PROGNOSTIC FACTORS FOR MORTALITY IN NASOPHARYNGEAL CANCER - ACCOUNTING FOR TIME-DEPENDENCE OF RELATIVE RISKS

Background Few studies have assessed the role of prognostic factors fo r mortality from nasopharyngeal cancer and even fewer used multivariab le methods. Most of these studies relied on the Cox model without test ing the proportional hazards assumption. Methods A cohort of 76 cases of nasopharyngeal cancer recorded in the Rhine, France, between 1980 a nd 1985, was followed until 1995. Proportional hazards assumption was tested for each putative prognostic factor. Two multivariable models w ere 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. Re sults Only Epstein Barr Virus Nuclear Antigen (EBNA) serology, a marke r of infection by the Epstein-Barr virus, and tumoral extent were sele cted in the analysis based on the Cox model. In contrast, four prognos tic factors were significant at alpha = 0.05 level in the flexible mod el: initial EBNA serology, tumoral histology, age and tumoral extent, the last two not verifying the proportional hazards assumption. The re lative risk of age increases with duration of follow-up whereas the ef fect of tumoral extent changes in a non-monotonic pattern. Conclusion We showed the importance of taking into account the non-proportionalit y of hazards which can influence results and yield new insights about the role of prognostic factors in nasopharyngeal cancer. Because of th e small size of our cohort, our results have to be confirmed in an ind ependent study.