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1.
JCO Clin Cancer Inform ; 7: e2200155, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36809022

RESUMO

PURPOSE: Develop a method for extracting smoking status and quantitative smoking history from clinician notes to facilitate cohort identification for low-dose computed tomography (LDCT) scanning for early detection of lung cancer. MATERIALS AND METHODS: A sample of 4,615 adult patients were randomly selected from the Multiparameter Intelligent Monitoring in Critical Care (MIMIC-III) database. The structured data were obtained by queries of the diagnosis tables using the International Classification of Diseases codes in use at that time. Unstructured data were drawn from clinician notes via natural language processing (NLP) using named entity recognition and our clinical data processing and extraction algorithms to identify two main clinical criteria for each smoking patient: (1) pack years smoked and (2) time from quit date (if applicable). A subset of 10% of the patient charts were manually reviewed for accuracy and precision. RESULTS: The structured data revealed 575 (12.5%) ever smokers (current plus past use). None of these patients had quantification of their smoking history, and 4,040 (87.5%) had no smoking information in the diagnosis tables; consequently, a cohort of patients eligible for LDCT could not be determined. Review of the physician notes by NLP disclosed 1,930 (41.8%) ever smokers of whom 537 were active smokers and 1,299 former smokers, and in 94 cases, it could not be determined if they were active or former smokers. A total of 1365 patients (29.6%) had no smoking data recorded. When the smoking and the age criteria for LDCT were applied to this group, 276 were found to be eligible for LDCT using the USPSTF criteria. As determined by clinician review, our F-score for identifying patients eligible for LDCT was 0.88. CONCLUSION: Unstructured data, obtained by NLP, can accurately identify a precise cohort that meets the USPSTF guidelines for LDCT.


Assuntos
Registros Eletrônicos de Saúde , Neoplasias Pulmonares , Adulto , Humanos , Fumar/efeitos adversos , Neoplasias Pulmonares/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Detecção Precoce de Câncer
2.
J Am Heart Assoc ; 11(15): e025206, 2022 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-35876414

RESUMO

Background Several cancer therapies have been associated with cardiovascular harm in early-phase clinical trials. However, some cardiovascular harms do not manifest until later-phase trials. To limit interdisease variability, we focused on breast cancer. Thus, we assessed the reporting of cardiovascular safety monitoring and outcomes in phase 2 and 3 contemporary breast cancer clinical trials. Methods and Results We searched Embase and Medline records for phase 2 and 3 breast cancer pharmacotherapy trials. We examined exclusion criterion as a result of cardiovascular conditions, adverse cardiovascular event reporting, and cardiovascular safety assessment through cardiovascular imaging, ECG, troponin, or natriuretic peptides. Fisher's exact test was utilized to compare reporting. Fifty clinical trials were included in our study. Patients were excluded because of cardiovascular conditions in 42 (84%) trials. Heart failure was a frequent exclusion criterion (n=31; 62% trials). Adverse cardiovascular events were reported in 43 (86%) trials. Cardiovascular safety assessments were not reported in 23 (46%) trials, whereas natriuretic peptide and troponin assessments were not reported in any trial. Cardiovascular safety assessments were more frequently reported in industry-funded trials (69.2% versus 0.0%; P<0.001), and in trials administering targeted/immunotherapy agents compared with only hormonal/conventional chemotherapy (78.6% versus 22.7%, P<0.001). Conclusions Our findings demonstrate significant under-representation of patients with cardiovascular conditions or prevalent cardiovascular disease in contemporary later-phase breast cancer trials. Additionally, cardiovascular safety is not routinely monitored in these trials. Therefore, contemporary breast cancer clinical trials may possibly underestimate the cardiovascular risks of cancer pharmacotherapy agents for use in clinical practice.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Troponina
4.
Clin Lung Cancer ; 18(3): 299-302, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28063799

