A clinical study of 407 cases of nasopharyngeal carcinoma in Hong Kong.

Four hundred and seven cases of nasopharyngeal carcinoma were analyzed retrospectively; 403/407 were evaluable for recurrence and survival. Parapharyngeal boost significantly decreased local recurrences in parapharyngeal diseases without base of skull involvement (T2p), but not with base of skull involvement (T3p). Enhanced local control of T2p with boost was significant without neoadjuvant chemotherapy. Tumors localized within the nasopharynx (T1) and tumors with nasal involvement (T2n) suffering from local persistences after external radiation therapy were treated with an intracavitary afterloading method. They had survival and recurrence rates comparable to complete responders to external radiation therapy. Patients with bulky cervical nodes (maximal diameter greater than or equal to 4 cm, N1-N3), treated with neoadjuvant chemotherapy with cis-diamminedichloroplatinum II and 5-fluorouracil, had a regional failure rate, distant metastasis rate, actuarial survival rate, and disease-free survival rate comparable to those with smaller nodes treated with external radiation therapy alone. A simple modification of the Ho's classification by regrouping the T-stages into 'early T-stages' and 'advanced T-stages' and by combining the N1 and the N2 has greatly increased the power of the system in predicting local recurrence and distant metastasis, respectively. There was an overall improvement of the actuarial survival rate and disease-free survival rate over the historical control, and its significance is discussed.

A proposed modification of the Ho stage-classification for nasopharyngeal carcinoma.

Based on the clinical data of a retrospective study of 659 NPC patients with routine computed tomography of the nasopharyngeal region, a refinement of Ho's stage-classification for NPC is proposed with reduction in the number of overall stages without sacrificing the accuracy in predicting prognosis in the short term. Classifying the cervical lymph nodal metastasis into supraclavicular (Ho's N3) and above supraclavicular (Ho's N1 + N2) and the nasopharyngeal primary into early (Ho's T1 + T2n + T20) and advanced (Ho's T2p + T3 + T3p) forms the conceptual backbone of the present proposed modification of the original Ho stage-classification. Power in predicting the occurrence of distant metastases and the local failures has been enhanced by the proposed T-stage and N-stage re-grouping. Retrospective comparison between Ho's and the UICC stage-classifications showed a more even patients number distribution among the overall stages and a greater power in predicting NPC prognosis for the former. Prospective studies to compare the value of the different stage-classifications are required for recommendation of a single classification for general acceptance to facilitate comparison of treatment results between centres.

No association between HLA-DQ and -DR genotypes with nasopharyngeal carcinoma in southern Chinese.

The pathogenesis of nasopharyngeal carcinoma (NPC) is multifactorial. Associations have been reported between HLA and NPC. We studied the HLA-DR and -DQ regions on the molecular level in 136 persons (51 NPC patients and 85 healthy controls) from southern China, a particularly high-prevalence area for NPC. Restriction fragment-length polymorphism (RFLP) was used to genotype the MHC class II DR beta, DQ alpha, and DQ beta regions of the subjects. Polymerase chain reaction (PCR) using sequence-specific primer (SSP) for DQ beta genes was also performed. By RFLP, no significant difference was observed with respect to DRB, DQA, and DQB genes. By PCR SSP typing, we confirmed that there was no significant difference between NPC patients and controls with respect to DQ beta alleles. Our study suggests that HLA-DQ and -DR genes are not associated with NPC in southern Chinese and there may be other gene loci that predispose them to have such a high prevalence of the disease.

Loss of heterozygosity on the short arm of chromosome 3 in nasopharyngeal carcinoma.

