Occupational exposure to arsenic, mercury and UV radiation and risk of melanoma: a case-control study from Italy.

BACKGROUND: Melanoma is mainly caused by sunlight radiation, but other environmental risk factors are not well known. We investigated the association between cutaneous melanoma and occupational exposure to arsenic, mercury and UV radiation. METHODS: A hospital-based case-control study was conducted in the inpatient wards of IDI-San Carlo Rome, Italy, including 304 incident cases of cutaneous melanoma and 305 frequency-matched controls. Detailed sociodemographic, clinical and host-related factors were collected, and all participants were physically examined using dermoscopy and following standard protocol for recording pigmented lesions. Four experts assessed exposure to arsenic, mercury and UV radiation based on occupational history. A multidimensional variable was created for each risk factor, by combining intensity and probability of exposure. Multivariable logistic regression models were run to calculate odds ratios (OR) and 95% confidence intervals (CI) of the association between exposure to these agents and melanoma. RESULTS: A total of 5.4% of the cases vs 2.4% of the controls were exposed to arsenic (OR = 3.12; 95% CI = 1.10-8.86 for high probability and high exposure to arsenic) after controlling for sex, age, smoking status, number of nevi, phototype and history of sunburns in childhood/adolescence. Occupational exposure to mercury and UV radiation was not associated with the risk of melanoma. CONCLUSIONS: Subjects exposed to arsenic at the workplace may be at increased risk of developing cutaneous melanoma in comparison to subjects not exposed to this agent. Further studies should be designed to investigate occupational exposure to arsenic and mercury and melanoma and confirm the findings are warranted.

Differences in individual and environmental factors between cutaneous melanoma and atypical Spitz tumour in children and adolescents.

It is not known if children and adolescents with atypical Spitz tumour and cutaneous melanoma differ in terms of etiological factors. The aim of this study was to explain differences in individual and environmental factors between cutaneous melanoma and atypical Spitz tumour. In the context of a study on melanocytic lesions, all subjects aged under 20 years with either cutaneous melanoma or atypical Spitz tumour were included (N = 105). Information on socio-demographic characteristics, individual and environmental factors were collected for both mother and child. The Fisher's exact test and the Mann-Whitney U test were used for categorical variables and continuous variables respectively. A multivariate logistic model was used to explain differences in outcome by differences in explanatory variables. In comparison to patients with cutaneous melanoma, patients with atypical Spitz tumour had less freckles (p = 0.020), lower number of common nevi (p = 0.002), and lower body mass index (p = 0.001) and experienced less sunburns episodes (p = 0.008). However, in the multivariate analysis, only a low number of common nevi remained statistically significant. Children and adolescents with cutaneous melanoma have a high number of nevi in comparison to the same-age group with atypical Spitz tumour.Conclusion: The results of this study suggest that the only difference in individual and environmental risk factors between cutaneous melanoma and atypical Spitz tumour in children and adolescents is the number of nevi. What is Known: •Atypical Spitz tumours and cutaneous melanoma in children and adolescents are clinically similar, but compared with melanoma, they have a good overall prognosis. •Risk factors for cutaneous melanoma in children and adolescents are similar to the ones found in adults in the literature What is New: •Differences in individual and environmental risk factors for atypical Spitz tumour in children and adolescents are described for the first time in this study. •Individual and environmental factors for atypical Spitz tumour in children and adolescents are comparable to cutaneous melanoma, except for the presence of low number of nevi.

Mediterranean diet, walking outdoors and polypharmacy in older patients with type II diabetes.

