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Monitoring cancer and aging in vivo remains experimentally challenging. Here, we describe a luciferase knockin mouse (p16(LUC)), which faithfully reports expression of p16(INK4a), a tumor suppressor and aging biomarker. Lifelong assessment of luminescence in p16(+/LUC) mice revealed an exponential increase with aging, which was highly variable in a cohort of contemporaneously housed, syngeneic mice. Expression of p16(INK4a) with aging did not predict cancer development, suggesting that the accumulation of senescent cells is not a principal determinant of cancer-related death. In 14 of 14 tested tumor models, expression of p16(LUC) was focally activated by early neoplastic events, enabling visualization of tumors with sensitivity exceeding other imaging modalities. Activation of p16(INK4a) was noted in the emerging neoplasm and surrounding stromal cells. This work suggests that p16(INK4a) activation is a characteristic of all emerging cancers, making the p16(LUC) allele a sensitive, unbiased reporter of neoplastic transformation.
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Envelhecimento/genética , Biomarcadores , Transformação Celular Neoplásica , Inibidor p16 de Quinase Dependente de Ciclina/genética , Luciferases/genética , Neoplasias/genética , Animais , Senescência Celular , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Feminino , Técnicas de Introdução de Genes , Camundongos , Neoplasias/fisiopatologia , Ferimentos e Lesões/genéticaRESUMO
BACKGROUND: To describe reasons for deviations from planned chemotherapy treatments in women with nonmetastatic breast cancer that contribute to less-than-planned receipt of chemotherapy. METHODS: Electronic medical records for patients receiving chemotherapy were reviewed for adverse events and treatment modifications. Log-binomial regression models were used to estimate relative risks (RRs) with 95% CIs to examine associations between chemotherapy modifications, patient characteristics, and treatment modalities. RESULTS: Delays in chemotherapy initiation (7%) were for surgical complications (58%), personal reasons (16%), and other (26%; port malfunction, infections, and obtaining extra imaging). Delays during chemotherapy (38%) were for infections (20%), neutropenia (13%), and personal reasons (13%). Dose reductions (38%) were for neuropathy (36%), unknown causes (9%), anemia (9%), and neutropenia (8%). Early treatment discontinuations (23%) were for neuropathy (29%). Patients receiving paclitaxel/nab-paclitaxel (RR 2.05; 95% CI, 1.47-2.87) and an anthracycline (RR 1.89; 95% CI, 1.39-2.57) reported more dose delays during chemotherapy. Black race (RR 1.46; 95% CI, 1.07-2.00), stage 3 (RR 1.79; 95% CI, 1.09-2.93), and paclitaxel/nab-paclitaxel receipt (RR 1.39; 95% CI, 1.02-1.90) increased the likelihood of dose reduction. Both Black race (RR 2.06; 95% CI, 1.35-3.15) and receipt of paclitaxel/nab-paclitaxel (RR 1.93; 95% CI, 1.19-3.13) increased the likelihood of early discontinuation. Patients receiving anthracyclines had higher rates of hospitalizations during chemotherapy (RR: 1.79; 95% CI, 1.11-2.89). CONCLUSION: Toxicities are the most common reason for treatment modifications and need close monitoring in high-risk groups for timely intervention. Dose reductions and early treatment discontinuations occurred more for Black patients and need further study.
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INTRODUCTION: Standard investigator-based adverse events (AE) assessment is via CTCAE for clinical trials. However, including the patient perspective through PRO (patient-reported outcomes) enhances clinicians' understanding of patient toxicity and fosters early detection of AEs. We assessed longitudinal integration of PRO-CTCAE within clinical workflow in a phase II trial. MATERIALS AND METHODS: As a sub-study in a phase II trial of genotype-directed irinotecan dosing evaluating efficacy in patients with metastatic colorectal cancer receiving FOLFIRI and bevacizumab, patients reported on 13 AEs generating a PRO-CTCAE form. The primary objective was to estimate forms completed by patients and clinicians at least 80% of time. Secondary objectives were estimating concordance and time to first score of specific symptoms between patient and clinician pairs. RESULTS: Feasibility of longitudinal PRO-CTCAE integration was met as 96% of patients and clinician-patient pairs completed at least 80% of PRO-CTCAE forms available to them with 79% achieving 100% completion. Concordance between patient and clinician reporting a severe symptom was 73% with 24 disconcordant pairs, 21 involved patients who reported a severe symptom that the clinician did not. Although protocol-mandated dose reductions were guided by CTCAE not PRO-CTCAE responses, the median time to dose reduction of 2.53 months, and the time-to-event curve closely approximated time to patient-reported toxicity. CONCLUSION: Longitudinal integration of PRO-CTCAE paired CTCAE proved feasible. Compared to clinicians, patients reported severe symptoms more frequently and earlier. Patient-reported toxicity more closely aligned with dose decreases indicating incorporation into routine clinical practice may enhance early detection of toxicity improving patient safety and quality of life.
