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1.
Contemp Clin Trials ; 143: 107563, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38723860

RESUMEN

BACKGROUND: Wearable technology is used to monitor and motivate physical activity (PA) and provides continuous, objective PA and sleep data outside the clinical setting. We reviewed the literature to understand how wearables are integrated into prostate cancer (PC) investigations in order to identify current practices, gaps, and research opportunities. METHODS: We conducted a literature search for articles using wearables, among PC survivors published between 2012 and 2022. We extracted study details, interventions and outcomes, participant baseline characteristics, and device characteristics and grouped them by study type: randomized control trials (RCTs) and non-randomized studies. RESULTS: Of 354 articles screened, 44 met eligibility criteria (23 RCTs, and 21 non-randomized). 89% used wearables to monitor PA metrics, 11%, sleep metrics, and 6.8%, both. Most studies involved exercise (70% RCTs, 9% non-randomized studies) or lifestyle interventions (30% RCTs, 9% non-randomized studies). Intervention delivery methods included personalized computer-based (48%), in-person (e.g., trainer) (20%), and education web or print-based (20%). Interventions occurred at the participant's home (48%) or at a gym (20%). 57% of the studies evaluated the feasibility and acceptability of the wearable as an activity-measuring device or as part of a remotely delivered computer-based intervention. Studies used wearables to monitor adherence to PA interventions, motivate behavior change, to assess patient outcomes (e.g., patient function, quality of life, mood), or as data collection tools. CONCLUSIONS: Wearables are primarily being used to assess daily activity and monitor adherence to exercise interventions in clinical studies involving PC survivors. Findings suggest that they are feasible for use in this population. More research is needed to understand how to integrate wearables into routine clinical care, expand their use to predict clinical outcomes, or to deliver tailored interventions for PC survivors.

2.
Cancer Prev Res (Phila) ; 16(11): 631-639, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37756580

RESUMEN

Predicting an individual's risk of treatment discontinuation is critical for the implementation of precision chemoprevention. We developed partly conditional survival models to predict discontinuation of tamoxifen or anastrozole using patient-reported outcome (PRO) data from postmenopausal women with ductal carcinoma in situ enrolled in the NSABP B-35 clinical trial. In a secondary analysis of the NSABP B-35 clinical trial PRO data, we proposed two models for treatment discontinuation within each treatment arm (anastrozole or tamoxifen treated patients) using partly conditional Cox-type models with time-dependent covariates. A 70/30 split of the sample was used for the training and validation datasets. The predictive performance of the models was evaluated using calibration and discrimination measures based on the Brier score and AUC from time-dependent ROC curves. The predictive models stratified high-risk versus low-risk early discontinuation at a 6-month horizon. For anastrozole-treated patients, predictive factors included baseline body mass index (BMI) and longitudinal patient-reported symptoms such as insomnia, joint pain, hot flashes, headaches, gynecologic symptoms, and vaginal discharge, all collected up to 12 months [Brier score, 0.039; AUC, 0.76; 95% confidence interval (CI), 0.57-0.95]. As for tamoxifen-treated patients, predictive factors included baseline BMI, and time-dependent covariates: cognitive problems, feelings of happiness, calmness, weight problems, and pain (Brier score, 0.032; AUC, 0.78; 95% CI, 0.65-0.91). A real-time calculator based on these models was developed in Shiny to create a web-based application with a future goal to aid healthcare professionals in decision-making. PREVENTION RELEVANCE: The dynamic prediction provided by partly conditional models offers valuable insights into the treatment discontinuation risks using PRO data collected over time from clinical trial participants. This tool may benefit healthcare professionals in identifying patients at high risk of premature treatment discontinuation and support interventions to prevent potential discontinuation.


