medical oncologists participated in focus groups. Interviews and focus groups were audio-recorded, transcribed, and analyzed using NVivo. Using an a priori model based on the Ottawa Framework, two independent coders analyzed transcripts using a constant comparative method. Major themes and exemplary quotes were extracted. RESULTS: Participants included 20 patients with MBC, 6 community oncologists, and 5 academic oncologists. Analysis of patient interviews revealed a decision-making process characterized by the following themes: decision-making style, contextual factors, and preferences. Patient preference subthemes include treatment efficacy, physical side effects of treatment, emotional side effects of treatment, cognitive side effects of treatment, cost and financial toxicity, salience of cutting-edge treatment options (clinical trial or newly approved medication), treatment logistics and convenience, personal and family responsibilities, treatment impact on daily activities, participation in self-defining endeavors, attending important events, and pursuing important goals. Physician decisions emphasized drug-specific characteristics (treatment efficacy, side effects, cost) rather than patient preferences, which might impact treatment choice. CONCLUSION: Although both patients with MBC and oncologists considered treatment characteristics when making decisions, patients' considerations were broader than oncologists', incorporating contextual factors such as the innovative value of the treatment and life responsibilities. Differences in perspectives between patients and oncologists suggests the value of tools to facilitate systematic communication of preferences in the setting of MBC. IMPLICATIONS FOR PRACTICE: Both patients with metastatic breast cancer (MBC) and oncologists emphasized importance of efficacy and physical side effects when making treatment decisions. However, other patient considerations for making treatment decisions were broader, incorporating contextual factors such as the logistics of treatments, personal and family responsibilities, and ability to attend important events. Furthermore, individual patients varied substantially in priorities that they want considered in treatment decisions. Differences in perspectives between patients and oncologists suggest the value of tools to facilitate systematic elicitation of preferences and communication of those preferences to oncologists for integration into decision-making in MBC.
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Neoplasias de la Mama/complicaciones , Oncólogos/normas , Adulto , Anciano , Toma de Decisiones , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la NeoplasiaRESUMEN
BACKGROUND: American Society of Radiation Oncology Choosing Wisely campaign recommends hypofractionated radiation and against routine use of intensity-modulated radiation therapy (IMRT) in early-stage estrogen receptor-positive breast cancer. We analyzed guideline recommendation adherence and financial implications in a modern Medicare cohort of women treated across the southeastern United States. METHODS: Our study population comprised Medicare patients over 65 years of age with breast cancer diagnosis from 12 cancer centers in the Southeast United States with stage 0-II breast treated with lumpectomy from 2012 to 2015. Hypofractionation was defined as 4 or fewer weeks of radiation treatments. Factors associated with utilization of hypofractionation and IMRT were identified using Poisson regression. Median costs during radiation treatments were compared for hypofractionation and IMRT. RESULTS: In older women (median age 71), 75% were treated with conventional fractionation, and 20% received IMRT. Hypofractionated women were more likely to have a positive estrogen(ER) or progestorone(PR) receptor status, lower comorbidity scores, and be treated at a high volume center (all P < 0.05). IMRT was utilized in 20% of patients and was more common in women treated with conventional fractionation (P < 0.001). Positive ER/PR status (P < 0.001) and utilization of hormonal blockade (P = 0.02) were associated with increased utilization of IMRT. CONCLUSION: In an older cohort of patients with early-stage breast cancer, a majority were treated with conventional fractionated radiation, while approximately 20% were treated with IMRT. Both of which were associated with increased cost relative to hypofractionation.
