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Purpose: Chromosomal instability is a fundamental property of cancer, which can be quantified by next-generation sequencing (NGS) from plasma/serum-derived cell-free DNA (cfDNA). We hypothesized that cfDNA could be used as a real-time surrogate for imaging analysis of disease status as a function of response to immunotherapy and as a more reliable tool than tumor biomarkers.Experimental Design: Plasma cfDNA sequences from 56 patients with diverse advanced cancers were prospectively collected and analyzed in a single-blind study for copy number variations, expressed as a quantitative chromosomal number instability (CNI) score versus 126 noncancer controls in a training set of 23 and a blinded validation set of 33. Tumor biomarker concentrations and a surrogate marker for T regulatory cells (Tregs) were comparatively analyzed.Results: Elevated CNI scores were observed in 51 of 56 patients prior to therapy. The blinded validation cohort provided an overall prediction accuracy of 83% (25/30) and a positive predictive value of CNI score for progression of 92% (11/12). The combination of CNI score before cycle (Cy) 2 and 3 yielded a correct prediction for progression in all 13 patients. The CNI score also correctly identified cases of pseudo-tumor progression from hyperprogression. Before Cy2 and Cy3, there was no significant correlation for protein tumor markers, total cfDNA, or surrogate Tregs.Conclusions: Chromosomal instability quantification in plasma cfDNA can serve as an early indicator of response to immunotherapy. The method has the potential to reduce health care costs and disease burden for cancer patients following further validation. Clin Cancer Res; 23(17); 5074-81. ©2017 AACR.
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Biomarcadores de Tumor/sangre , ADN Tumoral Circulante/sangre , Inmunoterapia , Neoplasias/sangre , Adulto , Anciano , Biomarcadores de Tumor/inmunología , Inestabilidad Cromosómica/inmunología , Variaciones en el Número de Copia de ADN/genética , Progresión de la Enfermedad , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Mutación , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Neoplasias/patología , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/patologíaRESUMEN
Most studies of Wnt signaling in malignant tissues have focused on the canonical Wnt pathway (CWP) due to its role in stimulating cellular proliferation. The role of the non-canonical Wnt pathway (NCWP) in tissues with dysregulated Wnt signaling is not fully understood. Understanding NCWP's role is important since these opposing pathways act in concert to maintain homeostasis in healthy tissues. Our preliminary studies demonstrated that LiCl inhibited proliferation of primary cells derived from colorectal cancer (CRC). Since LiCl stimulates cell proliferation in normal tissues and NCWP suppresses it, the present study was designed to investigate the impact of NCWP components in LiCl-mediated effects. LiCl-mediated inhibition of CRC cell proliferation (p < 0.001) and increased apoptosis (p < 0.01) coincided with 23-fold increase (p < 0.025) in the expression of the NCWP ligand, Wnt9A. LiCl also suppressed ß-catenin mRNA (p < 0.03), total ß-catenin protein (p < 0.025) and the active form of ß-catenin. LiCl-mediated inhibition of CRC cell proliferation was partially reversed by IWP-2, and Wnt9A antibody. Recombinant Wnt9A protein emulated LiCl effects by suppressing ß-catenin protein (p < 0.001), inhibiting proliferation (p < 0.001) and increasing apoptosis (p < 0.03). This is the first study to demonstrate induction of a NCWP ligand, Wnt9A as part of a mechanism for LiCl-mediated suppression of CRC cell proliferation.
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Antineoplásicos/farmacología , Proliferación Celular/efectos de los fármacos , Colon/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Cloruro de Litio/farmacología , Recto/efectos de los fármacos , Proteínas Wnt/metabolismo , Adulto , Antimaníacos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Colon/metabolismo , Colon/patología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Humanos , Persona de Mediana Edad , Recto/metabolismo , Recto/patología , Vía de Señalización Wnt/efectos de los fármacos , beta Catenina/metabolismoRESUMEN
BACKGROUND: This manuscript describes an approach for analyzing large amounts of disparate clinical data to elucidate the most impactful factor(s) that relate to a meaningful clinical outcome, in this case, the quality of life of cancer patients. The relationships between clinical and quality of life variables were evaluated using the EORTC QLQ-C30 global health domain--a validated surrogate variable for overall cancer patient well-being. METHODS: A cross-sectional study design was used to evaluate the determinants of global health in cancer patients who initiated treatment at two regional medical centers between January 2001 and December 2009. Variables analyzed included 15 EORTC QLQ-C30 scales, age at diagnosis, gender, newly diagnosed/ recurrent disease status, and stage. The decision tree algorithm, perhaps unfamiliar to practicing clinicians, evaluates the relative contribution of individual parameters in classifying a clinically meaningful functional endpoint, such as the global health of a patient. FINDINGS: Multiple patient characteristics were identified as important contributors. Fatigue, in particular, emerged as the most prevalent indicator of cancer patients' quality of life in 16/23 clinically relevant subsets. This analysis allowed results to be stated in a clinically-intuitive, rule set format using the language and quantities of the Quality of Life (QoL) tool itself. INTERPRETATION: By applying the classification algorithms to a large data set, identification of fatigue as a root factor in driving global health and overall QoL was revealed. The ability to practice mining of clinical data sets to uncover critical clinical insights that are immediately applicable to patient care practices is illustrated.
