Advertisement
Original Study|Articles in Press

Prognostic Value of Body Mass Index in Stage II/III Colon Cancer: Posthoc Analysis From the TOSCA Trial

Published:February 04, 2023DOI:https://doi.org/10.1016/j.clcc.2023.01.004

      Highlights

      • High body mass index (BMI) plays a key role in the development of several cancer types, including colon cancer.
      • To date, the prognostic impact of BMI in colon cancer is not fully elucidated.
      • In this post-hoc analysis of TOSCA trial, obesity with BMI ≥30 kg/m2 was an independent prognostic factor for relapse-free survival and overall survival.
      • BMI could provide additional and clinical important prognostic information in stage II/III colon cancer patients.
      • Body composition measurement should be tested to better classify visceral fat and refine risk assessment.

      Abstract

      Background

      High body mass index (BMI) plays a key role in the development of colon cancer (CC). Our post-hoc analysis from the TOSCA trial analyzed the association between BMI and survival outcomes in terms of relapse-free survival (RFS) and overall survival (OS) in stage II/III CC patients.

      Patients and methods

      Patients enrolled in the TOSCA trial between 2007-2013 with BMI data entered the study. The prognostic impact of BMI on survival outcomes was investigated through uni- and multivariable Cox regression analyses.

      Results

      Overall, 1455 patients with stage II/III CC patients were included. The median follow-up was of 61.5 months; 16.1% of patients relapsed, 11.2% died and 19.5% patients relapsed or died. No impact of BMI on RFS was detected at univariate or multivariable analyses. By univariate analysis for OS, a significantly impact of a BMI > 30 kg/m2 was reported (HR [>30 vs <25] 1.57, 95% CI 1.00-2.47, p = 0.049; HR [>30 vs <30] 1.55, 95% CI 1.01-2.37, p = 0.045). Multivariable analyses did not confirm this data. In the subgroup of stage III patients, a negative survival impact of BMI was found in univariate and multivariable models both for RFS and for OS.

      Conclusions

      In our study, obesity with BMI > 30 kg/m2 was an independent prognostic factor for RFS and OS in CC patients treated with adjuvant chemotherapy, regardless of its duration (3 or 6 months). However, the prognostic impact of adiposity and body composition measurement should be considered to better classify patients with high visceral fat and refine their risk assessment.

      Keywords

      Abbreviations:

      BMI (Body Mass Index)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Clinical Colorectal Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Bray F
        • Ferlay J
        • Soerjomataram I
        • Siegel RL
        • Torre LA
        • Jemal A.
        Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.
        CA Cancer J Clin. 2018; 68: 394-424https://doi.org/10.3322/caac.21492
        • Tárraga López PJ
        • Albero JS
        • Rodríguez-Montes JA
        Primary and secondary prevention of colorectal cancer.
        Clin Med Insights Gastroenterol. 2014; 7: 33-46https://doi.org/10.4137/CGast.S14039
        • Arnold M
        • Sierra MS
        • Laversanne M
        • Soerjomataram I
        • Jemal A
        • Bray F.
        Global patterns and trends in colorectal cancer incidence and mortality.
        Gut. 2017; 66: 683-691https://doi.org/10.1136/gutjnl-2015-310912
        • Bianchini F
        • Kaaks R
        • Vainio H.
        Overweight, obesity, and cancer risk.
        Lancet Oncol. 2002; 3: 565-574https://doi.org/10.1016/s1470-2045(02)00849-5
        • Renehan AG
        • Tyson M
        • Egger M
        • Heller RF
        • Zwahlen M.
        Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies.
        Lancet. 2008; 371: 569-578https://doi.org/10.1016/S0140-6736(08)60269-X
        • Terry P
        • Giovannucci E
        • Michels KB
        • et al.
        Fruit, Vegetables, dietary fiber, and risk of colorectal cancer.
        J Natl Cancer Inst. 2001; 93: 525-533https://doi.org/10.1093/jnci/93.7.525
        • Nam SY
        • Kim BC
        • Han KS
        • et al.
        Abdominal visceral adipose tissue predicts risk of colorectal adenoma in both sexes.
        Clin Gastroenterol Hepatol. 2010; 8 (.e1-2): 443-450https://doi.org/10.1016/j.cgh.2010.02.001
        • Erarslan E
        • Turkay C
        • Koktener A
        • Koca C
        • Uz B
        • Bavbek N.
        Association of visceral fat accumulation and adiponectin levels with colorectal neoplasia.
        Dig Dis Sci. 2009; 54: 862-868https://doi.org/10.1007/s10620-008-0440-6
        • Barb D
        • Williams CJ
        • Neuwirth AK
        • Mantzoros CS.
        Adiponectin in relation to malignancies: a review of existing basic research and clinical evidence.
        Am J Clin Nutr. 2007; 86: s858-s866https://doi.org/10.1093/ajcn/86.3.858S
        • Bardou M
        • Barkun AN
        • Martel M.
        Obesity and colorectal cancer.
        Gut. 2013; 62: 933-947https://doi.org/10.1136/gutjnl-2013-304701
      1. Body mass index - BMI. 2019. Accessed December 24, 2019. Available at: http://www.euro.who.int/en/health-topics/disease-prevention/nutrition/a-healthy-lifestyle/body-mass-index-bmi

