Novel genetic and epigenetic alterations in ... - Ous-research.no

DiscussionThese examples underline that we have molecular knowledge that can help to determine amore optimal treatment regime in a more individualized way than what is performed today.The problem is that studies seeking to establish these facts all are lacking, preventing themolecular knowledge from being adapted into clinical use[130;179].Survival analysesSurvival analyses are often used to measure the effect of a certain drug or a certain markeron clinical outcome. The different endpoints are plentiful and the meaning of each can beconfusing as the same clinical endpoint can have different definitions. These differencesmake it complicated to compare results from different studies and highlights the need formore uniform and well-defined definitions of endpoints[198].Overall survival is maybe the most unambiguous of the endpoints in survival analyses. It iseasy to define, simple to measure and straightforward to interpret[199]. However, the factthat all kinds of mortalities are registered as events may lead to misinterpretation of theresults as colorectal patients often are of old age and may die of other reasons than cancerwithin the follow-up period[200]. Disease-specific survival is an attempt to improve this. Aproblem that presents itself with this type of analysis is that sudden deaths of cancer patientsare often registered as cancer-related deaths while the real cause may be different, leading toan overestimation of cancer-related deaths[200]. This problem is circumvented with overallsurvival, but again, that approach has its limitations in being over simplistic. Anotherchallenge with survival analyses is the requirement/need for long (and partly costly) followup period. A large study showed with a correlation of 0.89 that 3-year disease-free survival isa good surrogate endpoint to 5-year overall survival as most of the disease-specific eventswhich occurred within the first three years (such as local recurrences and metastases) led todeath within 5 years as most patients with a recurrent disease had died[199]. This finding canhave a significant impact on development and clinical testing of novel drugs as the time ofclinical trails could be reduced to almost the half of its origin, dramatically reducing theexpenses.60