Familial Nasopharyngeal Carcinoma 6

276 S. S. Lo, J. J. Lu, and L. Kongsurvival of NPC patients exceed 80% at 5 years (Weeet al. 2005; Cheng et al. 2000).However, the advances in the management of NPCand the improved outcome are not without consequences.Although we celebrate the progresses in cancermanagement, better understanding of treatmentrelated,long-term complications is imperative. Amongall treatment-induced side effects in the managementof NPC, late complications including xerostomia, hearingdeficit, and soft-tissue fibrosis are commonlyobserved. Other late complications such as radiationinducedspinal cord myelopathy, brain stem and temporallobe necrosis, and second primary tumor (SPT),although rare, are usually devastating to patients andare associated with severe impairment of quality oflife. Clearly, treatment-induced late complication is animportant entity in the management of NPC. Thischapter aims to discuss the pathogenesis, diagnosis,prevention, and management of the long-term complicationssecondary to the treatment of NPC.22.2XerostomiaSaliva is produced by the major and minor salivaryglands. The average daily production of saliva of ahealthy individual is approximately 1,000–1,500 ml.The three major glands including the parotid, submandibular,and submental glands are responsiblefor 90% of the total saliva production. The parotidglands account for approximately 80% of the totalsaliva from major glands. As radiation therapy is themain treatment modality for nasopharyngeal cancerand parotid glands are positioned close to thenasopharynx, dysfunction of the parotid gland is oneof the major concerns in NPC treatment.22.2.1Pathogenesis of Radiation-InducedSalivary HypofunctionThe serous acinar cells of the parotid glands are verysensitive to ionizing radiation (Stephens et al. 1986),and is affected earlier in the course of radiation therapywhen compared with mucous cells (Parsons 1994).Radiation damage of acinar cells in the forms of apoptosiscan be observed at low dose of irradiation.Clinically, xerostomia has been reported after merely 2or 3 fractions of irradiation at conventional dose. Within1–2 weeks of radiation therapy and a dose of merely20 Gy or less encompassing the major salivary glands,the salivary output declines by up to 60% (Wescott etal. 1978), thereby making saliva more viscous. However,the mechanism of the high sensitivity of salivary glandsin the early phase of radiotherapy with relatively lowdose of radiation is not fully understood.The probability and severity of long-term salivaryhypofunction and xerostomia are directly related tothe volume and dose of parotid gland irradiated (Liuet al. 1990). Once the mean dose to the parotid glandsexceeds 26 Gy, recovery of salivary function is uncommon(Eisbruch et al. 2001). Conventional radiotherapyfor NPC usually causes high-dose irradiation tothe bilateral parotid glands. With a dose approachingcurative dose for NPC, degenerative changes, fibrosis,and/or atrophy of the parotid and/or submandibularglands are nearly universal.The use of chemotherapy in the treatment of NPCmay also cause an increased risk for xerostomia.Certain medications such as 5-FU may have synergisticeffect with ionizing irradiation for xerostomia(Kies et al. 2001). However, whether the most commonlyused chemotherapy drug in NPC, i.e., cisplatinis significantly associated with xerostomia is largelyunknown.The reduction of saliva reduces the wetting mediumfor the function of chemoreceptors on the tongue andpalate. This hypofunction, together with radiationinduceddamage to the taste buds, diminish the stimulifrom foods for salivation, and induce a viciouscycle for salivary dysfunction in radiotherapy for headand neck cancer including NPC.22.2.2Clinical Manifestations and DiagnosisAs both parotid glands are usually irradiated in conventionalradiation therapy for NPC, salivary hypofunctionwith resultant xerostomia is one of the mostcommon acute and late side effects in the management.Although radiation-induced xerostomia is usually discussedas a late complication, reduction of saliva productionusually begins soon after the initiation ofradiotherapy, as mentioned above. Approximately 95%of patients treated with conventional radiation therapyfor their head and neck malignancies experience xerostomia.Furthermore, more than 70% of the symptomswere reported as moderate or severe (Eisbruch et al.2001). Xerostomia may result in dry and burning sensationof the tongue, oral mucosa, and throat. Some othercommonly observed long-term complications such asinfection (particularly oral candidiasis), dental decay,