ESPEN Congress Madrid 2018

Transcription

1 ESPEN Congress Madrid 2018 The Role Of Obesity In Cancer Survival And Cancer Recurrence Body Composition And Outcomes In Cancer Patients M-C. Gonzalez (BR)

2 The role of obesity in cancer survival and cancer recurrence Body composition and outcomes in cancer patients M. Cristina Gonzalez, MD, PhD Catholic University of Pelotas, RS, Brazil Pennington Biomedical Research Center, Baton Rouge, LA

3 Conflict of interest I have no conflict of interest in this lecture.

4 Learning objectives After this lecture, the audience should: Know the relationship between body composition and oncology treatment toxicity Know the influence of body composition on postoperative outcome Know the influence of body composition on survival

5 Hypothesized mechanism for loss of muscle mass in cancer Feliciano et al. Ann Rev Nutr 2018;38:9-1

6 6 Skeletal muscle index SMI (cm 2 /m 2 ) = skeletal muscle L3 CT (cm 2 )/ height 2 (m 2 ) Whole-body FFM (kg) = 0.30 X [skeletal muscle L3 CT (cm 2 )] Appendicular skeletal muscle/height (kg/m 2 ) = 0.11 X [skeletal muscle L3 CT/ht 2 (cm 2 /m 2 )] to 150 HU to 50 HU to 30 HU to 30 HU Mourtzakis et al. Appl Physiol Nutr Metab 2008;33:997

7 Low muscle mass High fat mass Normal Myopenia/sarcopenia Obesity 7 Low muscle mass Sarcopenic obesity High fat mass 7

8 Muscle attenuation = myosteatosis Muscle quality = function Martin et al. J Clin Oncol 2013;31:1539

9 SARCOPENIA EWGSOP Defining low muscle mass in cancer: Age-related Pre Sarcopenia Low muscle mass sarcopenia or myopenia? Low muscle mass CT cm 2 /m 2 men cm 2 /m 2 women Prevalence: 11 to 90% Disease-related Myopenia Low or sarcopenia muscle mass? Metabolic stress Low strength and low performance Negative outcomes Low strength and low performance Myosteatosis Negative outcomes Daly et al. Proc Nutr Soc 2018;77:135

10 Defining low muscle mass and sarcopenia in cancer 22 different ways to define low muscle mass and sarcopenia Simonsen et al. Ann Surg 2018;268:58

11 Body composition and oncology treatment toxicity

12 16.3 mg 5-FU/kg LBM 17.9 mg 5-FU/kg LBM Prado et al. Clin Cancer Res 2007;13:3264

13 13 Sarcopenia and toxicity 26/32 studies: association between low muscle mass and toxicity Advanced or early stages of almost all types of cancer LEANOX study (LEan body mass Normalization of OXaliplatin based chemotherapy): LBM versus BSA-based dosing and sever toxicity Daly et al. Proc Nutr Soc 2018;77:135; Baracos et al. Ann Oncol 2018;29 (Suppl 2):ii1

14 14 Prospective observational or interventional studies Sarcopenia: CT, MRI, DXA or BIA Sarcopenia prevalence before chemotherapy 29% [95%CI ] 5/6 studies found association with toxicity: esophageal, solid and hematological and renal cell Pamoukdjian et al. Clin Nutr 2018;37:1101

15 Anandavadivelan et al. Clin Nutr 2016;35:724

16 (adjusted for age, gender and tumor stage) Sarcopenic obese have a 5 times higher risk of toxicity Anandavadivelan et al. Clin Nutr 2016;35:724

17 Body composition and postoperative complications

18 Postoperative pneumonia Body composition assessment: 18 CT, 10 BIA e 1 DEXA No association with early mortality No association with non-pulmonary postoperative complications Boshier et al. Dis Esophagus 2018;31(8).

19 Sarcopenia using EWGSOP criteria: additive risks Higher risks when function in included to define sarcopenia Yang et al. J Gastrointest Surg 2018;epub ahead of print; Shen et al. BMC Geriatric 2017;17:188; Simonsen et al. Ann Surg 2018;268:58

20 20 Sarcopenia: CT L3 SMI and EWGSOP in 2 studies No effect in intestinal obstruction or anastomosis leakage Hospital stay Postoperative morbidity 3.45 Postoperative mortality 2.21 Infection Sun et al. Int J Colorectal Dis 2018;epub ahead of print

21 Population CT assessment Outcomes 376 patients undergoing colorectal cancer surgery 50.8% visceral obesity 24.5% sarcopenia Higher incidence of total, surgical and medical complications Longer hospital stays Higher hospitalization costs Chen et al. Dig Dis Sciences 2018;63:1620