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BACKGROUND: FOLFIRI is a standard regimen for metastatic colorectal cancer (mCRC). We hypothesized that a pharmacogenomic-directed strategy where more efficient irinotecan metabolizers (UGT1A1 *1/*1 homozygotes and *1/*28 heterozygotes) receive higher-than-standard irinotecan doses would improve progression-free survival (PFS) compared to non-genotype selected historical controls with acceptable toxicity. METHODS: In this phase II multicenter study irinotecan dosing in first-line FOLFIRI and bevacizumab for mCRC was based on UGT1A1 genotype with *1/*1, *1/*28, and *28/*28 patients receiving 310 mg/m2, 260 mg/m2, and 180 mg/m2, respectively. Primary endpoint was PFS. Secondary endpoints were investigator and patient-reported adverse events, and estimation of overall survival (OS). RESULTS: One-hundred patients were enrolled with 91 evaluable for PFS and 83 evaluable for best response. Median PFS was 12.5 months (90% CI 10.9, 15.4), shorter than the anticipated alternative hypothesis of 14 months. PFS by genotype was 12.5 months (90% CI 10.9, 17.4) for *1/*1, 14.6 months (90% CI 11.8, 17.5) for *1/*28, and 6 months (90% CI 2.3, 7.7) for *28/28, respectively. OS was 24.5 months (90% CI 19.1, 30.7) and by genotype was 26.5 (90% CI 19.1, 32.9), 25.9 (90% CI 17.6, 37.7), and 13.4 (90% CI 2.3, 20.5) months for *1/*1, *1/*28, and *28/*28, respectively. G3/4 toxicity was similar between all subgroups, including diarrhea and neutropenia. CONCLUSIONS: A pharmacogenomic-directed irinotecan strategy improved PFS in the *1/*1 and *1/*28 genotypes with higher rates of neutropenia and similar rates of diarrhea compared to expected with standard FOLFIRI dosing. However, improvements in response rate and PFS were modest. This strategy should not change standard practice for mCRC patients in the first-line setting.
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PURPOSE: Because multiple management options exist for clinical T1 renal masses, patients may experience a state of uncertainty about the course of action to pursue (ie, decisional conflict). To better support patients, we examined patient, clinical, and decision-making factors associated with decisional conflict among patients newly diagnosed with clinical T1 renal masses suspicious for kidney cancer. MATERIALS AND METHODS: From a prospective clinical trial, participants completed the Decisional Conflict Scale (DCS), scored 0 to 100 with < 25 associated with implementing decisions, at 2 time points during the initial decision-making period. The trial further characterized patient demographics, health status, tumor burden, and patient-centered communication, while a subcohort completed additional questionnaires on decision-making. Associations of patient, clinical, and decision-making factors with DCS scores were evaluated using generalized estimating equations to account for repeated measures per patient. RESULTS: Of 274 enrollees, 250 completed a DCS survey; 74% had masses ≤ 4 cm in size, while 11% had high-complexity tumors. Model-based estimated mean DCS score across both time points was 17.6 (95% CI 16.0-19.3), though 50% reported a DCS score ≥ 25 at least once. On multivariable analysis, DCS scores increased with age (+2.64, 95% CI 1.04-4.23), high- vs low-complexity tumors (+6.50, 95% CI 0.35-12.65), and cystic vs solid masses (+9.78, 95% CI 5.27-14.28). Among decision-making factors, DCS scores decreased with higher self-efficacy (-3.31, 95% CI -5.77 to -0.86]) and information-seeking behavior (-4.44, 95% CI -7.32 to -1.56). DCS scores decreased with higher patient-centered communication scores (-8.89, 95% CI -11.85 to -5.94). CONCLUSIONS: In addition to patient and clinical factors, decision-making factors and patient-centered communication relate with decisional conflict, highlighting potential avenues to better support patient decision-making for clinical T1 renal masses.