A consistent loss of constitutional heterozygosity within a specific chromosome locus in a tumor type is suggestive of a tumor suppressor gene important in the genesis of that tumor. We studied whether such genetic alterations are involved, in the development of nasopharyngeal carcinoma (NPC). Tumor and matched blood leukocytes DNA from eleven Hong Kong Chinese patients with primary NPC stages I to IV were subjected to restriction fragment length polymorphism (RFLP) analysis using chromosome 3-specific polymorphic probes. Such probes are assigned to chromosomal region 3p25 (RAF-1), 3p24-22.1 (ERBA beta), 3p21 (DNF15S2), 3p14 (D3S3), and 3q12 (D3S1). The breakpoint varied among tumors, ranging in extent from 3p21-14. However, 100% frequency of complete loss of heterozygosity was observed at two chromosomal loci: RAF-1 locus (ten of ten cases at 3p25) and D3S3 locus (nine of nine cases at 3p14), in all evaluable NPC patients, suggesting the presence of putative tumor suppressor gene(s) within or close to these defined regions. The observed consistent deletion of alleles on the short arm of chromosome 3 in the NPC cases, which is in line with our previously reported and present cytogenetic findings, may represent a critical event in the multistep genesis of NPC. The present report also identifies defined loci for linkage studies on NPC families.

Asymptomatic temporal lobe injury after radiotherapy for nasopharyngeal carcinoma: incidence and determinants.

Computed tomography (CT) scans were performed on a cohort of 60 patients for detection of temporal lobe injury (TLI) at 1-3.5 years after radiation therapy for nasopharyngeal carcinoma. Nine cases of TLI were identified, five of which were asymptomatic. The earliest case of asymptomatic TLI was found at 2.2 years after radiation therapy and the earliest symptomatic case at 2.3 years. A significantly higher incidence of TLI was found in patients with decreased temporal lobe shielding consequent to omitted eyeshield to the anterior photon beam and in patients treated with a hyperfractionation schedule giving 67.2 Gy in 42 fractions in 6 weeks. The incidence in these subgroups at 2-3.5 years after radiation therapy was 56% (5/9 patients) and 35% (8/23 patients), respectively. No patient in this study had TLI in the absence of these two factors. The implications of the results are discussed.

Treatment outcome of spinal cord compression by nasopharyngeal carcinoma.

Spinal cord compression occurred in 1.6% of a cohort of 626 patients with nasopharyngeal carcinoma during a median follow-up period of 22 months. The degree of motor deficit before treatment was the most important predictor of subsequent motor recovery. One patient had complete reversal of motor deficit and returned to an ambulatory state by chemotherapy alone. The development of spinal cord compression was associated with a short life expectancy in nasopharyngeal carcinoma.

Ovarian ablation failures by radiation: a comparison of two dose schedules.

Sixty Chinese breast cancer patients underwent ovarian irradiation with one of two dose schedules: 12 Gy/4 fractions/4-6 days or 14 Gy/4 fractions/4-6 days. The ovarian ablation failure rates were 14% and 0% respectively in patients above 40 years of age. The overall ablation failure rate in younger patients was unacceptably high at 35%. The significance of the findings is discussed.

Cranial nerve involvement by nasopharyngeal carcinoma: response to treatment and clinical significance.

The incidence of cranial nerve involvement in a group of 564 patients with nasopharyngeal carcinoma was 12%. Most of these patients had multiple cranial nerve involvement with the fifth and sixth nerves being most commonly affected. Different cranial nerves had different chances of recovery after radiotherapy. About half the patients with cranial nerve palsies had complete neurological recovery after radiotherapy. The cranial nerve response, however, was not a significant predictor of local tumour control.

High-dose-rate remote afterloading irradiation of carcinoma of the cervix in Hong Kong: unexpectedly high complication rate.

One hundred and thirty-six patients with biopsy-proven carcinoma of cervix were treated with external beam irradiation to the whole pelvis (46 Gy in 23 fractions) and three weekly applications of high-dose-rate (HDR) intracavitary brachytherapy of 7 or 8 Gy per fraction to point A (2 cm above and 2 cm lateral to the cervical os). The actuarial 5-year survival rate was 72% (Stage IB 85%; IIA 64%; IIB 70%; IIIA 25%; IIIB 53%). Patient age above 61 years and Stage III disease were adverse determinants for survival as shown by multivariate analysis. Late complications developed in 47% (65/137) of patients. Grade 3 or above complications occurred in the bladder, small bowel and sigmoid colon/rectum in 5%, 3% and 7% of patients, respectively. The most significant determinant of severe rectal complications was the addition of a lower vaginal tandem (P less than 0.01); the other determinants of rectal complications included a uterine length greater than 5 cm, a total biologically effective dose to the rectum of more than 120 Gy3 and Stage III disease.

