Eleni Linos

Increasing Burden of Melanoma in the United States

It is controversial whether worldwide increases in melanoma incidence represent a true epidemic. Dramatic increases in incidence in the setting of relatively stable mortality trends have also been attributed to expanded skin screening and detection of biologically indolent tumors with low metastatic potential. To better understand how melanoma incidence trends varied by severity at diagnosis and factors relevant to screening access, we assessed recent United States incidence and mortality trends by histologic type, tumor thickness, and area-level socioeconomic status (SES). We obtained population-based data regarding diagnoses of invasive melanoma among non-Hispanic whites from nearly 291 million person-years of observation by the Surveillance Epidemiology and End Results (SEER) program (1992-2004). Age-adjusted incidence and mortality rates were calculated for SEER and a subset (California) for which small-area SES measure was available. Overall, melanoma incidence increased at 3.1% (P<0.001) per year. Statistically significant rises occurred for tumors of all histologic subtypes and thicknesses, including those >4 mm. Melanoma incidence rates doubled in all SES groups over a 10-year period whereas melanoma mortality rates did not increase significantly. We conclude that screening-associated diagnosis of thinner melanomas cannot explain the increasing rates of thicker melanomas among low SES populations with poorer access to screening.

Indoor tanning and non-melanoma skin cancer: systematic review and meta-analysis

Objective To synthesise the literature on indoor tanning and non-melanoma skin cancer. Design Systematic review and meta-analysis. Data sources PubMed (1966 to present), Embase (1974 to present), and Web of Science (1898 to present). Study selection All articles that reported an original effect statistic for indoor tanning and non-melanoma skin cancer were included. Articles that presented no data, such as review articles and editorials, were excluded, as were articles in languages other than English. Data extraction Two investigators independently extracted data. Random effects meta-analysis was used to summarise the relative risk of ever use versus never use of indoor tanning. Dose-response effects and exposure to indoor tanning during early life were also examined. The population attributable risk fraction for the United States population was calculated. Results 12 studies with 9328 cases of non-melanoma skin cancer were included. Among people who reported ever using indoor tanning compared with those who never used indoor tanning, the summary relative risk for squamous cell carcinoma was 1.67 (95% confidence interval 1.29 to 2.17) and that for basal cell carcinoma was 1.29 (1.08 to 1.53). No significant heterogeneity existed between studies. The population attributable risk fraction for the United States was estimated to be 8.2% for squamous cell carcinoma and 3.7% for basal cell carcinoma. This corresponds to more than 170 000 cases of non-melanoma skin cancer each year attributable to indoor tanning. On the basis of data from three studies, use of indoor tanning before age 25 was more strongly associated with both squamous cell carcinoma (relative risk 2.02, 0.70 to 5.86) and basal cell carcinoma (1.40, 1.29 to 1.52). Conclusions Indoor tanning is associated with a significantly increased risk of both basal and squamous cell skin cancer. The risk is higher with use in early life (<25 years). This modifiable risk factor may account for hundreds of thousands of cases of non-melanoma skin cancer each year in the United States alone and many more worldwide. These findings contribute to the growing body of evidence on the harms of indoor tanning and support public health campaigns and regulation to reduce exposure to this carcinogen.

International prevalence of indoor tanning: a systematic review and meta-analysis.

IMPORTANCE Indoor tanning is a known carcinogen, but the scope of exposure to this hazard is not known. OBJECTIVE To summarize the international prevalence of exposure to indoor tanning. DATA SOURCES Studies were identified through systematic searches of PubMed (1966 to present), Scopus (1823 to present), and Web of Science (1898 to present) databases, last performed on March 16, 2013. We also hand searched reference lists to identify records missed by database searches and publicly available data not yet published in the scientific literature. STUDY SELECTION Records reporting a prevalence of indoor tanning were eligible for inclusion. We excluded case-control studies, reports with insufficient study information, and reports of groups recruited using factors related to indoor tanning. Two independent investigators performed searches and study selection. Our search yielded 1976 unique records. After exclusions, 161 records were assessed for eligibility in full text, and 88 were included. DATA EXTRACTION AND SYNTHESIS Two independent investigators extracted data on characteristics of study participants, inclusion/exclusion criteria, data collection format, outcomes, and statistical methods. Random-effects meta-analyses were used to summarize the prevalence of indoor tanning in different age categories. We calculated the population proportional attributable risk of indoor tanning in the United States, Europe, and Australia for nonmelanoma skin cancer (NMSC) and melanoma. MAIN OUTCOMES AND MEASURES Ever and past-year exposure to indoor tanning. RESULTS The summary prevalence of ever exposure was 35.7% (95% CI, 27.5%-44.0%) for adults, 55.0% (33.0%-77.1%) for university students, and 19.3% (14.7%-24.0%) for adolescents. The summary prevalence of past-year exposure was 14.0% (95% CI, 11.5%-16.5%) for adults, 43.1% (21.7%-64.5%) for university students, and 18.3% (12.6%-24.0%) for adolescents. These results included data from 406 696 participants. The population proportional attributable risk were 3.0% to 21.8% for NMSC and 2.6% to 9.4% for melanoma, corresponding to more than 450 000 NMSC cases and more than 10 000 melanoma cases each year attributable to indoor tanning in the United States, Europe, and Australia. CONCLUSIONS AND RELEVANCE Exposure to indoor tanning is common in Western countries, especially among young persons. Given the large number of skin cancer cases attributable to indoor tanning, these findings highlight a major public health issue.

