RESUMEN
Multicancer detection (MCD) tests use a single, easily obtainable biospecimen, such as blood, to screen for more than one cancer concurrently. MCD tests can potentially be used to improve early cancer detection, including cancers that currently lack effective screening methods. However, these tests have unknown and unquantified benefits and harms. MCD tests differ from conventional cancer screening tests in that the organ responsible for a positive test is unknown, and a broad diagnostic workup may be necessary to confirm the location and type of underlying cancer. Among two prospective studies involving greater than 16,000 individuals, MCD tests identified those who had some cancers without currently recommended screening tests, including pancreas, ovary, liver, uterus, small intestine, oropharyngeal, bone, thyroid, and hematologic malignancies, at early stages. Reported MCD test sensitivities range from 27% to 95% but differ by organ and are lower for early stage cancers, for which treatment toxicity would be lowest and the potential for cure might be highest. False reassurance from a negative MCD result may reduce screening adherence, risking a loss in proven public health benefits from standard-of-care screening. Prospective clinical trials are needed to address uncertainties about MCD accuracy to detect different cancers in asymptomatic individuals, whether these tests can detect cancer sufficiently early for effective treatment and mortality reduction, the degree to which these tests may contribute to cancer overdiagnosis and overtreatment, whether MCD tests work equally well across all populations, and the appropriate diagnostic evaluation and follow-up for patients with a positive test.
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Detección Precoz del Cáncer , Neoplasias , Humanos , Neoplasias/diagnóstico , Detección Precoz del Cáncer/métodos , Investigación Biomédica Traslacional , Sensibilidad y Especificidad , Tamizaje Masivo/métodosRESUMEN
Advances in cancer treatments have led to nearly 17 million survivors in the US today. Cardiovascular complications attributed to cancer treatments are the leading cause of morbidity and mortality in cancer survivors. In response, NCI and NHLBI held 2 workshops and issued funding opportunities to strengthen research on cardiotoxicity. A representative portfolio of NIH grants categorizing basic, interventional, and observational projects is presented. Compared with anthracyclines, research on radiation therapy and newer treatments is underrepresented. Multidisciplinary collaborative research that considers the cardiotoxicity stage and optimizes the balance between cardiovascular risk and cancer-treatment benefit might support continued improvements in cancer outcomes.
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Cardiotoxicidad , Neoplasias , Antraciclinas/uso terapéutico , Cardiotoxicidad/etiología , Humanos , Oncología Médica , National Institutes of Health (U.S.) , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: The importance of capturing and reporting health-related quality of life (HRQOL) in clinical trials has been increasingly recognized in the oncology field. As a result, the National Cancer Institute (NCI) began to provide support for correlative HRQOL studies in cancer treatment trials. The current study was conducted to assess the publication rate of HRQOL correlative studies in NCI-supported treatment trials and to identify potential factors positively or negatively associated with publication rates. METHODS: The NCI conducted a retrospective review of existing NCI databases to identify cancer treatment trials that had obtained additional NCI funding for the assessment of HRQOL and to determine the extent to which funded HRQOL studies have been completed and published in a peer-reviewed journal. RESULTS: Of the 108 included trials, 58 (54%) had a parent trial (PT) publication; of these, 36 trials (62%) had a published HRQOL result: 20 as an independent publication and 16 that were included and/or reported in the PT publication. The length of time between trial activation and closure, as well as the specific cancer, appeared to be associated with the publication rates. CONCLUSIONS: The results of the current study demonstrated that approximately 45% of the PT publications were followed by a HRQOL publication within 1 year, to allow the knowledge to be used in patient treatment decision making. The authors believe the current analysis is an important first step toward a better understand of the challenges that researchers face when reporting HRQOL endpoints.
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Ensayos Clínicos como Asunto , Neoplasias/terapia , Calidad de Vida , Humanos , National Cancer Institute (U.S.) , Neoplasias/psicología , Estudios Retrospectivos , Factores de Tiempo , Estados UnidosRESUMEN
BACKGROUND: To the authors' knowledge, the empiric identification of agents and interventions to mitigate chemotherapy-induced peripheral neuropathy (CIPN) has resulted in only 1 agent that modestly mitigates it and no agents or interventions that prevent its development. This speaks to the need for a mechanistic understanding of CIPN to develop effective interventions. METHODS: To understand the extent to which mechanistic understanding of CIPN is being translated into the development of interventions, the National Cancer Institute conducted a review of the National Institutes of Health (NIH)'s portfolio of investigator-initiated grants, the literature regarding CIPN mechanisms, and the clinical trials listed in the ClinicalTrials.gov database from January 1, 2011, to May 22, 2019. RESULTS: A total of 69 NIH-supported grants and 95 published articles were identified that evaluated mechanistic pathways of 7 different chemotherapy agents that cause CIPN. The review also identified 35 clinical trials that investigated agents or devices with which to treat CIPN. Only 3 trials incorporated a mechanistic rationale to support the choice of the intervention. CONCLUSIONS: To the authors' knowledge, very little of the mechanistic understanding of the development of CIPN is being translated into intervention rationale in clinical trials that evaluate interventions to mitigate CIPN. Efforts to incentivize this translation are needed.