Nasopharyngeal carcinoma: modes of presentation.

Nasopharyngeal carcinoma (NPC) is a common malignancy among the southern Chinese people and has a poor prognosis. The aim of this study was to describe in detail the presentation of NPC as found between 1984 and 1988 at Prince of Wales Hospital, Hong Kong. Our study confirmed that patients present with an advanced stage of malignancy; 70% were stage III to V. Eighty-two percent of patients were between 21 and 60 years of age. The symptoms often suggested benign disease and most patients would delay seeking treatment for at least 5 months. We recommend inspection of the nasopharynx with flexible nasoendoscopy for all persons in high-risk areas on a regular basis and advise a policy of active health education for both physicians and the general population to reduce the stage of NPC at first presentation.

Prospective study of the effects of ventilation tubes on hearing after radiotherapy for carcinoma of nasopharynx.

In patients with nasopharyngeal carcinoma, deafness sometimes occurs following radiotherapy. It is usually conductive, but may be sensorineural. Tinnitus is present frequently and usually is distressing. The role of ventilation tubes (grommets) in relieving these problems was assessed in a prospective randomized controlled trial of 115 patients. In the group with grommets, there was an improvement in hearing, with a reduction of the averaged air-bone gap (p less than .01). This was not found in the control group without ventilation tubes, who developed a larger conductive loss (p less than .01) and, in addition, a slight deterioration of the averaged bone conduction threshold (p less than .01). Surprisingly, the group with grommets did not develop this sensorineural loss (p less than .01). In addition, tinnitus was improved significantly by the insertion of ventilation tubes (p less than .01). Neither necrosis nor stenosis of the external auditory meatus was found in either group.

A clinical study of adenocarcinoma of unknown primary site in Hong Kong.

Forty-two patients with adenocarcinoma of unknown primary (ACUP) presented to the Prince of Wales Hospital in Hong Kong from 1984 to 1985. They were studied for the site of symptomatic metastases at presentation, survival, and response to treatment. Bony (21) and lymph nodal (14) metastases were common. Survival was short with a median duration of 32 weeks and was not affected by sex, site of metastases at presentation, and development of new metastases. Response to combination chemotherapy with cisplatinum, adriamycin and cyclophosphamide (CAP) occurred in 4/31 (12.9%) patients with two complete responses and two partial responses and the responders survived significantly longer than non-responders with a median survival of 51 and 29 weeks respectively (P less than 0.05). Twenty out of 36 (55.6%) treated with radiotherapy had a positive response including five complete responses and fifteen partial responses but there was no demonstrable improvement in survival for the responders.

Nasopharyngeal cancer treated in Singapore.

With effect from July 1987 CT-scans of the nasopharynx became routinely available in the staging of nasopharyngeal cancer (NPC) in our department. Eighty-four evaluable cases during these first six months were studied and the results at a median follow-up period of 34 months revealed that 74% were alive at 2 years. The local relapse rate were 4% for T1; 10% for T2 and 35% for T3 tumours.

Nasopharyngeal carcinoma--a review of radiotherapy techniques.

With modern megavoltage external X-ray treatment for nasopharyngeal carcinoma, results have improved but late sequelae, which are more often associated with the treatment of advanced tumours or multiple courses of external treatment, have also surfaced. Life-threatening complications include temporal lobe necrosis and hypothalamic-pituitary dysfunction. As CT scanning is superior to conventional radiography in tumour mapping, a new dedicated working staging system, catering for cross-sectional imaging parameters, is proposed for a prospective, multi-centre exercise to finalise on a badly needed common system. With it, case selection for more conservative (to minimise complications) or intensified treatments is facilitated. Intracavitary radiation has now been developed well enough for the nasopharynx. For earlier cases, based on the new staging system, this method has the potential to complement a "sub-radical" external treatment dose designed to minimise complications. A multi-centre trial is indicated. To reach cancericidal doses for the more advanced tumours coming very close to vital structures, extra machine time, though precious, is fully justified so that smaller treatment fractions delivered with facial shells for accurate reproduction of precise machine geometry and field geography can be implemented. Otherwise, subsequent management of possible serious treatment complications may cost more than the treatment itself. Various possible complications of radiotherapy and avoidance and management are outlined.

