RESUMEN
Older women are under-represented in breast cancer (BC) clinical trials, and treatment guidelines are primarily based on BC studies in younger women. Studies uniformly report an increased incidence of local relapse with omission of breast radiation therapy. Review of the available literature suggests very low rates of distant relapse in women ≥70 years of age. The incremental benefit of endocrine therapy in decreasing rate of distant relapse and improving disease-free survival in older patients with low-risk BC remains unclear. Integration of molecular genomic assays in diagnosis and treatment of estrogen receptor positive BC presents an opportunity for optimizing risk-tailored adjuvant therapies in ways that may permit treatment de-escalation among older women with early-stage BC. The prevailing knowledge gap and lack of risk-specific adjuvant therapy guidelines suggests a compelling need for prospective trials to inform selection of optimal adjuvant therapy, including omission of adjuvant endocrine therapy in older women with low risk BC.
RESUMEN
Conformational rearrangements are critical to regulating the assembly and activity of the spliceosome. The spliceosomal protein Prp8 undergoes multiple conformational changes during the course of spliceosome assembly, activation, and catalytic activity. Most of these rearrangements of Prp8 involve the disposition of the C-terminal Jab-MPN and RH domains with respect to the core of Prp8. Here we use x-ray structural analysis to show that a previously characterized and highly conserved ß-hairpin structure in the RH domain that acts as a toggle in the spliceosome is absent in Prp8 from the reduced spliceosome of the red alga Cyanidioschyzon merolae. Using comparative sequence analysis, we show that the presence or absence of this hairpin corresponds to the presence or absence of protein partners that interact with this hairpin as observed by x-ray and cryo-EM studies. The presence of the toggle correlates with increasing intron number suggesting a role in the regulation of splicing.
Asunto(s)
Proteínas Algáceas/química , Proteínas Algáceas/genética , Empalme del ARN/genética , Rhodophyta/genética , Empalmosomas/genética , Secuencia de Aminoácidos , Modelos Moleculares , Conformación Proteica , Rhodophyta/clasificación , Homología de SecuenciaRESUMEN
Integrated positron emission tomography and magnetic resonance imaging (PET/MRI) is an imaging technology that provides complementary anatomical and functional information for medical diagnostics. Both PET and MRI are highly susceptible to motion artifacts due, in part, to long acquisition times. The simultaneous acquisition of the two modalities presents the opportunity to use MRI navigator techniques for motion correction of both PET and MRI data. For this task, we propose spherical navigator echoes (SNAVs)-3D k-space navigators that can accurately and rapidly measure rigid body motion in all six degrees of freedom. SNAVs were incorporated into turbo FLASH (tfl)-a product fast gradient echo sequence-to create the tfl-SNAV pulse sequence. Acquiring in vivo brain images from a healthy volunteer with both sequences first compared the tfl-SNAV and product tfl sequences. It was observed that incorporation of the SNAVs into the image sequence did not have any detrimental impact on the image quality. The SNAV motion correction technique was evaluated using an anthropomorphic brain phantom. Following a stationary reference image where the tfl-SNAV sequence was acquired along with simultaneous list-mode PET, three identical PET/MRI scans were performed where the phantom was moved several times throughout each acquisition. This motion-up to 11° and 14 mm-resulted in motion artifacts in both PET and MR images. Following SNAV motion correction of the MRI and PET list-mode data, artifact reduction was achieved for both the PET and MR images in all three motion trials. The corrected images have improved image quality and are quantitatively more similar to the ground truth reference images.
