Abstract
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.
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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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK, VSZLJ
Limited tools exist to predict the risk of chemotherapy toxicity in older adults with early-stage breast cancer.
Patients of age ≥ 65 years with stage I-III breast cancer from 16 institutions treated ...with neoadjuvant or adjuvant chemotherapy were prospectively evaluated for geriatric and clinical features predictive of grade 3-5 chemotherapy toxicity. Logistic regression with best-subsets selection was used to identify and incorporate independent predictors of toxicity into a model with weighted variable scoring. Model performance was evaluated using area under the ROC curve (AUC) and goodness-of-fit statistics. The model was internally and externally validated.
In 473 patients (283 in development and 190 in validation cohort), 46% developed grade 3-5 chemotherapy toxicities. Eight independent predictors were identified (each assigned weighted points): anthracycline use (1 point), stage II or III (3 points), planned treatment duration > 3 months (4 points), abnormal liver function (3 points), low hemoglobin (3 points), falls (4 points), limited walking (3 points), and lack of social support (3 points). We calculated risk scores for each patient and defined three risk groups: low (0-5 points), intermediate (6-11 points), or high (≥ 12 points). In the development cohort, the rates of grade 3-5 chemotherapy toxicity for these three groups were 19%, 54%, and 87%, respectively (
< .01). In the validation cohort, the corresponding toxicity rates were 27%, 45%, and 76%. The AUC was 0.75 (95% CI, 0.70 to 0.81) in the development cohort and 0.69 (95% CI, 0.62 to 0.77) in the validation cohort. Risk groups were also associated with hospitalizations and reduced dose intensity (
< .01).
The Cancer and Aging Research Group-Breast Cancer (CARG-BC) score was developed and validated to predict grade 3-5 chemotherapy toxicity in older adults with early-stage breast cancer.
Accelerated aging in older cancer survivors Sedrak, Mina S.; Kirkland, James L.; Tchkonia, Tamar ...
Journal of the American Geriatrics Society (JAGS),
November 2021, Volume:
69, Issue:
11
Journal Article
Peer reviewed
Open access
This editorial comments on the article by Siddique et al.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Although geriatric assessment-driven intervention improves patient-centered outcomes, its influence on chemotherapy-related toxic effects remains unknown.
To assess whether specific geriatric ...assessment-driven intervention (GAIN) can reduce chemotherapy-related toxic effects in older adults with cancer.
A randomized clinical trial enrolled 613 participants from a National Cancer Institute-designated cancer center between 2015 and 2019. Patients were 65 years and older with a solid malignant neoplasm, were starting a new chemotherapy regimen, and completed a geriatric assessment. Patients were followed up until chemotherapy completion or 6 months after initiation, whichever occurred first. Data analysis was done by intention-to-treat principle.
Patients were randomized (2:1) to either the GAIN (intervention) or standard of care (SOC) arm. In the GAIN arm, a geriatrics-trained multidisciplinary team composed of an oncologist, nurse practitioner, social worker, physical/occupation therapist, nutritionist, and pharmacist reviewed geriatric assessment results and implemented interventions based on prespecified thresholds built into the geriatric assessment's domains. In the SOC arm, geriatric assessment results were sent to treating oncologists for consideration.
The primary outcome was incidence of grade 3 or higher chemotherapy-related toxic effects (graded using National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0). Secondary outcomes included advance directive completion, emergency department visits, unplanned hospitalizations, average length of stay, unplanned hospital readmissions, chemotherapy dose modifications, and early discontinuation. Overall survival analysis was performed up to 12 months after chemotherapy initiation.
Among the 605 eligible participants for analysis, median (range) age was 71 (65-91) years, 357 (59.0%) were women, and 432 (71.4%) had stage IV disease. Cancer types included gastrointestinal (202 33.4%), breast (136 22.5%), lung (97 16.0%), genitourinary (91 15.0%), gynecologic (54 8.9%), and other (25 4.1%). Incidence of grade 3 or higher chemotherapy-related toxic effects was 50.5% (95% CI, 45.6% to 55.4%) in the GAIN arm and 60.6% (95% CI, 53.9% to 67.3%) in the SOC arm, resulting in a significant 10.1% reduction (95% CI, -1.5 to -18.2%; P = .02). A significant absolute increase in advance directive completion of 28.4% with GAIN vs 13.3% with SOC (P < .001) was observed. No significant differences were observed in emergency department visits, unplanned hospitalizations, average length of stay, unplanned readmissions, chemotherapy dose modifications or discontinuations, or overall survival.
In this randomized clinical trial, integration of multidisciplinary GAIN significantly reduced grade 3 or higher chemotherapy-related toxic effects in older adults with cancer. Implementation of GAIN into oncology clinical practice should be considered among older adults receiving chemotherapy.
ClinicalTrials.gov Identifier: NCT02517034.
The combination of immunotherapy and radiotherapy/chemoradiation has demonstrated promising results in some disease sites for cancer patients. However, translation to real-world practice is ...complicated by limited representation in clinical trials of older adults with comorbidities who comprise a significant percentage of patients treated in the clinic. The purpose of this review is to outline the current evidence for multimodality treatment in the older adult population including extrapolation from single modality therapies and the rationale for combinatorial treatment. Although few in number, ongoing trials specifically targeting older cancer patients are highlighted. Looking toward the future, current gaps in the field are identified with recommendations to consider both in the preclinical setting and when designing clinical trials in order to better inform the use of multimodality therapy in the clinic as this data evolves.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Based on aging of the cancer population and growth in the number of cancer survivors, this is an opportune time to invest in and accelerate research of interventions to mitigate the risk of ...accelerated aging. The discoveries emerging from such research will be far reaching, because they ultimately will improve the well‐being and quality of life of the growing population of older cancer survivors.
See also pages 1279‐1287.
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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.
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.
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;
= .003) odds of chemotherapy-induced decline in frailty status compared with women with low IL-6 and CRP.
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.
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.
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.
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.
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.
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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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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