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Neoplasias de la Mama , Utilización de Procedimientos y Técnicas , Hipofraccionamiento de la Dosis de Radiación/normas , Radioterapia de Intensidad Modulada , Anciano , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Neoplasias de la Mama/radioterapia , Femenino , Adhesión a Directriz , Humanos , Medicare/estadística & datos numéricos , Estadificación de Neoplasias , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina/normas , Pautas de la Práctica en Medicina/estadística & datos numéricos , Utilización de Procedimientos y Técnicas/economía , Utilización de Procedimientos y Técnicas/estadística & datos numéricos , Radioterapia de Intensidad Modulada/economía , Radioterapia de Intensidad Modulada/métodos , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: There is increasing evidence that radiation therapy (RT) can be omitted for select older patients who are compliant with hormonal blockade, but there is no recent claim-based analysis for determining patterns of care and guiding possible treatment recommendations. METHODS: Medicare beneficiaries who were 65 years old or older and were diagnosed with breast cancer at 1 of 12 cancer centers affiliated with an academic center in the southeastern United States were analyzed. Stage 0 or I patients treated with lumpectomy from 2012 to 2014 were identified. Patient, treatment, and center characteristics were analyzed for the utilization of RT. RESULTS: Among 800 women treated with lumpectomy, 64% received adjuvant radiation. The median age was 74 years. The omission of RT was more likely in older patients, stage 0 patients, and patients with more comorbidities (P < .01). Hormonal blockade was used in 41% of the patients who did not receive RT. The utilization of hormonal blockade with the omission of RT was more likely in patients with fewer comorbidities (P < .01). CONCLUSIONS: In an older cohort of patients who otherwise would have qualified for the omission of radiation, two-thirds were treated with radiation. Future guideline recommendations should address omission in the context of hormonal blockade compliance because only 41% of the patients used hormonal blockade when radiation was not delivered. Cancer 2018;124:475-81. © 2017 American Cancer Society.
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Neoplasias de la Mama/radioterapia , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Medicare , Estados UnidosRESUMEN
BACKGROUND: Mastectomy remains an effective treatment for ductal carcinoma in situ (DCIS) but whether further therapy is warranted for close or positive margins is controversial. We aim to characterize the treatment practices of DCIS throughout the United States in patients who undergo mastectomy with close or positive margins to better understand the use of postmastectomy radiation therapy (PMRT). MATERIALS AND METHODS: Using the 2004-2013 National Cancer Database, we identified all female patients with a diagnosis of DCIS who underwent mastectomy. Distributional characteristics were summarized for overall and margin-stratified samples. Characteristic differences were assessed by region and receipt of radiation. Chi-square and independent sample t-tests were used to assess differences for categorical and continuous variables, respectively. RESULTS: In 21,591 patients who met inclusion criteria, 470 patients with close/positive margins were identified. Sixteen percent of patients with close/positive margins received PMRT compared to 1.5% with negative margins (P < 0.01). There was no difference in PMRT and patient race, insurance status, treatment facility, or endocrine therapy. Patients with close/positive margins who received PMRT were more likely to be in an urban setting from the Midwest (24.6%) and Northeast (21.8%) compared to the West (11.0%) and South (10.7%) (P < 0.01). CONCLUSIONS: Use of PMRT for DCIS following mastectomy with close/positive margins differs across the country. Regional variations in treatment patterns reinforce a need to determine whether PMRT improves survival to establish treatment guidelines.
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Neoplasias de la Mama/radioterapia , Carcinoma Intraductal no Infiltrante/radioterapia , Márgenes de Escisión , Adulto , Anciano , Neoplasias de la Mama/cirugía , Carcinoma Intraductal no Infiltrante/cirugía , Femenino , Humanos , Mastectomía , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Accelerated partial breast irradiation (APBI) is an increasingly utilized modality for early stage breast cancer as part of breast conservation therapy (BCT). There remains concern regarding local recurrence, requiring more frequent post-radiation surveillance imaging. The purpose of this study is to determine clinical significance of frequent surveillance in this perceived higher risk population. Patients treated at a community academic medical center from 2005 to 2013 with partial breast radiation were retrospectively identified. All patients were treated with lumpectomy followed by balloon based APBI. Diagnostic, clinical, radiographic, and outcomes data were collected. One hundred and sixty-nine patients were identified. Median age at time of diagnosis was 63. Stage was 0, I, and II in 27%, 64%, and 9%, respectively. Most patients had pure invasive ductal cancer. Ninety-two percent and 99% of patients had imaging performed by 6 and 12 months (± 3 months) respectively. Median interval between end of radiation and first image, and subsequent 3 images were 6, 6, 9, and 12 months, respectively. Median follow-up was 49 months for all patients (range 7-106). Six patients experienced local recurrence: 4 invasive, all clinically detected, and none within the first 2 years. One patient had mammographically detected recurrent ductal carcinoma in situ. No mammographic images within the first year lead to diagnosis of recurrent cancer. APBI via balloon base brachytherapy offered women excellent locoregional control rates. Frequent mammographic surveillance did not result in increased detection of early recurrent disease. The result of our study are in line with the Choosing Wisely campaign recommendations to perform no more than annual follow-up for women who have completed radiation as part of BCT, with first imaging done at 6-12 months. We recommend mammographic surveillance be performed no more frequently than annually, with first image after BCT to be done 12 months from completion of radiation.
