Cognitive function of patients with nasopharyngeal carcinoma with and without temporal lobe radionecrosis.

BACKGROUND: Radiotherapy is the primary treatment for nasopharyngeal carcinoma, and temporal lobe necrosis is observed in about 7% of patients after radiotherapy. Although some studies reported that these patients demonstrated cognitive impairment after radiotherapy, it is still unclear if the cognitive deficits are related to the radiation exposure or the radiation-induced necrosis. OBJECTIVE: To compare the cognitive function of patients with and without temporal lobe necrosis after radiotherapy for nasopharyngeal carcinoma. METHODS: A comprehensive neuropsychological battery was administered to 53 patients with nasopharyngeal carcinoma who had completed their radiotherapy at least 1 year previously. As evidenced by magnetic resonance imaging, 31 patients developed necrosis after treatment. Thirty-one age- and education-matched individuals were recruited as normal control subjects. RESULTS: Whereas the performance of patients without temporal lobe necrosis was similar to that of normal control subjects, patients with temporal lobe necrosis demonstrated significant impairment on tests of verbal (P<.001) and visual memory (range, P<.001 to P =.03), language (range, P<.001 to P =.01), motor ability (P =.02), planning (P =.02), cognitive ability (P =.007), and abstract thinking (range, P =.009 to P =.04). However, the performance of patients with necrosis on tests of general intelligence (range, P =.08 to P =.15), attention (range, P =.06 to P =.55), and visual abilities (range, P =.06 to P =.47) was not significantly different from that of normal control subjects and patients without necrosis. CONCLUSIONS: Radiotherapy for nasopharyngeal carcinoma seemed to have adverse but insignificant effects on the cognitive functions of the patients. However, for patients who developed temporal lobe necrosis after radiotherapy, memory, language, motor ability, and executive functions were significantly impaired, although their general intelligence remained relatively intact.

Measuring quality of life of Chinese cancer patients: A validation of the Chinese version of the Functional Assessment of Cancer Therapy-General (FACT-G) scale.

BACKGROUND: Few cancer specific quality-of-life (QoL) measures from the West have been translated for use with Chinese-speaking patients, and no substantial validation of these translations with adequately large cohorts has been published previously, to the authors' knowledge. The Functional Assessment of Cancer Therapy-General (FACT-G) is a well-validated QoL instrument that is specific to cancer patients. The scale was translated into Chinese and the psychometric properties of this translated scale (FACT-G [Ch]) were tested with a Chinese sample in Hong Kong, China. METHODS: A total of 1262 Chinese cancer patients were selected in 3 samples from 5 Hong Kong regional hospitals. Quantitative and qualitative data were used to assess the cultural equivalence, factor structure, reliability, and validity of the FACT-G (Ch). RESULTS: Focus group discussions indicated that the FACT-G was seen as covering QoL domains identified as important and relevant to Chinese cancer patients, though in some respects it was seen as having limited scope in this sample. Psychometrically, the factor structure of the FACT-G deviated from that of the original work. The FACT-G (Ch) had acceptable reliability (Cronbach alpha 0.85). The convergent validity of the FACT-G (Ch) with a generic QoL measure (WHOQOL-BREF[HK]) was 0.72 (P < 0.001), and divergent validity showed low correlations of less than 0.15 (P < 0.05) with non-QoL measures. CONCLUSIONS: Focus group data indicated that the FACT-G translation into Chinese was seen as a conceptually relevant and moderately sufficient QoL measure. Psychometrically, the instrument had acceptable properties, but conceptual differences from the original version were suggested. Although more work is needed to increase its adequacy, the translated scale has reasonable utility for use with Chinese populations in clinical settings.

Effects of cranial irradiation on hypothalamic-pituitary function--a 5-year longitudinal study in patients with nasopharyngeal carcinoma.

