Familial Nasopharyngeal Carcinoma 6

300 E. Ozyar and I. Ayanchemotherapy, EBRT, and high dose-rate brachytherapyboost and adjuvant chemotherapy. The total doseof 10 Gy was given in two fractions under local anesthesiausing metallic applicators. At the median follow-uptime of 54 months, the local control wasachieved in 15 out of 16 patients. However, one shouldbe cautious when evaluating these results as otherseries had high rates of local control with similarexternal radiotherapy doses.It was shown that IMRT provides superior targetcoverage and normal tissue sparing when comparedwith conventional radiotherapy (CRT) in adultpatients with NPC (Kam et al. 2004). However, whencompared with CRT, a twofold increase in the integraldose has been theoretically estimated with theuse of IMRT due to the larger treatment volumes. Inthe pediatric setting, the risk could be significant dueto a higher inherent susceptibility of tissues. However,as the risk of secondary cancers related with IMRTwas estimated to be 2% when compared with 1% forCRT, it seems logical to utilize IMRT in pediatric NPCto decrease the significant late effects. The efficacy ofIMRT in reducing the acute and late toxicity in childrenwith NPC was recently reported by two centers(Louis et al. 2007; Laskar et al. 2008). A single institutionexperience with five pediatric NPC patientswho were treated with chemotherapy and IMRT wasreported (Louis et al. 2007). With a median follow-upof 6.3 years, all the patients experienced ≥3 of acuteand late toxicities. The most common toxicities werereported to be hypothyroidism, xerostomia, hearingloss, and dental disease. The authors concluded thatthey did not observe a significant decrease in thelong-term toxicities with IMRT plus chemotherapyin their small cohort of pediatric NPC patients. Thesecond study was reported from the Tata MemorialCenter in India (Laskar et al. 2008). A total of 36children were included in this retrospective study. Allthe patients had undifferentiated carcinoma andwere treated with a combination of chemotherapyand radiation therapy. Of the 36 patients, 19 underwentIMRT and 17 underwent CRT. The average meandose to the first and second planning target volumewas 71.8 and 62.5 Gy with IMRT, when comparedwith 66.3 and 64.4 Gy with CRT, respectively. After amedian follow-up of 27 months, the 2-year locoregionalcontrol, DFS, and OS rate was 76.5%, 60.6%,and 71.3%, respectively. A significant reduction inacute Grade 3 toxicities of the skin, mucous membrane,and pharynx was noted with the use of IMRT.The median time to the development of Grade 2 toxicitywas delayed with IMRT (skin, 35 vs. 25 days;mucous-membrane, 39 vs. 27 days; and larynx, 50 vs.28 days). They concluded that IMRT could significantlyreduce and delay the onset of acute toxicity,resulting in improved tolerance and treatment compliancefor children with NPC. However, the numberof studies with IMRT in pediatric NPC was very limitedand other centers’ experiences are required.Integration of new chemotherapeutic agents ormodifiying their administration sequence when managingpediatric NPCs is another way to improveresults. In a randomized phase III study, it was demonstratedthat patients with squamous-cell carcinomaof the head and neck who received docetaxel plus cisplatinand fluorouracil induction chemotherapy pluschemoradiotherapy had a significantly longer survivalthan those who received cisplatin and fluorouracilinduction chemotherapy plus chemoradiotherapy(Posner et al. 2007). This study led the investigatorsto explore the role of docetaxel in pediatric NPC. Aninternational randomized study recently comparedtwo- vs. three-drug regimen including docetaxel in 72pediatric NPC. The results of this study are expectedfor the optimal chemotherapy regimen for neoadjuvantuse.Another recent major modification of treatmentalgorithm is to use concomitant chemoradiotherapyafter the induction chemotherapy in pediatric NPC.This modification was introduced based on adultstudies that revealed improved survival and is currentlyevaluated by the German and U. S. groupswithin randomized studies. However, one should becautious on the synergistic effect of cisplatin on hearingapparatus when used concurrent with radiotherapy,until the mature results of these studies areavailable.The investigations should be encouraged to determinethe optimal radiotherapy dose and field reductionsin selected patients, while investigating theoptimal chemotherapy schedule and timing. Regionalor international collaboration would facilitate toclarify and refine the etiology, pathogenesis, andtreatment of this rare malignancy.23.5Systemic TreatmentsOwing to the rarity of NPC in children and adolescents,the majority of published studies on chemotherapyfor the disease are of retrospective naturewith long-term experiences. This type of literature is