RESUMO

INTRODUCTION: Platinum-based chemotherapy is standard for untreated, advanced non-small-cell lung cancer (NSCLC). We investigated the activity and tolerability of the novel combination of dose-dense pemetrexed, gemcitabine, and bevacizumab in patients with advanced NSCLC. METHODS: This multicenter phase II trial evaluated the safety and efficacy of the combination of pemetrexed (400 mg/m2), gemcitabine (1200 mg/m2), and bevacizumab (10 mg/kg), given every 14 days in patients with untreated, advanced NSCLC. The primary endpoint was progression-free survival with secondary endpoints of response rate and overall survival. RESULTS: Thirty-nine patients were enrolled. Treatment was well tolerated; the most common grade 3-4 toxicities were neutropenia and fatigue. Of the 38 patients evaluable for tumor response, 1 (3%) had complete response, 15 (39%) had partial response, 12 (31%) had stable disease, and 10 (26%) had progressive disease. Median progression-free survival was 6.1 months (95% confidence interval [CI], 4.2-7.9) and median overall survival was 18.4 months (95% CI, 13.1-29.5). The 1-year overall survival rate was 64% (95% CI, 51%-81%) and the 2-year overall survival rate was 41% (95% CI, 28%-60%). CONCLUSIONS: Treatment with dose-dense pemetrexed, gemcitabine, and bevacizumab met the primary endpoint with promising efficacy and a manageable safety profile in patients with untreated advanced NSCLC. This regimen represents a reasonable therapeutic option.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/dietoterapia , Pemetrexede/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Cálculos da Dosagem de Medicamento , Fadiga/etiologia , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neutropenia/etiologia , Pemetrexede/efeitos adversos , Análise de Sobrevida , Gencitabina
5.
J Am Coll Radiol ; 13(6): 733-7, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27131618

RESUMO

PURPOSE: Lung cancer screening with low-dose CT (LDCT) demonstrated reduced mortality in the National Lung Screening Trial, yet there is debate as to whether the reported efficacy can translate into comparable effectiveness with community-based screening. The authors' purpose is to report the baseline patient characteristics and malignancy rate in the first 18 months after implementing a lung cancer screening program in an integrated community health system. METHODS: Patients were screened at 1 of 10 participating community-based centers within a 22-hospital system from 2013 to 2015. LDCT examinations were interpreted by 1 of 20 radiologists using structured reporting and an internally developed tracking system. Manual chart review was performed to ascertain the malignancy detection rate. RESULTS: A total of 357 patients were screened with LDCT. Of these, 80 patients were ineligible and 3 declined enrollment. The remaining 274 patients satisfied accepted screening criteria and were enrolled in the program. Malignancy was detected in a total of 11 enrollees (4.0%), 8 with lung cancer and 3 with extrapulmonary primary malignancies. Three patients (1.1%) were diagnosed with early-stage lung cancer and received definitive therapy. CONCLUSIONS: Early-stage lung cancer was detected with LDCT screening in an integrated community health system at a rate similar to other trials.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Programas de Rastreamento/métodos , Sistemas Multi-Institucionais , Tomografia Computadorizada por Raios X/métodos , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Detecção Precoce de Câncer , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Melhoria de Qualidade , Estudos Retrospectivos , Fumar/epidemiologia , Utah/epidemiologia
6.
Cancer ; 122(6): 908-16, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26650715