BACKGROUND: Polypharmacy and its adverse health effects is an emerging public health issue, with increasing prevalence among patients with multiple chronic conditions, such as older adults with diabetes. A healthy lifestyle has been shown to improve both diabetes and polypharmacy incidence. We conducted a cross-sectional study to investigate the association of a healthy lifestyle with polypharmacy and comorbidities in older people with diabetes. METHODS: All out-patients from January 2013 to June 2015 with type II diabetes aged 65 years or more from a Lazio Region reference centre for diabetes were included in the study. Socio-demographic, clinical and lifestyle data were collected from medical records and through face-to-face standardized questionnaires. The comorbidity-polypharmacy score (CPS) was used to characterize the overall patients' frailty, by assessing concurrently the presence of comorbidities and polypharmacy. The cumulative logit model was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Adjusted ORs for age, sex, body mass index, physical activity and cognitive status, showed that CPS score was inversely related to weekly consumption of cruciferous vegetables (OR: 0.56, 95% CI: 0.35-0.90; P-trend = 0.015), leafy green vegetables (OR: 0.54, 95% CI: 0.33-0.87; P-trend = 0.013) and daily intake of fruits (OR: 0.63, 95% CI: 0.41-0.97; P-trend = 0.036). Walking outdoors was found inversely related to CPS score (age- and sex-adjusted OR: 0.60, 95% CI: 0.42-0.86). CONCLUSION: Our findings suggest that eating some dietary factors present in the Mediterranean diet and walking outdoors regularly is associated with a lower intensity of medicines need to treat comorbidities among older people with diabetes.

Melanoma and Vitiligo: In Good Company.

Cutaneous melanoma represents the most aggressive form of skin cancer, whereas vitiligo is an autoimmune disorder that leads to progressive destruction of skin melanocytes. However, vitiligo has been associated with cutaneous melanoma since the 1970s. Most of the antigens recognized by the immune system are expressed by both melanoma cells and normal melanocytes, explaining why the autoimmune response against melanocytes that led to vitiligo could be also present in melanoma patients. Leukoderma has been also observed as a side effect of melanoma immunotherapy and has always been associated with a favorable prognosis. In this review, we discuss several characteristics of the immune system responses shared by melanoma and vitiligo patients, as well as the significance of occurrence of leukoderma during immunotherapy, with special attention to check-point inhibitors.

Occupational prestige, social mobility and the association with lung cancer in men.

BACKGROUND: The nature of the association between occupational social prestige, social mobility, and risk of lung cancer remains uncertain. Using data from the international pooled SYNERGY case-control study, we studied the association between lung cancer and the level of time-weighted average occupational social prestige as well as its lifetime trajectory. METHODS: We included 11,433 male cases and 14,147 male control subjects. Each job was translated into an occupational social prestige score by applying Treiman's Standard International Occupational Prestige Scale (SIOPS). SIOPS scores were categorized as low, medium, and high prestige (reference). We calculated odds ratios (OR) with 95 % confidence intervals (CI), adjusting for study center, age, smoking, ever employment in a job with known lung carcinogen exposure, and education. Trajectories in SIOPS categories from first to last and first to longest job were defined as consistent, downward, or upward. We conducted several subgroup and sensitivity analyses to assess the robustness of our results. RESULTS: We observed increased lung cancer risk estimates for men with medium (OR = 1.23; 95 % CI 1.13-1.33) and low occupational prestige (OR = 1.44; 95 % CI 1.32-1.57). Although adjustment for smoking and education reduced the associations between occupational prestige and lung cancer, they did not explain the association entirely. Traditional occupational exposures reduced the associations only slightly. We observed small associations with downward prestige trajectories, with ORs of 1.13, 95 % CI 0.88-1.46 for high to low, and 1.24; 95 % CI 1.08-1.41 for medium to low trajectories. CONCLUSIONS: Our results indicate that occupational prestige is independently associated with lung cancer among men.

Determinants of exclusive breastfeeding cessation: identifying an "at risk population" for special support.

