Familial Nasopharyngeal Carcinoma 6

320 B. O’Sullivan and E. YuFig. 24.7. Actuarial survivalcurve for early stage (I andII) nasopharyngeal carcinomasegregated accordingto high vs. low Epstein–Barrvirus (EBV) DNA titer priorto treatment. Low DNAdenotes low EBV DNAlevels of less than 4,000copies/mL, and high DNAdenotes high EBV DNAlevels equal or greater than4,000 copies/mL. The subgroupwith high titers haveoutcome that appears inferiorto Stage III disease inthe remainder of the study.Reproduced with permissionfrom reference (Leung et al.2006)Alive (%)1.00.80.60.40.2 Low DNAHigh DNA0No. of patients at risk:24 6 8YearLow DNA 108High DNA 471064294 48316and manpower considerations, alternative more simplemethods have also been suggested, includingstandard bidimensional measurements (King et al.2007; Lee et al. 2009). While there seems to be nodoubt that tumor volume provides a robust predictorof outcome in NPC, the manpower issues and otherproblems have not yet been resolved, including thedetermination of agreed potential cut-points thatmight be used to create a classification that meets theneeds of clinicians and scientists throughout theregions where NPC is prevalent.24.6.2Assessment of EB Viral Copy NumberAmong mucosal head and neck cancers, NPC hasadditional uniqueness in possessing a robust circulatingtumor marker that can be expected to be employedclinically. One of the uses is the correlation of circulatingEBV DNA with disease staging, using quantitativereal-time polymerase chain reaction (PCR) technology(Lo 2001). By means of its production by NPCcells, EBV DNA level has been shown to be more powerfulthan existing staging system in predicting outcomesby providing an index of disease burden in theindividual patient and has been investigated now bynumerous authors (Chan and Lo 2002). In particular,Leung et al. showed that pretherapy circulation ofEBV DNA load is an independent prognostic factorfor overall survival in NPC. Thus patients with earlystage disease can be segregated by EBV DNA levelsinto a poor-risk subgroup with survival similar to thatof stage III disease and a good-risk subgroup withsurvival similar to stage I disease (Leung et al. 2006)(Fig. 24.7). While this provides a very attractive andundeniable concept, it also faces challenges in whetherit can be applied universally at this time, especially inregions where the disease is most prevalent andresources are not as plentiful as in the developedworld. A possibility may be to use it presently as anadditional tool within clinical trials to augment prognosticassessment and disease monitoring.24.7SummaryThe dominant theme of prognosis in NPC continuesto be the complex anatomic issues that occur in thisdisease and in particular, the proximity of disease tocritical adjacent anatomy which may be injured byhigh dose radiotherapy. For this reason, the developmentof a relevant world-wide anatomic staging systemwas an important step forward in the 5th editionof TNM. The classification remained stable for the6th edition but changes are to be included it the 7thedition, largely related to the ability to spatially targetregions that were previously less accessible to