Asunto(s)
Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Movimiento (Física) , Imagen Multimodal/métodos , Artefactos , Encéfalo/diagnóstico por imagen , Humanos , Fantasmas de ImagenRESUMEN
BACKGROUND: We hypothesized that increased baseline BMI and BMI change would negatively impact clinical outcomes with adjuvant breast cancer systemic therapy. METHODS: Data from chemotherapy trials MA.5 and MA.21; endocrine therapy MA.12, MA.14 and MA.27; and trastuzumab HERA/MA.24 were analyzed. The primary objective was to examine the effect of BMI change on breast cancer-free interval (BCFI) landmarked at 5 years; secondary objectives included BMI changes at 1 and 3 years; BMI changes on disease-specific survival (DSS) and overall survival (OS); and effects of baseline BMI. Stratified analyses included trial therapy and composite trial stratification factors. RESULTS: In pre-/peri-/early post-menopausal chemotherapy trials (N = 2793), baseline BMI did not impact any endpoint and increased BMI from baseline did not significantly affect BCFI (P = 0.85) after 5 years although it was associated with worse BCFI (P = 0.03) and DSS (P = 0.07) after 1 year. BMI increase by 3 and 5 years was associated with better DSS (P = 0.01; 0.01) and OS (P = 0.003; 0.05). In pre-menopausal endocrine therapy trial MA.12 (N = 672), patients with higher baseline BMI had worse BCFI (P = 0.02) after 1 year, worse DSS (P = 0.05; 0.004) after 1 and 5 years and worse OS (P = 0.01) after 5 years. Increased BMI did not impact BCFI (P = 0.90) after 5 years, although it was associated with worse BCFI (P = 0.01) after 1 year. In post-menopausal endocrine therapy trials MA.14 and MA.27 (N = 8236), baseline BMI did not significantly impact outcome for any endpoint. BMI change did not impact BCFI or DSS after 1 or 3 years, although a mean increased BMI of 0.3 was associated with better OS (P = 0.02) after 1 year. With the administration of trastuzumab (N = 1395) baseline BMI and BMI change did not significantly impact outcomes. CONCLUSIONS: Higher baseline BMI and BMI increases negatively affected outcomes only in pre-/peri-/early post-menopausal trial patients. Otherwise, BMI increases similar to those expected in healthy women either did not impact outcome or were associated with better outcomes. CLINICAL TRIALS NUMBERS: CAN-NCIC-MA5; National Cancer Institute (NCI)-V90-0027; MA.12-NCT00002542; MA.14-NCT00002864; MA.21-NCT00014222; HERA, NCT00045032;CAN-NCIC-MA24; MA-27-NCT00066573.
Asunto(s)
Antineoplásicos/administración & dosificación , Índice de Masa Corporal , Neoplasias de la Mama/tratamiento farmacológico , Terapia Neoadyuvante , Aumento de Peso , Antineoplásicos/efectos adversos , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Perimenopausia , Posmenopausia , Premenopausia , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Lymph node (LN) status is the most important prognostic variable used to guide ER positive (+) breast cancer treatment. While a positive nodal status is traditionally associated with a poor prognosis, a subset of these patients respond well to treatment and achieve long-term survival. Several gene signatures have been established as a means of predicting outcome of breast cancer patients, but the development and indication for use of these assays varies. Here we compare the capacity of two approved gene signatures and a third novel signature to predict outcome in distinct LN negative (-) and LN+ populations. We also examine biological differences between tumours associated with LN- and LN+ disease. METHODS: Gene expression data from publically available data sets was used to compare the ability of Oncotype DX and Prosigna to predict Distant Metastasis Free Survival (DMFS) using an in silico platform. A novel gene signature (Ellen) was developed by including patients with both LN- and LN+ disease and using Prediction Analysis of Microarrays (PAM) software. Gene Set Enrichment Analysis (GSEA) was used to determine biological pathways associated with patient outcome in both LN- and LN+ tumors. RESULTS: The Oncotype DX gene signature, which only used LN- patients during development, significantly predicted outcome in LN- patients, but not LN+ patients. The Prosigna gene signature, which included both LN- and LN+ patients during development, predicted outcome in both LN- and LN+ patient groups. Ellen was also able to predict outcome in both LN- and LN+ patient groups. GSEA suggested that epigenetic modification may be related to poor outcome in LN- disease, whereas immune response may be related to good outcome in LN+ disease. CONCLUSIONS: We demonstrate the importance of incorporating lymph node status during the development of prognostic gene signatures. Ellen may be a useful tool to predict outcome of patients regardless of lymph node status, or for those with unknown lymph node status. Finally we present candidate biological processes, unique to LN- and LN+ disease, that may indicate risk of relapse.