UNLABELLED: A study was conducted with 542 women, who gave birth in the hospital G.B. Grassi in Rome, to investigate risk factors for exclusive breastfeeding. Clinical data was collected from clinical records at delivery. Information on psycho-socio-demographic characteristics was obtained by standardized questionnaires at delivery. Data on breastfeeding practice and the use of pacifier were collected at delivery and for 24 weeks' postpartum. The outcome of the study was exclusive breastfeeding for at least 4 months (yes/no). In the multivariate analysis, planned caesarean (OR 2.40, 95 % CI 1.06-5.43) and women with two or more psychological distress conditions (past episodes of depression, insomnia, perceive birth as a traumatic event) versus none were at a greater odds of stopping exclusive breastfeeding before 4 months (OR 3.42, 95 % CI 1.15-10.2). The use of pacifiers within the first 2 weeks postpartum (OR 2.38, 95 % CI 1.35-4.20) but not after 2 weeks (OR 0.86, 95 % CI 0.43-1.72) versus no use was also associated with an increased odds. A protective effect was found for antenatal classes (OR 0.57, 95 % CI 0.35-0.95). CONCLUSION: This study suggests that the type of delivery, antenatal classes, psychological distress conditions and the use of pacifiers in the first 2 weeks of a baby's life are independent factors associated with exclusive breastfeeding.

The potential impact of dietary choices on melanoma risk: an anti-inflammatory diet.

The role of inflammation in the aetiology of cancer is recognized. However, no study yet examined the association between an anti-inflammatory diet and cutaneous melanoma and explored whether it could be modified by genetic variations in cyclooxygenase-2 (COX-2), a key enzyme in inflammation. A case-control study was conducted in the IDI-IRCCS hospital in Rome, Italy with 273 cases of primary cutaneous melanoma and 269 controls frequency matched to cases. Information on socio-demographic and pigmentary characteristics, medical history, sun exposure and dietary habits were collected for all subjects. The - 765G > C polymorphism was identified in DNA extracted from blood samples. An anti-inflammatory diet score was created. Logistic regression models were fitted to obtain odds ratios (ORs) and 95% confidence intervals (CIs). A high anti-inflammatory diet score (≥ 8 anti-inflammatory dietary items) was associated with a decreased risk of cutaneous melanoma (OR: 0.29; 95%CI: 0.17-0.49, Ptrend < 0.0001) after adjusting for sex, age, education, number of common nevi, skin photo-type, solar lentigines and sunburns in childhood. COX-2 -765 G > C polymorphism was not an independent risk factor for cutaneous melanoma. Although interaction between - 765G > C genotypes and anti-inflammatory diet score was not statistically significant (p = 0.25), when stratified by -765 G > C genotypes the effect of the anti-inflammatory diet was slightly more pronounced for participants carrying - 765GG (OR: 0.17; 95%CI: 0.06-0.47, Ptrend < 0.001). Our study findings suggest that adherence to an anti-inflammatory diet is associated with a decreased risk of developing cutaneous melanoma. These results suggest the potential impact of dietary choices on melanoma risk.

Lung cancer risk among hairdressers: a pooled analysis of case-control studies conducted between 1985 and 2010.

Increased lung cancer risks among hairdressers were observed in large registry-based cohort studies from Scandinavia, but these studies could not adjust for smoking. Our objective was to evaluate the lung cancer risk among hairdressers while adjusting for smoking and other confounders in a pooled database of 16 case-control studies conducted in Europe, Canada, China, and New Zealand between 1985 and 2010 (the Pooled Analysis of Case-Control Studies on the Joint Effects of Occupational Carcinogens in the Development of Lung Cancer). Lifetime occupational and smoking information was collected through interviews with 19,369 cases of lung cancer and 23,674 matched population or hospital controls. Overall, 170 cases and 167 controls had ever worked as hairdresser or barber. The odds ratios for lung cancer in women were 1.65 (95% confidence interval (CI): 1.16, 2.35) without adjustment for smoking and 1.12 (95% CI: 0.75, 1.68) with adjustment for smoking; however, women employed before 1954 also experienced an increased lung cancer risk after adjustment for smoking (odds ratio = 2.66, 95% CI: 1.09, 6.47). The odds ratios in male hairdressers/barbers were generally not elevated, except for an increased odds ratio for adenocarcinoma in long-term barbers (odds ratio = 2.20, 95% CI: 1.02, 4.77). Our results suggest that the increased lung cancer risks among hairdressers are due to their smoking behavior; single elevated risk estimates should be interpreted with caution and need replication in other studies.

