Familial Nasopharyngeal Carcinoma 6

Staging of Nasopharyngeal carcinoma 311nasopharyngeal inspection and biopsy as well as chestimaging to exclude distant metastases (NCCN 2009).For imaging of the nasopharynx and base of skull,MRI with gadolinium is normally recommended andwould usually include the regional lymph node regionsdown to the level of clavicles. Alternatively, positronemission tomography–computerized tomography(PET/CT) and CT with contrast may be performed.Imaging for distant metastases is essential, especiallyfor nonkeratinizing lesions and in patients with N2and N3 disease. Evaluation of at risk patients shouldinclude bone scan and CT of the chest and liver.Alternatively, PET/CT may be preferred to exclude distantdisease (NCCN 2009). In general, evidence suggeststhat MRI is superior to PET/CT for the assessmentof locoregional invasion and retropharyngeal nodalmetastasis (Liao et al. 2008). PET/CT seems moreaccurate than MRI in determining cervical lymphnode metastasis, and its sensitivity, specificity, andaccuracy suggest that PET/CT can replace conventionalwork-up in the detection of distant metastasis(Chua et al. 2009). Therefore, a combination of PET/CT and head-and-neck MRI has been suggested forthe initial staging of NPC patients (Ng et al. 2009).24.3A Milestone in the TNM Classification24.3.1The 5th edition TNMSince anatomic features are so important in NPC, arelevant and reproducible system of stage classificationhas always been a priority. The absence of aninternational consensus had previously resulted inthe proliferation of stage classifications (Lee et al.1996b). The majority were derived from the anatomicextent of disease, but one also used nonanatomic factors(Neel and Taylor 1989). Mounting enthusiasmfor the revision of UICC/AJCC TNM commenced inthe early 1990s, in preparation for the publication ofthe 5th edition TNM in 1997. This initiative arosefrom a recognition that the staging system in frequentuse in southeast Asia was that of Ho and that this andother classifications were superior to the UICC andAJCC TNM (Teo et al. 1991a; Teo et al. 1991b; Lee etal. 1996a). The consequence was a complete revisionof the earlier UICC/AJCC 4th edition classification(Fleming et al. 1997; Sobin and Wittekind 1997),establishing a milestone for the classification that wasdeveloped jointly, and by consultation involving aninternational task force comprised mainly of radiationoncologists in south-east Asia and elsewhere, incollaboration with the UICC and the AJCC.24.3.2Background to Changes in the 5th Edition TNM24.3.2.1Modification of the Ho T-ClassificationThe Ho classification had never separated differentsubsites of involvement within the nasopharynx,which the UICC and AJCC had classified as T1 and T2categories, a subdivision that lacked validity (Shamet al. 1992). The absence of attention to PPS involvementin the TNM was considered a weakness, althoughits true place in the stage classification was problematiceven then (Sham and Choy 1991; Chua et al.1996; Teo et al. 1996a). This was, in part, because ofthe changing ability to identify PPS disease with contemporaryimaging (thereby introducing “stage creep”effect), the influence of treatment modifications toaccount for it in many centers (thereby potentiallymodifying its effect), and the problem of definitions(thereby rendering the data difficult to interpret).However, the view at the time of the 5th edition revisionwas that PPS should be included in an intermediateT-category (e.g., within categories T2 or T3 of afour category T system, and identified separately).Complicating the discussions were the differentways of subdividing the involvement of the PPS. Onesystem involved classification based on lateral extensionby NPC across the PPS (Sham and Choy 1991),another separated the pre vs. poststyloid componentsof the PPS (Min et al. 1994), while another subdividedthe PPS into paranasopharynx vs. paraoropharynxat the C1/C2 interspace (Tsao 1993).For the TNM 5th edition revision, much reliancewas given at the time to unpublished data concerningPPS involvement from the Queen Elizabeth Hospital(QEH) in Hong Kong for Ho T2 disease (tumor extensionto adjacent soft tissue). Although cancer specificsurvival was worse in the presence of PPS involvement,this was largely explained on multivariate analysisby the fact that PPS extension was associated withhigher neck stage (William Foo, personal communication).Nevertheless, the need for a consistent classificationovershadowed the problem of discordantbeliefs about the importance of PPS invasion or howit should be weighted or described. It was incorporated