Asunto(s)
Neoplasias de la Mama , Femenino , Humanos , Anastrozol , Neoplasias de la Mama/tratamiento farmacológico , Medición de Resultados Informados por el Paciente , Tamoxifeno/uso terapéutico , Ensayos Clínicos Fase III como Asunto
4.
BMJ Open ; 13(6): e071041, 2023 06 16.
Artículo en Inglés | MEDLINE | ID: mdl-37328178

RESUMEN

INTRODUCTION: Physical activity (PA) promotes significant physical and psychosocial benefits for breast cancer survivors. While evidence exists regarding recommendations for the frequency, duration and intensity of exercise that optimise PA benefits for cancer survivors, the role of the environment in achieving optimal outcomes has yet to be determined. This paper presents a protocol for a clinical trial to evaluate the feasibility of a 3-month nature-based walking programme for breast cancer survivors. Secondary outcomes assessed include the impact of the intervention on fitness, quality of life outcomes, and biomarkers of ageing and inflammation. METHODS AND ANALYSIS: The trial is a 12-week single-arm pilot study. Twenty female breast cancer survivors will engage in a supervised moderate intensity walking intervention in small groups in a nature reserve for 50 minutes three times per week. Data will be collected at baseline and end of study, and include assessment of inflammatory cytokines and anti-inflammatory myokines (TNF-α, IL-1ß, IL-6, CRP, TGF-ß, IL-10, IL-13), as well as ageing (DNA methylation, ageing genes) biomarkers; surveys (Patient-Reported Outcomes Measurement Information System-29, Functional Assessment of Cancer Therapy-General, Post-Traumatic Growth Inventory); and fitness assessments (6 min Walk Test, Grip-Strength, One Repetition-Maximum Leg Press). Participants will also complete weekly surveys assessing social support and participate in an exit interview. This is an important first step for future research on the influence of exercise environment on cancer survivor PA outcomes. ETHICS AND DISSEMINATION: This study was approved by the Cedars Sinai Medical Center Institutional Review Board (IIT2020-20). Findings will be disseminated through academic manuscripts, conferences, and community presentations. TRIAL REGISTRATION NUMBER: NCT04896580.


Asunto(s)
Neoplasias de la Mama , Supervivientes de Cáncer , Humanos , Femenino , Calidad de Vida/psicología , Proyectos Piloto , Caminata/psicología , Biomarcadores
5.
Methods Protoc ; 6(3)2023 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-37218911

RESUMEN

BACKGROUND: Despite the known benefits of physical activity in cancer survivors, adherence to exercise guidelines remains low. Known barriers to adhering to guidelines include a lack of time and an unwillingness to return to treatment facilities. Virtual exercise programming could assist in mitigating these barriers. This protocol presents a single arm pilot study exploring the feasibility of personalized Zoom-delivered exercise training for breast and prostate cancer survivors. A secondary objective is to determine the preliminary efficacy of participation on body composition, estimated VO2max, hand grip, one repetition maximum leg press, resting heart rate, resting blood pressure, exercise self-efficacy, and intentions to remain active. METHODS: Breast (n = 10) and prostate (n = 10) cancer survivors will participate in a 24-week feasibility study, including (1) 12 weeks of one-on-one virtual personal training with an exercise physiologist (EP) via Zoom, and (2) individual exercise for a 12-week follow-up period using recordings of Zoom sessions for guidance. Physical assessments and surveys will be implemented at baseline, 12 weeks, and at the end of the study (24 weeks from baseline). CONCLUSIONS: While virtual exercise programming became popularized during the pandemic, evidence is still required to understand whether it can successfully address barriers and promote participation.

7.
Contemp Clin Trials Commun ; 32: 101081, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36875555

RESUMEN

Increased physical activity (PA), improved sleep, and decreased sedentary behavior (SB) are essential components of supportive care for cancer survivors. However, researchers and health care professionals have achieved limited success in improving these behaviors among cancer survivors. One potential reasoning is that, over the past two decades, guidelines for promoting and measuring PA, sleep, and SB have been largely siloed. With greater understanding of these three behaviors, health behavior researchers have recently developed a new paradigm: the 24-Hour movement approach. This approach considers PA, SB, and sleep as movement behaviors along a continuum that represent low through vigorous intensity activity. Together these three behaviors form the sum of an individual's movement across a 24-hour day. While this paradigm has been studied in the general population, its usage is still limited in cancer populations. Here, we seek to highlight (a) the potential benefits of this new paradigm for clinical trial design in oncology; (b) how this approach can allow for greater integration of wearable technology as a means of assessing and monitoring patient health outside the clinical setting, improving patient autonomy through self-monitoring of movement behavior. Ultimately, implementation of the 24-Hour movement paradigm will allow health behavior research in oncology to better promote and assess critical health behaviors to support the long-term well-being for cancer patients and survivors.

