Effect of muscle mass on toxicity and survival in patients with colon cancer undergoing adjuvant chemotherapy
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The purpose of this study was to elucidate the effect of decreased muscle mass on the toxicity and survival of patients with colon cancer treated with adjuvant chemotherapy after surgery.
We reviewed the data of 229 consecutive patients with stage III colon cancer who received adjuvant oxaliplatin, 5-fluorouracil, and leucovorin chemotherapy at a single center between 2003 and 2010. Baseline muscle mass was assessed by measuring the cross-sectional area of the psoas muscle at the level of the fourth lumbar vertebra on computed tomography images. Effects of muscle mass on toxicity of chemotherapy and survival were assessed.
The median age of the 229 patients was 61 years (range, 28–80) and 134 (58.5 %) were men. The mean psoas muscle mass index (PI, psoas muscle area divided by height2 [mm2/m2]) was 548.3. A 1 SD decrement in the PI was associated with an increase in all grade 3–4 toxicities in univariate (OR = 1.69, 95 % CI = 1.18–2.27) and multivariate (OR = 1.56, 95 % CI = 1.05–2.38) analyses. In univariate analysis, the PI was not associated with overall survival. However, multivariate analysis showed that a 1 SD decrement in the PI increased the hazard of overall mortality by 85 % (HR = 1.85, 95 % CI = 1.10–3.13). This effect of the PI on mortality was maintained in subgroup analyses, especially in older and obese patients.
Decreased muscle mass was associated with increased risk of grade 3–4 toxicity and poor prognosis in patients with stage III colon cancer.
KeywordsColon cancer Toxicity Mortality Sarcopenia
Sources of funding
This study was supported in part by grant number 02-2014-046 from the SNUBH Research Fund and by study number 1320370 from the National R&D Program for Cancer Control, Ministry for Health and Welfare, Republic of Korea.
Conflicts of interest
- 3.Cesari M, Leeuwenburgh C, Lauretani F, Onder G, Bandinelli S, Maraldi C, Guralnik JM, Pahor M, Ferrucci L (2006) Frailty syndrome and skeletal muscle: results from the Invecchiare in Chianti study. Am J Clin nutri 83(5):1142–1148Google Scholar
- 5.Jung HW, Kim SW, Ahn S, Lim JY, Han JW, Kim TH, Kim KW, Kim KI, Kim CH (2014) Prevalence and outcomes of frailty in Korean elderly population: comparisons of a multidimensional frailty index with two phenotype models. PLoS One 9(2):e87958. doi: 10.1371/journal.pone.0087958 PubMedCentralPubMedCrossRefGoogle Scholar
- 10.Schaap LA, Pluijm SM, Deeg DJ, Harris TB, Kritchevsky SB, Newman AB, Colbert LH, Pahor M, Rubin SM, Tylavsky FA, Visser M (2009) Higher inflammatory marker levels in older persons: associations with 5-year change in muscle mass and muscle strength. J Gerontol A: Biol Med Sci 64(11):1183–1189. doi: 10.1093/gerona/glp097 CrossRefGoogle Scholar
- 15.Hasselager R, Gogenur I (2014) Core muscle size assessed by perioperative abdominal CT scan is related to mortality, postoperative complications, and hospitalization after major abdominal surgery: a systematic review. Langenbecks Archives surg 399(3):287–295. doi: 10.1007/s00423-014-1174-x CrossRefGoogle Scholar
- 19.Prado CM, Baracos VE, McCargar LJ, Reiman T, Mourtzakis M, Tonkin K, Mackey JR, Koski S, Pituskin E, Sawyer MB (2009) Sarcopenia as a determinant of chemotherapy toxicity and time to tumor progression in metastatic breast cancer patients receiving capecitabine treatment. Clin Cancer Res 15(8):2920–2926. doi: 10.1158/1078-0432.CCR-08-2242 PubMedCrossRefGoogle Scholar
- 20.Dodson RM, Firoozmand A, Hyder O, Tacher V, Cosgrove DP, Bhagat N, Herman JM, Wolfgang CL, Geschwind JF, Kamel IR, Pawlik TM (2013) Impact of sarcopenia on outcomes following intra-arterial therapy of hepatic malignancies. J Gastrointest Surg 17(12):2123–2132. doi: 10.1007/s11605-013-2348-5 PubMedCentralPubMedCrossRefGoogle Scholar