RESUMO

BACKGROUND: Advanced imaging and serum biomarkers are commonly used for surveillance in patients with early-stage breast cancer, despite recommendations against this practice. Incentives to perform such low-value testing may be less prominent in integrated health care delivery systems. The purpose of the current study was to evaluate and compare the use of these services within 2 integrated systems: Kaiser Permanente (KP) and Intermountain Healthcare (IH). The authors also sought to distinguish the indication for testing: diagnostic purposes or routine surveillance. METHODS: Patients with American Joint Committee on Cancer stage 0 to II breast cancer diagnosed between 2009 and 2010 were identified and the use of imaging and biomarker tests over an 18-month period were quantified, starting at 1 year after diagnosis. Chart abstraction was performed on a random sample of patients who received testing to identify the indication for testing. Multivariate regression was used to explore associations with the use of nonrecommended care. RESULTS: A total of 6585 patients were identified; 22% had stage 0 disease, 44% had stage I disease, and 34% had stage II disease. Overall, 24% of patients received at least 1 imaging test (25% at KP vs 22% at IH; P = .009) and 28% of patients received at least 1 biomarker (36% at KP vs 13% at IH; P<.001). Chart abstraction revealed that 84% of imaging tests were performed to evaluate symptoms or signs. Virtually all biomarkers were ordered for routine surveillance. Stage of disease, medical center that provided the services, and provider experience were found to be significantly associated with the use of biomarkers. CONCLUSIONS: Advanced imaging was most often performed for appropriate indications, but biomarkers were used for nonrecommended surveillance. Distinguishing between inappropriate use for surveillance and appropriate diagnostic testing is essential when evaluating adherence to recommendations.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico , Prestação Integrada de Cuidados de Saúde/estatística & dados numéricos , Vigilância da População/métodos , Padrões de Prática Médica/estatística & dados numéricos , Procedimentos Desnecessários/estatística & dados numéricos , Adulto , Idoso , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Neoplasias da Mama/etnologia , Neoplasias da Mama/patologia , Neoplasias da Mama/prevenção & controle , California/epidemiologia , Feminino , Fidelidade a Diretrizes , Humanos , Mamografia/estatística & dados numéricos , Prontuários Médicos , Mid-Atlantic Region/epidemiologia , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Noroeste dos Estados Unidos/epidemiologia , Razão de Chances , Tomografia por Emissão de Pósitrons/estatística & dados numéricos , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Estudos de Amostragem , Sobreviventes , Tomografia Computadorizada por Raios X/estatística & dados numéricos
7.
J Oncol Pract ; 11(3): e320-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25901056

RESUMO

PURPOSE: Advanced imaging is commonly used for staging of early-stage breast cancer, despite recommendations against this practice. The objective of this study was to evaluate and compare use of imaging for staging of breast cancer in two integrated health care systems, Kaiser Permanente (KP) and Intermountain Healthcare (IH). We also sought to distinguish whether imaging was routine or used for diagnostic purposes. METHODS: We identified patients with stages 0 to IIB breast cancer diagnosed between 2010 and 2012. Using KP and IH electronic health records, we identified use of computed tomography, positron emission tomography, or bone scintigraphy 30 days before diagnosis to 30 days postsurgery. We performed chart abstraction on a random sample of patients who received a presurgical imaging test to identify indication. RESULTS: For the sample of 10,010 patients, mean age at diagnosis was 60 years (range, 22 to 99 years); with 21% stage 0, 47% stage I, and 32% stage II. Overall, 15% of patients (n = 1,480) received at least one imaging test during the staging window, 15% at KP and 14% at IH (P = .5). Eight percent of patients received imaging before surgery, and 7% postsurgery. We found significant intraregional variation in imaging use. Chart abstraction (n = 129, 16% of patients who received presurgical imaging) revealed that 48% of presurgical imaging was diagnostic. CONCLUSION: Use of imaging for staging of low-risk breast cancer was similar in both systems, and slightly lower than has been reported in the literature. Approximately half of imaging tests were ordered in response to a sign or symptom.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Prestação Integrada de Cuidados de Saúde/normas , Diagnóstico por Imagem/estatística & dados numéricos , Diagnóstico por Imagem/normas , Fidelidade a Diretrizes/normas , Sistemas Pré-Pagos de Saúde/normas , Guias de Prática Clínica como Assunto/normas , Padrões de Prática Médica/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Registros Eletrônicos de Saúde , Feminino , Disparidades em Assistência à Saúde/normas , Humanos , Mamografia/normas , Mamografia/estatística & dados numéricos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons/normas , Tomografia por Emissão de Pósitrons/estatística & dados numéricos , Valor Preditivo dos Testes , Sistema de Registros , Fatores de Tempo , Estados Unidos , Adulto Jovem
8.
J Clin Oncol ; 31(33): 4179-87, 2013 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-24002495

