Abstracts of the British Association of Head and Neck Oncologists 32nd Annual General Meeting and Scientific Meeting held at the Royal College of Physicians, London, 28th April 2000

Clinical Oncology

Clinical Oncology (2000)12:260±269 # The Royal College of Radiologists

Abstracts Abstracts of the British Association of Head and Neck Oncologists 32nd Annual General Meeting and Scienti®c Meeting held at the Royal College of Physicians, London, 28th April 2000 Future Studies of Sentinel Node Biopsy in Head and Neck Cancer

The Role of Sentinel Node Imaging/Biopsy and 18F-FDG PET in the Management of the N0 Neck in Oral Cancer

T. Shoaib1, D. S. Soutar1, I. G. Camilleri1, H. W. Gray2, A. G. Robertson3 and D. G. MacDonald4, 1Plastic Surgery Unit, Canniesburn Hospital, 2Department of Nuclear Medicine, Royal In®rmary, 3Beatson Oncology Centre, Western In®rmary and 4 Oral Pathology Unit, Glasgow Dental Hospital and School, Glasgow, UK

N. Hyde1, L. Newman1, E. Prvulovich2, W. Waddington2, M. Keshtgar2 and P. J. Ell2, 1Department of Maxillofacial Surgery and 2 The Institute of Nuclear Medicine, University College London Hospitals NHS Trust, London, UK

Sentinel node biopsy (SNB) is an accurate means of staging the regional lymph nodes in breast cancer and melanoma. In head and neck cancer, the technique may have a role in the management of the neck to identify patients with nodal metastases. The aim of the study was to determine if the sentinel lymph node (SLN) accurately re¯ects the nodal status of patients with head and neck cancer. The study material comprised 80 neck sides from patients with oral and oropharyneal cancers that were accessible to injection. An observational design was used in an NHS trust setting combining resources from nuclear medicine, plastic surgery and oral pathology. The main outcome measures were the identi®cation of the SLN; the presence of tumour within the SLN; and the presence of tumour within non-sentinel lymph nodes from the neck dissection, if performed. Up to 40 MBq of 99mTc-labelled human serum albumin was injected to surround the primary tumour. Lymphoscintigraphy identi®ed the anatomical position of radioactive SLNs. During surgery, Patent Blue V dye was injected at the same site as radiocolloid. SLNs were identi®ed using blue dye visualization and a hand-held gamma probe. SLN pathology was compared with that of the remaining neck dissection, if performed. Eighty necks were explored. In clinically N0 necks, SLNs were found in 17 necks with metastases and contained tumour in 16. Thirteen N0 necks were explored for SLNs without completion of a neck dissection. SLNs were found in 12 and a neck dissection was subsequently performed in two after pathological examination of the node. In the clinically N+ neck, SLNs did not commonly contain tumour, but performing the procedure in this group permitted greater experience with SNB. Our study suggests that the SLN, when found, accurately re¯ects the pathology of the clinically N0 neck. A future study will be required in which SNB is performed on patients undergoing no elective neck surgery or irradiation. To achieve adequate power, this study will require co-operation between different units performing the procedure. In this multicentre study, clinically N0 patients will undergo SNB using a combination of blue dye and radiocolloid injection. SLNs will be examined pathologically using both routine and special stains. If the SLN is found to contain tumour, a neck dissection will be performed and if it is free of viable tumour cells, no further elective treatment will be given to the neck. Follow-up will be for a minimum of 2 years.

Accurate staging of the neck is essential in patients with oral cancer. However, conventional imaging techniques (computed tomography, ultrasound, magnetic resonance imaging) are associated with high false-negative rates. Histologically proven rates of occult disease in the clinically N0 neck are reported at 25%±27%. The presence of metastatic disease in the neck reduces 5-year survival rates by 50%, irrespective of T stage. There is an obvious need to improve our ability to detect occult nodal disease preoperatively. Sentinel node imaging and biopsy is a largely untested diagnostic tool in this area. The aim was to assess and compare the accuracy of positron emission tomography (PET) and sentinel node imaging/biopsy in determining the status of the cervical lymphatics. Seven patients presenting with biopsy proven oral carcinoma, and clinically N0 necks, underwent pre-operative 18F-¯uorodeoxy-glucose (FDG) PET and lymphoscintigraphy, the latter utilizing a peritumoral injection of 99mTc human albumin (albures/ nanocolloid). On the day of surgery, 2% Patent Blue dye and the Neoprobe (hand-held gamma probe), were used in combination to guide sentinel node harvest. Histological examination was correlated with preoperative ®ndings. In all patients the sentinel nodes were successfully retrieved; they were both blue and radioactive. In ®ve patients the sentinel nodes and the residual neck dissection were negative for tumour. In one patient the sentinel node was positive as was the neck. In one patient the sentinel node was negative, but a positive node was found in the neck. PET failed to identify nodal disease in the two patients with histologically proven neck metastases. These preliminary data suggest that PET may be less useful in staging the neck than sentinel node imaging/biopsy.

Sentinel Node Biopsy for Head and Neck Melanoma B. S. Dheansa, R. Allen, M. G. Cook and B. W. E. M. Powell, St George's Hospital, London, UK The management of head and neck melanoma is challenging. Sentinel node biopsy may have a role in the management of the lymph node basin but, in our experience, this presents more dif®culties than either the groin or the axilla. In our series of 200 patients who have undergone sentinel node biopsy, the largest reported series in the UK, 32 had primary head and neck melanoma. We report our early results and compare sentinel node biopsy in the head and neck with the groin and axilla. All patients with a vertical growth phase melanoma were considered for sentinel node biopsy. Primaries were located in the

cheek (10), ear (8), forehead (7), neck (5) and nose (2). Nodes identi®ed by using lymphoscintigraphy were de®ned as sentinel nodes if they were the ®rst to be localized. Patients with positive nodes were considered for adjuvant vaccine therapy after nodal clearance. All patients have been regularly followed up and any recurrences or metastases documented. The Breslow thickness of the tumours ranged from 0.5 to 16 mm (mean 2.4) and up to four sentinel nodes could be marked in any one patient. Seventy-two sentinel nodes were identi®ed with lymphoscintigraphy but only 62 (86%) could be harvested. This compares with a 99% success rate in the groin and axilla. Lymphoscintigraphy did not localize a sentinel node in two patients, while in a further two it was not possible to harvest any of the nodes identi®ed. In ®ve patients only some of the marked nodes could be excised. The technical dif®culties encountered with lymphoscintigraphy and surgery for sentinel node biopsy are discussed. Two patients were found to have metastatic melanoma in the sentinel nodes. To date no recurrences or lymph node spread has been noted in the negative node group. Our early data support the use of sentinel node biopsy in the management of melanoma but the head and neck region has potential pitfalls that could reduce the success of this technique.

Lateral Neck Masses in the Over Forties are Malignant Until Otherwise Proven Z. G. G. Makura1, B. Hickerton1, G. Cox1, J. E. Fenton1, S. R. Jackson1, L. Turnbull2, P. Smith2 and A. S. Jones1, 1Department of Otolaryngology/Head and Neck Surgery and 2Department of Pathology, Royal Liverpool University Hospital, Liverpool, UK Neck lumps may herald benign or malignant disease, the differentiation of which is imperative for patient management. The aim of this investigation was to calculate what proportion of neck lumps in two age groups (over and under 40 years) are malignant. The subjects were adult patients in a head and neck/ rapid access neck lump clinic. A retrospective audit was carried out in a large teaching hospital. The main outcome measure was the cytological diagnosis of the specimens (de®nitive histology was not included in the analysis). A retrospective analysis was carried out of all ®ne needle aspiration cytology specimens obtained during a 3-month period. Twenty-one of the 44 (48%) specimens in the over 40 years age group were malignant compared with two of 15 specimens (13%) in those under 40. Table 1. Histology according to sex Malignant masses

Male

Female

Total

Metastatic squamous cell carcinoma Hodgkin's lymphoma Non-Hodgkin's lymphoma Adenocarcinoma Anaplastic large cell lymphoma B-cell lymphoma

7 0 2 2 1 0

8 1 1 0 0 3

15 1 3 2 1 3

Total

25

In patients aged over 40 years a lateral neck mass should be considered malignant until otherwise proven.

