Familial Nasopharyngeal Carcinoma 6

Nasopharyngeal Cancer in Pediatric and Adolescent Patients 297Catonese, Arabs, and Inuits for NPC include highconsumption of preserved foods and dried meats inchildhood, when compared with the controls in anearlier study (Hubert and De-The 1982). In theintermediate- to high-risk Chinese populations suchas those from the Southern provinces, consumptionof salted fish, especially during weaning in childhood,has been found to be associated with increased riskof NPC (Yuan et al. 2000).Earlier reports and favorable treatment outcomeshave demonstrated that pediatric form of NPC hasfeatures reminiscent of lymphomas. Recently, a fewresearchers pointed to the role of EBV in the pathogenesisof various neoplasms including Hodgkin’sdisease and NPC, and indicated that both malignancieshave the same type II EBV latency and showbimodal age distribution (Barista et al. 2007).Specific human leukocyte antigens (HLA) andalleles have been associated with adult NPC in severalpopulations including Asian and North Africanpopulations (Goldsmith et al. 2002; Dardari et al.2001). A similar study was presented recently onyoung Turkish patients with an age of less than 30years (Daglikoca et al. 2007). In this study, four ofthe genes (BLU, RASSF1, p16-INK4a, and UBAP1),previously implied on adult NPC cases, were chosenand analyzed, with the hypothesis that these genesmay cause liability to childhood NPC in a recessivemanner. The homozygosity frequency of the patientgroup was found to be twice as high as the frequencyof the control group, and the authors concluded thattheir result provides strong evidence to support thehypothesis that p16-INK4a causes liability to NPC,but it is not sufficient to support the hypothesis thatit causes liability to childhood-specific NPC.Distinct clinical features of pediatric NPC led theinvestigators to search for biological characteristics,which may explain this clinical difference betweenthe pediatric and adult NPCs (Ayan and Altun 2003).Expression of p53, Bcl-2 family, Ki67, c-Kit, cyclooxygenase-2,epidermal growth factor receptor, and EBVlatent membrane protein (EBV LMP1) was evaluatedin a cohort of pediatric NPC patients, and predictionof survival, recurrence, lymph node metastasis wasfound in some (Khabir et al. 2000; Fang et al. 2007).Khabir et al. (2000) previously demonstrated thatp53 accumulation is much less frequent in youngerpatients. The same group of researchers investigatedBcl-2 and Bcl-X expression by immunohistochemistryin patients below 30 years of age or those agedover 30 years. The average Bcl-2 score was found tobe much lower for patients below 30 years of age, andconcluded that this finding strengthened theirhypothesis that oncologic mechanisms may be differentfor pediatric and adult patients. Their comparisonof clinical data revealed a major differencebetween patients below 30 years of age or older interms of frequency of lymph node involvement also.While all patients below 30 years of age had clinicallymph node invasion, the figure was 66% for patientsolder than 30 years of age. The same observation wasmade previously by Maalej et al. (1995), and theyfound that almost all the patients in their series withT4N0 disease were over 30 years of age.23.3Treatment StrategyThe optimal treatment modality for pediatric NPChas not been established; however, any potentialreduction in radiation field and doses is desirable dueto the significant chronic morbidity among long-termsurvivors. While the concomitant chemotherapy andradiation, with or without adjuvant chemotherapy, isthe current standard for adult patients with NPC,neoadjuvant chemotherapy with radiotherapy hasgained popularity parallel to other paediatric treatmentprotocols in various solid tumors (Al-Sarrafet al. 1998; Ayan et al. 2000).23.4Radiation TherapyRadiation therapy (RT) has been the mainstay of thetreatment in both adult and pediatric NPC (Wei andSham 2005; Ozyar et al. 1999). Owing to the rarity ofpediatric NPC, most of the published series are relativelyheterogeneous in terms of patient, tumor, andtreatment characteristics. Moreover, radiotherapydose for disease control in paediatric NPC has reportedlyranged from 50 to 70 Gy in the literature(Fernandez et al. 1976; Gasparini et al. 1988).Literature on RT for pediatric NPC can be classifiedinto the following three groups: historical retrospectiveseries published in the late 1970s and early1980s, more recent retrospective series, and prospectiveseries. Reports in the first group of literaturetypically included few patients, with inadequate staging,and with suboptimal treatment strategies suchas radiotherapy using orthovoltage or Co-60 techniquesand noncisplatin-based chemotherapy regi-