Gefitinib, cisplatin, and concurrent radiotherapy for locally advanced head and neck cancer: EGFR FISH, protein expression, and mutational status are not predictive biomarkers.

BACKGROUND: Gefitinib was demonstrated to be synergistic with cisplatin and radiotherapy (RT) in in vitro studies. Biomarkers predictive of response to gefitinib in squamous cell head and neck cancer is still lacking. METHODS: Thirty-one patients with locally advanced and easily accessible primary tumor sites for biopsies were recruited. Gefitinib was started 3 weeks before the start of cisplatin/concurrent radiotherapy (CTRT) and continued during the CTRT phase and thereafter for 4 months as consolidation phase. Two baselines and a repeat tumor sample were taken after 2 weeks of gefitinib alone to study its impact on tumor gene expression. Epidermal growth factor receptor (EGFR) protein expression, FISH and mutational status, and matrix metallopeptidase 11 (MMP11) protein expression were correlated with response and survival outcome. RESULTS: The overall response rate to gefitinib alone was 9.7%. The survival outcome is as follows: median disease free 1.3 years, median survival time 2.4 years, 3-year disease free 42.9%, and 3-year overall survival 48.4%. EGFR FISH, protein expression, and mutational status did not predict for response nor survival outcome of patients. Although MMP11 overexpression did not predict for response, it predicted significantly for a poorer survival outcome. CONCLUSIONS: Gefitinib can be combined safely with cisplatin/RT. More studies are needed to uncover predictive biomarkers of benefit to gefitinib.

Surgery and adjuvant radiotherapy vs concurrent chemoradiotherapy in stage III/IV nonmetastatic squamous cell head and neck cancer: a randomised comparison.

We compared concurrent combination chemotherapy and radiotherapy with surgery and adjuvant radiotherapy in patients with stage III/IV nonmetastatic squamous cell head and neck cancer. Patients with non-nasopharyngeal and nonsalivary resectable squamous cell head and neck cancer were randomised to receive either surgery followed by adjuvant radiotherapy (60 Gy over 30 fractions) or concurrent combination chemotherapy and radiotherapy (66 Gy in 33 fractions). Combination chemotherapy comprised two cycles of i.v. cisplatin 20 mg m(-2) day(-1) and i.v. 5-fluorouracil 1000 mg m(-2) day(-1), both to run over 96 h given on days 1 and 28 of the radiotherapy. A total of 119 patients were randomised. At a median follow-up of 6 years, there was no significant difference in the 3-year disease-free survival rate between the surgery and concurrent chemoradiotherapy (50 vs 40% respectively). The overall organ preservation rate or avoidance of surgery to primary site was 45%. Those with laryngeal/hypopharyngeal disease subsite had a higher organ-preservation rate than the rest (68 vs 30%). Combination chemotherapy and concurrent irradiation with salvage surgery was not superior to conventional surgery and postoperative radiotherapy for resectable advanced squamous cell head and neck cancer. However, this form of treatment schedule with a view to organ-preservation can be attempted especially for those with laryngeal/hypopharyngeal and possibly oropharyngeal disease subsites.

Why generic and disease-specific quality-of-life instruments should be used together for the evaluation of patients with persistent allergic rhinitis.

BACKGROUND: The importance of assessing health-related quality of life (HRQL) of patients with allergic rhinitis (AR) has been well established, but the specific roles of rhinitis-specific or general health instruments have not been delineated. OBJECTIVE: We analysed the psychometric properties of a disease-specific instrument, the Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ) and the general health instrument, the Medical Outcome Short-Form 36 (SF-36) as they are employed in combination in patients with persistent AR in clinical practice. METHOD: We analysed the data collected from a prospective study of 43 newly diagnosed patients with persistent AR and 44 controls. We interviewed the patients four times, at baseline, weeks 4, 8 and 10. RESULTS: The RQLQ and SF-36 have good discriminative property, internal consistency, and test-retest reliability. The RQLQ is superior to the SF-36 as an evaluative instrument because more of its domains respond to change, the magnitude of change was greater, and the response was faster. The SF-36 is more susceptible to floor and ceiling effects. Both instruments are unsuitable for mildly symptomatic patients based on Rasch model analysis. Each questionnaire assesses a distinct and significant portion of the total HRQL of persistent AR. CONCLUSION: The SF-36 and RQLQ are good for discriminating rhinitis patients from controls, but the former is poor for detecting changes in QOL. Both are inappropriate for mildly symptomatic patients. Each instrument measures non-overlapping halves of the measurable HRQL. For an assessment of the HRQL in persistent AR that is complete and responsive both instruments should be employed together.

Resurfacing of the nasopharynx after nasopharyngectomy using a free radial forearm flap.

BACKGROUND: Nasopharyngectomy is emerging as an important treatment option for salvaging locally recurrent nasopharyngeal carcinoma (NPC). After nasopharyngectomy, resurfacing the nasopharynx and covering the internal carotid artery is important to minimize the risk of infection, osteoradionecrosis, and carotid rupture. Previous authors have advocated the use of free grafts of skin and mucosa for this purpose but have also described significant rates of partial and total graft failure. METHODS: We believe that the best and most reliable way to resurface the nasopharynx is with vascularized tissue, and our preference is for the use of a free radial forearm flap. To illustrate our approach, we present two patients who underwent nasopharyngectomy by means of a maxillary swing approach and who had resurfacing of the surgical defect with a free radial forearm flap. RESULTS: Both patients had complete en bloc resection of tumor followed by the insetting of a free radial forearm flap to reline the surgical defect. Both flaps remained completely viable, and both patients achieved successful resurfacing of the entire nasopharynx. The morbidity of surgery was minimal, and there were no perioperative complications. On assessment 1 year later, the free radial forearm flap continues to reline the entire neonasopharynx, and the long-term functional recovery after surgery is excellent. CONCLUSION: Resurfacing the nasopharynx after nasopharyngectomy with a free radial forearm flap aids healing and minimizes the risk of complications. The morbidity of surgery is minimal and the functional recovery is excellent.