The State of Head and Neck Oncology Specialist Nursing in the UK: Descriptive Study J. Stych1, L. Potter2 and M. Birchall1, 1Department of Otorhinolaryngology, Southmead Hospital and 2British Association of Head and Neck Oncology Nurses and Southmead Hospital, Bristol, UK Published guidelines [1,2] emphasize the importance of specialist nurses as core members of head and neck oncology team. This was reinforced by a recent study [3] of patients' and carers' views. However, there are few data on the present organization of head and neck nursing in the UK or on how comfortable head and neck

nurses are with their jobs. The aim was: (1) to determine the workload of head and neck oncology nurse specialists across the UK; and (2) to assess nurses' satisfaction with their present jobs. The study design utilized a cross-sectional questionnaire administered to the 33 registered members of the British Association of Head and Neck Oncology Nurses. The main outcome measures were: population/hospitals served, numbers of new cases, and nurse satisfaction. A questionnaire was piloted, circulated and reinforced by telephone. Descriptive statistics were used. Two posts had disappeared since registration; 23 replies were received from 19 separate teams. The median population covered was 600 .000 (range 3.6±0.2 million). The median number of new patients in 1998 was 100 (44±210). Fifty-eight per cent of teams saw patients outside their catchment area (median 17, range 5±75). There was no relationship between the number of patients served and the number of nurses in the teams. Sixty-eight per cent of funding was NHS; 32% was Macmillan. Half accept referrals directly from GPs and General Dental Practitioner (GDPs). Nurses felt that referrals were `always' or `usually' appropriate 90% of the time. Only 50% offer valve-changing and bereavement support services. Fifty-three per cent of nurses spend time with non-head and neck cancer patients. Broadly, head and neck specialist nurses felt optimistic about their jobs, but most thought their workload was excessive, which limited the service they could offer. Many suggestions were made on ways to improve services. There is considerable variation in head and neck specialist nurse workload in the UK. Nurses feel that this is adversely affecting the service they can provide, although their job satisfaction appears to be high. A strategy is required to ensure that pump-priming money is placed where it is most required. References 1. Glaholm J. Quantity assurance in head and neck oncology. London: British Association of Head and Neck Oncologists, 1997. 2. Wilson J. Effective head and neck cancer management. London: British Association of Otolaryngologists, 1998. 3. Birchall M, Richardson A, Lee L. Finding their voices. Bristol: South and West Regional Cancer Organisation, 2000.

Accelerated Radiotherapy (CHART) After Surgery for Advanced Head and Neck Cancer M. I. Saunders1, N. Shah1, S. Dische1, M. K. B. Parmar2, G. Grif®ths2 and J. Lyddiard2, 1Marie Curie Research Wing, Centre for Cancer Treatment, Mount Vernon Hospital, Northwood and 2 MRC Cancer Trials Of®ce, London, UK There is a high incidence of local recurrence after surgery for advanced disease and radiotherapy is commonly used postoperatively. There is evidence to suggest that tumour cells left in the operative ®eld may proliferate extremely rapidly, so an accelerated course of radiotherapy may be most appropriate. CHART or CHARTWEL (without weekend) has been employed postoperatively in a series of 24 patients who have undergone surgery for advanced head and neck cancer. Eleven received CHART to 54 Gy and 13 CHARTWEL from 49.5 to 54 Gy. All patients completed treatment to the prescribed dose. In one patient, treatment was extended by 1 day owing to a feeding tube complication. Acute morbidity amounted to con¯uent mucositis in 82% of the patients; this was not signi®cantly different from that observed in the CHART randomized trial. Seven patients died owing to disease, six with local recurrence at between 1 and 26 months after treatment. Of the 18 who remain alive at between 8 and 75 months, one has local recurrence. Eighteen patients showed high risk factors and of these 72% have achieved long-term control. An accelerated regimen of radiotherapy has shown promising results in a pilot study. Plans for a randomized controlled trial have been presented to the Medical Research Council and have moved through the phrases of outline approval to gaining funding. The ®nal protocol is presently being devised and it is hoped that within the next few months it will be completed and the trial begun in a minimum of 10 centres within the UK. Abstracts

261

The Use of Iridium-192 implants for T1/T2N0 Squamous Cell Carcinoma of the Tongue and Floor of Mouth: Control and Complication S. Sothi, J. Townley, J. Glaholm and A. Goodman, The Cancer Centre, Queen Elizabeth Hospital, Birmingham, UK. T1/T2N0 squamous cell carcinomas of the tongue can be treated with surgical excision, interstitial radiotherapy or external beam radiotherapy. Our aim was to determine the outcome of patients with tongue and ¯oor of mouth cancers who had been treated with iridium-192 implants at our centre. All such patients treated between 1994 and 1998 were included in this retrospective review. The main outcome measures were: local and regional recurrence, survival and complication rates. Medical records were reviewed. Actuarial survival was calculated using the Kaplan±Meier method. Thirty-four patients were treated by two consultants. The median age was 61 years (range 35±84). Twenty-®ve had tongue cancers; the rest were ¯oor of mouth. Twenty-six were T1 tumours, eight were T2. The median tumour size was 2.0 cm (range microscopic to 3.5 cm). Seven patients underwent laser excision prior to brachytherapy, ®ve with incomplete excision and two with close margins. Twenty-seven patients were treated with brachytherapy alone (60 Gy) with a median dose rate of 0.52 Gy/h (range 0.34±0.87). Seven patients were treated with a combination of brachytherapy (30 Gy) and external beam radiotherapy (41.25 Gy in 15 fractions) to the primary site and ®rst station nodes. Median follow-up was 35 months (range 3±62). Two of 34 (6%) patients have recurred locally; both had simultaneous regional node recurrence and both had been treated with branchytherapy alone. Six patients (18%) developed regional node recurrence; ®ve had been treated with brachytherapy alone. Two patients with regional recurrence have undergone successfully salvage surgery. Five patients have died, three with recurrent disease. The actuarial 2year survival was 85%. Four patients developed osteoradionecrosis; three had been treated with brachytherapy alone. One healed with conservative treatment, two after hyperbaric oxygen, and the other required surgery and hyperbaric oxygen. Interstitial therapy with iridium-192 is effective treatment for small T1/T2N0 squamous carcinomas of the tongue and ¯oor of mouth. Supraregional specialization is required in view of small patient numbers.