Asunto(s)
Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Metástasis Linfática/genética , Transcriptoma , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Perfilación de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Metástasis Linfática/patología , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Modelos de Riesgos Proporcionales , Receptor ErbB-2/biosíntesis , Receptores de Estrógenos/biosíntesis , Tamoxifeno/uso terapéuticoRESUMEN
BACKGROUND: Postmastectomy radiotherapy was shown in previous meta-analyses to reduce the risks of both recurrence and breast cancer mortality in all women with node-positive disease considered together. However, the benefit in women with only one to three positive lymph nodes is uncertain. We aimed to assess the effect of radiotherapy in these women after mastectomy and axillary dissection. METHODS: We did a meta-analysis of individual data for 8135 women randomly assigned to treatment groups during 1964-86 in 22 trials of radiotherapy to the chest wall and regional lymph nodes after mastectomy and axillary surgery versus the same surgery but no radiotherapy. Follow-up lasted 10 years for recurrence and to Jan 1, 2009, for mortality. Analyses were stratified by trial, individual follow-up year, age at entry, and pathological nodal status. FINDINGS: 3786 women had axillary dissection to at least level II and had zero, one to three, or four or more positive nodes. All were in trials in which radiotherapy included the chest wall, supraclavicular or axillary fossa (or both), and internal mammary chain. For 700 women with axillary dissection and no positive nodes, radiotherapy had no significant effect on locoregional recurrence (two-sided significance level [2p]>0·1), overall recurrence (rate ratio [RR], irradiated vs not, 1·06, 95% CI 0·76-1·48, 2p>0·1), or breast cancer mortality (RR 1·18, 95% CI 0·89-1·55, 2p>0·1). For 1314 women with axillary dissection and one to three positive nodes, radiotherapy reduced locoregional recurrence (2p<0·00001), overall recurrence (RR 0·68, 95% CI 0·57-0·82, 2p=0·00006), and breast cancer mortality (RR 0·80, 95% CI 0·67-0·95, 2p=0·01). 1133 of these 1314 women were in trials in which systemic therapy (cyclophosphamide, methotrexate, and fluorouracil, or tamoxifen) was given in both trial groups and, for them, radiotherapy again reduced locoregional recurrence (2p<0·00001), overall recurrence (RR 0·67, 95% CI 0·55-0·82, 2p=0·00009), and breast cancer mortality (RR 0·78, 95% CI 0·64-0·94, 2p=0·01). For 1772 women with axillary dissection and four or more positive nodes, radiotherapy reduced locoregional recurrence (2p<0·00001), overall recurrence (RR 0·79, 95% CI 0·69-0·90, 2p=0·0003), and breast cancer mortality (RR 0·87, 95% CI 0·77-0·99, 2p=0·04). INTERPRETATION: After mastectomy and axillary dissection, radiotherapy reduced both recurrence and breast cancer mortality in the women with one to three positive lymph nodes in these trials even when systemic therapy was given. For today's women, who in many countries are at lower risk of recurrence, absolute gains might be smaller but proportional gains might be larger because of more effective radiotherapy. FUNDING: Cancer Research UK, British Heart Foundation, UK Medical Research Council.
Asunto(s)
Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/radioterapia , Metástasis Linfática , Axila , Neoplasias de la Mama/cirugía , Femenino , Humanos , Escisión del Ganglio Linfático , Mastectomía , Recurrencia Local de Neoplasia , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
PURPOSE: To determine whether tumor grade, molecular subtype and hypoxia predict response to hypofractionated versus standard radiotherapy (RT) following breast-conserving surgery (BCS) for node-negative breast cancer in a randomized controlled trial (RCT). PATIENTS AND METHODS: Formalin-fixed paraffin-embedded (FFPE) tumor blocks were available on 989 of 1234 patients enrolled in the Hypofractionation Whole Breast Irradiation (HWBI) Trial. A central pathology review and assessment of tumor grade using the Nottingham grading system was carried out. Tumors were classified by molecular subtype as luminal A, luminal B, HER2 enriched, basal-like or unclassified using a six-biomarker panel; ER, PR, HER-2, Ki67, CK5/6 and EGFR. Tumors were also classified as hypoxic based on the expression of HIF1α, CAIX or GLUT-1. The primary end point was local recurrence (LR). RESULTS: Median follow-up was 12 years. In the multivariable Cox model, molecular subtype was the only factor predictive of LR, the 10-year cumulative incidence was 4.5% for luminal A and basal-like, 7.9% for luminal B and 16.9% for HER-2 enriched tumors (P < 0.01). Tumor grade, molecular subtype or hypoxia did not predict response to hypofractionation. CONCLUSIONS: In women enrolled in the HWBI trial following BCS tumor molecular subtype predicted LR. However tumor grade, molecular subtype and hypoxia did not predict response to hypofractionation suggesting that patients with node-negative breast tumors of all grades and molecular subtypes may be safely treated with hypofractionated RT regimens.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/terapia , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Hipoxia de la Célula , Supervivencia sin Enfermedad , Fraccionamiento de la Dosis de Radiación , Femenino , Humanos , Estimación de Kaplan-Meier , Mastectomía Segmentaria , Persona de Mediana Edad , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/prevención & control , Modelos de Riesgos Proporcionales , Radioterapia Adyuvante , Resultado del TratamientoRESUMEN