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Fatiga/fisiopatología , Neoplasias/fisiopatología , Calidad de Vida , Árboles de Decisión , Demografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos TeóricosRESUMEN
BACKGROUND/AIM: Studies have shown that natural products could potentially be employed in combination therapies to decrease toxicity to healthy tissues by chemotherapy drugs. No studies however, have investigated the potential modulatory role of resveratrol (RV) on mitomycin C (MMC)-mediated effects on colorectal cancer. The aim of the present study was to investigate the impact of RV on MMC-mediated inhibition of colorectal cancer cell proliferation and to assess the potential mechanisms for such effects. MATERIALS AND METHODS: Primary cell lines generated from resected colorectal tumor specimens were treated with RV, MMC or RV+MMC and cell proliferation and gene expression analyses were performed. RESULTS: Suppression of cell proliferation by RV+MMC was significantly greater than individual treatments. RV+MMC synergistically modulated several genes but the up-regulation of p21(WAF1/CIP1) was several-fold greater. CONCLUSION: The up-regulation of p21(WAF1/CIP1), which inhibits the cell cycle at G0/G1 and G2/M phases, may represent the predominant mechanism for enhancement of MMC-mediated anti-cancer effects by resveratrol.
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Neoplasias Colorrectales/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Mitomicina/farmacología , Estilbenos/farmacología , Antibióticos Antineoplásicos/farmacología , Antineoplásicos Fitogénicos/farmacología , Ciclo Celular/efectos de los fármacos , Ciclo Celular/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Quinasas Ciclina-Dependientes/genética , Ciclinas/genética , Sinergismo Farmacológico , Humanos , Proteínas Mad2/genética , Proteínas Nucleares/genética , Resveratrol , Transactivadores/genética , Factores de Transcripción , Regulación hacia Arriba/efectos de los fármacos , alfa Carioferinas/genéticaRESUMEN
BACKGROUND: Rapidly evolving advances in the understanding of theorized unique driver mutations within individual patient's cancers, as well as dramatic reduction in the cost of genomic profiling, have stimulated major interest in the role of such testing in routine clinical practice. The aim of this study was to report our initial experience with genomic testing in heavily pretreated breast cancer patients. METHODS: Patients with primary or recurrent breast cancer managed at any of our five hospitals and whose malignancy had failed to respond to therapy or had progressed on all recognized standard-of-care options were offered the opportunity to have their cancer undergo next-generation sequencing genomic profiling. RESULTS: Of a total of 101 patients, 98 (97 %) had at least one specific genomic alteration identified. A total of 465 different somatic genetic abnormalities were revealed in this group of patients. Although 52 % of patients were found to have an abnormality for which an U.S. Food and Drug Administration (FDA)-approved drug was available, 69 % of patients had an FDA-approved agent for an indication other than breast cancer. The most common genomic alterations of potential clinical consequence were PIK3 (25 %), FGFR1 (16 %), AKT (11 %), PTEN (10 %), ERBB2 (8 %), JAK2 (6 %), and RAF1 (5 %). CONCLUSIONS: Almost all advanced breast cancers possess at least one well-characterized genomic alteration that might be actionable at the clinical level. Further, in most cases, a plausible argument can be advanced for the potential biological and clinical relevance of an FDA-approved antineoplastic agent not currently indicated in the treatment of breast cancer.