The protective effect of coffee consumption on cutaneous melanoma risk and the role of GSTM1 and GSTT1 polymorphisms.

PURPOSES: The authors examined the association between coffee consumption and cutaneous melanoma and the implication of GSTM1 and GSTT1 polymorphisms. METHODS: A hospital-based case-control study was conducted in the inpatient wards of IDI-San Carlo Rome, Italy, including 304 incident cases of cutaneous melanoma and 305 controls. Information on socio-demographic characteristics, medical history, smoking, sun exposure, pigmentary characteristics and diet was collected for all subjects. Within the study, individual patterns at two polymorphic genes (GSTM1 and GSTT1) belonging to glutathione S-transferases family were investigated in 188 cases of cutaneous melanoma and 152 controls. Logistic regression was the method used to estimate odds ratio and 95 % confidence intervals. RESULTS: High frequency of coffee drinking (>once daily), compared with low-frequency consumption of coffee (≤7 times weekly) was associated with a protective effect for cutaneous melanoma (OR 0.46; 95 % CI 0.31-0.68) after adjusting for sex, age, education, hair colour, common nevi, skin phototype, and sunburn episodes in childhood. When stratified by GSTM1 and GSTT1 genotype, the protective effect of coffee was extremely high for subjects with both GSTM1 and GSTT1 null polymorphisms (OR 0.01; 95 % CI 0.0003-0.54). CONCLUSIONS: Our results show a protective effect of coffee consumption for cutaneous melanoma, in particular for those with homozygous deletion for GSTM1 and GSTT1.

Early inflammatory biomarkers and melanoma survival.

BACKGROUND: Few studies have investigated the role of inflammatory markers in predicting cutaneous melanoma survival. The aim of the study was to identify, if any, early inflammatory markers in the prognosis of all stages of primary cutaneous melanoma. METHODS: We conducted a 10-year cohort study among 2,141 melanoma patients from the same geographic area (Lazio) with primary cutaneous melanoma diagnosed between January 2005 and December 2013. In situ cutaneous melanoma was excluded from the analysis (N = 288), leaving 1,853 cases of invasive cutaneous melanoma. The following hematological markers were obtained from clinical records: white blood cells count (WBC), count and percentages of neutrophils, basophils, monocytes, lymphocytes, and large unstained cells (LUC). Survival probability was estimated by Kaplan-Meier methods, and prognostic factors were evaluated by multivariate analysis (Cox proportional hazards model). RESULTS: In the multivariate analysis, high levels of NLR (>2.1 vs. ≤2.1, HR: 1.61; 95% CI: 1.14-2.29, P = 0.007) and high levels of d-NLR (>1.5 vs. ≤1.5, HR: 1.65; 95% CI: 1.16-2.35, P = 0.005) were independently associated with an increased risk of 10-year melanoma mortality. However, when we stratified by Breslow thickness and clinical stage, we observed that NLR and d-NLR were good markers of prognosis only for patients with Breslow thickness of 2.0 mm and more (NLR, HR: 1.62; 95% CI: 1.04-2.50; d-NLR, HR: 1.69; 95% CI: 1.09-2.62) or clinical stage II-IV (NLR, HR: 1.55; 95% CI: 1.01-2.37; d-NLR, HR: 1.72; 95% CI: 1.11-2.66), independent of other prognostic factors. CONCLUSION: We suggest that a combination of NLR and Breslow thickness may be a useful, cheap, and readily available prognostic marker for cutaneous melanoma survival.

