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134 Better photo-protection in patients with recent skin check does not prevent sunburn among adults with no history of skin cancer
ABSTRACTS | Clinical Research I: Epidemiology and Patient Outcomes Research 130
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Association of 25-hydroxyvitamin D levels and cutaneous melanoma in postmenopausal women in the Women’s Health Initiative study G Kwon1,2, C Gamba1, M Stefanick3, SM Swetter1, S Li1, R Shi5, CA Clarke4, D Feldman5, A Millen6, C Messina10, J Shikany7, J Manson8, R Chlebowski9 and J Tang1 1 Dermatology, Stanford University Medical Center, Redwood City, CA, 2 Medicine, Dermatology Division, University of Washington, Seattle, WA, 3 Medicine, Stanford University, Stanford, CA, 4 Cancer Prevention Institute of California, Walnut Creek, CA, 5 Stanford Medical Center, Stanford, CA, 6 University of Buffalo, Buffalo, NY, 7 University of Alabama, Birmingham, AL, 8 Harvard T.H. Chan School of Public Health, Boston, MA, 9 UCLA School of Medicine, Los Angeles, CA and 10 Stony Brook Medicine, Stony Brooke, NY To gain further insight into the relationship between serum 25-hydroxyvitamin D (25(OH)D) levels and the incidence of melanoma, we carried out a nested case-control study in a large group of Caucasian women who were part of the Women’s Health Initiative (WHI) Observational Study (OS). 718 melanoma cases and 718 controls without melanoma were selected. Control subjects were matched by age, race/ethnicity, and clinical center. 25(OH)D levels were measured on serum samples taken from WHI women at baseline. Baseline characteristics and melanoma risk factors were compared between three groups based on clinical categories of 25(OH)D levels: 20 ng/mL, 20-29 ng/mL, and 30 ng/mL. After adjustment for age, BMI, education, multivitamin and calcium intake, sun exposure history, prior history of skin cancer, physical activity, season of blood draw, smoking, time spent outdoors in the summer both in childhood and in adulthood, use of sunscreen, regional solar irradiance, and having a medical visit in the last year, the risk of melanoma remained higher in women with 25(OH)D levels between 20 and 29 ng/mL compared to the reference group (HR ¼ 1.79, CI ¼ 1.22-2.62). The risk of melanoma in women with 25(OH)D levels 30 ng/mL compared to those with %20 ng/mL was also higher (HR ¼ 1.59, CI ¼ 1.04 e 2.42). In summary, results of this nested case-control study support the hypothesis that higher baseline 25(OH)D levels is associated with a higher risk of melanoma in Caucasian women.
Body locations and gender differences in basal and squamous cell carcinoma of the skin MR Wehner1, KT Nead2, E Linos3 and M Chren3,4 1 Dermatology, University of Pennsylvania, Philadelphia, PA, 2 Radiation Oncology, University of Pennsylvania, Philadelphia, PA, 3 Dermatology, University of California San Francisco, San Francisco, CA and 4 Dermatology, San Francisco Veterans Affairs Medical Center, San Francisco, CA Historically, the vast majority of basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) have been reported to be located on the head and neck (BCCs 70-90%, SCCs 65%), with differing body location patterns in men and women. We investigated body locations and gender differences in a cross-sectional sample of all BCCs and SCCs diagnosed in a cohort of 1,536 consecutive patients with BCC or SCC (424 women and 1,112 men) enrolled over a 2 year period and followed for up to 12 years. There were 4,035 BCCs and 2,016 SCCs diagnosed during the study period. We evaluated five body location categories: head and neck, upper extremities, lower extremities, genitals, and trunk. Information on body location was obtained from pathology reports and was available for 99.3% of tumors. Chi-squared and Fisher’s exact tests were used to compare body locations by gender. We found that only 58.2% of BCCs and 54.37% of SCCs were located on the head and neck. Men were more likely than women to be diagnosed with BCCs of the upper extremities and of the trunk (upper extremities 8.8% vs 5.03%, p<0.001; trunk 30.0% vs 22.7%, p<0.001), while women were more likely than men to be diagnosed with BCCs of the head and neck (65.8% vs 55.6%, p<0.001). Men were more likely than women to be diagnosed with SCCs of the head and neck (55.6% vs 47.5%, p¼0.007), while women were more likely than men to be diagnosed with SCCs of the lower extremities (18.8% vs 7.3%, p<0.001). We conclude that while the most common location for both BCCs and SCCs is the head and neck, the proportions may be much lower than expected. Additionally, the head and neck was a more likely location for BCCs in women than in men, which has not been previously reported. These findings may reflect changes in population exposures, such as intentional tanning, that are contributing to BCC and SCC development.
