Malignes Melanom und Adipositas: eine Übersichtsarbeit

Zusammenfassung

Einleitung Die Inzidenz von Adipositas nimmt weltweit stetig zu. Übergewicht und Adipositas werden als mögliche Risikofaktoren für verschiedene Krebserkrankungen, einschließlich des malignen Melanoms, diskutiert. Dieser Review stellt die Evidenz zu der Assoziation zwischen Adipositas und dem malignen Melanom dar.

Methodik Selektive Literaturrecherche.

Ergebnisse Obwohl verschiedene Erklärungsansätze für eine mögliche Assoziation von Adipositas und dem malignen Melanom existieren, sind diese nicht vollständig bekannt und weiterhin Gegenstand der Forschung. Die Evidenz zur Assoziation zwischen Adipositas und Melanom-Outcomes für Patienten ohne Systemtherapie ist gering. Für Patienten mit Systemtherapie gibt es Evidenz, die einen protektiven Effekt unter Immuntherapien und zielgerichteten Therapien beschreibt.

Schlussfolgerung Insgesamt gibt es zu der Assoziation zwischen dem malignen Melanom und Adipositas nicht ausreichend Evidenz, um zu schlussfolgern, ob Adipositas einen unabhängigen protektiven Effekt hat oder ein Risikofaktor für die Entstehung von Melanomen darstellt. Weitere Forschung ist erforderlich, um das Wissen über diesen möglichen Zusammenhang zu vertiefen.

Abstract

Introduction The incidence of obesity continues to increase worldwide. Obesity is discussed as a potential risk factor for various types of cancer including malignant melanoma. This review presents the evidence for the association between obesity and malignant melanoma.

Methods Selective literature search.

Results Although several explanatory approaches for the association between obesity and malignant melanoma exist, these are currently not fully understood and remain subject of research. The evidence on the association between obesity and melanoma outcomes for patients without systemic therapy is low. For patients with systemic therapy existing evidence points to a protective effect of immuno- and targeted therapies.

Conclusion Overall, current evidence is insufficient to conclude whether obesity has an independent protective effect or is a risk factor for the development of malignant melanoma. Further research is needed to assess this potential association in greater depth.