The effects of cranial irradiation on hypothalamic-pituitary function were studied over a 5-year period in 31 adult patients with nasopharyngeal carcinoma. The estimated radiotherapy doses to the hypothalamus and pituitary were 3979 +/- 78 (+/- SD) and 6167 +/- 122 cGy, respectively. Within 2 years of radiotherapy, significant impairment in the secretion of growth hormone, gonadotrophins, corticotrophin and thyrotrophin were evident and 14 per cent of patients developed hyperprolactinaemia. Using life table analysis, the cumulative probability of endocrine dysfunction was estimated to be 62 per cent after 5 years with deficiencies in growth hormone, gonadotrophins, corticotrophin and thyrotrophin found in 63.5, 30.7, 26.7 and 14.9 per cent of patients, respectively. Growth hormone deficiency was the earliest endocrine dysfunction observed. Hyperprolactinaemia was uncommon in the male patients but occurred in five of eight women within 3 years of cranial irradiation. The alterations in gonadotrophin secretion suggest a defect in the pulsatile release of gonadotrophin releasing hormone. Twenty-eight patients developed a hypothalamic pattern of delayed thyrotrophin response to thyrotrophin releasing hormone one year after radiotherapy--four subsequently became hypothyroid. Patients who received radiotherapy for cervical lymph nodes were at greater risk of developing hypothyroidism. Thus, in these patients with no pre-existing disease in the hypothalamic-pituitary region, progressive impairment in hypothalamic pituitary function leading to endocrine dysfunction requiring treatment occurs in 50 per cent of patients 5 years after cranial irradiation. Regular endocrine assessment should be performed in all patients following cranial irradiation.

Magnetic resonance imaging in the clinical diagnosis of late temporal lobe necrosis following radiotherapy for nasopharyngeal carcinoma.

Magnetic resonance imaging (MRI) and computed tomography (CT) were performed on 13 patients with clinical features of late temporal lobe damage following radical radiotherapy for nasopharyngeal carcinoma, and their results compared. MRI was undoubtedly superior in sensitivity--revealing areas of prolonged T2 relaxation time in the inferior portions of the temporal lobes in all patients, while CT failed to show any gross abnormalities in seven. In patients with large lesions well-depicted on CT, the corresponding MRI changes were comparable in shape and extent. But MRI gave an additional sign for the presence of liquefactive necrosis, and revealed lesions in the contralateral lobes in two out of three patients with unilateral CT changes. Besides obvious improvement in detection rate, the contribution of MRI to the better selection of treatment protocols, and to the understanding of the pathological process are discussed.

Clinical diagnosis of late temporal lobe necrosis following radiation therapy for nasopharyngeal carcinoma.

This is a preliminary report of 102 patients with clinical diagnosis of late temporal lobe necrosis after radical radiation therapy for nasopharyngeal carcinoma during 1964 to 1983. Histologic verification was available in 12 cases. All but three patients had been treated in our institute using schedules with doses larger than the conventional 200 cGy per fraction. The incidence rate was 1.03%. In our 80 patients with only one course of external irradiation, the doses to the temporal lobes ranged from 1665 to 2127 ret, or 1286 to 1778 brain tolerance unit (btu). The latent interval ranged from 9 months to 16 years. The median observation period is 33 months. The symptomatology, working diagnosis, treatment, and outcome are described. Surgery was hazardous because of the bilaterality of the involvement and exploration for mere verification of diagnosis was unjustified in typical cases. Treatment with corticosteroid achieved durable objective response in 25 (35%) of 72 patients. The importance of early detection and corticosteroid treatment is discussed.

Symptomatic hypothalamic-pituitary dysfunction in nasopharyngeal carcinoma patients following radiation therapy: a retrospective study.