RESUMO

PURPOSE: Selenium has been reported to have chemopreventive benefits in lung cancer. We conducted a double-blind, placebo-controlled trial to evaluate the incidence of second primary tumors (SPTs) in patients with resected non-small-cell lung cancer (NSCLC) receiving selenium supplementation. PATIENTS AND METHODS: Patients with completely resected stage I NSCLC were randomly assigned to take selenized yeast 200 µg versus placebo daily for 48 months. Participation was 6 to 36 months postoperatively and required a negative mediastinal node biopsy, no excessive vitamin intake, normal liver function, negative chest x-ray, and no other evidence of recurrence. RESULTS: The first interim analysis in October 2009, with 46% of the projected end points accumulated, showed a trend in favor of the placebo group with a low likelihood that the trial would become positive; thus, the study was stopped. One thousand seven hundred seventy-two participants were enrolled, with 1,561 patients randomly assigned. Analysis was updated in June 2011 with the maturation of 54% of the planned end points. Two hundred fifty-two SPTs (from 224 patients) developed, of which 98 (from 97 patients) were lung cancer (38.9%). Lung and overall SPT incidence were 1.62 and 3.54 per 100 person-years, respectively, for selenium versus 1.30 and 3.39 per 100 person-years, respectively, for placebo (P = .294). Five-year disease-free survival was 74.4% for selenium recipients versus 79.6% for placebo recipients. Grade 1 to 2 toxicity occurred in 31% of selenium recipients and 26% of placebo recipients, and grade ≥ 3 toxicity occurred in less than 2% of selenium recipients versus 3% of placebo recipients. Compliance was excellent. No increase in diabetes mellitus or skin cancer was detected. CONCLUSION: Selenium was safe but conferred no benefit over placebo in the prevention of SPT in patients with resected NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/prevenção & controle , Suplementos Nutricionais , Neoplasias Pulmonares/prevenção & controle , Selênio/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Alopecia/induzido quimicamente , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Quimioprevenção/métodos , Constipação Intestinal/induzido quimicamente , Método Duplo-Cego , Fadiga/induzido quimicamente , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Selênio/efeitos adversos , Resultado do Tratamento , Adulto Jovem
9.
Psychooncology ; 22(3): 555-63, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22290823

RESUMO

BACKGROUND: Few intervention programs assist patients and their family caregivers to manage advanced cancer and maintain their quality of life (QOL). This study examined (i) whether patient-caregiver dyads (i.e., pairs) randomly assigned to a brief or extensive dyadic intervention (the FOCUS Program) had better outcomes than dyads randomly assigned to usual care and (ii) whether patients' risk for distress and other factors moderated the effect of the brief or extensive program on outcomes. METHODS: Advanced cancer patients and their caregivers (N = 484 dyads) were stratified by patients' baseline risk for distress (high versus low), cancer type (lung, colorectal, breast, or prostate), and research site and then randomly assigned to a brief (three-session) or extensive (six-session) intervention or control. The interventions offered dyads information and support. Intermediary outcomes were appraisals (i.e., appraisal of illness/caregiving, uncertainty, and hopelessness) and resources (i.e., coping, interpersonal relationships, and self-efficacy). The primary outcome was QOL. Data were collected prior to intervention and post-intervention (3 and 6 months from baseline). The final sample was 302 dyads. Repeated measures MANCOVA was used to evaluate outcomes. RESULTS: Significant group by time interactions showed that there was an improvement in dyads' coping (p < 0.05), self-efficacy (p < 0.05), and social QOL (p < 0.01) and in caregivers' emotional QOL (p < 0.05). Effects varied by intervention dose. Most effects were found at 3 months only. Risk for distress accounted for very few moderation effects. CONCLUSIONS: Both brief and extensive programs had positive outcomes for patient-caregiver dyads, but few sustained effects. Patient-caregiver dyads benefit when viewed as the 'unit of care'.