A Phase II Trial of Onyx-015 Attenuated Adenovirus in Combination with Systemic Chemotherapy in Recurrent, Refractory Squamous Carcinoma of the Head and Neck S. E. Morley1, I. Ganley1, D. S. Soutar1, D. Kirn2 and S. Kaye3, Department of Plastic Surgery, Canniesburn Hospital, Glasgow, 2 Department of Medical Oncology, Beatson Institute, Glasgow, UK and 3Onyx Pharmaceuticals, Richmond, California, USA 1

Onyx-015 is a gene deleted adenovirus that is under investigation as an anticancer agent. It preferentially replicates within and kills tumour cells that are de®cient in the tumour suppressor p53 protein, a defect present in >60% of human solid malignancies. We report its use with concomitant systemic chemotherapy to treat patients with advanced squamous cell carcinoma (SCC) of the head and neck. The aim was to determine the effectiveness of intra-tumoral injection of Onyx-015 in combination with intravenous chemotherapy in treating recurrent SCC of the head and neck. Thirty-eight patients with advanced recurrent SCC of the head and neck that was refractory to standard therapies were recruited. The median age was 64 years (range 23±78). Most patients had disease that had recurred after both surgery and radiotherapy. The study was a multicentre, open label Phase II trial. Treatment cycles comprised ®ve daily intra-tumoral injections of Onyx-015 concurrently with intravenous cisplatin and 5-¯uorouracil. Patients received between two and six cycles at 3-weekly intervals. Those with more than one tumour deposit could receive injections of saline to the second lesion, which then acted as a control. These patients were treated in the oncology department of a university teaching hospital. The main outcome measures were: tumour volume, measured using magnetic resonance imaging, computed tomography and clinical assessment; and side-effects of treatment were noted. Tumours were graded as having: a full response (complete

262

Abstracts

disappearance); a partial response (regression by >50% but <100%), or progressive disease at a minimum of 4 weeks posttreatment. Complete or partial response in injected tumours was observed in 19 of 30 evaluable patients (63%). In 11 patients with multiple lesions where saline was injected as a control, response was seen in nine of 11 virus-injected compared with three of 11 salineinjected lesions (P=0.014). Side effects of treatment, such as nausea and vomiting, were comparable with chemotherapy alone. Intratumoral injection of Onyx-015 combined with systemic chemotherapy is well tolerated and gives favourable results compared with standard treatment in recurrent SCC of the head and neck. These data support further investigation into the role of Onyx-015 in the treatment of head and neck cancer.

Differing Expression of Bax and bcl-2 May In¯uence Radioresponsive Behaviour in Mouth and Oropharyngeal Cancers N. Andrews1, T. Helliwell2, C. Walker3, and A. S. Jones1, Departments of 1Otolaryngology and 2Pathology, University of Liverpool, Liverpool and 3J. K. Douglas Laboratory, Clatterbridge Centre for Oncology, Clatterbridge, UK Bax and bcl-2 are two molecules from the same gene family and share sequence homology. These molecules, however, differ in their function within the cell. Bax promotes apoptosis, while bcl-2 promotes increased cellular survival. Owing to the function of these molecules, their expression in tumours are important in tissue radiosensitivity. Bjork-Eriksson et al. showed in 1999 that oral cancers were clinically more radioresistant than oropharyngeal carcinomas, but no explanation was put forward for the differing radiosensitivity. Our aim was to determine the reason for the varying radioresponsive behaviour between carcinomas of the mouth and the oropharynx. Thirty-one patients with oral carcinoma and 38 with oropharyngeal carcinoma were the subjects of a laboratory-based study. Immunohistochemistry was carried out on paraf®n-embedded 4 mm sections using the streptavidin-biotin/horseradish peroxidase method. A minimum of 200 cells were counted for each sample and the percentage of cells staining brown (expressing the antibody of interest) was calculated. The mean expression of each antibody for each site was then calculated. Chi-squared analysis was used to determine if there were any signi®cant differences in the expression of the molecules between the two sites. Tables 1 and 2 show the mean percentage of cells in tumours expressing bax and bcl-2 in the two sites and the percentage of specimens expressing bax exclusively, bcl-2 exclusively, and both proteins. Table 1. Protein Mouth (% cells)

Oropharynx (% cells)

Signi®cance

Bax bcl-2

56 97

P<0.05 ns

6.6 82

Table 2. Protein

Mouth (% cases)

Oropharynx (% cases)

Bax bcl-2 Bax/bcl-2

0 71 29

2.5 5.0 92.5

The predominance of anti-apoptotic bcl-2 over the pro-apoptotic bax may result in a survival advantage of cells in oral carcinomas over those in oropharyngeal carcinomas. The increased survival advantage of cells in oral carcinomas may determine the difference in responsive behaviour between the two sites. These ®ndings may have implications for radiotherapy because oral carcinomas may already have a survival advantage and be less likely to respond to treatment.

Hypoxia-Regulated Genes in Head and Neck Squamous Cell Carcinoma N. J. P. Beasley1,2, M. Alam2, G. Cox and A. L. Harris2, 1Oxford Centre for Head and Neck Oncology and 2ICRF Molecular Oncology Group, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK Areas of hypoxia are common within head and neck tumours. The degree of hypoxia predicts radioresistance and prognosis. Hypoxia induces the transcription of genes known to be important in the pathogenesis of cancer (e.g. vascular endothelial growth factor (VEGF) a proangiogenetic cytokine, glucose transreporter (Glut) 1, and lactate dehydrogenase (LDH), which is important in adaptation to anaerobic respiration). The increased transcription is in part due to upregulation of the hypoxia inducible factor (HIF1a), a nuclear transcription factor. We aimed to look at the expression of HIF-1a and its target genes, VEGF, Glut1 and LDH in head and neck squamous cell carcinoma (HNSCC). Two tongue squamous carcinoma cell lines were used (UMSCC 22A, SCC-25) and 19 paired tumour and normal tissue samples from primary HNSCC snap frozen in liquid nitrogen. Cell lines were grown in normoxia and hypoxia for 16 hours, and cell extracts were prepared. Tissue samples were homogenized and extracts prepared. HIF-1a and Glut1 expression were determined by immunoblotting and quanti®ed by spot densitometry. VEGF expression was determined by enzyme-linked immunosorbent assay and LDH by colorimetric assay. Statistical comparison between tumour tissue and normal samples was made using the Wilcoxon signed-rank test. HIF-1a, Glut1 and LDH were all overexpressed in cells grown in hypoxia. VEGF was overexpressed in normoxia and hypoxia. HIF-1a, Glut1, VEGF and LDH were overexpressed in tumour compared with normal tissue (HIF-1a: tumour (T) median 114, normal (N) median 69, P=0.023; Glut1: T median 133, N median 56, P=0.003; VEGF T mean 49 pg/ml, N mean 2.7 pg/ml, P=0.043; LDH: T median 161 iu, N median 76 iu, P=0.002). Overexpression of HIF-1a and three of its target genes indicates the importance of hypoxia-induced gene expression in HNSCC. These target genes give the tumour cell a survival advantage by promoting angiogenesis, increasing glucose transport and adapting to anaerobic metabolism. This may be another mechanism for hypoxic tumour radioresistance and help to explain why outcome is worse than well-oxygenated tumours. HIF-1a may be the common pathway for gene induction and is a potential target for therapy in the future.

Expression of Cylcin-Dependent Kinase Inhibitor p21(WAF1) and p53 Tumour Suppressor Genes in Laryngeal Cancer J.-P. Jeannon, J. Soames1,2, J. Lunec3, S. Awwad1, V. Ashton4 and J. A. Wilsons, 1Department of Otolaryngology ± Head and Neck Surgery, 2Department of Oral Pathology and 3Cancer Research Unit, University of Newcastle upon Tyne, Newcastle, 4Centre for Health and Medical Research, University of Teeside, Middlesborough and 5Department of Radiotherapy and Oncology, Royal Hospital, Shrewsbury, UK The cyclin-dependent kinase inhibitor p21 and the tumour suppressor p53 play a fundamental role in controlling the normal cell cycle [1]. p53 mutations are one of the commonest genetic events seen in cancer [2]. Thus far, these markers have failed to be useful in predicting prognosis. The aim of the investigation was to determine if p53 and p21 protein expression related to survival. Paraf®n embedded sections from formalin ®xed archival pathology specimens were taken at random from the diagnostic biopsies of 60 previously untreated patients with laryngeal cancer. The main outcome measures were 5-year actuarial and disease-free survival. Immunohistochemistry was performed with p21 and p53 monoclonal antibodies (Novocastra Laboratories, UK). Positive (breast cancer) and negative (no primary antibody) controls were used. Clinical data were retrieved from the patient notes. Multivariate analysis using stepwise Cox's proportional hazard method was used. Kaplan±Meier survival curves were constructed. Complete follow-up data were available on 45 of 60 patients. The median follow-up was 6 years. Multivariate analysis showed that T stage (P=0.003) and p21 (P=0.02) expression were signi®cantly associated with poor survival. p53 expression was