Tumoral inflammatory infiltrate does not predict metastases in thin primary cutaneous melanomas.

BACKGROUND: In cutaneous melanomas in general, tumor inflammatory infiltrate (TII) can protect against distant metastases, but there is no consensus when only thin primary cutaneous melanomas (TPCM) are considered. OBJECTIVE: To investigate the presence of TII in TPCM and the relationship between TII and the occurrence of metastases. METHODS: Case-control study including 50 patients with TPCM, 22 metastatic (MC group) and 28 non-metastatic (NMC group). The presence of TII was evaluated and, if present, qualified as mild, moderate or marked. RESULTS: The mean age was 50.7 years in the MC and 56.2 years in the NMC group (p = 0.234), and the male sex predominated in the MC group (63.6%). The average Breslow thickness was higher in the MC when compared to that observed in the NMC (respectively 0.8 vs. 0.6 mm, p = 0.012). The presence of ulceration occurred in 22.7% of the MC and 17.9% of the NMC (p = 0.732). TII was present in all 50 TPCM, being marked or moderate in 67.9% of the NMC and 54.5% in the MC group (p = 0.503). In the multivariate analysis, the presence of moderate and marked TII had an Odds Ratio (OR) of 0.57 (95% Confidence Interval [CI]: 0.18‒1.8) and adjusted OR of 0.68 (95% CI 0.13‒3.99). STUDY LIMITATIONS: Small sample size. CONCLUSIONS: TII was present in all TPCM (with and without metastases), and it was not possible to demonstrate a protective effect of TII against the appearance of metastases.

Re-evaluation of erythritol (E 968) as a food additive.

This opinion addresses the re-evaluation of erythritol (E 968) as food additive and an application for its exemption from the laxative warning label requirement as established under Regulation (EU) No 1169/2011. Erythritol is a polyol obtained by fermentation with Moniliella pollinis BC or Moniliella megachiliensis KW3-6, followed by purifications and drying. Erythritol is readily and dose-dependently absorbed in humans and can be metabolised to erythronate to a small extent. Erythritol is then excreted unchanged in the urine. It does not raise concerns regarding genotoxicity. The dataset evaluated consisted of human interventional studies. The Panel considered that erythritol has the potential to cause diarrhoea in humans, which was considered adverse because its potential association with electrolyte and water imbalance. The lower bound of the range of no observed adverse effect levels (NOAELs) for diarrhoea of 0.5 g/kg body weight (bw) was identified as reference point. The Panel considered appropriate to set a numerical acceptable daily intake (ADI) at the level of the reference point. An ADI of 0.5 g/kg bw per day was considered by the Panel to be protective for the immediate laxative effect as well as potential chronic effects, secondary to diarrhoea. The highest mean and 95th percentile chronic exposure was in children (742 mg/kg bw per day) and adolescents (1532 mg/kg bw per day). Acute exposure was maximally 3531 mg/kg bw per meal for children at the 99th percentile. Overall, the Panel considered both dietary exposure assessments an overestimation. The Panel concluded that the exposure estimates for both acute and chronic dietary exposure to erythritol (E 968) were above the ADI, indicating that individuals with high intake may be at risk of experiencing adverse effects after single and repeated exposure. Concerning the new application, the Panel concluded that the available data do not support the proposal for exemption.

Cigarette smoking and lung cancer--relative risk estimates for the major histological types from a pooled analysis of case-control studies.