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Conflito Psicológico , Tomada de Decisões , Neoplasias Renais , Humanos , Estudos Prospectivos , Neoplasias Renais/psicologia , Neoplasias Renais/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estadiamento de Neoplasias , Inquéritos e Questionários , Participação do Paciente , AdultoRESUMO
BACKGROUND: Pre-treatment characteristics of women with early breast cancer that are associated with persistent fatigue or suboptimal health-related quality of life (HRQOL) post-chemotherapy need to be identified as potential targets for pre-habilitation. PATIENTS AND METHODS: Ancillary analysis of previously collected data from patients with newly diagnosed Stage I-III breast cancer scheduled to receive chemotherapy. The objective was to identify baseline (pre-chemotherapy) variables associated with meaningful deteriorations in fatigue and other measures of HRQOL from pre-treatment to 6 months after chemotherapy completion. Percentages are reported along with unadjusted and adjusted relative risks. RESULTS: In a sample of 249 women post-chemotherapy, 32% reported worsening fatigue (FACIT-F), 35% worsening Physical Well-Being (PWB), 16% worsening Functional Well-Being (FWB), 8% worsening Emotional Well-Being (EWB), and 30% worsening Social Well-Being (SWB). In multivariable (MV) analysis, variables that were significant in univariate analysis - Black race, high BMI, and baseline poorer EWB - remained significant for worsening post-chemotherapy fatigue (FACIT-F). In MV analysis that included race, education, falls, and baseline EWB, Black race and a positive falls history remained significant for worsening PWB. In MV analysis inclusive of race, Short Physical Performance Battery (SPPB) and FWB, lower SPPB and FWB remained significant predictors of worsening FWB. In MV analysis that included baseline Mental Health Index-Anxiety, EWB and SWB, a higher SWB and lower EWB remained significant for worsening SWB. CONCLUSION: Pre-chemotherapy characteristics in women with early-stage breast cancer that are associated with increased fatigue and reduced HRQOL post-treatment could be used to identify patients who may benefit from pre-habilitation interventions.
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Antineoplásicos , Neoplasias da Mama , Fadiga , Qualidade de Vida , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Pessoa de Meia-Idade , Fadiga/induzido quimicamente , Fadiga/etiologia , Fadiga/epidemiologia , Adulto , Antineoplásicos/efeitos adversos , Antineoplásicos/administração & dosagem , IdosoRESUMO
PURPOSE: Clinical benefits result from electronic patient-reported outcome (ePRO) systems that enable remote symptom monitoring. Although clinically useful, real-time alert notifications for severe or worsening symptoms can overburden nurses. Thus, we aimed to algorithmically identify likely non-urgent alerts that could be suppressed. METHODS: We evaluated alerts from the PRO-TECT trial (Alliance AFT-39) in which oncology practices implemented remote symptom monitoring. Patients completed weekly at-home ePRO symptom surveys, and nurses received real-time alert notifications for severe or worsening symptoms. During parts of the trial, patients and nurses each indicated whether alerts were urgent or could wait until the next visit. We developed an algorithm for suppressing alerts based on patient assessment of urgency and model-based predictions of nurse assessment of urgency. RESULTS: 593 patients participated (median age = 64 years, 61% female, 80% white, 10% reported never using computers/tablets/smartphones). Patients completed 91% of expected weekly surveys. 34% of surveys generated an alert, and 59% of alerts prompted immediate nurse actions. Patients considered 10% of alerts urgent. Of the remaining cases, nurses considered alerts urgent more often when patients reported any worsening symptom compared to the prior week (33% of alerts with versus 26% without any worsening symptom, p = 0.009). The algorithm identified 38% of alerts as likely non-urgent that could be suppressed with acceptable discrimination (sensitivity = 80%, 95% CI [76%, 84%]; specificity = 52%, 95% CI [49%, 55%]). CONCLUSION: An algorithm can identify remote symptom monitoring alerts likely to be considered non-urgent by nurses, and may assist in fostering nurse acceptance and implementation feasibility of ePRO systems.
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Algoritmos , Medidas de Resultados Relatados pelo Paciente , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Neoplasias , Inquéritos e Questionários , AdultoRESUMO
BACKGROUND: Physical inactivity is common in young adult cancer survivors (YACS), but evidence regarding effects of physical activity (PA) interventions among YACS is limited. The IMproving Physical Activity after Cancer Treatment (IMPACT) trial evaluated a theory-based mobile PA intervention on total PA minutes/week (primary) and secondary outcomes (moderate-to-vigorous PA [MVPA], light PA, steps, sedentary behaviors) at 6 months in YACS. METHODS: YACS (N = 280) were randomized to an intervention group or self-help group. All participants received digital tools (activity tracker, smart scale, access to arm-specific Facebook group) and an individual video chat session. Intervention participants also received a 6-month program with behavioral lessons, adaptive goal-setting, tailored feedback, tailored text messages, and Facebook prompts. PA was assessed via accelerometry and questionnaires at baseline and 6 months. Generalized estimating equation analyses tested between-group differences in changes over time. RESULTS: Of 280 YACS, 251 (90%) completed the 6-month accelerometry measures. Accelerometer-measured total PA minutes/week changed from 1974.26 at baseline to 2024.34 at 6 months in the intervention (mean change, 55.14 [95% CI, -40.91 to 151.19]) and from 1814.93 to 1877.68 in the self-help group (40.94 [95% CI, -62.14 to 144.02]; between-group p = .84). Increases in MVPA were +24.67 minutes/week (95% CI, 14.77-34.57) in the intervention versus +11.41 minutes/week in the self-help (95% CI, 1.44-21.38; between-group p = .07). CONCLUSION: Although the intervention did not result in significant differences in total PA, the increase in MVPA relative to the self-help group might be associated with important health benefits. Future research should examine moderators to identify for whom, and under what conditions, the intervention might be effective. CLINICALTRIALS: gov Identifier: NCT03569605. PLAIN LANGUAGE SUMMARY: Physical inactivity is common in young adult cancer survivors. However, few interventions have focused on helping young adult cancer survivors to get more physical activity. The IMproving Physical Activity after Cancer Treatment trial compared a mobile health physical activity intervention with a self-help group on total amount of physical activity at 6 months in a nationwide sample of young adult cancer survivors. Intervention participants did not improve their total amount of physical activity, but they did increase their moderate-to-vigorous intensity physical activity by twice as much as the self-help participants. This increase in activity may be associated with health benefits.