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Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Perfilación de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Mutación/genética , Recurrencia Local de Neoplasia/genética , Medicina de Precisión , Adulto , Anciano , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Terapia Combinada , Femenino , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Genómica , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , Selección de Paciente , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Adulto JovenRESUMEN
PURPOSE: This research conducted a face validation study of patient responses to the application of an HRQOL assessment research tool in a comprehensive community cancer program setting across a heterogeneous cohort of cancer patients throughout the natural history of diagnosed malignant disease, many of whom would not be considered candidates for clinical research trial participation. METHODS: Cancer registries at two regional cancer treatment centers identified 11072 cancer patients over a period of nine years. The EORTC QLQ-C30 was administered to patients at the time of their initial clinical presentation to these centers. To determine the significance of differences between patient subgroups, two analytic criteria were used. The Mann-Whitney test was used to determine statistical significance; clinical relevance defined a range of point differences that could be perceived by patients with different health states. RESULTS: Univariate analyses were conducted across stratification variables for population, disease severity and demographic characteristics. The largest differences were associated with cancer diagnosis and recurrence of disease. Large differences were also found for site of origin, mortality and stage; minimal differences were observed for gender and age. Consistently sensitive QoL scales were appetite loss, fatigue and pain symptoms, and role (work-related), social and physical functions. CONCLUSIONS: 1) The EORTC QLQ-C30 collected meaningful patient health assessments in the context of non-research based clinical care, 2) patient assessment differences are manifested disparately across 15 QoL domains, and 3) in addition to indicating how a patient may feel at a point in time, QoL indicators may also reveal information about underlying biological responses to disease progression, treatments, and prospective survival.
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Neoplasias/fisiopatología , Calidad de Vida , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/psicologíaRESUMEN
BACKGROUND: The combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising treatment option for selected patients with peritoneal carcinomatosis. This retrospective study investigated the relationship between baseline nutritional assessment with subsequent parenteral nutritional (PN) and clinical outcomes in cancer patients undergoing CRS and HIPEC. METHODS: A consecutive series of 60 patients undergoing CRS and HIPEC at our institution between January 2009 and May 2011. Subjective Global Assessment (SGA) was used to assess nutritional status. Patients were classified preoperatively as: well nourished (SGA-A), mildly-moderately malnourished (SGA-B), and severely malnourished (SGA-C). For PN, patients were divided into 2 groups: those who received PN (PN+) and those who did not receive PN (PN-). The primary outcomes of interest were length of stay (LOS), postoperative complications, ECOG performance status (PS) and survival. LOS was calculated as the number of days in the hospital post surgery. Performance status was measured on a scale of 0-4. Survival was calculated from the date of first visit to the date of death/last contact. RESULTS: Of 60 patients, 19 were males and 41 females. The mean age at presentation was 50.3 years. The most common cancer types were colorectal (n = 24) and gynecologic (n = 19) with the majority of patients (n = 47) treated previously before coming to our institution. 33 patients were SGA-A, 22 SGA-B and 5 SGA-C prior to surgery. Of a total of 60 patients, 31 received PN. Mean LOS for the entire cohort was 16.2 days (SD = 9.8). Mean LOS for preoperative SGA-A, SGA-B and SGA-C were 15.0, 15.2 and 27.8 days respectively (ANOVA p = 0.02). Overall incidence of complications was 26.7% (16/60). Complications were recorded in 9 of 33 (27.3%) preoperative SGA-A patients and 7 of 27 (25.9%) SGA-B + C patients (p = 0.91). The median overall survival was 17.5 months (95% CI = 13.0 to 22.1 months). Median survival for preoperative SGA-A and SGA-B + C cohorts was 22.4 and 10.4 months respectively (p = 0.006). CONCLUSIONS: The preoperative SGA predicts LOS and survival in cancer patients undergoing HIPEC. Future randomized clinical trials in this patient population should investigate the systematic provision of PN to all malnourished patients in the preoperative period for a minimum of 7-10 days with the continuation of PN in the postoperative period.
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Estado Nutricional , Nutrición Parenteral/métodos , Neoplasias Peritoneales/terapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Evaluación Nutricional , Cuidados Posoperatorios/métodos , Cuidados Preoperatorios/métodos , Desnutrición Proteico-Calórica/dietoterapia , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Several studies in the oncology literature have demonstrated the prognostic value of baseline quality of life (QoL). We investigated whether changes in QoL could predict survival in prostate cancer patients. METHODS: We evaluated 250 prostate cancer patients treated at our institution between Jan 2001 and Dec 2009 who were available for a minimum follow-up of 3 months. QoL was evaluated at baseline and after 3 months of treatment initiation using EORTC-QLQ-C30. Cox regression evaluated the prognostic significance of baseline and changes in QoL scores after adjusting for relevant clinical and demographic variables. RESULTS: Median overall survival was 89.1 months (95% CI: 56.5-121.7). Baseline QoL scale predictive of survival upon multivariate analysis was fatigue (p = 0.001). Associations between changes in QoL and survival, upon multivariate analysis, were observed for dyspnea and cognitive functioning. Every 10-point increase (worsening) in dyspnea was associated with a 16% increased risk of death (HR = 1.16; 95% CI = 1.02 to 1.30, p = 0.02), and every 10-point increase (improvement) in cognitive functioning was associated with a 24% decreased risk of death (HR = 0.76; 95% CI = 0.54 to 0.98, p = 0.04). CONCLUSIONS: This study provides preliminary evidence to indicate that prostate cancer patients with better baseline fatigue and patients whose dyspnea and cognitive functioning improves within 3 months of treatment are at a significantly decreased risk of mortality.
