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BACKGROUND: Family physicians (fps) play a role in aspects of personalized medicine in cancer, including assessment of increased risk because of family history. Little is known about the potential role of fps in supporting cancer patients who undergo tumour gene expression profile (gep) testing. METHODS: We conducted a mixed-methods study with qualitative and quantitative components. Qualitative data from focus groups and interviews with fps and cancer specialists about the role of fps in breast cancer gep testing were obtained during studies conducted within the pan-Canadian canimpact research program. We determined the number of visits by breast cancer patients to a fp between the first medical oncology visit and the start of chemotherapy, a period when patients might be considering results of gep testing. RESULTS: The fps and cancer specialists felt that ordering gep tests and explaining the results was the role of the oncologist. A new fp role was identified relating to the fp-patient relationship: supporting patients in making adjuvant therapy decisions informed by gep tests by considering the patient's comorbid conditions, social situation, and preferences. Lack of fp knowledge and resources, and challenges in fp-oncologist communication were seen as significant barriers to that role. Between 28% and 38% of patients visited a fp between the first oncology visit and the start of chemotherapy. CONCLUSIONS: Our findings suggest an emerging role for fps in supporting patients who are making adjuvant treatment decisions after receiving the results of gep testing. For success in this new role, education and point-of-care tools, together with more effective communication strategies between fps and oncologists, are needed.
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The risk of P loss from manured soils is more related to P fractions than total P concentration in manure. This study examined the impact of manure P fractions on P losses from liquid swine manure- (LSM), solid cattle manure- (SCM), and monoammonium phosphate- (MAP) treated soils. Manure or fertilizer was applied at 50 mg P kg soil, mixed, and incubated at 20°C for 6 wk to simulate the interaction between applied P and soil when P is applied well in advance of a high risk period for runoff. Phosphorus fractions in manure were determined using the modified Hedley fractionation scheme. We used simulated rainfall (75 mm h⻹ for 1 h) to quantify P losses in runoff from two soils (sand and clay loam). The proportion of total labile P (total P in water+NaHCO fractions) in manure was significantly greater in LSM (70%) than SCM (44%). Mean dissolved reactive P (DRP) load in runoff over 60 min was greatest from MAP-treated soil (18.1 mg tray⻹), followed by LSM- (14.0 mg tray⻹) and SCM- (11.0 mg tray⻹) treated soils, all of which were greater than mean DRP load from the check (5.2 mg tray⻹). Total labile P (water+NaHCO) in manure was a more accurate predictor of runoff DRP loads than water extractable P, alone, for these two soils. Therefore, NaHCO extraction of manure P may be a useful tool for managing the risk of manure P runoff losses when manure is applied outside a high risk period for runoff loss.
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Estiércol/análisis , Fósforo/química , Suelo/química , Animales , Bovinos , Fertilizantes , Factores de Tiempo , Movimientos del AguaRESUMEN
The diagnostic phase of cancer care is an anxious time for patients. Patient navigation is a way of assisting and supporting individuals during this time. The aim of this review is to explore patient navigation and its role in the diagnostic phase of cancer care. We reviewed the literature for definitions and models of navigation, preparation for the role and impact on patient outcomes, specifically addressing the role of the nurse in patient navigation. Interviews and focus groups with healthcare providers and managers provided further insight from these stakeholder groups. Common to most definitions of navigation is the navigator's multifaceted role in facilitating processes of care, assisting patients to overcome barriers and providing information and support. Navigation may be provided by laypersons, clerical staff and/or healthcare professionals. In the diagnostic phase it has the potential to affect efficiency of diagnostic testing, patients' experience during this time and preparation for decision-making around treatment options. Patient care during the diagnostic phase requires various levels of navigation, according to individual informational, physical and psychosocial needs. Identifying those individuals who require more support--whether physical or psychosocial--during the diagnostic phase is of critical importance.