Schlüsselwörter

Melanom - Adipositas - Body-Mass-Index

Keywords

Melanoma - Obesity - Body mass index

Publikationsverlauf

Artikel online veröffentlicht:
01. September 2023

• Literatur

• 1 Zentrum für Krebsregisterdaten. Krebs in Deutschland für 2017/2018. Berlin: Robert Koch Institut; 2021 Zugriff am 16.05.2022: https://www.krebsdaten.de/Krebs/DE/Content/Publikationen/Krebs_in_Deutschland/kid_2021/krebs_in_deutschland_2021.pdf?__blob=publicationFile
• 2 Eigentler T. et al. S3-Leitlinie zur Diagnostik, Therapie und Nachsorge des Melanoms: Leitlinienprogramm Onkologie der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Deutschen Krebsgesellschaft e.V. (DKG) und Deutschen Krebshilfe (DKH). 2020 Zugriff am 16.05.2022: https://www.awmf.org/uploads/tx_szleitlinien/032-024OLl_S3_Melanom-Diagnostik-Therapie-Nachsorge_2020-08.pdf
• 3 Avgerinos KI, Spyrou N, Mantzoros CS. et al. Obesity and cancer risk: Emerging biological mechanisms and perspectives. Metabolism 2019; 92: 121-135
• 4 Bandera EV, Fay SH, Giovannucci E. et al. The use and interpretation of anthropometric measures in cancer epidemiology: A perspective from the world cancer research fund international continuous update project. Int J Cancer 2016; 139: 2391-2397
• 5 Thune I, Olsen A, Albrektsen G. et al. Cutaneous malignant melanoma: association with height, weight and body-surface area. a prospective study in Norway. Int J Cancer 1993; 55: 555-561
• 6 Veierød MB, Thelle DS, Laake P. Diet and risk of cutaneous malignant melanoma: a prospective study of 50,757 Norwegian men and women. Int J Cancer 1997; 71: 600-604
• 7 Shors AR, Solomon C, McTiernan A. et al. Melanoma risk in relation to height, weight, and exercise (United States). Cancer Causes Control 2001; 12: 599-606
• 8 Freedman DM, Sigurdson A, Doody MM. et al. Risk of melanoma in relation to smoking, alcohol intake, and other factors in a large occupational cohort. Cancer Causes Control 2003; 14: 847-857
• 9 Naldi L, Altieri A, Imberti GL. et al. Cutaneous malignant melanoma in women. Phenotypic characteristics, sun exposure, and hormonal factors: a case-control study from Italy. Ann Epidemiol 2005; 15: 545-550
• 10 Gallus S, Naldi L, Martin L. et al. Anthropometric measures and risk of cutaneous malignant melanoma: a case-control study from Italy. Melanoma Res 2006; 16: 83-87
• 11 Samanic C, Chow WH, Gridley G. et al. Relation of body mass index to cancer risk in 362,552 Swedish men. Cancer Causes Control 2006; 17: 901-909
• 12 Odenbro A, Gillgren P, Bellocco R. et al. The risk for cutaneous malignant melanoma, melanoma in situ and intraocular malignant melanoma in relation to tobacco use and body mass index. Br J Dermatol 2007; 156: 99-105
• 13 Dennis LK, Lowe JB, Lynch CF. et al. Cutaneous melanoma and obesity in the Agricultural Health Study. Ann Epidemiol 2008; 18: 214-221
• 14 Olsen CM, Green AC, Zens MS. et al. Anthropometric factors and risk of melanoma in women: a pooled analysis. Int J Cancer 2008; 122: 1100-1108
• 15 Renehan AG, Tyson M, Egger M. et al. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 2008; 371: 569-578
• 16 Lauby-Secretan B, Scoccianti C, Loomis D. et al. Body Fatness and Cancer--Viewpoint of the IARC Working Group. N Engl J Med 2016; 375: 794-798
• 17 Dobbins M, Decorby K, Choi BC. The Association between Obesity and Cancer Risk: A Meta-Analysis of Observational Studies from 1985 to 2011. ISRN Prev Med 2013; 2013: 680536
• 18 Tang JY, Henderson MT, Hernandez-Boussard T. et al. Lower skin cancer risk in women with higher body mass index: the women’s health initiative observational study. Cancer Epidemiol Biomarkers Prev 2013; 22: 2412-2415
• 19 Sergentanis TN, Antoniadis AG, Gogas HJ. et al. Obesity and risk of malignant melanoma: a meta-analysis of cohort and case-control studies. Eur J Cancer 2013; 49: 642-657
• 20 Fang S, Wang Y, Dang Y. et al. Association between Body Mass Index, C-Reactive Protein Levels, and Melanoma Patient Outcomes. J Invest Dermatol 2017; 137: 1792-1795