9.
NPJ Breast Cancer ; 8(1): 123, 2022 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-36402796

RESUMEN

Adjuvant chemotherapy improves breast cancer survival but is associated with bothersome short- and long-term toxicity. Factors associated with toxicity, especially subacute toxicity up to 2 years following chemotherapy, have not been fully elucidated. The NRG Oncology/NSABP B-30 clinical trial compared 3 different doxorubicin-, cyclophosphamide-, and docetaxel-based chemotherapy regimens given over 3-6 months. Patients with hormone receptor-positive breast cancer received subsequent adjuvant endocrine therapy. From baseline through 24 months, 2156 patients completed questionnaires serially. We used multivariable probabilistic index models to identify factors associated with acute (>0-12 months) and subacute (>12-24 months) difficulties with pain, cognition, vasomotor symptoms, and vaginal symptoms. For all symptom domains, presence of symptoms prior to chemotherapy initiation were associated with symptoms in the subacute period (all p < 0.001). In addition, different combinations of patient factors and breast cancer treatments were associated with increased likelihood of pain, vasomotor, and vaginal symptoms in the subacute period. Consideration of pre-treatment symptoms and patient factors, as well as treatments for breast cancer, can facilitate identification of groups of patients that may experience symptoms following completion of chemotherapy. This information may be important for treatment-decision-making when alternative regimens are equivalent in benefit.

10.
Sci Rep ; 12(1): 15013, 2022 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-36056179

RESUMEN

In this phase I dose-escalation trial, we assess the maximum tolerated dose (MTD) of Bermekimab in combination with Nanoliposomal Irinotecan (Nal-Iri) and 5-Fluorouracil/Folinic Acid (5-FU/FA). Secondarily, we investigate effects on weight, lean body mass, quality-of-life, the gut microbiome composition, inflammatory biomarkers, progression-free survival, and overall survival. This was a single-arm, open-label adaptive Bayesian dose-escalation study of Bermekimab combined with Nal-Iri and 5FU/FA in patients with advanced or locally advanced PDAC who failed gemcitabine-based chemotherapy. 22 patients enrolled between 2017 and 2019. 3 of 21 patients experienced dose-limiting toxicities attributable to the chemotherapy backbone. 58% (10/17) of patients exhibited weight stability. Physical performance status was preserved among all subjects. Patients reported improvements in quality-of-life metrics via QLQ-PAN26 questioner (-3.6, p = 0.18) and functional well-being (1.78, p = 0.02). Subjects exhibited a decrease in inflammatory cytokines, notably, vascular endothelial growth factor (-0.86, p = 0.017) with Bermekimab. Bermekimab treatment was associated with an increased abundance of gut health-promoting bacterial genera Akkermansia, with 3.82 Log2-fold change from baseline. In sum, Bermekimab is safe to be used in conjunction with Nal-Iri and 5-FU/FA chemotherapy. This benign toxicological profile warrants further Phase I/II investigation of Bermekimab in combinatorial strategies, and the impact of anti-IL-1α antibodies on the gut microbiome.Clinical trials registration: NCT03207724 05/07/2017.


Asunto(s)
Adenocarcinoma , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Pancreáticas , Adenocarcinoma/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Teorema de Bayes , Fluorouracilo/uso terapéutico , Humanos , Irinotecán , Leucovorina/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Factor A de Crecimiento Endotelial Vascular , Neoplasias Pancreáticas
11.
Cancer Epidemiol Biomarkers Prev ; 31(1): 293-295, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34758968

RESUMEN

BACKGROUND: Sex hormones have been implicated in the etiology of colorectal neoplasia in women for over 40 years, but there has been very little investigation of the role of these hormones in men. METHODS: Using data from an adenoma chemoprevention trial, we conducted a secondary analysis to examine serum hormone levels [testosterone, androstenedione, DHEA sulfate (DHEAS), and sex hormone binding globulin (SHBG)] and risk of colorectal precursors in 925 men. Multivariable logistic regression models were fit to evaluate adjusted associations between hormone levels and risk of "low-risk" (single tubular adenoma < 1 cm) and "high-risk" lesions (advanced adenoma or sessile serrated adenoma or right-sided serrated polyp or >2 adenomas of any size). RESULTS: Overall, levels of free testosterone, total testosterone, androstenedione, DHEAS, or SHBG were not associated with either "low-risk" or "high-risk" early precursor lesions in the colorectum. CONCLUSIONS: These findings do not support the role of sex hormones in early colorectal neoplasia among men. IMPACT: This large prospective study address a missing gap in knowledge by providing information on the role of sex hormones in colorectal neoplasia in males.


