Familial Nasopharyngeal Carcinoma 6

Long-Term Complication in the Treatment of Nasopharyngeal Carcinoma 287prevailing utilization of modern treatment techniquessuch as three-dimensional conformal andIMRT, it is possible to avoid overdosing the brainstemand spinal cord. With the use of IMRT, a highlyconcave isodose distribution can be achieved.Whenever possible, it is important to keep the maximumbrainstem and spinal cord doses to 50–54 Gyand 45 Gy, respectively (Emami et al. 1991).22.7Temporal Lobe NecrosisGiven the proximity of the temporal lobes to the sphenoidsinus, which is typically included in the radiationfield or clinical target volume in NPC, they are at risk forradiation-induced injury including necrosis. Temporallobe necrosis is one of the most feared complications inthe management of NPC because it accounts for 65% ofdeaths from radiation-induced complications (Leeet al. 1992). Fortunately, the reported rates of temporallobe necrosis are relatively low in most series and theyranged from 0% to 6% (Lee et al. 1992, 2009, 2002, 2005;Yeh et al. 2005; Kam et al. 2004).The incidence of temporal lobe necrosis dependson a number of factors including the fractional dose,total dose, and the volume of brain irradiated (Lee1999; Lee et al. 2002 1998, 1999; Jen et al. 2001). Whenaltered fractionation is used, the interfraction timeinterval impacts on the rate of temporal lobe necrosis.Clinical evidence suggested that an interfractioninterval of 6 h may not be adequate for complete repairof radiation damage (Lee et al. 1999). In a study by Leeet al., the incidence of temporal lobe necrosis was 0%for patients who received 66 Gy in 33 fractions (2 Gyper fraction, five times a week), 24% for those whoreceived 59.5 Gy in 17 fractions (3.5 Gy per fraction,three times a week), and 33% for those who received71.2 Gy in 40 fractions over 35 days (Lee et al. 2002).22.7.1PathogenesisIn radiation-induced necrosis of brain parenchyma,the histopathologic changes are typically limited tothe white matter but can occasionally extend to thegray matter. The pathologic changes seen under themicroscope include focal coagulative and fibrinoidnecrosis and demyelination (Schultheiss et al. 1995;Sloan et al. 2003). Recognizable cells and structuresare completely lost. The areas of necrosis are positivein fibrin stains but older lesions may lose the intensestaining for fibrin stain. At the margins of the necrosis,gliosis are present. Occasionally, stromal edema andmicrovascular proliferation are seen. Dystrophic calciumdeposits may be present in the necrotic focus.22.7.2Clinical Manifestation and DiagnosisPatients with temporal lobe necrosis can present withvery subtle symptoms that may be missed if the physiciandoes not have a high index of suspicion. In theseries by Lee et al., 16% of the 102 patients with temporallobe necrosis were asymptomatic and 39% presentedwith vague symptoms such as mild dizziness,memory impairment, or personality change. Only31% of patients with temporal lobe necrosis presentedwith classical temporal lobe epilepsy and 14%with nonspecific neurologic findings such as headache,mental confusion, or general seizures (Lee et al.1988). On physical examination, only a small percentageof patients showed signs of raised intracranialpressure such as papilledema (4%) or 6th nerve palsy(14%) (Lee 1999). The median latent period was 5years (range, 1.5–13 years). Neurocognitive deficitcan occur in patients with temporal lobe necrosis.The general intelligence is usually intact (Cheunget al. 2000). The degree of neurocognitive deficit isdependent on the volume and site of necrosis in thetemporal lobe (Cheung et al. 2003).The diagnosis of temporal lobe necrosis is usuallyconfirmed using imaging studies. Computerizedtomography (CT) of the brain usually demonstratesa small necrotic foci at the inferomedial aspect ofeach of the temporal lobes associated with edema.Irregular “finger-like” hypodense areas in the whitematter are seen (Lee 1999). In a minority of cases,well-defined lesions with central liquefaction maybe obvious. However, in some cases, patients withtemporal lobe necrosis may have a negative brainCT. In such cases, MRI of the brain will be useful.MRI is superior to CT in terms of sensitivity and candemonstrate a small area of necrotic focus in thebrain. On T1-weighted images, temporal lobe necrosisshows up as very low intensity areas; onT2-weighted spin echo sequence images, it shows upas high signal intensity areas (Lee 1999). Liquefactionwithin edematous brain parenchyma is ready demonstratedas a roundish area of hypointensity onproton-density sequence.