• 21 McQuade JL, Daniel CR, Hess KR. et al. Association of body-mass index and outcomes in patients with metastatic melanoma treated with targeted therapy, immunotherapy, or chemotherapy: a retrospective, multicohort analysis. Lancet Oncol 2018; 19: 310-322
• 22 Wang Z, Aguilar EG, Luna JI. et al. Paradoxical effects of obesity on T cell function during tumor progression and PD-1 checkpoint blockade. Nat Med 2019; 25: 141-151
• 23 Donnelly D, Bajaj S, Yu J. et al. The complex relationship between body mass index and response to immune checkpoint inhibition in metastatic melanoma patients. J Immunother Cancer 2019; 7: 222
• 24 Rutkowski P, Indini A, De Luca M. et al. Body mass index (BMI) and outcome of metastatic melanoma patients receiving targeted therapy and immunotherapy: a multicenter international retrospective study. J Immunother Cancer 2020; 8: e001117
• 25 Pandey V, Vijayakumar MV, Ajay AK. et al. Diet-induced obesity increases melanoma progression: involvement of Cav-1 and FASN. Int J Cancer 2012; 130: 497-508
• 26 Malvi P, Chaube B, Pandey V. et al. Obesity induced rapid melanoma progression is reversed by orlistat treatment and dietary intervention: role of adipokines. Mol Oncol 2015; 9: 689-703
• 27 Hopkins BD, Goncalves MD, Cantley LC. Obesity and Cancer Mechanisms: Cancer Metabolism. J Clin Oncol 2016; 34: 4277-4283
• 28 Smith LK, Arabi S, Lelliott EJ. et al. Obesity and the Impact on Cutaneous Melanoma: Friend or Foe?. Cancers (Basel) 2020; 12: 1583
• 29 Cao Y. Adipocyte and lipid metabolism in cancer drug resistance. J Clin Invest 2019; 129: 3006-3017
• 30 Kushiro K, Chu RA, Verma A. et al. Adipocytes Promote B16BL6 Melanoma Cell Invasion and the Epithelial-to-Mesenchymal Transition. Cancer Microenviron 2012; 5: 73-82
• 31 Lazar I, Clement E, Dauvillier S. et al. Adipocyte Exosomes Promote Melanoma Aggressiveness through Fatty Acid Oxidation: A Novel Mechanism Linking Obesity and Cancer. Cancer Res 2016; 76: 4051-4057
• 32 Coelho P, Almeida J, Prudêncio C. et al. Effect of Adipocyte Secretome in Melanoma Progression and Vasculogenic Mimicry. J Cell Biochem 2016; 117: 1697-1706
• 33 Robado de Lope L, Alcíbar OL, Amor López A. et al. Tumour-adipose tissue crosstalk: fuelling tumour metastasis by extracellular vesicles. Philos Trans R Soc Lond B Biol Sci 2018; 373: 20160485
• 34 Zhang M, Di Martino JS, Bowman RL. et al. Adipocyte-Derived Lipids Mediate Melanoma Progression via FATP Proteins. Cancer Discov 2018; 8: 1006-1025
• 35 Clement E, Lazar I, Attané C. et al. Adipocyte extracellular vesicles carry enzymes and fatty acids that stimulate mitochondrial metabolism and remodeling in tumor cells. Embo j 2020; 39: e102525
• 36 Olszańska J, Pietraszek-Gremplewicz K, Nowak D. Melanoma Progression under Obesity: Focus on Adipokines. Cancers (Basel) 2021; 13: 2281
• 37 Oba J, Wei W, Gershenwald JE. et al. Elevated Serum Leptin Levels are Associated With an Increased Risk of Sentinel Lymph Node Metastasis in Cutaneous Melanoma. Medicine (Baltimore) 2016; 95: e3073
• 38 Gogas H, Trakatelli M, Dessypris N. et al. Melanoma risk in association with serum leptin levels and lifestyle parameters: a case-control study. Ann Oncol 2008; 19: 384-389
• 39 Chen J, Chi M, Chen C. et al. Obesity and melanoma: exploring molecular links. J Cell Biochem 2013; 114: 1955-1961
• 40 Hotamisligil GS. Inflammation, metaflammation and immunometabolic disorders. Nature 2017; 542: 177-185
• 41 Sevim DG, Kiratli H. Serum adiponectin, insulin resistance, and uveal melanoma: clinicopathological correlations. Melanoma Res 2016; 26: 164-172
• 42 Tura A, Thieme C, Brosig A. et al. Lower Levels of Adiponectin and Its Receptor Adipor1 in the Uveal Melanomas With Monosomy-3. Invest Ophthalmol Vis Sci 2020; 61: 12
• 43 Aron-Wisnewsky J, Prifti E, Belda E. et al. Major microbiota dysbiosis in severe obesity: fate after bariatric surgery. Gut 2019; 68: 70-82
• 44 Abenavoli L, Scarpellini E, Colica C. et al. Gut Microbiota and Obesity: A Role for Probiotics. Nutrients 2019; 11: 2690