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Sobreviventes de Câncer , Neoplasias , Telemedicina , Humanos , Adulto Jovem , Exercício Físico , Comportamentos Relacionados com a Saúde , Acelerometria , Neoplasias/terapiaRESUMO
BACKGROUND: In this study, we explore recruitment, retention, and potential quality of life (QoL) and function benefits from a self-directed, home-based walking intervention in women during active treatment for metastatic breast cancer (MBC). METHODS: In this single-arm pilot study, women with stage IV BC wore an activity tracker (FitbitTM) to measure steps per week throughout the intervention study. Participants were asked to walk 150 min per week at a comfortable and safe pace. Patient-reported outcome measures (PRO) were collected at baseline and follow-up. RESULTS: Target recruitment of 60 patients was achieved. In 52 patients who completed all baseline measures, mean age was 55 (SD 11.1), 23% were pre-menopausal, and 19% non-White. Forty patients (77%) were retained at 3 months and 29 (56%) at 6 months. Baseline walking was the strongest predictor of retention at 3 months (P = .02). For 24 patients (46%) with analyzable Fitbit data at 3 months, mean steps/week rose from 19,175 to 31,306. Higher number of steps correlated with larger improvements FACT-G General well-being (FACT-G, rho = 0.55, P = .01), FACT-G Physical well-being (rho = 0.48, P = .03), and PROMIS Mental Health (rho = 0.55, P = .01). CONCLUSION: Recruitment into a walking intervention is feasible (a priory target of N = 60) in women during treatment for MBC, but retention at 3 months follow-up fell short (77% versus a priori 80%), yet there were potential benefits in general and physical well-being and mental health. CLINICALTRIALS.GOV IDENTIFIER: NCT02682836.
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Neoplasias da Mama , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias da Mama/terapia , Neoplasias da Mama/patologia , Exercício Físico , Projetos Piloto , Qualidade de Vida , CaminhadaRESUMO
BACKGROUND: Little is known about how the quality of decisions influences patient-reported outcomes (PROs). We hypothesized that higher decision quality for breast reconstruction would be independently associated with better PROs. METHODS: We conducted a prospective cohort study of patients undergoing mastectomy with or without reconstruction. Patients were enrolled before surgery and followed for 18 months. We used BREAST-Q scales to measure PROs and linear regression models to explore the relationship between decision quality (based on knowledge and preference concordance) and PROs. Final models were adjusted for baseline BREAST-Q score, radiation, chemotherapy, and major complications. RESULTS: The cohort included 101 patients who completed baseline and 18-month surveys. Breast reconstruction was independently associated with higher satisfaction with breasts (ß = 20.2, p = 0.0002), psychosocial well-being (ß = 14.4, p = 0.006), and sexual well-being (ß = 15.7, p = 0.007), but not physical well-being. Patients who made a high-quality decision had similar PROs as patients who did not. Among patients undergoing mastectomy with reconstruction, higher decision quality was associated with lower psychosocial well-being (ß = -14.2, p = 0.01). CONCLUSIONS: Breast reconstruction was associated with better PROs in some but not all domains. Overall, making a high-quality decision was not associated with better PROs. However, patients who did not have reconstruction had a trend toward better well-being after making a high-quality decision, whereas patients who did have reconstruction had poorer well-being after making a high-quality decision. Additional research on the relationship between decision quality and PROs is needed.