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Reason for referral to dermatologic care and non-melanoma skin cancer diagnoses in solid organ transplant recipients S Chundydyal, J Cheng, F Li and O Colegio Dermatology, Yale University, New Haven, CT Solid organ transplant recipients (SOTRs) have a 100-fold increased risk for non-melanoma skin cancer (NMSC); early detection is a critical part of their management. We sought to determine how the reasons for which SOTRs are referred to dermatologic care by nondermatologic providers might correlate with subsequent NMSC diagnoses. A total of 353 SOTRs referred to a specialized transplant dermatology clinic between 2007 and 2012 were examined in this nested case-control study. Eighty-one SOTRs with 491 lesions—192 actinic keratoses (AK), 106 basal cell carcinomas, and 193 squamous cell carcinomas—were compared with 272 SOTRs who did not develop any AKs or NMSCs within the study followup period. Of the SOTRs diagnosed with AK or NMSC within 6 months after their first dermatologic visit, 33% had been referred by non-dermatologic providers for “lesion of concern/skin cancer,” while 22% SOTRs were originally referred for “rash/acne.” Of the SOTRs who developed invasive NMSCs in the 6-year follow-up period, 27% had been referred for “lesion of concern/skin cancer,” while 34% were originally referred for “rash/ acne.” These results indicate that, despite the well-established heightened risk of NMSCs in SOTRs and care delivered in a multidisciplinary transplant clinic within a tertiary care center, a significant fraction of SOTRs who are referred to dermatologic care for benign skin disorders is still being incidentally diagnosed with cutaneous malignancies; this is especially concerning given that a referral for a benign skin condition could delay appropriate diagnosis and treatment of cutaneous malignancies, as well as SOTR risk-specific photo-education, prevention, and surveillance. Better risk stratification, improved interdisciplinary collaboration, prompt referral for routine skin cancer screening, and more timely referrals for suspicious lesions are needed in the care of SOTRs.
The incidence of cutaneous T-Cell lymphoma in the Veteran population C Del Guzzo1, A Levin1, A Dana1, R Vinnakota2, Y Park2, J Newman2, E Langhoff2 and L Geskin1 1 Columbia University, New York, NY and 2 Bronx VA Medical Center, Bronx, NY The Surveillance, Epidemiology, and End Results (SEER) Program does not contain the CTCL cases from the Veterans Affairs (VA) Medical Centers due to governmental protection and restrictions in reporting; thus, previously published CTCL incidence may not be complete and may underestimate the true incidence of the disease in the United States. An estimated 5-15% of all CTCL diagnosed each year occurs in veterans, a percentage far greater than the percentage of veterans in the total US patient population. The purpose of our study was to discover the previously unreported incidence of CTCL in the veteran population. We conducted an IRB-approved retrospective study using the VA Informatics and Computing (VINCI) database, a highly restricted, encrypted national VA database, to determine the incidence of CTCL amongst patients receiving care at the VA. The database was queried for the unique cases of CTCL, determined by the first ICD-9 code entry of Mycosis Fungoides or Sezary Syndrome into the database from 2004 to 2014 for a specific patient. The total number of patients accessing VA healthcare for each year was obtained from the Congressional Research Service. There were 4,446 unique patients with a diagnosis of CTCL entered into the database from 2004 to 2014. The annual number of new diagnoses of CTCL ranged from 62-79 (median 69) cases per one million persons per year. We found significant, 6-8 times higher incidence of CTCL in veterans than in the general population. The demographics and trends in the number of CTCL patients per conflict era showed great variations. Our data changes the CTCL incidence trends in the US. Our findings are suggestive of specific military exposures, such as Agent Orange during the Vietnam War, as a potential pathogenic drivers and warrant further exploration of the causes behind increased incidence of CTCL in veterans.
