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.
Objectives
To analyze self‐reported changes in physical function in older women with breast cancer receiving adjuvant chemotherapy.
Design
Secondary analysis of the Cancer and Leukemia Group B ...(CALGB) 49907 prospective randomized clinical trial.
Setting
CALGB institutions in the United States.
Participants
Women aged 65 and older with Stage I to III breast cancer enrolled in CALGB 49907 who had physical function data from before and after receipt of adjuvant chemotherapy (N=256; mean age 71.5, range 65–85).
Measurements
Participants were administered the physical function subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire before chemotherapy, at the end of chemotherapy, and 12 months after chemotherapy initiation. Functional decline was defined as a more than 10‐point decrease from baseline at each time point. Resilience was defined as return to within 10 points of baseline. Multivariable regression was used to examine pretreatment characteristics associated with physical function changes.
Results
Of 42% of participants who had physical function decline from before to the end of chemotherapy, 47% recovered by 12 months (were resilient). Almost one‐third experienced functional decline from before chemotherapy to 12 months later. Pretreatment fatigue was a risk factor for functional decline from before to the end of chemotherapy (P=.02). Risk factors for functional decline at 12 months included pretreatment dyspnea (P=.007) and being unmarried (P=.01).
Conclusion
Functional decline was common in older women receiving adjuvant chemotherapy for breast cancer in a clinical trial. Although half recovered their physical function, one‐third had a clinically meaningful decline at 12 months. Strategies are needed to prevent functional decline in older adults receiving chemotherapy. J Am Geriatr Soc 67:920–927, 2019.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Chemotherapy decreases the risk of relapse and mortality in early-stage breast cancer (BC), but it comes with the risk of toxicity. Chemotherapy efficacy depends on relative dose intensity (RDI), and ...an RDI < 85% is associated with worse overall survival. The pro-inflammatory (interleukin (IL)-6, C-reactive protein (CRP)) and coagulation factors (D-dimer) serve as biomarkers of aging. The purpose of this study is to determine if these biomarkers are associated with reduced RDI in women with stage I-III BC.
This study enrolled women with stage I-III BC. Prior to adjuvant or neoadjuvant chemotherapy, peripheral blood was collected for biomarker measurement. Dose reductions and delays were captured and utilized to calculate the RDI delivered. Univariate and multivariate analyses were performed to describe the association between pre-chemotherapy IL-6, CRP, and D-dimer levels and an RDI < 85%, controlling for relevant tumor and patient factors (age, stage, receptor status, chemotherapy regimen, and pre-chemotherapy physical function and comorbidity).
A total of 159 patients (mean age 58 years, range 30-81, SD 11.3) with stage I-III BC were enrolled. An RDI < 85% occurred in 22.6% (N = 36) of patients and was associated with higher pre-chemotherapy IL-6 (OR 1.14, 95% CI 1.04-1.25; p = 0.006) and D-dimer (OR 2.32, 95% CI 1.27-4.24; p = 0.006) levels, increased age (p = 0.001), increased number of comorbidities (p = 0.01), and decreased physical function by the Medical Outcomes Survey Activities of Daily Living (ADL) Scale (p = 0.009) in univariate analysis. A multivariate model, including two biomarkers (IL-6 and D-dimer), age, ADL, BC stage, and chemotherapy regimen, demonstrated a significant association between the increased biomarkers and reduced RDI < 85% (OR 2.54; p = 0.04).
Increased pre-chemotherapy biomarkers of aging (IL-6 and D-dimer) are associated with reduced RDI (<85%). Future studies are underway to validate these findings.
ClinicalTrials.gov, NCT01030250 . Registered on 3 November 2016.
Abstract
Background: Older adults with breast cancer receiving neo/adjuvant chemotherapy are at increased risk for toxicity and dose reductions, often leading to decreased relative dose intensity ...(dRDI < 85%) and potentially compromised chemotherapy benefits. Identifying which older patients are projected to have dRDI with standard regimens could help to optimize systemic treatment delivery and completion.
Methods: We prospectively enrolled patients aged ≥ 65 who were starting neo/adjuvant chemotherapy for HER2-negative, stage I-III breast cancer. Geriatric assessment and clinical variables were captured at baseline. Chemotherapy regimen, dosing, and treatment-related modifications (reductions, delays, discontinuation) were also captured. RDI was calculated as the ratio of actual dose delivered to intended dose. Our primary outcome was dRDI, which we defined as RDI < 85% (associated with poorer survival, Bonadonna et al. NEJM 1995). Bivariate logistic regression for dRDI was performed to elucidate the relationship with baseline factors. Stepwise regression was used to identify the significant factors that are independently associated with dRDI.