Assuntos
Adaptação Psicológica , Cuidadores/psicologia , Terapia Familiar/métodos , Neoplasias/psicologia , Autoeficácia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Família/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/enfermagem , Psicoterapia Breve/métodos , Qualidade de Vida , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
10.
J Fam Issues ; 33(10): 1299-1323, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25635153

RESUMO

With increasing numbers of communities harmed by exposures to toxic substances, greater understanding of the psychosocial consequences of these technological disasters is needed. One community living the consequences of a slow-motion technological disaster is Libby, Montana, where, for nearly 70 years, amphibole asbestos-contaminated vermiculite was mined and processed. Former mine employees and Libby area residents continue to cope with the health consequences of occupational and environmental asbestos exposure and with the psychosocial challenges accompanying chronic and often fatal asbestos-related diseases (ARD). Nine focus groups were conducted with Libby area residents. Transcripts were analyzed to explore patterns of family communication about ARD. The following five patterns emerged: Open/Supportive, Silent/Supportive, Open/Conflictual, Silent/Conflictual, and Silent/Denial. Open/Supportive communication included encouragement to be screened for ARD, information about ARD and related disaster topics, and emotional support for people with ARD. In contrast, communication patterns characterized by silence or conflict have the potential to hinder health-promoting communication and increase psychological distress.

11.
J Thorac Oncol ; 6(5): 927-33, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21415776

RESUMO

BACKGROUND: Pemetrexed has emerged as one of the most active agents for the treatment of patients with advanced non-small cell lung cancer (NSCLC). We conducted a phase II study to assess the efficacy and feasibility of integrating pemetrexed in a concurrent therapy plan for patients with stage III NSCLC. METHODS: Patients with stage III NSCLC with performance status 0 to 1, adequate organ function including pulmonary function, and V20 less than 40% were eligible. Patients were treated with cisplatin 75 mg/m² (first five patients 60 mg/m²) and pemetrexed 500 mg/m² every 21 days for three cycles with chest radiotherapy to 66 Gy. Patients then received three cycles of docetaxel 75 mg/m² every 21 days. Tumors were analyzed for Excision Repair Cross Complementation Group 1 and thymidylate synthase. RESULTS: Patient characteristics (N = 28) were median age, 60; males, 68%; stage IIIB, 64%; and squamous cell, 43%. Twenty-four patients (86%) completed all three cycles of cisplatin/pemetrexed. Of the 24 patients eligible for docetaxel, 21 (87%) received it. Grade 3/4 toxicities were neutropenia (39%), febrile neutropenia (14%), esophagitis (14%), and pneumonitis (4%). Median survival was 34 months, and 1-year survival was 66%. Survival was not significantly different in squamous and other histology patients. Tumor analysis in 16 patients showed that moderate/strong expression of thymidylate synthase was significantly associated with progression-free survival and overall survival. CONCLUSION: Integrating pemetrexed in a concurrent therapy regimen for patients with stage III NSCLC is feasible and was associated with a median survival of 34 months.


Assuntos
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Grandes/terapia , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma de Células Escamosas/terapia , Neoplasias Pulmonares/terapia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Grandes/tratamento farmacológico , Carcinoma de Células Grandes/radioterapia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Cisplatino/administração & dosagem , Terapia Combinada , Proteínas de Ligação a DNA/metabolismo , Docetaxel , Endonucleases/metabolismo , Estudos de Viabilidade , Feminino , Seguimentos , Glutamatos/administração & dosagem , Guanina/administração & dosagem , Guanina/análogos & derivados , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Pemetrexede , Taxa de Sobrevida , Taxoides/administração & dosagem , Timidilato Sintase/metabolismo , Resultado do Tratamento
12.
J Thorac Oncol ; 6(3): 633-8, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21266923

RESUMO

In recent years, there have been significant advances in the management of patients with lung cancer. This progress is associated with increased use of medical intensive care units (ICUs) for the management of a variety of complications related to cancer, its treatment, or comorbid illnesses. At the same time, there are advances in the care of critically ill patients in general. Over the last decade, there are several studies that report progressive improvement in the outcome of lung cancer patients admitted to the medical ICUs. On average, the ICU and hospital mortality rates of lung cancer patients are 36% and 51%, respectively. These rates are approaching those of critically ill general population. However, it is clear that not all lung cancer patients will benefit from this aggressive care. Although there are no absolute predictors, the current evidence suggests that advanced refractory cancer, poor baseline performance status, the need for mechanical ventilation, and multiple organ system failures are factors associated with worse ICU outcome. Further studies are needed to better triage patients who are going to benefit from ICU care; determine the optimal duration of this care; and assess the impact of this therapy on the long-term survival, cancer treatment, and quality of life of these patients.