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Antineoplásicos/efectos adversos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Ensayos Clínicos como Asunto , HumanosRESUMEN
OBJECTIVE: To examine whether blocking multiple points of the angiogenesis pathway by addition of sorafenib, a multi-kinase inhibitor against VEGFR2/3, Raf, c-Kit, and PDGFR, to bevacizumab would yield clinical activity in ovarian cancer (OvCa). METHODS: This phase II study tested bevacizumab plus sorafenib in two cohorts; bevacizumab-naïve and bevacizumab-exposed patients. Bevacizumab (5 mg/kg IV every 2 weeks) was given with sorafenib 200 mg bid 5 days-on/2 days-off. The primary objective was response rate using a Simon two-stage optimal design. Progression-free survival (PFS) and toxicity were the secondary endpoints. Exploratory correlative studies included plasma cytokine concentrations, tissue proteomics and dynamic contrast-enhanced-magnetic resonance imaging (DCE-MRI). RESULTS: Between March 2007 and August 2012, 54 women were enrolled, 41 bevacizumab-naive and 13 bevacizumab-prior, with median 5 (2-9) and 6 (5-9) prior systemic therapies, respectively. Nine of 35 (26%) evaluable bevacizumab-naive patients attained partial responses (PR), and 18 had stable disease (SD) ≥ 4 months. No responses were seen in the bevacizumab-prior group and 7 (54%) patients had SD ≥ 4 months, including one exceptional responder with SD of 27 months. The overall median PFS was 5.5 months (95%CI: 4.0-6.8 months). Treatment-related grade 3/4 adverse events (≥5%) included hypertension (17/54 [31%]; grade 3 in 16 patients and grade 4 in one patient) and venous thrombosis or pulmonary embolism (5/54 [9%]; grade 3 in 4 patients and grade 4 in one patient). Pretreatment low IL8 concentration was associated with PFS ≥ 4 months (p = .031). CONCLUSIONS: The bevacizumab and sorafenib combination did not meet the pre-specified primary endpoint although some clinical activity was seen in heavily-pretreated bevacizumab-naive OvCa patients with platinum-resistant disease. Anticipated class toxicities required close monitoring and dose modifications.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bevacizumab/administración & dosificación , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Sorafenib/administración & dosificación , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/efectos adversos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Resistencia a Antineoplásicos , Femenino , Estudios de Seguimiento , Humanos , Interleucina-8/sangre , Interleucina-8/inmunología , Persona de Mediana Edad , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/mortalidad , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Supervivencia sin Progresión , Criterios de Evaluación de Respuesta en Tumores Sólidos , Sorafenib/efectos adversosRESUMEN
To examine whether (a) non-minority participants differed from racial minority participants in the understanding of biospecimens collected for research purposes, (b) patients differed from comparison group in their understanding of the ways their biospecimens could be used by researchers, and (c) participants received adequate information before consenting to donate blood for research studies. We analyzed cross-sectional data from female breast cancer patients scheduled to receive chemotherapy at the National Cancer Institute (NCI) Community Oncology Research Program (NCORP) clinical sites and a healthy comparison group. After reading a consent form related to biospecimens and consenting to participate in a clinical trial, participants' understanding of biospecimen collection was evaluated. Linear models were used to compare scores between non-minority and racial minority participants as well as cancer and non-cancer comparisons adjusting for possible confounding factors. A total of 650 participants provided evaluable data; 592 were non-minority (Caucasian) and 58 participants were a racial minority (71% Black and 29% other). There were 427 cancer patients and 223 comparisons. Non-minority participants scored higher than racial minorities on relevance-to-care items (diff. = 0.48, CI 0.13-0.80, p = 0.001). Comparison group scored higher than cancer patients on relevance-to-care items (diff. = 0.58, CI 0.37-0.78). A moderate number of the participants exhibited a poor understanding of biospecimen collection across all racial/ethnic backgrounds, but racial minority participants' scores remained lower in the relevance-to-care subscale even after adjusting for education and reading level. Differences were also noted among the patients and comparison group. Researchers should facilitate comprehension of biospecimen collection for all study participants, especially racial minority participants.
