RESUMEN
Cancer is a disease of aging and, as the world's population ages, the number of older persons with cancer is increasing and will make up a growing share of the oncology population in virtually every country. Despite this, older patients remain vastly underrepresented in research that sets the standards for cancer treatments. Consequently, most of what we know about cancer therapeutics is based on clinical trials conducted in younger, healthier patients, and effective strategies to improve clinical trial participation of older adults with cancer remain sparse. For this systematic review, the authors evaluated published studies regarding barriers to participation and interventions to improve participation of older adults in cancer trials. The quality of the available evidence was low and, despite a literature describing multifaceted barriers, only one intervention study aimed to increase enrollment of older adults in trials. The findings starkly amplify the paucity of evidence-based, effective strategies to improve participation of this underrepresented population in cancer trials. Within these limitations, the authors provide their opinion on how the current cancer research infrastructure must be modified to accommodate the needs of older patients. Several underused solutions are offered to expand clinical trials to include older adults with cancer. However, as currently constructed, these recommendations alone will not solve the evidence gap in geriatric oncology, and efforts are needed to meet older and frail adults where they are by expanding clinical trials designed specifically for this population and leveraging real-world data.
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Geriatría/estadística & datos numéricos , Oncología Médica/estadística & datos numéricos , Neoplasias/terapia , Participación del Paciente/psicología , Selección de Paciente , Anciano , Anciano de 80 o más Años , Ensayos Clínicos como Asunto , Geriatría/métodos , Geriatría/tendencias , Humanos , Oncología Médica/métodos , Oncología Médica/tendencias , Neoplasias/diagnóstico , Participación del Paciente/estadística & datos numéricos , Estados UnidosRESUMEN
BACKGROUND: Older women with breast cancer frequently experience toxicity-related hospitalizations during adjuvant chemotherapy. Although the geriatric assessment can identify those at risk, its use in clinic remains limited. One simple, low-cost marker of vulnerability in older persons is fall history. Here, the authors examined whether falls prechemotherapy can identify older women at risk for toxicity-related hospitalization during adjuvant chemotherapy for breast cancer. METHODS: In a prospective study of women >65 years old with stage I-III breast cancer treated with adjuvant chemotherapy, the authors assessed baseline falls in the past 6 months as a categorical variable: no fall, one fall, and more than one fall. The primary end point was incident hospitalization during chemotherapy attributable to toxicity. Multivariable logistic regression was used to examine the association between falls and toxicity-related hospitalization, adjusting for sociodemographic, disease, and geriatric covariates. RESULTS: Of the 497 participants, 60 (12.1%) reported falling before chemotherapy, and 114 (22.9%) had one or more toxicity-related hospitalizations. After adjusting for sociodemographic, disease, and geriatric characteristics, women who fell more than once within 6 months before chemotherapy had greater odds of being hospitalized from toxicity during chemotherapy compared to women who did not fall (50.0% vs. 20.8% experienced toxicity-related hospitalization, odds ratio, 4.38; 95% confidence interval, 1.66-11.54, p = .003). CONCLUSIONS: In this cohort of older women with early breast cancer, women who experienced more than one fall before chemotherapy had an over 4-fold increased risk of toxicity-related hospitalization during chemotherapy, independent of sociodemographic, disease, and geriatric factors.
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Neoplasias de la Mama , Humanos , Femenino , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/tratamiento farmacológico , Estudios Prospectivos , Quimioterapia Adyuvante/efectos adversos , Evaluación Geriátrica/métodos , HospitalizaciónRESUMEN
INTRODUCTION: Older adults with cancer facing competing treatments must prioritize between various outcomes. This study assessed health outcome prioritization among older adults with cancer starting chemotherapy. METHODS: Secondary analysis of a randomized trial addressing vulnerabilities in older adults with cancer. Patients completed three validated outcome prioritization tools: 1) Health Outcomes Tool: prioritizes outcomes (survival, independence, symptoms) using a visual analog scale; 2) Now vs. Later Tool: rates the importance of quality of life at three times-today versus 1 or 5 years in the future; and 3) Attitude Scale: rates agreement with outcome-related statements. The authors measured the proportion of patients prioritizing various outcomes and evaluated their characteristics. RESULTS: A total of 219 patients (median [range] age 71 [65-88], 68% with metastatic disease) were included. On the Health Outcomes Tool, 60.7% prioritized survival over other outcomes. Having localized disease was associated with choosing survival as top priority. On the Now vs. Later Tool, 50% gave equal importance to current versus future quality of life. On the Attitude Scale, 53.4% disagreed with the statement "the most important thing to me is living as long as I can, no matter what my quality of life is"; and 82.2% agreed with the statement "it is more important to me to maintain my thinking ability than to live as long as possible". CONCLUSION: Although survival was the top priority for most participants, some older individuals with cancer prioritize other outcomes, such as cognition and function. Clinicians should elicit patient-defined priorities and include them in decision-making.