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Neoplasias da Mama , Mamoplastia , Humanos , Feminino , Mastectomia/psicologia , Estudos Prospectivos , Neoplasias da Mama/cirurgia , Satisfação do Paciente , Qualidade de Vida , Mamoplastia/psicologia , Medidas de Resultados Relatados pelo PacienteRESUMO
Time at home is a critically important outcome to adults with acute myeloid leukemia (AML) when selecting treatment; however, no study to date has adequately described the amount of time older adults spend at home following initiation of chemotherapy. We queried records from a multi-institution health system to identify adults aged ≥60 years newly diagnosed with AML who were treated with azacitidine or venetoclax and evaluated the proportion of days at home (PDH) following diagnosis. Days were considered "at home" if patients were not admitted or seen in the emergency department or oncology/infusion clinic. Assessed covariates included demographics and disease risk. Associations between PDH and baseline characteristics were evaluated via linear regression, adjusted for log length of follow-up. From 2015-2020, 113 older adults were identified. Most received azacitidine plus venetoclax (51.3%) followed by azacitidine monotherapy (38.9%). The mean PDH for all patients was 0.58 (95% confidence interval: 0.54-0.63, median 0.63). PDH increased among survivors over time. PDH did not differ between therapy groups (adjusted mean, azacitidine plus venetoclax: 0.68; azacitidine monotherapy: 0.66; P=0.64) or between disease risk categories (P=0.34). Compared to patients receiving azacitidine monotherapy, patients receiving azacitidine plus venetoclax had longer clinic visits (median minutes: 127.9 vs. 112.9, P<0.001) and infusion visits (median minutes: 194.3 vs. 132.5, P<0.001). The burden of care for older adults with AML treated with "less intense" chemotherapy is high. The addition of venetoclax to azacitidine did not translate into increased time at home. Future prospective studies should evaluate patient-centered outcomes, including time at home, to inform shared decision-making and drug development.
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Azacitidina , Leucemia Mieloide Aguda , Humanos , Idoso , Estudos Prospectivos , Compostos Bicíclicos Heterocíclicos com Pontes , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/etiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
BACKGROUND: This study investigates whether high body mass index (BMI) in women diagnosed with early breast cancer (BC) is associated with patient-reported symptom severity during chemotherapy. METHODS: Women with Stage I-III BC completed toxicity reports for 17 side effects throughout regularly scheduled chemotherapy infusions. Toxicity reports were compared in women with obesity (BMI > = 30) versus no obesity (BMI < 30). Fisher's exact tests and 2-sample t-tests compared baseline patient characteristics. Risk ratios (RR) for women with obesity as compared to no obesity were estimated for individual symptoms that were patient-rated as moderate, severe or very severe (MSVS) severity, adjusting for marital status and race. RESULTS: In a sample of 286 patients, Black women comprised 23% of the sample. The obesity rate was 76% among Black patients and 31% among White patients (p < .0001). Women with obesity rated an average of 6.9 side effects (standard deviation, SD 4.2) as MSVS vs 5.5 side effects (SD 3.7) among women with no obesity (p = .003). In adjusted analysis, women with obesity had significantly greater risk for MSVS fatigue (RR 1.18, 95% CI 1.01-1.36), dyspnea (RR 1.71, 95% CI 1.09-2.69), arthralgia (RR 1.47, 95% CI 1.10-1.97), peripheral neuropathy (RR 1.45, 95% CI 1.01-2.08), edema of limbs (RR 1.84, 95% CI 1.18-2.88), and abdominal pain (RR 1.75, 95% CI 1.07-2.87). There were no inter-group differences in BC stage or phenotype, chemotherapy treatment modifications, or hospitalizations. CONCLUSIONS: Among women with early BC, patients with obesity reported higher chemotherapy toxicity as compared to patients without obesity; however, this did not result in differences in treatment completion.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Neoplasias , Feminino , Humanos , Masculino , Índice de Massa Corporal , Qualidade de Vida , Quimioterapia Adjuvante , Obesidade , Medidas de Resultados Relatados pelo PacienteRESUMO
BACKGROUND: Little is known regarding the predictive value of the Cancer and Aging Research Group (CARG) score, a validated chemotherapy toxicity prediction tool for older adults with cancer, for survival outcomes. METHODS: This was a prospective observational study of patients ≥65 years old receiving first-line chemotherapy for advanced noncolorectal gastrointestinal cancer for which combination chemotherapy is the standard of care. Overall survival (OS), time to treatment failure (TTF), which was defined as the time from the start of first-line chemotherapy to the discontinuation of first-line chemotherapy for any reason, and toxicity were compared in 4 groups of patients: 1) non-high-risk (nHR) CARG score (<10) and standard-intensity therapy (ST), 2) nHR score and reduced-intensity therapy (RT), 3) high-risk (HR) CARG score (≥10) and ST, and 4) HR score and RT. RESULTS: Fifty patients (median age, 71 years) were enrolled. The median OS in months was 19.7 in nHR/ST (n = 19) group, 12.7 in nHR/RT (n = 9) group, 4.5 in HR/ST (n = 12) group, and 3.9 in HR/RT (n = 10) group (log-rank test, P = .005). The median TTF in months was 9.1 in nHR/ST group, 2.5 in nHR/RT group, 2.3 in HR/ST group, and 3.0 in HR/RT group (log-rank test, P = .04). The CARG-score category was prognostic of OS (HR, 3.04; 95% confidence interval [CI], 1.59-5.83, P = .001) and TTF (HR, 2.60; 95% CI, 1.31-5.20, P = .007). The incidence of grade 3-5 toxicity was 68% in nHR/ST group, 33% in nHR/RT group, 92% in HR/ST group, and 70% in HR/RT group (Fisher exact test, P = .048). CONCLUSIONS: Risk-adapted chemotherapy based on the CARG-score may improve treatment outcomes.