Lung cancer is mainly caused by smoking, but the quantitative relations between smoking and histologic subtypes of lung cancer remain inconclusive. By using one of the largest lung cancer datasets ever assembled, we explored the impact of smoking on risks of the major cell types of lung cancer. This pooled analysis included 13,169 cases and 16,010 controls from Europe and Canada. Studies with population controls comprised 66.5% of the subjects. Adenocarcinoma (AdCa) was the most prevalent subtype in never smokers and in women. Squamous cell carcinoma (SqCC) predominated in male smokers. Age-adjusted odds ratios (ORs) were estimated with logistic regression. ORs were elevated for all metrics of exposure to cigarette smoke and were higher for SqCC and small cell lung cancer (SCLC) than for AdCa. Current male smokers with an average daily dose of >30 cigarettes had ORs of 103.5 (95% confidence interval (CI): 74.8-143.2) for SqCC, 111.3 (95% CI: 69.8-177.5) for SCLC and 21.9 (95% CI: 16.6-29.0) for AdCa. In women, the corresponding ORs were 62.7 (95% CI: 31.5-124.6), 108.6 (95% CI: 50.7-232.8) and 16.8 (95% CI: 9.2-30.6), respectively. Although ORs started to decline soon after quitting, they did not fully return to the baseline risk of never smokers even 35 years after cessation. The major result that smoking exerted a steeper risk gradient on SqCC and SCLC than on AdCa is in line with previous population data and biological understanding of lung cancer development.

Expression of vascular endothelial growth factor-C in primary cutaneous melanoma predicts sentinel lymph node positivity.

BACKGROUND: Vascular endothelial growth factor-C (VEGF-C), a lymphatic vessel growth factor, has been involved in the formation of lymph nodal metastases in different tumor types. Early evidences indicate that VEGF-C expression in human primary melanoma could be predictive of lymph nodal metastases, whereas the role of lymphangiogenesis is still controversial. METHODS: By immunohistochemical analysis, we investigated VEGF-C or CC chemokine receptor 7 expression, together with the lymphatic and blood vessel network, in 36 patients with primary skin melanomas and metastases at the sentinel lymph node biopsy (SLN-positive), and 26 melanoma patients with negative SLN biopsy (SLN-negative). RESULTS: We found that VEGF-C expression in primary melanoma specimens was significantly associated with SLN-positive (p < 0.001), particularly in thin melanomas. An association between augmented peritumoral lymphatic vessel area and SLN-positive (p < 0.02) was also seen. Conversely, no association between either expression of the CC chemokine receptor 7 in the primary tumor, or intratumoral lymphatic vessel or peritumoral and intratumoral blood vessel area, and SLN-positive was found. CONCLUSIONS: Our results, taking into account the expression of either VEGF-C or related histopathological markers, indicated the possibility to use VEGF-C immunohistochemistry as a marker of metastatic progression, especially in thin cutaneous melanomas.

The combination of depressive symptoms and smoking shorten life expectancy among the aged.

BACKGROUND: Depression is a potential risk factor for mortality among the aged and it is also associated with other chronic diseases and unhealthy lifestyles that may also affect mortality. The purpose of this study was to investigate the association between depressive symptoms and mortality, controlling for health, nutritional status, and life-style factors. METHODS: A cohort of elderly people (N = 167) was followed-up for ten years. Information on socio-demographic characteristics, medical history, smoking, and alcohol consumption was collected. The primary outcome was all-cause mortality; the secondary outcome was cancer-specific mortality. The Geriatric Depression Scale (GDS-15) was used to assess depression. Using a multivariable Cox proportional hazards regression, we examined the association between depressive symptoms and mortality. RESULTS: Elderly people with depression (scoring above the depression cut-off of 7) had a 53% increased risk of mortality (relative risk (RR) 1.53; 95%CI: 1.05-2.24) compared to non-depressed subjects. The combination of depressive symptoms with smoking was associated with a particularly higher risk of mortality (RR: 2.61; 95%CI: 1.28-5.31), after controlling for potential confounders. CONCLUSIONS: Depressive symptoms are associated with a significantly increased risk of all-cause mortality. The combination of depressive symptoms and smoking shorten life expectancy among the aged.

