TY - JOUR
T1 - Body mass index is prognostic in metastatic colorectal cancer
T2 - Pooled analysis of patients from first-line clinical trials in the ARCAD database
AU - Renfro, Lindsay A.
AU - Loupakis, Fotios
AU - Adams, Richard A.
AU - Seymour, Matthew T.
AU - Heinemann, Volker
AU - Schmoll, Hans Joachim
AU - Douillard, Jean Yves
AU - Hurwitz, Herbert
AU - Fuchs, Charles S.
AU - Diaz-Rubio, Eduardo
AU - Porschen, Rainer
AU - Tournigand, Christophe
AU - Chibaudel, Benoist
AU - Falcone, Alfredo
AU - Tebbutt, Niall C.
AU - Punt, Cornelis J.A.
AU - Hecht, J. Randolph
AU - Bokemeyer, Carsten
AU - Van Cutsem, Eric
AU - Goldberg, Richard M.
AU - Saltz, Leonard B.
AU - De Gramont, Aimery
AU - Sargent, Daniel J.
AU - Lenz, Heinz Josef
N1 - Publisher Copyright:
Copyright © 2016 American Society of Clinical Oncology. All rights reserved.
PY - 2016/1/10
Y1 - 2016/1/10
N2 - Purpose. In recent retrospective analyses of early-stage colorectal cancer (CRC), low and high body mass index (BMI) scores were associated with worsened outcomes. Whether BMI is a prognostic or predictive factor in metastatic CRC (mCRC) is unclear. Patients and Methods. Individual data from 21,149 patients enrolled onto 25 first-line mCRC trials during 1997 to 2012 were pooled. We assessed both prognostic and predictive effects of BMI on overall survival and progression-free survival, and we accounted for patient and tumor characteristics and therapy type (targeted v nontargeted). Results. BMI was prognostic for overall survival (P < .001) and progression-free survival (P < .001), with an L-shaped pattern. That is, risk of progression and/or death was greatest for low BMI; risk decreased as BMI increased to approximately 28 kg/m2, and then it plateaued. Relative to obese patients, patients with a BMI of 18.5 kg/m2 had a 27% increased risk of having a PFS event (95% CI, 20% to 34%) and a 50% increased risk of death (95% CI, 43%to 56%). Low BMI was associated with poorer survival for men than women (interaction P < .001). BMI was not predictive of treatment effect. Conclusion. Low BMI is associated with an increased risk of progression and death among the patients enrolled on the mCRC trials, with no increased risk for elevated BMI, in contrast to the adjuvant setting. Possible explanations include negative effects related to cancer cachexia in patients with low BMI, increased drug delivery or selection bias in patients with high BMI, and potential for an interaction between BMI and molecular signaling pathways.
AB - Purpose. In recent retrospective analyses of early-stage colorectal cancer (CRC), low and high body mass index (BMI) scores were associated with worsened outcomes. Whether BMI is a prognostic or predictive factor in metastatic CRC (mCRC) is unclear. Patients and Methods. Individual data from 21,149 patients enrolled onto 25 first-line mCRC trials during 1997 to 2012 were pooled. We assessed both prognostic and predictive effects of BMI on overall survival and progression-free survival, and we accounted for patient and tumor characteristics and therapy type (targeted v nontargeted). Results. BMI was prognostic for overall survival (P < .001) and progression-free survival (P < .001), with an L-shaped pattern. That is, risk of progression and/or death was greatest for low BMI; risk decreased as BMI increased to approximately 28 kg/m2, and then it plateaued. Relative to obese patients, patients with a BMI of 18.5 kg/m2 had a 27% increased risk of having a PFS event (95% CI, 20% to 34%) and a 50% increased risk of death (95% CI, 43%to 56%). Low BMI was associated with poorer survival for men than women (interaction P < .001). BMI was not predictive of treatment effect. Conclusion. Low BMI is associated with an increased risk of progression and death among the patients enrolled on the mCRC trials, with no increased risk for elevated BMI, in contrast to the adjuvant setting. Possible explanations include negative effects related to cancer cachexia in patients with low BMI, increased drug delivery or selection bias in patients with high BMI, and potential for an interaction between BMI and molecular signaling pathways.
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U2 - 10.1200/JCO.2015.61.6441
DO - 10.1200/JCO.2015.61.6441
M3 - Article
C2 - 26503203
AN - SCOPUS:84954244943
SN - 0732-183X
VL - 34
SP - 144
EP - 150
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 2
ER -