The impact of visceral fat-to-muscle ratio on prognosis in patients with endometrial cancer

Year 2024, Volume: 24 Issue: 3, 118 - 128

Zeynep Aybikem Sağlam , Nur Zilan Yamiş , Ozge Pasin , Hatice Kübra Arslan , Sena Ekinci Ermiş , Mehmet Şeker , İsa Aykut Özdemir

Abstract

Aim: Obesity increases the risk of endometrial cancer (EC) by 2-5 times compared to non-obese individuals. This study investigates the relationship between radiological measurements of skeletal muscle, visceral, and subcutaneous fat tissue, and their association with clinical features and survival in EC patients.
Material and Method: This retrospective study included 109 EC patients who underwent primary surgery between 2014-2024, with preoperative CT/MR imaging and BMI data available. Measurements of visceral fat area (VFA), subcutaneous fat area (SFA), and skeletal muscle area (SMA) were taken at the L3-L4 vertebral level. Ratios of VFA/SMA, total fat area/SMA (TFA/SMA), and skeletal muscle index (SMI) were calculated. Associations between these metrics, clinical features, and survival outcomes were analyzed.
Results: The mean age was 61.5 years, with a BMI of 35.24; 74.3% were obese (BMI > 30). Mean disease-free survival was 96.1 months, and overall survival was 92.9 months. Advanced age and higher cancer stage correlated with recurrence and mortality. Higher SMA was associated with lower cancer stages, while lower SMA correlated with stages III-IV (p = 0.036). However, no significant differences in disease-free or overall survival were observed across groups.
Conclusions: Skeletal muscle area inversely correlates with cancer stage, indicating a potential protective effect. Obesity-related metrics (VFA, SFA, TFA) showed no significant impact on survival. Further studies are needed to explore underlying mechanisms and clinical relevance.

Keywords

adiposity, body composition, endometrial cancer, obesity, visceral fat

Endometrium kanseri hastalarında viseral yağ dokusu-kas oranının prognoza etkisi

Abstract

Amaç: Obezite, EK gelişimini obez olmayan hastalara göre 2-5 kat artıran önemli bir risk faktörüdür. Obeziteyi tanımlamakta genellikle vücut kitle indeksi (VKİ) kullanılır. Ancak bu ölçüt; kiloya yağ, kas ve kemiklerin etkisini ayırt etmekte yetersiz kalır. Bu çalışmadaki amaç; viseral ve subkutan yağ dokusu ile birlikte iskelet kasının radyolojik ölçümlerinin, endometrium kanserli hastalarda klinik özellikler ve prognoz ile ilişkisinin incelenmesidir.
Yöntem: Retrospektif yapılan bu çalışmaya 2014-2023 yılları arasında primer cerrahisi merkezimizde yapılmış ve endometrial karsinom tanılı, preoperatif BT/MR görüntülerine ve VKİ verilerine erişilen 109 hasta dahil edilmiştir. L3-L4 seviyesinden alınan tek aksiyel kesitte, viseral, subkutan yağ ve iskelet kası alanı ayrı ayrı ölçülmüştür. Bu ölçümler kullanılarak, viseral yağ alanı-kas oranı, toplam yağ alanı-kas oranı ve iskelet kas indeksi hesaplanmıştır.
Bulgular: Hastaların tanı anında ortalama yaşı 61,5, ortalama VKİ, 35,24 idi. Dört hastadan üçünün (%74,3) obez (VKİ>30) olduğu görüldü. Yapılan analizlerde ortalama hastalıksız sağkalım 96,1, toplam sağkalım 92,9 ay olarak bulundu. Tanı yaşı ve evre arttıkça rekürrens riskinin ve mortalitenin arttığı görülmüştür. Obezite ilişkili radyolojik ölçümler (SYA, VYA, TYA, İKA) ve bunlar kullanılarak hesaplanan oranların (VYA/İKA, TYA/İKA, SMI) yüksek ve düşük olmak üzere iki gruba bölünmüştür ve klinik özellikler ve sağkalım açısından karşılaştırılmışlardır. İskelet kas alanı yüksek olan hastaların genellikle daha düşük evreli olduğu, iskelet kas alanı düşük olan hastaların yüksek evreli (evre III-IV) olduğu saptanmıştır (p=0,036). Bu gruplar arasında hastalıksız ve toplam sağkalım açısından anlamlı farklılık görülmemiştir.
Sonuç: Obezite ve endometrium kanseri ilişkisinin altında yatan hücresel mekanizmaların aydınlatılması, bunların klinik sonuçlarının ve tedavi protokollerine etkisinin anlaşılabilmesi için ileri çalışmalara ihtiyaç vardır.