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Neoplasias , Prioridad del Paciente , Calidad de Vida , Humanos , Anciano , Femenino , Neoplasias/tratamiento farmacológico , Neoplasias/psicología , Masculino , Anciano de 80 o más Años , Resultado del TratamientoRESUMEN
PURPOSE: Aromatase inhibitor (AI) therapy reduces risk of recurrence and death for postmenopausal women with breast cancer (BC); however, AI-induced arthralgia (AIIA) can lead to discontinuation of treatment. Curcumin, a bioactive polyphenolic substance, may help ameliorate inflammation-related conditions including osteoarthritis and pain. METHODS: We conducted a multisite randomized placebo-controlled, double-blind pilot trial (Alliance A22_Pilot9) to evaluate the effects of nanoemulsion curcumin (NEC, 200 mg/day) in postmenopausal women experiencing AIIA for ≥ 3 months. The primary objective was to determine the feasibility of using Functional Assessment of Cancer Treatment-Endocrine Symptoms (FACT-ES) to detect changes from 0 (T0) to 3 months (T3) of NEC treatment in AI-induced symptoms and well-being; secondary objectives included evaluation of changes in Disabilities of the Shoulder, Arm, and Hand (DASH), Brief Pain Inventory-short form (BPI-SF), grip strength, and biomarkers at T0 and T3. RESULTS: Forty-two patients were randomized to NEC or placebo; 34 women completed the 3-month study. Patient-reported outcome measures (PROMs: FACT-ES, DASH, BPI-SF) and biospecimens were collected at T0-T3 in > 80% of participants. Adherence was ≥ 90% for both arms. PROMs and grip strength did not differ significantly by treatment arm. Plasma curcumin was detected only in NEC arm participants. Serum estradiol and estrone levels were below detection or low on study agent. Gastrointestinal adverse effects were commonly reported in both arms. CONCLUSION: NEC versus placebo in a multisite randomized trial is feasible and well-tolerated. Additional studies with larger sample size are needed to further evaluate the efficacy and safety of NEC in treatment of AIIA. CLINICALTRIALS: gov Identifier: NCT03865992, first posted March 7, 2019.
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Inhibidores de la Aromatasa , Neoplasias de la Mama , Curcumina , Humanos , Femenino , Curcumina/uso terapéutico , Curcumina/administración & dosificación , Inhibidores de la Aromatasa/efectos adversos , Inhibidores de la Aromatasa/administración & dosificación , Proyectos Piloto , Persona de Mediana Edad , Anciano , Neoplasias de la Mama/tratamiento farmacológico , Método Doble Ciego , Emulsiones , Resultado del Tratamiento , Posmenopausia , Artralgia/inducido químicamente , Artralgia/tratamiento farmacológicoRESUMEN
BACKGROUND: Patients undergoing hematopoietic cell transplantation (HCT) are at high risk of chronic health complications, including frailty and physical dysfunction. Conventional exercise programs have been shown to improve frailty in other cancer populations, but these have largely been based out of rehabilitation facilities that may act as geographic and logistical barriers. There is a paucity of information on the feasibility of implementing telehealth exercise interventions in long-term HCT survivors. METHODS: We conducted a pilot randomized trial to assess the feasibility of an 8-week telehealth exercise intervention in 20 pre-frail or frail HCT survivors. Participants were randomized to either a telehealth exercise (N = 10) or delayed control (N = 10). We administered a remote physical function assessment at baseline, followed by an 8-week telehealth exercise intervention (30-60 min/session, 3 sessions/week), and post-intervention. The primary endpoint was feasibility as determined by 1) > 70% of participants completing all remote physical functional assessments, and 2) > 70% of participants in the exercise group completing > 70% (17/24) of the prescribed exercise sessions. Exploratory outcomes included changes in gait speed, handgrip strength, and short physical performance battery. RESULTS: The mean [standard deviation] age at study enrollment was 64.7 [9.1] years old. Twelve had undergone allogenic and 8 had undergone autologous HCT at an average of 17 years from study enrollment. Both feasibility criteria were achieved. Nineteen patients (95%) completed all remote study outcome assessments at baseline and post-intervention, and nine participants in the exercise group completed > 70% of prescribed exercise sessions. Overall, no significant group x time interaction was observed on handgrip strength, fatigue, body mass index, and short physical performance battery test (P < 0.05). However, there were significant within-group improvements in four-meter gait speed (+ 13.9%; P = 0.004) and 5-minute gait speed (+ 25.4%; P = 0.04) in the exercise group whereas non-significant changes in four-meter gait speed (-3.8%) and 5-minute gait speed (-5.8%) were observed after 8 weeks. CONCLUSION: Implementing an 8-week telehealth exercise intervention for long-term HCT survivors was feasible. Our findings set the stage for innovative delivery of supervised exercise intervention that reduces the burden of frailty in HCT survivors as well as other at-risk cancer survivors. TRIAL REGISTRATION: The protocol and informed consent were approved by the institutional IRB (IRB#20731) and registered (ClinicalTrials.gov NCT04968119; date of registration: 20/07/2021).
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Fragilidad , Trasplante de Células Madre Hematopoyéticas , Telemedicina , Humanos , Anciano , Niño , Anciano Frágil , Fuerza de la Mano , Estudios de Factibilidad , Proyectos Piloto , Terapia por Ejercicio/métodos , SobrevivientesRESUMEN
BACKGROUND: When treating older women with breast cancer, life expectancy is an important consideration. ASCO recommends calculating 10-year mortality probabilities to inform treatment decisions. One useful tool is the Schonberg index, which predicts risk-based all-cause 10-year mortality. We investigated the use of this index in women aged ≥65 years with breast cancer in the Women's Health Initiative (WHI). METHODS: We calculated 10-year mortality risk scores for 2,549 WHI participants with breast cancer ("cases") and 2,549 age-matched breast cancer-free participants ("controls") using Schonberg index risk scoring. Risk scores were grouped into quintiles for comparisons. Risk-stratified observed mortality rates and 95% confidence intervals were compared across cases and controls. Observed 10-year mortality rates in cases and controls were also compared with Schonberg index-based predicted 10-year mortality rates. RESULTS: Compared with controls, cases were more often white (P=.005), had higher income and education levels (P<.001 for both), more often lived with their husband/partner (P<.001), scored higher on subjective health/happiness (P<.001), and needed less assistance in activities of daily living (P<.001). Participants with breast cancer had similar risk-stratified 10-year mortality rates compared with controls (34% vs 33%, respectively). Stratified results showed that cases had slightly higher mortality rates than controls in the lowest risk quintile and lower mortality rates in the 2 highest risk quintiles. Observed mortality rates in cases and controls were similar to Schonberg index-predicted mortality, with model c-indexes of 0.71 and 0.76, respectively. CONCLUSIONS: Among women aged ≥65 years with incident breast cancer, the Schonberg index-based risk-stratified 10-year mortality rates were similar to those in women without breast cancer, demonstrating a similar performance of the index among both populations. Along with other health measures, prognostic indexes can help predict survival among older women with breast cancer and support geriatric oncology guidelines that promote using life expectancy calculation tools for shared decision-making.
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Actividades Cotidianas , Neoplasias de la Mama , Femenino , Humanos , Anciano , Salud de la Mujer , Mama , Toma de Decisiones ConjuntaRESUMEN
BACKGROUND: Older adults account for 70% of cancer-related deaths, but previous studies have shown that they are underrepresented in cancer clinical trials. We sought to analyze the representation and outcomes of older adults in trials conducted in the era of novel targeted therapy and immunotherapy. METHODS: We searched the 2020 NCCN Clinical Practice Guidelines in Oncology and retrieved trials from the past 10 years leading to category 1 recommendations in the first-line metastatic setting for the 5 most common causes of cancer death. We categorized trials by cancer type, single-agent versus multiagent approach, and therapeutic class. We described the percentage of older adults (according to each trial's definition) and used a Mantel-Haenszel random-effects meta-analysis model to compare overall and progression-free survival by age. RESULTS: We identified 30 trials consisting of 24,416 patients. Across all trials, 44% of enrolled patients were older adults. Representation of older adults by cancer type within trials was 49% prostate cancer, 38% pancreatic cancer, 37% breast cancer, and 34% non-small cell lung cancer. Representation of older adults also varied by therapeutic class: 20% received immunotherapy, 44% received cytotoxic chemotherapy, 54% received targeted/hormonal therapy, and 34% received combination therapy (P<.001 for all comparisons). For each year since 2010, the percentage of older adults enrolled in trials increased by 1.9%, although this difference was not significant. We observed no difference in overall or progression-free survival between older and younger adults. In our analysis of practice-changing clinical trials, we found that 44% of clinical trial participants were older adults. Trials that included immunotherapy or a combination of therapeutic classes had a lower representation of older adults (<40%). CONCLUSIONS: We found that >40% of patients in practice-changing trials are older adults. Although they remain underrepresented in clinical trials compared with the general population, older adults in practice-changing trials seem to be better represented than in previously reported analyses of cooperative group trials.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Supervivencia sin ProgresiónRESUMEN
