Familial Nasopharyngeal Carcinoma 6

298 E. Ozyar and I. Ayanmens (Lombardi et al. 1982; Deutsch et al. 1978;Jenkin et al. 1981; Jereb et al. 1980; Berry et al.1980). Results of these reports generally proposedthe use of total tumor radiation doses in the range of35–86 Gy and pointed out the need for effective systemictreatment in addition to radiotherapy.The second group of papers were published in the1990s, with improved local and systemic staging ofthe disease and improved treatment parameters(mostly linear accelerator external-beam radiationtherapy (EBRT), including reports with CT treatmentplanning and cisplatin-based chemotherapy) (Paoet al. 1989; Ingersoll et al. 1990; Martin et al. 1994;Ghim et al. 1998; Wolden et al. 2000; Daoud et al.2003; Kupeli et al. 2005). The majority of these retrospectivestudies found the optimum dose to the primarytumor to be between 50 and 70 Gy, with thesuggestion of higher efficacy with doses greater than60–66 Gy in some reports (Laskar et al. 2004; Ozyaret al. 2006). Superior results were reported with theuse of cisplatin-based chemotherapy and neoadjuvantchemotherapy when compared with the regimenswithout cisplatin and adjuvant chemotherapyschedules (Ayan et al. 2000; Kupeli et al. 2005).The RCN study is the largest retrospective analysisin the literature aimed to analyze the results interms of local control, survival, and the possibleprognostic factors in 165 paediatric NPC patientscollected worldwide (Ozyar et al. 2006). The patient’sage at diagnosis ranged from 7 to 17 years. There wasa predominance of males (66.1%). Histopathologicalclassification revealed 23 (13.9%) patients with WHOtype II and 142 (86.1%) patients with WHO type III.All patients were treated with fractionated EBRT to amedian dose of 66 Gy. While 13% of the patients weretreated with radiotherapy alone, 87% of the patientsreceived chemotherapy in addition to radiotherapy.The actuarial overall 5-year survival (OS) was 78%,whereas the actuarial 5-year local relapse-free survival(LRFS), loco-regional relapse free survival(LRRFS), distant metastasis-free survival (DMFS),and disease-free survival (DFS) rates were 88%, 82%,81.5%, and 69%, respectively. In multivariate analysis,statistically significant unfavorable factors wereage older than 14 years for LRC; male gender forDMFS; T3, T4 disease for LRFS; N3 disease for DFSand OS; total nasopharyngeal EBRT dose of less than66 Gy for LRFS and LRRFS; and patients treated withradiotherapy alone for LRFS, LRRFS, and DFS. Thenodal tumor bulk seems to be the major parameteraffecting survival, and nasopharyngeal dose of≥66 Gy turned out to be still important in achievinglocal control according to this retrospective review.As this study is a retrospective comparison betweenexperiences at multiple institutions, one may arguethat patient-selection bias may have impacted theresults. Although a randomized study is always preferable,the results of this retrospective review wouldstill provide valuable contribution to understandingthe basic behavior of pediatric NPC, regarding theoutcome and treatment approach.Recently, retrospective analysis of 74 pediatricNPC patients treated between 1978 and 2004 at theGustave Roussy Institute (IGR) was reported in 2004as an abstract (Habrand et al. 2004). Almost 75% ofthe patients were originally from Maghreb countriesand treated with different cisplatin-based chemotherapymultiregimens. Either low-dose radiotherapy(50 Gy) was administered to good responders to neoadjuvantchemotherapy (54% of the patients) orhigh-dose radiotherapy (65–70 Gy). Despite a similarlocoregional recurrence rate in the two groups, eventfreesurvival (EFS) and OS rates were better in thelow-dose radiotherapy group. In addition, late toxicitywas improved in the low-dose group as well. Thus,the authors concluded that response-adapted dosereduction seems to be possible in selected pediatricNPC patients.Recent data supporting response-adapted dosereducedradiotherapy have been published by InstitutCurie, from France (Orbach et al. 2008). Thirty-fourchildren were treated for 27 years and 20 out of 34were reported to be of North African origin. The cervicalnodal irradiation dose was reduced to less than50 Gy in the case of a good response to chemotherapy.All but one child received neoadjuvant chemotherapywith various regimens, and the overall chemotherapyresponse rate was reported to be 78%. Fifteenpatients had dose-reduced cervical nodal irradiation(range: 45–50 Gy). The primary tumor dose rangedbetween 45 and 66 Gy. Local and distant failure rateswere 10% and 18%, respectively. The 5-year OS was73% and the EFS was 75%. The authors concludedthat cervical nodal failure rate was low despite radiotherapydose reduction in the case of a good responseto neoadjuvant chemotherapy, and they proposed adose reduction for primary disease less than 50 Gy inthe case of good response to initial chemotherapy.There are only two reported prospective studies inthe literature on the management of pediatric NPC,and these constitute the third group of publicationsin the literature (Mertens et al. 1997, 2005;Rodriguez-Galindo et al. 2005). A prospectiveGerman trial, conducted in the early 1990s, treated