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Bancos de Muestras Biológicas/estadística & datos numéricos , Neoplasias de la Mama/etnología , Ensayos Clínicos como Asunto/estadística & datos numéricos , Comprensión , Etnicidad/educación , Etnicidad/psicología , Disparidades en el Estado de Salud , Adulto , Negro o Afroamericano/educación , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/psicología , Estudios de Casos y Controles , Estudios Transversales , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Persona de Mediana Edad , Participación del Paciente , Manejo de Especímenes , Población Blanca/educación , Adulto JovenRESUMEN
PURPOSE: Although aromatase inhibitors (AIs) prolong survival in post-menopausal breast cancer (BC) patients, AI-associated arthralgia can lead to discontinuation. Obese patients have higher rates of AI arthralgia than non-obese patients, but treatment options are limited. Omega-3 fatty acid (O3-FA) treatment for AI arthralgia has produced mixed results. METHODS: We performed an exploratory analysis of SWOG S0927, a multicenter randomized placebo-controlled trial of O3-FA use for AI arthralgia. Post-menopausal women with stage I-III BC taking an AI were randomized to 24 weeks of O3-FAs or placebo. Brief Pain Inventory (BPI) questionnaires and fasting serum were collected at baseline, 12, and 24 weeks. The BPI assessment included worst pain, average pain, and pain interference scores (range 0-10). RESULTS: Among the 249 participants, 139 had BMI < 30 kg/m2 (56%) and 110 had BMI ≥ 30 kg/m2 (44%). Among obese patients, O3-FA use was associated with significantly lower BPI worst pain scores at 24 weeks compared with placebo (4.36 vs. 5.70, p = 0.02), whereas among non-obese patients, there was no significant difference in scores between treatment arms (5.27 vs. 4.58, p = 0.28; interaction p = 0.05). Similarly, O3-FA use was associated with lower BPI average pain and pain interference scores at 24 weeks compared with placebo among obese patients, but no significant difference between treatment arms in non-obese patients (interaction p = 0.005 and p = 0.01, respectively). CONCLUSIONS: In obese BC patients, O3-FA use was associated with significantly reduced AI arthralgia compared to placebo.
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Inhibidores de la Aromatasa/efectos adversos , Artralgia/prevención & control , Neoplasias de la Mama/tratamiento farmacológico , Ácidos Grasos Omega-3/administración & dosificación , Obesidad/complicaciones , Artralgia/inducido químicamente , Índice de Masa Corporal , Femenino , Humanos , Lípidos/sangre , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
OBJECTIVE: Many high-grade serous carcinomas initiate in fallopian tubes as serous tubal intraepithelial carcinoma (STIC), a microscopic lesion identified with specimen processing according to the Sectioning and Extensive Examination of the Fimbria protocol (SEE-Fim). Given that the tubal origin of these cancers was recently recognized, we conducted a survey of pathology practices to assess processing protocols that are applied to gynecologic surgical pathology specimens in clinical contexts in which finding STIC might have different implications. METHODS: We distributed a survey electronically to the American Society for Clinical Pathology list-serve to determine practice patterns and compared results between practice types by chi-square (χ2) tests for categorical variables. Free text comments were qualitatively reviewed. RESULTS: Survey responses were received from 159 laboratories (72 academic, 87 non-academic), which reported diverse specimen volumes and percentage of gynecologic samples. Overall, 74.1% of laboratories reported performing SEE-Fim for risk-reducing surgical specimens (82.5% academic versus 65.7% non-academic, pâ¯<â¯0.05). In specimens from surgery for benign indications in which initial microscopic sections showed an unanticipated suspicious finding, 75.9% of laboratories reported using SEE-Fim to process the remainder of the specimen (94.8% academic versus 76.4% non-academic, pâ¯<â¯0.01), and 84.6% submitted the entire fimbriae. CONCLUSIONS: Changes in the theories of pathogenesis of high-grade serous carcinoma have led to implementation of pathology specimen processing protocols that include detailed analysis of the fallopian tubes. These results have implications for interpreting trends in cancer incidence data and considering the feasibility of developing a bank of gynecologic tissues containing STIC or early cancer precursors.