Asunto(s)
Adenoma/sangre , Pólipos del Colon/sangre , Neoplasias Colorrectales/sangre , Hormonas Esteroides Gonadales/sangre , Anciano , California , Estudios de Casos y Controles , Colonoscopía , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Encuestas y Cuestionarios
12.
BMC Med Res Methodol ; 21(1): 244, 2021 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-34753452

RESUMEN

BACKGROUND: Graphical displays and data visualization are essential components of statistical analysis that can lead to improved understanding of clinical trial adverse event (AE) data. Correspondence analysis (CA) has been introduced decades ago as a multivariate technique that can communicate AE contingency tables using two-dimensional plots, while quantifying the loss of information as other dimension reduction techniques such as principal components and factor analysis. METHODS: We propose the application of stacked CA using contribution biplots as a tool to explore differences in AE data among treatments in clinical trials. We defined five levels of refinement for the analysis based on data derived from the Common Terminology Criteria for Adverse Events (CTCAE) grades, domains, terms and their combinations. In addition, we developed a Shiny app built in an R-package, visae, publicly available on Comprehensive R Archive Network (CRAN), to interactively investigate CA configurations based on the contribution to the explained variance and relative frequency of AEs. Data from two randomized controlled trials (RCT) were used to illustrate the proposed methods: NSABP R-04, a neoadjuvant rectal 2 × 2 factorial trial comparing radiation therapy with either capecitabine (Cape) or 5-fluorouracil (5-FU) alone with or without oxaliplatin (Oxa), and NSABP B-35, a double-blind RCT comparing tamoxifen to anastrozole in postmenopausal women with hormone-positive ductal carcinoma in situ. RESULTS: In the R04 trial (n = 1308), CA biplots displayed the discrepancies between single agent treatments and their combinations with Oxa at all levels of AE classes, such that these discrepancies were responsible for the largest portion of the explained variability among treatments. In addition, an interaction effect when adding Oxa to Cape/5-FU was identified when the distance between Cape+Oxa and 5-FU + Oxa was observed to be larger than the distance between 5-FU and Cape, with Cape+Oxa and 5-FU + Oxa in different quadrants of the CA biplots. In the B35 trial (n = 3009), CA biplots showed different patterns for non-adherent Anastrozole and Tamoxifen compared with their adherent counterparts. CONCLUSION: CA with contribution biplot is an effective tool that can be used to summarize AE data in a two-dimensional display while minimizing the loss of information and interpretation.


Asunto(s)
Fluorouracilo , Tamoxifeno , Método Doble Ciego , Femenino , Humanos
13.
J Cachexia Sarcopenia Muscle ; 12(6): 1959-1968, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34609081

RESUMEN

BACKGROUND: Advanced pancreatic ductal adenocarcinoma (PDAC) is characterized by progressive weight loss and nutritional deterioration. This wasting has been linked to poor survival outcomes, alterations in host defenses, decreased functional ability, and diminished health-related quality of life (HRQOL) in pancreatic cancer patients. There are currently no standardized approaches to the management of pancreatic cancer cachexia. This study explores the feasibility and efficacy of enteral tube feeding of a peptide-based formula to improve weight stability and patient-reported outcomes (PROs) in advanced PDAC patients with cachexia. METHODS: This was a single-institution, single-arm prospective trial conducted between April 2015 and March 2019. Eligible patients were adults (>18 years) diagnosed with advanced or locally advanced PDAC and cachexia, defined as greater than 5% unexplained weight loss within 6 months from screening. The study intervention included three 28 day cycles of a semi-elemental peptide-based formula, administered through a jejunal or gastrojejunal feeding tube. The primary outcome was weight stability at 3 months (Cycle 3), defined as weight change less than 0.1 kg/baseline BMI unit from baseline. Secondary outcomes included changes in lean body mass, appendicular lean mass, bone mineral density, fat mass, and percent body fat, as measured with a DEXA scan, HRQOL (EORTC QLQC30) and NIH PROMIS PROs assessed at each cycle. Daily activity (steps, distance, active minutes, heart rate, and sleep) were remotely monitored using a wearable activity monitor (Fitbit) over the 3 month study period. RESULTS: Thirty-six patients were screened for eligibility, 31 patients consented onto study and underwent jejunal tube placement, and 16 patients completed treatment: mean age 67 years (SD 9.3), 43.8% male. Among evaluable patients (n = 16), weight stability was achieved in 10 patients (62.5%), thus completing the trial early. Increases in lean body mass (1273.1, SD: 4078, P = 0.01) and appendicular lean mass (0.45, SD: 0.6, P = 0.02) were observed. Statistically significant improvements at Cycle 3 from baseline were also observed for QLQC30 role function [mean difference (MD): 20.1, P = 0.03], appetite (MD: 27.4, P = 0.02), and global health scores (MD: 13.3, P = 0.05) as well as for NIH PROMIS t-scores for depression (MD: -10.4, P = 0.006) and pain interference (MD: -7.5, P = 0.05). Objectively monitored (Fitbit) activity levels increased, although statistical significance was not reached. CONCLUSIONS: Our findings suggest that enteral nutrition support may improve weight stability, lean body mass, appendicular lean mass and PROs in PDAC patients with cachexia who completed treatment, representing a subsample of the study population. The feasibility and role of enteral feeding in routine care remain unclear, and larger and randomized controlled trials are warranted.


