TY - JOUR
T1 - Joint prognostic effect of obesity and chronic systemic inflammation in patients with metastatic colorectal cancer
AU - Shah, Manasi S.
AU - Fogelman, David R.
AU - Raghav, Kanwal Pratap Singh
AU - Heymach, John V.
AU - Tran, Hai T.
AU - Jiang, Zhi Qin
AU - Kopetz, Scott
AU - Daniel, Carrie R.
N1 - Publisher Copyright:
© 2015 American Cancer Society.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - BACKGROUND: Obesity is strongly linked with chronic systemic inflammation, and each has been linked with disease progression and survival in patients with colorectal cancer (CRC). The authors investigated the joint prognostic effects of obesity and circulating cytokines in patients with metastatic CRC (mCRC), an understudied patient group. METHODS: In 242 chemotherapy-naive patients with mCRC, the authors measured a multiplex cytokine panel and abstracted clinicopathological features, height, and weight from medical records. Overall survival (OS) was calculated from the date of mCRC diagnosis until the date of death from any cause and evaluated by Kaplan-Meier analysis and multivariable Cox proportional hazards regression models. Cut points for cytokines were determined by restricted cubic spline regression. RESULTS In multivariable models, elevated interleukin (IL)-8, IL-2 receptor alpha, and lactate dehydrogenase (LDH) emerged as significant predictors of poor OS (hazard ratio [HR] and 95% confidence interval [95% CI] for above vs below the (referent) knot point: 2.5 [95% CI, 1.7-3.7], 1.9 [95% CI, 1.3-2.7], and 2.2 [95% CI, 1.6-3.1], respectively; all P<.001). Obesity (body mass index ≥30 kg/m2) was not found to be associated with OS, but appeared to modify the relationships observed with IL-8 and LDH, which were associated with a significant 4-fold and 5-fold risk of death, respectively, in obese patients compared with a 2-fold risk of death in nonobese patients (P for interaction of.06 and.04, respectively). Similar results emerged from joint effects analysis, in which obese patients with high IL-8 (or LDH) experienced the highest risk of death. CONCLUSIONS: Although obesity itself was not found to be independently associated with survival in patients with mCRC, the adverse prognostic significance of LDH and IL-8 was found to be enhanced in obese patients. Cancer 2015;121:2968-2975.
AB - BACKGROUND: Obesity is strongly linked with chronic systemic inflammation, and each has been linked with disease progression and survival in patients with colorectal cancer (CRC). The authors investigated the joint prognostic effects of obesity and circulating cytokines in patients with metastatic CRC (mCRC), an understudied patient group. METHODS: In 242 chemotherapy-naive patients with mCRC, the authors measured a multiplex cytokine panel and abstracted clinicopathological features, height, and weight from medical records. Overall survival (OS) was calculated from the date of mCRC diagnosis until the date of death from any cause and evaluated by Kaplan-Meier analysis and multivariable Cox proportional hazards regression models. Cut points for cytokines were determined by restricted cubic spline regression. RESULTS In multivariable models, elevated interleukin (IL)-8, IL-2 receptor alpha, and lactate dehydrogenase (LDH) emerged as significant predictors of poor OS (hazard ratio [HR] and 95% confidence interval [95% CI] for above vs below the (referent) knot point: 2.5 [95% CI, 1.7-3.7], 1.9 [95% CI, 1.3-2.7], and 2.2 [95% CI, 1.6-3.1], respectively; all P<.001). Obesity (body mass index ≥30 kg/m2) was not found to be associated with OS, but appeared to modify the relationships observed with IL-8 and LDH, which were associated with a significant 4-fold and 5-fold risk of death, respectively, in obese patients compared with a 2-fold risk of death in nonobese patients (P for interaction of.06 and.04, respectively). Similar results emerged from joint effects analysis, in which obese patients with high IL-8 (or LDH) experienced the highest risk of death. CONCLUSIONS: Although obesity itself was not found to be independently associated with survival in patients with mCRC, the adverse prognostic significance of LDH and IL-8 was found to be enhanced in obese patients. Cancer 2015;121:2968-2975.
KW - body mass index
KW - inflammation
KW - interleukin-8
KW - lactate dehydrogenase
KW - metastatic colorectal cancer
KW - mortality
KW - obesity
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U2 - 10.1002/cncr.29440
DO - 10.1002/cncr.29440
M3 - Article
C2 - 25975416
AN - SCOPUS:84939565342
SN - 0008-543X
VL - 121
SP - 2968
EP - 2975
JO - Cancer
JF - Cancer
IS - 17
ER -