ATYPICAL RESPONDERS LANDSCAPE REVIEW ∙ OCTOBER, 2017 35 CATEGORY RESPONSETOTHERAPY DURATIONOFSURVIVAL METRICS/QUANTITATIVE CRITERIA Exceptional responder Apatientwhohasresponded unusuallyfavorably(dramatic tumorshrinkage,development ofnoevidenceofdisease,oran unusuallylongprogression-free oroverallsurvival)toaparticular therapycomparedwithothers onthesametherapywhohave thesamecancerstageand subtypeofdisease(andpossibly asimilarnumberofpriorlinesof therapy). Thepatient mayormaynot havesurvived well past hisorherprognosis. A patient within the top[X]* percentileofthemeantherapeutic responsetoaspecific treatment protocol asmeasuredbyendpoints such asprogressionfree survival, overall survival, tumorshrinkage,etc. Rapid progressor Apatientwhohasresponded unusuallypoorly(dramatic tumorgrowthoranunusually shortprogression-freeoroverall survival)toaparticulartherapy comparedwithothersonthe sametherapywhohavethe samecancerstageandsubtype ofdisease(andpossiblyasimilar numberofpriorlinesoftherapy). Thepatient mayormaynot havesurvived well past hisorherprognosis. A patient within the bottom [X]* percentileofthemeantherapeutic responsetoaspecific treatment protocol asmeasuredbyendpoints such asprogressionfree survival, overall survival, tumorshrinkage,etc. Exceptionalsurvivor Thepatientmayormaynothave exhibitedanatypicalresponseto aspecifictherapeuticregimen. An advancedstagepatient whohasfar outlivedtheprognosisforhisorhercancer subtype. An advancedstage patientwhohas outlivedtheaverage life expectancy forhisorhercancersubtype bya factorof[X]* ormore,regardless ofthetypeorquantityof therapies received. TABLE 4 FRAMEWORK FOR THREE CATEGORIES OF ATYPICAL RESPONDERS Quantitative metrics should be developed by the research community and stated in each published study. Metrics may include standard deviation, percentile, etc. Quantitative criteria may need to be considered in terms of the clinical context including cancer type or subtype, patient population, therapeutic regimen, and number of prior lines of therapy. * The most appropriate percentile and factor of survival to apply to a quantitative definition of an atypical response are not known. This lack of a clear definition is one of the problems with the current state of studying atypical responses. Quantitative criteria should be applicable across multiple cancer types, patient populations, and therapeutic regimens.