Fig. 1. Kaplan±Meier survival curve: group 1 <2% +ve cells; group 2 >50% +ve cells; group 3 >75% +ve cells. associated with decreased disease-free survival (P=0.03) (Fig. 1), p21 expression and survival. Patients expressing high p21 levels (group 3) were associated with poor survival (P=0.02). This is the ®rst paper to show that altered p53 and p21 expression can be useful independent prognostic indicators in laryngeal cancer. These tumour markers supplement the TNM classi®cation in determining actuarial and disease-free survival. References 1. Pines J. Cyclins and cyclin-dependent kinases: theme and variations. Adv Cancer Res 1995;66:181±215. 2. Zhang LF, Hemminki K, Szyfter K, et al. p53 mutations in larynx cancer. Carcinogenesis 1994;15:2929±51.

Suprafascial Dissection of the Radial Forearm Flap Combined with a Negative-Pressure Wound Dressing: Reducing Donor Site Morbidity C. M. E. Avery and A. E. Brown, Department of Maxillofacial Surgery, The Queen Victoria Hospital, East Grinstead, UK The free radial forearm ¯ap is one of the most widely used ¯aps in head and neck surgery. However, the donor site may by compromised by signi®cant postoperative morbidity such as skin graft loss, delayed healing, and tendon exposure. The problem is the poor quality of the forearm graft recipient bed. Suprafascial elevation of the radial forearm ¯ap is a new dissection technique. It may be harvested, without the underlying deep fascia, based upon multiple longitudinal septocutaneous perforators arising from the radial artery. Preservation of the deep fascial layer over the entire donor site provides a superior graft recipient bed. It also facilitates retention of the super®cial radial nerve. We have combined this dissection technique with the negative pressure wound dressing in an attempt to minimize donor site morbidity. Fifteen consecutive patients requiring a free radial forearm ¯ap were included in a prospective, non-randomized, open study. Comparisons were made with departmental historical data and the published literature. Outcome measures were: degree of graft take, time to healing, tendon exposure, wrist function and sensation. Graft take was measured with a transparent grid; the time to dry dressings was noted and motor and sensory functions were assessed. There was complete graft take by day 5 in 93.3% and by 1 month in 100%; the mean time to healing was 2 weeks. There was no delayed healing beyond 1 month and no tendon exposure. Motor and sensory functions were excellent. The suprafascial dissection technique in combination with a negative pressure wound dressing represents current `state of the art' management of the radial forearm donor site.

Reliability of Recipient Vessels in Head and Neck Reconstruction E. Arumugam and D. J. Gordon, Ulster Hospital, Belfast, Northern Ireland The objective was to study the reliability of recipient vessels and the anastomotic method used in head and neck microvascular reconstruction. Abstracts

263

Seventy-®ve consecutive free tissue transfers in 73 patients performed between June 96 and August 99 and the recipient blood vessels chosen for microsurgical anastomosis were studied. Seventy-three free ¯aps were used for extensive tumour resection and two free ¯aps for bony and soft tissue defects arising from shotgun injuries necessitating microvascular tissue reconstruction. The oldest patient was aged 87 years. The type of ¯ap used depended on the recipient site. The free radial forearm ¯ap was the true workhorse of intraoral reconstruction. The superior thyroid and facial arteries were the most commonly used recipient arteries in 59 free ¯aps, and the other recipient vessels being the external carotid and transverse cervical arteries. The thyroid vein and branches of the internal jugular vein were most commonly used for the venous anastomosis, followed by facial, external jugular and anterior jugular veins. The thyroid vein was often used because of its ability to sustain ¯ow in either direction. Adverse experience in the early part of this study when using the external jugular vein led to the development of a preference for branches of the internal jugular vein as recipient veins. There may be a signi®cant mismatch in lumen diameter when performing an end to end venous anastomosis in the external jugular vein. End to end anastomosis was the most preferred method in our series. Seven ¯aps had re-anastomosis owing to thrombosis (three arterial and four venous. Arterial and venous kinks, or twisting of the vessels, were common ®ndings during re-exploration at the site of anastomosis. One patient had a vein graft and re-anastomosis. There were two cases of complete ¯ap necrosis; one was pulled off by the patient and the other ¯ap died gradually. Seven patients had neck haematomas, which were evacuated. Our ¯ap success rate was 97%. Adjacent small vessels in the neck were the ®rst choice for ¯ap anastomosis. In dif®cult cases of free-¯ap transfer, it is of prime importance to select healthy recipient vessels. The superior thyroid and facial arteries were found to be reliable, were a good size match for the ¯ap vessels, and were in close proximity to the defect. The branches of the internal jugular vein were found to be effective as recipient veins.

Splenius Capitis Perforator-Based Skin Flap for Recurrent Tumours in the Parotid and Mastoid Region S. Azad, R. M. R. McAllister and N. S. Niranjan, St Andrew's Centre, Mid Essex Hospitals NHS Trust, Broom®eld Hospital, Chelmsford, UK Squamous cell carcinoma of the pinna is well known to have local and regional recurrence. The local recurrence rate is higher (up to 14%) than most other cutaneous squamous cell carcinomas. Local recurrence occurs in the periarticular region and is usually treated by aggressive surgery and/or postoperative radiotherapy. Many of these patients would already have undergone a radical neck dissection owing to which the sternocleidomastoid ¯ap cannot be used. The other reconstructive options after local resection have conventionally involved the pectoralis major myocutaneous ¯ap, the trapezius ¯ap, the latissimus dorsi ¯ap or a free ¯ap. All these are reliable and have been used for more than 25 years. However, all these muscles are functionally important and are remote from the site of reconstruction. Reconstructions using one of these regional ¯aps have well known complications, including excessive bulk, distortion of breast tissue, shoulder drop deformity and brachial plexus injury, among others. The use of a free ¯ap is the other option but this needs microsurgical expertise. It would seem to be ideal to use a local ¯ap that is without a functionally important muscle and which would incur minimal morbidity. This ¯ap would be the ®rst option for these recurrent tumours, leaving the conventional ¯aps for any further recurrences. Our aim was to use a local perforator-based splenius capitis myocutaneous ¯ap for reconstruction of the defect. The ¯ap has been used on three patients with recurrent squamous cell carcinoma of the pinna. The main outcome measures were procedural ease, patient morbidity and cosmetic outcome. This ¯ap is local, simple, quick, complication free, cosmetically superior (being in the hairline), avoids the extensive mobilizatioin of muscle, has no donor site morbidity, is not excessively bulky, and avoids the use of major muscle. In addition, the vascular anatomy of this ¯ap is well de®ned and it has a rich vascular anatomosis. Carcinoma of the pinna affects older individuals and

264

Abstracts

this local ¯ap involves a much smaller procedure and is well tolerated. We conclude that this is a new, simple and effective method of reconstructing periauricular defects.