Asunto(s)
Caquexia , Nutrición Enteral , Neoplasias Pancreáticas , Anciano , Caquexia/etiología , Caquexia/terapia , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/terapia , Medición de Resultados Informados por el Paciente , Estudios Prospectivos , Calidad de Vida
15.
J Natl Compr Canc Netw ; 18(8): 1075-1083, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32755983

RESUMEN

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is associated with high symptom burden. However, treatment decisions currently depend heavily on physician interpretation of clinical parameters and may not consider patients' health preferences. The NIH Patient-Reported Outcomes Measurement Information System (PROMIS) initiative standardized a set of patient-reported outcomes for use in chronic diseases. This study identifies preference rankings among patients with PDAC and physicians for PROMIS domains and compares the priorities of patients and their providers. METHODS: We condensed the 96 NIH PROMIS adult domains into 31 domains and created a Maximum Difference Scaling questionnaire. Domain preference scores were generated from the responses of patients with PDAC and physicians, which were compared using Maximum Difference Scaling software across demographic and clinical variables. RESULTS: Participants included 135 patients with PDAC (53% male; median age, 68 years) and 54 physicians (76% male; median years of experience, 10). Patients selected physical functioning (PF) as their top priority, whereas physicians identified pain as most important. PF, ability to perform activities of daily living, and symptom management were within the top 5 domains for both patients and physicians, and varied only slightly across age, sex, and ethnicity. However, several domains were ranked significantly higher by patients than by physicians, including but not limited to PF; ability to do things for yourself, family, and friends; ability to interact with others to obtain help; and sleep quality. Physicians ranked pain, anxiety, and depression higher than patients did. CONCLUSIONS: Our findings suggest that patients with PDAC value PF and engaging in daily and social activities the most, whereas physicians prioritize symptoms such as pain. Patient-reported outcomes need to become more integrated into PDAC care and research to better identify unmet patient needs, inform treatment decisions, and develop therapies that address outcomes valued by patients.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Medición de Resultados Informados por el Paciente , Actividades Cotidianas , Anciano , Carcinoma Ductal Pancreático/terapia , Femenino , Humanos , Masculino , Neoplasias Pancreáticas/terapia , Médicos
16.
Front Neurosci ; 14: 661, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32670013

RESUMEN

[This corrects the article DOI: 10.3389/fnins.2020.00390.].

