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.
Frailty is associated with an increased risk of chemotherapy toxicity. Cellular markers of inflammation can help identify patients with frailty characteristics. However, the role of cellular markers ...of inflammation in identifying patients at risk of developing chemotherapy-induced frailty and their clinical utility are not fully understood.
This study was a secondary analysis of a large nationwide cohort study of women with stage I-IIIC breast cancer (n = 581, mean age 53.4; range 22-81). Measures were completed pre-chemotherapy (T1), post-chemotherapy (T2), and 6 months post-chemotherapy (T3). Frailty was assessed at all three time points using a modified Fried score consisting of four self-reported measures (weakness, exhaustion, physical activity, and walking speed; 0-4, 1 point for each). Immune cell counts as well as neutrophil to lymphocyte ratio (NLR) and lymphocyte to monocyte ratio (LMR) were obtained at T1 and T2 time points. Separate linear regressions were used to evaluate the associations of (1) cell counts at T1 with frailty at T1, T2, and T3 and (2) change in cell counts (T2-T1) with frailty at T2 and T3. We controlled for relevant covariates and frailty at the T1 time point.
From T1 to T2, the mean frailty score increased (1.3 vs 2.0; p < 0.01) and returned to T1 levels by the T3 time point (1.3 vs 1.3; p = 0.85). At the T1 time point, there was a positive association between cellular markers of inflammation and frailty: WBC (β = 0.04; p < 0.05), neutrophils (β = 0.04; p < 0.05), and NLR (β = 0.04; p < 0.01). From T1 to T2, a greater increase in cellular markers of inflammation was associated with frailty at T2 (WBC: β = 0.02, p < 0.05; neutrophils: β = 0.03, p < 0.05; NLR: β = 0.03; p < 0.01). These associations remained significant after controlling for the receipt of growth factors with chemotherapy and the time between when laboratory data was provided and the start or end of chemotherapy.
In patients with breast cancer undergoing chemotherapy, cellular markers of inflammation are associated with frailty. Immune cell counts may help clinicians identify patients at risk of frailty during chemotherapy.
ClinicalTrials.gov , NCT01382082.
Elevated markers of inflammation, such as interleukin-6 (IL-6), are associated with aging, cancer, and functional decline. We assessed the association of pre-diagnosis IL-6 levels with post-diagnosis ...functional trajectories among older adults with cancer. Black and White participants experience different social structures, therefore we sought to understand whether these associations differ between Black and White participants.
We conducted secondary analysis of the Health Aging, Body, and Composition (ABC) prospective longitudinal cohort study. Participants were recruited from 4/1997 to 6/1998. We included 179 participants with a new cancer diagnosis and IL-6 level measured within 2 years before diagnosis. Primary endpoint was functional measures (self-reported ability to walk 1/4, 20-meter gait speed). Nonparametric longitudinal models were used to cluster the trajectories; multinomial and logistic regressions to model associations.
Mean age was 74 (SD 2.9); 36 % identified as Black. For self-reported functional status, we identified 3 clusters: high stable, decline, low stable. For gait speed, we identified 2 clusters: resilient, decline. The relationship between cluster trajectory and IL-6 was different between Black and White participants (p for interaction<0.05). For gait speed, among White participants, a greater log IL-6 level was associated with greater odds of being in the decline vs. resilient cluster Adjusted Odds Ratio (AOR): 4.31, 95 % CI: 1.43, 17.46. Among Black participants, a greater log IL-6 levels were associated with lower odds of being in the decline vs. resilient cluster (AOR: 0.49, 95 % CI: 0.10, 2.08). Directionality was similar for self-reported ability to walk ¼ mile (high stable vs. low stable). Among White participants, a higher log IL-6 level was associated numerically with greater odds of being in the low stable vs. high stable cluster (AOR: 1.99, 95 % CI: 0.82, 4.85). Among Black participants, a higher log IL-6 level was associated numerically with lower odds of being in the low stable cluster vs. high stable cluster (AOR: 0.78, 95 % CI: 0.30, 2.00).
The association between IL-6 levels and functional trajectories of older adults differed by race. Future analyses exploring stressors faces by other minoritized racial backgrounds are needed to determine the association between IL-6 and functional trajectories.
Evidence before this study: Previous research has shown that aging is the greatest risk factor for cancer and older adults with cancer experience a higher burden of comorbidities, increasing their risk of functional decline. Race has also been shown to be associated with increased risk for functional decline. Black individuals are exposed to more chronic negative social determinants, compared to White individuals. Previous work has shown that chronic exposure to negative social determinants leads to elevated levels of inflammatory markers, such as IL-6, but studies investigating the relationship between inflammatory markers and functional decline are limited.