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Manejo de Caso/organización & administración , Neoplasias/diagnóstico , Rol de la Enfermera , Enfermería Oncológica/organización & administración , Actitud del Personal de Salud , Grupos Focales , Humanos , Relaciones Interprofesionales , Modelos Organizacionales , Neoplasias/enfermería , Rol de la Enfermera/psicología , Enfermería Oncológica/educación , Apoyo Social , Encuestas y CuestionariosRESUMEN
With next generation sequencing, physicians are faced with more complex and uncertain data, particularly incidental findings (IF). Guidelines for the return of IF have been published by learned societies. However, little is known about how patients are affected by these results in a context of oncogenetic testing. Over 4 years, 2500 patients with an indication for genetic testing underwent a gene cancer panel. If an IF was detected, patients were contacted by a physician/genetic counsellor and invited to take part in a semi-structured interview to assess their understanding of the result, the change in medical care, the psychological impact, and the transmission of results to the family. Fourteen patients (0.56%) were delivered an IF in a cancer predisposition gene (RAD51C, PMS2, SDHC, RET, BRCA2, CHEK2, CDKN2A, CDH1, SUFU). Two patients did not collect the results and another two died before the return of results. Within the 10 patients recontacted, most of them reported surprise at the delivery of IF, but not anxiety. The majority felt they had chosen to obtain the result and enough information to understand it. They all initiated the recommended follow-up and did not regret the procedure. Information regarding the IF was transmitted to their offspring but siblings or second-degree relatives were not consistently informed. No major adverse psychological events were found in our experience. IF will be inherent to the development of sequencing, even for restricted gene panels, so it is important to increase our knowledge on the impact of such results in different contexts.
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Actitud , Predisposición Genética a la Enfermedad/psicología , Neoplasias/genética , Pacientes/psicología , Adulto , Anciano , Femenino , Pruebas Genéticas , Humanos , Hallazgos Incidentales , Masculino , Persona de Mediana Edad , Neoplasias/psicologíaRESUMEN
With the development of next generation sequencing, beyond identifying the cause of manifestations that justified prescription of the test, other information with potential interest for patients and their families, defined as secondary findings (SF), can be provided once patients have given informed consent, in particular when therapeutic and preventive options are available. The disclosure of such findings has caused much debate. The aim of this work was to summarize all opinion-based studies focusing on SF, so as to shed light on the concerns that this question generate. A review of the literature was performed, focusing on all PubMed articles reporting qualitative, quantitative or mixed studies that interviewed healthcare providers, participants, or society regarding this subject. The methodology was carefully analysed, in particular whether or not studies made the distinction between actionable and non-actionable SF, in a clinical or research context. From 2010 to 2016, 39 articles were compiled. A total of 14,868 people were interviewed (1259 participants, 6104 healthcare providers, 7505 representatives of society). When actionable and non-actionable SF were distinguished (20 articles), 92% of respondents were keen to have results regarding actionable SF (participants: 88%, healthcare providers: 86%, society: 97%), against 70% (participants: 83%, healthcare providers: 62%, society: 73%) for non-actionable SF. These percentages were slightly lower in the specific situation of children probands. For respondents, the notion of the «patient's choice¼ is crucial. For healthcare providers, the importance of defining policies for SF among diagnostic lab, learning societies and/or countries is outlined, in particular regarding the content and extension of the list of actionable genes to propose, the modalities of information, and the access to information about adult-onset diseases in minors. However, the existing literature should be taken with caution, since most articles lack a clear definition of SF and actionability, and referred to hypothetical scenarios with limited information to respondents. Studies conducted by multidisciplinary teams involving patients with access to results are sadly lacking, in particular in the medium term after the results have been given. Such studies would feed the debate and make it possible to measure the impact of such findings and their benefit-risk ratio.