Effects of Reproductive and Demographic Changes on Breast Cancer Incidence in China: A Modeling Analysis

BACKGROUND Breast cancer incidence is currently low in China. However, the distribution of reproductive and lifestyle risk factors for breast cancer among Chinese women is changing rapidly. We quantified the expected effect of changes in breast cancer risk factors on future rates of breast cancer in China. METHODS We first validated and calibrated the Rosner-Colditz log-incidence breast cancer model in Chinese women who participated in the Shanghai Womens Health Study cohort (N = 74,942). We then applied the calibrated model to a representative sample of Chinese women who were aged 35-49 years in 2001 using data from the Chinese National Family Planning and Reproductive Health Survey (NFPRHS, N = 17,078) to predict the age-specific and cumulative breast cancer incidence among all Chinese women of this age group. We evaluated the relative impact of changes in modifiable risk factors, including alcohol intake, parity, postmenopausal hormone use, and adult weight gain, on cumulative incidence of breast cancer. RESULTS Breast cancer incidence in China is expected to increase substantially from current rates, estimated at 10-60 cases per 100,000 women, to more than 100 new cases per 100,000 women aged 55-69 years by 2021. We predicted 2.5 million cases of breast cancer by 2021 among Chinese women who were 35-49 years old in 2001. Modest reductions in hormone and alcohol use, and weight maintenance could prevent 270,000 of these cases. CONCLUSIONS China is on the cusp of a breast cancer epidemic. Although some risk factors associated with economic development are largely unavoidable, the substantial predicted increase in new cases of breast cancer calls for urgent incorporation of this disease in future health care infrastructure planning.

Tumor Recurrence 5 Years after Treatment of Cutaneous Basal Cell Carcinoma and Squamous Cell Carcinoma

For most cutaneous basal cell and squamous cell carcinomas (nonmelanoma skin cancers [NMSC]) data are insufficient to permit evidence-based choices among treatments. To compare tumor recurrence after treatments, we conducted a prospective cohort study of consecutive patients with primary NMSC treated with the most common treatments in two practices in 1999–2000. Recurrence was determined from medical records by observers blinded to treatment type. 24.3% of tumors (N=361) were treated with destruction with electrodessication / curettage, 38.3% (N=571) with excision, and 37.4% (N=556) with histologically-guided serial excision (Mohs surgery). Follow-up was available for 1174 patients with 1488 tumors (93.8%) at median 7.4 years; overall 5-year tumor recurrence rate [95% Confidence Interval] was 3.3% [2.3, 4.4]. Unadjusted recurrence rates did not differ after treatments: 4.9% [2.3, 7.4] after destruction, 3.5% [1.8, 5.2] after excision, and 2.1% [0.6, 3.5] after Mohs surgery (P=0.26), and no difference was seen after adjustment for risk factors. In tumors treated only with excision or Mohs surgery, the hazard of recurrence was not significantly different, even after adjustment for propensity for treatment with Mohs surgery. These data indicate that common treatments for NMSC were at least 95% effective, and further studies are needed to guide therapeutic choices for different clinical subgroups.

Calcium Plus Vitamin D Supplementation and the Risk of Nonmelanoma and Melanoma Skin Cancer: Post Hoc Analyses of the Women's Health Initiative Randomized Controlled Trial

PURPOSE In light of inverse relationships reported in observational studies of vitamin D intake and serum 25-hydroxyvitamin D levels with risk of nonmelanoma skin cancer (NMSC) and melanoma, we evaluated the effects of vitamin D combined with calcium supplementation on skin cancer in a randomized placebo-controlled trial. METHODS Postmenopausal women age 50 to 79 years (N = 36,282) enrolled onto the Womens Health Initiative (WHI) calcium/vitamin D clinical trial were randomly assigned to receive 1,000 mg of elemental calcium plus 400 IU of vitamin D3 (CaD) daily or placebo for a mean follow-up period of 7.0 years. NMSC and melanoma skin cancers were ascertained by annual self-report; melanoma skin cancers underwent physician adjudication. RESULTS Neither incident NMSC nor melanoma rates differed between treatment (hazard ratio [HR], 1.02; 95% CI, 0.95 to 1.07) and placebo groups (HR, 0.86; 95% CI, 0.64 to 1.16). In subgroup analyses, women with history of NMSC assigned to CaD had a reduced risk of melanoma versus those receiving placebo (HR, 0.43; 95% CI, 0.21 to 0.90; P(interaction) = .038), which was not observed in women without history of NMSC. CONCLUSION Vitamin D supplementation at a relatively low dose plus calcium did not reduce the overall incidence of NMSC or melanoma. However, in women with history of NMSC, CaD supplementation reduced melanoma risk, suggesting a potential role for calcium and vitamin D supplements in this high-risk group. Results from this post hoc subgroup analysis should be interpreted with caution but warrant additional investigation.