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Trastornos del Conocimiento/mortalidad , Disnea/mortalidad , Fatiga/mortalidad , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/psicología , Calidad de Vida/psicología , Adulto , Distribución por Edad , Anciano , Trastornos del Conocimiento/psicología , Estudios de Cohortes , Comorbilidad , Supervivencia sin Enfermedad , Disnea/psicología , Fatiga/psicología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Pronóstico , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/terapia , Reproducibilidad de los Resultados , Estudios Retrospectivos , Factores de Riesgo , Sensibilidad y Especificidad , Análisis de Supervivencia , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: There is no information in the literature on the impact of changes in quality of life (QoL) scores on prognosis in ovarian cancer. We investigated whether changes in QoL during treatment could predict survival in ovarian cancer patients. METHODS: We evaluated 137 ovarian cancer patients treated at our institution between Jan 2001 and Dec 2009 who were available for a minimum follow-up of 3 months. QoL was evaluated at baseline and after 3 months of treatment using EORTC-QLQ-C30. Cox regression evaluated the prognostic significance of baseline and changes in QoL scores after adjusting for clinical and demographic variables. RESULTS: Associations between changes in QoL and survival were observed for global function, appetite loss and constipation. Every 10-point increase (improvement) in global function from baseline to 3 months was associated with a 10% decreased risk of death (HR=0.90; 95% CI: 0.81 to 0.99, p=0.03). The corresponding HRs for 10-point increase (deterioration) in appetite loss and constipation scales were 1.20 (95% CI: 1.06 to 1.35; p=0.005) and 1.13 (95% CI: 1.02 to 1.24; p=0.02) respectively. CONCLUSIONS: This exploratory study provides evidence that an improvement in appetite, constipation and global health scores during the first 3 months of treatment is significantly associated with improved survival time in ovarian cancer. These findings justify serial, systematic assessment of global health, appetite and constipation in ovarian cancer patients being treated, and suggest that modalities designed to improve these functions may be beneficial clinically.
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OBJECTIVES: We investigated whether changes in quality of life (QoL) during treatment could predict survival in stage IV pancreatic cancer. METHODS: Quality of life was evaluated at baseline and after 3 months of treatment using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) in 186 patients with stage IV pancreatic cancer. Cox regression evaluated the prognostic significance of baseline and changes in QoL scores after adjusting for age, sex, and treatment history. RESULTS: One hundred twenty-one patients were males and 65 were females. One hundred twenty-seven patients' condition was newly diagnosed, whereas 59 were previously treated. The mean age at diagnosis was 55.1 years. Baseline QoL scale predictive of survival upon multivariate analysis was global health (hazard ratio, 0.88; 95% confidence interval, 0.81-0.95; P = 0.001). On multivariate analysis, QoL change variable that was significantly predictive of survival after 3 months of treatment was cognitive function (hazard ratio, 0.89; 95% confidence interval, 0.79-0.99; P = 0.04). CONCLUSIONS: This study provides preliminary evidence to indicate that patients with stage IV pancreatic cancer who have a better global health at baseline as well as those whose cognitive function improves within 3 months of treatment have a significantly increased probability of survival.
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Estado de Salud , Neoplasias Pancreáticas/psicología , Neoplasias Pancreáticas/terapia , Calidad de Vida , Adulto , Anciano , Anciano de 80 o más Años , Cognición , Emociones , Femenino , Humanos , Estimación de Kaplan-Meier , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Modelos de Riesgos Proporcionales , Sistema de Registros , Estudios Retrospectivos , Conducta Social , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos , Adulto JovenRESUMEN
OBJECTIVES: Use of naturopathic and nutritional supplements (NNS) with antioxidant activity is controversial in patients receiving radiation therapy. The effects of concomitant use of NNS with antioxidant activity during radiation therapy for prostate cancer were investigated in terms of clinical tumor responsiveness, kinetics, and durability. MATERIALS AND METHODS: A retrospective investigation was done of 134 patients treated with curative intent for limited-stage prostate cancer by radiation therapy. Patients self-selected to receive NNS as part of their treatment and maintenance during an extended post-treatment interval of at least 2 years. The outcome measures were the following: prostate-specific antigen (PSA) nadir; ≥24 months post-treatment PSA; time to reach nadir; and time to last follow-up were compared across +NNS and -NNS. RESULTS: Sixty-nine (69) patients elected to receive NNS while 65 did not. Seventy-seven (77) (+NNS 39, -NNS 38) patients received hormone therapy while 57 (+NNS 30, -NNS 27) did not. In the nonhormone cohort, median pretreatment PSA, nadir, post-treatment PSA, time to reach nadir, and time to follow-up were 5.5 ng/mL, 0.56 ng/mL, 0.61 ng/mL, 25 months, and 39.7 months for the -NNS group and 5.1 ng/mL, 0.32 ng/mL, 0.44 ng/mL, 27 months, and 50.1 months for the +NNS group, respectively (p>0.05 for all). Similarly, no significant differences were observed between +NNS and -NNS in the hormone-receiving cohort. CONCLUSIONS: The clinical tumor response to radiation therapy in patients with limited-stage prostate cancer is not inhibited by concomitant NNS based on the magnitude of the PSA response, the velocity of the PSA nadir, and the duration of PSA normalization.