BACKGROUND: Maintaining functional status is important to older adults with cancer, but data are limited on how systemic treatments affect functional status. We systematically reviewed changes in functional status during systemic cancer treatments and identified characteristics associated with functional decline and improvement. METHODS: We searched PubMed, Embase, Web of Science, and Cochrane Register of Controlled Trials for articles examining characteristics associated with functional changes in older adults during systemic cancer treatment published in English between database inception and January 11, 2019 (PROSPERO CRD42019123125). Findings were summarized with descriptive statistics. Study characteristics between older adult-specific and non-older adult-specific studies were compared using the Fisher exact test. RESULTS: We screened 15,244 titles/abstracts and 519 full texts. The final analysis included 44 studies, which enrolled >8,400 patients; 39% of studies focused on older adults (1 study enrolled adults aged ≥60 years, 10 enrolled adults aged ≥65 years, and 6 enrolled adults aged ≥70 years). Almost all studies (98%) used patient-reported outcomes to measure functional status; only 20% used physical performance tests. Reporting of functional change was heterogeneous, with 48% reporting change scores. Older adult-specific studies were more likely to analyze functional change dichotomously (29% vs 4%; P=.008). Functional decline ranged widely, from 6% to 90%. The most common patient characteristics associated with functional decline were older age (n=7 studies), worse performance status (n=4), progressive disease status (n=4), pain (n=4), anemia (n=4), and worse nutritional status (n=4). Twelve studies examined functional improvement and identified 11 unique associated characteristics. CONCLUSIONS: Functional decline is increasingly recognized as an important outcome in older adults with cancer, but definitions and analyses are heterogeneous, leading to a wide range of prevalence. To identify patients at highest risk of functional decline during systemic cancer treatments, trials need to routinely analyze functional outcomes and measure characteristics associated with decline (eg, nutrition).
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Neoplasias , Anciano , Humanos , Persona de Mediana Edad , Neoplasias/epidemiología , Neoplasias/terapiaRESUMEN
BACKGROUND: Understanding how older patients with chronic illnesses use the internet to obtain health information is relevant for the design of digital interventions aimed at improving the health and well-being of adults aged 65 years and older; this cohort represents the sickest, most expensive, and fastest-growing segment of the US population. OBJECTIVE: The objective of our study was to describe online health information-seeking behavior among older patients with chronic illnesses and to compare the characteristics of patients who report using the internet to obtain health information with those who do not. METHODS: The study population included 72,806 women aged 65 years and older enrolled in the Women's Health Initiative (WHI), a national cohort study, who completed a 2014 supplemental questionnaire assessing everyday technology use and internet use for researching health conditions. Comparisons were made between participants with and without a history of chronic illness and between users and nonusers of online sources for health information. Multivariate logistic regression was used to estimate odds ratios (ORs) and 95% CIs. RESULTS: Of the total, 59% (42,887/72,806) of older women used the internet for health information. Compared with women who did not use the internet to obtain health information, those who used the internet were younger (median age: 76 vs 81 years), more likely to be non-Hispanic white (90% [38,481/42,887] vs 87% [26,017/29,919]), earned a higher income (over $US 50,000: 55% [23,410/42,887] vs 33% [9991/29,919]), achieved a higher educational level (more than high school: 87% [37,493/42,887] vs 75% [22,377/29,919]), and were more likely to live with a partner (52% [22,457/42,887] vs 36% [10,759/29,919]) (all P<.001). Women with Alzheimer disease were least likely to report online health information-seeking compared to those without the disease (OR 0.41, 95% CI 0.38-0.43). In contrast, women with a recent diagnosis of cancer, within the previous 2 years (OR 1.23, 95% CI 1.11-1.36) or 2-5 years ago (OR 1.09, 95% CI 1.00-1.19), were most likely to use the internet for health information. CONCLUSIONS: Nearly 6 in 10 older women participating in the WHI reported using the internet to obtain health information. Patients recently diagnosed with cancer are more likely to be looking for health information online, even after adjustment for age, suggesting that these patients may have a greater need for digital health resources.
