RESUMO
AIMS: Total dose, dose per fraction, number of fractions and treatment time are important determinants of the biological effect of a radiation regimen. Several randomised clinical trials (RCTs) have tested a variety of dosing regimens in advanced unresected non-small cell lung cancer, but survival remains poor. This work used past RCT data to develop and validate a predictive model that could help in designing new radiation regimens for successful testing in RCTs. MATERIALS AND METHODS: Eleven RCTs that compared radiation regimens alone were used to define the relationship between radiation regimens and 2-year survival. On the basis of this relationship, predictive models were developed. Predicted values were internally and externally validated against observed values from the same 11 RCTs and 21 other RCTs. Scatter plots and Pearson's correlation coefficient (r) were used for validation. Finally, regimens were explored that could improve survival. RESULTS: Increments in the total dose, dose per day and the number of treatment days were associated with improved survival; increments in dose-squared and treatment weeks were associated with reduced survival. The observed and predicted values were similar on internal (r = 0.96) and external validation (r = 0.76). Regimens that delivered a higher total dose over a shorter time had higher survival rates compared with the standard (60 Gy, 30 fractions, 6 weeks); survival may be improved by delivering the standard treatment in 5 weeks rather than 6 weeks. CONCLUSION: The developed model can predict the effect of thoracic radiation on survival in advanced non-small cell lung cancer patients. It is a useful tool for designing new radiation regimens for clinical trials.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/radioterapia , Modelos Biológicos , Planejamento da Radioterapia Assistida por Computador/métodos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Fracionamento da Dose de Radiação , Relação Dose-Resposta a Droga , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Dosagem Radioterapêutica , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes , Fatores de Risco , Taxa de Sobrevida , Resultado do TratamentoRESUMO
AIMS: To examine the effect of the daily use of micronutrients (including zinc) or the same micronutrients plus heat inactivated lactic acid bacteria (LAB), on diarrhoea in children compared to placebo. METHODS: A triple blind randomised clinical trial in an urban slum of Karachi, Pakistan. Micronutrients (including zinc), micronutrients (including zinc and LAB), or placebo, were provided daily for two months to 75 young children (aged 6-12 months) identified at high risk for diarrhoea related mortality on the basis of history of at least one episode of diarrhoea in the preceding two weeks. The longitudinal prevalence of diarrhoea was defined as the percentage of days a child had diarrhoea out of the days the child was observed. RESULTS: Mean longitudinal prevalence of diarrhoea in the micronutrient-zinc group was 15% (SD = 10%) child-days compared to 26% (SD = 20%) child-days in the placebo group and 26% (SD = 19%) child-days in the micronutrient-zinc-LAB group. The difference between the micronutrient-zinc-LAB and placebo groups was not significant. CONCLUSION: The daily provision of micronutrients (including zinc) reduces the longitudinal prevalence of diarrhoea and thus may also reduce diarrhoea related mortality in young children; heat inactivated LAB has negative effects in these children.
