Familial Nasopharyngeal Carcinoma 6

102 J-C. Lintumor volume was found to be the only independentfactor in predicting local control and one of independentfactors in predicting disease-specific survival;nodal volume was the only independent factor inpredicting neck control. In a subsequent study on116 patients with stage I–II NPC using similarmethod, Chua et al. (2004b) found that patients witha primary disease volume of >15 ml had significantlyworse 5-year local control rates (82% vs. 93%, p =0.033), but no statistically significant difference wasnoted in survival (5-year disease-specific survivalrates, 83% vs. 89%, p = 0.30). Multivariate analyses,however, demonstrated that only parapharyngealextension (T2b) and N1 stage were independent factorsthat predicted locoregional control and survival,and N1 stage was the only factor that predicted distantfailure. The authors concluded that the pretreatmentvolume of the primary disease has a limitedprognostic value in early-stage NPC compared withthe usual T- and N-classification, with stage T2b andN1 as independent factors that predicted treatmentoutcome.Willner et al. (1999) tried to estimate the correlationbetween CT scan-derived tumor volume and adose-response relation. The authors demonstratedthat tumor volume was an important factor influencinglocal control of NPC, and suggested that tumorvolume larger than 64 ml are unlikely to be controlledwith a total dose of 72 Gy.Four groups from Mainland China, Taiwan, andKorea using CT scan-derived measurement consistentlydemonstrated results similar to the aforementionedtrials (Shen et al. 2008; Chen et al. 2004; Changet al. 2002; Lee et al. 2008; Kim and Lee 2005). Shenet al. (2008) analyzed 154 NPC patients treated byaccelerated hyperfractionated radiation alone. After amedian follow-up of 61 months, the 5-year local failure-freerate, disease-free survival, and distant failurefreesurvival rates were 89.4% vs. 48.9% (p = 0.002),56.6% vs. 0% (p = 0.001), and 66.9% vs. 16.5% (p =0.0001), respectively, for patients whose primarytumor volume were £60 cm 3 and >60 cm 3 . Multivariateanalysis revealed that primary tumor volume is anindependent prognostic factor for local control (hazardratio = 3.568, p = 0.035). Two studies from Taiwanincluded 129 NPC patients with Stage I–IV (Chenet al. 2004) or 76 patients with Stage III–IV (Changet al. 2002) showed that tumor volume was a significantprognostic factor in both univariate and multivariateanalyses. The validation results with receiveroperating characteristic (ROC) curves also revealedthat, in predicting patient outcome, primary tumorvolume (area under the ROC = 83.33%) was superiorto T-classification (area under the ROC = 66.53%), andoverall stage (area under the ROC = 58.61%). Anotherstudy of 91 NPC patients treated by radiation alone orconcurrent chemoradiotherapy from Taiwan demonstratedthat primary tumor volume could separatedisease-specific survival more clearly than overallstage or T-classification and was the only independentprognostic factor by multivariate analysis (Lee et al.2008). In addition, Kim and Lee (2005) from Koreainvestigated 60 NPC patients with Stage I–IV andfound that large primary disease of >30 ml in volumewas associated with a significantly lower local control(46.9% vs. 84.2%, p = 0.004) and large cervical nodaldisease of >5 ml was associated with a significantlylower nodal control (64% vs. 100%, p = 0.019) andlower disease-specific survival (49.0% vs. 73.6%, p =0.046). In multivariate analysis, the primary tumorvolume and neck nodal volume were found to be independentfactors in predicting the local (p = 0.015) andnodal (p = 0.039) control, respectively.MRI has good soft tissue contrast resolution andthe capacity of obtaining different multiplanar imaging(Casselman 1994). It has been proven to besuperior to CT scan in determining the primarytumor extent of NPC in many studies (Jian et al.1998; Chong et al. 1999; King et al. 1999, 2000;Sakata et al. 1999; Chung et al. 2004). The studiesregarding volumetric analysis for NPC patients usingMRI, however, were sparse (Sze et al. 2004; Zhouet al. 2007; Chen et al. 2009). Zhou et al. (2007) demonstratedthat mean primary tumor volume increasedsignificantly with advanced T-classification; however,the authors did not analyze the impact of primarytumor volume on prognosis. Two studies addressedthe prognostic impact of tumor volume measured byMRI. Sze et al. (2004) collected 308 NPC patients inHong Kong with stage I–IV disease and retrospectivelymeasured the primary tumor volume includingretropharyngeal nodes on MRI. The 3-year ratesof local failure-free survival (97% vs. 82%, p < 0.01),progression-free survival (85% vs. 65%, p < 0.01),and overall survival (93% vs. 80%, p = 0.13) weremore superior for patients with a volume