Melanoma on tattoos: a case study and review of the literature

Background: Decorative tattooing is a very widespread and constantly increasing practice, especially among young people. Objectives: Here, we report a case study of melanoma occurring on a tattoo on the left arm and provide an overview of all cases reported so far. Materials & Methods: A systematic literature search of publications was conducted from inception to September 2021 via Medline (PubMed), Scopus and Google Scholar, in order to identify all cases of primitive melanomas arising on tattoos. Results: In total, 35 cases (32 males, three females) of melanoma arising on tattoos on skin were identified. Interestingly, most melanomas occurred on dark blue (10/35), black (12/35) or blue tattoos (3/35). Conclusion: Due to the low number of melanoma cases arising on tattoos, it is not possible to confirm whether tattoos play a cancerogenic role. However, tattooing may make it more difficult to detect and monitor pigmented lesions, potentially delaying the diagnosis of cutaneous malignancies. Patients at high risk of melanoma should be warned about the risks associated with such procedures.

Vitiligo-specific soluble biomarkers as early indicators of response to immune checkpoint inhibitors in metastatic melanoma patients.

Immunotherapy with checkpoint inhibitors (CPIs) strongly improved the outcome of metastatic melanoma patients. However, not all the patients respond to treatment and identification of prognostic biomarkers able to select responding patients is currently of outmost importance. Considering that development of vitiligo-like depigmentation in melanoma patients represents both an adverse event of CPIs and a favorable prognostic factor, we analyzed soluble biomarkers of vitiligo to validate them as early indicators of response to CPIs. Fifty-seven metastatic melanoma patients receiving CPIs were enrolled and divided according to the best overall response to treatment. Patient sera were evaluated at pre-treatment and after 1 and 3 months of therapy. We found that basal CD25 serum levels were higher in stable and responding patients and remained higher during the first 3 months of CPI therapy compared to non-responders. CXCL9 was absent in non-responding patients before therapy beginning. Moreover, an increase of CXCL9 levels was observed at 1 and 3 months of therapy for all patients, although higher CXCL9 amounts were present in stable and responding compared to non-responding patients. Variations in circulating immune cell subsets was also analyzed, revealing a reduced number of regulatory T lymphocytes in responding patients. Altogether, our data indicate that a pre-existing and maintained activation of the immune system could be an indication of response to CPI treatment in melanoma patients.

Vitiligo-like leukoderma as an indicator of clinical response to immune checkpoint inhibitors in late-stage melanoma patients.

PURPOSE: Although development of immune checkpoint inhibitors has revolutionized the treatment of metastatic melanoma, more than a half of treated patients experience disease progression during therapy. Cases of spontaneous vitiligo-like leukoderma have been described in melanoma patients and have been associated with a favorable outcome. This vitiligo-like leukoderma can also appear in melanoma patients undergoing immune therapies such as immune checkpoint inhibitors. However, no consensus exists about the relationship between vitiligo-like leukoderma onset and improved overall survival. Our study investigates the possible association between the onset of vitiligo-like leukoderma during immune checkpoint inhibitor treatment and a better prognosis. METHODS: A non-concurrent cohort study was conducted by identifying retrospectively 280 patients who had inoperable or metastatic melanoma and had undergone immune therapy with checkpoint inhibitors in any line of treatment. Toxicities developed during therapy were evaluated. RESULTS: Among the 280 study participants, 50% developed at least one type of toxicity, and vitiligo-like leukoderma was observed in 43 patients (15.4%). In the multivariate Cox model, a protective effect for mortality was observed for patients with vitiligo-like leukoderma development (HR : 0.23; 95% CI 0.11-0.44, p < 0.0001). In a sub-group analysis comprising only cutaneous melanoma in first line of treatment (N = 153), occurrence of vitiligo-like leukoderma was also an independent predictor factor for duration of clinical benefits measured by time to the next treatment (HR: 0.17; 95% CI 0.06-0.44). CONCLUSION: Our findings indicate that onset of vitiligo-like leukoderma during melanoma treatment could be a marker of favorable outcome in patients treated with immune checkpoint inhibitors.