Keywords

adipozite, endometrium kanseri, obezite, viseral yağ dokusu, vücut bileşenleri

References

• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA A Cancer J Clinicians. 2021 May;71(3):209–49.
• Onstad MA, Schmandt RE, Lu KH. Addressing the Role of Obesity in Endometrial Cancer Risk, Prevention, and Treat-ment. J Clin Oncol. 2016 Dec 10;34(35):4225–30.
• McCullough ML, Patel AV, Patel R, Rodriguez C, Feigelson HS, Bandera EV, et al. Body Mass and Endometrial Cancer Risk by Hormone Replacement Therapy and Cancer Subtype. Cancer Epidemiology, Biomarkers & Prevention. 2008 Jan 1;17(1):73–9.
• Renehan AG, Zwahlen M, Egger M. Adiposity and cancer risk: new mechanistic insights from epidemiology. Nat Rev Cancer. 2015 Aug;15(8):484–98.
• Nead KT, Sharp SJ, Thompson DJ, Painter JN, Savage DB, Semple RK, et al. Evidence of a Causal Association Between Insulinemia and Endometrial Cancer: A Mendelian Randomization Analysis. J Natl Cancer Inst. 2015 Jul 1;107(9):djv178.
• Müller MJ, Lagerpusch M, Enderle J, Schautz B, Heller M, Bosy-Westphal A. Beyond the body mass index: tracking body composition in the pathogenesis of obesity and the metabolic syndrome. Obesity Reviews. 2012 Dec;13(S2):6–13.
• Doyle SL, Donohoe CL, Lysaght J, Reynolds JV. Visceral obesity, metabolic syndrome, insulin resistance and cancer. Proc Nutr Soc. 2012 Feb;71(1):181–9.
• Ibrahim MM. Subcutaneous and visceral adipose tissue: structural and functional differences. Obesity Reviews. 2010 Jan;11(1):11–8.
• Mauland KK, Eng Ø, Ytre-Hauge S, Berg A, Salvesen HB, Salvesen ØO, et al. High visceral fat percentage is associated with poor outcome in endometrial cancer.
• Machann J, Thamer C, Schnoedt B, Haap M, Haring H, Claussen CD, et al. Standardized assessment of whole body adi-pose tissue topography by MRI. Magnetic Resonance Imaging. 2005 Apr;21(4):455–62.
• Maurovich-Horvat P, Massaro J, Fox CS, Moselewski F, O’Donnell CJ, Hoffmann U. Comparison of anthropometric, area- and volume-based assessment of abdominal subcutaneous and visceral adipose tissue volumes using multi-detector computed tomography. Int J Obes. 2007 Mar;31(3):500–6.
• Wilhelm Poll L, Wittsack HJ, Koch JA, Willers R, Cohnen M, Kapitza C, et al. A rapid and reliable semiautomated method for measurement of total abdominal fat volumes using magnetic resonance imaging. Magnetic Resonance Imaging. 2003 Jul;21(6):631–6.
• Graffy PM, Pickhardt PJ. Quantification of hepatic and visceral fat by CT and MR imaging: relevance to the obesity epi-demic, metabolic syndrome and NAFLD. BJR. 2016 Jun;89(1062):20151024.
• Xu Z, Luo J, Yang D, Xu H, Jia J, Yang Z. Agreement and correlation of abdominal skeletal muscle area measured by CT and MR imaging in cirrhotic patients. BMC Med Imaging. 2022 Nov 24;22(1):205.
• Tandon P, Mourtzakis M, Low G, Zenith L, Ney M, Carbonneau M, et al. Comparing the Variability Between Measure-ments for Sarcopenia Using Magnetic Resonance Imaging and Computed Tomography Imaging. American Journal of Transplantation. 2016 Sep;16(9):2766–7.
• Sinelnikov A, Qu C, Fetzer DT, Pelletier JS, Dunn MA, Tsung A, et al. Measurement of skeletal muscle area: Comparison of CT and MR imaging. European Journal of Radiology. 2016 Oct;85(10):1716–21.
• Khan AI, Reiter DA, Sekhar A, Sharma P, Safdar NM, Patil DH, et al. MRI quantitation of abdominal skeletal muscle cor-relates with CT-based analysis: implications for sarcopenia measurement. Appl Physiol Nutr Metab. 2019 Aug;44(8):814–9.
• Wang FZ, Sun H, Zhou J, Sun LL, Pan SN. Reliability and Validity of Abdominal Skeletal Muscle Area Measurement Using Magnetic Resonance Imaging. Academic Radiology. 2021 Dec;28(12):1692–8.
• Yoshizumi T, Nakamura T, Yamane M, Waliul Islam AHM, Menju M, Yamasaki K, et al. Abdominal Fat: Standardized Technique for Measurement at CT. Radiology. 1999 Apr;211(1):283–6.