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Neoplasias de la Mama/diagnóstico por imagen , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/prevención & control , Braquiterapia , Neoplasias de la Mama/radioterapia , Femenino , Humanos , Imagen por Resonancia Magnética , Mamografía , Uso Excesivo de los Servicios de Salud/economía , Uso Excesivo de los Servicios de Salud/prevención & control , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Ultrasonografía MamariaRESUMEN
PURPOSE: Little is known about long-term radiographic findings after treatment with accelerated partial breast irradiation (APBI). METHODS: Univariate and multivariate analysis of factors leading to formation and resolution of seroma were performed in patients treated with lumpectomy and APBI. RESULTS: Post-treatment images of 129 patients were reviewed by one radiologist. Median surgical excision volume was 108.9 cc (range 20.5-681.9). Primary mode of imaging was mammogram. Median time from end of RT to first and last surveillance image was 6 and 54 months, respectively. Median number of images was 7 (range 3-12). Seroma was identified in 98 (76%) patients, with median maximum diameter of 3.9 cm. Forty (41%) patients experienced resolution of seroma, at a median time of 29 months (range 6-74). On univariate analysis, surgical excision volume was associated with seroma formation, and tumor stage and margin re-excision were significant on univariate and multivariate analysis. No factors were associated with seroma resolution. CONCLUSION: Seroma formation after APBI resolves around 2.5 years for many patients, but persists for others possibly due to primary tumor and surgical excision volumes. With revised criteria on the definition of positive margins, smaller volumes may lead to decreased risk of seroma formation for future patients.
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Braquiterapia , Neoplasias de la Mama/terapia , Mastectomía Segmentaria , Seroma/diagnóstico por imagen , Seroma/etiología , Braquiterapia/efectos adversos , Carcinoma de Mama in situ/patología , Carcinoma de Mama in situ/terapia , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/terapia , Diagnóstico por Imagen/métodos , Femenino , Humanos , Márgenes de Escisión , Persona de Mediana Edad , Análisis Multivariante , Estudios RetrospectivosRESUMEN
PURPOSE: The aim of this study was to update our experience in treating pleomorphic adenoma with radiotherapy (RT). MATERIALS AND METHODS: This is a retrospective analysis of 25 patients treated with RT alone (2 patients) or combined with surgery (23 patients), with follow-up ranging from 1.8 to 34.9 years (median, 10.5 years). RESULTS: Local control was achieved in 13 (75%) of 16 patients with subclinical disease and 5 (56%) of 9 patients with gross disease. Overall local control was achieved in 18 (72%) of 25 patients. The 5-, 10-, and 15-year overall local control rates were 76 %, 76%, and 68%, respectively. Ten patients died of the following causes: recurrent disease, 2; malignant transformation, 2; and intercurrent disease, 6. At last follow-up, 14 patients were alive without evidence of disease, and 1 patient was alive with disease. Dental carries and transient facial nerve deficits were the most common complications. No patients developed severe complications subsequent to RT. CONCLUSIONS: In patients at high risk for developing recurrent pleomorphic adenoma after surgery, RT is effective in controlling subclinical disease.