Intracavitary radiotherapy for nasopharyngeal carcinoma--palliation or cure?

Although nasopharyngeal carcinoma is classically treated by external irradiation, the technique invariably results in decreased parotid secretions and rapid tooth decay. For the treatment of locally relapsed tumours, nasopharyngectomy, though effective, may not always be available for routine salvage, especially in endemic areas. A pilot study was made of ten patients having limited local relapses who were treated by intracavitary irradiation (ICI) with or without an abbreviated dose of external irradiation. With ICI alone, relapses outside the nasopharynx occurred in two patients but the combination with even an abbreviated dose of external irradiation was more successful. Nevertheless, even with relapse, patients were free from local symptoms for a median time of over two years--an excellent palliation result. More work, preferably at the multi-centre level, should be done to define more precisely the role of intracavitary irradiation for nasopharyngeal carcinoma.

Current problems in radiotherapy, chemotherapy and staging of nasopharyngeal carcinoma (NPC).

Nasopharyngeal carcinoma (NPC) in South East Asia is almost entirely of the undifferentiated or poorly differentiated squamous cell types which are more radiosensitive and have better prospect for locoregional control. Cross-sectional imaging can now detect disease in the parapharynx which is commonly involved by this carcinoma. This has resulted in up-staging and technique modification for better local control. Poor prognostic factors include parapharyngeal, skull bone, cranial nerve or other wide-spread involvements locally. Neck nodes in the supraclavicular fossae or bulky nodes also confer poor prognoses. A simplified staging classification system is proposed. With the availability of afterloading machines, a booster dose of intracavitary radiotherapy can conveniently be given. When given shortly after the usual external radiotherapy, the desired high dose to the primary can be achieved without increasing the risk of long-term side effects. Chemotherapy given before radiotherapy helps to achieve prompt control of bulky neck nodes which distort the anatomy and pose problems in radiotherapy dosimetry. However, the eventual survival rate is still not improved. As staging and major prognostic factors are better defined, trials of adjuvant chemotherapy given after radiotherapy should be undertaken. However, the ultimate control of NPC may rest on the feasibility studies on screening for early NPC.

Treatment of residual and recurrent cervical metastasis from nasopharyngeal carcinoma.

Eleven patients with cervical metastases from nasopharyngeal carcinoma were studied. Even after adequate radiotherapy treatment, viable tumour cells were detected in all patients. Nine patients underwent radical neck dissection and the histological study of the specimens confirmed the operative findings. The extent of the disease was far greater than the clinical assessment suggesting that simple lymphadenectomy is an inadequate form of treatment.

Radiotherapy and chemotherapy for nasopharyngeal carcinoma.

NPC is unique among head and neck cancers, in that it is radiocurable and moderately chemosensitive. Modern diagnostic techniques have facilitated tumor definition, with consequent improvement in staging accuracy and radiotherapy planning. Our standard radiotherapy technique incorporates routine prophylactic neck irradiation of early tumors. Special techniques for more advanced tumors are described. Neoadjuvant cis-platinum-containing chemotherapy has proved useful in controlling regional and distant metastatic disease.

Computed tomography contrast enhancement of cervical lymphadenopathy.

In a prospective study of 51 cases of lymphadenopathy (44 with cervical metastatic nasopharyngeal carcinoma, NPC) using intravenous contrast and computed tomography (CT), a ring enhancement was observed. A retrospective review of 105 cervical carcinomatous lymph nodes (64 with metastatic NPC) showed a prominent peripheral hypervascular pattern not seen in 48 lymphomas and 60 normal controls. We conclude that in carcinomatous cervical lymphadenopathy, enhancement can be achieved by intravenous contrast and CT; and the peripheral hypervascularity is the anatomical basis for the ring appearances seen radiographically.