Dataset Information

Long-Term Risk of Skin Cancer Among Childhood Cancer Survivors: A DCOG-LATER Cohort Study.

ABSTRACT:

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.

SUBMITTER: Teepen JC

PROVIDER: S-EPMC6695299 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

Long-Term Risk of Skin Cancer Among Childhood Cancer Survivors: A DCOG-LATER Cohort Study.

Teepen Jop C JC Kok Judith L JL Kremer Leontien C LC Tissing Wim J E WJE van den Heuvel-Eibrink Marry M MM Loonen Jacqueline J JJ Bresters Dorine D van der Pal Helena J HJ Versluys Birgitta B van Dulmen-den Broeder Eline E Nijsten Tamar T Hauptmann Michael M Hollema Nynke N Dolsma Wil V WV van Leeuwen Flora E FE Ronckers Cécile M CM

Journal of the National Cancer Institute 20190801 8

<h4>Background</h4>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.<h4>Methods</h4>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 compare ...[more]

PMID: 30802904

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Project description:Simple Summary We studied survivors of childhood cancer who received cancer treatment that might affect the kidneys and compared them to controls from the general population. We investigated if there was a difference in the occurrence of tubular dysfunction. The tubules are the part of the kidney responsible for reabsorption of needed substances to the blood and the removal of wastes. After around 25 years since their cancer diagnosis, we found that in general there were no differences between survivors and controls, but survivors more often had losses of small proteins in the urine. Yet, some survivors of childhood cancer were found to have an increased risk of tubular dysfunction. Namely, survivors treated with the chemotherapeutic agents ifosfamide, cisplatin or carboplatin. Therefore, these patients should be monitored during their follow-up. Abstract The aim of this nationwide cross-sectional cohort study was to determine the prevalence of and risk factors for tubular dysfunction in childhood cancer survivors (CCS). In the DCCSS-LATER 2 Renal study, 1024 CCS (≥5 years after diagnosis), aged ≥ 18 years at study, treated between 1963 and 2001 with potentially nephrotoxic therapy (i.e., nephrectomy, abdominal radiotherapy, total body irradiation, cisplatin, carboplatin, ifosfamide, high-dose cyclophosphamide, or hematopoietic stem cell transplantation) participated, and 500 age- and sex-matched participants from Lifelines acted as controls. Tubular electrolyte loss was defined as low serum levels (magnesium < 0.7 mmol/L, phosphate < 0.7 mmol/L and potassium < 3.6 mmol/L) with increased renal excretion or supplementation. A α1-microglobulin:creatinine ratio > 1.7 mg/mmol was considered as low-molecular weight proteinuria (LMWP). Multivariable risk analyses were performed. After median 25.5 years follow-up, overall prevalence of electrolyte losses in CCS (magnesium 5.6%, potassium 4.5%, phosphate 5.5%) was not higher compared to controls. LMWP was more prevalent (CCS 20.1% versus controls 0.4%). LMWP and magnesium loss were associated with glomerular dysfunction. Ifosfamide was associated with potassium loss, phosphate loss (with cumulative dose > 42 g/m2) and LMWP. Cisplatin was associated with magnesium loss and a cumulative dose > 500 mg/m2 with potassium and phosphate loss. Carboplatin cumulative dose > 2800 mg/m2 was associated with potassium loss. In conclusion, long-term tubular dysfunction is infrequent. Yet, ifosfamide, cisplatin and carboplatin are risk factors.

Project description:BackgroundSurvivors of childhood cancer are at increased risk for a wide range of late effects. However, no large population-based studies have included the whole range of somatic diagnoses including subgroup diagnoses and all main types of childhood cancers. Therefore, we aimed to provide the most detailed overview of the long-term risk of hospitalisation in survivors of childhood cancer.Methods and findingsFrom the national cancer registers of Denmark, Finland, Iceland, and Sweden, we identified 21,297 5-year survivors of childhood cancer diagnosed with cancer before the age of 20 years in the periods 1943-2008 in Denmark, 1971-2008 in Finland, 1955-2008 in Iceland, and 1958-2008 in Sweden. We randomly selected 152,231 population comparison individuals matched by age, sex, year, and country (or municipality in Sweden) from the national population registers. Using a cohort design, study participants were followed in the national hospital registers in Denmark, 1977-2010; Finland, 1975-2012; Iceland, 1999-2008; and Sweden, 1968-2009. Disease-specific hospitalisation rates in survivors and comparison individuals were used to calculate survivors' standardised hospitalisation rate ratios (RRs), absolute excess risks (AERs), and standardised bed day ratios (SBDRs) based on length of stay in hospital. We adjusted for sex, age, and year by indirect standardisation. During 336,554 person-years of follow-up (mean: 16 years; range: 0-42 years), childhood cancer survivors experienced 21,325 first hospitalisations for diseases in one or more of 120 disease categories (cancer recurrence not included), when 10,999 were expected, yielding an overall RR of 1.94 (95% confidence interval [95% CI] 1.91-1.97). The AER was 3,068 (2,980-3,156) per 100,000 person-years, meaning that for each additional year of follow-up, an average of 3 of 100 survivors were hospitalised for a new excess disease beyond the background rates. Approximately 50% of the excess hospitalisations were for diseases of the nervous system (19.1% of all excess hospitalisations), endocrine system (11.1%), digestive organs (10.5%), and respiratory system (10.0%). Survivors of all types of childhood cancer were at increased, persistent risk for subsequent hospitalisation, the highest risks being those of survivors of neuroblastoma (RR: 2.6 [2.4-2.8]; n = 876), hepatic tumours (RR: 2.5 [2.0-3.1]; n = 92), central nervous system tumours (RR: 2.4 [2.3-2.5]; n = 6,175), and Hodgkin lymphoma (RR: 2.4 [2.3-2.5]; n = 2,027). Survivors spent on average five times as many days in hospital as comparison individuals (SBDR: 4.96 [4.94-4.98]; n = 422,218). The analyses of bed days in hospital included new primary cancers and recurrences. Of the total 422,218 days survivors spent in hospital, 47% (197,596 bed days) were for new primary cancers and recurrences. Our study is likely to underestimate the absolute overall disease burden experienced by survivors, as less severe late effects are missed if they are treated sufficiently in the outpatient setting or in the primary health care system.ConclusionsChildhood cancer survivors were at increased long-term risk for diseases requiring inpatient treatment even decades after their initial cancer. Health care providers who do not work in the area of late effects, especially those in primary health care, should be aware of this highly challenged group of patients in order to avoid or postpone hospitalisations by prevention, early detection, and appropriate treatments.

Dataset Information

Long-Term Risk of Skin Cancer Among Childhood Cancer Survivors: A DCOG-LATER Cohort Study.

Background

Methods

Results

Conclusion

Publications

Long-Term Risk of Skin Cancer Among Childhood Cancer Survivors: A DCOG-LATER Cohort Study.

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