Sex disparities in melanoma outcomes: The role of biology

Nosrati, Adi; Wei, Maria L.

doi:10.1016/j.abb.2014.06.018

Cited by 56 publications

(55 citation statements)

References 143 publications

(193 reference statements)

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“…Although female sex was found to be a negative prognostic indicator in our model, the mechanisms of this remain poorly defined. Indeed, much of the current literature actually supports a survival benefit for females with advanced melanoma, although of note, much of this data preceded the advent of immune checkpoint inhibition (Manola et al , 2000; Dronca et al , 2013; Nosrati and Wei, 2014). Though it is speculated that the increased number and/or improved function of tumour-specific T-helper cells in women could underlie this clinical observation, data regarding the role of sex-hormone modulation of PD-1 are currently limited to preclinical models (Polanczyk et al , 2006, 2007).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of clinicopathological factors in PD-1 response: derivation and validation of a prediction scale for response to PD-1 monotherapy

et al. 2017

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Background:Anti-PD-1 therapy has shown significant clinical activity in advanced melanoma. We developed and validated a clinical prediction scale for response to anti- PD-1 monotherapy.Methods:A total of 315 patients with advanced melanoma treated with pembrolizumab (2 or 10 mg kg−1 Q2W or Q3W) or nivolumab (3 mg kg−1 Q2W) at four cancer centres between 2011 to 2013 served as the setting for the present cohort study. Variables with significant association to response on a univariate analysis were entered into a forward stepwise logistic regression model and were given a score based on ORs to calculate a clinical prediction scale.Results:The developed clinical prediction scale included elevated LDH (1 point), age <65 years (1 point), female sex (1 point), history of ipilimumab treatment (2 points) and the presence of liver metastasis (2 points). The scale had an area under the receiver-operating curve (AUC) of 0.73 (95% CI 0.67, 0.80) in predicting response to therapy. The predictive performance of the score was maintained in the validation cohort (AUC 0.70 (95% CI 0.58, 0.81)) and the goodness-to-fit model demonstrated good calibration.Conclusions:Based on a large cohort of patients, we developed and validated a simple five-factor prediction scale for the clinical activity of PD-1 antibodies in advanced melanoma patients. This scale can be used to stratify patients participating in clinical trials.

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Section: Discussionmentioning

confidence: 99%

Evaluation of clinicopathological factors in PD-1 response: derivation and validation of a prediction scale for response to PD-1 monotherapy

et al. 2017

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“…Lastly, melanomas have been shown to clinically respond to treatment with tamoxifen, follicle-stimulating, melatonin, and nerve growth factor hormones [24, 25]. The outcome of melanoma treatment is different in men and women [26], which also implies a role for hormones in response to treatment.…”

Section: Discussionmentioning

confidence: 99%

Sex differences in the association of cutaneous melanoma incidence rates and geographic ultraviolet light exposure

Liu‐Smith

Farhat

Arce

et al. 2017

Journal of the American Academy of Dermatology

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Background Cutaneous melanoma (CM) incidence rates continue to increase, and the reasons are unknown. Previously, we reported a unique age-specific gender difference in melanoma that suggested additional causes other than solar UV radiation. Objective This study attempted to understand whether and how UV radiation differentially impacts the CM incidence in men and women. Methods CM data and daily UV index (UVI) from 31 cancer registries were collected for association analysis. A second dataset from 42 states of the U.S.A. was used for validation. Results There was no association between log-transformed female CM rates and levels of UVI but there was a significant association between male rates and UVI and a significant association between overall rates and UVI. The 5 year age-specific rate-UVI association levels (represented by Pearson’s coefficient ρ) increased with age in men, but age-specific ρ levels remained low and unchanged in women. The significant rate-UVI association in men and non-association in women was validated in the US white population. Limitations Confounders including temperature and latitude are difficult to separate from UVI Conclusions: Ambient UVI appears to be associated with melanoma incidence in males but not in females.

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“…[24] Compared to women, men over 65 with melanoma have increased mortality rate, but the biologic factors on why this may be true remain unclear. [25] In our cohort, patients older than 50 years were less likely to be vitamin D deficient compared to those who were younger than 50 years; however, this result was borderline statistically significant (P=0.048).…”

Section: Discussionmentioning

confidence: 99%

Vitamin D deficiency is associated with a worse prognosis in metastatic melanoma

et al. 2016

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Vitamin D deficiency (≤20 ng/mL) is associated with an increased incidence and worse prognosis of various types of cancer including melanoma. A retrospective, single-center study of individuals diagnosed with melanoma from January 2007 through June 2013 who had a vitamin D (25(OH)D3) level measured within one year of diagnosis was performed to determine whether vitamin D deficiency and repletion are associated with melanoma outcome. A total of 409 individuals diagnosed with histopathology-confirmed melanoma who had an ever measured serum 25(OH)D3 level were identified. 252 individuals with a 25(OH)D3 level recorded within one year after diagnosis were included in the study and the individual and melanoma characteristics such as age, sex, Breslow thickness, ulceration, stage, mitotic rate, and LDH were obtained from the medical record. A worse melanoma prognosis was associated with vitamin D deficiency (P=0.012), higher stage (P<0.001), ulceration (P=0.001), and higher mitotic rate (P=0.001) (HR 1.93, 95% CI 1.15-3.22). In patients with stage IV metastatic melanoma, vitamin D deficiency was associated with significantly worse melanoma-specific mortality (adjusted HR 2.06, 95% CI 1.10-3.87). Patients with metastatic melanoma who were initially vitamin D deficient and subsequently had a decrease or ≤20 ng/mL increase in their 25(OH)D3 concentration had significantly worse outcomes (HR 4.68, 95% CI 1.05-20.88) compared to non-deficient patients who had a >20 ng/mL increase. Our results suggest that initial vitamin D deficiency and insufficient repletion is associated with a worse prognosis in patients with metastatic melanoma.

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Sex disparities in melanoma outcomes: The role of biology

Cited by 56 publications

References 143 publications

Evaluation of clinicopathological factors in PD-1 response: derivation and validation of a prediction scale for response to PD-1 monotherapy

Evaluation of clinicopathological factors in PD-1 response: derivation and validation of a prediction scale for response to PD-1 monotherapy

Sex differences in the association of cutaneous melanoma incidence rates and geographic ultraviolet light exposure

Vitamin D deficiency is associated with a worse prognosis in metastatic melanoma

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