Sylvie Guérin

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.

Frequency Distribution of Second Solid Cancer Locations in Relation to the Irradiated Volume Among 115 Patients Treated for Childhood Cancer

PURPOSE To provide better estimates of the frequency distribution of second malignant neoplasm (SMN) sites in relation to previous irradiated volumes, and better estimates of the doses delivered to these sites during radiotherapy (RT) of the first malignant neoplasm (FMN). METHODS AND MATERIALS The study focused on 115 patients who developed a solid SMN among a cohort of 4581 individuals. The homemade software package Dos_EG was used to estimate the radiation doses delivered to SMN sites during RT of the FMN. Three-dimensional geometry was used to evaluate the distances between the irradiated volume, for RT delivered to each FMN, and the site of the subsequent SMN. RESULTS The spatial distribution of SMN relative to the irradiated volumes in our cohort was as follows: 12% in the central area of the irradiated volume, which corresponds to the planning target volume (PTV), 66% in the beam-bordering region (i.e., the area surrounding the PTV), and 22% in regions located more than 5 cm from the irradiated volume. At the SMN site, all dose levels ranging from almost zero to >75 Gy were represented. A peak SMN frequency of approximately 31% was identified in volumes that received <2.5 Gy. CONCLUSION A greater volume of tissues receives low or intermediate doses in regions bordering the irradiated volume with modern multiple-beam RT arrangements. These results should be considered for risk-benefit evaluations of RT.

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.

L’épidémiologie des cancers en France en 2010 : comparaison avec les États-Unis

In 2007, a total number of 149,000 cancer deaths were observed in France, 89,100 in the male population and 60,600 in the female population, and in 2009, the number of new diagnoses of cancer is estimated to be 346,500, 197,500 among men and 149,000 among women. The most frequent cancers are prostate, lung and colorectal cancers in men, and breast, colorectal and lung cancers in women. Cancer mortality is higher in France than in the USA for men and lower for women. The largest differences between the two countries are observed for lung cancer and for head and neck (mouth, pharynx, larynx and oesophagus) cancers in men. Lung cancer mortality is higher in the USA than in France for men and much higher for women. These differences are explained by the difference in past tobacco consumption. For head and neck cancers in men, despite a very large decrease in France due mostly to the reduction in alcohol consumption, mortality remains today higher in France than in the USA.

Alcohol-attributable mortality in France.

BACKGROUND Alcohol consumption is high in France. AIM Estimation of alcohol-attributable mortality in France by sex, age and dose, for year 2009. METHOD We combined survey and sales data to estimate the prevalence of alcohol consumption by age, sex and dose category. For each cause of death, the relative risk of death as a function of dose was obtained from a meta-analysis and combined with prevalence data to obtain the attributable fraction; this fraction multiplied by the number of deaths gave the alcohol-attributable mortality. RESULTS A total of 36,500 deaths in men are attributable to alcohol in France in 2009 (13% of total mortality) versus 12,500 in women (5% of total mortality). Overall, this includes 15,000 deaths from cancer, 12,000 from circulatory disease, 8000 from digestive system disease, 8000 from external causes and 3000 from mental and behavioural disorder. The alcohol-attributable fractions are 22% and 18% in the population aged 15 to 34 and 35 to 64, respectively, versus 7% among individuals aged 65 or more. Alcohol is detrimental even at a low dose of 13 g per day, causing 1100 deaths. CONCLUSION With 49 000 deaths in France for the year 2009, the alcohol toll is high, and the effect of alcohol is detrimental even at low dose. Alcohol consumption is responsible for a large proportion of premature deaths. These results stress the importance of public health policies aimed at reducing alcohol consumption in France.

La fréquence des cancers en France en 2006 et les évolutions de la mortalité depuis 1950 et de l’incidence depuis 1980

In 2006, a total number of 149,000 cancer deaths were observed in France, 88,500 in the male population and 60,500 in the female population. In 2005, the number of new diagnoses of cancer is estimated to be 319,000, 183,000 among men and 136,000 among women. Age-standardised mortality rates are decreasing for most frequent cancer sites, at least in recent years, the main exceptions being lung in the female population, and pancreas in both male and female populations. Age-standardised incidence rate has increased by 38% between 1980 and 2005, when one takes demographic changes into account. This trend is the consequence of the increase in prostate cancer incidence among men and mostly of the increases in breast and lung cancers incidence, among women.

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 Hodgkins 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 Hodgkins 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 Hodgkins lymphoma, retinoblastoma, malignant bone tumor, STS, and germ cell tumor should receive close surveillance because they are at increased risk of developing any SMN.