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Better photo-protection in patients with recent skin check does not prevent sunburn among adults with no history of skin cancer AH Fischer, T Wang, G Yenokyan, S Kang and AL Chien Dept of Derm, Johns Hopkins Univ, Baltimore, MD Patients coming in for skin checks are taking a positive step in early skin cancer identification. However, whether they adequately adopt primary skin cancer prevention methods (e.g., photo-protection) remains unclear. We aim to determine whether full-body skin check in the last year is associated with better sun-protective practices and sunburn prevention. We used data from US non-Hispanic whites aged 18-75 (529 with and 13,144 without previous skin cancer) from the 2010 National Health Interview Survey to compute adjusted prevalence odds ratios (aPOR) of sun-protective practices associated with skin check, taking into account the complex survey design and adjusting for age, gender, region, sun sensitivity, family history of skin cancer, education, outdoor occupation, and physical activity. Individuals reporting recent skin check (compared to individuals not reporting recent skin check) were more likely to engage in multimodal photo-protection both among subjects with previous skin cancer (aPOR¼1.8; 95% CI¼1.1-3.1) and among subjects without previous skin cancer (aPOR¼1.5; 95% CI¼1.2-1.8; P-interaction¼0.6). Among subjects with previous skin cancer, recent skin check was associated with decreased odds of recent sunburn (aPOR¼0.6; 0.3-0.95); however, among subjects without previous skin cancer, recent skin check was not associated with a reduction in recent sunburn (aPOR¼1.0; 0.9-1.2; P-interaction¼0.04). Association with sunburn among subjects without previous skin cancer was not different by sun-protective practices, reason for skin check, or self-perceived risk of cancer. Better sun-protective practices observed in subjects with recent skin check may not necessarily translate into better sunburn prevention, unless subjects have also had previous skin cancer. Health care providers should not assume adequate sun protection among patients coming in for skin checks; rather, providers should use all visits as a chance to reinforce sunburn prevention and the role of UV exposure in skin cancer and skin aging/photodamage.
S24 Journal of Investigative Dermatology (2016), Volume 136
Direct gene expression measurement in skin predicts long-term clinical outcome in patients with cutaneous T-cell lymphomas A De Masson, CP Elco, J O’Malley, S Garcia, S Divito, EL Lowry, J Teague, N LeBoeuf, R Clark and TS Kupper Dermatology, BWH/HMS, Boston, MA Cutaneous T-cell lymphomas (CTCL) are rare diseases that often have a good prognosis. However, some patients progress to advanced-stage, aggressive disease. Early identification of the molecular factors that govern CTCL progression could enable a predictive personalized treatment strategy. NanoString technology allows the direct quantification of multiple mRNA transcripts in old and partially degraded biological samples such as formalin-fixed, paraffinembedded (FFPE) biopsies. We validated the use of NanoString technology on skin samples from 48 CTCL patients included in previous gene expression studies at Dana Farber between 2003 and 2005. Disease stage and progression were assessed using the international ISCL/ EORTC criteria for CTCL. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier and hazard ratios (HR) for PFS computed using the MantelHaenszel univariate method. The gene expression data as measured by NanoString and Affymetrix were highly correlated (Spearman r¼0.81, p<0.0001). With a median follow-up of 10 years, estimated 10-year OS and PFS were 67% and 58%. Advanced stage and older age were significantly associated with reduced PFS in univariate analysis (HR: 7.7, p¼0.0001, and 2.9, p¼0.02, respectively). Eight genes out of 52 (POU2AF1, TOX, GTSF1, LEF1, IL-21, SELL, PLK1 and STAT5A) were differentially expressed (FDR<0.05) between progressors and nonprogressors, and significantly associated with PFS (HR, 3.7 to 8.1, p<0.01). These genes are all expressed by T cells and play a role in the regulation of the cell cycle. These long-term follow-up data provide biological information on the key molecular events leading to CTCL progression. After validation of the model on an independent cohort, it could provide a simple, widely usable prognostic test for CTCL patients.
