TY - JOUR
T1 - Long-Term Risk of Skin Cancer Among Childhood Cancer Survivors
T2 - A DCOG-LATER Cohort Study
AU - DCOG-LATER Study Group
AU - Teepen, Jop C
AU - Kok, Judith L
AU - Kremer, Leontien C
AU - Tissing, Wim J E
AU - van den Heuvel-Eibrink, Marry M
AU - Loonen, Jacqueline J
AU - Bresters, Dorine
AU - van der Pal, Helena J
AU - Versluys, Birgitta
AU - van Dulmen-den Broeder, Eline
AU - Nijsten, Tamar
AU - Hauptmann, Michael
AU - Hollema, Nynke
AU - Dolsma, Wil V
AU - van Leeuwen, Flora E
AU - Ronckers, Cécile M
N1 - © The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: [email protected].
PY - 2019/8/1
Y1 - 2019/8/1
N2 - BACKGROUND: Skin cancer is common after radiotherapy among childhood cancer survivors (CCSs). We studied risks and risk factors for subsequent skin cancers, with emphasis on radiation dose, exposed skin surface area, and chemotherapeutic agents.METHODS: The DCOG-LATER cohort study includes 5-year Dutch CCSs diagnosed 1963-2001. Subsequent skin cancers were identified from record linkages with the Netherlands Cancer Registry and Dutch Pathology Registry. Incidence rates were compared with general population rates. Multivariable Cox regression models were used, applying a novel method of case-control sampling enabling use of tumor location in cohort analyses. All statistical tests were two-sided.RESULTS: Among 5843 CCSs, 259 developed 1061 basal cell carcinomas (BCCs) (standardized incidence ratio [SIR] = 29.8, 95% confidence interval [CI] = 26.3 to 33.6; excess absolute risk per 10 000 person-years (EAR) = 24.6), 20 had melanoma (SIR = 2.3, 95% CI = 1.4 to 3.5; EAR = 1.1), and 10 had squamous cell carcinoma (SIR = 7.5, 95% CI = 3.6 to 13.8; EAR = 0.8). Cumulative incidence of BCC 40 years after childhood cancer was 19.1% (95% CI = 16.6 to 21.8%) after radiotherapy vs 0.6% expected based on general population rates. After a first BCC, 46.7% had more BCCs later. BCC risk was associated with any radiotherapy to the skin compartment of interest (hazard ratio [HR] = 14.32, 95% CI = 10.10 to 20.29) and with estimated percentage in-field skin surface area (26-75%: HR = 1.99, 95% CI = 1.24 to 3.20; 76-100%: HR = 2.16, 95% CI = 1.33 to 3.53, vs 1-25% exposed; Ptrend among exposed = .002), but not with prescribed radiation dose and likelihood of sun-exposed skin-area. Of all chemotherapy groups examined, only vinca alkaloids increased BCC risk (HR = 1.54, 95% CI = 1.04 to 2.27).CONCLUSION: CCSs have a strongly, 30-fold increased BCC risk. BCC risk appears to increase with increasing skin surface area exposed. This knowledge underscores the need for awareness by survivors and their health care providers.
AB - BACKGROUND: Skin cancer is common after radiotherapy among childhood cancer survivors (CCSs). We studied risks and risk factors for subsequent skin cancers, with emphasis on radiation dose, exposed skin surface area, and chemotherapeutic agents.METHODS: The DCOG-LATER cohort study includes 5-year Dutch CCSs diagnosed 1963-2001. Subsequent skin cancers were identified from record linkages with the Netherlands Cancer Registry and Dutch Pathology Registry. Incidence rates were compared with general population rates. Multivariable Cox regression models were used, applying a novel method of case-control sampling enabling use of tumor location in cohort analyses. All statistical tests were two-sided.RESULTS: Among 5843 CCSs, 259 developed 1061 basal cell carcinomas (BCCs) (standardized incidence ratio [SIR] = 29.8, 95% confidence interval [CI] = 26.3 to 33.6; excess absolute risk per 10 000 person-years (EAR) = 24.6), 20 had melanoma (SIR = 2.3, 95% CI = 1.4 to 3.5; EAR = 1.1), and 10 had squamous cell carcinoma (SIR = 7.5, 95% CI = 3.6 to 13.8; EAR = 0.8). Cumulative incidence of BCC 40 years after childhood cancer was 19.1% (95% CI = 16.6 to 21.8%) after radiotherapy vs 0.6% expected based on general population rates. After a first BCC, 46.7% had more BCCs later. BCC risk was associated with any radiotherapy to the skin compartment of interest (hazard ratio [HR] = 14.32, 95% CI = 10.10 to 20.29) and with estimated percentage in-field skin surface area (26-75%: HR = 1.99, 95% CI = 1.24 to 3.20; 76-100%: HR = 2.16, 95% CI = 1.33 to 3.53, vs 1-25% exposed; Ptrend among exposed = .002), but not with prescribed radiation dose and likelihood of sun-exposed skin-area. Of all chemotherapy groups examined, only vinca alkaloids increased BCC risk (HR = 1.54, 95% CI = 1.04 to 2.27).CONCLUSION: CCSs have a strongly, 30-fold increased BCC risk. BCC risk appears to increase with increasing skin surface area exposed. This knowledge underscores the need for awareness by survivors and their health care providers.
KW - Adolescent
KW - Adult
KW - Cancer Survivors
KW - Carcinoma, Basal Cell/epidemiology
KW - Carcinoma, Squamous Cell/epidemiology
KW - Child
KW - Child, Preschool
KW - Cohort Studies
KW - Drug Therapy
KW - Drug-Related Side Effects and Adverse Reactions/epidemiology
KW - Female
KW - Humans
KW - Male
KW - Melanoma/epidemiology
KW - Middle Aged
KW - Neoplasms/complications
KW - Neoplasms, Radiation-Induced/epidemiology
KW - Proportional Hazards Models
KW - Radiation Dosage
KW - Radiotherapy/adverse effects
KW - Risk Factors
KW - Vinca Alkaloids/adverse effects
KW - Young Adult
UR - http://www.scopus.com/inward/record.url?scp=85068928835&partnerID=8YFLogxK
U2 - 10.1093/jnci/djy212
DO - 10.1093/jnci/djy212
M3 - Article
C2 - 30802904
SN - 0027-8874
VL - 111
SP - 845
EP - 853
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 8
ER -