17.
Front Neurosci ; 14: 390, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32508561

RESUMEN

Background: Recently, the ketogenic diet has been proposed as an adjunct treatment for a range of medical conditions including weight loss, diabetes, cancer, and neurodegenerative diseases. Because malignant CNS tumors are highly dependent on glucose, the use of a ketogenic diet as an adjunct therapy is currently being explored. This case series summarizes our experience implementing a ketogenic diet for patients with CNS malignancies. Methods: Patients diagnosed with CNS malignancies following a ketogenic diet were identified between 2015 and 2017. Malignancies included confirmed diagnoses of glioblastoma (GBM), astrocytoma, or oligodendroglioma. With guidance from a registered dietitian, ketone levels, glucose levels, and weight were regularly collected for several patients along with patient-reported symptoms and adverse effects. Interested patients were asked to follow a 3:1 ketogenic diet for 120 days. The ketogenic diet is a high-fat, moderate protein, and very low carbohydrate diet, where patients limited carbohydrate intake to ≤20 g per day. Brain imaging was reviewed. A series of descriptive analyses were conducted. Results: The ketogenic diet was initiated in 12 patients of which 8 patients contributed data on their blood glucose and ketone levels. The majority of patients were male (n = 10) with a median age of 45 (range 32-62). Diagnoses included GBM (n = 6), grade 2/3 astrocytomas (n = 5) and one patient with a grade 2 spinal cord astrocytoma. Ten of the 12 patients were receiving concurrent treatment; two received supportive care only. The majority of patients with evaluable data (n = 8) maintained ketone levels above 0.5 mM for the duration of 120-day period. Ketone levels generally increased from baseline while glucose levels and BMI decreased. Overall, patients reported improved symptoms over the course of the diet. Imaging also suggested improved disease control and reduction in vasogenic edema. Conclusion: Taking advantage of a tumor's metabolic inflexibility can have a positive impact on patients, particularly those with CNS malignancies. More structured and statistically planned clinical trials are needed to determine the margin of impact of a ketogenic diet.

18.
J Natl Cancer Inst ; 112(12): 1266-1274, 2020 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-32091598

RESUMEN

BACKGROUND: The National Cancer Institute Moonshot research initiative calls for improvements in the analysis and reporting of treatment toxicity to advise key stakeholders on treatment tolerability and inform regulatory and clinical decision making. This study illustrates alternative approaches to toxicity evaluation using the National Surgical Adjuvant Breast and Bowel Project R-04 clinical trial as an example. METHODS: National Surgical Adjuvant Breast and Bowel Project R-04 was a neoadjuvant chemoradiation trial in stage II-III rectal cancer patients. A 2 x 2 factorial design was used to evaluate whether the addition of oxaliplatin (Oxa) to 5-fluorouracil (5FU) or capecitabine (Cape) with radiation therapy improved local-regional tumor control. The toxicity index (TI), which accounts for the frequency and severity of toxicities, was compared across treatments using multivariable probabilistic index models, where Pr A < B indicates the probability that higher values of TI were observed for A when compared with B. Baseline age, sex, performance status, body mass index, surgery type, and stage were evaluated as independent risk factors. RESULTS: A total of 4560 toxicities from 1558 patients were analyzed. Results from adjusted probabilistic index models indicate that oxaliplatin-containing regimens had statistically significant (P < .001) probability (Pr) for higher TI compared with regimens without oxaliplatin (Pr 5FU < 5FU + Oxa = 0.619, 95% confidence interval [CI] = 0.560 to 0.674; Pr 5FU < Cape + Oxa = 0.627, 95% CI = 0.568 to 0.682; Pr Cape < 5FU + Oxa = 0.587, 95% 0.527 to 0.644; and Pr Cape < Cape + Oxa = 0.596, 95% 0.536 to 0.653). When compared with other existing toxicity analysis methods, TI provided greater power to detect differences between treatments. CONCLUSIONS: This article uses standard data collected in a cancer clinical trial to introduce descriptive and analytic methods that account for the additional burden of multiple toxicities. These methods may provide a more accurate description of a patient's treatment experience that could lead to individualized dosing for better toxicity control. Future research will evaluate the generalizability of these findings in trials with similar drugs.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Indicadores de Salud , Neoplasias/tratamiento farmacológico , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/epidemiología , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Ensayos Clínicos Fase III como Asunto/métodos , Ensayos Clínicos Fase III como Asunto/estadística & datos numéricos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Monitoreo Fisiológico/métodos , Neoplasias/epidemiología , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/epidemiología , Neoplasias del Recto/patología , Proyectos de Investigación , Resultado del Tratamiento
19.
Clin Colorectal Cancer ; 18(4): e309-e315, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31547963