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Adenoma Pleomórfico/radioterapia , Neoplasias de las Glándulas Salivales/radioterapia , Adenoma Pleomórfico/patología , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Dosis de Radiación , Estudios Retrospectivos , Neoplasias de las Glándulas Salivales/patología , Factores de Tiempo , Resultado del TratamientoRESUMEN
PURPOSE: The purpose of this work was to develop and validate fully automated methods for uptake measurement of cerebellum, liver, and aortic arch in full-body PET/CT scans. Such measurements are of interest in the context of uptake normalization for quantitative assessment of metabolic activity and/or automated image quality control. METHODS: Cerebellum, liver, and aortic arch regions were segmented with different automated approaches. Cerebella were segmented in PET volumes by means of a robust active shape model (ASM) based method. For liver segmentation, a largest possible hyperellipsoid was fitted to the liver in PET scans. The aortic arch was first segmented in CT images of a PET/CT scan by a tubular structure analysis approach, and the segmented result was then mapped to the corresponding PET scan. For each of the segmented structures, the average standardized uptake value (SUV) was calculated. To generate an independent reference standard for method validation, expert image analysts were asked to segment several cross sections of each of the three structures in 134 F-18 fluorodeoxyglucose (FDG) PET/CT scans. For each case, the true average SUV was estimated by utilizing statistical models and served as the independent reference standard. RESULTS: For automated aorta and liver SUV measurements, no statistically significant scale or shift differences were observed between automated results and the independent standard. In the case of the cerebellum, the scale and shift were not significantly different, if measured in the same cross sections that were utilized for generating the reference. In contrast, automated results were scaled 5% lower on average although not shifted, if FDG uptake was calculated from the whole segmented cerebellum volume. The estimated reduction in total SUV measurement error ranged between 54.7% and 99.2%, and the reduction was found to be statistically significant for cerebellum and aortic arch. CONCLUSIONS: With the proposed methods, the authors have demonstrated that automated SUV uptake measurements in cerebellum, liver, and aortic arch agree with expert-defined independent standards. The proposed methods were found to be accurate and showed less intra- and interobserver variability, compared to manual analysis. The approach provides an alternative to manual uptake quantification, which is time-consuming. Such an approach will be important for application of quantitative PET imaging to large scale clinical trials.
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Aorta Torácica/metabolismo , Cerebelo/metabolismo , Fluorodesoxiglucosa F18/metabolismo , Hígado/metabolismo , Imagen Multimodal , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Imagen de Cuerpo Entero , Aorta Torácica/diagnóstico por imagen , Automatización , Transporte Biológico , Cerebelo/diagnóstico por imagen , Humanos , Hígado/diagnóstico por imagen , Reproducibilidad de los ResultadosRESUMEN
Although the S3 pocket of the thrombin active site is lined with lipophilic amino acid residues, the accommodation of polarity within the lipophilic P3 moiety of small molecule inhibitors is possible provided that the polar functionality is capable of pointing away from the binding pocket outwards toward solvent while simultaneously allowing the lipophilic portion of the P3 ligand to interact with the S3 amino acid residues. Manipulation of this motif provided the means to effect optimization of functional potency, in vivo antithrombotic efficacy and oral bioavailability in a series of 3-aminopyrazinone thrombin inhibitors which contained non-charged groups at the P1 position.
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Anticoagulantes/síntesis química , Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , Diseño de Fármacos , Pirazinas/síntesis química , Trombina/antagonistas & inhibidores , Administración Oral , Animales , Anticoagulantes/química , Anticoagulantes/farmacología , Sitios de Unión , Disponibilidad Biológica , Perros , Estructura Molecular , Pirazinas/química , Pirazinas/farmacología , Ratas , Relación Estructura-ActividadRESUMEN
A novel 1,3,5-trisubstituted benzamide thrombin inhibitor template was designed via hybridization of a known aminopyridinoneacetamide and a known 1,3,5-trisubstituted phenyl ether. Optimization of this lead afforded a novel potent series of biaryl 1,3,5-trisubstituted benzenes with excellent functional anticoagulant potency.
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Antitrombinas/síntesis química , Benceno/síntesis química , Diseño de Fármacos , Trombina/antagonistas & inhibidores , Antitrombinas/química , Antitrombinas/farmacología , Benceno/química , Benceno/farmacología , Humanos , Modelos Moleculares , Estructura Molecular , Relación Estructura-ActividadRESUMEN
BACKGROUND: The purpose of this study is to present our experience treating patients with squamous cell carcinoma (SCC) from an unknown head and neck primary site and to determine whether a policy change eliminating the larynx and hypopharynx from the radiotherapy (RT) portals has impacted outcome. METHODS: One hundred seventy-nine patients received definitive RT with or without a neck dissection for SCC from an unknown head and neck primary site. RT was delivered to the ipsilateral neck alone or both sides of the neck and, usually, the potential mucosal primary sites. The median mucosal dose was 5670 cGy. The median neck dose was 6500 cGy. One hundred nine patients (61%) received a planned neck dissection. RESULTS: Mucosal control at 5 years was 92%. The mucosal control rate in patients with RT limited to the nasopharynx and oropharynx was 100%. The 5-year neck-control rates were as follows: N(1), 94%; N(2a), 98%; N(2b), 86%; N(2c), 86%; N(3), 57%; and overall, 81%. The 5-year cause-specific survival rates were as follows: N(1), 94%; N(2a), 88%; N(2b), 82%; N(2c), 71%; N(3), 48%; and overall, 73%. The 5-year overall survival rates were as follows: N(1), 50%; N(2a), 70%; N(2b), 59%; N(2c), 45%; N(3), 34%; and overall, 52%. Eleven patients (7%) developed severe complications. CONCLUSION: RT alone or combined with neck dissection results in a high probability of cure with a low risk of severe complications. Eliminating the larynx and hypopharynx from the RT portals did not compromise outcome and likely reduces treatment toxicity.