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Conducta de Elección , Secuenciación del Exoma/ética , Asesoramiento Genético/psicología , Pruebas Genéticas/ética , Hallazgos Incidentales , Participación de los Interesados , Actitud , Revelación , Asesoramiento Genético/normas , Humanos , Pacientes/psicologíaRESUMEN
Tamoxifen was evaluated as initial hormone therapy for metastatic breast cancer in 85 premenopausal patients. Tamoxifen responders continued on tamoxifen, while tamoxifen failures and initial responders who later progressed were to receive ovarian ablation next. Of 74 evaluable patients, 5 had complete responses (CR) and 15 had partial responses (PR) while 12 remained stable (ST), giving response rates of 27% (CR + PR) or 43% (CR + PR + ST). Of the 23 patients who initially responded (CR + PR + ST) to tamoxifen but then progressed and received ovarian ablation alone, 15 are assessable. Nine (60%) responded (CR + PR + ST) to ovarian ablation. Sixteen patients who failed tamoxifen had ovarian ablation alone, and of 14 assessable patients 2 had ST while 12 progressed. Thus response to tamoxifen strongly predicted response to ovarian ablation (P = 0.021). Serial follicle stimulating hormone, prolactin, and estradiol levels suggested that tamoxifen does not act by induction of a "medical ovariectomy" or by alteration of prolactin levels in premenopausal patients.
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Neoplasias de la Mama/tratamiento farmacológico , Tamoxifeno/uso terapéutico , Estradiol/sangre , Femenino , Hormona Folículo Estimulante/sangre , Humanos , Menopausia , Menstruación , Metástasis de la Neoplasia , Ovario/cirugía , Progesterona/sangre , Prolactina/sangre , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Tamoxifeno/efectos adversos , Tamoxifeno/farmacologíaRESUMEN
PURPOSE: The purpose of this review was to assess the outcome of patients with non-Hodgkin's lymphoma (NHL) who achieve an incomplete or slow response to front-line chemotherapy and to determine whether salvage treatment with intensive combination chemotherapy with or without autologous bone marrow transplantation (ABMT) is successful in such patients. METHODS: A comprehensive literature search of studies using combination chemotherapy for the front-line therapy of advanced-stage intermediate- and high-grade NHL and for salvage therapy of patients with a partial response (PR) was reviewed. RESULTS: The median survival duration of patients with a PR ranged between 5 to 14 months, while the median survival duration of patients with a complete response (CR) was not reached in many studies. For patients in CR, the probability of survival at 24 months ranged between 0.79 to 1, while for patients in PR it ranged from 0 to 0.31. The rapidity of a response to front-line therapy was often found to be of prognostic importance. Patients who relapsed after a PR to front-line therapy had similar outcomes to intensive salvage therapy as those who relapsed after a CR. ABMT performed immediately after a PR to induction therapy, before progressive disease occurred, resulted in high CR rates in nonrandomized studies. CONCLUSION: Patients with aggressive NHL who experience a PR or who respond slowly to front-line chemotherapy have a poor prognosis. Early introduction of dose-intensive salvage therapy before the development of progressive disease may benefit patients with a PR and requires testing in randomized clinical trials.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma no Hodgkin/tratamiento farmacológico , Terapia Recuperativa , Trasplante de Médula Ósea , Quimioterapia Adyuvante , Humanos , Linfoma no Hodgkin/mortalidad , Linfoma no Hodgkin/terapia , Inducción de Remisión , Análisis de SupervivenciaRESUMEN
PURPOSE: To review critically the literature regarding effects of estrogen replacement therapy (ERT)/combined estrogen and progesterone replacement therapy (HRT) on the risk of breast cancer and on other health risks and benefits in postmenopausal women, with a focus on risks and benefits in women with a previous diagnosis of breast cancer. METHOD: A literature search was conducted using Medline, Cancerline, and the bibliographies of reports published as of March 1995. All five published meta-analyses that examined the risk of breast cancer in relation to ERT/HRT in otherwise healthy women were critically reviewed. All known reports of women with a history of breast cancer given ERT/HRT subsequent to diagnosis and additional reports regarding the benefits of ERT/HRT were also reviewed. RESULTS: None of the five meta-analyses demonstrated a significantly increased risk of developing breast cancer in ever users compared with never users of ERT/HRT. Current use may be associated with a small increased risk. This increased risk should be balanced by the expected benefits of ERT/HRT on quality of life, bone metabolism, and cardiovascular function. Preliminary information does not suggest a major detrimental effect of ERT/HRT in women with a previous diagnosis of breast cancer, but these reports include few women with limited follow-up data. There are no randomized trials in women with a previous diagnosis of breast cancer. CONCLUSION: In healthy postmenopausal women, the benefits associated with ERT/HRT outweigh the risks. In women with a previous diagnosis of breast cancer, the balance of risks and benefits should be explored in randomized controlled trials.