22 816 patients with stage I-III colorectal cancer with CT scan: skeletal muscle mass and density 50.5% with low muscle mass and 64.1% with low muscle density Operative outcomes Muscle mass Muscle density Complications Skeletal overall muscle mass and Severe complications density are associated Y with Complication short-term index outcomes, but not Length of stay with long-term outcomes (overall and disease-free Not discharged survival to home Mortality Van Vugt et al. Eur J Surg Oncol 2018;44:1354

23 Only 28% patients with no features and 4% with sarcopenia, myosteatosis and visceral obesity LOS 30-d hospital readmission No complication 10,72 6,8 Myosteatosis alone or combined with sarcopenia/vo VO alone or combined with myosteatosis/ sarcopenia Major complication days days S + Myo + VO No feature 25,9 16, Martin et al. Ann Surg Oncol 2018;25:2669

24 26% patients with low SMA & high IMAC Harimoto et al. Anticancer Res 2018;38:4933

25 Body composition and survival

26 Feliciano et al. Annu Rev Nutr 2018;38:9.1

27 27 Prospective observational or interventional studies any cancer Sarcopenia: CT, MRI, DXA or BIA Overall sarcopenia prevalence 38.6% [95%CI ] 19/22 studies found association with overall survival and with relapsed-free survival in 5 studies Pamoukdjian et al. Clin Nutr 2018;37:1101

28 22 studies assessing the impact of visceral adiposity on survival Methodological limitations: lack of standardization for VAT measurements 4 of 6 studies 3 of 5 studies 4 of 5 studies Xiao et al. Eur J Cancer Care 2018;27:e12611

29 Overall survival Disease-free survival Cancer-specific survival Sun et al. Int J Colorectal Dis 2018;epub ahead of print

30 3262 patients from Kaiser Permanent Northern California 2,54 Low SMD Low SMI 2,02 Stage I-II CRC 1,57 Low SMD normal SMI 1,63 Skeletal muscle density (SMD) and mass (SMI) Sex-specific cutoffs from 1,42 optimal stratification Normal SMD low SMI 1,3 Effects of muscle components on survival CRC mortality Normal SMD normal SMI Overall mortality SMD only 1 SMD + SMI Kroenke et al. Cancer 2018;124:3008

31 Choi et al. J Cachexia Sarcopenia Muscle 2018;9:53 Overall survival Disease-free survival 39.4% sarcopenic No association with disease-free survival 51.6% viscerally obese No association with overall survival

32 Low muscle High adiposity & low muscle High adiposity Normal Caan et al. Cancer Epidemiol Biomarkers Prev 2017;26:1008; Gonzalez et al. Am J Clin Nutr 2014;99:999

33 Obesity paradox: only with adequate muscle mass and high adiposity Caan et al. Cancer Epidemiol Biomarkers Prev 2017;26:1008; Gonzalez et al. Am J Clin Nutr 2014;99:999

34 Bian et al. Medicine 2018;97:22(e10988)

35 Bian et al. Medicine 2018;97:22(e10988)

36 Low SMD Low SMD Disease-free survival Overall survival 224 patients using specific cutoff for SMD: 51.8% with low SMD Chu et al. J Cachexia Sarcopenia Muscle 2017;8:298 Prognostic factor for overall survival even after adjustment for Revised International Prognostic Index

37 Caan et al. JAMA Oncology 2018;4:798 3,241 women with nonmetastatic breast cancer: 34% sarcopenia Sarcopenia < 40 cm 2 /m 2 Radiodensity < 37.8HU Adiposity 3rd tertile

38 Caan et al. JAMA Oncology 2018;4:798

39 Hopkins et al. Ann Surg Oncol 2018;25: studies (8895 patients) with colorectal cancer and survival Sarcopenia, myosteatosis and visceral obesity CTassessment: lack of consensus of specific cutoffs Sarcopenia and myosteatosis: consistently associated with worse survival Population specific cutoff points by optimal stratification should be used

40 Cancer Take home messages Worse prognostic Higher toxicity Higher PO complications Lower survival Nutritional therapy Exercise Pharmacotherapy?

41 Thank you for your attention! Recommended further reading Daly LE, Prado CM, Ryan AM. A window beneath the skin: how computed tomography assessment of body composition can assist in the identification of hidden wasting conditions in oncology that profoundly impact outcomes. Proc Nutr Soc 2018;77: Baracos VE, Arribas L. Sarcopenic obesity: hidden muscle wasting and its impact for survival and complications of cancer therapy. Ann Oncol 2018;29 (suppl 2):ii1-ii9 Feliciano EMC, Kroenk CH, Caan BJ. The obesity paradox in cancer: how important is muscle? Annu Rev Nutr 2018;38: