Obesity and risk of malignant melanoma: A meta-analysis of cohort and case–control studies

Sergentanis, Theodoros N.; Antoniadis, Antonios G.; Gogas, Helen; Antonopoulos, Constantine N.; Adami, Hans‐Olov; Ekbom, Anders; Petridou, Eleni

doi:10.1016/j.ejca.2012.08.028

Cited by 150 publications

(152 citation statements)

References 59 publications

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“…The current findings among metastatic melanoma patients contrast with prior data linking obesity with a slightly increased risk of developing melanoma, 11,12 as well as a recent analysis of melanoma patients with clinically localized disease in which higher BMI was associated with worse survival. 22 In aggregate, the findings support the presence of an “obesity paradox” across the spectrum of melanoma development, progression, and treatment response.…”

Section: Discussioncontrasting

confidence: 99%

“…5,6 However, higher BMI has also been associated with improved outcomes in some cancers, 7–9 a phenomenon dubbed the “obesity paradox.” 10 The role of obesity in melanoma has not been well-studied to date. 5 Existing data suggests that obesity is associated with an increased risk of melanoma in men 11 and increased primary tumor Breslow thickness. 12 We recently demonstrated that obesity is associated with worse outcomes in a large cohort of patients with surgically resected melanoma.…”

Section: Introductionmentioning

confidence: 99%

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Association of body-mass index and outcomes in patients with metastatic melanoma treated with targeted therapy, immunotherapy, or chemotherapy: a retrospective, multicohort analysis

McQuade

Daniel

Hess

et al. 2018

The Lancet Oncology

527

459

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Background Obesity has been linked to increased mortality in several cancer types; however, the relationship between obesity and survival in metastatic melanoma is unknown. The aim of this study was to examine the association between BMI, progression-free survival (PFS), and overall survival (OS) in metastatic melanoma. Methods This study included 6 independent cohorts for a total of 1918 metastatic melanoma patients. These included two targeted therapy cohorts [randomized control trials (RCTs) of dabrafenib and trametinib (n=599) and vemurafenib and cobimetinib (n=240)], two immunotherapy cohorts [RCT of ipilimumab + dacarbazine (DTIC) (n=207) and a retrospective cohort treated with anti-PD-1/PDL-1 (n=331)], and two chemotherapy cohorts [RCT DTIC cohorts (n=320 and n=221)]. BMI was classified as normal (BMI 18 to <25; n=694 of 1918, 36.1%) overweight (BMI 25-29.9; n=711, 37.1%) or obese (BMI≥30; n=513, 26.7%). The primary outcomes were the association between BMI, PFS, and OS, stratified by treatment type and sex. These exploratory analyses were based on previously reported intention-to-treat data from the RCTs. The effect of BMI on PFS and OS was assessed by multivariable-adjusted Cox models in independent cohorts. In order to provide a more precise estimate of the association between BMI and outcomes, as well as the interaction between BMI, sex, and therapy type, adjusted hazard ratios were combined in mixed-effects meta-analyses and heterogeneity was explored with meta-regression analyses. Findings In the pooled analysis, obesity, as compared to normal BMI, was associated with improved survival in patients with metastatic melanoma [average adjusted hazard ratio (HR) and 95% CI: 0.77 (0.66-0.90) and 0.74 (0.58-0.95) for PFS and OS, respectively]. The survival benefit associated with obesity was restricted to patients treated with targeted therapy [0.72 (0.57-0.91) and 0.60 (0.45-0.79) for PFS and OS, respectively] and immunotherapy [0.75 (0.56-1.00) and 0.64 (0.47-0.86)]. No associations were observed with chemotherapy [0.87 (0.65-1.17) and 1.03 (0.80-1.34); treatment p for interaction = 0.61 and 0.01, for PFS and OS, respectively]. The prognostic effect of BMI with targeted and immune therapies differed by sex with pronounced inverse associations in males [PFS 0.67 (0.53-0.84) and OS 0.53 (0.40-0.70)], but not females [PFS 0.92 (0.70-1.23) and OS 0.85 (0.61-1.18), sex p for interaction= 0.08 and 0.03, for PFS and OS, respectively] Interpretation Obesity is associated with improved PFS and OS in metastatic melanoma, driven by strong associations observed in males treated with targeted or immune therapy. The magnitude of the benefit detected supports the need for investigation into the underlying mechanism of these unexpected observations Funding ASCO/CCF Young Investigator Award and ASCO/CCF Career Development Award to JLM

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association of body-mass index and outcomes in patients with metastatic melanoma treated with targeted therapy, immunotherapy, or chemotherapy: a retrospective, multicohort analysis

McQuade

Daniel

Hess

et al. 2018

The Lancet Oncology

527

459

View full text Add to dashboard Cite

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“…In these analyses, a 1-unit increase was defined as a 10-point increase in HEI-2010, a 3-point increase in DASH index, and a 1-point increase in the GMI or IMI; these increments each correspond to ;10% of the total score range. We also investigated age, gender, and skin phototype as potential effect modifiers by conducting analyses stratified on these factors (4,(55)(56)(57). Because these analyses involved smaller sample sizes, rather than use cutoffs, which requires more df, we tested for linear trend by entering the diet quality scores as continuous variables in conditional logistic regression models.…”

Section: Methodsmentioning

confidence: 99%

Diet Quality and Risk of Melanoma in an Italian Population

Malagoli

Malavolti

Agnoli

et al. 2015

The Journal of Nutrition

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“…On average metastatic melanoma patients can only survive for 6 -9 months after diagnosis (15). It is worth noting that epidemiological studies showed a positive correlation between obesity and melanoma incidence (16,17). Mouse melanoma models also showed that obesity promoted melanoma development and progression (18,19).…”

Section: Tumorigenesis Involves Constant Communication Between Tumor mentioning

confidence: 99%

Subcutaneous Adipocytes Promote Melanoma Cell Growth by Activating the Akt Signaling Pathway

Kwan

Liu

et al. 2014

Journal of Biological Chemistry

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Background: Fatty acids affect cancer growth. Results: Melanoma in co-cultivation with subcutaneous adipocytes has an elevated level of palmitic acid that promotes melanoma growth by activating Akt signaling in a PTEN-independent manner. Conclusion: Subcutaneous adipocytes may be an exogenous source of palmitic acid for melanoma growth. Significance: Targeting an exogenous supply of palmitic acid suggests a novel therapeutic in melanoma treatment.

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Obesity and risk of malignant melanoma: A meta-analysis of cohort and case–control studies

Cited by 150 publications

References 59 publications

Association of body-mass index and outcomes in patients with metastatic melanoma treated with targeted therapy, immunotherapy, or chemotherapy: a retrospective, multicohort analysis

Association of body-mass index and outcomes in patients with metastatic melanoma treated with targeted therapy, immunotherapy, or chemotherapy: a retrospective, multicohort analysis

Diet Quality and Risk of Melanoma in an Italian Population

Subcutaneous Adipocytes Promote Melanoma Cell Growth by Activating the Akt Signaling Pathway

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