The AJCC staging criteria consider tumor size to be the largest dimension of largest tumor. Some case series suggest using summation of all tumor dimensions in patients with multicentric/multifocal (MC/MF) disease. We used data from NCIC CTG MA.5 and MA.12 clinical trials to examine alternative methods of assessing tumor size on breast-cancer-free-interval (BCFI). The 710 MA.5 pre-/peri-menopausal node positive and 672 MA.12 pre-menopausal node-negative/-positive patients have 10-year median follow-up. All patients received adjuvant chemotherapy. Tumors were centrally reviewed for grade, hormone receptor, and HER2 status. Continuous pathologic tumor size was: (1) largest dimension of largest tumor (cm); (2) tumor area (cm(2)); (3) volume of tumor (cm(3)); (4) with MC/MF disease, summation of (1)-(3) for up to 3 foci. We examined univariate and multivariate effects of tumor size on BCFI utilizing (un)stratified Cox regression and the Wald test statistic. In univariate analysis, larger tumor dimension was significantly associated with worse BFCI in node positive patients: p < 0.0001 for MA.5; p = 0.01 for MA.12. In MA.5 multivariate analysis, larger summation of largest tumor dimensions was associated with worse BCFI (p = 0.0003), while larger single dimension was associated with worse BCFI (p = 0.02) for MA.12. Presence of MC/MF and other tumor size measurements were not associated (p > 0.05) with BFCI. While physicians could consider the largest diameter of the largest focus of disease or the sum of the largest diameters of all foci in their T-stage determination, it appears that the current method of T-staging offers equivalent determinations of prognosis.
Asunto(s)
Neoplasias de la Mama/patología , Adulto , Anciano , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Ensayos Clínicos Fase III como Asunto , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Factores de Riesgo , Carga TumoralRESUMEN
BACKGROUND: MA17 showed improved outcomes in postmenopausal women given extended letrozole (LET) after completing 5 years of adjuvant tamoxifen. PATIENTS AND METHODS: Exploratory subgroup analyses of disease-free survival (DFS), distant DFS (DDFS), overall survival (OS), toxic effects and quality of life (QOL) in MA17 were performed based on menopausal status at breast cancer diagnosis. RESULTS: At diagnosis, 877 women were premenopausal and 4289 were postmenopausal. Extended LET was significantly better than placebo (PLAC) in DFS for premenopausal [hazard ratio (HR) = 0.26, 95% confidence interval (CI) 0.13-0.55; P = 0.0003] and postmenopausal women (HR = 0.67; 95% CI 0.51-0.89; P = 0.006), with greater DFS benefit in those premenopausal (interaction P = 0.03). In adjusted post-unblinding analysis, those who switched from PLAC to LET improved DDFS in premenopausal (HR = 0.15; 95% CI 0.03-0.79; P = 0.02) and postmenopausal women (HR = 0.45; 95% CI 0.22-0.94; P = 0.03). CONCLUSIONS: Extended LET after 5 years of tamoxifen was effective in pre- and postmenopausal women at diagnosis, and significantly better in those premenopausal. Women premenopausal at diagnosis should be considered for extended adjuvant therapy with LET if menopausal after completing tamoxifen.
Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Nitrilos/uso terapéutico , Premenopausia , Triazoles/uso terapéutico , Anciano , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Inhibidores de la Aromatasa/efectos adversos , Inhibidores de la Aromatasa/uso terapéutico , Neoplasias de la Mama/diagnóstico , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Letrozol , Persona de Mediana Edad , Nitrilos/efectos adversos , Placebos , Posmenopausia , Calidad de Vida , Sobrevida , Tamoxifeno/uso terapéutico , Resultado del Tratamiento , Triazoles/efectos adversosRESUMEN
Major hurricanes Emily and Wilma hit the Mexican Caribbean in 2005. Changes in trace metals in the seagrass Thalassia testudinum prior to (May 2004, 2005) and following passage of these hurricanes (May, June 2006) were determined at four locations along a ≈ 130 km long stretch of coast. Before the hurricanes, essential metals were likely limiting and concentrations of potentially toxic Pb were high in a contaminated lagoon (27.5 µg g(-1)) and near submarine springs (6.10 µg g(-1)); the likely sources were inland sewage disposal or excessive boat traffic. After the hurricanes, Pb decreased to 2.0 µg g(-1) in the contaminated lagoon probably through flushing. At the northern sites, essential Fe increased >2-fold (from 26.8 to 68.3 µg g(-1) on average), possibly from remobilization of anoxic sediments or upwelling of deep seawater during Wilma. Thus, hurricanes can be beneficial to seagrass beds in flushing toxic metals and replenishing essential elements.