RESUMEN

BACKGROUND: KRAS mutations occur in 40% of colorectal cancers (CRCs), affecting the efficacy of agents targeting the epidermal growth factor receptor. However, the effect of KRAS mutation status on the activity of non-epidermal growth factor receptor-targeting chemotherapy has not been fully elucidated. The aim of the present study is to evaluate the effect of KRAS status on the activity of different chemotherapeutic regimens. PATIENTS AND METHODS: A retrospective chart review of chemotherapy-treated patients with metastatic CRC with known KRAS status was undertaken. Chemotherapy effects were measured by progression-free survival, time to chemotherapy resistance, and overall survival. Analysis was performed for the different chemotherapy regimens, and according to the KRAS mutation status while adjusting for potential confounders. RESULTS: KRAS mutations were detected in 43% of 223 patients with metastatic CRC who were treated at the Ottawa Hospital. The baseline distribution of KRAS wild-type (WT) and mutant status was similar. The median follow-up was 27.2 months. Regimens received included single agents or combinations of 2 or 3 chemotherapies. Among those treated with capecitabine-based regimens, survival was longer for patients with KRAS WT status (hazard ratio, 0.47; 95% confidence interval, 0.23-0.95; P < .0001) when compared with those with mutant status. The median overall survival was 46.7 versus 32.6 months for patients with KRAS WT versus mutant status, respectively. The time to chemotherapy resistance was also significantly longer for patients with WT status (hazard ratio, 0.49; 95% confidence interval, 0.25-0.97; P = .0398). A trend for progression-free survival did not reach statistical significance. CONCLUSION: Patients with KRAS WT tumors may benefit more from capecitabine-based treatments than patients with mutant status. Further research is needed to explain this data.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/patología , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/secundario , Mutación , Proteínas Proto-Oncogénicas p21(ras)/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia
20.
Oncologist ; 24(12): e1460-e1466, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31227648

RESUMEN

BACKGROUND: The Eastern Cooperative Oncology Group Performance Status (ECOG-PS) scale is commonly used by physicians and nurses in oncology, as it correlates with cancer morbidity, mortality, and complications from chemotherapy and can help direct clinical decisions and prognostication. This retrospective cohort study aimed to identify whether ECOG-PS scores rated by oncologist versus nurses differ in their ability to predict clinical outcomes. MATERIALS AND METHODS: Over 19 months, 32 oncologists and 41 chemotherapy nurses from a single academic comprehensive cancer center independently scored ECOG-PS (range: 0-5) for a random sample of 311 patients with cancer receiving chemotherapy. Logistic regression models were fit to evaluate the ability of nurse and physician ECOG-PS scores, as well as the nurse-physician ECOG-PS score difference (nurse minus physician), to predict the occurrence of chemotherapy toxicity (CTCAE v4, grade ≥3) and hospitalizations within 1 month from ECOG-PS ratings, as well as 6-month mortality or hospice referrals. RESULTS: Physician/nurse ECOG-PS agreement was 71% (Cohen's κ = 0.486, p < .0001). Nurse ECOG-PS scores had stronger odds ratio for 6-month mortality or hospice (odds ratio [OR], 3.29, p < .0001) than physician ECOG-PS scores (OR, 2.71, p = .001). Furthermore, ECOG-PS ratings by nurses, but not physicians, correlated with 1-month chemotherapy toxicity (OR, 1.44, p = .021) and 1-month hospitalizations (OR, 1.57, p = .041). Nurse-physician disagreement, but only when physicians gave "healthier" (lower) ratings, was also associated with worse outcomes (chemotherapy toxicity OR = 1.51, p = .045; 1-month hospitalization OR, 1.86, p = .037; 6-month mortality or hospice OR, 2.99, p < .0001). CONCLUSION: Nurse ECOG-PS ratings seem more predictive of important outcomes than those of physicians, and physician-nurse disagreement in ECOG-PS ratings predicts worse outcomes; scoring by nurses may result in additional clinical benefit. IMPLICATIONS FOR PRACTICE: Nurse-rated Eastern Cooperative Oncology Group Performance Status (ECOG-PS) scores, compared with those rated by oncologists, better predicted hospitalizations and severe chemotherapy toxicity within 1 month from ECOG-PS assessment, as well as mortality or hospice referrals within 6 months. Physician-nurse disagreement in ECOG-PS scoring was associated with worse hospitalization, chemotherapy toxicity, and mortality and hospice referral rates. Rating performance statuses of patients with cancer by nurses instead or in addition to oncologists can result in additional clinical benefits, such as improved prognostication, as well as better informed clinical decision making regarding whether or not to administer chemotherapy, the need for additional supportive care, and goals of care discussions.


Asunto(s)
Neoplasias/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermeras y Enfermeros , Médicos , Estudios Retrospectivos , Adulto Joven
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