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J Clin Oncol. 2016 Jan 10;34(2):144-50. doi: 10.1200/JCO.2015.61.6441. Epub 2015 Oct 26.

Body Mass Index Is Prognostic in Metastatic Colorectal Cancer: Pooled Analysis of Patients From First-Line Clinical Trials in the ARCAD Database.

Author information

1
Lindsay A. Renfro and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Fotios Loupakis and Alfredo Falcone, Azienda Ospedaliero-Universitaria Pisana and Università di Pisa, Pisa, Italy; Richard Adams, Cardiff University, Cardiff; Matthew T. Seymour, St James's Hospital and University of Leeds, Leeds, United Kingdom; Volker Heinemann, University of Munich, Munich; Hans-Joachim Schmoll, University Clinic Halle (Saale), Halle; Rainer Porschen, Klinikum Bremen-Ost Klinik für Innere Medizin, Bremen; Carsten Bokemeyer, University Hospital Cancer Center, University Hospital, Hamburg-Eppendorf, Germany; Jean-Yves Douillard, Institut de Cancerologie, Centre René Gauducheau, Nantes; Christophe Tournigand, University of Paris Est Creteil, Henri-Mondor Hospital, Créteil; Benoist Chibaudel and Aimery de Gramont, Franco-British Institute, Levallois-Perret, France; Herbert Hurwitz, Duke University Medical Center, Durham, NC; Charles S. Fuchs, Dana-Farber Cancer Institute Boston, MA; Eduardo Diaz-Rubio, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Madrid, Spain; Niall C. Tebbutt, Austin Health, Heidelberg, Victoria, Australia; Cornelis J.A. Punt, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; J. Randolph Hecht, David Geffen School of Medicine at the University of California at Los Angeles; Heinz-Josef Lenz, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA; Eric Van Cutsem, University Hospital Leuven, Leuven, Belgium; Richard M. Goldberg, Ohio State University, Columbus, OH; and Leonard B. Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY. renfro.lindsay@mayo.edu.
2
Lindsay A. Renfro and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Fotios Loupakis and Alfredo Falcone, Azienda Ospedaliero-Universitaria Pisana and Università di Pisa, Pisa, Italy; Richard Adams, Cardiff University, Cardiff; Matthew T. Seymour, St James's Hospital and University of Leeds, Leeds, United Kingdom; Volker Heinemann, University of Munich, Munich; Hans-Joachim Schmoll, University Clinic Halle (Saale), Halle; Rainer Porschen, Klinikum Bremen-Ost Klinik für Innere Medizin, Bremen; Carsten Bokemeyer, University Hospital Cancer Center, University Hospital, Hamburg-Eppendorf, Germany; Jean-Yves Douillard, Institut de Cancerologie, Centre René Gauducheau, Nantes; Christophe Tournigand, University of Paris Est Creteil, Henri-Mondor Hospital, Créteil; Benoist Chibaudel and Aimery de Gramont, Franco-British Institute, Levallois-Perret, France; Herbert Hurwitz, Duke University Medical Center, Durham, NC; Charles S. Fuchs, Dana-Farber Cancer Institute Boston, MA; Eduardo Diaz-Rubio, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Madrid, Spain; Niall C. Tebbutt, Austin Health, Heidelberg, Victoria, Australia; Cornelis J.A. Punt, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; J. Randolph Hecht, David Geffen School of Medicine at the University of California at Los Angeles; Heinz-Josef Lenz, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA; Eric Van Cutsem, University Hospital Leuven, Leuven, Belgium; Richard M. Goldberg, Ohio State University, Columbus, OH; and Leonard B. Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY.

Abstract

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/m(2), and then it plateaued. Relative to obese patients, patients with a BMI of 18.5 kg/m(2) 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.

PMID:
26503203
PMCID:
PMC5070548
DOI:
10.1200/JCO.2015.61.6441
[Indexed for MEDLINE]
Free PMC Article

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