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Nadia Haddy,
Abdeddahir Mousannif,
Catherine Paoletti, Marie-Gabrielle Dondon,
Akhtar Shamsaldin,
Françoise Doyon,
Marie-Françoise Avril,
Philippe Fragu,
Martine Labbé,
Dimitry Lefkopoulos,
Jean Chavaudra,
Caroline Robert,
Ibrahima Diallo,
Florent de Vathaire
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ABSTRACT: 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.
Melanoma research 11/2011; 22(1):77-85. · 2.06 Impact Factor
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Nadia Haddy, Marie-Gabrielle Dondon,
Catherine Paoletti,
Carole Rubino,
Abdeddahir Mousannif,
Akhtar Shamsaldin,
Françoise Doyon,
Martine Labbé,
Caroline Robert,
Marie-Françoise Avril,
Rogers Demars,
Florence Molinie,
Dimitri Lefkopoulos,
Ibrahima Diallo,
Florent de Vathaire
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ABSTRACT: 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.
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.
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.
This study confirms that radiation treatment performed in the past for hemangioma during childhood increases the risk of BC.
Cancer Causes and Control 11/2010; 21(11):1807-16. · 2.88 Impact Factor
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Nadia Haddy,
Tianarimanana Andriamboavonjy,
Catherine Paoletti, Marie-Gabrielle Dondon,
Abdeddahir Mousannif,
Akhtar Shamsaldin,
Françoise Doyon,
Martine Labbé,
Caroline Robert,
Marie-Françoise Avril,
Philippe Fragu,
François Eschwege,
Jean Chavaudra,
Claire Schvartz,
Dimitri Lefkopoulos,
Martin Schlumberger,
Ibrahima Diallo,
Florent de Vathaire
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ABSTRACT: 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.
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.
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).
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.
Radiotherapy and Oncology 07/2009; 93(2):377-82. · 5.58 Impact Factor
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Sylvie Guérin,
Catherine Guibout,
Akthar Shamsaldin, Marie-Gabrielle Dondon,
Ibrahima Diallo,
Mike Hawkins,
Odile Oberlin,
Olivier Hartmann,
Jean Michon,
Marie-Cécile Le Deley,
Florent de Vathaire
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ABSTRACT: Radiotherapy and chemotherapy are associated with an increased risk of a second malignant neoplasm (SMN) after a cancer during childhood. This study specified the dose-effect relationship between radiotherapy, chemotherapy and the risk of a SMN, and investigated the effect of chemo-radiotherapy on the risk of SMN. A case-control study nested in a European cohort of 4,581 patients treated for a solid cancer during childhood was conducted. One hundred and fifty three cases with a SMN and 442 controls were matched according to sex, age at first cancer, calendar year, type of first cancer and follow-up. The local radiation dose was estimated at the site of the SMN, for each case and at the same site, for the matched controls. The local dose of radiation significantly increased the risk of a SMN. The best model was linear with an excess relative risk per Gray equal to 0.13 (95% CI, 0.06; 0.26). Any chemotherapy significantly increased the risk of a SMN, odd ratio(adjusted) (OR(adjusted)) = 2.4 (95% confidence interval (95% CI), 1.4-4.1), but no dose-effect relationship was observed between any drug category and the risk of a SMN. Patients who had received concomitant chemo-radiotherapy were significantly more at risk of developing a SMN than patients who had been treated with sequential chemo-radiotherapy, even after adjustment for the local dose of radiation and the 6 most frequently administered drugs, OR(adjusted) = 2.3 (95%CI, 1.1-4.8). Radiation was found to be the foremost treatment-related risk factor for the occurrence of a SMN. Compared to sequential treatment, concomitant chemo-radiotherapy may lead to a higher risk of a SMN.
International Journal of Cancer 02/2007; 120(1):96-102. · 5.44 Impact Factor
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ABSTRACT: A design combining both related and unrelated controls, named the case-combined-control design, was recently proposed to increase the power for detecting gene-environment (GxE) interaction. Under a conditional analytic approach, the case-combined-control design appeared to be more efficient and feasible than a classical case-control study for detecting interaction involving rare events.
We now propose an unconditional analytic strategy to further increase the power for detecting gene-environment (GxE) interactions. This strategy allows the estimation of GxE interaction and exposure (E) main effects under certain assumptions (e.g. no correlation in E between siblings and the same exposure frequency in both control groups). Only the genetic (G) main effect cannot be estimated because it is biased.
Using simulations, we show that unconditional logistic regression analysis is often more efficient than conditional analysis for detecting GxE interaction, particularly for a rare gene and strong effects. The unconditional analysis is also at least as efficient as the conditional analysis when the gene is common and the main and joint effects of E and G are small.
Under the required assumptions, the unconditional analysis retains more information than does the conditional analysis for which only discordant case-control pairs are informative leading to more precise estimates of the odds ratios.
International Journal of Epidemiology 09/2006; 35(4):1067-73. · 6.41 Impact Factor
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ABSTRACT: Interest is increasing in studying gene-environment (G x E) interaction in disease etiology. Study designs using related controls as a more appropriate control group for evaluating G x E interactions have been proposed but often assume unrealistic numbers of available relative controls. To evaluate a more realistic design, we studied the relative efficiency of a 1:0.5 case-sibling-control design compared with a classical 1:1 case-unrelated-control design and examined the effect of the analysis strategy.
Simulations were performed to assess the efficiency of a 1:0.5 case-sibling-control design relative to a classical 1:1 case-unrelated-control design under a variety of assumptions for estimating G x E interaction. Both matched and unmatched analysis strategies were examined.