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Neoplasias de la Mama/inducido químicamente , Terapia de Reemplazo de Estrógeno/efectos adversos , Estrógenos/efectos adversos , Recurrencia Local de Neoplasia/inducido químicamente , Posmenopausia , Progesterona/efectos adversos , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Estudios Cruzados , Estrógenos/administración & dosificación , Femenino , Humanos , Metaanálisis como Asunto , Osteoporosis Posmenopáusica/etiología , Osteoporosis Posmenopáusica/prevención & control , Posmenopausia/efectos de los fármacos , Posmenopausia/fisiología , Posmenopausia/psicología , Progesterona/administración & dosificación , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , RiesgoRESUMEN
PURPOSE: The object of this study was to compare the relative sensitivities of morphologic, immunophenotypic, gene rearrangement, cytogenetic, and polymerase chain reaction (PCR) analyses in the detection of lymphoma cells in the bone marrow and peripheral blood of patients with follicular lymphoma. PATIENTS AND METHODS: Bone marrow and peripheral-blood samples from 28 newly diagnosed patients with follicular lymphoma referred from several different medical centers were assessed. Routine morphologic assessment was performed initially and the remainder of the sample was aliquoted for DNA extraction to be used for gene rearrangement and PCR analyses and for immunophenotypic and cytogenetic analyses where a sufficient amount of sample remained. RESULTS: Morphologic assessment of the bone marrow was positive for lymphoma cells in 11 of 28 patients. PCR amplification of t(14;18) breakpoint DNA detected lymphoma cells in 17 of 24 patients assessed. Morphologic assessment detected lymphoma cells in three bone marrow samples that were negative by PCR. PCR analysis was the only method able to detect circulating lymphoma cells in peripheral blood at diagnosis and was positive in 15 of 24 samples. The other methods of assessment did not show lymphoma in any samples in which lymphoma was not detected by morphologic or PCR analysis. Lymphoma cells were found in the bone marrow and/or peripheral blood as frequently in early-stage patients as in advanced-stage patients. CONCLUSION: PCR amplification of t(14;18) breakpoint DNA together with morphologic assessment had the highest yield of detecting lymphoma cells in the bone marrow and/or peripheral blood of our population of newly diagnosed patients with follicular lymphoma. The clinical significance and prognostic importance of lymphoma cells detected by PCR in the bone marrow and/or peripheral blood of newly diagnosed follicular lymphoma patients awaits long-term follow-up data of these and additional patients.
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Linfoma Folicular/diagnóstico , Secuencia de Bases , Médula Ósea/patología , Cromosomas Humanos Par 14 , Cromosomas Humanos Par 18 , Reordenamiento Génico , Humanos , Inmunofenotipificación , Linfoma Folicular/sangre , Linfoma Folicular/genética , Linfoma Folicular/patología , Datos de Secuencia Molecular , Estadificación de Neoplasias , Reacción en Cadena de la Polimerasa , Sensibilidad y Especificidad , Translocación GenéticaRESUMEN
PURPOSE: Practice guidelines for cancer management have been in use in the province of British Columbia (BC), Canada, since the mid 1970s. To evaluate practice guideline compliance, treatment received was compared with treatment recommended in a population-based cohort of women with breast cancer. METHODS: All incident cases (n = 939) of invasive, pathologically node-negative breast cancer diagnosed in 1991 were identified from the BC Cancer Registry. Treatment details were abstracted from cancer clinic records for cases referred to the BC Cancer Agency (BCCA) (n = 661) and original source documents for nonreferred cases. Management decisions were considered compliant if the patient received the recommended treatment or was entered onto a randomized trial of the modality being assessed. RESULTS: Overall compliance with adjuvant therapy guidelines was 97% for radiotherapy, 96% for chemotherapy, and 89% for tamoxifen. An oncology specialist was consulted by 94% of patients with an indication for adjuvant treatment and by 58% of those without an indication (odds ratio [OR] = 10.7; 95% confidence interval, 7.0 to 16.4). Compliance with a guideline to deliver radiotherapy was 95%; with chemotherapy, 77%; and with tamoxifen, 68%. Compliance with a guideline that stated no adjuvant treatment was indicated was 99% for radiotherapy, 98% for chemotherapy, and 92% for tamoxifen. Noncompliance among patients with an indication for treatment was related to nonreferral to an oncology specialist and less complete implementation of guideline changes in the community as compared with cancer center practices. CONCLUSION: Compliance was high, but scheduled updating and more effective community implementation could further improve consistency of care.
