Familial Nasopharyngeal Carcinoma 6

Prognostic Factors in Nasopharyngeal Cancer 121(p = 0.007) and multivariate (p = 0.02) analyses. Twolarger series containing more patient numbers fromSingapore (677 cases) and Mainland China (621cases), further divided PPS invasion into two subgroups:paranasopharyngeal space and paraoropharyngealspace invasion with distinction at the C1/C2interspace (Heng et al. 1999; Ma et al. 2001a). Bothstudies found that the PPS invasion was not a significantprognostic factor. Whereas, the paraoropharyngealspace invasion itself was an independent variableon overall survival (p = 0.02) in Heng’s study and onoverall (p = 0.0028), local failure-free (p = 0.0116),and metastasis-free (p = 0.0050) survivals in Ma’sstudy. Using similar definition of PPS invasion, severallarge studies from endemic regions (Xiao et al.2002; Yeh et al. 2005; Cheng et al. 2005) consistentlyshowed that PPS invasion was an important prognosticfactor for various survival analyses. Amongseries using CT scan as a detection tool for PPS invasion,two studies failed to support the prognosticvalue of PPS invasion. Teo et al. (1996) from HongKong reported that PPS invasion had no survivalimpact for 903 patients as a whole when a parapharyngealboost radiation was given, except for the Ho’sstage T2N0M0 subgroup. An additional study of 1294patients by Au et al. (2003) also illustrated that PPSinvasion was not a significant factor for survival orfailure at any site on multivariate analysis.Two recent studies used MRI and 3D conformalradiation technique as a diagnostic and therapeuticmodality. Of the 364 Stage I–III NPC patients enrolledin the study reported by Cheng et al. (2005), 201 (55.2%)had PPS invasion or skull base involvement. The 5-yeardistant metastasis-free survival rates in Stage I–IIA (30cases), Stage II–III without PPS invasion/T3 disease(133 cases), and Stage IIB-III with PPS invasion/T3 diseasewere 100%, 95.8%, and 83.0%, respectively (p =0.004). They suggest that PPS invasion/T3 is a poorprognostic factor for distant failure in Stage I–III NPCpatients. In addition, their data also demonstrate significantimprovement of overall (p = 0.005) and recurrence-free(p = 0.01) survival using adjuvantchemotherapy for Stage II–III NPC patient with PPSinvasion/T3 disease. With the advancement of 3D conformalradiation therapy, better dosimetric coverageof the PPS can be achieved. Ng et al. (2008) postulatedthat the poor clinical outcome of PPS invasion waspredominantly related to the suboptimal dose. Theyretrospectively analyzed the prognostic value of PPSinvasion after conformal radiation therapy for 700NPC patients. In their series, the whole incidence ofPPS invasion was high (74%) by MRI detection. Onunivariate analysis, the degree of PPS invasion seemedto predict for overall, local failure-free, metastasis-freesurvivals. However, after stratification according toT-Classification, the prognostic value of PPS invasionwas lost for local failure-free and metastasis-free survivals,and it only reached statistical significance inpredicting overall survival for T3 patients. MultivariateCox regression analysis revealed that the extent of PPSinvasion was not an independent prognostic factor foroverall, local failure-free, and metastasis-free survivals.The authors suggested that PPS invasion per se nolonger predicts disease outcome.The significance of RPLN metastasis in clinicalstaging and prognosis has not been defined clearlyfor NPC. The current version of AJCC/UICC stagingsystem does not include the status of RPLN. The reasonsmay be (1) very rare reports addressed the prognosticimpact of RPLN metastasis and results werecontroversial; (2) most previous studies used CT scanfor RPLN detection, which was less sensitive thanMRI; (3) the criteria of RPLN metastasis differed indifferent studies. MRI has proven to be superior to CTscan in delineating primary soft tissue invasion, subtleintracranial invasion, and RPLN metastasis andhas become more valuable in both staging and treatmentplanning for NPC management. The reporteddetection rates of RPLN in NPC were 11.2%–51.8%with CT scan (Chong et al. 1995; Chua et al. 1997a;Xiao et al. 2002; Kalogera-Fountzila et al. 2006;Ma et al. 2007) and 51.8%–89% with MRI (Chonget al. 1995; Lam et al. 1997; Sakata et al. 1999; Kinget al. 2000; Ng et al. 2004, 2007; Liu et al. 2006; Lu et al.2006; Tang et al. 2008; Wang et al. 2009). Six studiesreported the prognostic value of RPLN metastasis inNPC. Using CT scan and size of 10 mm or more aspositive for RPLN metastasis, Chua et al. (1997a)observed no significant difference in treatment outcomebetween patients with or without RPLN metastasis.Without mention of the cutoff size of positiveRPLN metastasis, Kalogera-Fountzila et al. (2006)reported no significant effect of RPLN on overall survivalanalysis. Using CT scan and nodal size 5 mm ormore, Ma et al. (2007) found 51.5% of 749 NPCpatients had RPLN metastasis. The 5-year overall survivaland metastasis-free survival rates were 58.7% vs.72.2% (p < 0.001) and 75.0% vs. 84.6% (p < 0.001) forpatient with or without RPLN metastasis. Afteradjusting for T-calssification and N-calssification, theprognostic value became less significant for overallsurvival (p = 0.118) and metastasis-free survival (p =0.079). One of the three MRI-based studies reportedthat RPLN metastasis was an independent prognostic