J. Sham

Transpalatal insertion of radioactive gold grain for the treatment of persistent and recurrent nasopharyngeal carcinoma

PURPOSE To evaluate the efficacy of radioactive gold grain implant via the split palate approach in the control of locally recurrent or persistent nasopharyngeal carcinoma. METHODS AND MATERIAL Forty-three patients, 10 for persistent NPC, 28 for first relapse in the nasopharynx, and five for second relapse in the nasopharynx, were treated. The diameter of the tumors at the time of gold grain implant ranged from 0.5 to 5 cm, the number of gold grains inserted varied from 4 to 14, the median number was seven. RESULTS There was no significant difference in the control of the primary tumor for persistent disease (80% at 5 years), first relapse (61% at 5 years) and second relapse (80% at 3 years), p = 0.8845. The difference in survival between the three subgroups of patients, however, was highly significant (p = 0.0040). Thirty patients had CT evaluation before gold grain implant and the tumor was found confined to the nasopharynx in 21, in the remaining nine patients erosion of the sphenoid sinus or other parts of the base of skull was noted. The difference in the control between those patients with tumors confined to the nasopharynx and those patients with extranasopharyngeal extension of tumor almost reached statistical significance (81% and 44% respectively at 5 years, p = 0.0554). For the six patients who developed local recurrence after gold grain implant and were evaluable for the pattern of failure, the recurrent tumors were considered originating from another region of the nasopharynx in four, and in-field failure in the other two cases. CONCLUSION Radioactive gold grain implant as salvage treatment provides satisfactory control of persistent and recurrent nasopharyngeal carcinoma. The local control was better when the tumor was localized to the nasopharynx, thus underlines the importance of close follow-up for early recognition of relapse and persistent tumor. However, such patients still suffered from high incidence of regional and distant failure, the pathophysiology and management of which require further investigation.

Sustained elevation of Epstein-Barr virus antibody levels preceding clinical onset of nasopharyngeal carcinoma

We have monitored Epstein–Barr virus (EBV) IgA antibody levels of 39 nasopharyngeal carcinoma (NPC) cases for up to 15 years before clinical onset of NPC, and assessed preclinical serologic status of another 68 cases. Our results identify a serologic window preceding diagnosis when antibody levels are raised and sustained. This window can persist for as long as 10 years, with a mean duration estimated to as 37±28 months. Ninety-seven of these 107 NPC cases exhibited such a window. Cases that did not may reflect individual antibody response to EBV. Serologic screening at enrollment identified those cases who had already entered the window and became clinically manifested earlier (median=28 months) than those who entered the window after enrollment (median=90 months). The former account for 19 of 21 cases diagnosed within 2 years of screening. Nasopharyngeal carcinoma risk levels among seropositive subjects were also highest during this period. Both prediction rates and risk levels declined thereafter; cases detected at later times were composed of increasing proportions of individuals who entered the serological window after screening. Our findings establish EBV antibody as an early marker of NPC and suggest that repeated screening to monitor cases as they enter this window has considerable predictive value, with practical consequences for cancer treatment.

Treatment of persistent and recurrent nasopharyngeal carcinoma by brachytherapy.

The early results of brachytherapy for persistent and recurrent nasopharyngeal carcinoma in 30 patients is presented. Fifteen patients were treated by intracavitary caesium, 12 patients were treated by interstitial gold grain implant using the split-palate approach and three patients were treated by both intracavitary caesium and interstitial gold grain implant for the first and second relapse in the nasopharynx, respectively. The overall tumour control rate for intracavitary caesium was 5/18 (28%) with median follow-up of 25.2 months, and for interstitial gold grain implant it was 9/14 (64%) with median follow-up of 16.5 months. Interstitial gold grain implantation appears to be effective in the treatment of persistent and recurrent nasopharyngeal carcinoma.

Early changes of auditory brain stem evoked response after radiotherapy for nasopharyngeal carcinoma--a prospective study.