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Antineoplásicos , Neoplasias Gastrointestinais , Idoso , Antineoplásicos/uso terapêutico , Neoplasias Gastrointestinais/tratamento farmacológico , Gerociência , Humanos , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND: Young adult cancer survivors experience frailty and decreased muscle mass at rates equivalent to much older noncancer populations, which indicate accelerated aging. Although frailty and low muscle mass can be identified in survivors, their implications for health-related quality of life are not well understood. METHODS: Through a cross-sectional analysis of young adult cancer survivors, frailty was assessed with the Fried frailty phenotype and skeletal muscle mass in relation to functional and quality of life outcomes measured by the Medical Outcomes Survey Short-Form 36 (SF-36). z tests compared survivors with US population means, and multivariable linear regression models estimated mean SF-36 scores by frailty and muscle mass with adjustments made for comorbidities, sex, and time from treatment. RESULTS: Sixty survivors (median age, 21 years; range, 18-29) participated in the study. Twenty-five (42%) had low muscle mass, and 25 were either frail or prefrail. Compared with US population means, survivors reported worse health and functional impairments across SF-36 domains that were more common among survivors with (pre)frailty or low muscle mass. In multivariable linear modeling, (pre)frail survivors (vs nonfrail) exhibited lower mean scores for general health (-9.1; P = .05), physical function (-14.9; P < .01), and overall physical health (-5.6; P = .02) independent of comorbid conditions. CONCLUSIONS: Measures of frailty and skeletal muscle mass identify subgroups of young adult cancer survivors with significantly impaired health, functional status, and quality of life independent of medical comorbidities. Identifying survivors with frailty or low muscle mass may provide opportunities for interventions to prevent functional and health declines or to reverse this process. LAY SUMMARY: Young adult cancer survivors age more quickly than peers without cancer, which is evidenced by a syndrome of decreased resilience known as frailty. The relationship between frailty (and one of its common components, decreased muscle mass) and quality of life among young adult cancer survivors was examined. Measuring decreased muscle mass and frailty identifies young survivors with poor quality of life, including worse general health, fatigue, physical function, and overall physical health, compared with nonfrail survivors. Interventions to address components of frailty (low muscle mass and weakness) may improve function and quality of life among young adult cancer survivors.
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Sobreviventes de Câncer , Fragilidade , Neoplasias , Idoso , Estudos Transversais , Idoso Fragilizado , Fragilidade/epidemiologia , Avaliação Geriátrica , Humanos , Neoplasias/terapia , Qualidade de Vida , Adulto JovemRESUMO
BACKGROUND: The plasma cell disorders (PCDs), multiple myeloma (MM), and light-chain amyloidosis (AL) are disproportionately diseases of older adults, whose care may be complicated by frailty associated with advancing age. We sought to evaluate the prevalence of functional deficits and symptoms in a cohort of persons with PCDs and associations of demographic, disease-related, functional, and psychosocial measures with quality of life (QoL). PATIENTS AND METHODS: Adults with PCDs were recruited into an observational registry in 2018-2020. Patients completed a functional assessment and European Organization for Research and Treatment of Cancer QoL questionnaire (QLQ-C30). Associations of covariates of interest with QoL were evaluated via univariate linear regression. RESULTS: Among 121 adults, the mean age was 68.6. Diagnoses were 74% MM, 14% AL, 7% both MM and AL, and 5% other PCDs. The median time from diagnosis was 34.9 months. Median lines of therapy were 2, with 11% having received ≥4th-line therapy.Patients with functional deficits had lower mean QoL scores: dependence in IADLs (66.3 vs. 79.9, P = .001) and recent falls (56.7 vs. 76.8, P = .001). Patients ≤6 months from diagnosis had lower QoL (66.7) than those ≥2 years from diagnosis (77.3, P = .03). However, patients on later lines of therapy (≥4th-line) had lower QoL (62.2) than those on 1st-line treatment (76.0, P = .04). CONCLUSIONS: Patients with physical impairments and more advanced PCDs had lower QoL than those without deficits or earlier in their disease course. Early identification of physical impairments may facilitate interventions that mitigate these deficits and thereby improve QoL for patients with PCDs.