• 45 Breton J, Galmiche M, Déchelotte P. Dysbiotic Gut Bacteria in Obesity: An Overview of the Metabolic Mechanisms and Therapeutic Perspectives of Next-Generation Probiotics. Microorganisms 2022; 10: 452
• 46 Liu BN, Liu XT, Liang ZH. et al. Gut microbiota in obesity. World J Gastroenterol 2021; 27: 3837-3850
• 47 John GK, Mullin GE. The Gut Microbiome and Obesity. Curr Oncol Rep 2016; 18: 45
• 48 Walters WA, Xu Z, Knight R. Meta-analyses of human gut microbes associated with obesity and IBD. FEBS Lett 2014; 588: 4223-4233
• 49 Jumpertz R, Le DS, Turnbaugh PJ. et al. Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans. Am J Clin Nutr 2011; 94: 58-65
• 50 Ley RE, Bäckhed F, Turnbaugh P. et al. Obesity alters gut microbial ecology. Proc Natl Acad Sci USA 2005; 102: 11070-11075
• 51 Ley RE, Turnbaugh PJ, Klein S. et al. Microbial ecology: human gut microbes associated with obesity. Nature 2006; 444: 1022-1023
• 52 Hossain F, Majumder S, David J. et al. Obesity Modulates the Gut Microbiome in Triple-Negative Breast Cancer. Nutrients 2021; 13: 3656
• 53 Parker BJ, Wearsch PA, Veloo ACM. et al. The Genus Alistipes: Gut Bacteria With Emerging Implications to Inflammation, Cancer, and Mental Health. Front Immunol 2020; 11: 906
• 54 Kovács T, Mikó E, Ujlaki G. et al. The Microbiome as a Component of the Tumor Microenvironment. Adv Exp Med Biol 2020; 1225: 137-153
• 55 Frankel AE, Coughlin LA, Kim J. et al. Metagenomic Shotgun Sequencing and Unbiased Metabolomic Profiling Identify Specific Human Gut Microbiota and Metabolites Associated with Immune Checkpoint Therapy Efficacy in Melanoma Patients. Neoplasia 2017; 19: 848-855
• 56 Davar D, Dzutsev AK, McCulloch JA. et al. Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients. Science 2021; 371: 595-602
• 57 Gopalakrishnan V, Spencer CN, Nezi L. et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science 2018; 359: 97-103
• 58 Dai Z, Zhang J, Wu Q. et al. Intestinal microbiota: a new force in cancer immunotherapy. Cell Commun Signal 2020; 18: 90
• 59 Matson V, Fessler J, Bao R. et al. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science 2018; 359: 104-108
• 60 Ansaldo E, Belkaid Y. How microbiota improve immunotherapy. Science 2021; 373: 966-967
• 61 Baruch EN, Youngster I, Ben-Betzalel G. et al. Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients. Science 2021; 371: 602-609
• 62 Limeta A, Ji B, Levin M. et al. Meta-analysis of the gut microbiota in predicting response to cancer immunotherapy in metastatic melanoma. JCI Insight 2020; 5: e140940
• 63 Warner AB, McQuade JL. Modifiable Host Factors in Melanoma: Emerging Evidence for Obesity, Diet, Exercise, and the Microbiome. Curr Oncol Rep 2019; 21: 72
• 64 Shaikh FY, Gills JJ, Sears CL. Impact of the microbiome on checkpoint inhibitor treatment in patients with non-small cell lung cancer and melanoma. EBioMedicine 2019; 48: 642-647
• 65 Spencer CN, McQuade JL, Gopalakrishnan V. et al. Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response. Science 2021; 374: 1632-1640
• 66 Clement E, Lazar I, Muller C. et al. Obesity and melanoma: could fat be fueling malignancy?. Pigment Cell Melanoma Res 2017; 30: 294-306
• 67 Li X, Liang L, Zhang M. et al. Obesity-related genetic variants, human pigmentation, and risk of melanoma. Hum Genet 2013; 132: 793-801
• 68 Yang S, Wei J, Cui YH. et al. m(6)A mRNA demethylase FTO regulates melanoma tumorigenicity and response to anti-PD-1 blockade. Nat Commun 2019; 10: 2782
• 69 de Giorgi V, Sestini S, Gori A. et al. Polymorphisms of estrogen receptors: risk factors for invasive melanoma – a prospective study. Oncology 2011; 80: 232-237
• 70 Randerson-Moor JA, Taylor JC, Elliott F. et al. Vitamin D receptor gene polymorphisms, serum 25-hydroxyvitamin D levels, and melanoma: UK case-control comparisons and a meta-analysis of published VDR data. Eur J Cancer 2009; 45: 3271-3281
• 71 Köstner K, Denzer N, Müller CS. et al. The relevance of vitamin D receptor (VDR) gene polymorphisms for cancer: a review of the literature. Anticancer Res 2009; 29: 3511-3536
