Body mass index is prognostic in metastatic colorectal cancer

Pooled analysis of patients from first-line clinical trials in the ARCAD database

Lindsay A. Renfro, Fotios Loupakis, Richard A. Adams, Matthew T. Seymour, Volker Heinemann, Hans Joachim Schmoll, Jean Yves Douillard, Herbert Hurwitz, Charles S. Fuchs, Eduardo Diaz-Rubio, Rainer Porschen, Christophe Tournigand, Benoist Chibaudel, Alfredo Falcone, Niall C. Tebbutt, Cornelis J A Punt, J. Randolph Hecht, Carsten Bokemeyer, Eric Van Cutsem, Richard M. Goldberg & 4 others Leonard B. Saltz, Aimery De Gramont, Daniel J. Sargent, Heinz Josef Lenz

Research output: Contribution to journalArticle

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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/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.

Original languageEnglish (US)
Pages (from-to)144-150
Number of pages7
JournalJournal of Clinical Oncology
Volume34
Issue number2
DOIs
StatePublished - Jan 10 2016

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Colorectal Neoplasms
Body Mass Index
Clinical Trials
Databases
Disease-Free Survival
Survival
Cachexia
Selection Bias
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Body mass index is prognostic in metastatic colorectal cancer : Pooled analysis of patients from first-line clinical trials in the ARCAD database. / Renfro, Lindsay A.; Loupakis, Fotios; Adams, Richard A.; Seymour, Matthew T.; Heinemann, Volker; Schmoll, Hans Joachim; Douillard, Jean Yves; Hurwitz, Herbert; Fuchs, Charles S.; Diaz-Rubio, Eduardo; Porschen, Rainer; Tournigand, Christophe; Chibaudel, Benoist; Falcone, Alfredo; Tebbutt, Niall C.; Punt, Cornelis J A; Hecht, J. Randolph; Bokemeyer, Carsten; Van Cutsem, Eric; Goldberg, Richard M.; Saltz, Leonard B.; De Gramont, Aimery; Sargent, Daniel J.; Lenz, Heinz Josef.

In: Journal of Clinical Oncology, Vol. 34, No. 2, 10.01.2016, p. 144-150.

Research output: Contribution to journalArticle

Renfro, LA, Loupakis, F, Adams, RA, Seymour, MT, Heinemann, V, Schmoll, HJ, Douillard, JY, Hurwitz, H, Fuchs, CS, Diaz-Rubio, E, Porschen, R, Tournigand, C, Chibaudel, B, Falcone, A, Tebbutt, NC, Punt, CJA, Hecht, JR, Bokemeyer, C, Van Cutsem, E, Goldberg, RM, Saltz, LB, De Gramont, A, Sargent, DJ & Lenz, HJ 2016, 'Body mass index is prognostic in metastatic colorectal cancer: Pooled analysis of patients from first-line clinical trials in the ARCAD database', Journal of Clinical Oncology, vol. 34, no. 2, pp. 144-150. https://doi.org/10.1200/JCO.2015.61.6441
Renfro, Lindsay A. ; Loupakis, Fotios ; Adams, Richard A. ; Seymour, Matthew T. ; Heinemann, Volker ; Schmoll, Hans Joachim ; Douillard, Jean Yves ; Hurwitz, Herbert ; Fuchs, Charles S. ; Diaz-Rubio, Eduardo ; Porschen, Rainer ; Tournigand, Christophe ; Chibaudel, Benoist ; Falcone, Alfredo ; Tebbutt, Niall C. ; Punt, Cornelis J A ; Hecht, J. Randolph ; Bokemeyer, Carsten ; Van Cutsem, Eric ; Goldberg, Richard M. ; Saltz, Leonard B. ; De Gramont, Aimery ; Sargent, Daniel J. ; Lenz, Heinz Josef. / Body mass index is prognostic in metastatic colorectal cancer : Pooled analysis of patients from first-line clinical trials in the ARCAD database. In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 2. pp. 144-150.
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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/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.",
author = "Renfro, {Lindsay A.} and Fotios Loupakis and Adams, {Richard A.} and Seymour, {Matthew T.} and Volker Heinemann and Schmoll, {Hans Joachim} and Douillard, {Jean Yves} and Herbert Hurwitz and Fuchs, {Charles S.} and Eduardo Diaz-Rubio and Rainer Porschen and Christophe Tournigand and Benoist Chibaudel and Alfredo Falcone and Tebbutt, {Niall C.} and Punt, {Cornelis J A} and Hecht, {J. Randolph} and Carsten Bokemeyer and {Van Cutsem}, Eric and Goldberg, {Richard M.} and Saltz, {Leonard B.} and {De Gramont}, Aimery and Sargent, {Daniel J.} and Lenz, {Heinz Josef}",
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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

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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