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Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Guías de Práctica Clínica como Asunto/normas , Anciano , Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Colombia Británica , Femenino , Humanos , Persona de Mediana Edad , Derivación y Consulta , Tamoxifeno/uso terapéuticoRESUMEN
PURPOSE: Interferon alfa alone has shown antitumor activity against Kaposi's sarcoma (KS), and phase I and II clinical trials showed that interferon and zidovudine could be administered safely to patients with human immunodeficiency virus (HIV)-associated KS. These observations led to our trial of zidovudine with two dose levels of interferon alfa. METHODS: HIV-positive patients with KS were eligible if they were older than 18 years of age, had a performance status of 0 to 2, and were free of active infection. All patients received zidovudine 500 mg daily and were randomized to receive-interferon alfa 1 million U or 8 million U subcutaneously daily. RESULTS: The 108 eligible and assessable patients were well balanced for known prognostic factors. Response was reported in 31% of high-dose therapy and 8% of low-dose therapy patients (P=.011). Response at both dose levels was higher for patients with CD4 counts greater than 150 x 10(9)/L. The median time to progression was longer for patients in the 8-million U arm (18 v 13 weeks; P=.002). Both hematologic and nonhematologic toxicities were higher in the high-dose arm; 50 of 54 patients who received 8 million U required dose alterations in the first 4 months compared with only 19 of 53 patients who received 1 million U (P=.0002). No significant differences were reported with respect to improvement in CD4 count, elimination of p24 antigen, or development of opportunistic infections. CONCLUSION: Zidovudine and moderate-dose-interferon alfa may be combined safely for the treatment of HIV-associated KS, and both response to treatment and toxicity are dose related.
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Fármacos Anti-VIH/administración & dosificación , Antineoplásicos/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , Interferón-alfa/administración & dosificación , Sarcoma de Kaposi/tratamiento farmacológico , Zidovudina/administración & dosificación , Adulto , Fármacos Anti-VIH/efectos adversos , Antineoplásicos/efectos adversos , Recuento de Linfocito CD4 , Progresión de la Enfermedad , Femenino , Infecciones por VIH/complicaciones , Humanos , Interferón-alfa/efectos adversos , Masculino , Estudios Prospectivos , Sarcoma de Kaposi/complicaciones , Zidovudina/efectos adversosRESUMEN
PURPOSE: To determine the prevalence of use of complementary/alternative medicine (CAM) by breast cancer survivors in Ontario, Canada, and to compare the characteristics of CAM users and CAM nonusers. PATIENTS AND METHODS: A questionnaire was mailed to a random sample of Ontario women diagnosed with breast cancer in 1994 or 1995. RESULTS: The response rate was 76.3%. Overall, 66.7% of the respondents reported using CAM, most often in an attempt to boost the immune system. CAM practitioners (most commonly chiropractors, herbalists, acupuncturists, traditional Chinese medicine practitioners, and/or naturopathic practitioners) were visited by 39.4% of the respondents. In addition, 62.0% reported use of CAM products (most frequently vitamins/minerals, herbal medicines, green tea, special foods, and essiac). Almost one half of the respondents informed their physicians of their use of CAM. Multiple logistic regression analysis determined that support group attendance was the only factor significantly associated with CAM use. CONCLUSION: CAM use is common among Canadian breast cancer survivors, many of whom are discussing CAM therapy options with their physicians. Knowledge of CAM therapies is necessary for physicians and other health care practitioners to help patients make informed choices. CAM use may play a role in the positive benefits associated with support group attendance.