Asunto(s)
Monitoreo del Ambiente/métodos , Hydrocharitaceae/metabolismo , Metales Pesados/metabolismo , Tormentas Ciclónicas , Metales Pesados/análisis , México , Estaciones del Año , Oligoelementos/análisis , Oligoelementos/metabolismoRESUMEN
BACKGROUND: After breast-conserving surgery, radiotherapy reduces recurrence and breast cancer death, but it may do so more for some groups of women than for others. We describe the absolute magnitude of these reductions according to various prognostic and other patient characteristics, and relate the absolute reduction in 15-year risk of breast cancer death to the absolute reduction in 10-year recurrence risk. METHODS: We undertook a meta-analysis of individual patient data for 10,801 women in 17 randomised trials of radiotherapy versus no radiotherapy after breast-conserving surgery, 8337 of whom had pathologically confirmed node-negative (pN0) or node-positive (pN+) disease. FINDINGS: Overall, radiotherapy reduced the 10-year risk of any (ie, locoregional or distant) first recurrence from 35·0% to 19·3% (absolute reduction 15·7%, 95% CI 13·7-17·7, 2p<0·00001) and reduced the 15-year risk of breast cancer death from 25·2% to 21·4% (absolute reduction 3·8%, 1·6-6·0, 2p=0·00005). In women with pN0 disease (n=7287), radiotherapy reduced these risks from 31·0% to 15·6% (absolute recurrence reduction 15·4%, 13·2-17·6, 2p<0·00001) and from 20·5% to 17·2% (absolute mortality reduction 3·3%, 0·8-5·8, 2p=0·005), respectively. In these women with pN0 disease, the absolute recurrence reduction varied according to age, grade, oestrogen-receptor status, tamoxifen use, and extent of surgery, and these characteristics were used to predict large (≥20%), intermediate (10-19%), or lower (<10%) absolute reductions in the 10-year recurrence risk. Absolute reductions in 15-year risk of breast cancer death in these three prediction categories were 7·8% (95% CI 3·1-12·5), 1·1% (-2·0 to 4·2), and 0·1% (-7·5 to 7·7) respectively (trend in absolute mortality reduction 2p=0·03). In the few women with pN+ disease (n=1050), radiotherapy reduced the 10-year recurrence risk from 63·7% to 42·5% (absolute reduction 21·2%, 95% CI 14·5-27·9, 2p<0·00001) and the 15-year risk of breast cancer death from 51·3% to 42·8% (absolute reduction 8·5%, 1·8-15·2, 2p=0·01). Overall, about one breast cancer death was avoided by year 15 for every four recurrences avoided by year 10, and the mortality reduction did not differ significantly from this overall relationship in any of the three prediction categories for pN0 disease or for pN+ disease. INTERPRETATION: After breast-conserving surgery, radiotherapy to the conserved breast halves the rate at which the disease recurs and reduces the breast cancer death rate by about a sixth. These proportional benefits vary little between different groups of women. By contrast, the absolute benefits from radiotherapy vary substantially according to the characteristics of the patient and they can be predicted at the time when treatment decisions need to be made. FUNDING: Cancer Research UK, British Heart Foundation, and UK Medical Research Council.
