Adolescents and young adults (AYA; 15-39 years) with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) experience inferior survival when compared with children. Impact of care at ...NCI-designated Comprehensive Cancer Centers (CCC) or Children's Oncology Group sites (COG) on survival disparities remains unstudied.
Using the Los Angeles cancer registry, we identified 1,870 ALL or AML patients between 1 and 39 years at diagnosis. Cox regression analyses assessed risk of mortality; younger age + CCC/COG served as the referent group. Logistic regression was used to determine odds of care at CCC/COG, adjusting for variables above.
ALL outcome: AYAs at non-CCC/COG experienced inferior survival (15-21 years: HR = 1.9,
= 0.005; 22-29 years: HR = 2.6,
< 0.001; 30-39 years: HR = 3.0,
< 0.001). Outcome at CCC/COG was comparable between children and young AYAs (15-21 years: HR = 1.3,
= 0.3; 22-29 years: HR = 1.2,
= 0.2) but was inferior for 30- to 39-year-olds (HR = 3.4,
< 0.001). AML outcome: AYAs at non-CCC/COG experienced inferior outcome (15-21 years: HR = 1.8,
= 0.02; 22-39 years: HR = 1.4,
= 0.06). Outcome at CCC/COG was comparable between children and 15- to 21-year-olds (HR = 1.3,
= 0.4) but was inferior for 22- to 39-year-olds (HR = 1.7,
= 0.05). Access: 15- to 21-year-olds were less likely to use CCC/COG than children (
< 0.001). In 22- to 39-year-olds, public/uninsured (ALL:
= 0.004; AML<0.001), African American/Hispanics (ALL:
= 0.03), and 30- to 39-year-olds (ALL:
= 0.03) were less likely to use CCC/COG.
Poor survival in AYAs with ALL and AML is mitigated by care at CCC/COG. Barriers to CCC/COG care include public/uninsured, and African American/Hispanic race/ethnicity.
Care at CCC/COG explains, in part, inferior outcomes in AYAs with ALL and AML. Key sociodemographic factors serve as barriers to care at specialized centers.
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Background
Nutritional status can directly affect morbidity and mortality in older adults with cancer. This study evaluated the association between pretreatment body mass index (BMI), albumin level, ...and unintentional weight loss (UWL) in the prior 6 months and chemotherapy toxicity among older adults with solid tumors.
Methods
This was a secondary analysis of a prospective, multicenter study involving chemotherapy‐treated patients 65 years old or older. Geriatric assessment, BMI, albumin level, and UWL data were collected before treatment. Multivariable logistic regression models evaluated the associations between nutritional factors and the risk of grade 3 or higher (grade 3+) chemotherapy toxicity.
Results
Seven hundred fifty patients with a median age of 72 years (range, 65‐94 years) and mostly stage IV disease were enrolled. The median pretreatment BMI and albumin values were 26 kg/m2 (range, 15.1‐52.1 kg/m2) and 3.9 mg/dL (range, 1.0‐5.0 mg/dL), respectively. Nearly 50% of the patients reported UWL, with 17.6% reporting >10% UWL. Multivariable analysis revealed no association between >10% UWL and a risk for grade 3+ chemotherapy toxicity (adjusted odds ratio AOR, 0.87; P = .58). Multivariable analysis showed a trend toward an association between a BMI ≥ 30 kg/m2 and a decreased risk of grade 3+ chemotherapy toxicity (AOR, 0.65; P = .06), whereas a low albumin level (≤3.6 mg/dL) was associated with a higher risk of grade 3+ chemotherapy toxicity (AOR, 1.50; P = .03). An analysis of the joint effect of BMI and albumin demonstrated the lowest risk of grade 3+ chemotherapy toxicity among patients with high BMIs (≥30 kg/m2) and normal albumin levels (AOR, 0.41; P = .008).
Conclusions
Among older adults with solid tumors, higher BMIs and normal albumin levels are associated with a lower risk of grade 3+ chemotherapy toxicity. Additional research is warranted to define the clinical significance of nutritional markers and to inform future interventions.