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Antioxidantes/farmacología , Suplementos Dietéticos , Antígeno Prostático Específico/metabolismo , Neoplasias de la Próstata/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Hormonas/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Naturopatía , Evaluación de Resultado en la Atención de Salud , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/radioterapia , Estudios RetrospectivosRESUMEN
PURPOSE: While the use of quality of life (QoL) assessment has been increasing in clinical oncology, few studies have examined its prognostic significance in prostate cancer. We investigated the association between QoL at presentation and survival in prostate cancer. METHODS: We retrospectively reviewed 673 patients treated at two single-system cancer centers between January 2001 and December 2008. QoL was evaluated using EORTC-QLQ-C30. Patient survival was defined as the time interval between the date of first patient visit and the date of death/date of last contact. Univariate and multivariate Cox regression was performed to evaluate the prognostic significance of QoL. RESULTS: Mean age at presentation was 63.2 years. Patient stage of disease at diagnosis was I, 4; II, 464; III, 76; IV, 107; and 22 indeterminate. Median overall survival was 89.1 months (95% CI: 46.1-132.0). QoL scales predictive of survival upon univariate analysis were physical, role, emotional, social, fatigue, nausea/vomiting, pain, dyspnea, insomnia, loss of appetite, and constipation (p < 0.01 for all). Multivariate analyses found fatigue (p = 0.02) and constipation (p = 0.01) to be significantly associated with survival. CONCLUSIONS: Baseline QoL provides useful prognostic information in prostate cancer. These findings have important implications for patient stratification in clinical trials and may aid decision making in clinical practice.
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Estreñimiento/epidemiología , Fatiga/epidemiología , Neoplasias de la Próstata/patología , Calidad de Vida , Adulto , Anciano , Anciano de 80 o más Años , Estreñimiento/etiología , Fatiga/etiología , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Neoplasias de la Próstata/psicología , Estudios Retrospectivos , Análisis de Supervivencia , Tasa de SupervivenciaRESUMEN
BACKGROUND: Length of stay (LOS) has been used as a surrogate marker for patients' well-being during hospital treatment. We systematically reviewed all pertinent literature on the role of nutritional status in predicting LOS in cancer. METHODS: A systematic search of human studies published in English was conducted using the MEDLINE data base (all articles published as of December 2010). We searched using the terms 'nutritional status' and 'nutritional assessment' and 'nutritional screening' and 'malnutrition' in combination with the following terms: length of stay, length of hospital stay, duration of stay, and duration of hospitalization together with 'cancer' or 'oncology'. RESULTS: The MEDLINE search identified a total of 149 articles, of which only 21 met the selection criteria. Of the 21 studies, 10 studies investigated gastrointestinal cancer patients, 4 gynecological cancer, and 7 heterogeneous cancer. Eight studies used subjective global assessment (SGA) or patient-generated SGA (PG-SGA), 9 used serum albumin and/or BMI, and 4 used other methods of nutritional assessment. CONCLUSIONS: Validated nutritional tools such as SGA/PG-SGA are better predictors of LOS in gastrointestinal cancers requiring surgery than in nonsurgical gastrointestinal cancer patients. Correcting malnutrition may decrease the LOS and perhaps even lower the rate of hospital readmissions in this population.