Asunto(s)
Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/terapia , Mastectomía Segmentaria , Recurrencia Local de Neoplasia/epidemiología , Factores de Edad , Antagonistas de Estrógenos/uso terapéutico , Femenino , Humanos , Metástasis Linfática , Clasificación del Tumor , Radioterapia Adyuvante , Ensayos Clínicos Controlados Aleatorios como Asunto , Receptores de Estrógenos/metabolismo , Tamoxifeno/uso terapéuticoRESUMEN
OBJECTIVE: This research explores the treatment decision-making (TDM) experiences of women with recurrent ovarian cancer (ROC) with regard to treatment options; their understanding of risks and benefits of various treatment options; the decision-making role they want for themselves and for their oncologist; and the social context of the consultation as it pertains to the decision. METHODS: We conducted semi-structured interviews with 26 women at the time of first recurrence. Through inductive data analysis key themes were identified. RESULTS: Many women describe self-identifying the cancer recurrence fairly quickly due to new symptoms. Many feel that the goal for treating their recurrence is to control versus cure the cancer. They describe the subsequent process of diagnosis and TDM for ROC as quick and straightforward with all women accepting the oncologists' treatment recommendation. They feel that the type and number of treatment options are limited. They have a strong desire for physician continuity in their care. Participants feel that their doctor's recommendations as well as their previous experience with ovarian cancer are strong factors influencing their current TDM process. CONCLUSIONS: Shared decision making is based on a simultaneous participation of both the physician and patient in TDM. When faced with ROC, women feel that their doctor's recommendation and their past experience with treatment and TDM are prominent factors influencing the current TDM process.
Asunto(s)
Neoplasias Ováricas/terapia , Adulto , Anciano , Toma de Decisiones , Femenino , Humanos , Entrevistas como Asunto , Persona de Mediana Edad , Neoplasias Ováricas/psicología , Aceptación de la Atención de Salud/psicología , Participación del Paciente/psicología , Relaciones Médico-Paciente , Recurrencia , Apoyo SocialRESUMEN
As the applications for stents expand, contract manufacturers have responded with improvements in manufacturing operations.
Asunto(s)
Prótesis Vascular , Stents/tendencias , Diseño de Equipo , Análisis de Falla de Equipo , Propiedades de SuperficieRESUMEN
BACKGROUND: Early endometrial cancer with low-risk pathological features can be successfully treated by surgery alone. External beam radiotherapy added to surgery has been investigated in several small trials, which have mainly included women at intermediate risk of recurrence. In these trials, postoperative radiotherapy has been shown to reduce the risk of isolated local recurrence but there is no evidence that it improves recurrence-free or overall survival. We report the findings from the ASTEC and EN.5 trials, which investigated adjuvant external beam radiotherapy in women with early-stage disease and pathological features suggestive of intermediate or high risk of recurrence and death from endometrial cancer. METHODS: Between July, 1996, and March, 2005, 905 (789 ASTEC, 116 EN.5) women with intermediate-risk or high-risk early-stage disease from 112 centres in seven countries (UK, Canada, Poland, Norway, New Zealand, Australia, USA) were randomly assigned after surgery to observation (453) or to external beam radiotherapy (452). A target dose of 40-46 Gy in 20-25 daily fractions to the pelvis, treating five times a week, was specified. Primary outcome measure was overall survival, and all analyses were by intention to treat. These trials were registered ISRCTN 16571884 (ASTEC) and NCT 00002807 (EN.5). FINDINGS: After a median follow-up of 58 months, 135 women (68 observation, 67 external beam radiotherapy) had died. There was no evidence that overall survival with external beam radiotherapy was better than observation, hazard ratio 1.05 (95% CI 0.75-1.48; p=0.77). 5-year overall survival was 84% in both groups. Combining data from ASTEC and EN.5 in a meta-analysis of trials confirmed that there was no benefit in terms of overall survival (hazard ratio 1.04; 95% CI 0.84-1.29) and can reliably exclude an absolute benefit of external beam radiotherapy at 5 years of more than 3%. With brachytherapy used in 53% of women in ASTEC/EN.5, the local recurrence rate in the observation group at 5 years was 6.1%. INTERPRETATION: Adjuvant external beam radiotherapy cannot be recommended as part of routine treatment for women with intermediate-risk or high-risk early-stage endometrial cancer with the aim of improving survival. The absolute benefit of external beam radiotherapy in preventing isolated local recurrence is small and is not without toxicity.
Asunto(s)
Neoplasias Endometriales , Braquiterapia/efectos adversos , Braquiterapia/métodos , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/patología , Neoplasias Endometriales/radioterapia , Femenino , Humanos , Estimación de Kaplan-Meier , Estudios Multicéntricos como Asunto , Recurrencia Local de Neoplasia , Periodo Posoperatorio , Radioterapia Adyuvante/efectos adversos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Micro blasting is used in a range of applications including catheter, stent and pacemaker manufacturing. The correct media to use for the required surface is defined here together with some of the finer points of the process to ensure successful results.
