Familial Nasopharyngeal Carcinoma 6

Post-treatment Follow-Up of Patients with Nasopharyngeal Cancer 237detecting a metastatic focus in patients with no clinicalindication such as bone pain, pathological fracture,hemoptysis, excessive cough, or impaired liverfunction is anticipated if all stages are included.Secondly, NPC with distant metastasis is usually consideredan incurable condition. Although NPC is achemo-sensitive disease and usually responds well tocisplatin-based chemotherapy, systemic treatment ishardly curative for NPC at its metastatic stage. PhaseII studies using platinum-based chemotherapy havesuggested a response rate of 50–90% in the metastaticsetting, with median overall survival of 12–15 months(Loong et al. 2008). While long-term survival hasbeen reported in a small subset of patients with metastaticdisease (Fandi et al. 2000), particularly withisolated pulmonary metastasis after aggressive multimodalitytreatment (Cheng et al. 1996), it is unclearwhether earlier detection and treatment of asymptomaticmetastatic disease, whether isolated or multiplesynchronous disease, would lead to improvedsurvival, when compared with palliative treatmentonce active symptoms occur. In addition, the poorcost-effectiveness of PET/CT during routine followupof NPC patients after definitive treatment, inabsence of clear clinical indication of disease recurrence,prevents the routine utilization of PET/CT inNPC follow-up.Early detection of distant recurrence after definitivetreatment of NPC is challenging, and the value of earlydetection and treatment on ultimate disease control,patients’ overall survival, and quality of life is largelyunknown. Currently, the AHNS recommends annualchest radiographs for follow-up, whereas NCCN andESMO advocate imaging only when clinically indicated.Clearly, further investigation on the clinical valueof early diagnosis and treatment of metastatic NPC isnecessary. However, with the absence of clinical evidencesupporting aggressive treatment to metastaticNPC, it may be reasonable to limit radiological investigationssuch as bone scan, liver ultrasound, CT of thoraxor abdomen, or PET/CT to patients with clinicalsymptoms suggestive of metastases (NCCN 2009).18.3.4Plasma EBV DNA MeasurementReal-time quantitative polymerase chain reaction canbe performed to quantify circulating tumor-derivedEBV DNA in the follow-up management of patientswith NPC. In a prospective study of 170 patients withlocally advanced NPC, Chan et al. (2002) reportedthat plasma EBV DNA was a powerful prognosticmarker with a relative risk for recurrence of 11.9 inpatients with elevated levels after radiotherapy. Thistest also had positive and negative predictive valuesof 87 and 83%, respectively. Similarly, Lin et al. (2004)demonstrated that patients with detectable EBV DNAlevels after radiotherapy had a poorer survival whencompared with those with undetectable levels, andthis was the most important prognostic factor forboth overall and relapse-free survival in their study.However, plasma EBV DNA in itself is noted to berelatively insensitive in detecting local recurrenceafter RT (Loong et al. 2008).18.3.5EBV Serology MeasurementSerologic testing for immunoglobulin A (IgA) antibodiesto viral capsid antigen (VCA) and EBV earlyantigen (EA) has been found to be useful as a markerfor NPC in endemic areas (Gan et al. 1996). However,measurement of serum antibody titers of EBV VCA/IgA using the enzyme-linked immunoadsorbentassay method was shown to be less sensitive and specificwhen compared with measurement of plasmaEBV DNA levels in the detection of recurrent disease(Shao et al. 2004). The same study suggested thatchange of the EBV titers after radiation therapy providedno significant association with outcome.Therefore, although measurement of EBV titers hasbeen suggested by ESMO and AHNS, the justificationfor such a test requires further discussion.18.4Assessment of Treatment-RelatedLate ToxicitiesThe treatment of NPC with radiation therapy, with orwithout chemotherapy, has been associated with multiplelate toxicities, including xerostomia, hormonaldysfunction, central nervous system abnormalities,and second malignancies. A detailed discussion on themechanisms, prevalence, and treatment of radiationinducedlong-term adverse effects is out of the scope ofthis discussion, and has been addressed in anotherchapter; however, accurate detection of these adverseeffects is one of the crucial purposes of post-treatmentfollow-up for NPC. Effective preventative and treatmentmeasures are lacking for some of the severe