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Tiempo de Internación , Desnutrición/epidemiología , Neoplasias/epidemiología , Estado Nutricional , Índice de Masa Corporal , Recolección de Datos , Guías como Asunto , Hospitalización , Humanos , Evaluación Nutricional , Albúmina Sérica/análisis , Estudios de Validación como AsuntoRESUMEN
While the use of quality of life (QoL) assessments has been increasing in oncology, few studies have examined the prognostic significance of QoL in breast cancer. We investigated the association between QoL at presentation and survival in breast cancer. We examined 1,511 breast cancer patients treated at two single-system cancer centers between January 2001 and December 2008. QoL was evaluated using the validated survey instrument EORTC-QLQ-C30. Patient survival was defined as the time interval between the date of first patient visit and the date of death from any cause/date of last contact. Univariate and multivariate Cox regression analyses were performed to evaluate the prognostic significance of QoL after controlling for the effects of age, tumor stage, and prior treatment history. Mean age at presentation was 52.5 years. There were 590 analytic and 921 non-analytic patients. Patient stage of disease at diagnosis was I, 335; II, 591; III, 290; IV, 159; and 136 indeterminate. Median overall survival was 32.8 months (95% CI: 27.6-38.0). On univariate analysis, QoL function and symptom scales that were predictive of survival were physical (p < 0.001), role (p < 0.001), cognitive (p = 0.003), social (p < 0.001), fatigue (p < 0.001), nausea/vomiting (p < 0.001), pain (p < 0.001), dyspnea (p < 0.001), loss of appetite (p < 0.001), and constipation (p < 0.001). On multivariate analyses, only role function (degree of impairment of work and/or leisure/hobby related activities) was significantly associated with survival. This study suggests that baseline QoL (in particular, the role function) provides useful prognostic information in breast cancer.
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Neoplasias de la Mama/psicología , Calidad de Vida , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/mortalidad , Femenino , Humanos , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Modelos de Riesgos ProporcionalesRESUMEN
BACKGROUND: There are conflicting and inconsistent results in the literature on the prognostic role of quality of life (QoL) in cancer. We investigated whether QoL at admission could predict survival in lung cancer patients. METHODS: The study population consisted of 1194 non-small cell lung cancer patients treated at our institution between Jan 2001 and Dec 2008. QoL was evaluated using EORTC-QLQ-C30 prior to initiation of treatment. Patient survival was defined as the time interval between the date of first patient visit and the date of death from any cause/date of last contact. Univariate and multivariate Cox regression evaluated the prognostic significance of QoL. RESULTS: Mean age at presentation was 58.3 years. There were 605 newly diagnosed and 589 previously treated patients; 601 males and 593 females. Stage of disease at diagnosis was I, 100; II, 63; III, 348; IV, 656; and 27 indeterminate. Upon multivariate analyses, global QoL as well as physical function predicted patient survival in the entire study population. Every 10-point increase in physical function was associated with a 10% increase in survival (95% CI = 6% to 14%, p < 0.001). Similarly, every 10-point increase in global QoL was associated with a 9% increase in survival (95% CI = 6% to 11%, p < 0.001). Furthermore, physical function, nausea/vomiting, insomnia, and diarrhea (p < 0.05 for all) in newly diagnosed patients, but only physical function (p < 0.001) in previously treated patients were predictive of survival. CONCLUSIONS: Baseline global QoL and physical function provide useful prognostic information in non-small cell lung cancer patients.
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Carcinoma de Pulmón de Células no Pequeñas/fisiopatología , Carcinoma de Pulmón de Células no Pequeñas/psicología , Neoplasias Pulmonares/fisiopatología , Neoplasias Pulmonares/psicología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Calidad de Vida , Encuestas y CuestionariosRESUMEN
BACKGROUND: Several studies have demonstrated the predictive significance on survival of baseline quality of life (QoL) in colorectal cancer (CRC) with little information on the impact of changes in QoL scores on prognosis in CRC. We investigated whether changes in QoL during treatment could predict survival in CRC. METHODS: We evaluated 396 stages III-IV CRC patients available for a minimum follow-up of 3 months. QoL was evaluated at baseline and after 3 months of treatment using EORTC QLQ-C30. Cox regression evaluated the prognostic significance of baseline, 3-month and changes in QoL scores after adjusting for age, gender and stage at diagnosis. RESULTS: After adjusting for covariates, every 10-point increase in both baseline appetite loss and global QoL score was associated with a 7% increased risk of death with HR = 1.07 (95% CI, 1.01-1.14; P = 0.02) and (HR = 0.93 (95% CI, 0.87-0.98; P = 0.01) respectively. A lower risk of death was associated with a 10-point improvement in physical function at 3 months (HR, 0.86; 95% CI, 0.78-0.94; P = 0.001). Surprisingly, a higher risk of death was associated with a 10-point improvement in social function at 3 months (HR, 1.08; 95% CI, 1.02-1.13; P = 0.008). CONCLUSIONS: This study provides preliminary evidence to indicate that CRC patients whose physical function improves within 3 months of treatment have a significantly increased probability of survival. These findings should be used in clinical practice to systematically address QoL-related problems of CRC patients throughout their treatment course.