Endocrine assessment was performed in 32 relapse-free southern Chinese patients (21 males and 11 females, aged 27-50 years at the time of assessment) 5-17 years following radiation therapy (RT) alone for early nasopharyngeal carcinoma (NPC). Initial screening was done using questionnaires emphasizing on impaired sexual function and menstrual disturbance plus measurement of serum levels of thyroxine, free thyroxine index, thyrotropic hormone, prolactin, and additionally testosterone for males only. Those showing abnormalities were subjected to detailed pituitary function tests. Hypothalamic-pituitary dysfunction was found in 7 female patients and only 1 male patient. A delayed TSH response to thyrotropin releasing hormone suggesting a hypothalamic disorder was seen in 6 of the affected female patients, and hyperprolactinaemia in also 6. None of the patients had evidence of diabetes insipidus. Hypopituitarism became symptomatic 2-5 years after RT with a mean latent interval of 3.8 years. A practical protocol for regular endocrine assessment for NPC patients after RT has been proposed. Multiple linear regression analysis of the radiotherapeutic data from the 11 female patients indicates that the likelihood of late occurrence of symptomatic hypothalamic-pituitary dysfunction following RT is dependent on the TDF of the target dose to the nasopharyngeal region and the height of the upper margin of the opposed lateral facial fields above the diaphragma sellae (coefficient of multiple correlation = 0.9025). Except when the sphenoid sinus or the middle cranial fossa is involved, it is advisable to set the height of the upper margin of the lateral facial field at a level no higher than the diaphragma sellae. The hypothalamus and possibly the pituitary stalk as well may sustain permanent damage by doses of radiation within the conventional radiotherapeutic range for carcinomas.

Early effects of cranial irradiation on hypothalamic-pituitary function.

Hypothalamic-pituitary function was studied in 31 patients before and after cranial irradiation for nasopharyngeal carcinoma. The estimated radiotherapy (RT) doses to the hypothalamus and pituitary were 3979 +/- 78 (+/- SD) and 6167 +/- 122 centiGrays, respectively. All patients had normal pituitary function before RT. One year after RT, there was a significant decrease in the integrated serum GH response to insulin-induced hypoglycemia. In the male patients, basal serum FSH significantly increased, while basal serum LH and testosterone did not change. Moreover, in response to LHRH, the integrated FSH response was increased while that of LH was decreased. Such discordant changes in FSH and LH may be explained by a defect in LHRH pulsatile release involving predominantly a decrease in pulse frequency. The peak serum TSH response to TRH became delayed in 28 patients, suggesting a defect in TRH release. Twenty-one patients were reassessed 2 yr after RT. Their mean basal serum T4 and plasma cortisol levels had significantly decreased. Hyperprolactinemia associated with oligomenorrhoea was found in 3 women. Further impairment in the secretion of GH, FSH, LH, TSH, and ACTH had occurred, and 4 patients had hypopituitarism. Thus, progressive impairment in hypothalamic-pituitary function occurs after cranial irradiation and can be demonstrated as early as 1 yr after RT.

Hypothalamic hypopituitarism following cranial irradiation for nasopharyngeal carcinoma.

Eight patients, one male and seven females, with no pre-existing hypothalamic-pituitary disease, who developed symptoms of hypopituitarism following cranial irradiation for nasopharyngeal carcinoma were studied 5 years or more after radiotherapy. All were GH deficient. Four of the patients with no GH response during insulin tolerance tests (ITT) showed increased GH in response to synthetic human growth hormone releasing factor (GRF-44). Four patients had impaired cortisol responses to ITT, and gradual but diminished cortisol responses to ovine corticotrophin releasing factor (CRF-41). There was no significant difference between mean peak increments in response to ITT and those in response to CRF-41. TSH responses to TRH were delayed in five and absent in two patients; four of these had low free T4 index. Prolactin was raised in all seven women and increased further in response to TRH. Two patients had impaired gonadotrophin responses to LHRH. None of the patients had clinical or biochemical evidence of diabetes insipidus. These data suggest that post-irradiation hypopituitarism in these patients results from radiation damage to the hypothalamus leading to varying degrees of deficiency of the hypothalamic releasing or inhibitory factors.