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Fragilidade , Mieloma Múltiplo , Idoso , Humanos , Mieloma Múltiplo/terapia , Plasmócitos , Qualidade de Vida/psicologia , Inquéritos e QuestionáriosRESUMO
PURPOSE: This study evaluated whether patients with de novo metastatic breast cancer (MBC) have superior outcomes compared to those with recurrent MBC in a contemporary treatment era and examined factors related to outcome differentials. METHODS: Using an institutional database, we examined patient and tumor characteristics, treatment response, and outcome among 232 patients with de novo and 612 patients with recurrent MBC diagnosed between 2011 and 2017. RESULTS: De novo MBC had 9-month (m) longer overall survival (OS) than recurrent MBC (36.4 vs 27.4 m, p < 0.001). Contributions to this difference included nearly twofold more HER2-positive (29.3% vs 15.2%) and significantly fewer triple-negative breast cancers (20.3% vs 32.4%, both p < 0.001) in de novo compared with recurrent MBC cohorts. Stratified by clinical subtype, progression-free survival (PFS) on first-line therapy was significantly longer in de novo MBC in all but the triple-negative subtype, 25.5 vs 11.6 m (p < 0.001) among 390 patients with hormone receptor-positive, HER2-negative, 11.4 vs 5.4 m (p = 0.002) among 142 patients with HER2-positive, and 4.0 vs 3.0 m (p = 0.121) among 162 with triple-negative MBC. In multivariable analysis, de novo status remained independently associated with improved OS (hazard ratio 0.63, 95% CI 0.49-0.80), regardless of subtype and other features. CONCLUSION: Patients with de novo MBC have better outcomes than those with recurrent MBC. Differences in clinical subtype and response to therapy in the metastatic setting contribute to, but do not fully explain, this difference. Longer PFS to first-line therapy in de novo MBC suggests biologic differences compared to recurrent MBC, which may be intrinsic or due to acquired resistance from treatment for prior localized breast cancer in recurrent disease.
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Produtos Biológicos , Neoplasias da Mama , Produtos Biológicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Recidiva Local de Neoplasia/patologia , Prognóstico , Receptor ErbB-2RESUMO
OBJECTIVES: A patient's understanding of surgery is often limited, especially in the setting of complex oncologic procedures. The use of supplemental materials can improve patients' knowledge of their procedure and satisfaction with decision making. We sought to determine if a multimedia-supplemented approach in patients undergoing robotic endometrial cancer staging improves satisfaction with preoperative counseling. Secondary objectives were patient comprehension, physician satisfaction, and visit length. METHODS: From 2018 to 2019, patients were randomized to standard physician education (SPE) or multimedia-based education (MBE), which included watching two novel videos followed by focused physician counseling. Basic demographic information was collected. Patient satisfaction was assessed using the Client Satisfaction Questionnaire-8 (CSQ-8, a validated satisfaction survey, scored 8-32) and a global satisfaction score (GGS, 10-point scale). Physician satisfaction was assessed using a GGS. Comprehension was assessed with a study-specific 9-question survey at three time points. t-tests and linear mixed models were used to compare groups. RESULTS: Of the 75 patients included in the analysis, the majority were white (70%), 50-70 years old (72%), and had at least some college education (74%). The MBE group reported higher satisfaction on the CSQ-8 (31.69 vs 30.69, p < 0.01) and global satisfaction score (9.95 vs 9.74, p = 0.04). There was no difference in comprehension scores over time (p = 0.84) or between groups (p = 0.23). Visit lengths were significantly longer in the MBE group (90.36 vs 80.46 min, p = 0.04). CONCLUSIONS: Patients had high satisfaction and comprehension with both SPE and MBE. Multimedia education may be implemented in preoperative counseling based on provider preference and consideration should be made for further study of satisfaction, both patient and physician, and visit length after the initial implementation period.
Assuntos
Neoplasias do Endométrio , Multimídia , Idoso , Aconselhamento , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Consentimento Livre e Esclarecido , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
PURPOSE: Many patients with breast cancer experience depression and anxiety for years after completing systemic chemotherapy, which negatively impact overall symptom burden, quality of life, and treatment outcomes. The objective of this study was to examine the utility of patient-reported outcome (PRO) measures to predict mental health needs in patients with breast cancer during post-chemotherapy follow-up care. METHODS: In a sample of women with non-metastatic breast cancer, associations between patient-reported depression and anxiety at end of chemotherapy and post-chemotherapy mental health needs were evaluated using log-binomial regression adjusted for functional status, social activity limitations, and time from chemotherapy. RESULTS: In a sample of 149 women, 40% reported at least mild depressive symptoms and 52% reported at least mild anxiety at the end of chemotherapy. Over an average 3.2 years post-chemotherapy (range: 0.7-5.6 years), 23% received new psychiatric diagnoses, 21% engaged in mental health specialty care, and 62% were prescribed psychotropic medications. End of chemotherapy depression and anxiety were associated with future prescription of psychotropic medications (RR 1.52; 95% CI 1.14-2.03), as well as greater number of psychotropics. Associations were strongest with serotonin-norepinephrine reuptake inhibitors [(depression: RR 4.75; 95% CI 2.06-10.95); (anxiety: RR 3.68; 95% CI 1.62-8.36); (depression and anxiety: RR 2.98; 95% CI 1.65-5.36)]. CONCLUSION: Diagnosis of and treatment for depression and anxiety are common among women with breast cancer after completing chemotherapy. Prescriptions for psychotropic medications during the initial years after systemic chemotherapy can be anticipated by depression and anxiety screening at end of chemotherapy.
