Familial Nasopharyngeal Carcinoma 6

Early Stage Nasopharyngeal Cancer: A Highly Curative Disease with Radiation Therapy 143higher risk patients despite that fact that risk factorsappeared balanced, and also the time span over,which these patients were accrued (1986–2004).However, most nasopharyngeal series show improvedoutcomes for patients treated in more modern times,and the opposite is seen here.Locally advanced chemoradiation trials fornasopharyngeal cancer show a clear benefit to concurrentchemotherapy, and less certain benefit tosequential chemotherapy. Trials exploring the benefitof concurrent chemotherapy in the setting of a highriskpopulation of early-stage disease are lacking.10.4Radiation Therapy Technique in theTreatment of Early Stage NPC10.4.1Altered FractionationAltered fractionation regimens, including hyperfractionationand concomitant boost accelerated fractionation,have been explored in multiple head andneck cancer trials, and typically nasopharyngeal primariesare excluded. The U. S. Intergroup Study trial0099 trial (Al-Sarraf et al. 1998) employed oncedaily radiation therapy with or without chemotherapy.There has been some activity exploring nasopharyngealcancer with altered fractionation regimensbecause they have led to local control improvementsin other sites such as the oropharynx (Horiot et al.1992; Fu et al. 2000).Few randomized trials addressing the role of twicea-dayirradiation vs. once-a-day irradiation in headand neck cancer have included tumors of thenasopharynx (Sanchiz et al. 1990; Teo et al. 2000).Sanchiz and colleagues’ (1990) trial included 892locally advanced head and neck cancers (UICC stageT3-T4, N0–3, M0). The patients were randomized todaily radiotherapy (Group A), twice-daily irradiation(Group B), and once daily irradiation with 5-fluorouracil(5-FU) (Group C). This study included 92 patientswith nasopharyngeal cancer, a practice that stoppedonce results of the Intergroup 0099 study determineda standard of care for nasopharyngeal cancer. Diseasefreesurvival and survival were improved with bothhyperfractionation and chemotherapy (Groups B andC), in comparison with Group A. No difference wasseen between the hyperfractionation group and thechemotherapy group. Inadequate details and patientnumbers are available to assess the efficacy of hyperfractionationfor early stage disease.A randomized trial specific to the nasopharynxwas conducted in Hong Kong and accrued 159patients, and compared conventional radiotherapywith accelerated hyperfractionated radiotherapy(Teo et al. 2000). All patients in this study were N0 orN1 (Ho stage). Data at 5 years demonstrated no differencein survival or disease control, but there wasan increased incidence of neurological injury withthe experimental arm, with increased temporal lobenecrosis, optic apparatus injury, and brainstem/cordinjury. Conventional two-dimensional radiotherapytechnique was employed in this study, and it is possiblethat with modern technique and increased interfractioninterval the results could be improved. Anincrease in acute and late complications secondary toaccelerated fractionation for nasopharyngeal carcinoma,without improvement in disease control, hasbeen reported elsewhere (El-Weshi et al. 2001). TheUniversity of Florida employed hyperfractionation in45 of 82 patients undergoing radiotherapy (with orwithout chemotherapy) for nasopharyngeal carcinoma,and reported no increase in efficacy or complications(Mendenhall et al. 2006).10.4.2Intensity ModulationIMRT has essentially become standard of care for themajority of head and neck cancer sites. IMRT is auseful technique for the nasopharynx, due to theproximity of critical structures to the target. Withconventional therapy, there is considerable risk oflate morbidity. Several dosimetric studies have demonstratedan improvement for IMRT over conventionaltechniques and 3D conformal techniques inthe setting of nasopharyngeal cancer (Verhey 1999;Sultanem et al. 2000; Hunt et al. 2001; Munteret al. 2002; Lee et al. 2003). There are several singleinstitution series demonstrating the efficacy of IMRTfor head and neck cancer in general (Chao et al.2003) and for the nasopharynx in particular (Leeet al. 2002), and a phase II multiinstitutional trial hasbeen conducted by the RTOG (RTOG 0225).RTOG 0225 utilized an integrated boost techniqueof the boost, with 2.12 Gy delivered to the primaryPTV while 1.8 Gy is delivered to an intermediate subclinicalPTV, both over 33 fractions. The low neckand regions at lesser risk received lesser doses. Theregimen was based on UCSF experience, showing