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Neoplasias de la Mama/terapia , Terapias Complementarias/estadística & datos numéricos , Actitud , Neoplasias de la Mama/psicología , Comunicación , Femenino , Humanos , Persona de Mediana Edad , Ontario , Relaciones Médico-PacienteRESUMEN
PURPOSE: To examine variations in physicians' recommendations for systemic adjuvant therapy in the treatment of women with node-negative breast cancer (NNBC) and to determine factors used in making specific recommendations. MATERIALS AND METHODS: A questionnaire was sent by mail to all 149 Ontario physicians who actively treated breast cancer in 1993. The questionnaire described 48 clinical scenarios of women with NNBC, which included all possible combinations of the following factors: menopausal status, tumor size, hormone receptor status, histologic and nuclear grade, and lymphatic and/or vascular invasion. Respondents rated the appropriateness of administering tamoxifen, combination chemotherapy, or both tamoxifen and combination chemotherapy on a nine-point scale from extremely inappropriate to extremely appropriate. Respondent agreement and disagreement were tabulated for each scenario, and factors associated with specific treatment ratings were analyzed by logistic regression. RESULTS: The response rate was 87%. Agreement for the appropriateness of specific therapies was most evident where clinical trials have demonstrated efficacy, whereas disagreement was observed in scenarios in which support for a specific treatment is not available in the current literature. Relevant tumor- and patient-specific factors were used in decision-making; personal characteristics of the respondents had no statistically significant impact on appropriateness ratings. CONCLUSION: The physicians surveyed had good knowledge of NNBC prognostic factors, but had a range of opinion on optimal therapy for many clinical scenarios, which reflects current knowledge of the benefits of adjuvant therapy for NNBC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Actitud del Personal de Salud , Neoplasias de la Mama/tratamiento farmacológico , Adulto , Neoplasias de la Mama/química , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Estudios Transversales , Recolección de Datos , Femenino , Humanos , Masculino , Menopausia , Persona de Mediana Edad , Ontario , Análisis de Regresión , Factores de Riesgo , Tamoxifeno/uso terapéuticoRESUMEN
PURPOSE: To compare the safety and efficacy of liposomal daunorubicin (DaunoXome; NeXstar Pharmaceuticals, Inc, Boulder, CO) with a reference regimen of doxorubicin, bleomycin, and vincristine (ABV) in advanced AIDS-related Kaposi's sarcoma (KS). PATIENTS AND METHODS: In a prospective randomized phase III trial, 232 patients were randomized to receive DaunoXome 40 mg/m2 or a combination regimen of doxorubicin 10 mg/m2, bleomycin 15 U, and vincristine 1 mg, administered intravenously every 2 weeks. Treatment was continued until complete response (CR), disease progression, or unacceptable toxicity. RESULTS: Of 232 patients randomized, 227 were treated: 116 with DaunoXome and 111 with ABV. The overall response rate (CR or partial response [PR]) was 25% (three CRs and 26 PRs) for DaunoXome and 28% (one CR and 30 PRs) for ABV. The difference in response rates was not statistically significant. The median survival time was 369 days for DaunoXome patients and 342 days for ABV patients (P = .19). The median time to treatment failure was 115 days for DaunoXome and 99 days for ABV (P = .13). ABV patients experienced significantly more alopecia and neuropathy (P < .0001). DaunoXome patients experienced more grade 4 neutropenia (P = .021). Cardiac function remained stable, with no instances of congestive heart failure on either treatment arm. CONCLUSION: In this large phase III trial, the efficacy of DaunoXome was comparable to that of ABV. Response rates, time to treatment failure, and overall survival were similar on both treatment arms. DaunoXome is a safe and effective primary therapy for advanced AIDS-related KS.
