Familial Nasopharyngeal Carcinoma 6

128 J-C. Linthat it may trigger the accelerated repopulation andcross-resistance during subsequent radiation therapy.The dose intensity of concurrent chemotherapy thatcan be delivered safely during 7–8 weeks radiationtherapy is usually lower than neoadjuvant or adjuvantchemotherapy. This may compromise its efficacy ineradication of micrometastasis. Poor compliance andcompromised blood supply are the two major problemsof adjuvant chemotherapy.So far, there are 17 randomized trials to investigatecombined chemoradiotherapy versus radiotherapyalone in NPC (Rossi et al. 1988; Chan et al.1995, 2002b, 2005; Cvitkovic 1996; Al-Sarraf et al.1998; Chua et al. 1998; Ma et al. 2001b; Chi et al.2002; Hareyama et al. 2002; Lin et al. 2003b; Kwonget al. 2004b; Lee et al. 2005a, 2006; Wee et al. 2005;Zhang et al. 2005; Chen et al. 2008; Hui et al. 2009).Summaries of three meta-analyses (Huncharekand Kupelnick 2002; Langendijk et al. 2004;Baujat et al. 2006) from parts of these randomizedtrials indicate that concurrent chemotherapy hasthe largest benefit and adjuvant chemotherapy theleast. A detailed discussion of the application of chemotherapyin the management of NPC is out of thescope of this chapter, and is detailed in Chaps 11–15,and 21.Treatment failures in advanced NPC included bothhigh rates of local recurrence and distant metastasis.Because of recent advances in radiation oncology andthe combined use of chemotherapy, the patterns offailure have been predominantly due to distantmetastasis. Chemotherapy may become an importantprognostic factor in the management of NPC. Infuture trials, researchers may need to differentiatethe risk groups of patients and identify the potentialmode of treatment failure in different subgroup ofpatients to guide the designing of chemotherapystrategy (neoadjuvant, concurrent, adjuvant, or theircombination). For example, patients with persistentlydetectable plasma EBV DNA after chemoradiotherapyor radiation therapy alone will have a very highrisk of distant failure. Effective adjuvant chemotherapyfor micrometastases may be indicated for thisgroup of patients. A Phase III randomized trial toaddress this problem has been ongoing using adjuvantchemotherapy consists of gemcitabine + cisplatinin Hong Kong. It is important to recognize that anegative result may just indicate an ineffective regimen,and the high incidence of distant metastasisindicates that the strategy of adjuvant therapy usingan effective regimen is urgently needed for specialsubgroup patients.9.6SummaryAmong all suggested disease-related prognosticators,stage of NPC at diagnosis, plasma/serum EBV DNA,serum LDH, tumor volume, cranial nerve palsy, andthe presence of tumor-associated genes in peripheralblood cells are proven significant prognostic factors.PPS invasion, RPLN metastasis, and skull base erosion/destructionare probably significant factorsaffecting prognosis. Serum anti-EBV antibodies, otherserum tumor markers, and tissue biomarkers arepotential prognostic factors which need further studieswith well-designed and larger patient numbers tovalidate. Pathological types or features have highpotential to affect prognosis, but are hampered bythree factors to be verified – consensus of objectiveclassification criteria between different pathologists,representative of sampling (too small specimen bypunch biopsy), and the presence of different pathologicaltypes or features in different parts of the specimenin the same patients.Patients’ age at diagnosis is a proven and significantpatient-related prognosticator, and young age is a definitefavorable prognostic factor for patients with nonmetastaticNPC. The significance of gender, race,performance status, weight loss, and anemia at diagnosisor during the course of radiation therapy on predictionof prognosis after treatment is debatable. Amongtreatment-related prognosticators, MRI-staged patientshave a significantly improved outcome than patientsstaged using CT scan. However, the prevailing use ofMRI in the management of NPC makes the diagnosisand staging of NPC more precise. Last but not least,treatment itself is also a determinant prognostic factorfor NPC. Advances in radiation therapy technique suchas the use of IMRT and brachytherapy, and combinedchemoradiotherapy have significantly improvedpatients’ prognoses. Future researches should be orientedto tailor various treatment strategies accordingto predictive factors of treatment failure to realize individualizedmanagement for patients with NPC.ReferencesAl-Sarraf M, LeBlanc M, Giri PG, Fu KK, Cooper J, Vuong T,Forastiere AA, Adams G, Sakr WA, Schuller DE, Ensley JF(1998) Chemoradiotherapy versus radiotherapy in patientswith advanced nasopharyngeal cancer: phase III randomizedintergroup study 0099. J Clin Oncol 16:1310–1317