Perioperative Transfusion in Head and Neck Squamous Cell Carcinoma Patients P. W. Baxter and M. J. Fardy, University Dental Hospital, University Hospital of Wales, Cardiff, UK The NHS Executive, in its document Better blood transfusion, has directed all trusts and clinicians who prescribe transfusions to decrease allogeneic transfusion. Our aim was to ®nd and record our transfusion rates, compare them with published data, and devise ways to decrease our blood usage. The subjects were sixty consecutive patients undergoing resection of primary squamous cell carcinoma of the head and neck, cervical lymphadenectomy, and reconstruction using free tissue transfer. An exploratory data analysis of a prospectively recorded operative log and transfusion database was carried out at a university teaching hospital. The main outcome measures were: number of units of blood transfused perioperatively and correlation with preoperative haemoglobin concentration, age of the patient, primary site, primary size, soft tissue only or composite resection, cervical lymph node metastasis, number and type of neck dissection, and site, number and type of free tissue transfers performed. Ninety per cent of our patients were transfused compared with the literature average of 50% for head and neck squamous cell carcinoma. Exploratory data analysis revealed that this was partly due to our larger number of oral and oropharyngeal carcinomas, a larger proportion of composite resections, and reconstruction using free tissue transfer. We concluded that the transfusion rate is high and needs to be reduced. A strategy to reduce allogeneic blood transfusion rates is outlined. This includes correcting a low preoperative haemoglobin concentration, acute normovolaemic haemodilution, positioning the patient head up on the operating table, adrenaline in®ltration before skin and mucosal incisions, controlled moderate hypotension during primary tumour resection and neck dissection, and modifying the transfusion trigger.

A Retrospective Review of PEG Placement in 80 Consecutive Patients K. M. Lavery, P. Stenhouse and A. D. MacBean, Department of Maxillofacial Surgery. Queen Victoria Hospital, East Grinstead, UK Percutaneous endoscopic gastrectomy (PEG) placement during the management of head and neck cancer is a well-established procedure. Some recently published series have reported considerable morbidity, suggesting that a group of vulnerable patients may be further compromised by invasive enteral feeding. However, it is well recognized that when postopereative radiotherapy is required it is extremely undesirable to have a break in treatment because of feeding dif®culties and any delay may also lead to an increased risk of recurrence of the primary disease. In our experience the use of enteral feeding via a PEG has been extremely favourable. We aim to review the indications for PEG placement, assess its duration of use, identify the incidence of major and minor complications, and attempt to identify those patients in whom PEG placement has proved most bene®cial for the longest period of time. We studied respectively 80 patients who have undergone PEG placement at Queen Victoria Hospital over the last 6 years. The main outcome measures were: (1) timing of PEG placement; (2) duration of PEG placement; (3) percentage of patients self-feeding at home; (4) percentage of minor and major complications; (5) failure rate for PEG placement; and (6) percentage of patients with PEG in situ at commencement of radiotherapy. Data were collected retrospectively from medical notes. The results were: (1) 68% of PEGs inserted at primary surgery; (2) 30% of PEG tubes in situ at >12 months; (3) 98% of patients self-feeding via PEG at home; (4) 2% major complication rate, 11.5% minor complication rate; (5) 0% failure rate for PEG placement; and (6) 87% of patients started radiotherapy with PEG in situ.

We intend to produce an algorithm for deciding when PEG placement is most likely to be bene®cial in head and neck oncology surgery, based on the ®ndings of this study.

Palliative Therapy in Head and Neck Squamous Cell Carcinoma: Pro®le of Typical Outcome C. Timon and K. Reilly, Department of Otolaryngology/Head and Neck Surgery, St James's Hospital, Dublin, Irish Republic On initial presentation many patients with head and neck squamous cell carcinoma (HNSCC) are not considered suitable for curative treatment and are instead managed palliatively. The objective of this study was to address the paucity of research documenting typical functional outcome for this group. Such insight is central to guiding therapeutic intervention and is fundamental to facilitating fully informed patient consent. A comprehensive, retrospective analysis was carried out of the medical records for all patients with HNSCC who were deemed to require palliative therapy and were referred to the ®rst author between 1994 and 1999. Strict exclusion criteria were employed. Information was collated on 60 parameters from multicentre sources (medical records from three major Dublin hospitals, radiotherapy records, Irish National Cancer Registry, Palliative Care database, general practitioner questionnaires). Of 286 patients with HNSCC (mucosal), 60 (21%) were deemed palliative at diagnosis (advanced disease 39, poor medical condition 13, refused 8). The average age of presentation for palliative patients was 70 years (range 47±90) compared with 63 years (range 20±94) for a curative group. The duration of symptoms prior to presentation was 101 days (range 1±365). Overall six (10%) patients died in hospital during initial admission. Following an average inpatient stay of 23 days, 66% were discharged to home and 17% to hospice care; 17% were transferred to other institutions. Including deaths on initial admission, 29% of patients never returned to home residence post-diagnosis. Palliative treatment, apart from analgesia, included operative interventions in 35% (tracheostomy 20%, percutaneous endoscopic gastrostomy insertion 25%, both 10%) and palliative radiotherapy in 43% of patients. The average subsequent hospital inpatient stay was 14 days (equating to 8% of life expectancy). Average survival was 165 days with 1-month, 3-month and 1-year mortality rates of 10%, 30% and 62% respectively; 47% eventually died in hospital as opposed to hospice or home care settings. One in ®ve patients with HNSCC are not curable. They survive on average for less than 6 months, of which over 1 month is spent in hospital care. More than one-third require surgical interventions for airway or feeding dif®culties, with one in four never returning home following initial admission at diagnosis. This pro®le has important implications for counselling patients. It also highlights the need for increased awareness, early diagnosis and ef®cient referral processes.

Should Head and Neck Cancer Services be Aimed at the More Materially Deprived? A. M. Monaghan, Department of Oral and Maxillofacial Surgery, Selly Oak Hospital, Birmingham, UK It is recognized that the highest rates of oral cancer are found in some of the poorer parts of the world and it is less common in more af¯uent countries. Little is known about the effect of poverty on oral cancer in the UK. This study compares the frequency distribution of Townsend deprivation scores for incident cases of oral cancer in the West Midlands for the period of 1983±1992 with those of the region's population as a whole. The two populations were compared using the Statistical Package for Social Sciences. The results showed that those with oral cancer were signi®cantly more deprived than the population in general, with a difference between mean Townsend scores of 2.4 (SE=0.088). Possible reasons for these differences are discussed. They are likely to be due to differing risk factor exposure between the two groups. The importance of directing head and neck cancer services to the areas of most need is emphasized.

An Evaluation of Oral Cancer Information on the Internet S. O'Ceallaigh, S. Rea and S. T. O'Sullivan, Department of Plastic and Reconstructive Surgery, Cork University Hospital, Cork, Ireland The rapid growth of the Internet to over 320 million web pages has led to an unprecedented information revolution. Patients now have the resources to access information regarding all forms of medical and surgical procedures and their consequences. This myriad of information is unregulated both in terms of its source and content. It is feared that this availability, with the inherent risks of misinformation, could result in potentially harmful effects on patients and healthcare professionals who do not use it cautiously. The aim of this study was to evaluate cancer information on the Internet from a patient's perspective, with speci®c regard to oral cancer. It was evaluated by using a specially developed algorithm to assess: (1) source; (2) accuracy and (3) credibility. The methods involved included a systematic search using ten search engines, and a thorough review of the ®rst 100 pages of four selected search engines. This study con®rmed the widely diverse nature of the information available. There was, as expected, a large US bias to web site content. Thirteen per cent of the pages evaluated were from government agencies such as the National Cancer Institute; individual dental or oral surgeons accounted for 15%, while medical institutions represented 10.6%. Patients' support groups were represented in 4.5% of the web sites. Diagnostic or general information appeared in 37% and preventative and screening recommendations in a further 32%. Forty-six per cent of all pages reviewed cited no references. The results of this study reveal that patients may access an overwhelming supply of unregulated information from sources as diverse as patient support groups, scienti®c publications by respected institutions, and treatment advertisements from individual surgeons and clinics. The content of the information has been evaluated with regard to source, accuracy and content.