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Enfermedad Crónica/epidemiología , Conducta en la Búsqueda de Información/fisiología , Telemedicina/métodos , Salud de la Mujer/normas , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Masculino , Encuestas y CuestionariosRESUMEN
BACKGROUND: Less than 3% of older patients with cancer are enrolled in clinical trials. To reverse this underrepresentation, we compared older patients enrolled with older-patient-specific trials, defined as those designed for older patients with cancer, with those enrolled in age-unspecified trials. MATERIALS AND METHODS: We focused on individual patient data from those ≥65 years (younger patients excluded) and included all Alliance phase III adjuvant breast cancer trials from 1985-2012. RESULTS: Among 2,277 patients, 1,014 had been enrolled to older-patient-specific and 1,263 to age-unspecified trials. The median age (range) in the older-patient-specific trials was 72 (65-89) years compared with 68 (65-84) years in the cohort of older patients in age-unspecified trials; p < .0001. A greater percentage of patients 75 years or older had enrolled in older-patient-specific trials compared with the cohort of age-unspecified trials: 26% versus 6% (p < .0001). Median overall survival (OS) was 12.8 years (95% confidence interval [CI], 11.9-13.7) and 13.5 years (95% CI, 12.9-14.1) for older-patient-specific and age-unspecified trials, respectively. OS was comparable (hazard ratio [HR], 1.08; 95% CI, 0.92-1.28; p = .34; referent: age-unspecified trials), after adjusting for age, estrogen receptor status, tumor size, and lymph node status. Similar findings were reached for recurrence-free survival. A lower rate of grade 3-5 adverse events (hematologic and nonhematologic) was reported in older-patient-specific trials (43% vs. 58%; p < .0001). Sensitivity analysis with chemotherapy only trials and subset analysis, adjusted for performance score, yielded similar OS results. CONCLUSION: Older-patient-specific trials appear to address this underrepresentation of older patients with ostensibly comparable outcomes. Clinical trial identification numbers. NCT00003088 (CALGB 9741); NCT00024102 (CALGB 49907); NCT00068601 (CALGB 40401); NCT00005970 (NCCTG N9831) IMPLICATIONS FOR PRACTICE: This work underscores the importance of clinical trials that focus on the recruitment of older patients with cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/terapia , Ensayos Clínicos Fase III como Asunto/estadística & datos numéricos , Recurrencia Local de Neoplasia/epidemiología , Selección de Paciente , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Factores de Edad , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Quimioterapia Adyuvante/métodos , Ensayos Clínicos Fase III como Asunto/normas , Supervivencia sin Enfermedad , Femenino , Humanos , Mastectomía , Recurrencia Local de Neoplasia/patología , Modelos de Riesgos Proporcionales , Ensayos Clínicos Controlados Aleatorios como Asunto/normasRESUMEN
PURPOSE: Older cancer patients are at increased risk of cancer-related cognitive impairment. The purpose of this study was to assess the alterations in intrinsic brain activity associated with adjuvant chemotherapy in older women with breast cancer. METHODS: Chemotherapy treatment (CT) group included sixteen women aged ≥ 60 years (range 60-82 years) with stage I-III breast cancers, who underwent both resting-state functional magnetic resonance imaging (rs-fMRI) and neuropsychological testing with NIH Toolbox for Cognition before adjuvant chemotherapy, at time point 1 (TP1), and again within 1 month after completing chemotherapy, at time point 2 (TP2). Fourteen age- and sex-matched healthy controls (HC) underwent the same assessments at matched intervals. Three voxel-wise rs-fMRI parameters: amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity, were computed at each time point. The changes in rs-fMRI parameters from TP1 to TP2 for each group, the group differences in changes (the CT group vs. the HC group), and the group difference in the baseline rs-fMRI parameters were assessed. In addition, correlative analysis between the rs-fMRI parameters and neuropsychological testing scores was also performed. RESULTS: In the CT group, one brain region, which included parts of the bilateral subcallosal gyri and right anterior cingulate gyrus, displayed increased ALFF from TP1 to TP2 (cluster p-corrected = 0.024); another brain region in the left precuneus displayed decreased fALFF from TP1 to TP2 (cluster level p-corrected = 0.025). No significant changes in the rs-fMRI parameters from TP1 to TP2 were observed in the HC group. Although ALFF and fALFF alterations were observed only in the CT group, none of the between-group differences in rs-fMRI parameter changes reached statistical significance. CONCLUSIONS: Our study results of ALFF and fALFF alterations in the chemotherapy-treated women suggest that adjuvant chemotherapy may affect intrinsic brain activity in older women with breast cancer.