Assuntos
Cuidados Críticos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Humanos , Prognóstico , Taxa de Sobrevida
14.
Clin Lung Cancer ; 11(4): 223-7, 2010 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-20630823

RESUMO

BACKGROUND: The prognosis for patients with extensive-stage small-cell lung cancer remains poor. This trial was designed to evaluate irinotecan/cisplatin plus maintenance imatinib in patients with c-Kit-positive disease (the transmembrane receptor c-Kit is the product of the c-KIT protooncogene). PATIENTS AND METHODS: Immunohistochemistry for c-Kit was performed before enrollment. Treatment consisted of irinotecan 65 mg/m2 on days 1 and 8 plus cisplatin 60 mg/m2 on day 1 and every 21 days for 4 cycles. Imatinib was administered at 400 mg twice a day until progression or unacceptable toxicity occurred. RESULTS: Fourteen patients were enrolled. Slow accrual led to early study termination. Six patients did not begin treatment with imatinib because of disease progression, persistent toxicity, or referral for radiation therapy. Eight patients had a partial response with irinotecan/cisplatin and received imatinib. The median number of weeks on imatinib was 6.1 (range, 4.1-25.1 weeks). Reasons for imatinib discontinuation included disease progression (n = 7) and persistent neutropenia (n = 1). No objective responses to imatinib were evident, but 3 patients (21%) exhibited stable disease for 12, 15, and 25 weeks. The median progression-free survival was 4.3 months (95% CI, 2.9-4.8 months). The median overall survival was 7.8 months (95% CI, 5.7-10.0 months). The irinotecan/cisplatin regimen was well tolerated (grade 1/2 neutropenia, 29%; anemia, 43%; thrombocytopenia, 14%; and diarrhea, 29%), except in 1 patient with grade 3 vomiting. Imatinib toxicity included grade 1/2 nausea in 50% of the patients, peripheral edema in 75% of the patients, grade 3 fatigue in 13% of the patients, and neutropenia in 13% of the patients. CONCLUSION: Despite the selection of tumors expressing c-Kit, imatinib did not appear to delay disease progression after response to chemotherapy. However, this trial was underpowered because of its early termination. Although disease stability with imatinib was evident in 3 patients and the therapy was well tolerated, this approach does not appear to warrant further clinical study.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/tratamento farmacológico , Proteínas Proto-Oncogênicas c-kit/metabolismo , Terapia de Salvação , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Idoso , Benzamidas , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Cisplatino/administração & dosagem , Progressão da Doença , Feminino , Humanos , Mesilato de Imatinib , Técnicas Imunoenzimáticas , Irinotecano , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Piperazinas/administração & dosagem , Pirimidinas/administração & dosagem , Indução de Remissão , Carcinoma de Pequenas Células do Pulmão/metabolismo , Carcinoma de Pequenas Células do Pulmão/patologia , Taxa de Sobrevida , Resultado do Tratamento
15.
Am J Community Psychol ; 46(1-2): 1-18, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20526664

RESUMO

Social support is an important resource for communities experiencing disasters. However, a disaster's nature (rapid- versus slow-onset, natural versus technological) may influence community-level responses. Disaster research on social support focuses primarily on rapid-onset natural disasters and, to a lesser extent, rapid-onset technological disasters. Little research has addressed slow-onset disasters. This study explores social support processes in Libby, MT, a community experiencing a "slow-motion technological disaster" due to widespread amphibole asbestos exposure. A comprehensive social support coding system was applied to focus-group and in-depth-interview transcripts. Results reveal that, although the community has a history of normative supportiveness during community and individual crises, that norm has been violated in the asbestos disaster context. Results are interpreted as a failure to achieve an "emergent altruistic community." Specifically, community-level conflict appears to interfere with previously established social support patterns. The observed phenomenon can be understood as the deterioration of a previously supportive community.