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Síndrome de Inmunodeficiencia Adquirida/complicaciones , Antibióticos Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Daunorrubicina/administración & dosificación , Sarcoma de Kaposi/tratamiento farmacológico , Adulto , Alopecia/inducido químicamente , Antibióticos Antineoplásicos/efectos adversos , Antibióticos Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bleomicina/administración & dosificación , Bleomicina/efectos adversos , Canadá , Daunorrubicina/efectos adversos , Daunorrubicina/uso terapéutico , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Portadores de Fármacos , Femenino , Humanos , Liposomas , Masculino , Persona de Mediana Edad , Neutropenia/inducido químicamente , Estudios Prospectivos , Inducción de Remisión , Sarcoma de Kaposi/etiología , Sarcoma de Kaposi/mortalidad , Tasa de Supervivencia , Insuficiencia del Tratamiento , Estados Unidos , Vincristina/administración & dosificación , Vincristina/efectos adversosRESUMEN
The t(14;18) translocation juxtaposes the bcl-2 gene on chromosome 18 to a joining (J) gene segment of the immunoglobulin heavy chain gene (IgH) on chromosome 14. Up to 85% of non-Hodgkin's lymphomas (NHL) are t(14;18) positive. Recent reports have documented point mutations in the second exon of translocated bcl-2 alleles and postulated that immunoglobulin variable (V) region somatic hypermutation, related to Ig sequences approximately 250 Kb downstream, may be mediating these mutations. We have examined the third exon of bcl-2, directly adjacent to Ig sequences in the t(14;18), for point mutations. In particular, we studied the translated region of exon 3 in 45 NHLs by SSCP analysis and failed to detect a single point mutation. Further, we sequenced eleven t(14;18) breakpoints, including both bcl-2 and JH sequences, and detected only one point mutation, in a JH-derived sequence. We conclude that immunoglobulin V region somatic hypermutation does not induce point mutations into the t(14;18) breakpoint region or into the translated region of the third exon of bcl-2 alleles involved in the t(14;18) translocation, conserving the membrane insertion properties of the carboxyl tail of this protein.
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Linfoma no Hodgkin/genética , Proto-Oncogenes , Secuencia de Bases , Cromosomas Humanos Par 14 , Cromosomas Humanos Par 18 , Cartilla de ADN/química , Exones , Humanos , Datos de Secuencia Molecular , Mutación Puntual , Polimorfismo Conformacional Retorcido-Simple , Translocación GenéticaRESUMEN
The role of monocytes, T-lymphocytes, and Ia antigen expression in the mediation of prostaglandin E1 (PGE1) stimulation of in vitro erythroid progenitor cells was studied. Human peripheral blood mononuclear cells were selectively depleted of monocytes or T-lymphocytes. Stimulation of burst formation was noted at PGE1 concentrations of 10(-7) and 10(-8) M in the presence or absence of monocytes or T-lymphocytes in the cultures. The role of Ia antigen expression in the stimulatory response to PGE1 was explored by performing clonogenic assays on monocyte-depleted cells that had been pretreated with complement alone, monoclonal anti-Ia (NEI-011) and complement, or anti-Ia alone. Colony formation was reduced by 50%-89% after treatment with anti-Ia and complement. The stimulatory response to PGE1 was abrogated following anti-Ia-complement treatment, but was preserved following treatment with anti-Ia alone. These results suggest that monocytes and T-lymphocytes are not required for PGE1-induced stimulation of burst formation and that Ia antigen expression correlates with sensitivity to the stimulatory effect of PGE1.
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Alprostadil/farmacología , Células Madre Hematopoyéticas/efectos de los fármacos , Antígenos de Histocompatibilidad Clase II/biosíntesis , Anticuerpos Monoclonales , Separación Celular , Humanos , Monocitos , Linfocitos TRESUMEN
Recently, there has been a proliferation of new biomarkers, some of which may lead to an improved prognostic index or may influence treatment selection. However, there are methodological and statistical issues that require attention in assessing the role and use of these prognostic factors. Between 1977 and 1986, 1097 primary breast cancer patients were accrued for multidisciplinary research at the Henrietta Banting Breast Centre, Women's College Hospital; follow-up to 1990 is complete for 96% of the patients. Data for these patients are used here to illustrate strategies: (1) for the comparison of results from diverse assessments of biomarkers; (2) for the improved comparability of inter-laboratory results; (3) for the examination of the results from monoclonal or polyclonal antibody assays for possible clinically relevant bimodality; (4) for good statistical resolution of overlapping distributions; (5) that involve the use of quantitative values for prognostic factors whenever possible; and (6) for improved multivariate analyses. Good data handling and analyses may enable more accurate and rapid assessment of new prognostic factors, thereby expediting and improving their clinical application.