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Association of 25-hydroxyvitamin D levels and cutaneous melanoma in postmenopausal women in the Women’s Health Initiative study G Kwon1,2, C Gamba1, M Stefanick3, SM Swetter1, S Li1, R Shi5, CA Clarke4, D Feldman5, A Millen6, C Messina10, J Shikany7, J Manson8, R Chlebowski9 and J Tang1 1 Dermatology, Stanford University Medical Center, Redwood City, CA, 2 Medicine, Dermatology Division, University of Washington, Seattle, WA, 3 Medicine, Stanford University, Stanford, CA, 4 Cancer Prevention Institute of California, Walnut Creek, CA, 5 Stanford Medical Center, Stanford, CA, 6 University of Buffalo, Buffalo, NY, 7 University of Alabama, Birmingham, AL, 8 Harvard T.H. Chan School of Public Health, Boston, MA, 9 UCLA School of Medicine, Los Angeles, CA and 10 Stony Brook Medicine, Stony Brooke, NY To gain further insight into the relationship between serum 25-hydroxyvitamin D (25(OH)D) levels and the incidence of melanoma, we carried out a nested case-control study in a large group of Caucasian women who were part of the Women’s Health Initiative (WHI) Observational Study (OS). 718 melanoma cases and 718 controls without melanoma were selected. Control subjects were matched by age, race/ethnicity, and clinical center. 25(OH)D levels were measured on serum samples taken from WHI women at baseline. Baseline characteristics and melanoma risk factors were compared between three groups based on clinical categories of 25(OH)D levels: 20 ng/mL, 20-29 ng/mL, and 30 ng/mL. After adjustment for age, BMI, education, multivitamin and calcium intake, sun exposure history, prior history of skin cancer, physical activity, season of blood draw, smoking, time spent outdoors in the summer both in childhood and in adulthood, use of sunscreen, regional solar irradiance, and having a medical visit in the last year, the risk of melanoma remained higher in women with 25(OH)D levels between 20 and 29 ng/mL compared to the reference group (HR ¼ 1.79, CI ¼ 1.22-2.62). The risk of melanoma in women with 25(OH)D levels 30 ng/mL compared to those with %20 ng/mL was also higher (HR ¼ 1.59, CI ¼ 1.04 e 2.42). In summary, results of this nested case-control study support the hypothesis that higher baseline 25(OH)D levels is associated with a higher risk of melanoma in Caucasian women.
Body locations and gender differences in basal and squamous cell carcinoma of the skin MR Wehner1, KT Nead2, E Linos3 and M Chren3,4 1 Dermatology, University of Pennsylvania, Philadelphia, PA, 2 Radiation Oncology, University of Pennsylvania, Philadelphia, PA, 3 Dermatology, University of California San Francisco, San Francisco, CA and 4 Dermatology, San Francisco Veterans Affairs Medical Center, San Francisco, CA Historically, the vast majority of basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) have been reported to be located on the head and neck (BCCs 70-90%, SCCs 65%), with differing body location patterns in men and women. We investigated body locations and gender differences in a cross-sectional sample of all BCCs and SCCs diagnosed in a cohort of 1,536 consecutive patients with BCC or SCC (424 women and 1,112 men) enrolled over a 2 year period and followed for up to 12 years. There were 4,035 BCCs and 2,016 SCCs diagnosed during the study period. We evaluated five body location categories: head and neck, upper extremities, lower extremities, genitals, and trunk. Information on body location was obtained from pathology reports and was available for 99.3% of tumors. Chi-squared and Fisher’s exact tests were used to compare body locations by gender. We found that only 58.2% of BCCs and 54.37% of SCCs were located on the head and neck. Men were more likely than women to be diagnosed with BCCs of the upper extremities and of the trunk (upper extremities 8.8% vs 5.03%, p<0.001; trunk 30.0% vs 22.7%, p<0.001), while women were more likely than men to be diagnosed with BCCs of the head and neck (65.8% vs 55.6%, p<0.001). Men were more likely than women to be diagnosed with SCCs of the head and neck (55.6% vs 47.5%, p¼0.007), while women were more likely than men to be diagnosed with SCCs of the lower extremities (18.8% vs 7.3%, p<0.001). We conclude that while the most common location for both BCCs and SCCs is the head and neck, the proportions may be much lower than expected. Additionally, the head and neck was a more likely location for BCCs in women than in men, which has not been previously reported. These findings may reflect changes in population exposures, such as intentional tanning, that are contributing to BCC and SCC development.