Added value of this study: Authors of this study sought to understand the association between pre-diagnosis IL-6 levels and functional trajectories post-diagnosis in older adults with cancer, and whether these associations differed between Black and White participants with cancer. Authors decided to utilize the data from the Health, Aging and Body Composition (Health ABC) Study. The Health ACB study was a prospective longitudinal cohort study that has a high representation of Black older adults and collected inflammatory cytokines and physical function data over time.
Implications of all available evidence: This work adds to the literature by providing an opportunity to study the difference in the relationships between IL-6 levels and functional trajectories between older Black and White participants with cancer. Identifying factors associated with functional decline and its trajectories may inform treatment decision making and guide development of supportive care interventions to prevent functional decline. Additionally, given the disparities in clinical outcomes for Black individuals, a better understanding of the difference in functional decline based on race will allow more equitable care to be distributed.
•Identifying factors associated with functional trajectories may inform treatment decision making and guide interventions.•The association between IL-6 levels and functional trajectories of older adults differed by race.•Further studies are needed to examine reasons for these racial differences.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background Although research has advanced the field of oncologic geriatrics with survivors to assess their cancer-related needs and devise patient-centered interventions, most of that research has ...excluded rural populations. This study aimed to understand the survivorship challenges and recommendations in the perspective of rural older adults. Methods This was a qualitative study that explored the survivorship challenges and recommendations of rural older adults who have completed curative intent chemotherapy for a solid tumor malignancy in the 12 months prior to enrollment in the present study. Results Twenty-seven older adult survivors from rural areas completed open-ended semi-structured interviews. The mean age was 73.4 (SD = 5.0). Most participants were non-Hispanic White (96.3%), female (59.3%), married (63.0%), and had up to a high school education (51.9%). Rural older survivors reported a general lack of awareness of survivorship care plans, communication challenges with healthcare team, transportation challenges, financial toxicity, psychological challenges, and diet and physical challenges. Rural older survivors recommend the provision of nutritional advice referral to exercise programs, and social support groups and for their healthcare providers to discuss their survivorship plan with them. Conclusions Although study participants reported similar survivorship challenges as urban older adult survivors, additional challenges reported regarding transportation and consideration of farm animals have not been previously reported. Heightened awareness of the survivorship needs of rural older adults may result in better survivorship care for this population. Keywords: Older adults, Rural populations, Cancer survivorship, Geriatric oncology
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cancer cachexia, characterized by weight loss and sarcopenia, leads to a decline in physical function and is associated with poorer survival. Cancer cachexia remains poorly described in older adults ...with cancer. This study aims to characterize cancer cachexia in older adults by assessing its prevalence utilizing standard definitions and evaluating associations with components of the geriatric assessment (GA) and survival.
Patients with cancer older than 65 years of age who underwent a GA and had baseline CT imaging were eligible in this cross-sectional study. Cancer cachexia was defined by the international consensus definition reported in 2011. Sarcopenia was measured using cross-sectional imaging and utilizing sex-specific cut-offs. Associations between cachexia, sarcopenia, and weight loss with survival and GA domains were explored.
Mean age of 100 subjects was 79.9 years (66–95) and 65% met criteria for cancer cachexia. Cachexia was associated with impairment in instrumental activities of daily living (IADL) (p = .017); no significant association was found between sarcopenia or weight loss and IADL impairment. Cachexia was significantly associated with poorer survival (median 1.0 vs 2.1 years, p = .011).
Cancer cachexia as defined by the international consensus definition is prevalent in older adults with cancer and is associated with functional impairment and decreased survival. Larger prospective studies are needed to further describe cancer cachexia in this population.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cancer-related fatigue is a common, burdensome symptom of cancer and a side-effect of chemotherapy. While a Mediterranean Diet (MedDiet) promotes energy metabolism and overall health, its effects on ...cancer-related fatigue remain unknown. In a randomized controlled trial, we evaluated a rigorous MedDiet intervention for feasibility and safety as well as preliminary effects on cancer-related fatigue and metabolism compared to usual care. Participants had stage I−III cancer and at least six weeks of chemotherapy scheduled. After baseline assessments, randomization occurred 2:1, MedDiet:usual care. Measures were collected at baseline, week 4, and week 8 including MedDiet adherence (score 0−14), dietary intake, and blood-based metabolic measures. Mitochondrial respiration from freshly isolated T cells was measured at baseline and four weeks. Participants (n = 33) were 51.0 ± 14.6 years old, 94% were female, and 91% were being treated for breast cancer. The study was feasible, with 100% completing the study and >70% increasing their MedDiet adherence at four and eight weeks compared to baseline. Overall, the MedDiet intervention vs. usual care had a small-moderate effect on change in fatigue at weeks 4 and 8 (ES = 0.31, 0.25, respectively). For those with a baseline MedDiet score <5 (n = 21), the MedDiet intervention had a moderate-large effect of 0.67 and 0.48 at weeks 4 and 8, respectively. The MedDiet did not affect blood-based lipids, though it had a beneficial effect on fructosamine (ES = −0.55). Fatigue was associated with mitochondrial dysfunction including lower basal respiration, maximal respiration, and spare capacity (p < 0.05 for FACIT-F fatigue subscale and BFI, usual fatigue). In conclusion, the MedDiet was feasible and attenuated cancer-related fatigue among patients undergoing chemotherapy, especially those with lower MedDiet scores at baseline.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Cognitive impairment (CI) increases chemotherapy toxicity risk with need to understand this association utilizing publicly available short screening tools. We evaluated this utilizing a lower ...threshold on a short screening tool in older adults with cancer.