Assuntos
Amiantos Anfibólicos/intoxicação , Asbestose/psicologia , Desastres , Exposição Ambiental/efeitos adversos , Apoio Social , Adulto , Idoso , Altruísmo , Asbestose/epidemiologia , Participação da Comunidade/psicologia , Feminino , Grupos Focais , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Mineração , Montana/epidemiologia , Serviço Social
16.
Cancer Chemother Pharmacol ; 66(3): 455-66, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19960346

RESUMO

INTRODUCTION: Thoracic malignancies and human breast cancer (HBC) continue to be aggressive solid tumors that are poor responders to the existing conventional standard chemotherapeutic approaches. Malignant pleural mesothelioma (MPM) is an asbestos-related tumor of the thoracic pleura that lacks effective treatment options. Altered ubiquitin proteasome pathway is frequently encountered in many malignancies including HBC and MPM and thus serves as an important target for therapeutic intervention strategies. Although proteasome inhibitor Velcade (Bortezomib) has been under clinical investigation for a number of cancers, limited preclinical studies with this agent have thus far been conducted in HBC and MPM malignancies. PURPOSE: To study the biological and molecular responses of MPM and HBC cells to Velcade treatments, and to identify mechanisms involved in transducing growth inhibitory effects of this agent. METHODS: Flow-cytometric analyses coupled with western immunoblotting and gene-array methodologies were utilized to determine mechanisms of Velcade-dependent growth suppression of five MPM (H2595, H2373, H2452, H2461, and H2714) and two breast cancer (MDA MB-468, SKBR-3) cell lines. RESULTS: Our data revealed significant reduction in cell growth properties that were dose and time dependent. Velcade treatment resulted in G2M phase arrest, increased expression of cyclin-dependent kinase inhibitor p21 and pro-apoptotic protein Bax. Pretreatment of mesothelioma cells with Velcade showed synergistic effect with cisplatin combination regimens. High-throughput gene expression profiling among Velcade treated and untreated mesothelioma cell lines resulted in identification of novel transducers of apoptosis such as CARP-1, XAF1, and Troy proteins. CONCLUSIONS: Velcade targets cell cycle and apoptosis signaling to suppress MPM and HBC growth in part by activating novel transducers of apoptosis. This pilot study has paved way for further in-depth analysis of the downstream target molecules associated with presensitization of mesothelioma cells in finding effective therapeutic treatment options for both mesothelioma and recalcitrant breast cancers.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Mesotelioma/tratamento farmacológico , Inibidores de Proteases/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Western Blotting , Ácidos Borônicos/administração & dosagem , Bortezomib , Neoplasias da Mama/patologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cisplatino/administração & dosagem , Relação Dose-Resposta a Droga , Sistemas de Liberação de Medicamentos , Sinergismo Farmacológico , Feminino , Citometria de Fluxo , Humanos , Mesotelioma/patologia , Projetos Piloto , Inibidores de Proteases/administração & dosagem , Inibidores de Proteassoma , Pirazinas/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo
18.
J Health Commun ; 14 Suppl 1: 47-56, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19449268

RESUMO

Much cancer-related health communication research has involved studies of the effects of media campaigns and strategies on secondary prevention. Cancer diagnosis rates, however, continue to affect millions of people. The need exists for communication studies to address the quality of the clinical interaction, the point of actual care delivery in addressing diagnosis, treatment, and survivorship. Using examples from a 6-year communication and behavioral oncology research program established at the Karmanos Cancer Institute (KCI) in Detroit, Michigan, we describe selected empirical issues; models, particularly the "convergence model" (adapted from Rogers & Kincaid, 1981); and associated constructs that are relevant and promising foundations for building future research in cancer clinical settings. Two examples from our empirical research program are described.