        • Meyerhardt JA
        • Niedzwiecki D
        • Hollis D
        • et al.
        Impact of body mass index and weight change after treatment on cancer recurrence and survival in patients with stage III colon cancer: findings from cancer and leukemia group B 89803.
        J Clin Oncol. 2008; 26: 4109-4115https://doi.org/10.1200/JCO.2007.15.6687
        • Dignam JJ
        • Polite BN
        • Yothers G
        • et al.
        Body mass index and outcomes in patients who receive adjuvant chemotherapy for colon cancer.
        J Natl Cancer Inst. 2006; 98: 1647-1654https://doi.org/10.1093/jnci/djj442
        • Sobrero A
        • Lonardi S
        • Rosati G
        • et al.
        FOLFOX or CAPOX in stage II to III colon cancer: efficacy results of the Italian three or six colon adjuvant trial.
        JCO. 2018; 36: 1478-1485https://doi.org/10.1200/JCO.2017.76.2187
        • Petrelli F
        • Rulli E
        • Labianca R
        • et al.
        Overall survival with 3 or 6 months of adjuvant chemotherapy in Italian TOSCA phase 3 randomised trial.
        Ann Oncol. 2021; 32: 66-76https://doi.org/10.1016/j.annonc.2020.10.477
        • Lonardi S
        • Sobrero A
        • Rosati G
        • et al.
        Phase III trial comparing 3-6 months of adjuvant FOLFOX4/XELOX in stage II-III colon cancer: safety and compliance in the TOSCA trial.
        Ann Oncol. 2016; 27: 2074-2081https://doi.org/10.1093/annonc/mdw404
        • Lonardi S
        • Sobrero A
        • Rosati G
        • et al.
        Phase III trial comparing 3-6 months of adjuvant FOLFOX4/XELOX in stage II-III colon cancer: safety and compliance in the TOSCA trial.
        Ann Oncol. 2017; 28: 3110https://doi.org/10.1093/annonc/mdx021
        • Shaukat A
        • Dostal A
        • Menk J
        • Church TR.
        BMI is a risk factor for colorectal cancer mortality.
        Dig Dis Sci. 2017; 62: 2511-2517https://doi.org/10.1007/s10620-017-4682-z
        • Vernieri C
        • Galli F
        • Ferrari L
        • et al.
        Impact of metformin use and diabetic status during adjuvant fluoropyrimidine-oxaliplatin chemotherapy on the outcome of patients with resected colon cancer: a TOSCA study subanalysis.
        Oncologist. 2019; 24: 385-393https://doi.org/10.1634/theoncologist.2018-0442
        • Donohoe CL
        • Doyle SL
        • Reynolds JV.
        Visceral adiposity, insulin resistance and cancer risk.
        Diabetol Metab Syndr. 2011; 3: 12https://doi.org/10.1186/1758-5996-3-12
        • Riondino S
        • Roselli M
        • Palmirotta R
        • Della-Morte D
        • Ferroni P
        • Guadagni F.
        Obesity and colorectal cancer: role of adipokines in tumor initiation and progression.
        World J Gastroenterol. 2014; 20: 5177-5190https://doi.org/10.3748/wjg.v20.i18.5177
        • Kadowaki T
        • Yamauchi T.
        Adiponectin and adiponectin receptors.
        Endocr Rev. 2005; 26: 439-451https://doi.org/10.1210/er.2005-0005
        • Deng Y
        • Scherer PE.
        Adipokines as novel biomarkers and regulators of the metabolic syndrome.
        Ann N Y Acad Sci. 2010; 1212: E1-E19https://doi.org/10.1111/j.1749-6632.2010.05875.x
        • Baier PK
        • Eggstein S
        • Wolff-Vorbeck G
        • Baumgartner U
        • Hopt UT.
        Chemokines in human colorectal carcinoma.
        Anticancer Res. 2005; 25: 3581-3584
        • Waldner MJ
        • Foersch S
        • Neurath MF.
        Interleukin-6 - a key regulator of colorectal cancer development.
        Int J Biol Sci. 2012; 8: 1248-1253https://doi.org/10.7150/ijbs.4614
        • Matthews CE
        • Sui X
        • LaMonte MJ
        • Adams SA
        • Hébert JR
        • Blair SN.
        Metabolic syndrome and risk of death from cancers of the digestive system.
        Metabolism. 2010; 59: 1231-1239https://doi.org/10.1016/j.metabol.2009.11.019
        • Haydon AMM
        • MacInnis RJ
        • English DR