• 72 Santonocito C, Paradisi A, Capizzi R. et al. Insulin-like growth factor I (CA) repeats are associated with higher melanoma’s Breslow index but not associated with the presence of the melanoma. A pilot study. . Clin Chim Acta 2008; 390: 104-109
• 73 Mai XM, Chen Y, Camargo Jr CA. et al. Cross-sectional and prospective cohort study of serum 25-hydroxyvitamin D level and obesity in adults: the HUNT study. Am J Epidemiol 2012; 175: 1029-1036
• 74 Foss YJ. Vitamin D deficiency is the cause of common obesity. Med Hypotheses 2009; 72: 314-321
• 75 Holick MF. Vitamin D deficiency. N Engl J Med 2007; 357: 266-281
• 76 Pereira-Santos M, Costa PR, Assis AM. et al. Obesity and vitamin D deficiency: a systematic review and meta-analysis. Obes Rev 2015; 16: 341-349
• 77 Vanlint S. Vitamin D and obesity. Nutrients 2013; 5: 949-956
• 78 Carrelli A, Bucovsky M, Horst R. et al. Vitamin D Storage in Adipose Tissue of Obese and Normal Weight Women. J Bone Miner Res 2017; 32: 237-242
• 79 Garland CF, Garland FC. Do sunlight and vitamin D reduce the likelihood of colon cancer?. Int J Epidemiol 1980; 9: 227-231
• 80 Reichrath J, Saternus R, Vogt T. Endocrine actions of vitamin D in skin: Relevance for photocarcinogenesis of non-melanoma skin cancer, and beyond. Mol Cell Endocrinol 2017; 453: 96-102
• 81 Reichrath J, Reichrath S. The relevance of the vitamin D endocrine system (VDES) for tumorigenesis, prevention, and treatment of non-melanoma skin cancer (NMSC): Present concepts and future perspectives. Dermatoendocrinol 2013; 5: 38-50
• 82 Moukayed M, Grant WB. The roles of UVB and vitamin D in reducing risk of cancer incidence and mortality: A review of the epidemiology, clinical trials, and mechanisms. Rev Endocr Metab Disord 2017; 18: 167-182
• 83 Grant WB. Roles of Solar UVB and Vitamin D in Reducing Cancer Risk and Increasing Survival. Anticancer Res 2016; 36: 1357-1370
• 84 Moukayed M, Grant WB. Molecular link between vitamin D and cancer prevention. Nutrients 2013; 5: 3993-4021
• 85 Slominski AT, Brożyna AA, Zmijewski MA. et al. Vitamin D signaling and melanoma: role of vitamin D and its receptors in melanoma progression and management. Lab Invest 2017; 97: 706-724
• 86 Reichrath J, Rass K. Ultraviolet damage, DNA repair and vitamin D in nonmelanoma skin cancer and in malignant melanoma: an update. Adv Exp Med Biol 2014; 810: 208-233
• 87 Reichrath J, Reichrath S, Heyne K. et al. Tumor suppression in skin and other tissues via cross-talk between vitamin D- and p53-signaling. Front Physiol 2014; 5: 166
• 88 Brożyna AA, Hoffman RM, Slominski AT. Relevance of Vitamin D in Melanoma Development, Progression and Therapy. Anticancer Res 2020; 40: 473-489
• 89 Campbell MJ, Elstner E, Holden S. et al. Inhibition of proliferation of prostate cancer cells by a 19-nor-hexafluoride vitamin D3 analogue involves the induction of p21waf1, p27kip1 and E-cadherin. J Mol Endocrinol 1997; 19: 15-27
• 90 Kawa S, Nikaido T, Aoki Y. et al. Vitamin D analogues up-regulate p21 and p27 during growth inhibition of pancreatic cancer cell lines. Br J Cancer 1997; 76: 884-889
• 91 Chen K, Perez-Stable C, D’Ippolito G. et al. Human bone marrowderived stem cell proliferation is inhibited by hepatocyte growth factor via increasing the cell cycle inhibitors p53, p21 and p27. Bone 2011; 49: 1194-1204
• 92 Luo W, Chen Y, Liu M. et al. EB1089 induces Skp2-dependent p27 accumulation, leading to cell growth inhibition and cell cycle G1 phase arrest in human hepatoma cells. Cancer Invest 2009; 27: 29-37
• 93 Newton-Bishop JA, Beswick S, Randerson-Moor J. et al. Serum 25-hydroxyvitamin D3 levels are associated with breslow thickness at presentation and survival from melanoma. J Clin Oncol 2009; 27: 5439-5444
• 94 Wyatt C, Lucas RM, Hurst C. et al. Vitamin D deficiency at melanoma diagnosis is associated with higher Breslow thickness. PLoS One 2015; 10: e0126394
• 95 Fang S, Sui D, Wang Y. et al. Association of Vitamin D Levels With Outcome in Patients With Melanoma After Adjustment For C-Reactive Protein. J Clin Oncol 2016; 34: 1741-1747