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Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/epidemiología , Quimioterapia Adyuvante/efectos adversos , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/etiología , Factores de Edad , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante/métodos , Disfunción Cognitiva/diagnóstico , Femenino , Encuestas de Atención de la Salud , Humanos , Procesamiento de Imagen Asistido por Computador , Estudios Longitudinales , Imagen por Resonancia Magnética , Persona de Mediana Edad , Neuroimagen/métodos , Proyectos PilotoRESUMEN
Purpose: The objective of this study was to assess changes in hippocampal volume and shape in older long-term breast cancer survivors who were exposed to chemotherapy 5-15 years prior. Methods: This study recruited female long-term breast cancer survivors aged 65 years or older with a history of chemotherapy (C+), age-matched breast cancer survivors who did not receive chemotherapy (C-), and healthy controls (HC). The participants were recruited 5-15 years after chemotherapy at time point 1 (TP1) and were followed up for 2 years at time point 2 (TP2). Assessments included hippocampal volume and shape from brain MRI scans and neuropsychological (NP) tests. Results: At TP1, each of the three groups was comprised of 20 participants. The C+ group exhibited a hippocampal volume loss estimated in proportion with total intracranial volume (ICV) in both the left and right hemispheres from TP1 to TP2. Regarding the hippocampal shape at TP1, the C+ group displayed inward changes compared to the control groups. Within the C+ group, changes in right hippocampal volume adjusted with ICV were positively correlated with crystalized composite scores (R = 0.450, p = 0.044). Additionally, in C+ groups, chronological age was negatively correlated with right hippocampal volume adjusted with ICV (R = -0.585, p = 0.007). Conclusion: The observed hippocampal volume reduction and inward shape deformation within the C+ group may serve as neural basis for cognitive changes in older long-term breast cancer survivors with history of chemotherapy treatment.
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PURPOSE: To assess white matter microstructural changes in older long-term breast cancer survivors 5-15 years post-chemotherapy treatment. METHODS: Breast cancer survivors aged 65 years or older who underwent chemotherapy (C+) and who did not undergo chemotherapy (C-) and age- and sex-matched healthy controls (HC) were enrolled at time point 1 (TP1) and followed for 2 years for time point 2 (TP2). All participants underwent brain MRI with diffusion tensor images and neuropsychological (NP) testing with the NIH Toolbox Cognition Battery. Tract-based spatial statistics (TBSS) analysis was performed on the diffusion tensor images to assess white matter microstructural changes with the fractional anisotropy (FA) parameter. RESULTS: There were significant longitudinal alterations in FA within the C+ group over time. The C+ group showed diminished FA in the body and genu of corpus callosum, anterior corona radiate, and external capsule on both the whole brain and region of interest (ROI) based analyses after p < 0.05 family-wise error (FWE) correction. However, there were no significant group differences between the groups at TP1. Additionally, at TP1, a positive correlation (R = 0.58, p = 0.04) was observed between the FA value of the anterior corona radiata and the crystallized composite score in the C+ group. CONCLUSIONS: Brain white matter microstructural alterations may be the underlying neural correlates of cognitive changes in older breast cancer survivors who had chemotherapy treatment years ago.
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Neoplasias de la Mama , Supervivientes de Cáncer , Imagen de Difusión Tensora , Sustancia Blanca , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/diagnóstico por imagen , Anciano , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/efectos de los fármacos , Sustancia Blanca/patología , Pruebas Neuropsicológicas , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encéfalo/efectos de los fármacos , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversos , Estudios de Casos y Controles , Anciano de 80 o más AñosRESUMEN
PURPOSE: This study aimed to assess whether physical functional decline in older women with early-stage breast cancer is driven by cancer, chemotherapy, or a combination of both. METHODS: We prospectively sampled three groups of women aged ≥ 65: 444 with early-stage breast cancer receiving chemotherapy (BC Chemo), 98 with early-stage breast cancer not receiving chemotherapy (BC Control), and 100 non-cancer controls (NC Control). Physical function was assessed at two timepoints (T1 [baseline] and T2 [3, 4, or 6 months]) using the Physical Functioning Subscale (PF-10) of the RAND 36-item Short Form. The primary endpoint was the change in PF-10 scores from T1 to T2, analyzed continuously and dichotomously (Yes/No, with "yes" indicating a PF-10 decline > 10 points, i.e., a substantial and clinically meaningful difference). RESULTS: Baseline PF-10 scores were similar across all groups. The BC Chemo group experienced a significant decline at T2, with a median change in PF-10 of -5 (interquartile range [IQR], -20, 0), while BC Control and NC Control groups showed a median change of 0 (IQR, -5, 5; p < 0.001). Over 30% of BC Chemo participants had a substantial decline in PF-10 vs. 8% in the BC Control and 5% in the NC Control groups (p < 0.001). CONCLUSION: In this cohort of older adults with early-stage breast cancer, the combination of breast cancer and chemotherapy contributes to accelerated functional decline. Our findings reinforce the need to develop interventions aimed at preserving physical function, particularly during and after chemotherapy. IMPLICATIONS FOR CANCER SURVIVORS: The high prevalence of accelerated functional decline in older women undergoing breast cancer chemotherapy underscores the urgency to develop interventions aimed at preserving physical function and improving health outcomes. CLINICAL TRIAL: NCT01472094, Hurria Older PatiEnts (HOPE) with Breast Cancer Study.