Assuntos
Neoplasias da Mama , Saúde Mental , Ansiedade/epidemiologia , Ansiedade/etiologia , Neoplasias da Mama/psicologia , Depressão/diagnóstico , Depressão/epidemiologia , Depressão/etiologia , Detecção Precoce de Câncer , Feminino , Humanos , Medidas de Resultados Relatados pelo Paciente , Qualidade de VidaRESUMO
PURPOSE: Although parents with cancer report that talking with their children about cancer and dying is distressing, accessible support is rare. We assessed the feasibility, acceptability, and preliminary effects of Families Addressing Cancer Together (FACT), a web-based, tailored psychosocial intervention to help parents talk about their cancer with their children. METHODS: This pilot study used a pre-posttest design. Eligible participants were parents with new or metastatic solid tumors who had minor (ages 3-18) children. Participants who completed baseline assessments received online access to FACT. We assessed feasibility through enrollment and retention rates and reasons for study refusal. Acceptability was evaluated by satisfaction ratings. We examined participants' selection of intervention content and preliminary effects on communication self-efficacy and other psychosocial outcomes (depression and anxiety symptoms, health-related quality of life, family functioning) at 2- and 12-week post-intervention. RESULTS: Of 68 parents we approached, 53 (78%) agreed to participate. Forty-six parents completed baseline assessments and received the FACT intervention. Of the 46 participants, 35 (76%) completed 2-week assessments, and 25 (54%) completed 12-week assessments. Parents reported that FACT was helpful (90%), relevant (95%), and easy to understand (100%). Parents' psychosocial outcomes did not significantly improve post-intervention, but parents endorsed less worry about talking with their child (46% vs. 37%) and reductions in the number of communication concerns (3.4 to 1.8). CONCLUSION: The FACT intervention was feasible, acceptable, and has potential to address communication concerns of parents with cancer. A randomized trial is needed to test its efficacy in improving psychological and parenting outcomes. TRIAL REGISTRATION: This study was IRB-approved and registered with clinicaltrials.gov (NCT04342871).
Assuntos
Intervenção Baseada em Internet , Neoplasias , Adolescente , Criança , Pré-Escolar , Estudos de Viabilidade , Humanos , Neoplasias/psicologia , Neoplasias/terapia , Poder Familiar , Pais/psicologia , Projetos Piloto , Intervenção Psicossocial , Qualidade de VidaRESUMO
BACKGROUND: Increased p16INK4a (p16) expression is directly related to cellular senescence and is a robust biomarker of aging in humans. Prior studies have shown that levels of p16 dramatically increase in breast cancer patients who have received adjuvant chemotherapy. This study investigated whether moderate physical activity during chemotherapy would attenuate the expected rise in p16 expression. METHODS: Participants were women with Stage I-III breast cancer enrolled in a walking study for the duration of their chemotherapy (NCT02167932, NCT02328313, NCT03761706). Participants were asked to walk at least 30 min or 6200 steps/day following a structured walking program and to wear an activity tracker. p16 mRNA levels were measured in peripheral blood T-cells before chemotherapy initiation and at approximately 6 months after last chemotherapy treatment (mean 200 days, SD 40 days). RESULTS: In total, 141 participants met inclusion criteria and 10% (n = 14) averaged > 6200 steps/day. There was no significant association of daily steps with change in p16 levels pre- to post-chemotherapy (Pearson correlation coefficient = 0.11, p = 0.17). After adjusting for age, stage, anthracycline-based chemotherapy, and baseline p16, the change in log2 p16 for each 1000 steps was estimated to be 0.03 (p = 0.35). Most participants were sedentary prior to chemotherapy and achieved modest levels of physical activity during treatment. CONCLUSION: A self-guided walking program achieved only modest levels of physical activity and was unable to ameliorate chemotherapy-induced change in p16 levels in women undergoing chemotherapy for early-stage breast cancer. More structured and vigorous exercise programs should be tested for a more definitive exploration of their impact on post-chemotherapy p16 levels.