Results: Of 323 patients (median age 69, range 65-86), 216 had HR+/HER2- breast cancer and 107 had triple negative breast cancer (TNBC). Patients were treated with taxotere and cyclophosphamide TC (47%), anthracycline-based regimens (46%), and cyclophosphamide, methotrexate, and 5-fluorouracil CMF (7%). Overall, the mean RDI was 90.1% (median 100%, range 16.7%-100%), and 69 patients (21%) had dRDI (i.e. RDI <85%). HR+/HER2- and TNBC had similar RDI (p = 0.74). In bivariate analysis, older age > 70, higher stage (II/III), use of non-TC regimens (anthracycline-based or CMF), abnormal liver function, KPS < 90, poor physical function, lack of social support, and cardiac conditions were associated with reduced RDI. Multivariate stepwise regression identified that anthracycline-based or CMF regimens (28% dRDI, OR=3.34, 95% CI 1.77-6.29), age >70 (27% dRDI, OR = 2.01, 95% CI 1.11-3.63), abnormal liver function (41% dRDI, OR = 2.50, 95% CI 1.10-5.66), and KPS < 90 (48% dRDI, OR = 4.31, 95% CI 2.06-9.03) were significantly associated with dRDI. dRDI was significantly associated with grade 3 or higher toxicities, hospitalization, dose reduction, dose delay, and early discontinuation of chemotherapy (all p < 0.001).
Conclusion: Among older patients receiving neo/adjuvant chemotherapy for HER2-negative early-stage breast cancer, those aged > 70, treated with anthracycline or CMF regimens, with abnormal liver functions, and KPS < 90 were at substantially higher risk for reduced RDI (actual/planned dose) likely due to increased rates of toxicities, hospitalizations, dose modifications, and/or early treatment discontinuation. Future targeted supportive care interventions and/or alternative treatment regimens are needed to improve the delivery of chemotherapy in older patients who are predicted to have dRDI and better understand whether dRDI impacts outcomes in this population.
Citation Format: Mina S Sedrak, Can-Lan Sun, Allison Magnuson, Hyman Muss, Rachel Freedman, Cary P Gross, William P Tew, Heidi Klepin, Tanya M Wildes, Efrat Dotan, Tracey O'Connor, Harvey J Cohen, Heeyoung Kim, Vani Katheria, Reena Jayani, Anait Arsenyan, Abrahm Levi, Kemeberly Charles, Arti Hurria, William Dale. Factors associated with decreased relative dose intensity in older adults with early-stage breast cancer receiving chemotherapy abstract. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD10-10.
Purpose
Older cancer survivors required medical care during the COVID-19 pandemic, but there are limited data on medical care in this age group.
Methods
We evaluated care disruptions in a ...longitudinal cohort of non-metastatic breast cancer survivors aged 60–98 from five US regions (
n
= 321). Survivors completed a web-based or telephone survey from May 27, 2020 to September 11, 2020. Care disruptions included interruptions in seeing or speaking to doctors, receiving medical treatment or supportive therapies, or filling prescriptions since the pandemic began. Logistic regression models evaluated associations between care disruptions and education, medical, psychosocial, and COVID-19-related factors. Multivariate models included age, county COVID-19 death rates, comorbidity, and post-diagnosis time.
Results
There was a high response rate (
n
= 262, 81.6%). Survivors were 32.2 months post-diagnosis (SD 17.5, range 4–73). Nearly half (48%) reported a medical disruption. The unadjusted odds of care disruptions were higher with each year of education (OR 1.22, 95% CI 1.08–1.37,
p
= < 0.001) and increased depression by CES-D score (OR 1.04, CI 1.003–1.08,
p
= 0.033) while increased tangible support decreased the odds of disruptions (OR 0.99, 95% CI 0.97–0.99,
p
= 0.012). There was a trend between disruptions and comorbidities (unadjusted OR 1.13 per comorbidity, 95% CI 0.99–1.29,
p
= 0.07). Adjusting for covariates, higher education years (OR1.23, 95% CI 1.09–1.39, p = 0.001) and tangible social support (OR 0.98 95% CI 0.97–1.00,
p
= 0.006) remained significantly associated with having care disruptions.
Conclusion
Older breast cancer survivors reported high rates of medical care disruptions during the COVID-19 pandemic and psychosocial factors were associated with care disruptions.
Clinicaltrials.gov Identifier
NCT03451383
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Older adults with cancer are at higher risk for costly and potentially dangerous hospital readmissions. Identifying risk factors for readmission in this population is important for future prevention ...of readmission.
Hospital discharges among patients ≥ 65 years with solid tumors on non-surgical services from 2006-2011 were reviewed in this matched case-control study. We abstracted patient/cancer characteristics; functional status; fall risk; chemotherapy line; comorbidities; laboratory values; discharge parameters; and miscellaneous information (Do Not Resuscitate Order, pain scores) from medical records. Conditional logistic regression was used for univariate and multivariable analysis.