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Neoplasias Colorrectales/patología , Calidad de Vida , Perfil de Impacto de Enfermedad , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Pronóstico , Análisis de Supervivencia , Estados Unidos , Adulto JovenRESUMEN
BACKGROUND: Cancer patients routinely develop symptoms consistent with profound circadian disruption, which causes circadian disruption diminished quality of life. This study was initiated to determine the relationship between the severity of potentially remediable cancer-associated circadian disruption and quality of life among patients with advanced lung cancer. METHODS: We concurrently investigated the relationship between the circadian rhythms of 84 advanced lung cancer patients and their quality of life outcomes as measured by the EORTC QLQ C30 and Ferrans and Powers QLI. The robustness and stability of activity/sleep circadian daily rhythms were measured by actigraphy. Fifty three of the patients in the study were starting their definitive therapy following diagnosis and thirty one patients were beginning second-line therapy. Among the patients who failed prior therapy, the median time between completing definitive therapy and baseline actigraphy was 4.3 months, (interquartile range 2.1 to 9.8 months). RESULTS: We found that circadian disruption is universal and severe among these patients compared to non-cancer-bearing individuals. We found that each of these patient's EORTC QLQ C30 domain scores revealed a compromised capacity to perform the routine activities of daily life. The severity of several, but not all, EORTC QLQ C30 symptom items correlate strongly with the degree of individual circadian disruption. In addition, the scores of all four Ferrans/Powers QLI domains correlate strongly with the degree of circadian disruption. Although Ferrans/Powers QLI domain scores show that cancer and its treatment spared these patients' emotional and psychological health, the QLI Health/Function domain score revealed high levels of patients' dissatisfaction with their health which is much worse when circadian disruption is severe. Circadian disruption selectively affects specific Quality of Life domains, such as the Ferrans/Powers Health/Function domain, and not others, such as EORTC QLQ C30 Physical Domain. CONCLUSIONS: These data suggest the testable possibility that behavioral, hormonal and/or light-based strategies to improve circadian organization may help patients suffering from advanced lung cancer to feel and function better.
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Ritmo Circadiano , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/psicología , Calidad de Vida , Actigrafía , Adulto , Anciano , Anciano de 80 o más Años , Ritmo Circadiano/fisiología , Femenino , Humanos , Neoplasias Pulmonares/epidemiología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Calidad de Vida/psicología , Encuestas y CuestionariosRESUMEN
BACKGROUND: The association between vitamin D deficiency and obesity in healthy populations and different disease states remains unsettled with studies reporting conflicting findings. Moreover, current dietary recommendations for vitamin D do not take into account a person's body mass index (BMI). We investigated the relationship between serum 25-hydroxy-vitamin D [25(OH)D] and BMI in cancer. METHODS: A consecutive case series of 738 cancer patients. Serum 25(OH)D was measured at presentation to the hospital. The cohort was divided into 4 BMI groups (underweight: <18.5, normal weight: 18.5-24.9, overweight: 25-29.9, and obese: >30.0 kg/m²). Mean 25(OH)D was compared across the 4 BMI groups using ANOVA. Linear regression was used to quantify the relationship between BMI and 25(OH)D. RESULTS: 303 were males and 435 females. Mean age at diagnosis was 55.6 years. The mean BMI was 27.9 kg/m² and mean serum 25(OH)D was 21.9 ng/ml. Most common cancers were lung (134), breast (131), colorectal (97), pancreas (86) and prostate (45). Obese patients had significantly lower serum 25(OH)D levels (17.9 ng/ml) as compared to normal weight (24.6 ng/ml) and overweight (22.8 ng/ml) patients; p < 0.001. After adjusting for age, every 1 kg/m² increase in BMI was significantly associated with 0.42 ng/ml decline in serum 25(OH)D levels. CONCLUSIONS: Obese cancer patients (BMI ≥ 30 kg/m²) had significantly lower levels of serum 25(OH)D as compared to non-obese patients (BMI <30 kg/m²). BMI should be taken into account when assessing a patient's vitamin D status and more aggressive vitamin D supplementation should be considered in obese cancer patients.
