© 1998 Oxford University Press
research-article |
Prognostic factors for mortality in nasopharyngeal cancer: accounting for time-dependence of relative risks
aUnit of Epidemiology for Cancer Prevention, International Agency for Research Cancer 150 Cours Albert Thomas, 69372 Lyon Cedex 08, France
bOn secondment from the Institut National de la Santé et de la Recherche Médicale (INSERM) France
cDepartment of Epidemiology and Biostatistics, McGill University, and Division of Clinical Epidemiology, Department of Medidne, Montreal General Hospital Montreal Quebec Canada
Reprint requests: Dr Annie J Sasco, Unit of Epidemiology for Cancer Prevention, International Agency for Research on Cancer, 150 Court Albert Thomas, 69372 Lyon Cedex 08. France
BACKGROUND: Few studies have assessed the role of prognostic factors for mortality from nasopharyngeal cancer and even fewer used multivariable methods. Most of these studies relied on the Cox model without testing the proportional hazards assumption.
METHODS: A cohort of 76 cases of nasopharyngeal cancer recorded in the Rhône, France, between 1980 and 1985, was followed until 1995. Proportional hazards assumption was tested for each putative prognostic factor. Two multivariable models were built using forward selection of prognostic factors: the Cox model and a flexible model in which variables not meeting the proportional hazards assumption were represented by a time-varying hazard ratio.
RESULTS: Only Epstein Barr Virus Nuclear Antigen (EBNA) serology, a marker of infection by the Epstein-Barr virus, and tumoral extent were selected in the analysis based on the Cox model. In contrast, four prognostic factors were significant at
=0.05 level in the flexible model: initial EBNA serology, tumoral histology, age and tumoral extent, the last two not verifying the proportional hazards assumption. The relative risk of age increases with duration of follow-up whereas the effect of tumoral extent changes in a non-monotonic pattern.
CONCLUSION: We showed the importance of taking into account the non-proportionality of hazards which can influence results and yield new insights about the role of prognostic factors in nasopharyngeal cancer. Because of the small size of our cohort, our results have to be confirmed in an independent study.
Keywords Nasopharyngeal neoplasm, prognostic factors, proportional hazards tests, parental occupation, Epstein-Barr Virus serology
Accepted 17 March 1998