Asunto(s)
Biotecnología/instrumentación , Biotecnología/métodos , Diseño de Equipo/instrumentación , Diseño de Equipo/métodos , Equipos y Suministros , Propiedades de SuperficieRESUMEN
GOALS OF WORK: The study purpose was to evaluate a nurse-led supportive care clinical case management program in the community using multi-methods to delineate care processes prior to outcome evaluation. MATERIALS AND METHODS: Multiple data sources including program service records, chart reviews and interviews with nurses and key interdisciplinary informants were used to identify population served (coverage and reach), processes of care (implementation), and providers' perceptions of the effectiveness of the nurse-led program (reaction). MAIN RESULTS: The program provided care to over 700 cancer patients in a 1-year period. Nurse-led support interventions were focused on direct care inclusive of teaching/coaching for symptom management, counseling and support, and mobilization of services through system navigation based on an initial comprehensive assessment of supportive care needs. CONCLUSIONS: Nurse-led models of supportive care have the potential to reduce unmet supportive care needs, improve continuity of care, and overall health-related quality of life that should be tested in future trials.
Asunto(s)
Servicios de Salud Comunitaria , Neoplasias/terapia , Enfermeras Clínicas , Planificación de Atención al Paciente , Adulto , Anciano , Anciano de 80 o más Años , Manejo de Caso , Continuidad de la Atención al Paciente , Femenino , Servicios de Atención de Salud a Domicilio , Humanos , Masculino , Persona de Mediana Edad , Apoyo Social , Adulto JovenRESUMEN
INTRODUCTION: Accrual rates for a randomized trial of decongestive therapy in breast cancer patients with lymphedema were lower than anticipated. In two centres, patients presenting to lymphedema clinic were screened for eligibility to understand the accrual process and help define the patient population. MATERIALS AND METHODS: All breast cancer patients presenting to two lymphedema clinics in regional cancer centres were screened for study entry. Circumferential arm measurements were taken and volumes calculated. Patients were then screened for trial eligibility. All report forms were sent to the trial coordinating centre. RESULTS: A total of 408 patients were screened. Median arm volume excess was 239 ml (9.5%). One third of patients had little or no excess volume. Only 28.3% of patients had sufficient excess volume for trial eligibility. Of these, a significant number of patients were excluded because of active malignancy or previous decongestive therapy. CONCLUSIONS: The finding of moderate to severe lymphedema observed in clinics screening for trial eligibility was less than expected. The natural history of lymphedema in breast cancer patients is potentially changing. Some patients may be presenting with sensory changes suggestive of lymphedema but due to other causes, such as nerve disruption following axillary dissection.
Asunto(s)
Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/terapia , Linfedema/etiología , Selección de Paciente , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de Investigación , Brazo/patología , Axila/cirugía , Femenino , Humanos , Escisión del Ganglio Linfático/efectos adversos , Ganglios Linfáticos/cirugía , Metástasis Linfática/patología , Linfedema/diagnóstico , Tamizaje Masivo , Cooperación del Paciente , Calidad de VidaRESUMEN
The relationships between the concentration of metal in the growth medium, Cs, the concentration of metal absorbed by the plant, Cp, and the total biomass achieved, M, all of which are factors relevant to the efficiency of metal uptake and tolerance by the plant, have been investigated via the physiological response of Brassica juncea seedlings to Ni stress. The factorial growth experiments treated the Ni concentration in agar medium and the diurnal light quanta as independently variable parameters. Observations included the evidence of light enhancement of Ni toxicity in the root, as well as at the whole-plant level. The shoot mass index possibly is an indicator of the amount of shoot metal sequestration in B. juncea, as are the logarithmic variation of Cp with Cs and the power-law dependence of M on Cp. The sum total of these observations indicates that, for the Ni accumulating plant B. juncea, the overall metabolic allocation to either growth or metal tolerance of the plant is important. Neither a rapid biomass increase nor a high metal absorbed concentration favored the removal of high metal mass from the medium. Rather, the plants with a moderate rate of biomass growth and a moderate absorbed metal concentration demonstrated the ability to remove the maximum mass of metal from the medium. The implication of these results as related to the extant model of phyoextraction efficiency is discussed.