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Reason for referral to dermatologic care and non-melanoma skin cancer diagnoses in solid organ transplant recipients S Chundydyal, J Cheng, F Li and O Colegio Dermatology, Yale University, New Haven, CT Solid organ transplant recipients (SOTRs) have a 100-fold increased risk for non-melanoma skin cancer (NMSC); early detection is a critical part of their management. We sought to determine how the reasons for which SOTRs are referred to dermatologic care by nondermatologic providers might correlate with subsequent NMSC diagnoses. A total of 353 SOTRs referred to a specialized transplant dermatology clinic between 2007 and 2012 were examined in this nested case-control study. Eighty-one SOTRs with 491 lesions—192 actinic keratoses (AK), 106 basal cell carcinomas, and 193 squamous cell carcinomas—were compared with 272 SOTRs who did not develop any AKs or NMSCs within the study followup period. Of the SOTRs diagnosed with AK or NMSC within 6 months after their first dermatologic visit, 33% had been referred by non-dermatologic providers for “lesion of concern/skin cancer,” while 22% SOTRs were originally referred for “rash/acne.” Of the SOTRs who developed invasive NMSCs in the 6-year follow-up period, 27% had been referred for “lesion of concern/skin cancer,” while 34% were originally referred for “rash/ acne.” These results indicate that, despite the well-established heightened risk of NMSCs in SOTRs and care delivered in a multidisciplinary transplant clinic within a tertiary care center, a significant fraction of SOTRs who are referred to dermatologic care for benign skin disorders is still being incidentally diagnosed with cutaneous malignancies; this is especially concerning given that a referral for a benign skin condition could delay appropriate diagnosis and treatment of cutaneous malignancies, as well as SOTR risk-specific photo-education, prevention, and surveillance. Better risk stratification, improved interdisciplinary collaboration, prompt referral for routine skin cancer screening, and more timely referrals for suspicious lesions are needed in the care of SOTRs.
The incidence of cutaneous T-Cell lymphoma in the Veteran population C Del Guzzo1, A Levin1, A Dana1, R Vinnakota2, Y Park2, J Newman2, E Langhoff2 and L Geskin1 1 Columbia University, New York, NY and 2 Bronx VA Medical Center, Bronx, NY The Surveillance, Epidemiology, and End Results (SEER) Program does not contain the CTCL cases from the Veterans Affairs (VA) Medical Centers due to governmental protection and restrictions in reporting; thus, previously published CTCL incidence may not be complete and may underestimate the true incidence of the disease in the United States. An estimated 5-15% of all CTCL diagnosed each year occurs in veterans, a percentage far greater than the percentage of veterans in the total US patient population. The purpose of our study was to discover the previously unreported incidence of CTCL in the veteran population. We conducted an IRB-approved retrospective study using the VA Informatics and Computing (VINCI) database, a highly restricted, encrypted national VA database, to determine the incidence of CTCL amongst patients receiving care at the VA. The database was queried for the unique cases of CTCL, determined by the first ICD-9 code entry of Mycosis Fungoides or Sezary Syndrome into the database from 2004 to 2014 for a specific patient. The total number of patients accessing VA healthcare for each year was obtained from the Congressional Research Service. There were 4,446 unique patients with a diagnosis of CTCL entered into the database from 2004 to 2014. The annual number of new diagnoses of CTCL ranged from 62-79 (median 69) cases per one million persons per year. We found significant, 6-8 times higher incidence of CTCL in veterans than in the general population. The demographics and trends in the number of CTCL patients per conflict era showed great variations. Our data changes the CTCL incidence trends in the US. Our findings are suggestive of specific military exposures, such as Agent Orange during the Vietnam War, as a potential pathogenic drivers and warrant further exploration of the causes behind increased incidence of CTCL in veterans.