When using a matched analysis, the 1:1 case-unrelated-control design was almost always more powerful than the 1:0.5 case-sibling-control design. In contrast, when using an unmatched analysis, the 1:0.5 case-sibling-control design was almost always more powerful than the 1:1 case-unrelated-control design. The unconditional analysis of the case-sibling-control design to estimate G x E interaction, however, requires no correlation in E between siblings.
In most settings, a matched analysis may be required and a 1:1 case-unrelated-control design will be more powerful than a 1:0.5 case-sibling-control design.
Annals of Epidemiology 11/2005; 15(9):705-11. · 3.21 Impact Factor
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Marie-Gabrielle Dondon,
Florent de Vathaire,
Akhtar Shamsaldin,
Françoise Doyon,
Ibrahima Diallo,
Laurent Ligot,
Catherine Paoletti,
Martine Labbé,
Moncef Abbas,
Jean Chavaudra,
Marie-Françoise Avril,
Philippe Fragu,
François Eschwège
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ABSTRACT: A cohort study was performed as part of a European Radiation Protection Program to investigate the carcinogenic effect of treatment with ionizing radiation in early childhood. This paper presents mortality after radiotherapy in this cohort.
The cohort comprised 7037 patients under 15 years of age treated for a skin hemangioma between 1940 and 1973 at the Institut Gustave-Roussy, among whom 4940 received radiotherapy. The vital status and causes of death were obtained as well as the mortality rates in the general French population. External and internal analyses were performed. Standardized mortality ratio (SMR) and relative risk (RR) variations according to exposure to radiotherapy or not and the type of treatment were studied.
During the 1969-1997 follow-up period, 16 cohort patients died of cancer, 14 after radiotherapy. A non-significant excess of cancer-related mortality was observed for irradiated patients as compared to the general population (SMR=1.53; 95% CI=0.86-2.48). Treatment with (226)Ra seemed to play a significant role (RR=2.53; 95% CI=0.84-7.07) compared to no radiotherapy.
This study suggests an excess risk of cancer-related mortality in patients treated during early childhood with radiotherapy for skin hemangioma, and especially with (226)Ra. These patients need to be followed up in the future.
Radiotherapy and Oncology 08/2004; 72(1):87-93. · 5.58 Impact Factor
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Axelle Menu-Branthomme,
Carole Rubino,
Akhtar Shamsaldin,
Michael M Hawkins,
Emmanuel Grimaud, Marie-Gabrielle Dondon,
Claire Hardiman,
Gilles Vassal,
Sarah Campbell,
Xavier Panis,
Nicolas Daly-Schveitzer,
Jean-Leon Lagrange,
Jean-Michel Zucker,
Jean Chavaudra,
Olivier Hartman,
Florent de Vathaire
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ABSTRACT: Soft tissue sarcoma (STS) is one of the most frequent second primary cancer that occurs during the first 20 years following treatment for a solid cancer in childhood. Our aim was to quantify the risk of STS as a second malignant neoplasm and to investigate its relationship with radiotherapy and chemotherapy. A cohort study of 4,400 3-year survivors of a first solid cancer diagnosed during childhood in France or the United Kingdom, between 1942 and 1985, was followed 15 years on average. In a partially nested case-control study, we matched 25 cases of STS and 121 controls for sex, type of first cancer, age at first cancer and duration of follow-up. Sixteen STS occurred in the cohort, as compared to 0.3 expected from the general population (Standardized Incidence Radio, SIR = 54 (95%CI: 34-89)). The SIR was 113 (95% CI: 62-185) after chemotherapy plus radiotherapy (13 STS), whereas it was 28 (95%CI: 2-125) after chemotherapy alone (1 STS) and 19 (95%CI: 3-60) after radiotherapy alone (2 STS). After adjustment for treatment, there was no evidence of variation in the annual excess of incidence or in the SIR with either age at first cancer or time since 1st cancer. In the case-control study, the risk of a STS was increased with the square of the dose of radiation to the site of STS development and with the administration of Procarbazine. The increased risk of soft tissue sarcoma that occurred after childhood cancer is independently related to exposure to radiotherapy and Procarbazine. A closer surveillance of children treated with this treatment combination is strongly recommended.
International Journal of Cancer 06/2004; 110(1):87-93. · 5.44 Impact Factor
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ABSTRACT: The aim of our study was to quantify the risk of second malignant neoplasms (SMNs) among long-term survivors of neuroblastoma and to study the influence of treatment on this risk. We studied data from 544 5-year survival patients diagnosed with neuroblastoma before age 16 years at 8 French and British treatment centres from 1948 to 1986. After an average follow-up of 15 years (range, 5-38 years), 12 children developed a total of 13 SMNs, whereas 1.19 were expected from general population rates. Among these SMNs, there were 5 thyroid and 3 breast cancers. Increases of the risks of SMN were observed with time since neuroblastoma diagnosis and attained age. In a multivariate analysis, the relative risk of SMN associated with radiotherapy was 4.3 (95% CI 0.8-78), whereas no increased risk of SMN was associated with the administration of chemotherapy as a whole (RR = 0.4, 95% CI 0.1-1.9). Young children treated for a neuroblastoma have significantly increased risks of SMN over 3 decades of follow-up. Radiotherapy treatment was found to be an important risk factor for developing SMNs, whereas no effect of chemotherapy was evidenced. Although our findings reflect the late effects of past therapeutic modalities, they underscore the importance of long-term surveillance of young children treated for a neuroblastoma. For these patients, many more years of follow-up are required to appreciate their overall risks of treatment-related SMNs.
International Journal of Cancer 01/2004; 107(5):791-6. · 5.44 Impact Factor