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Índice de Masa Corporal , Neoplasias/epidemiología , Obesidad/epidemiología , Deficiencia de Vitamina D/epidemiología , Vitamina D/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Composición Corporal , Estudios de Casos y Controles , Estudios Transversales , Dieta , Suplementos Dietéticos , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Neoplasias/prevención & control , Obesidad/sangre , Obesidad/complicaciones , Prevalencia , Estudios Retrospectivos , Vitamina D/sangre , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/complicacionesRESUMEN
BACKGROUND: Serum 25-hydroxyvitamin D [25(OH)D] is the major circulating form of vitamin D and a standard indicator of vitamin D status. Emerging evidence in the literature suggests a high prevalence of suboptimal vitamin D (as defined by serum 25(OH)D levels of <32 ng/ml) as well as an association between lower serum levels and higher mortality in cancer. We investigated the effect of oral vitamin D supplementation as a means for restoring suboptimal levels to optimal levels in cancer. METHODS: This is a retrospective observational study of 2198 cancer patients who had a baseline test prior to initiation of cancer therapy at our hospital to evaluate serum 25(OH)D levels between Jan 08 and Dec 09 as part of their initial nutritional evaluation. Patients with baseline levels of < = 32 ng/ml (n = 1651) were considered to have suboptimal serum 25(OH)D levels and were supplemented with 8000 IU of Vitamin D3 (four 2000 IU D3 capsules) daily as part of their nutritional care plan. The patients were retested at their first follow-up visit. Of 1651 patients, 799 were available for follow up assessment. The mean serum 25(OH)D levels were compared in these 799 patients across the 2 time points (baseline and first follow-up) using paired sample t-test. We also investigated the factors associated with response to vitamin D supplementation. RESULTS: Of 2198 patients, 814 were males and 1384 females. 1051 were newly diagnosed and treated at our hospital while 1147 were diagnosed and treated elsewhere. The mean age at presentation was 55.4 years. The most common cancer types were breast (500, 22.7%), lung (328, 14.9%), pancreas (214, 9.7%), colorectal (204, 9.3%) and prostate (185, 8.4%). The mean time duration between baseline and first follow-up assessment was 14.7 weeks (median 10.9 weeks and range 4 weeks to 97.1 weeks). The mean serum 25(OH)D levels were 19.1 ng/ml (SD = 7.5) and 36.2 ng/ml (SD = 17.1) at baseline and first follow-up respectively; p < 0.001. Patients with prostate and lung cancer had the highest percentage of responders (70% and 69.2% respectively) while those with colorectal and pancreas had the lowest (46.7% each). Similarly, patients with serum levels 20-32 ng/ml at baseline were most likely to attain levels > 32 ng/ml compared to patients with baseline levels < 20 ng/ml. CONCLUSIONS: The response to supplementation from suboptimal to optimal levels was greatest in patients with prostate and lung cancer as well as those with baseline levels between 20-32 ng/ml. Characteristics of non-responders as well as those who take longer to respond to supplementation need to be further studied and defined. Additionally, the impact of improved serum 25(OH)D levels on patient survival and quality of life needs to be investigated.
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Colecalciferol/uso terapéutico , Neoplasias/sangre , Deficiencia de Vitamina D/dietoterapia , Deficiencia de Vitamina D/etiología , Vitamina D/análogos & derivados , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Colorrectales/sangre , Femenino , Humanos , Neoplasias Pulmonares/sangre , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Neoplasias Pancreáticas/sangre , Neoplasias de la Próstata/sangre , Estudios Retrospectivos , Vitamina D/sangre , Deficiencia de Vitamina D/sangreRESUMEN
BACKGROUND: We investigated the prognostic impact of changes in serum CA125 levels during the first 3 months of therapy in ovarian cancer. METHODS: A case series of 170 ovarian cancer patients treated at Cancer Treatment Centers of America. Based on CA125 levels at baseline and 3 months, patients were classified into 4 groups: 1) Normal (0-35 U/ml) at baseline and three months; 2) High (>35 U/ml) at baseline, normal at three months; 3) Normal at baseline, high at 3 months; 4) High at baseline and three months. Kaplan Meier method was used to calculate survival across the 4 categories. RESULTS: Of 170 patients, 36 were newly diagnosed while 134 had received prior treatment. 25 had stage I disease at diagnosis, 15 stage II, 106 stage III and 14 stage IV. The median age at presentation was 54.2 years (range 23.1 - 82.5 years). At baseline, 31 patients had normal (0-35 U/ml) serum CA125 levels while 139 had high (>35 U/ml) levels. At 3 months, 59 had normal while 111 had high levels. Patients with a reduced CA125 at 3 months had a significantly better survival than those with increased CA125 at 3 months. Patients with normal values of CA125 at both baseline and 3 months had the best overall survival. CONCLUSIONS: These data show that reduction in CA125 after 3 months of therapy is associated with better overall survival in ovarian cancer. Patients without a significant decline in CA125 after 3 months of therapy have a particularly poor prognosis.