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Biomarcadores de Tumor/análisis , Neoplasias de la Mama/diagnóstico , Estadística como Asunto/métodos , Análisis de Varianza , Anticuerpos Monoclonales , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Ciclo Celular , ADN de Neoplasias/análisis , Femenino , Estudios de Seguimiento , Humanos , Laboratorios/normas , Pronóstico , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisisRESUMEN
The cohort study design has been used successfully in clinical cancer research. Cohorts, however, are valuable only if they produce results which are valid and generalizable. Some hospital-based inception cohorts satisfy both these requirements and may thus be useful research tools. The development of one such hospital-based cohort, the Henrietta Banting Breast Centre database, is described. This cohort is composed of 1097 women diagnosed with primary breast cancer at Women's College Hospital, Toronto, from January 1977 through December 1986. Details of diagnostic procedures, pathology, treatment, dates and sites of recurrence, and date of death are available on 96% of women. By comparison with published series and with the Ontario Cancer Registry, we have demonstrated validity and generalizability. A major advantage is the ready availability of paraffin tissue blocks on virtually all cases, facilitating analyses of the prognostic importance of specific biologic variables and immunocytochemical hormone assays. Other completed studies and future uses of the cohort are described.
Asunto(s)
Neoplasias de la Mama/epidemiología , Bases de Datos Factuales , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/cirugía , Estudios de Cohortes , Recolección de Datos/normas , Estudios de Evaluación como Asunto , Femenino , Hospitalización , Humanos , Persona de Mediana Edad , Modelos Estadísticos , Recurrencia Local de Neoplasia , Ontario/epidemiología , Pronóstico , Análisis de SupervivenciaRESUMEN
Tumour estrogen receptor (ER) status may determine the medical treatment of a patient with breast cancer; yet inter-laboratory results can vary markedly, particularly when absolute cut-offs in fmol/mg cytosol protein are used. The use of standardized log units is proposed to permit greater inter-laboratory comparability. We have assessed the biochemical ER values using the dextran-coated charcoal method with three data sets, two quality control (QC) sets for Ontario laboratories and a data set with values for 184 primary breast cancer patients seen at Women's College Hospital (WCH) between 1985 and 1986. The distributions for all the raw data were skewed toward the lower end of the range; a log transformation improved the symmetry of the distributions. There was marked inter-laboratory variation in the QC data, and standardized log units greatly reduced this variability. The WCH data had similar differentiation by tumour size and nodal status with both the raw data and standardized log units. However, standardized log units provided more consistent evidence of an association between ER and immunohistochemical ERICA. The standardized log units provide quantitative receptor values suitable for multi-centre research, for future work with clinical outcomes, and for the daily management of patients.
Asunto(s)
Neoplasias de la Mama/química , Química Clínica/normas , Receptores de Estrógenos/análisis , Carbón Orgánico , Dextranos , Femenino , Humanos , Inmunohistoquímica/normas , Control de CalidadRESUMEN
Oestrogen and progesterone receptor (ER and PgR) assay values are frequently used in medical decision-making for breast cancer patients. We have proposed statistical standardization of receptor assay values to improve inter-laboratory comparability, and now report the use of standardized log units (SLU) to investigate the effects of ER and PgR cut-points on time to first recurrence outside the breast (DFS). Between 1980 and 1986, there were 678 primary breast cancer patients treated at the Henrietta Banting Breast Centre (HBBC). The effects of ER and PgR cut-points were examined with multivariate analyses considering the variables: age, tumour size, nodal status, weight and adjuvant treatment. We considered receptor assay cut-points ranging from - 1.0 to + 1.0 SLU (ER between 7 and 166 fmol/mg protein; PgR between 7 and 181 fmol/mg protein). PgR was included in the multivariate prognostic models more often than ER, although patients had a better prognosis with both larger ER and PgR values. There was no best cut-point for ER or PgR, and there was strong evidence that ER and PgR should be considered as continuous rather than dichotomous (negative, positive) variables. Patient prognosis should also be more comparable with SLU.