We analyzed data from the Cancer and Aging Research Group (CARG) Chemotherapy Toxicity Risk tool (CARG score) development and validation cohorts (n = 703), which recruited adults age ≥ 65 with cancer from academic centers. Cognition was evaluated with the Blessed Orientation-Memory-Concentration test (BOMC). Patients with BOMC score ≥ 11 were excluded. Utilizing cut-points for older adults, we considered moderate BOMC scores (5-10) as potential CI. Logistic regression was used for analysis.
Patient baseline characteristics included: mean age 73; 85% white; 63% college or higher education; 250 (36%) potential CI; 385 (55%) severe toxicity. Patients with potential CI were more likely non-white (p ≤ 0.01) and to have high school or lower education (p ≤ 0.01) and high CARG score (p = 0.04). Potential CI was associated with increased severe toxicity risk (OR = 1.54, p ≤ 0.01). After adjusting for CARG score, this association became nonsignificant (OR = 1.35; p = 0.08). Among patients with lower education (n = 258; 36.7%), potential CI remained associated with severe toxicity, even after adjusting for CARG score (OR = 1.87, p = 0.03).
Our findings suggest potential cognitive impairment, defined by BOMC score 5–10, in older adults with cancer and lower education is associated with increased severe toxicity risk. Future studies are needed to validate these findings. Healthcare providers should consider cognitive testing before treatment for these vulnerable patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract The objective of the study is to assess impact of systemic disease (SD) status on overall survival and brain metastasis (BM) control, adopting a novel landmark approach to categorize SD ...among breast cancer (BC) patients. This single institution retrospective study included BCBM patients who have received stereotactic radiosurgery (SRS) to brain. Separate endpoints CNS failure-free survival (cFFS), overall survival (OS) were analyzed from each Landmark (LM): LM1 (3-months), LM2 (6-months). Patients were categorized into early and non-early progression (EP, NEP) groups depending on SD status before LMs. Median survivals from LM were assessed with Kaplan Meier plots, compared with Log-Rank test. EP was associated with worse median cFFS and OS vs NEP in both LM analyses (cFFS- LM1: 3.6 vs. 9.7 months, p = 0.0016; LM2: 2.3 vs. 12.5 months, p < 0.0001; OS- LM1: 3.6 vs. 24.3 months, p < 0.0001; LM2: 5.3 vs. 30.2 months, p < 0.0001). In multivariate analyses, EP was associated with shorter cFFS LM1: Hazard Ratio (HR) with 95% confidence interval (CI) 3.16, 1.46–6.83, p = 0.0034; LM2: 5.32, 2.33–12.15, p = <0.0001 and shorter OS (LM1: HR with 95% CI 4.28, 1.98–9.12, p = 0.0002; LM2: 7.40, 3.10–17.63, p = <0.0001) vs NEP. Early systemic disease progressions after 1st SRS to brain is associated with worse cFFS and OS in patients with BCBM.
To review existing exercise guidelines for cancer patients and survivors for the management of symptom clusters.
Review of PubMed literature and published exercise guidelines.
Cancer and its ...treatments are responsible for a copious number of incapacitating symptoms that markedly impair quality of life. The exercise oncology literature provides consistent support for the safety and efficacy of exercise interventions in managing cancer- and treatment-related symptoms, as well as improving quality of life in cancer patients and survivors.
Effective management of symptoms enhances recovery, resumption of normal life activities and quality of life for patients and survivors. Exercise is a safe, appropriate, and effective therapeutic option before, during, and after the completion of treatment for alleviating symptoms and symptom clusters.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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