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Neoplasias de la Mama , Supervivientes de Cáncer , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Estudios de Casos y Controles , Estudios Prospectivos , Calidad de VidaRESUMEN
INTRODUCTION: Palbociclib is a widely used treatment for advanced breast cancer in older adults. However, the existing evidence regarding its safety and tolerability in this age group is inconsistent and limited to retrospective subgroup or pooled analyses. MATERIALS AND METHODS: We conducted a prospective single-arm multicenter phase 2 study to evaluate the safety and tolerability of palbociclib in participants aged 70 years or older with advanced hormone receptor-positive breast cancer. Participants were given palbociclib in combination with their physician's choice of endocrine therapy (letrozole or fulvestrant). The primary endpoint was the incidence of grade 3+ adverse events (AEs) by six months. Secondary endpoints included AE-related dose delays, dose reductions, early discontinuations, and hospitalizations. Additionally, we compared these endpoints by age groups (70-74 and ≥ 75 years). RESULTS: Of the 90 participants (median age 74 years [70-87]) enrolled, 75.6% (95% confidence interval [CI], 65.4-84.0) had grade 3+ AEs by six months. The most frequent grade 3+ AEs were neutropenia (61%), fatigue (4%), and nausea (3%). Febrile neutropenia was uncommon (1.1%). Due to AEs, 36% had dose delays, 34% had dose reductions, 10% had early discontinuations, and 10% had hospitalizations. Compared to those aged 70-74 years, participants aged ≥75 years had higher rates of early discontinuations (5.9% vs 15.9%, a difference of 9.5% [95% CI 3.5%-22.5%]). DISCUSSION: Palbociclib has an overall favorable safety profile in adults aged ≥70 with advanced breast cancer. However, adults ≥75 years had a trend toward higher rates of AE-related early discontinuations compared to those 70-74 years. Further research is needed to evaluate tolerability and improve the delivery of palbociclib in older adults. CLINICALTRIALS: gov:NCT03633331.
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Neoplasias de la Mama , Piperazinas , Piridinas , Humanos , Piridinas/efectos adversos , Piridinas/administración & dosificación , Piridinas/uso terapéutico , Anciano , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Piperazinas/efectos adversos , Piperazinas/administración & dosificación , Piperazinas/uso terapéutico , Anciano de 80 o más Años , Estudios Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Fulvestrant/administración & dosificación , Fulvestrant/uso terapéutico , Letrozol/administración & dosificación , Letrozol/uso terapéutico , Factores de EdadAsunto(s)
Supervivientes de Cáncer , Neoplasias , Anciano , Baltimore , Humanos , Estudios Longitudinales , InvestigaciónRESUMEN
BACKGROUND & AIMS: An association between inflammatory activity and colorectal neoplasia (CRN) has been documented in patients with ulcerative colitis (UC). However, previous studies did not address the duration of inflammation or the effects of therapy on risk for CRN. We investigated the effects of inflammation, therapies, and characteristics of patients with UC on their risk for CRN. METHODS: We collected data from 141 patients with UC without CRN (controls) and 59 matched patients with UC who developed CRN (cases), comparing disease extent and duration and patients' ages. We used a new 6-point histologic inflammatory activity (HIA) scale to score biopsy fragments (n = 4449). Information on medications, smoking status, primary sclerosing cholangitis, and family history of CRN were collected from the University of Chicago Inflammatory Bowel Disease Endoscopy Database. Relationships between HIA, clinical features, and CRN were assessed by conditional logistic regression. RESULTS: Cases and controls were similar in numbers of procedures and biopsies, exposure to steroids or mesalamine, smoking status, and family history of CRN. They differed in proportion of men vs women, exposure to immune modulators, and primary sclerosing cholangitis prevalence. In univariate analysis, HIA was positively associated with CRN (odds ratio [OR], 2.56 per unit increase; P = .001), whereas immune modulators (including azathioprine, 6-mercaptopurine, and methotrexate) reduced the risk for CRN (OR, 0.35; P < .01). HIA was also associated with CRN in multivariate analysis (OR, 3.68; P = .001). CONCLUSIONS: In a case-control study, we associated increased inflammation with CRN in patients with UC. Use of immune modulators reduced the risk for CRN, indicating that these drugs have chemoprotective effects. On the basis of these data, we propose new stratified surveillance and treatment strategies to prevent and detect CRN in patients with UC.