This analysis included 184 case-patients readmitted within 30 days after discharge from the index admission and 184 sex- and age-matched control-patients discharged from index admission within three months of the cases with no readmission. Cases and controls had no differences in terms of primary cancer type, treatment, and index admission reason. Cases were more likely to have abnormal hemoglobin, albumin, sodium, and SGOT on discharge. Compared to those with ≤1 abnormal laboratory test, patients with 2 or more abnormal test results were 3 times more likely to be readmitted within 30 days.
This study demonstrated that older adults with cancer who had at least 2 abnormal laboratory results (hemoglobin, albumin, sodium, and SGOT) at discharge were 3 times more likely to be readmitted within 30 days compared to those with ≤1 abnormal results. These laboratory values may be predictive of the risk of readmission, and should be monitored before discharge to potentially prevent readmission.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Oncology nurses are key in caring for older adults with cancer, but few have received specialized training in gerontology. To address this, a geriatric oncology curriculum was developed for oncology ...nurses.
The Geriatric Oncology Workshop (GrOW) was developed and delivered to oncology nurses (n = 387) from 2016 to 2019. Workshops were evaluated using: 1) Assessment of preparedness, comfort, and skills; 2) Knowledge gained; 3) Participant evaluations of workshop (4-point Likert-type scale); 4) Faculty evaluations (10-point Likert-type scale); and 5) Follow-up assessment of goals. Descriptive statistics (frequencies, proportions, medians, means) were used to describe participants and results. Paired t-test was used to evaluate participants' knowledge gain, and linear mixed modeling was used to evaluate longitudinal changes in preparedness, comfort, and skill levels.
Overall, 387 oncology nurses participated in GrOW. Participant-rated workshop evaluation means were 3.7 to 3.9. Overall, nurses had statistically significant increases in pre- to post- questionnaire scores of 18.8% (p < 0.001) in workshop 1, 26.8% (p < 0.001) in workshop 2, 24.9% (p < 0.001) in workshop 3, and 18.6% (p < 0.001) in workshop 4, with an overall mean of 22.4% (p < 0.001) knowledge gained for all four workshops. Nurses reported an increase in skill, comfort, and preparedness at 18 months for workshop 1, 2, and 3 and in skill and comfort at 12 months for workshop 4 (p < 0.01). Faculty evaluation scores ranged from 9.3 to 10.0.
A geriatric oncology curriculum designed for oncology nurses can improve levels of evidence-based knowledge and provide more skill, comfort, and preparedness in caring for 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
nab-Paclitaxel may be an attractive therapy for older adults because of its efficacy, the infrequency of allergic reactions, and the lack of need for steroid pre-medications. We evaluated the ...tolerability and efficacy of nab-paclitaxel in older adults with metastatic breast cancer, as well as the relationship between a geriatric assessment-based toxicity risk score and chemotherapy toxicity, dose reductions, dose delays, and hospitalizations. Patients with intermediate/high toxicity risk scores had higher risk of grade ≥ 3 toxicity than those with low risk scores, and a higher mean risk score was associated with higher likelihood of dose reductions and hospitalizations. A geriatric assessment-based risk score can help weigh the risks and benefits of chemotherapy in older adults, and should be incorporated into future trials testing new therapies in this population.
Phase II clinical trials including geriatric assessment (GA) measures are critical for improving the evidence base for older adults with cancer. We assessed the efficacy and tolerability of nab-paclitaxel in older adults with metastatic breast cancer (MBC).
Patients aged ≥ 65 years with MBC and ≤ 1 previous line of chemotherapy received 100 mg of nab-paclitaxel on days 1, 8, and 15 of a 28-day cycle. A GA was completed pre-chemotherapy, and the validated Cancer and Aging Research Group (CARG) chemotherapy toxicity risk score was calculated. Relationships between tolerability (number of courses, hospitalizations, dose reductions, and toxicity) and risk score were assessed using general linear models, Student t tests, and the Fisher test. Response rate and progression-free survival were evaluated using the Kaplan-Meier method.
Forty patients (mean age, 73 years; range, 65-87 years) were included. The median number of cycles was 6, 75% (n = 30) of patients had ≥ 1 dose hold, and 50% (n = 20) had ≥ 1 dose reduction. Fifty-eight percent (n = 23) had treatment-related ≥ grade 3 toxicities, and 30% (n = 12) were hospitalized owing to toxicity. Thirty-five percent (n = 14) responded, and the median progression-free survival was 6.5 months (95% confidence interval, 5.5 months to undefined). Patients with intermediate/high toxicity risk scores had higher risk of grade ≥ 3 toxicity than those with low risk scores (odds ratio, 5.8; 95% confidence interval, 1.3-33.1; P = .01). A higher mean risk score was associated with higher likelihood of dose reductions and hospitalizations.
Among older adults with MBC receiving weekly nab-paclitaxel, more than one-half experienced ≥ grade 3 chemotherapy toxicity. However, a GA-based risk score could predict treatment tolerability.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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