Association of pre-chemotherapy peripheral blood pro-inflammatory and coagulation factors with reduced relative dose intensity in women with breast cancer.
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ABSTRACT:
SUBMITTER: Yuan Y
PROVIDER: S-EPMC5576099 | biostudies-literature | 2017 Aug
REPOSITORIES: biostudies-literature
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Association of pre-chemotherapy peripheral blood pro-inflammatory and coagulation factors with reduced relative dose intensity in women with breast cancer.
Yuan Yuan Y Vora Nilesh N Sun Can-Lan CL Li Daneng D Soto-Perez-de-Celis Enrique E Mortimer Joanne J Luu The-Hang TH Somlo George G Waisman James J Smith David D Chao Joseph J Katheria Vani V Synold Timothy T Tran Vivi V Mi Shu S Levi Abrahm A Arsenyan Anait A Choi Jennifer J Zavala Laura L Yost Susan S Hurria Arti A
Breast cancer research : BCR 20170829 1
<h4>Background</h4>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 ...[more]
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Project description:Pro-inflammatory and coagulation factors serve as biomarkers of aging and functional reserve. The purpose of this study was to determine if pro-inflammatory (interleukin-6 [IL-6], C-reactive protein [CRP]), and coagulation (D-dimer) factors were associated with pre-chemotherapy functional status in women with stage I-III breast cancer.Prior to chemotherapy initiation in patients with stage I-III breast cancer, the following was captured: IL-6, CRP, D-dimer blood levels, and physical function measures including activities of daily living (ADL, subscale of Medical Outcomes Study Physical Health); instrumental activities of daily living (IADL, subscale of the Older Americans Resources and Services Program); Timed Up and Go (TUG); physician-rated Karnofsky Performance Status (KPS); and self-rated KPS. The association of these biomarkers with physical function measures was evaluated.One hundred sixty patients (mean age 58.3 years, range 30-81 years) with stage I-III breast cancer (stages I [n?=?34; 21.5%], II [n?=?88; 55.7%], III [n?=?36; 22.8%]) were enrolled. The group with poorest physical function (defined by ADL <70, IADL <14, and TUG ?10 seconds) had higher levels of IL-6 (p?=?.05), D-dimer (p?=?.0004), and CRP (p?=?.05). There was no significant association between these biomarkers and KPS. Patients with at least two biomarkers in the highest quartile were more likely to have poorer physical function (odds ration [OR] 18.75, p?<?.001). In multivariate analysis adjusting for age, stage, number of comorbidities, and body mass index, the association remained (OR 14.6, p?=?.002).Pre-chemotherapy biomarkers of aging are associated with poorer physical function among patients with breast cancer across the aging spectrum. The Oncologist 2017;22:1189-1196 IMPLICATIONS FOR PRACTICE: Commonly used physical function assessment tools may not reflect the diverse nature of physical function and risk for chemotherapy toxicity, particularly in older adults. No laboratory test reflects functional reserve. Pro-inflammatory and coagulation factors, such as IL-6, CRP, and D-dimer, can serve as biomarkers of aging and physical function; however, few studies have evaluated their utility in patients with cancer. This study was designed to understand the association between pre-chemotherapy biomarkers and physical function in women with early stage breast cancer undergoing adjuvant chemotherapy. Results indicate that elevated pre-chemotherapy levels in two of the three peripheral biomarkers are associated with the poorest physical function among patients with breast cancer across the aging spectrum.
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Project description:BackgroundMost patients with advanced pancreatic adenocarcinoma (PA) treated with FOLFIRINOX experience adverse events requiring dose reduction. We aimed to assess the association between relative dose intensity (RDI) and disease control in a European setting.MethodsWe retrospectively included patients with advanced PA treated with three or more cycles of FOLFIRINOX between 2011 and 2018 in six French centers. We computed the cumulative single-agent RDI (csRDI) before the first reassessment for each FOLFIRINOX agent (oxaliplatin, irinotecan, 5FU bolus, and 5FU intravenous infusion) and the cumulative multi-drug RDI (cmRDI) of their combination. The association between RDI and disease control or objective response at first reassessment was evaluated using multivariable logistic regression models controlling for performance status, liver metastases, and center.ResultsWe included 243 patients. Median csRDIs were 81%, 79%, 75%, and 85% for oxaliplatin, irinotecan, 5FU bolus, and 5FU intravenous infusion, respectively. Median cmRDI was 80%. None of the RDIs was significantly associated with disease control or objective response. Including RDI in a clinical model did not improve its ability to predict disease control; the area under the curve was 0.79 (95% CI: 0.73-0.85) with RDI versus 0.78 (95% CI: 0.72-0.85) without. Similar results were observed for the objective response.ConclusionPragmatic dose adjustments of FOLFIRINOX should be made by oncologists without considering a loss of effect.
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