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Better photo-protection in patients with recent skin check does not prevent sunburn among adults with no history of skin cancer AH Fischer, T Wang, G Yenokyan, S Kang and AL Chien Dept of Derm, Johns Hopkins Univ, Baltimore, MD Patients coming in for skin checks are taking a positive step in early skin cancer identification. However, whether they adequately adopt primary skin cancer prevention methods (e.g., photo-protection) remains unclear. We aim to determine whether full-body skin check in the last year is associated with better sun-protective practices and sunburn prevention. We used data from US non-Hispanic whites aged 18-75 (529 with and 13,144 without previous skin cancer) from the 2010 National Health Interview Survey to compute adjusted prevalence odds ratios (aPOR) of sun-protective practices associated with skin check, taking into account the complex survey design and adjusting for age, gender, region, sun sensitivity, family history of skin cancer, education, outdoor occupation, and physical activity. Individuals reporting recent skin check (compared to individuals not reporting recent skin check) were more likely to engage in multimodal photo-protection both among subjects with previous skin cancer (aPOR¼1.8; 95% CI¼1.1-3.1) and among subjects without previous skin cancer (aPOR¼1.5; 95% CI¼1.2-1.8; P-interaction¼0.6). Among subjects with previous skin cancer, recent skin check was associated with decreased odds of recent sunburn (aPOR¼0.6; 0.3-0.95); however, among subjects without previous skin cancer, recent skin check was not associated with a reduction in recent sunburn (aPOR¼1.0; 0.9-1.2; P-interaction¼0.04). Association with sunburn among subjects without previous skin cancer was not different by sun-protective practices, reason for skin check, or self-perceived risk of cancer. Better sun-protective practices observed in subjects with recent skin check may not necessarily translate into better sunburn prevention, unless subjects have also had previous skin cancer. Health care providers should not assume adequate sun protection among patients coming in for skin checks; rather, providers should use all visits as a chance to reinforce sunburn prevention and the role of UV exposure in skin cancer and skin aging/photodamage.
S24 Journal of Investigative Dermatology (2016), Volume 136
Direct gene expression measurement in skin predicts long-term clinical outcome in patients with cutaneous T-cell lymphomas A De Masson, CP Elco, J O’Malley, S Garcia, S Divito, EL Lowry, J Teague, N LeBoeuf, R Clark and TS Kupper Dermatology, BWH/HMS, Boston, MA Cutaneous T-cell lymphomas (CTCL) are rare diseases that often have a good prognosis. However, some patients progress to advanced-stage, aggressive disease. Early identification of the molecular factors that govern CTCL progression could enable a predictive personalized treatment strategy. NanoString technology allows the direct quantification of multiple mRNA transcripts in old and partially degraded biological samples such as formalin-fixed, paraffinembedded (FFPE) biopsies. We validated the use of NanoString technology on skin samples from 48 CTCL patients included in previous gene expression studies at Dana Farber between 2003 and 2005. Disease stage and progression were assessed using the international ISCL/ EORTC criteria for CTCL. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier and hazard ratios (HR) for PFS computed using the MantelHaenszel univariate method. The gene expression data as measured by NanoString and Affymetrix were highly correlated (Spearman r¼0.81, p<0.0001). With a median follow-up of 10 years, estimated 10-year OS and PFS were 67% and 58%. Advanced stage and older age were significantly associated with reduced PFS in univariate analysis (HR: 7.7, p¼0.0001, and 2.9, p¼0.02, respectively). Eight genes out of 52 (POU2AF1, TOX, GTSF1, LEF1, IL-21, SELL, PLK1 and STAT5A) were differentially expressed (FDR<0.05) between progressors and nonprogressors, and significantly associated with PFS (HR, 3.7 to 8.1, p<0.01). These genes are all expressed by T cells and play a role in the regulation of the cell cycle. These long-term follow-up data provide biological information on the key molecular events leading to CTCL progression. After validation of the model on an independent cohort, it could provide a simple, widely usable prognostic test for CTCL patients.