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Carcinoma in Situ/patología , Endometrio/patología , Trompas Uterinas/patología , Neoplasias de los Genitales Femeninos/patología , Neoplasias Quísticas, Mucinosas y Serosas/patología , Ovario/patología , Patología Quirúrgica/métodos , Pautas de la Práctica en Medicina , Manejo de Especímenes/métodos , Carcinoma in Situ/diagnóstico , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/patología , Endometrio/cirugía , Neoplasias de las Trompas Uterinas/diagnóstico , Neoplasias de las Trompas Uterinas/patología , Trompas Uterinas/cirugía , Femenino , Neoplasias de los Genitales Femeninos/diagnóstico , Humanos , Neoplasias Quísticas, Mucinosas y Serosas/diagnóstico , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/patología , Ovario/cirugía , Encuestas y Cuestionarios , Estados UnidosRESUMEN
Importance: Musculoskeletal symptoms are the most common adverse effects of aromatase inhibitors and often result in therapy discontinuation. Small studies suggest that acupuncture may decrease aromatase inhibitor-related joint symptoms. Objective: To determine the effect of acupuncture in reducing aromatase inhibitor-related joint pain. Design, Setting, and Patients: Randomized clinical trial conducted at 11 academic centers and clinical sites in the United States from March 2012 to February 2017 (final date of follow-up, September 5, 2017). Eligible patients were postmenopausal women with early-stage breast cancer who were taking an aromatase inhibitor and scored at least 3 on the Brief Pain Inventory Worst Pain (BPI-WP) item (score range, 0-10; higher scores indicate greater pain). Interventions: Patients were randomized 2:1:1 to the true acupuncture (n = 110), sham acupuncture (n = 59), or waitlist control (n = 57) group. True acupuncture and sham acupuncture protocols consisted of 12 acupuncture sessions over 6 weeks (2 sessions per week), followed by 1 session per week for 6 weeks. The waitlist control group did not receive any intervention. All participants were offered 10 acupuncture sessions to be used between weeks 24 and 52. Main Outcomes and Measures: The primary end point was the 6-week BPI-WP score. Mean 6-week BPI-WP scores were compared by study group using linear regression, adjusted for baseline pain and stratification factors (clinically meaningful difference specified as 2 points). Results: Among 226 randomized patients (mean [SD] age, 60.7 [8.6] years; 88% white; mean [SD] baseline BPI-WP score, 6.6 [1.5]), 206 (91.1%) completed the trial. From baseline to 6 weeks, the mean observed BPI-WP score decreased by 2.05 points (reduced pain) in the true acupuncture group, by 1.07 points in the sham acupuncture group, and by 0.99 points in the waitlist control group. The adjusted difference for true acupuncture vs sham acupuncture was 0.92 points (95% CI, 0.20-1.65; P = .01) and for true acupuncture vs waitlist control was 0.96 points (95% CI, 0.24-1.67; P = .01). Patients in the true acupuncture group experienced more grade 1 bruising compared with patients in the sham acupuncture group (47% vs 25%; P = .01). Conclusions and Relevance: Among postmenopausal women with early-stage breast cancer and aromatase inhibitor-related arthralgias, true acupuncture compared with sham acupuncture or with waitlist control resulted in a statistically significant reduction in joint pain at 6 weeks, although the observed improvement was of uncertain clinical importance. Trial Registration: ClinicalTrials.gov Identifier: NCT01535066.
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Terapia por Acupuntura , Inhibidores de la Aromatasa/efectos adversos , Artralgia/terapia , Neoplasias de la Mama/tratamiento farmacológico , Terapia por Acupuntura/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Inhibidores de la Aromatasa/uso terapéutico , Artralgia/inducido químicamente , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Posmenopausia , Método Simple Ciego , Listas de EsperaAsunto(s)
Finasterida/uso terapéutico , Neoplasias de la Próstata/mortalidad , Inhibidores de 5-alfa-Reductasa/efectos adversos , Inhibidores de 5-alfa-Reductasa/uso terapéutico , Detección Precoz del Cáncer , Finasterida/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/inducido químicamente , Neoplasias de la Próstata/prevención & controlRESUMEN
In advanced stage patients enrolled in dose-finding trials, it is difficult to assess delayed toxicities because frequently patients discontinue after one or two cycles of treatment. Patients enrolled in phase 2 trials are typically followed longer to assess efficacy. Thus, their data may be useful for evaluating long-term tolerability. We illustrate this using as example two phase 2 bortezomib trials (total N = 172) conducted by SWOG. While treatment-related severe toxicity rates based on cycle 1 were acceptable (23% and 31%), they were notably higher over extended administration (37% and 70%). This additional information should be considered when designing subsequent trials.