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Carcinoma de Células Escamosas/secundario , Neoplasias de Cabeza y Cuello/secundario , Neoplasias Primarias Desconocidas/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/radioterapia , Estudios de Seguimiento , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Primarias Desconocidas/mortalidad , Dosis de Radiación , Estudios Retrospectivos , Tasa de Supervivencia , Estados Unidos/epidemiologíaRESUMEN
Antagonism of the bradykinin B(1) receptor represents a potential treatment for chronic pain and inflammation. Novel antagonists incorporating alpha-hydroxy amides were designed that display low-nanomolar affinity for the human bradykinin B(1) receptor and good bioavailability in the rat and dog. In addition, these functionally active compounds show high passive permeability and low susceptibility to phosphoglycoprotein mediated efflux, predictive of good CNS exposure.
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Amidas/farmacología , Antagonistas del Receptor de Bradiquinina B1 , Amidas/química , Amidas/farmacocinética , Animales , Disponibilidad Biológica , Barrera Hematoencefálica , Inhibidores Enzimáticos del Citocromo P-450 , Perros , Semivida , Humanos , Ratas , Ratas Sprague-Dawley , Relación Estructura-ActividadRESUMEN
PURPOSE: American Society for Radiation Choosing Wisely guidelines recommend ≤10 fractions of radiation therapy (RT) for bone metastasis, with consideration for 1 fraction in patients with a poor prognosis. The purpose of this analysis was to evaluate characteristic differences in guideline concordance to fractionation regimens in a modern cohort of older patients with a diagnosis of bone metastasis. METHODS AND MATERIALS: Medicare beneficiaries aged ≥65 years treated with RT for bone metastasis from 2012 to 2015 were identified. Guideline-concordant RT fractionation was defined in the entire cohort as ≤10 fractions. Utilization of 1 fraction versus ≥2 fractions was analyzed in deceased patients. Patient demographic, disease, and facility characteristics associated with shorter fractionation were analyzed. RESULTS: In 569 patients treated with RT, the median age at diagnosis was 73 years. The most common cancer types were lung (37%), genitourinary (26%), breast (15%), and gastrointestinal (10%). Among all patients, 34%, 30%, and 36% received 1 fraction, 2 to 10 fractions, and ≥11 fractions, respectively. In comparison with receipt of 1 to 10 fractions, receipt of ≥11 fractions was associated with a $1467 increase in per-patient cost to Medicare during the calendar quarter of RT. Almost two-thirds of patients who died within 30 days of RT completion were treated with >1 fraction. CONCLUSIONS: Although guideline concordance was high overall, a large number of patients received longer courses of RT at the end of life. Strong consideration should be made for utilization of shorter courses, particularly in patients with a limited prognosis.
Asunto(s)
Neoplasias Óseas/radioterapia , Neoplasias Óseas/secundario , Cuidados Paliativos/métodos , Anciano , Neoplasias Óseas/mortalidad , Fraccionamiento de la Dosis de Radiación , Femenino , Humanos , Masculino , Medicare/economía , Cuidados Paliativos/economía , Estados UnidosRESUMEN
CONTEXT: Shared decisions between health care providers and patients and families are replacing the traditional physician-driven plans of care. Hospice philosophy recognizes the patient and family as a unit of care and embraces their role in decision making. OBJECTIVE: The goal of this study was to evaluate the shared decisions between hospice nurses and patients and family members. METHODS: A secondary analysis of audio recordings of 65 home hospice nurse visits from 65 home hospice nurse visits in 11 different U.S. hospice programs. RESULTS: To varying degrees, hospice nurses used all the recommended elements of shared decision making during home visits with patients and families; however, not all elements were used in every visit. The most commonly used element was defining a problem, and the least used element was the assessment of patient and family understanding. CONCLUSIONS: Hospice staff can benefit from a more purposeful shared decision-making process and a greater focus on assessment of patient and family understanding and ability to implement plans of care.