SummaryThe variation in the risk of solid second malignant neoplasms (SMN) with time since first cancer during childhood has been previously reported. However, no study has been performed that controls for the distribution of radiation dose and the aggressiveness of past chemotherapy, which could be responsible for the observed temporal variation of the risk. The purpose of this study was to investigate the influence of the treatment on the long-term pattern of the incidence of solid SMN after a first cancer in childhood. We studied a cohort of 4400 patients from eight centres in France and the UK. Patients had to be alive 3 years or more after a first cancer treated before the age of 17 years and before the end of 1985. For each patient in the cohort, the complete clinical, chemotherapy and radiotherapy history was recorded. For each patient who had received external radiotherapy, the dose of radiation received by 151 sites of the body were estimated. After a mean follow-up of 15 years, 113 children developed a solid SMN, compared to 12.3 expected from general population rates. A similar distribution pattern was observed among the 1045 patients treated with radiotherapy alone and the 2064 patients treated with radiotherapy plus chemotherapy; the relative risk, but not the excess absolute risk, of solid SMN decreased with time after first treatment; the excess absolute risk increased during a period of at least 30 years after the first cancer. This pattern remained after controlling for chemotherapy and for the average dose of radiation to the major sites of SMN. It also remained when excluding patients with a first cancer type or an associated syndrome known to predispose to SMN. When compared with radiotherapy alone, the addition of chemotherapy increases the risk of solid SMN after a first cancer in childhood, but does not significantly modify the variation of this risk during the time after the first cancer.
Background
The efficacy of influenza vaccines may vary annually. In 2004–2005, when antigenically drifted viruses were circulating, a randomized, placebo-controlled trial involving healthy adults showed that inactivated vaccine appeared to be efficacious, whereas live attenuated vaccine appeared to be less so.
Methods
In 2005–2006, we continued our trial, examining the absolute and relative efficacies of the live attenuated and inactivated vaccines in preventing laboratory-confirmed symptomatic influenza.
Results
A total of 2058 persons were vaccinated in October and November 2005. Studywide influenza activity was prolonged but of low intensity; type A (H3N2) virus was circulating, which was antigenically similar to the vaccine strain. The absolute efficacy of the inactivated vaccine was 16% (95% confidence interval [CI], −171% to 70%) for the virus identification end point (virus isolation in cell culture or identification through polymerase chain reaction) and 54% (95% CI, 4%–77%) for the primary end point (virus isolation or increase in serum antibody titer). The absolute efficacies of the live attenuated vaccine for these end points were 8% (95% CI, −194% to 67%) and 43% (95% CI, −15% to 71%), respectively.
Conclusions
With serologic end points included, efficacy was demonstrated for the inactivated vaccine in a year with low influenza attack rates. The efficacy of the live attenuated vaccine was slightly less than that of the inactivated vaccine, but not statistically greater than that of the placebo.
Trial registration
ClinicalTrials.gov identifier: NCT00133523.
Although we cannot estimate the exact proportion, it is probable that some or all children who are treated for cancer are predisposed to developing a thyroid carcinoma.
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