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Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Bortezomib/administración & dosificación , Bortezomib/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Cálculo de Dosificación de Drogas , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/patología , Dosis Máxima Tolerada , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: In the Prostate Cancer Prevention Trial (PCPT), finasteride significantly reduced the risk of prostate cancer but was associated with an increased risk of high-grade disease. With up to 18 years of follow-up, we analyzed rates of survival among all study participants and among those with prostate cancer. METHODS: We collected data on the incidence of prostate cancer among PCPT participants for an additional year after our first report was published in 2003 and searched the Social Security Death Index to assess survival status through October 31, 2011. RESULTS: Among 18,880 eligible men who underwent randomization, prostate cancer was diagnosed in 989 of 9423 (10.5%) in the finasteride group and 1412 of 9457 (14.9%) in the placebo group (relative risk in the finasteride group, 0.70; 95% confidence interval [CI], 0.65 to 0.76; P<0.001). Of the men who were evaluated, 333 (3.5%) in the finasteride group and 286 (3.0%) in the placebo group had high-grade cancer (Gleason score, 7 to 10) (relative risk, 1.17; 95% CI, 1.00 to 1.37; P=0.05). Of the men who died, 2538 were in the finasteride group and 2496 were in the placebo group, for 15-year survival rates of 78.0% and 78.2%, respectively. The unadjusted hazard ratio for death in the finasteride group was 1.02 (95% CI, 0.97 to 1.08; P=0.46). Ten-year survival rates were 83.0% in the finasteride group and 80.9% in the placebo group for men with low-grade prostate cancer and 73.0% and 73.6%, respectively, for those with high-grade prostate cancer. CONCLUSIONS: Finasteride reduced the risk of prostate cancer by about one third. High-grade prostate cancer was more common in the finasteride group than in the placebo group, but after 18 years of follow-up, there was no significant between-group difference in the rates of overall survival or survival after the diagnosis of prostate cancer. (Funded by the National Cancer Institute.).
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Inhibidores de 5-alfa-Reductasa/uso terapéutico , Finasterida/uso terapéutico , Neoplasias de la Próstata/prevención & control , Estudios de Seguimiento , Humanos , Incidencia , Estimación de Kaplan-Meier , Masculino , Clasificación del Tumor , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Riesgo , Tasa de SupervivenciaRESUMEN
OBJECTIVES: Enrollment of a representative population to cancer clinical trials ensures scientific reliability and generalizability of results. This study evaluated the similarity of patients enrolled in NCI-supported group gynecologic cancer trials to the incident US population. METHODS: Accrual to NCI-sponsored ovarian, uterine, and cervical cancer treatment trials between 2003 and 2012 were examined. Race, ethnicity, age, and insurance status were compared to the analogous US patient population estimated using adjusted SEER incidence data. RESULTS: There were 18,913 accruals to 156 NCI-sponsored gynecologic cancer treatment trials, ovarian (56%), uterine (32%), and cervical cancers (12%). Ovarian cancer trials included the least racial, ethnic and age diversity. Black women were notably underrepresented in ovarian trials (4% versus 11%). Hispanic patients were underrepresented in ovarian and uterine trials (4% and 5% versus 18% and 19%, respectively), but not in cervical cancer trials (14 versus 11%). Elderly patients were underrepresented in each disease area, with the greatest underrepresentation seen in ovarian cancer patients over the age of 75 (7% versus 29%). Privately insured women were overrepresented among accrued ovarian cancer patients (87% versus 76%), and the uninsured were overrepresented among women with uterine or cervical cancers. These patterns did not change over time. CONCLUSIONS: Several notable differences were observed between the patients accrued to NCI funded trials and the incident population. Improving representation of racial and ethnic minorities and elderly patients on cancer clinical trials continues to be a challenge and priority.