- 22.Greene FL, American Joint Committee on Cancer, American Cancer Society (2002) AJCC cancer staging manual, 6th edn. Springer, New YorkGoogle Scholar
- 23.Kim JY, Kim YJ, Lee KW, Lee JS, Kim DW, Kang SB, Lee HS, Jang NY, Kim JS, Kim JH (2013) Practical outcome of adjuvant FOLFOX4 chemotherapy in elderly patients with stage III colon cancer: single-center study in Korea. Jpn J Clin Oncol 43(2):132–138. doi: 10.1093/jjco/hys195 PubMedCrossRefGoogle Scholar
- 26.Ribic CM, Sargent DJ, Moore MJ, Thibodeau SN, French AJ, Goldberg RM, Hamilton SR, Laurent-Puig P, Gryfe R, Shepherd LE, Tu D, Redston M, Gallinger S (2003) Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med 349(3):247–257. doi: 10.1056/NEJMoa022289 PubMedCentralPubMedCrossRefGoogle Scholar
- 27.Compton CC, Fielding LP, Burgart LJ, Conley B, Cooper HS, Hamilton SR, Hammond ME, Henson DE, Hutter RV, Nagle RB, Nielsen ML, Sargent DJ, Taylor CR, Welton M, Willett C (2000) Prognostic factors in colorectal cancer. College of American Pathologists Consensus Statement 1999. Archives pathol lab med 124(7):979–994. doi: 10.1043/0003-9985(2000)124<0979:PFICC>2.0.CO;2 Google Scholar
- 31.Andre T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, Topham C, Zaninelli M, Clingan P, Bridgewater J, Tabah-Fisch I, de Gramont A (2004) Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 350(23):2343–2351. doi: 10.1056/NEJMoa032709 PubMedCrossRefGoogle Scholar
- 32.National Cancer Institute (U.S.) (2009) Common terminology criteria for adverse events (CTCAE). NIH publication, vol no 10–5410, Rev. edn. U.S. Dept. of Health and Human Services, National Institutes of Health, National Cancer Institute, Bethesda, Md.Google Scholar
- 33.Martin L, Birdsell L, Macdonald N, Reiman T, Clandinin MT, McCargar LJ, Murphy R, Ghosh S, Sawyer MB, Baracos VE (2013) Cancer cachexia in the age of obesity: skeletal muscle depletion is a powerful prognostic factor, independent of body mass index. J Clin Oncol 31(12):1539–1547. doi: 10.1200/JCO.2012.45.2722 PubMedCrossRefGoogle Scholar
- 34.Prado CM, Lieffers JR, McCargar LJ, Reiman T, Sawyer MB, Martin L, Baracos VE (2008) Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. lancet oncol 9(7):629–635. doi: 10.1016/S1470-2045(08)70153-0 PubMedCrossRefGoogle Scholar
- 39.Sinicrope FA, Foster NR, Yothers G, Benson A, Seitz JF, Labianca R, Goldberg RM, DeGramont A, O’Connell MJ, Sargent DJ, Adjuvant Colon Canc E (2013) Body mass index at diagnosis and survival among colon cancer patients enrolled in clinical trials of adjuvant chemotherapy. Cancer 119(8):1528–1536. doi: 10.1002/cncr.27938 PubMedCentralPubMedCrossRefGoogle Scholar
- 43.Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, Martin FC, Michel JP, Rolland Y, Schneider SM, Topinkova E, Vandewoude M, Zamboni M (2010) Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing 39(4):412–423. doi: 10.1093/ageing/afq034 PubMedCentralPubMedCrossRefGoogle Scholar
- 44.Chen LK, Liu LK, Woo J, Assantachai P, Auyeung TW, Bahyah KS, Chou MY, Chen LY, Hsu PS, Krairit O, Lee JS, Lee WJ, Lee Y, Liang CK, Limpawattana P, Lin CS, Peng LN, Satake S, Suzuki T, Won CW, Wu CH, Wu SN, Zhang T, Zeng P, Akishita M, Arai H (2014) Sarcopenia in Asia: consensus report of the Asian working group for sarcopenia. J Am Med Direc Assoc 15(2):95–101. doi: 10.1016/j.jamda.2013.11.025 CrossRefGoogle Scholar
- 45.Studenski SA, Peters KW, Alley DE, Cawthon PM, McLean RR, Harris TB, Ferrucci L, Guralnik JM, Fragala MS, Kenny AM, Kiel DP, Kritchevsky SB, Shardell MD, Dam TT, Vassileva MT (2014) The FNIH sarcopenia project: rationale, study description, conference recommendations, and final estimates. J Gerontol A: Biol Med Sci 69(5):547–558. doi: 10.1093/gerona/glu010 CrossRefGoogle Scholar