Detection of Regional Cervical Lymph Node Metastases in Oral Cancer: A Comparison of Ultrasound, Computed Tomography and Magnetic Resonance Imaging St J. Crean1, L. Newman1, A. Hoffman2, S. Halpin2, C. Hopper1, P. Speight1, J. Potts2 and M. Fardy2, 1University College London Hospitals and 2University Hospital Wales, Cardiff, UK In squamous cell carcinoma of the oral cavity, the presence of nodal metastases greatly in¯uences prognosis. Accurate evaluation is crucial in the correct management of these neoplasms. The aim of this study was to assess the value of ultrasound, alone or with ®ne needle aspiration biopsy, computed tomographic (CT) scanning and magnetic resonance imaging (MRI) in the detection of regional lymph node metastases. The case notes were examined of 124 patients (from two centres) with biopsy proven oral squamous cell carcinoma, who underwent either elective or therapeutic neck dissection between January 1997 and December 1999. All ultrasound, CT and MRI reports were correlated with the histopathological results of the neck dissections. Ultrasound had an overall accuracy (OA) of 82%, a sensitivity (Sn) of 74% and a speci®city (Sp) of 90%. Ultrasound-guided biopsies had an OA of 86%, and an Sp and Sn of 100% and 78% respectively. MRI had OA 87%, an Sp of 90% and an Sn of 80%. Finally, CT scanning had an OA, Sp and Sn of 70%, 82% and 66% respectively. We have found that ultrasound and MRI were the most accurate in staging the neck in these patients. The most speci®c test was ultrasound ®ne needle guided biopsy. CT scanning, in accordance with many other studies, was unable to provide accurate information and its continued use in the estimation of neck metastases must be questioned. Abstracts

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Globus Pharyngeus: A Postal Questionnaire Survey of UK ENT Consultants C. J. Webb, Z. G. G. Makura, J. E. Fenton, S. R. Jackson, M. S. McCormick and A. S. Jones, Department of Otolaryngology, Head and Neck Surgery, Royal Liverpool University Hospital, Liverpool UK Globus pharyngeus is a common complaint among patients referred to the ENT outpatient department. The precise nature of globus pharyngeus and its aetiology remain something of a mystery. There is no uniform policy of management of this condition. A postal questionnaire was sent to all UK-based ENT consultants registered with the British Association of Otorhinolaryngology ± Head and Neck Surgery (BAO±HNS). The aim of this study was to ascertain if there was a management policy favoured by the majority of consultants. Our results indicate that there is a lack of consensus on the investigation and management of globus pharyngeus. Fourteen per cent of ENT consultants do not perform any investigations, but would prescribe antacid medication if clinically indicated. The remainder would investigate in a variety of ways. The most common investigation is rigid endoscopy, which is performed by 61% of respondents, followed by barium swallow (56%). The combination of endoscopy and barium swallow is routinely performed by 17.5% of respondents. Globus pharyngeus is a clinical diagnosis, not a diagnosis of exclusion. Therefore it is likely that these patients are being unnecessarily investigated. It is our opinion that, in patients with a typical history of globus and normal examination ®ndings, reassurance is suf®cient. Any patient who has symptoms of gastro-oesophageal re¯ux should be treated with antacid medication. Any patient with atypical features in the history or examination must be investigated.

Diagrammatic Recording of Head and Neck Tumours R. Simo, P. Pracy and L. Yong, Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Lewisham, London, UK The increasing demands of audit have resulted in the need for accurate data collection. The use of tumour maps allows standardization of the records of patients with head and neck cancer, which facilitates the collation of data in multicentre studies and makes interdepartmental comparisons more meaningful. The aim was to develop an improved standard set of tumour maps for recording the stage of head and neck tumours, using the anatomical diagrams currently available for recording the site of these tumours. A review was carried out of the existing tumour diagrams to identify those anatomical areas that are not adequately represented or where ambiguity exists. The criterion for adequacy used was the ability to represent head and neck tumours according to the TNM classi®cation. The areas where improvements could be made were identi®ed: (1) the anterior commissure of the larynx: In the current maps, the anterior commissure is not seen. In the proposed version, an adequate view of this area is clearly demonstrated; (2) coronal and sagittal views of the larynx: In the current diagrams, the vocal cords touch each other in the middle and the anatomical shape of the laryngeal ventricle is not adequately represented. In the proposed diagrams, these de®ciencies have been corrected; (3) the pyriform fossa and cervical oesophagus: In the current diagrams, these areas are incompletely represented. In the proposed diagrams, a full view of the pyriform sinus and the cervical oesophagus is demonstrated; (4) the oropharynx and vallecula: In the current diagrams, the shadowing is too dark and does not allow a clear representation of the tumour. In the proposed diagrams, the shadowing has been reduced and therefore the tumours can be drawn clearly; (5) the nasal cavity and paranasal sinuses: In the current diagrams, there is no coronal representation. In the proposed diagrams, an effort has been made to represent two coronal levels from anterior to posterior; hence a more threedimensional representation can be demonstrated: (6) cervical nodal involvement: In the current diagrams, there is no division of the neck into anatomical levels. In the proposed diagrams, levels I to VI are clearly demarcated and a slight tilt in the head position allows full representation of level I. A new set of tumour maps is presented in an attempt to correct

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some of the limitations of the existing diagrams. In our opinion, the proposed set would allow a more accurate representation of tumours in their anatomical site. At the same time the exact level of any cervical lymph nodes can be demonstrated with less room for misinterpretation. Silver-Binding Nuclear Organizer Regions (AgNORs) as a Routine Prognostic Factor in Laryngeal and Pharyngeal Squamous Cell Carcinoma P. Deron1, M. Voordeckers2 and A. Goossens3, Departments of Otolaryngology ± Head and Neck Surgery, 2Radiotherapy and 3 Pathology, Akademisch Ziekenhuis, Vrije Universiteit Brussel, Belgium 1

This retrospective study was part of an ongoing search for prognostic factors. The aim of the investigation was to assess the routine use of the mean AgNOR count as a prognostic factor in laryngeal and pharyngeal squamous cell carcinoma. The subjects were 31 consecutive patients with squamous cell carcinoma of the larynx (11) or pharynx (20). The main outcome measures were: AgNOR, clinical outcome, age, sex, TNM classi®cation and histological differentiation. A silver colloid technique that shows interphase AgNORs was applied to representative paraf®n sections from all 31 patients. The mean AgNOR count/cell was obtained by averaging after counting 100 tumour cells with a light microscope at magni®cation 61000 with oil immersion. Clinical outcome was de®ned as good when patients survived longer than 2 years and bad if they died within 2 years after diagnosis. The overall mean AgNOR count/cell was 3.84 + 1.41. In the group with good clinical outcome the mean AgNOR count/cell was 3.63 + 1.22 versus 4.09 + 1.6 in the group with poor clinical outcome. Statistical analysis of these data, as well as correlation of the mean AgNOR count/cell with age, sex, TNM-classi®cation and histological differentiation, did not show any statistically signi®cant difference between the two clinical outcome groups. We conclude that the assessment of mean AgNOR count/cell in laryngeal and pharyngeal squamous cell carcinoma is of no routine clinical use as a prognostic factor. The Treatment of Early Laryngeal Cancers: Surgery or Irradiation A. S. Jones, J. E. Fenton, S. Jackson, D. Husband and B. Fish, Department of Otolaryngology Head and Neck Surgery, University of Liverpool, Liverpool, UK Carcinoma of the larynx is the commonest cancer affecting the head and neck. Early laryngeal cancer is usually treated by irradiation in northern Europe but by surgery elsewhere. The aim was to determine if there is any difference in survival between the two main therapeutic options. The subjects were 418 patients treated by irradiation and 68 by surgery over a 30-year period at the Royal Liverpool University Hospital Head and Neck Oncology Department. Retrospective data were collected in a prospective manner on preprinted cards. The main outcome measures were: recurrence at the primary site; recurrence at the neck; and survival. Data were entered into a purpose designed computer database. Statistical analysis was by the chi-squared test, multiple logistic regression, actuarial calculations of recurrence rates and survival, and Cox's proportional hazards model. Surgery included horizontal or vertical partial laryngectomy and various procedures on the glottis, including cordectomy. Over a 30-year period, radiotherapy was administered to a dose of 60±66 Gy given over 25±35 fractions. The 5-year tumour-speci®c survival for those treated by irradiation was 86% (95% con®dence interval (CI) 83±91) and for surgery it was 82% (95% CI 63±89). The difference was not statistically signi®cant. Five patients in the radiotherapy group and 12 in the surgery group had serious complications. Voice, as assessed subjectively by three people, including a speech therapist, was better in those who received radiotherapy rather than surgery. It appears that both surgery and irradiation are effective ways of treating carcinoma of the larynx. Surgery had a higher morbidity, with more postoperative problems and usually adverse affects on the voice. However, few complications and an improvement in the voice in almost all patients accompany the administration of radiation therapy.