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Ensayos Clínicos como Asunto/estadística & datos numéricos , Etnicidad/estadística & datos numéricos , Neoplasias de los Genitales Femeninos/terapia , Seguro de Salud/estadística & datos numéricos , Pacientes no Asegurados/estadística & datos numéricos , Grupos Minoritarios/estadística & datos numéricos , Selección de Paciente , Adulto , Negro o Afroamericano/estadística & datos numéricos , Factores de Edad , Anciano , Femenino , Geografía , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Persona de Mediana Edad , National Cancer Institute (U.S.) , Neoplasias Ováricas/terapia , Programa de VERF , Estados Unidos , Neoplasias del Cuello Uterino/terapia , Neoplasias Uterinas/terapiaRESUMEN
BACKGROUND: The intake of nutrients with antioxidant properties is hypothesized to augment antioxidant defenses, decrease oxidant damage to tissues, and attenuate age-related rate of decline in lung function. The objective was to determine whether long-term intervention with selenium and/or vitamin E supplements attenuates the annual rate of decline in lung function, particularly in cigarette smokers. METHODS: The Respiratory Ancillary Study (RAS) tested the single and joint effects of selenium (200 µg/d L-selenomethionine) and vitamin E (400 IU/day all rac-α-tocopheryl acetate) in a randomized double-blind placebo-controlled trial. At the end of the intervention, 1,641 men had repeated pulmonary function tests separated by an average of 3 years. Linear mixed-effects regression models estimated the effect of intervention on annual rate of decline in lung function. RESULTS: Compared to placebo, intervention had no main effect on either forced expiratory volume in the first second (FEV1) or forced expiratory flow (FEF25-75). There was no evidence for a smoking by treatment interaction for FEV1, but selenium attenuated rate of decline in FEF25-75 in current smokers (P = 0.0219). For current smokers randomized to selenium, annual rate of decline in FEF25-75 was similar to the annual decline experienced by never smokers randomized to placebo, with consistent effects for selenium alone and combined with vitamin E. CONCLUSIONS: Among all men, there was no effect of selenium and/or vitamin E supplementation on rate of lung function decline. However, current smokers randomized to selenium had an attenuated rate of decline in FEF25-75, a marker of airflow. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00241865 .
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Pulmón/efectos de los fármacos , Pulmón/fisiología , Selenio/administración & dosificación , Fumar/tratamiento farmacológico , Vitamina E/administración & dosificación , Anciano , Antioxidantes/administración & dosificación , Suplementos Dietéticos , Método Doble Ciego , Quimioterapia Combinada , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pruebas de Función Respiratoria/tendencias , Fumar/metabolismoRESUMEN
Prostate cancer is a common malignancy in men and the worldwide burden of this disease is rising. Lifestyle modifications such as smoking cessation, exercise, and weight control offer opportunities to reduce the risk of developing prostate cancer. Early detection of prostate cancer by prostate-specific antigen (PSA) screening is controversial, but changes in the PSA threshold, frequency of screening, and the use of other biomarkers have the potential to minimise the overdiagnosis associated with PSA screening. Several new biomarkers for individuals with raised PSA concentrations or those diagnosed with prostate cancer are likely to identify individuals who can be spared aggressive treatment. Several pharmacological agents such as 5α-reductase inhibitors and aspirin could prevent development of prostate cancer. In this Review, we discuss the present evidence and research questions regarding prevention, early detection of prostate cancer, and management of men either at high risk of prostate cancer or diagnosed with low-grade prostate cancer.
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Detección Precoz del Cáncer/métodos , Estilo de Vida , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/prevención & control , Neoplasias de la Próstata/terapia , Factores de Edad , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Biopsia con Aguja , Medicina Basada en la Evidencia , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/patología , Prevención Primaria/métodos , Pronóstico , Neoplasias de la Próstata/diagnóstico , Factores de Riesgo , Conducta de Reducción del RiesgoRESUMEN
Chemoprevention refers to the use of pharmacologic interventions to delay, prevent, or reverse carcinogenesis with the ultimate goal of reducing cancer incidence. Two large, population-based, phase 3 prostate cancer prevention trials reported that 5-alpha reductase inhibitors significantly reduce prostate cancer risk. However, this class of agents were also associated with increased detection of high-grade prostate cancer. Another large, phase 3 prostate cancer prevention clinical trial showed no benefit for long-term supplementation with the trace element Se, given in the form of selenomethionine, or vitamin E, either individually or in combination. Paradoxically, a significant increase in prostate cancer was observed among men randomized to receive vitamin E alone. A great deal of progress had been made in the field of prostate cancer prevention over the past decade. Future studies will focus on prevention of disease progression in men on Active Surveillance, immunotherapy, mechanistically based drug combinations, and novel biomarkers of risk and benefit.