Assuntos
Pesquisa Biomédica , Comunicação , Conhecimentos, Atitudes e Prática em Saúde , Neoplasias , Educação de Pacientes como Assunto , Humanos , Modelos Teóricos , Relações Pais-Filho , Avaliação de Programas e Projetos de Saúde
19.
J Thorac Oncol ; 4(3): 291-9, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19190518

RESUMO

INTRODUCTION: The link between lung cancer and chronic obstructive lung diseases (COPD) has not been well studied in women even though lung cancer and COPD account for significant and growing morbidity and mortality among women. METHODS: We evaluated the relationship between COPD and non-small cell lung cancer in a population-based case-control study of women and constructed a time course of chronic lung diseases in relation to onset of lung cancer. Five hundred sixty-two women aged 18 to 74, diagnosed with non-small cell lung cancer and 564 population-based controls matched on race and age participated. Multivariable unconditional logistic regression models were used to estimate risk associated with a history of COPD, chronic bronchitis, or emphysema. RESULTS: Lung cancer risk increased significantly for white women with a history of COPD (odds ratios [OR] = 1.85; 95% confidence intervals [CI]: 1.21-2.81), but this was not seen in African American women. Risk associated with a history of chronic bronchitis was strongest when diagnosed at age 25 or earlier (OR = 2.35, 95% CI: 1.17-4.72); emphysema diagnosed within 9 years of lung cancer was also associated with substantial risk (OR = 6.36, 95% CI: 2.36-17.13). Race, pack-years of smoking, exposure to environmental tobacco smoke as an adult, childhood asthma, and exposure to asbestos were associated with a history of COPD among lung cancer cases. CONCLUSIONS: In women, COPD is associated with risk of lung cancer differentially by race. Untangling whether COPD is in the causal pathway or simply shares risk factors will require future studies to focus on specific COPD features, while exploring underlying genetic susceptibility to these diseases.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Neoplasias Pulmonares/epidemiologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Fumar/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Estudos de Coortes , Comorbidade , Feminino , Humanos , Incidência , Modelos Logísticos , Neoplasias Pulmonares/diagnóstico , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Valores de Referência , Medição de Risco , Fumar/efeitos adversos , Análise de Sobrevida , Estados Unidos/epidemiologia , Adulto Jovem
20.
Patient Educ Couns ; 75(2): 263-9, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19147315

RESUMO

OBJECTIVE: To test whether cancer patients' expectations for cure prior to interacting with their oncologist influence their decisions to follow treatment recommendations. Further, to test whether patients' expectations for cure are affected by the strength of the oncologist-patient alliance or the extent to which companions (if present) share patients' expectations for cure. METHODS: Interactions of 101 patients (and 114 companions) with oncologists about treatment were coded for the strength of the oncologist-patient alliance. Prior to the interaction, patients and companions reported expectations about whether the patient would be cured of cancer. After the interaction, patients reported whether they intended to follow the recommended treatment. RESULTS: Patients who expected a cure were more likely to report an intention to follow oncologists' treatment recommendation when the strength of their alliance with their oncologist was weaker (B=-0.51, p<.05). Patients whose expectations for cure matched their companions' expectations were less likely to report intentions to follow treatment recommendations (B=-0.28, p<.05). CONCLUSION: Patients who have an expectation of being cured of cancer prior to meeting with their oncologist are more likely to intend to follow recommended treatment when their alliance with the oncologist is weaker and their companions do not believe they will be cured. PRACTICE IMPLICATIONS: To better understand patient treatment decisions and improve overall cancer care, oncologists should be aware of the complex ways that patients' expectations about cure influence treatment choices.


Assuntos
Relações Familiares , Intenção , Neoplasias/terapia , Cooperação do Paciente/psicologia , Relações Médico-Paciente , Adulto , Idoso , Idoso de 80 Anos ou mais , Tomada de Decisões , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Cônjuges/psicologia , Estados Unidos
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