Familial Nasopharyngeal Carcinoma 6

Long-Term Complication in the Treatment of Nasopharyngeal Carcinoma 281treatment (Jereczek-Fossa et al. 2003). Microscopicotoscopy allows for evaluation of different forms ofexternal and middle ear inflammation. Air and boneconduction pure tone audiometry, which is usuallyperformed at frequencies of the speech range, evaluatessubjective hearing thresholds and detects anddefines the nature of hearing loss. Tympanometrymeasures acoustic impedance of the middle ear andevaluates aeration of the middle ear, the mobility of theossicles, and the function of Eustachian tube. The testingof stapedial reflexes provides information on theintegrity of the neural reflex loop (Jereczek-Fossaet al. 2003). If any of the above tests is abnormal, a moreextensive otologic examination is necessary. Radiationinducedinjury to the auditory pathway such as labyrinthitis,neuronitis, inner ear space hemorrhage, andwhite matter changes are readily detectable on magneticresonance imaging (MRI) (Jereczek-Fossaet al. 2003).22.3.3ManagementThe best strategy is to avoid the occurrence of hearingdeficit by limiting the radiation dose to the auditorysystem, particularly the inner ear. With advancesin radiation therapy treatment planning, it is possibleto achieve this goal. With the use of intensity-modulatedradiation therapy technique, it is possible tosteer the radiation dose away from the cochlea whilestill adequately covering the target volume. Data inthe literature shows that when the mean dose to thecochlea exceeds 48 Gy, there is an increased risk ofsensorineural deficit (Chen et al. 2006). With the useof intensity-modulated radiation therapy, the dose tobilateral cochlea can be limited to below the tolerancelevel. In patients receiving concurrent cisplatin,the dose constraint of the cochlea should be furtherlowered because it has been shown that the thresholdcochlear dose for hearing loss is as low as 10 Gy whenconcurrent cisplatin is given (Hitchcock et al.2009).Some investigators recommended the insertion ofventilation tubes prophylactically to decrease therisk of conductive hearing loss. In a study from HongKong, 115 patients with NPC were randomized toundergoing insertion of ventilation tubes or no interventionafter radiotherapy for NPC. There was animprovement in hearing, with a reduction of averagedair-bone gap among patients with ventilationtubes (Chowdhury et al. 1988). However, other studiesdid not show similar benefits of using ventilationtubes (Skinner et al. 1988; Lau et al. 1992).There is no standard therapy for sensorineuralhearing loss. Steroid therapy has been used to treatedema and inflammation of the inner ear caused byradiation (Jereczek-Fossa et al. 2003). However, it isnot consistently effective. Hyperbaric oxygen has alsobeen used with variable success. Classical conductionhearing aid may be used to improve hearing in patientswith sensorineural hearing loss. Successful cochlearimplants have been reported in a patient who developedbilateral deafness as a result of radiation-inducedacoustic neuritis and labyrinthitis (Formanek et al.1998).22.4Soft Tissue FibrosisA high dose of radiation is required to control NPCand as a result, the head and neck region includingthe skull base are typically treated to a high dose.Radiation-induced fibrosis can manifest as neck softtissue fibrosis, cranial nerve entrapment (discussedin Sect. 20.5), trismus, or dysphagia. Cancer centerswith anecdotal experience with the use of hypofractionatedregimens have observed a higher incidenceof symptomatic radiation-induced fibrosis of the softtissue (Lee et al. 1992). In modern series where typicallya more conventional fractionation (£2 Gy) wasused, the reported rates of radiation fibrosis weremuch lower (Lee et al. 2002, 2009, 2005; Sultanem etal. 2000; Kam et al. 2004). In a study by Lee et al.,major late toxicities after conformal radiotherapy forNPC in 422 patients were analyzed. The rate of grade2 or higher soft tissue damage ranged from 0 to 4.3%.The rate of grade 3 or higher trismus ranged from 0to 1% (Lee et al. 2009).22.4.1PathogenesisTraditional teaching attributed late radiation injuryto vascular/microvascular damage that led to tissuehypoxia and nutritional depletion (O’Sullivan andLevin 2003). Subsequently, it was believed that thelinear-quadratic equation could predict the normaltissue response, which was determined by the