A prospective study of the effect of radiotherapy for nasopharyngeal carcinoma on hearing was carried out on 49 patients who had pure tone, impedance audiometry and auditory brain stem evoked response (ABR) recordings before, immediately, three, six and 12 months after radiotherapy. Fourteen patients complained of intermittent tinnitus after radiotherapy. We found that 11 initially normal ears of nine patients developed a middle ear effusion, three to six months after radiotherapy. There was mixed sensorineural and conductive hearing impairment after radiotherapy. Persistent impairment of ABR was detected immediately after completion of radiotherapy. The waves I-III and I-V interpeak latency intervals were significantly prolonged one year after radiotherapy. The study shows that radiotherapy for nasopharyngeal carcinoma impairs hearing by acting on the middle ear, the cochlea and the brain stem auditory pathway.

Telomerase activation in nasopharyngeal carcinomas.

Nasopharyngeal carcinomas (NPC) are common in Hong Kong and southern China but rare in Western countries. Telomerase activation is common in human cancers but has not been reported previously in NPC. Telomerase activation in NPC was determined using the sensitive TRAP (telomerase rapid amplification protocol) assay in 45 nasopharyngeal biopsies (36 NPC, nine normal nasopharyngeal mucosae) in four xenografted NPC tumours established in nude mice and in five in vitro NPC cell lines. Telomerase activation is common in NPC and can be detected at high frequencies (85% in primary tumours and 100% in recurrent tumours). The frequency of telomerase activation was lowest in NPC biopsies without lymph node involvement (60%) compared with those with positive lymph node involvement (100%), and the difference is statistically significant (P < 0.05; Fisher exact test). All the xenografted NPC tumours and in vitro NPC cell lines were strongly positive for telomerase activity. Our results suggest that telomerase activation is common in NPC and it may be useful as a diagnostic marker in the detection of tumour cells in nasopharyngeal biopsies. The high frequency of telomerase activation in stage I NPC (80% positive) suggests that it is an early event in tumour progression.

Osteosarcoma of the maxilla in Hong Kong Chinese postirradiation for nasopharyngeal carcinoma. A report of four cases.

Postirradiation osteosarcoma of the maxilla was seen in four Hong Kong Chinese patients treated for nasopharyngeal carcinoma. These cases represent four of 42 (9%) cases of osteosarcoma at all sites in this institution during the period 1979 to 1989, when more than 1000 patients were treated with radiotherapy for nasopharyngeal carcinoma. The latent periods varied from 8 to 11 years from completion of radiotherapy treatment to development of osteosarcoma. The radiation dosage varied from 6000 to 6280 cGy in three of the patients. These cases fit the criteria for diagnosis of postirradiation sarcomas. Maxillary osteosarcomas after irradiation for nasopharyngeal carcinoma do not appear to have been described. The very high incidence of nasopharyngeal carcinoma (for which radiotherapy is the treatment of choice) in Hong Kong Chinese would make the occurrence of such tumors more likely in Hong Kong, although the small risk does not contraindicate the use of radiation in the treatment of nasopharyngeal carcinoma in view of its well‐documented efficacy.

The cytological diagnosis of nasopharyngeal carcinoma using a silk swab stick.

A prospective study was carried out to investigate the efficacy of exfoliative cytology for the diagnosis of nasopharyngeal carcinoma. Exfoliated nasopharyngeal cells were collected from patients with a clinical suspicion of carcinoma by scraping the nasopharyngeal mucosa with a piece of silk wrapped around one end of a wooden stick. Ninety‐eight patients were investigated in this manner, and the results of cytological investigation compared with the histological findings. the sensitivity of cytological investigation was 71% and the overall accuracy was 86%. the combined use of cytology and serology as a method of screening for nasopharyngeal carcinomas is discussed.

Brainstem auditory evoked potentials after irradiation of nasopharyngeal carcinoma—Report on two cases with myelopathy of the brainstem

Brainstem auditory evoked potentials (BAEP) were recorded in two patients with nasopharyngeal carcinoma (NPC) irradiated 14 and three years ago respectively and compared with 15 healthy controls. The patients had features of post-irradiation myelopathy of the brainstem with reduced gag reflex, unilateral vocal cord paralysis and fasciculation of the tongue. The first patient had a blind left eye. The second patient had quadriparesis. All ears revealed post-irradiation otitis media changes and mixed deafness. BAEP was not recognizable in the left ear of the first patient and was normal in the left ear of the second patient. Simultaneous electrocochleogram and BAEP were recorded from the right ear of the first case. The wave I-V latency interval were prolonged in both right ears. In the absence of local recurrence and brain secondaries, these BAEP changes are attributed to the post-irradiation myelopathy of brainstem.