Board-certified specialty training program in radiation oncology in a war-torn country: Challenges, solutions and outcomes.

BACKGROUND: Residency programs leading to board certification are important for safe and competent Radiation Oncology (RO) practice. In some developing nations, there is a gap in this field. This work addresses the experience that was accomplished to establish such a program in Iraq despite all the challenges that faces a country under war. METHODS: Descriptive report of challenges faced in a developing country that is still reeling from war, the steps taken to overcome these challenges and outcomes after graduation of two classes. RESULTS: After over 18 months of prerequisite technical and logistical preparations, a group of local and external faculty members were invited to establish the required syllabus of a structured RO residency program in Iraq. It is comprised of a total of 100 post-graduate academic credits over a 48-months period after clinical internship. First year evaluations included regular practical assessments; seven in-house papers covering RO, cancer and radiation biology, medical physics, radiological anatomy and diagnostic oncology, tumor pathology, onco-pharmacology, and medical statistics, research methodology, and cancer epidemiology, followed by a comprehensive examination. Subsequent evaluations were on an annual bases with enrollment in the American College of Radiology In-Training examination in RO. Final assessment included logbook and skills' reviews, graduation thesis or peer-review publication, two-papers' written examination, and an exit practical examination. CONCLUSIONS: Given the political, economic and social difficulties in post-war Iraq, it was a major challenge to establish a residency program in RO. Despite the significant difficulties, the first residency program leading to board certification in RO was successfully started in Iraq. The new specialists will help in addressing the shortage of radiation oncologists in the country.

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.

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.

Long-term mortality from second malignant neoplasms in 5-year survivors of solid childhood tumors: temporal pattern of risk according to type of treatment.

BACKGROUND: The temporal pattern in mortality from late second malignant neoplasms in solid childhood cancer survivors, according to the type of treatment, has not been investigated in detail. METHODS: We studied 4,230 5-year survivors of solid childhood cancer diagnosed between 1942 and 1986 in France and the United Kingdom. Complete clinical, chemotherapy, and radiotherapy data were recorded and the integral radiation dose was estimated for 2,701 of the 2,948 patients who had received radiotherapy. RESULTS: After a median follow-up of 28 years, 134 fatal events were due to second malignancies, compared with the 13.3 expected from the general France-UK population rates. The standardized mortality ratio was of a similar magnitude after radiotherapy alone and chemotherapy alone and higher after both treatments. The standardized mortality ratio decreased with follow-up, whereas the absolute excess risk increased significantly over a period of at least 25 years after the first cancer. This temporal pattern was similar after chemotherapy alone, radiotherapy alone, or both treatments. We observed a similar long-term temporal pattern among survivors who had died of a second malignant neoplasm of the gastrointestinal tract and breast. Survivors who had received a higher integral radiation dose during radiotherapy were at a particularly high risk, as well as those who had received alkylating agents and epipodophyllotoxins. CONCLUSIONS: Five-year survivors of childhood cancer run a high long-term mortality risk for all types of second malignant neoplasms whatever the treatment received and require careful long-term screening well beyond 25 years after the diagnosis.

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.

Treatment-adjusted predisposition to second malignant neoplasms after a solid cancer in childhood: a case-control study.

PURPOSE: Previous therapy, genetic susceptibility, and the type of first malignant neoplasm (FMN) are known to be associated with the risk of second malignant neoplasm (SMN) among patients treated for a childhood cancer. The aim of this study was to investigate the independent role of the FMN in the onset of any SMN. PATIENTS AND METHODS: A case-control study nested in a European cohort of 4,581 patients treated for a solid cancer during childhood was conducted. One hundred forty-six patients with an SMN and 417 controls were matched for sex, age at FMN, chemotherapy, radiotherapy, the local radiation dose received at the site of SMN for patient cases and at the same site for the matched controls, and follow-up. RESULTS: A significantly increased risk of developing any SMN was observed after Hodgkin's lymphoma, retinoblastoma, malignant bone tumor, soft tissue sarcoma (STS), and germ cell tumor as FMN, after adjustment for chemotherapy and family cancer syndrome. No significant risk of developing a carcinoma was observed among patients who had developed Hodgkin's lymphoma as FMN. A significantly increased risk of developing a sarcoma was observed among patients who had developed a retinoblastoma (adjusted odds ratio [ORa] = 7.5; 95% CI, 1.2 to 46), a malignant bone tumor (ORa = 13.3; 95% CI, 1.5 to 117), an STS (ORa = 4.8; 95% CI, 1.3 to 18), or a carcinoma (ORa = 9.4; 95% CI, 1.1 to 82) as FMN. CONCLUSION: Survivors of Hodgkin's lymphoma, retinoblastoma, malignant bone tumor, STS, and germ cell tumor should receive close surveillance because they are at increased risk of developing any SMN.

Radiation exposure and familial aggregation of cancers as risk factors for colorectal cancer after radioiodine treatment for thyroid carcinoma.

PURPOSE: In thyroid cancer patients, radioiodine treatment has been shown to be associated with an increased risk of colon carcinoma. The aim of this study in thyroid cancer patients was to evaluate the role of familial factors in the risk of colorectal cancer and their potential interaction with radioiodine exposure. METHODS AND MATERIALS: We performed a case-control study on 15 colorectal cancer patients and 76 matched control subjects, nested in a cohort of 3708 thyroid cancer patients treated between 1933 and 1998. For each patient, the radiation dose delivered to the colon by radioiodine was estimated by use of standard tables. In those who received external radiation therapy, the average radiation doses delivered to the colon and rectum were estimated by use of DOS_Eg software. A complete familial history was obtained by face-to-face interviews, and a familial index was defined to evaluate the degree of familial aggregation. RESULTS: The risk of colorectal cancer increased with familial aggregation of colorectal cancer (p = 0.02). After adjustment for the radiation dose delivered to the colon and rectum, the risk of colorectal cancer was 2.8-fold higher (95% CI, 1.0-8.0) for patients with at least one relative affected by colorectal cancer than for patients without such a family history (p = 0.05). The radiation dose delivered to the colon and rectum by (131)I and external radiation therapy was associated with an increase of risk near the significance threshold (p = 0.1). No significant interaction was found between radiation dose and having an affected relative (p = 0.9). CONCLUSIONS: The role of familial background in the risk of colorectal cancer following a differentiated thyroid carcinoma appears to increase with the radiation dose delivered to the colon and rectum. However, the study population was small and no interaction was found between these two factors.

Cancer mortality after radiotherapy for a skin hemangioma during childhood.

BACKGROUND AND PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Radiation dose, chemotherapy and risk of soft tissue sarcoma after solid tumours during childhood.

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.

Long-term risk of second malignant neoplasms after neuroblastoma in childhood: role of treatment.

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.