This study evaluates the association between nutritional factors and the risk of chemotherapy toxicity among older adults with solid tumors. Body mass index and albumin are identified as the strongest predictors for chemotherapy tolerance in this patient population.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Older adults are at increased risk for chemotherapy toxicity, and standard oncology assessment measures cannot identify those at risk. A predictive model for chemotherapy toxicity was developed (N = ...500) that consisted of geriatric assessment questions and other clinical variables. This study aims to externally validate this model in an independent cohort (N = 250).
Patients age ≥ 65 years with a solid tumor, fluent in English, and who were scheduled to receive a new chemotherapy regimen were recruited from eight institutions. Risk of chemotherapy toxicity was calculated (low, medium, or high risk) on the basis of the prediction model before the start of chemotherapy. Chemotherapy-related toxicity was captured (grade 3 hospitalization indicated, grade 4 life threatening, and grade 5 treatment-related death). Validation of the prediction model was performed by calculating the area under the receiver-operating characteristic curve.
The study sample (N = 250) had a mean age of 73 years (range, 65 to 94 standard deviation, 5.8). More than one half of patients (58%) experienced grade ≥ 3 toxicity. Risk of toxicity increased with increasing risk score (36.7% low, 62.4% medium, 70.2% high risk; P < .001). The area under the curve of the receiver-operating characteristic curve was 0.65 (95% CI, 0.58 to 0.71), which was not statistically different from the development cohort (0.72; 95% CI, 0.68 to 0.77; P = .09). There was no association between Karnofsky Performance Status and chemotherapy toxicity (P = .25).
This study externally validated a chemotherapy toxicity predictive model for older adults with cancer. This predictive model should be considered when discussing the risks and benefits of chemotherapy with older adults.
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.
In this study, nearly one in four older women with early breast cancer experienced toxicity‐related hospitalization during chemotherapy. Women who reported more than one fall in the 6 months leading up to chemotherapy had a greater than four times higher odds of experiencing toxicity‐related hospitalization during treatment than women who reported no falls.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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.
Abstract
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.
Carbonyl reductases (CBRs) catalyze reduction of anthracyclines to cardiotoxic alcohol metabolites. Polymorphisms in CBR1 and CBR3 influence synthesis of these metabolites. We examined whether single ...nucleotide polymorphisms in CBR1 (CBR1 1096G>A) and/or CBR3 (CBR3 V244M) modified the dose-dependent risk of anthracycline-related cardiomyopathy in childhood cancer survivors.
One hundred seventy survivors with cardiomyopathy (patient cases) were compared with 317 survivors with no cardiomyopathy (controls; matched on cancer diagnosis, year of diagnosis, length of follow-up, and race/ethnicity) using conditional logistic regression techniques.
A dose-dependent association was observed between cumulative anthracycline exposure and cardiomyopathy risk (0 mg/m(2): reference; 1 to 100 mg/m(2): odds ratio OR, 1.65; 101 to 150 mg/m(2): OR, 3.85; 151 to 200 mg/m(2): OR, 3.69; 201 to 250 mg/m(2): OR, 7.23; 251 to 300 mg/m(2): OR, 23.47; > 300 mg/m(2): OR, 27.59; P(trend) < .001). Among individuals carrying the variant A allele (CBR1:GA/AA and/or CBR3:GA/AA), exposure to low- to moderate-dose anthracyclines (1 to 250 mg/m(2)) did not increase the risk of cardiomyopathy. Among individuals with CBR3 V244M homozygous G genotypes (CBR3:GG), exposure to low- to moderate-dose anthracyclines increased cardiomyopathy risk when compared with individuals with CBR3:GA/AA genotypes unexposed to anthracyclines (OR, 5.48; P = .003), as well as exposed to low- to moderate-dose anthracyclines (OR, 3.30; P = .006). High-dose anthracyclines (> 250 mg/m(2)) were associated with increased cardiomyopathy risk, irrespective of CBR genotype status.
This study demonstrates increased anthracycline-related cardiomyopathy risk at doses as low as 101 to 150 mg/m(2). Homozygosis for G allele in CBR3 contributes to increased cardiomyopathy risk associated with low- to moderate-dose anthracyclines, such that there seems to be no safe dose for patients homozygous for the CBR3 V244M G allele. These results suggest a need for targeted intervention for those at increased risk of cardiomyopathy.
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