• Shen W, Punyanitya M, Wang Z, Gallagher D, St.-Onge MP, Albu J, et al. Total body skeletal muscle and adipose tissue volumes: estimation from a single abdominal cross-sectional image. Journal of Applied Physiology. 2004 Dec;97(6):2333–8.
• Prado CM, Lieffers JR, McCargar LJ, Reiman T, Sawyer MB, Martin L, et al. Prevalence and clinical implications of sar-copenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. The Lancet Oncology. 2008 Jul;9(7):629–35.
• Creutzberg CL, Wárlám-Rodenhuis CC, van de Steen-Banasik E, Beerman H, van Lent M. Surgery and postoperative ra-diotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. THE LANCET. 2000;355.
• Calle EE. Overweight, Obesity, and Mortality from Cancer in a Prospectively Studied Cohort of U.S. Adults. The New England Journal of Medicine. 2003;
• Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K. Body Fatness and Cancer — Viewpoint of the IARC Working Group. N Engl J Med. 2016 Aug 25;375(8):794–8.
• Kaaks R, Kurzer MS, Annekatrin Lukanova. Obesity, Endogenous Hormones, and Endometrial Cancer Risk: A Synthetic Review. Cancer Epidemiol Biomarkers Prev. 2002 Dec;11:1531–43.
• Buckley E, Mullen MM, Nizamuddin RA, Stein JH, Kuroki LM, Fuh KC, et al. High visceral fat to subcutaneous fat ratios portend a poor prognosis in patients with advanced endometrial cancer. Gynecologic Oncology. 2022 Dec;167(3):496–501.
• Donkers H, Fasmer KE, Mcgrane J, Pijnenborg JMA, Bekkers R, Haldorsen IS, et al. Obesity and visceral fat: Survival im-pact in high-grade endometrial cancer. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2021 Jan;256:425–32.
• Ye S, Wen H, Jiang Z, Wu X. The effect of visceral obesity on clinicopathological features in patients with endometrial cancer: a retrospective analysis of 200 Chinese patients. BMC Cancer. 2016 Dec;16(1):209.
• Celik E, Kizildag Yirgin I, Goksever Celik H, Engin G, Sozen H, Ak N, et al. Does visceral adiposity have an effect on the survival outcomes of the patients with endometrial cancer? J of Obstet and Gynaecol. 2021 Feb;47(2):560–9.
• Basile D, Bartoletti M, Polano M, Bortot L, Gerratana L, Di Nardo P, et al. Prognostic role of visceral fat for overall sur-vival in metastatic colorectal cancer: A pilot study. Clinical Nutrition. 2021 Jan;40(1):286–94.
• Harada K, Baba Y, Ishimoto T, Kosumi K, Tokunaga R, Izumi D, et al. Low Visceral Fat Content is Associated with Poor Prognosis in a Database of 507 Upper Gastrointestinal Cancers. Ann Surg Oncol. 2015 Nov;22(12):3946–53.
• Nattenmüller J, Rom J, Buckner T, Arvin J, Bau B, Sohn C, et al. Visceral abdominal fat measured by computer tomog-raphy as a prognostic factor for gynecological malignancies? Oncotarget. 2018 Mar 27;9(23):16330–42.
• Ham S, Choi JH, Shin SG, Lee EJ. High visceral fat-to-muscle ratio is an independent factor that predicts worse overall survival in patients with primary epithelial ovarian, fallopian tube, and peritoneal cancer. J Ovarian Res. 2023 Jan 21;16(1):19.
• Batsis JA, Villareal DT. Sarcopenic obesity in older adults: aetiology, epidemiology and treatment strategies. Nat Rev Endocrinol. 2018 Sep;14(9):513–37.
• Elcin Aydin, Ezgi Guvel Verdi, Mucahit Furkan Balci, Begüm Ergin, Yeşim Yekta Yürük, Mehmet Simsar, et al. The relati-onship between imaging-based body composition parameters and disease prognosis in patients with endometrial can-cer. Journal of Obstetrics and Gynaecology Research. 2024;
• Khandekar MJ, Cohen P, Spiegelman BM. Molecular mechanisms of cancer development in obesity. Nat Rev Cancer. 2011 Dec;11(12):886–95.
• Quail DF, Dannenberg AJ. The obese adipose tissue microenvironment in cancer development and progression. Nat Rev Endocrinol. 2019 Mar;15(3):139–54.
• Strulov Shachar S, Williams GR. The Obesity Paradox in Cancer—Moving Beyond BMI. Cancer Epid