Radiotherapy as a risk factor for malignant melanoma after childhood skin hemangioma.

The aim of this study was to determine therapy-related risk factors for the development of melanoma after hemangioma. A cohort study was conducted among 4620 patients treated before 16 years of age for skin hemangioma in France. A nested case-control study was also conducted on 13 patients who developed a melanoma (cases) matched with five controls in cohort according to sex, age at the hemangioma diagnostic, the calendar year of occurrence of the hemangioma, and follow-up. The radiation dose received at the site of the melanoma and at the same site in controls was estimated, and named 'local dose'. A total of 13 melanomas were registered during an average follow-up of overall 35 years, the risk of developing melanoma after a hemangioma treatment was 2.5-fold higher [95% confidence interval (CI): 1.4-4.1] compared with that of the general population, this ratio being only 0.8 (95% CI: 0.05-3.6) in 896 patients who did not receive radiotherapy, but 3.0 (95% CI: 1.6-5.1) after radiotherapy. When adjusting on sex, age, and year of the treatment and follow-up duration, melanoma risk was 11.9 (95% CI: 1.4-123) times higher in patients treated with ytrium 90 than in the ones who did not received radiotherapy. In the case-control study, the risk of melanoma was not linked to the local radiation dose. Indeed, the increase in melanoma risk was observed even for very low local doses. Compared with the corresponding skin areas in patients who did not receive radiotherapy, the ones having received less than 0.001 Gy had a melanoma risk of 3.9 (95% CI: 0.5-32) and those who received more than 0.01 Gy had a risk of 6.9 (0.5-99). This study suggests that radiation therapy of skin hemangioma increases the risk of further melanoma, but we were not able to evidence a relation with the local dose. Nevertheless, childhood treated for hemangioma should be considered at risk for developing melanoma and suspicious pigmented lesions should be carefully evaluated even far from treated areas.

Relationship between the brain radiation dose for the treatment of childhood cancer and the risk of long-term cerebrovascular mortality.

To date, very little is known about the long-term risk of death from cerebrovascular sequelae following childhood cancer treatment. The purpose of this study was to assess the role of treatment in very long-term cerebrovascular mortality following childhood cancer. We studied 4227 5-year survivors of a childhood cancer. Information on chemotherapy was collected and the radiation dose delivered to 11 anatomical sites in the brain was estimated. The main outcome that was considered was death due to cerebrovascular disease occurring before 1 January 2008. After a median follow-up of 29 years, 23 deaths due to cerebrovascular diseases had occurred. In the brain, the radiation dose delivered to the prepontine cistern seemed to play a greater role than the average radiation dose received throughout the brain or the dose to any other specific anatomical site in the brain. The risk of death from cerebrovascular disease increased linearly with the local radiation dose to the prepontine cistern. Each unit of absorbed radiation (Gray) delivered to this area increased the risk by 22% (95% confidence interval: 1-44%). Compared with patients who had not received radiotherapy or who had received <0.1 Gray in the prepontine cistern area, those who had received >50 Gray had a 17.8-fold (4.4-73.0) higher hazard ratio of death from cerebrovascular disease. In conclusion, among 5-year survivors of childhood cancer, the radiation dose to the brain during radiotherapy was significantly associated with long-term cerebrovascular mortality.

Long-term cardiovascular mortality after radiotherapy for breast cancer.

OBJECTIVES: This study sought to investigate long-term cardiovascular mortality and its relationship to the use of radiotherapy for breast cancer. BACKGROUND: Cardiovascular diseases are among the main long-term complications of radiotherapy, but knowledge is limited regarding long-term risks because published studies have, on average, <20 years of follow-up. METHODS: A total of 4,456 women who survived at least 5 years after treatment of a breast cancer at the Institut Gustave Roussy between 1954 and 1984 were followed up for mortality until the end of 2003, for over 28 years on average. RESULTS: A total of 421 deaths due to cardiovascular diseases were observed, of which 236 were due to cardiac disease. Women who had received radiotherapy had a 1.76-fold (95% confidence interval [CI]: 1.34 to 2.31) higher risk of dying of cardiac disease and a 1.33-fold (95% CI: 0.99 to 1.80) higher risk of dying of vascular disease than those who had not received radiotherapy. Among women who had received radiotherapy, those who had been treated for a left-sided breast cancer had a 1.56-fold (95% CI: 1.27 to 1.90) higher risk of dying of cardiac disease than those treated for a right-sided breast cancer. This relative risk increased with time since the breast cancer diagnosis (p = 0.05). CONCLUSIONS: This study confirmed that radiotherapy, as delivered until the mid-1980s, increased the long-term risk of dying of cardiovascular diseases. The long-term risk of dying of cardiac disease is a particular concern for women treated for a left-sided breast cancer with contemporary tangential breast or chest wall radiotherapy. This risk may increase with a longer follow-up, even after 20 years following radiotherapy.

Breast cancer following radiotherapy for a hemangioma during childhood.