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Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/patología , Neoplasias del Colon/epidemiología , Adulto , Estudios de Casos y Controles , Femenino , Histocitoquímica , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de TiempoRESUMEN
Aging is the largest risk factor for the development of cancer. A growing body of literature indicates that aging and cancer often play a somewhat reciprocal relationship at various times. On the one hand, aging is a "driver" of cancer, and on the other, cancer is a "disease driver" of aging. Here, we synthesize our reflections on the current literature linking cancer and aging, with an eye on fundamental aging processes, such as cellular senescence. Additionally, we consider how interventions that target fundamental aging processes can potentially transform cancer care, from preventing cancer development and progression to reducing the burden of accelerated aging in cancer survivors. Finally, we conclude with a reflection highlighting our vision for future directions to advance the science of cancer and aging and its applicability to improve the care of older adults with cancer.
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Envejecimiento , Neoplasias , Humanos , Anciano , Senescencia Celular , Factores de Riesgo , Neoplasias/prevención & control , PredicciónRESUMEN
PURPOSE: Older breast cancer survivors are at increased risk of clinical decline after adjuvant chemotherapy. This study aimed to evaluate whether inflammatory markers assessed before adjuvant chemotherapy are associated with chemotherapy-induced clinical decline in a population of fit older adults with breast cancer. METHODS: In a prospective study of women age ≥ 65 years with stage I-III breast cancer treated with chemotherapy, we measured interleukin-6 (IL-6) and C-reactive protein (CRP) prechemotherapy (T1). We assessed frailty status, using a Deficit Accumulation Index (DAI; categorized as robust, prefrail, and frail), at T1 and postchemotherapy (T2). The population of interest was robust women at T1. The primary outcome was chemotherapy-induced decline in frailty status, defined as decline in DAI from robust (T1) to prefrail or frail (T2). Multivariable logistic regression was used to examine the association between inflammatory markers and the primary outcome, adjusted for sociodemographic and clinical characteristics. RESULTS: Of the 295 robust women at T1, 76 (26%) experienced chemotherapy-induced decline in frailty status, among whom 66% had high IL-6, 63% had high CRP, and 46% had high IL-6 and CRP at T1. After adjusting for sociodemographic and clinical characteristics, women with high IL-6 and CRP had a > three-fold (odds ratio, 3.52; 95% CI, 1.55 to 8.01; P = .003) odds of chemotherapy-induced decline in frailty status compared with women with low IL-6 and CRP. CONCLUSION: In this cohort of older women with early breast cancer who were clinically fit before chemotherapy initiation, high IL-6 and CRP prechemotherapy were associated with chemotherapy-induced decline in frailty status independent of sociodemographic and clinical risk factors. Further research is needed to examine whether inflammatory markers can inform more personalized approaches to treating older breast cancer survivors.
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Antineoplásicos , Neoplasias de la Mama , Fragilidad , Humanos , Femenino , Anciano , Estudios Prospectivos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/etiología , Fragilidad/inducido químicamente , Fragilidad/epidemiología , Interleucina-6 , Inflamación , Quimioterapia Adyuvante/efectos adversos , Proteína C-Reactiva , Antineoplásicos/uso terapéutico , Anciano FrágilRESUMEN
BACKGROUND: Chemotoxicity risk scores were developed to predict grade 3-5 chemotherapy toxicity in older women with early breast cancer. However, whether these toxicity risk scores are associated with clinically meaningful decline in patient health remains unknown. METHODS: In a prospective study of women aged 65 years and older with stage I-III breast cancer treated with chemotherapy, we assessed chemotoxicity risk using the Cancer and Aging Research Group-Breast Cancer (CARG-BC) score (categorized as low, intermediate, and high). We measured patient health status before (T1) and after (T2) chemotherapy using a clinical frailty index (Deficit Accumulation Index, categorized as robust, prefrail, and frail). The population of interest was robust women at T1. The primary outcome was decline in health status after chemotherapy, defined as a decline in Deficit Accumulation Index from robust at T1 to prefrail or frail at T2. Multivariable logistic regression was used to examine the association between T1 CARG-BC score and decline in health status, adjusted for sociodemographic and clinical characteristics. RESULTS: Of the 348 robust women at T1, 83 (24%) experienced declining health status after chemotherapy, of whom 63% had intermediate or high CARG-BC scores. After adjusting for sociodemographic and clinical characteristics, women with intermediate (odds ratio = 3.14, 95% confidence interval = 1.60 to 6.14, P < .001) or high (odds ratio = 3.80, 95% confidence interval = 1.35 to 10.67, P = .01) CARG-BC scores had greater odds of decline in health status compared with women with low scores. CONCLUSIONS: In this cohort of older women with early breast cancer, higher CARG-BC scores before chemotherapy were associated with decline in health status after chemotherapy independent of sociodemographic and clinical risk factors.