        • Giles GG.
        Effect of physical activity and body size on survival after diagnosis with colorectal cancer.
        Gut. 2006; 55: 62-67https://doi.org/10.1136/gut.2005.068189
        • Campbell PT
        • Newton CC
        • Dehal AN
        • Jacobs EJ
        • Patel AV
        • Gapstur SM.
        Impact of body mass index on survival after colorectal cancer diagnosis: the Cancer Prevention Study-II Nutrition Cohort.
        J Clin Oncol. 2012; 30: 42-52https://doi.org/10.1200/JCO.2011.38.0287
        • Prado CMM
        • Lieffers JR
        • McCargar LJ
        • et al.
        Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study.
        Lancet Oncol. 2008; 9: 629-635https://doi.org/10.1016/S1470-2045(08)70153-0
        • Ryan AM
        • Power DG
        • Daly L
        • Cushen SJ
        • Ní Bhuachalla Ē
        • Prado CM
        Cancer-associated malnutrition, cachexia and sarcopenia: the skeleton in the hospital closet 40 years later.
        Proc Nutr Soc. 2016; 75: 199-211https://doi.org/10.1017/S002966511500419X
        • Shahjehan F
        • Merchea A
        • Cochuyt JJ
        • Li Z
        • Colibaseanu DT
        • Kasi PM.
        Body mass index and long-term outcomes in patients with colorectal cancer.
        Front Oncol. 2018; 8https://doi.org/10.3389/fonc.2018.00620
        • Zha JM
        • Di WJ
        • Zhu T
        • et al.
        Comparison of gene transcription between subcutaneous and visceral adipose tissue in Chinese adults.
        Endocr J. 2009; 56: 935-944https://doi.org/10.1507/endocrj.k09e-091
        • Nimri L
        • Peri I
        • Yehuda-Shnaidman E
        • Schwartz B
        Adipocytes isolated from visceral and subcutaneous depots of donors differing in BMI crosstalk with colon cancer cells and modulate their invasive phenotype.
        Transl Oncol. 2019; 12: 1404-1415https://doi.org/10.1016/j.tranon.2019.07.010
        • Peinado JR
        • Jimenez-Gomez Y
        • Pulido MR
        • et al.
        The stromal-vascular fraction of adipose tissue contributes to major differences between subcutaneous and visceral fat depots.
        Proteomics. 2010; 10: 3356-3366https://doi.org/10.1002/pmic.201000350
        • Villaret A
        • Galitzky J
        • Decaunes P
        • et al.
        Adipose tissue endothelial cells from obese human subjects: differences among depots in angiogenic, metabolic, and inflammatory gene expression and cellular senescence.
        Diabetes. 2010; 59: 2755-2763https://doi.org/10.2337/db10-0398
        • Silva A
        • Faria G
        • Araújo A
        • Monteiro MP.
        Impact of adiposity on staging and prognosis of colorectal cancer.
        Crit Rev Oncol Hematol. 2020; 145102857https://doi.org/10.1016/j.critrevonc.2019.102857
        • Blauwhoff-Buskermolen S
        • Versteeg KS
        • de van der Schueren MAE
        • et al.
        Loss of muscle mass during chemotherapy is predictive for poor survival of patients with metastatic colorectal cancer.
        J Clin Oncol. 2016; 34: 1339-1344https://doi.org/10.1200/JCO.2015.63.6043
        • Caan BJ
        • Feliciano EMC
        • Kroenke CH.
        The importance of body composition in explaining the overweight paradox in cancer: counterpoint.
        Cancer Res. 2018; 78: 1906-1912https://doi.org/10.1158/0008-5472.CAN-17-3287
        • Caan BJ
        • Meyerhardt JA
        • Kroenke CH
        • et al.
        Explaining the obesity paradox: the association between body composition and colorectal cancer survival (C-SCANS Study).
        Cancer Epidemiol Biomarkers Prev. 2017; 26: 1008-1015https://doi.org/10.1158/1055-9965.EPI-17-0200
        • Aleixo GFP
        • Shachar SS
        • Nyrop KA
        • Muss HB
        • Malpica L
        • Williams GR.
        Myosteatosis and prognosis in cancer: systematic review and meta-analysis.
        Crit Rev Oncol Hematol. 2020; 145102839https://doi.org/10.1016/j.critrevonc.2019.102839