Familial Nasopharyngeal Carcinoma 6

Staging of Nasopharyngeal carcinoma 313of radiotherapy delivery with enhanced spatial targeting,principally related to computerized planningand delivery systems such as intensity modulatedradiotherapy, as well as in more universal use of MRIto evaluate the local region of invasion by the tumor.As noted earlier, the PPS has held a special place inthe staging of NPC. But evidence appears to suggestthat the spatial importance of parapharyngeal extensionis diminishing due to the ability to encompassthis postero-lateral extension with modern radiotherapytechnique (Ng et al. 2008). At the same time,parapharyngeal extension seems also to be associatedwith a unique predisposition for risk of distantmetastases (approximately 11%) potentially mediatedby the passage of tumor through the parapharyngealvenous plexus and seems to be associatedwith risk as great or greater than regional lymphnode involvement (Cheng et al. 2005). Differences inidentifying this risk may also relate to differences inthe imaging techniques used by different investigators(i.e., CT vs. MRI) or to differences in the definitionof the regional anatomy (King et al. 2000; Liaoet al. 2008).24.4.2Adjustment in T1, T2a, and T2b CategoriesIn considering potential modifications to TNM, severalgroups in Asia have reminded us of the contributionand importance of the 5th and 6th edition TNM,but have also identified areas for improvement (Leeet al. 2004; Low et al. 2004; Liu et al. 2008). Thisextends to definitions of some of the elements: forexample within the spectrum of the existing T2a subcategory,different interpretations of nasal fossainvolvement seem to have prevailed with differentincidences of this subcategory between series (Auet al. 2003; Low et al. 2004; Liu et al. 2008). Multivariateanalysis quantifying different hazards of failure anddeath have shown discrepancies in the stage classification,though some of these may relate to smallnumber of patients in some groups and the consequencethis may have on subset analysis and the decisionto modify the classification. Nonetheless, arelatively consistent finding has been the absence ofa difference in outcome between T1 and T2a tumors,other than potentially for very extensive nasalinvolvement (Low et al. 2004), leading to a recommendationfor reclassification of patients with softtissue disease involvement of the oropharynx andnasal fossa to the T1 category (Lee et al. 2004; Liuet al. 2008) This will be included in the forthcomingclassification (Table 24.1).As well, in the substantial series from Hong Kongthat influenced the preceding recommendation concerningthe T2a category, 1,006 patients had T2bdisease (those with parapharyngeal extension).Analysis of this subset indicated that they remain asa distinct group with unfavorable prognosis comparedto the proposed T1 category, exhibiting a significantlyhigher hazard of local and distant failure,with consequent significant impact on cancer-specificdeath (Table 24.2). This effect was even moreapparent when restricted to patients without lymphnode involvement (Lee et al. 2004). An additionallarge series from mainland China that included 309patients with T2b disease confirmed these findings,therefore justifying that this sub-category continueindependently as a T2 category within the TNM (Liuet al. 2008). The latter series and that of Lee et al. fromHong Kong both demonstrated a more even rise inthe hazard ratio for adverse events with the redistributednew T-categories contained in the upcoming 7thedition TNM (i.e., T2a is reassigned to T1, and T2bremains as a T2 category) (Table 24.2).24.4.3Regional Lymph Nodes (EspeciallyRetropharyngeal Nodes)Retropharyngeal nodes have an iconic presence inNPC but have not been classified uniformly. Forexample, heterogeneous approaches among centershave considered them as N1 if unilateral, N2 if bilateral,N1 irrespective of laterality, N1 if discrete, orT2b if abutting adjacent soft tissue tissues, or unclassified(Lee et al. 2004). Some of these approachesreflect historic inadequacies in imaging prior to theera of cross-sectional imaging, especially MRI, andconsistent principles have not been identified inTNM. Recent series have assessed the prognosticimportance of retropharyngeal nodes including themethod by which they should be classified. In general,it seems compelling that MRI is superior to CTand resulted in the identification of abnormal retropharyngealnodes in an excess of 70% of patients in alarge series from Guangzhou, China (Tang et al.2008), compared to approximately 50% in a seriesfrom Singapore, where CT was the predominantimaging modality (Tham et al. 2009). Evidence from