Evaluating the utility of non–echo‐planar diffusion‐weighted imaging in the preoperative evaluation of cholesteatoma: A meta‐analysis

To describe the accuracy of non–echo‐planar diffusion‐weighted magnetic resonance imaging (DW MRI) in identifying middle ear cholesteatoma.

The Risk of Melanoma in Airline Pilots and Cabin Crew: A Meta-analysis

IMPORTANCE Airline pilots and cabin crew are occupationally exposed to higher levels of cosmic and UV radiation than the general population, but their risk of developing melanoma is not yet established. OBJECTIVE To assess the risk of melanoma in pilots and airline crew. DATA SOURCES PubMed (1966 to October 30, 2013), Web of Science (1898 to January 27, 2014), and Scopus (1823 to January 27, 2014). STUDY SELECTION All studies were included that reported a standardized incidence ratio (SIR), standardized mortality ratio (SMR), or data on expected and observed cases of melanoma or death caused by melanoma that could be used to calculate an SIR or SMR in any flight-based occupation. DATA EXTRACTION AND SYNTHESIS Primary random-effect meta-analyses were used to summarize SIR and SMR for melanoma in any flight-based occupation. Heterogeneity was assessed using the χ2 test and I2 statistic. To assess the potential bias of small studies, we used funnel plots, the Begg rank correlation test, and the Egger weighted linear regression test. MAIN OUTCOMES AND MEASURES Summary SIR and SMR of melanoma in pilots and cabin crew. RESULTS Of the 3527 citations retrieved, 19 studies were included, with more than 266 431 participants. The overall summary SIR of participants in any flight-based occupation was 2.21 (95% CI, 1.76-2.77; P < .001; 14 records). The summary SIR for pilots was 2.22 (95% CI, 1.67-2.93; P = .001; 12 records). The summary SIR for cabin crew was 2.09 (95% CI, 1.67-2.62; P = .45; 2 records). The overall summary SMR of participants in any flight-based occupation was 1.42 (95% CI, 0.89-2.26; P = .002; 6 records). The summary SMR for pilots was 1.83 (95% CI, 1.27-2.63, P = .33; 4 records). The summary SMR for cabin crew was 0.90 (95% CI, 0.80-1.01; P = .97; 2 records). CONCLUSIONS AND RELEVANCE Pilots and cabin crew have approximately twice the incidence of melanoma compared with the general population. Further research on mechanisms and optimal occupational protection is needed.

Treatment of Nonfatal Conditions at the End of Life: Nonmelanoma Skin Cancer

IMPORTANCE Nonmelanoma skin cancer (NMSC) is the most common cancer and predominantly affects older patients. Because NMSCs do not typically affect survival or short-term quality of life, the decision about whether and how to treat patients with limited life expectancy (LLE) is challenging, especially for asymptomatic tumors. OBJECTIVE To compare treatment patterns and clinical outcomes of patients with NMSC with and without LLE. DESIGN, SETTING, AND PARTICIPANTS A prospective cohort study of 1536 consecutive patients diagnosed with NMSC at 2 dermatology clinics: a university-based private practice and a Veterans Affairs Medical Center in San Francisco, California. Patients were recruited in 1999 through 2000 and followed up for a median of 9 years. A total of 1360 patients with 1739 tumors (90%) were included in the final analysis. Limited life expectancy was defined as patients either 85 years or older at the time of diagnosis or patients with multiple comorbidities (Charlson Comorbidity Index of ≥ 3). Treatment options included no treatment, destruction, or 2 types of surgery-elliptical excision or Mohs surgery. MAIN OUTCOMES AND MEASURES Treatment type. RESULTS Most NMSCs (69%) were treated surgically, regardless of patient life expectancy. The choice of surgery was not influenced by patient prognosis in univariate or multivariable models adjusted for tumor and patient characteristics. Many patients with LLE (43%) died within 5 years, none of NMSC. Tumor recurrence was rare (3.7% at 5 years [95% CI, 2.6%-4.7%]) in all patients. Although serious complications were unusual, approximately 20% of patients with LLE reported complications of therapy, compared with 15% of other patients. CONCLUSIONS AND RELEVANCE Most NMSCs are treated surgically, regardless of the patients life expectancy. Given the very low tumor recurrence rates and high mortality from causes unrelated to NMSC in patients with LLE, clinicians should consider whether these patients would prefer less invasive treatment strategies.

Recurrence rates associated with incompletely excised low-risk nonmelanoma skin cancer

Background: Reported recurrence rates for transected nonmelanoma skin cancer (NMSC) vary widely, and few studies have addressed recurrence of tumors followed clinically or treated with nonsurgical modalities.