PURPOSE: A cohort study was performed to investigate the carcinogenic effect of treatment of skin hemangioma with ionizing radiation in early childhood. This paper presents the incidence of breast cancer (BC) in this cohort and its association with radiotherapy. METHODS AND MATERIALS: In an incidence study, 3,316 women treated for a skin hemangioma between 1941 and 1977 at the Institut Gustave-Roussy were included, among whom 2,697 had received radiotherapy. The mean age at first exposure was 0.7 years, and the mean absorbed dose to the breast was 70 mGy. Treatment reconstruction and the estimation of radiation doses delivered to the breast were obtained for 92% of the women who had received radiotherapy. External and internal analyses were performed. RESULTS: During an average follow-up of 35 years, a total of 17 women developed an invasive BC, compared to 7.5 expected in the French general population (SIR = 2.3, 95% CI, 1.4-3.5), and the absolute excess risk strongly increased with attained age. Compared to individuals with no radiotherapy, the risk of BC increased with increasing radiation dose with RRs of 3.2, 6.3, and 8.0 for dose categories of >0-10, 10-100, and >100 mGy, respectively; however, dose-response relationship was not significant. CONCLUSION: This study confirms that radiation treatment performed in the past for hemangioma during childhood increases the risk of BC.

Role of cancer treatment in long-term overall and cardiovascular mortality after childhood cancer.

PURPOSE: The purpose of this study was to assess the role of treatment in long-term overall and cardiovascular mortality after childhood cancer. PATIENTS AND METHODS: We studied 4,122 5-year survivors of a childhood cancer diagnosed before 1986 in France and the United Kingdom. Information on chemotherapy was collected, and the radiation dose delivered to the heart was estimated for 2,870 patients who had received radiotherapy. RESULTS: After 86,453 person-years of follow-up (average, 27 years), 603 deaths had occurred. The overall standardized mortality ratio (SMR) was 8.3-fold higher (95% CI, 7.6-fold to 9.0-fold higher) in relation to the general populations in France and the United Kingdom. Thirty-two patients had died as a result of cardiovascular diseases (ie, 5.0-fold [95% CI, 3.3-fold to 6.7-fold] more than expected). The risk of dying as a result of cardiac diseases (n = 21) was significantly higher in individuals who had received a cumulative anthracycline dose greater than 360 mg/m(2) (relative risk [RR], 4.4; 95% CI, 1.3 to 15.3) and in individuals who received an average radiation dose that exceeded 5 Gy (RR, 12.5 and 25.1 for 5 to 14.9 Gy and > 15 Gy, respectively) to the heart. A linear relationship was found between the average dose of radiation to the heart and the risk of cardiac mortality (estimated excess [corrected] RR at 1 Gy, 60%). CONCLUSION: This study is the first, to our knowledge, to establish a relationship between the radiation dose received by the heart during radiotherapy for a childhood cancer and long-term cardiac mortality. This study also confirms a significant excess risk of cardiac mortality associated with a high cumulative dose of anthracyclines.

Thyroid adenomas and carcinomas following radiotherapy for a hemangioma during infancy.

BACKGROUND AND PURPOSE: A cohort study was performed to investigate the carcinogenic effect of treating skin hemangioma with ionizing radiation during early childhood. This paper presents the incidence of differentiated thyroid adenomas and carcinomas after radiotherapy in this cohort. METHODS AND MATERIALS: Of a total of 8307 patients treated for a skin hemangioma between 1940 and 1973 at the Institut Gustave-Roussy, 4767 were included in an incidence study, among whom 3795 had received radiotherapy. Seventy-three percent were less than 1-year-old at the time of treatment. External radiotherapy, Radium 226, Strontium 90, Yttrium 90, and Phosphorus 32 were used. The radiation dose received by the thyroid during radiotherapy, estimated in 3497 of the 3795 patients using specific software, was 41 mGy on average. Thyroid tumor cases were obtained by sending out a questionnaire, and were verified in pathological reports. Estimates of thyroid cancer specific incidence rates in the French population were obtained from the French cancer registry network. External and internal analyses were performed. RESULTS: During an average follow-up of 35 years, 11 patients developed a differentiated thyroid carcinoma and 44 a thyroid adenoma. The incidence of thyroid adenoma was found to be higher among taller and heavier individuals. The incidence of both thyroid carcinoma and adenoma was higher among non-smoker patients. A significant dose-response relationship was found between the radiation dose received by thyroid and the risk of thyroid cancer (Excess Relative Risk per GY, ERR/Gy: 14.7, 95%CI: 1.6-62.9) and of adenoma (ERR/Gy: 5.7, 95%CI: 0.7-19.4). CONCLUSION: This study confirms that radiation treatment performed in the past for hemangioma during infancy increased the risk of thyroid carcinoma and adenoma. Patients treated with external radiotherapy or with Radium 226 applicators for hemangiomas have to be more specifically followed up because this is the subgroup in whom the highest doses were received by the thyroid gland (more than 90% of the radiation doses were higher than 100 mGy). They are therefore more at risk of developing thyroid cancer.