The Results of Treatment of 458 Patients with Early Laryngeal Squamous Cell Carcinoma by Irradiation A. S. Jones, D. J. Husband, J. E. Fenton, S. Jackson and Z. Makura, Department of Otolaryngology Head and Neck Surgery, University of Liverpool, Liverpool, UK Early carcinoma of the larynx is usually treated by irradiation. It is generally supposed that the results of irradiation for T1 and T2 lesions are extremely good in terms of survival. The aim of this study was to investigate if this assumption is merited. A total of 458 patients with early squamous cell carcinoma of the larynx attending the Head and Neck Oncology Unit at the Royal Liverpool University Hospital were studied. The procedure was basically retrospective but all data were included in a computer database in a prospective manner over a 30-year period. The main outcome measures were recurrence at the primary site, recurrence in the neck, and patient survival. All data were entered into a microcomputer database and analysed. Statistical methods included actuarial calculation of recurrence rates, actuarial calculation of survival rates, and further study of factors affecting survival using Cox's proportional hazards model. Patients were treated with radical radiation to a dose of 60±66 Gy using 25±35 fractions. The 5-year actuarial recurrence rate for T1 cancers was 19%; for T2 cancers it was 31%. Recurrence in the neck was 2% for T1 cancer and 10% for T2 cancer. Actuarial cause-speci®c survival for all patients was 86%; T1 patients had 91% 5-year survival and T2 patients had 70% 5-year survival. Patients with glottic cancer did best, with a 91% 5-year survival and supraglottic cancer showed 72% survival at 5 years. Multivariate analysis using Cox's proportional hazards modal con®rmed that glottic cancer did best and those with T1 disease also did well. Neck node metastases at the time of presentation were an adverse prognostic sign. Radical irradiation is an extremely effective way of curing early laryngeal cancer. While some complacency is justi®ed in patients with T1 disease, T2 cancer has a 70% survival at 5 years. The results, therefore, are not as good for T2 cancer as one might have supposed and it remains a serious life-threatening disease.

Radiotherapy for T1 Laryngeal Cancer: 10-Year Results from one Centre N. G. Mikhaeel and F. M. B. Calman, Clinical Oncology Department, Guy's and St Thomas' Hospital, London, UK Radiotherapy is an effective treatment for early laryngeal cancer, with the advantage of larynx preservation. Radiotherapy involves many variables, each of which and the interaction between them, could potentially affect the outcome. We reviewed the records of all patients with T1 laryngeal cancer treated at Guy's and St Thomas' Cancer Centre between 1989 and August 1998. We collected data on patient characteristics, tumour and treatment parameters, local control and survival. A total of 118 consecutive patients with T1 laryngeal cancer were identi®ed: 104 had T1 glottic (G) cancer and 14 had T1 supraglottic (SG) cancer. The male to female ratio was 101:17 (G 92:12; SG 9:5). The median follow-up was 30 months (range 2± 99). Overall, there were seven relapses (four G; three SG), with a local control rate of 94% (G 96%; SG 79%). All four G relapses were local in the larynx; however, two of three SG relapses were nodal. All ®ve patients with laryngeal recurrence underwent salvage laryngectomy. One patient developed further nodal relapse, and a second developed primary lung cancer. Despite radical salvage surgery for the two patients with nodal relapse, they developed further recurrence. Relapses were analysed in relation to various tumour and treatment characteristics. Patients with carcinoma in situ (8) had no relapses. Patients with welldifferentiated (27) and moderately differentiated (27) squamous cell carcinoma (SCC) had a 4% relapse rate. Patients with poorly differentiated SCC (4) and spindle-cell carcinoma (3) had relapse rates of 25% and 33% respectively. There was no relapse in 35 patients with SCC not otherwise speci®ed. Relapse rates were 0% for stage Tis, 2.5% for stage T1a, and 11% for stage T1b. Bulky tumours had a relapse rate of 7% compared with 2% for non-bulky tumours. Patients with anterior commissure involvement had a relapse rate of 6% compared with 3% in the absence of this feature. Apart from overall treatment time, none of the treatment

parameters analysed (machine, ®eld arrangement, ®eld size, dose± fractionation schedule, dose homogeneity, and treating consultant) had any signi®cant effect on relapse rate. Radiotherapy is a very effective treatment for T1 laryngeal cancer, especially for glottic tumours. Unfavourable histology, involvement of both vocal cords (T1b), bulky tumours, involvement of the anterior commissure, and unplanned prolongation of overall treatment time for more than 2 days, were detrimental to local control. Laryngeal recurrences can be salvaged more successfully than nodal recurrences.

Neoadjuvant Chemoradiotherapy in Advanced Pharyngolaryngeal Tumours: A Prospective Study W. M. C. Martin1 and D. J. Premachandra2, 1Department of Oncology, Norfolk and Norwich Hospital, Norwich and 2ENT Department, James Paget Hospital, Great Yarmouth, UK Radical surgery followed by radiotherapy (RT), the traditional management for pharyngolaryngeal cancer, results in handicap from either a tracheostomy or swallowing dif®culties caused by insensate ¯aps in the mouth. ChemoRT offers the possibility of preservation of function. The aim was to assess chemoRT as primary treatment in advanced pharyngolaryngeal tumours. Twenty-nine consecutive patients (26M, 3F; median age 59 years) presenting to district general hospitals in East Norfolk between November 1995 and September 1999 were treated by chemoRT consisting of 2±3 cycles of cisplatin±5-¯uorouracil (5FU) infusion (PF) chemotherapy followed by radical RT. Tumour sites were: oropharynx 22 (76%), larynx 5 (17%) and pyriform fossa 2 (7%). TNM stage-grouping was: II, 2 (7%); III, 4 (14%); IVa, 18 (62%); IVb 5 (17%) (i.e. 79% in Stage IV). All were squamous carcinomas except one, which revised histology showed to be of neuroendocrine origin. The PF chemotherapy regimen was: cisplatin 100 mg/m2 i.v. day 1, 5-FU 1 g/m2 i.v. infusion days 2±6, q 21±28 days. The RT doses were: 66 Gy/33 F to the primary in two phases, 50 Gy/25F to the neck. The outcome measures were: chemoresponse, overall response, present status, and toxicity. Complete response (CR) was de®ned as no clinically or radiologically detectable disease; partial response (PR) was 550% reduction in disease; no response (NR) was <50% reduction in disease. Results were as follows. Chemoresponse: (of 20 patients clinically assessed following PF prior to RT) CR 9 (45%), PR 10 (50%), NR 1 (5%). Overall response (on completion of chemoRT): of 29 patients, CR 24 (83%), PR 3 (10%), NR 1 (3%), toxic death 1 (3%), toxic death 1 (3%). Present status of 29 patients: alive without disease, 20 (69%); with disease, 3 (10%) (two neck recurrences awaiting neck dissection, one neuroendocrine tumour with ®ts); and dead 6 (21%). Causes of death were: 1 NR, 1 PR with advanced disease, 2 recurrent tumour (1 locoregional, 1 pulmonary metastases), 1 toxic death (perforation following second cycle of PF), 1 cardiac death a few months after the end of treatment. The principle chemotoxicities were fatigue, oral mucositis and potentiation of RT toxicity, with a dry mouth and loss of taste for several months; also nausea, alopecia and marrow suppression. ChemoRT according to the above regimen gives promising results, with 69% of patients alive and well, with good function preservation and normal activity. Randomized studies are needed to compare quality of life in patients treated by chemoRT versus surgery + RT.