• 96 Cattaruzza MS, Pisani D, Fidanza L. et al. 25-Hydroxyvitamin D serum levels and melanoma risk: a case-control study and evidence synthesis of clinical epidemiological studies. Eur J Cancer Prev 2019; 28: 203-211
• 97 Hardie CM, Elliott F, Chan M. et al. Environmental Exposures Such as Smoking and Low Vitamin D Are Predictive of Poor Outcome in Cutaneous Melanoma rather than Other Deprivation Measures. J Invest Dermatol 2020; 140: 327-337.e2
• 98 Moreno-Arrones OM, Zegeer J, Gerbo M. et al. Decreased vitamin D serum levels at melanoma diagnosis are associated with tumor ulceration and high tumor mitotic rate. Melanoma Res 2019; 29: 664-667
• 99 Johansson H, Spadola G, Tosti G. et al. Vitamin D Supplementation and Disease-Free Survival in Stage II Melanoma: A Randomized Placebo Controlled Trial. Nutrients 2021; 13: 1931
• 100 Stenehjem JS, Veierød MB, Nilsen LT. et al. Anthropometric factors and Breslow thickness: prospective data on 2570 cases of cutaneous melanoma in the population-based Janus Cohort. BrJ Dermatol 2018; 179: 632-641
• 101 Skowron F, Bérard F, Balme B. et al. Role of obesity on the thickness of primary cutaneous melanoma. J Eur Acad Dermatol Venereol 2015; 29: 262-269
• 102 Reeves GK, Pirie K, Beral V. et al. Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study. Bmj 2007; 335: 1134
• 103 Calle EE, Rodriguez C, Walker-Thurmond K. et al. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 2003; 348: 1625-1638
• 104 Moliterni E, Paolino G, Veronese N. et al. Prognostic correlation between vitamin D serological levels, Body Mass Index and clinical-pathological features in melanoma patients. G Ital Dermatol Venereol 2018; 153: 732-733
• 105 Newton-Bishop JA, Davies JR, Latheef F. et al. 25-Hydroxyvitamin D2/D3 levels and factors associated with systemic inflammation and melanoma survival in the Leeds Melanoma Cohort. Int J Cancer 2015; 136: 2890-2899
• 106 Beswick S, Affleck P, Elliott F. et al. Environmental risk factors for relapse of melanoma. Eur J Cancer 2008; 44: 1717-1725
• 107 Zopfs DA-O, Theurich S, Große Hokamp N. et al. Single-slice CT measurements allow for accurate assessment of sarcopenia and body composition. Eur Radiol 2020; 30: 1701-1708
• 108 Jee SH, Sull JW, Park J. et al. Body-mass index and mortality in Korean men and women. N Engl J Med 2006; 355: 779-787
• 109 Seo MH, Lee WY, Kim SS. et al. 2018 Korean Society for the Study of Obesity Guideline for the Management of Obesity in Korea. J Obes Metab Syndr 2019; 28: 40-45
• 110 World Health Organization (WHO) Regional Office for the Western Pacific. The Asia-Pacific perspective: redefining obesity and its treatment. Sydney: Health Communications Australia; 2000
• 111 Kim JE, Chung BY, Sim CY. et al. Clinicopathologic Features and Prognostic Factors of Primary Cutaneous Melanoma: a Multicenter Study in Korea. J Korean Med Sci 2019; 34: e126
• 112 Pflug NA-O, Vitus M, Knuever J. et al. Treatment-specific evaluation of the modified Glasgow-Prognostic-Score in patients with advanced cutaneous melanoma. J Eur Acad Dermatol Venereol 2021; 35: e879-e883
• 113 Trommer MA-O, Kinsky J, Adams AA-O. et al. Addition of Radiotherapy to Immunotherapy: Effects on Outcome of Different Subgroups Using a Propensity Score Matching. Cancers (Basel) 2020; 12: 2429
• 114 Naik GS, Waikar SS, Johnson AEW. et al. Complex inter-relationship of body mass index, gender and serum creatinine on survival: exploring the obesity paradox in melanoma patients treated with checkpoint inhibition. J Immunother Cancer 2019; 7: 89
• 115 Cortellini A, Bersanelli M, Buti S. et al. A multicenter study of body mass index in cancer patients treated with anti-PD-1/PD-L1 immune checkpoint inhibitors: when overweight becomes favorable. J Immunother Cancer 2019; 7: 57
• 116 Richtig G, Hoeller C, Wolf M. et al. Body mass index may predict the response to ipilimumab in metastatic melanoma: An observational multi-centre study. PLoS One 2018; 13: e0204729