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Quimioprevención/métodos , Ensayos Clínicos Fase III como Asunto , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/prevención & control , Inhibidores de 5-alfa-Reductasa/efectos adversos , Inhibidores de 5-alfa-Reductasa/uso terapéutico , Antioxidantes/efectos adversos , Antioxidantes/uso terapéutico , Quimioprevención/efectos adversos , Humanos , Masculino , Neoplasias de la Próstata/inducido químicamente , Factores de Riesgo , Selenometionina/efectos adversos , Selenometionina/uso terapéutico , Resultado del Tratamiento , Vitamina E/efectos adversos , Vitamina E/uso terapéuticoRESUMEN
PURPOSE: The National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is a library of question items that enables patient reporting of adverse events (AEs) in clinical trials. This study contributes content validity evidence of the PRO-CTCAE by incorporating cancer patient input of the relevance and comprehensiveness of the item library. METHODS: Cognitive interviews were conducted among patients undergoing chemotherapy or radiation therapy at multiple sites to evaluate comprehension, memory retrieval, judgment, and response mapping related to AE terms (e.g., nausea), attribute terms (regarding frequency, severity, or interference), response options, and recall period. Three interview rounds were conducted with ≥20 patients completing each item per round. Items were modified and retested if ≥3 patients exhibited cognitive difficulties or if experienced by ≤25% patients. RESULTS: One hundred and twenty-seven patients participated (35% ≤high school, 28% non-white, and 59% female). Most AE terms (63/80) generated no cognitive difficulties. The remaining 17 were modified without further difficulties by Round 3. Terms were comprehended regardless of education level. Attribute terms and response options required no modifications. Patient adherence to recall period (7 days) was improved when the reference period was incorporated. CONCLUSIONS: This study provides evidence confirming comprehension of the US English language versions of items in the PRO-CTCAE library for measuring symptomatic AEs from the patient perspective within the context of cancer treatment. Several minor changes were made to the items to improve item clarity, comprehension, and ease of response judgment. This study helps to establish the content validity of PRO-CTCAE items for patient reporting of AEs during cancer treatment.
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Trastornos del Conocimiento/psicología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/clasificación , Entrevista Psicológica/métodos , Entrevista Psicológica/normas , National Cancer Institute (U.S.) , Autoinforme , Sistemas de Registro de Reacción Adversa a Medicamentos/normas , Antineoplásicos/efectos adversos , Antineoplásicos/toxicidad , Trastornos del Conocimiento/complicaciones , Trastornos del Conocimiento/etiología , Etiquetado de Medicamentos/normas , Femenino , Humanos , Masculino , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico , Neoplasias/radioterapia , Evaluación de Procesos y Resultados en Atención de Salud/métodos , Psicometría , Reproducibilidad de los Resultados , Terminología como Asunto , Estados UnidosRESUMEN
BACKGROUND: Our purpose was to identify physicians' individual characteristics, attitudes, and organizational contextual factors associated with higher enrollment of patients in cancer clinical trials among physician participants in the National Cancer Institute's Community Clinical Oncology Program (CCOP). We hypothesized that physicians' individual characteristics, such as age, medical specialty, tenure, CCOP organizational factors (i.e. policies and procedures to encourage enrollment), and attitudes toward participating in CCOP would directly determine enrollment. We also hypothesized that physicians' characteristics and CCOP organizational factors would influence physicians' attitudes toward participating in CCOP, which in turn would predict enrollment. METHODS: We evaluated enrollment in National Cancer Institute-sponsored cancer clinical trials in 2011 among 481 physician participants using Structural Equation Modeling. The data sources include CCOP Annual Progress Reports, two surveys of CCOP administrators and physician participants, and the American Medical Association Masterfile. RESULTS: Physicians with more positive attitudes toward participating in CCOP enrolled more patients than physicians with less positive attitudes. In addition, physicians who practiced in CCOPs that had more supportive policies and practices in place to encourage enrollment (i.e. offered trainings, provided support to screen and enroll patients, gave incentives to enroll patients, instituted minimum accrual expectations) also significantly enrolled more patients. Physician status as CCOP Principal Investigator had a positive direct effect on enrollment, while physician age and non-oncology medical specialty had negative direct effects on enrollment. Neither physicians' characteristics nor CCOP organizational factors indirectly influenced enrollment through an effect on physician attitudes. CONCLUSION: We examined whether individual physicians' characteristics and attitudes, as well as CCOP organizational factors, influenced patient enrollment in cancer clinical trials among CCOP physicians. Physician attitudes and CCOP organizational factors had positive direct effects, but not indirect effects, on physician enrollment of patients. Our results could be used to develop physician-directed strategies aimed at increasing involvement in clinical research. For example, administrators may want to ensure physicians have access to support staff to help screen and enroll patients or institute minimum accrual expectations. Our results also highlight the importance of recruiting physicians for volunteer clinical research programs whose attitudes and values align with programmatic goals. Given that physician involvement is a key determinant of patient enrollment in clinical trials, these interventions could expand the overall number of patients involved in cancer research. These strategies will be increasingly important as the CCOP network continues to evolve.