Management of intraparotid facial nerve schwannomas.

BACKGROUND: The purpose of the present paper was to review the management of intraparotid facial nerve schwannoma so as to discuss its clinical presentation, evaluate the various possible diagnostic investigations, and compare the various surgical options and outcome. METHODS: Case series was undertaken of five (1.3%) patients with facial nerve schwannoma out of 400 consecutive parotidectomies at Singapore General Hospital. RESULTS: There were three men and two women with an age range of 29-65 years. Three patients presented with painless parotid lumps while two had painful parotid swellings. None had facial nerve paresis. Only one patient had preoperative diagnosis suspicious of schwannoma by fine-needle aspiration cytology (FNAC). Diagnoses were made intraoperatively. Four patients had excision with cable grafting of the nerve defect. achieving facial nerve grade II-IV (House-Brackmann scale). One patient who underwent enucleation of tumour with nerve preservation achieved grade II. CONCLUSIONS: Preoperative diagnosis is difficult but it is important for discussion of the extent and options of surgery. Fine-needle aspiration cytology holds promise in making a preoperative diagnosis. Enucleation with nerve preservation where possible seems to offer better facial function whereas nerve excision with cable graft can give satisfactory results.

The pattern of nodal recurrence following definitive radiotherapy for nasopharyngeal carcinoma.

BACKGROUND: The pattern of nodal metastasis in previously untreated nasopharyngeal carcinoma (NPC) has been studied and reported. In order to analyse the pattern of recurrent nodal disease in previously treated NPC, a retrospective study on 68 patients who underwent radical neck dissection for regionally recurrent NPC was conducted. METHODS: Seventy-four neck dissections were performed on 68 patients who developed nodal recurrence after a mean disease-free interval of 39.2 months. None of the patients had evidence of local or systemic disease at the time of surgery. Histopathological reports of the 74 neck dissections were analysed with regard to the number of positive nodes as well as the number of involved nodal levels. RESULTS: Of the 65 neck dissection specimens with analysable data, 31 showed metastatic disease at a single nodal level with a mean number of positive nodes of 1.2, while 34 showed metastatic disease at multiple levels with a mean number of positive nodes of 6.6. Nodal recurrence occurred at level II with the greatest frequency (78.5%). Of the 31 specimens with single level nodal involvement, 21 (67.7%) occurred at level II. Isolated involvement at the other levels did occur, but was uncommon (range 3-16%). Of the 34 specimens with multiple level nodal involvement, 30 (88.2%) showed involvement at level II. Once more than one level was involved, the frequency of involvement at any given level was at least 30%. CONCLUSION: The predominant involvement at level II and the high frequencies of involvement at all levels support the use of a classical radical neck dissection in treating recurrent nodal disease in NPC.

Epidemiology of Warthin's tumour of the parotid gland in an Asian population.

BACKGROUND: Recent studies have documented a number of changing demographic features in the occurrence of Warthin's tumour (adenolymphoma) of the parotid gland. In order to analyse its epidemiology in an Asian population, a retrospective study was performed on all parotid neoplasms (n = 289) operated on between 1988 and 1998. PATIENTS AND METHODS: A total of 209 consecutive patients were selected for study, 136 with pleomorphic adenomas (one bilateral) and 73 with Warthin's tumours (seven bilateral). Patients were analysed with regard to tumour incidence, age, sex and race. Smoking as an aetiological factor in the development of Warthin's tumour was also studied. RESULTS: Warthin's tumour formed 25 per cent of parotid tumours and its ratio to pleomorphic adenomas was 1 : 1.9. Multicentricity was found in 14 patients (19 per cent). The male : female ratio for Warthin's tumours was 4.6 : 1. The proportion of Warthin's tumours did not show any increasing trend relative to pleomorphic adenomas. The racial distribution of Warthin's tumours showed an increased incidence among Chinese and a reduced incidence among Malays and Indians. The adjusted odds ratio for sex and age favouring an association between smoking and Warthin's tumour was 39.5 (95 per cent confidence interval 10.5-149. 0; P < 0.0001). CONCLUSION: The incidence of Warthin's tumour is considerable among Asians although there is still male predominance. There is no rising incidence of Warthin's tumour; the trend parallels the declining smoking rate in the population. The lower incidence among ethnic groups with dark skin seems to suggest concomitant genetic factors other than environmental factors alone in histogenesis. Smokers have a 40-fold greater risk than non-smokers of developing a Warthin's tumour.

Quality of life of patients with perennial allergic rhinitis: preliminary validation of the Rhinoconjunctivitis Quality of Life Questionnaire in Singapore.

Though sufferers of perennial allergic rhinitis do not die from their ailment, they endure years of chronic nose disease that Interferes with many important aspects of their lives. A rhinitis-specific instrument to gauge the quality of life of patients with this disease was published in 1991. Here, we validated the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) for use in English-speaking patients with perennial allergic rhinitis. We established that the RQLQ distinguishes between patients and control, demonstrates internal consistency and is sensitive to change. This study suggests that the RQLQ can be used to assess the quality of life of patients with perennial allergic rhinitis in Singapore.