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Ensayos Clínicos como Asunto , Cirugía General/estadística & datos numéricos , Hematología/estadística & datos numéricos , Oncología Médica/estadística & datos numéricos , Neoplasias/terapia , Selección de Paciente , Médicos/estadística & datos numéricos , Oncología por Radiación/estadística & datos numéricos , Adulto , Factores de Edad , Actitud del Personal de Salud , Femenino , Cirugía General/organización & administración , Hematología/organización & administración , Humanos , Masculino , Oncología Médica/organización & administración , Persona de Mediana Edad , National Cancer Institute (U.S.) , Oncología por Radiación/organización & administración , Estados UnidosRESUMEN
BACKGROUND: Cancer screening trials have required large sample sizes and long time-horizons to demonstrate cancer mortality reductions, the primary goal of cancer screening. We examine assumptions and potential power gains from exploiting information from testing control-arm specimens, which we call the "intended effect" (IE) analysis that we explain in detail herein. The IE analysis is particularly suited to tests that can be conducted on stored specimens in the control arm, such as stored blood for multicancer detection (MCD) tests. METHODS: We simulated hypothetical MCD screening trials to compare power and sample size for the standard vs IE analysis. Under two assumptions that we detail herein, we projected the IE analysis for 3 existing screening trials (National Lung Screening Trial [NLST], Minnesota Colon Cancer Control Study [MINN-FOBT-A], and Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial-colorectal component [PLCO-CRC]). RESULTS: Compared with the standard analysis for the 3 existing trials, the IE design could have reduced cancer-specific mortality P values 5-fold (NLST), 33-fold (MINN-FOBT-A), or 14â160-fold (PLCO-CRC) or, alternately, reduced sample size (90% power) by 26% (NLST), 48% (MINN-FOBT-A), or 59% (PLCO-CRC). For potential MCD trial designs requiring 100â000 subjects per arm to achieve 90% power for multicancer mortality for the standard analysis, the IE analysis achieves 90% power for only 37â500-50â000 per arm, depending on assumptions concerning control-arm test-positives. CONCLUSIONS: Testing stored specimens in the control arm of screening trials to conduct the IE analysis could substantially increase power to reduce sample size or accelerate trials and could provide particularly strong power gains for MCD tests.
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Neoplasias Colorrectales , Detección Precoz del Cáncer , Neoplasias Pulmonares , Tamizaje Masivo , Neoplasias de la Próstata , Humanos , Detección Precoz del Cáncer/métodos , Femenino , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/mortalidad , Masculino , Tamaño de la Muestra , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidad , Tamizaje Masivo/métodos , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/prevención & control , Neoplasias/diagnóstico , Neoplasias/mortalidad , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/prevención & control , Sangre Oculta , Proyectos de Investigación , Neoplasias del Colon/diagnóstico , Neoplasias del Colon/mortalidad , Persona de Mediana Edad , Ensayos Clínicos como Asunto , Minnesota/epidemiología , Anciano , Estados Unidos/epidemiologíaRESUMEN
Deep learning-based mammographic evaluations could noninvasively assess response to breast cancer chemoprevention. We evaluated change in a convolutional neural network-based breast cancer risk model applied to mammograms among women enrolled in SWOG S0812, which randomly assigned 208 premenopausal high-risk women to receive oral vitamin D3 20â000 IU weekly or placebo for 12 months. We applied the convolutional neural network model to mammograms collected at baseline (n = 109), 12 months (n = 97), and 24 months (n = 67) and compared changes in convolutional neural network-based risk score between treatment groups. Change in convolutional neural network-based risk score was not statistically significantly different between vitamin D and placebo groups at 12 months (0.005 vs 0.002, P = .875) or at 24 months (0.020 vs 0.001, P = .563). The findings are consistent with the primary analysis of S0812, which did not demonstrate statistically significant changes in mammographic density with vitamin D supplementation compared with placebo. There is an ongoing need to evaluate biomarkers of response to novel breast cancer chemopreventive agents.