Malignant Minor Salivary Gland Tumours: A 20-Year Review M. J. Strick, J. V. Soames, C. Kelly and N. R. McLean, Department of Plastic and Reconstructive Surgery, Royal Victoria In®rmary and Department of Oncology, Newcastle General Hospital, Newcastle upon Tyne, UK Minor salivary gland malignancies are uncommon (0.6/million population/year in the UK) and as a consequence their management is controversial. The aim of this study was to review the presentation and management of minor salivary gland malignancies in our department over a 20-year period. We identi®ed retrospectively patients with minor salivary malignancies treated Abstracts

267

at the Department of Plastic Surgery between 1979 and 1999, and analysed the management of head and neck tumours in a combined plastic surgery and oncology service. The main outcome measures were: presentation, management and progress; local and distant recurrence rates; and survival rates. The case notes of 20 patients with minor salivary gland malignancies were reviewed. Postoperative follow-up was from 6 months to 13 years. The most common sites of occurrence were the hard or the soft palate (5) and the maxillary antrum (5). The majority of malignancies were either adenoid cystic carcinoma (7) or mucoepidermoid (6). The remainder were polymorphous lowgrade adenocarcinoma (4) or carcinoma ex-pleomorphic salivary adenoma (3). All patients were treated with surgery including a neck dissection in 25%; 13 patients received postoperative radiotherapy. Reconstruction with free rectus abdominus or radial forearm ¯ap was required in one-third of the patients. Two (of 7) adenoid cystic carcinomas and 1 (of 6) mucoepidermoid carcinomas recurred locally. At 5 years of follow-up, 4 (of 6) adenoid cystic carcinoma patients and 3 (of 4) mucoepidermoid carcinoma patients were alive. Minor salivary gland malignancies are uncommon tumours with variable presentation and morphology. They can occur in any age group, including young people. Management includes surgery, reconstruction and radiotherapy. Outcome depends on tumour type and anatomical location. Late recurrences occur.

The Regulatory Roles of C-erbB Ligands in Vascular Endothelial Growth Factor Family (VEGF) Expression in Head and Neck Squamous Cell Carcinoma (HNSCC) P. O-charoenrat1,2, S. Eccles2 and P. Rhys-Evans1, 1Department of Head and Neck Surgery, Royal Marsden Hospital, London and 2 Section of Cancer Therapeutics, Institute of Cancer Research, Surrey, UK Aberrant expression of c-erbB receptors contributes to the progression of HNSCC, possibly via potentiation of angiogenesis, because upregulation of VEGF expression by activation of epidermal growth factor receptor (EGFR) and/or c-erbB-2 has been described in other tumour types. In HNSCC, the regulatory roles of c-erbB signalling pathways on VEGF family expression (VEGF-A, VEGF-B, VEGF-C, VEGF-D) were largely unknown. The aim of the study was to examine the pro®les of VEGF family members and their correlation with c-erbB signalling pathways in both experimental and clinical models of HNSCC. The VEGF mRNA and protein levels were examined in a panel of 15 HNSCC cell lines using semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis respectively. The effects of three major ligands with different selectivities of binding to c-erbB receptors, namely TGFa, BTC and HRG-b1, with or without antagonistic monclonal antibodies (mAb) against EGFR (ICR62) and c-erbB-2 (ICR12), were studied in HNSCC lines. Tissue samples (54 matched sets of primary, secondary and normal mucosae where feasible) were obtained from patients with HNSCC who underwent major surgery at the Royal Marsden Hospital. We demonstrated for the ®rst time the expression of four members of the VEGF family in HNSCC lines and tissues. A direct correlation between the levels of EGFR and VEGF expression in tissue specimens was also observed. All three cerbB ligands upregulated all four isoforms (most notably isoform 121) of VEGF-A and also VEGF-C but had no effect on VEGF-B. It is interesting that all ligands simultaneously downregulated the expression of VEGF-D. An anti-EGFR mAb (ICR62) downregulated the basal mRNA levels of VEGF-A and VEGF-C, but had no detectable effects on VEGF-B and VEGF-D. ICR62 also reversed the effects of all three c-erbB ligands on VEGF-A, VEGF-C and VEGF-D expression. An anti-c-erbB-2 mAb (ICR12) had no effect on basal or ligand-modulated expression of any VEGF in these cell lines, although they co-express this receptor, which is known to heterodimerize readily with EGFR. The four VEGF genes are regulated by the EGFR signalling pathway in a strikingly different manner, suggesting that they serve distinct, although perhaps complementary (VEGF-A and VEGF-C) or antagonistic (VEGF-D) functions. The EGFR signalling pathway plays a major role in VEGF regulation in

268

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HNSCC, even in response to ligands that bind primarily (HRG-b1) or additionally (BTC) to other c-erbB receptors, notably c-erbB-4.

Head and Neck Cancer: The Poor Relation; A Study of Patterns of Distribution of Cancer Research Funds in the United Kingdom J. Savage and M. Birchall, Department of Otolaryngology, University of Bristol, Southmead Hospital, Bristol, UK Head and neck cancer has a huge impact on quality of life. Although advances in surgical techniques have somewhat improved functional outcomes, mortality has not reduced for decades. Clearly, a large amount of research into new and more effective therapies is required. According to the Maxi-Min principle, society has an obligation to advance the most deprived sectors more than more privileged groups. However, super®cially, it appears that little research into head and neck cancer is being supported in the UK. We hypothesized that the major cancer funding bodies in the UK provide a disproportionately low amount of funding for head and neck cancer research compared with breast and colorectal cancer. A retrospective review of the distribution of funding was carried out using information derived from records and correspondence with of®cial bodies. The main outcome measures were: amounts of funds given towards research commencing in 1995±1997 inclusive for each index cancer. We contacted (by letter and telephone follow-up) the three major funders of cancer research in the UK: Medical Research Council (MRC), Cancer Research Campaign (CRC) and Imperial Cancer Research Fund (ICRF). We requested details of the amounts of money they gave towards the funding of basic science and clinical/translational projects in these years. Data were compared with relative incidence rates for each of the three cancers. The ICRF did not fund any head and neck cancer projects during these years. The relative incidence of breast:colorectal:head and neck was 4.5:4.6:1. Corresponding amounts of funding for research from the MRC were 61:29:1 and from the CRC 12:3.6:1. Much funding was given to non-speci®c basic science projects. These results show that in the UK in 1995±1997, funding for head and neck cancer research from the principal funding bodies was dramatically out of proportion to this cancer's incidence, and importance, to the UK population.

Oral Cancer in the Northeast of England: Aspects Relating to Risk Factors and the Patient Population M. Greenwood and P. J. Thomson, Department of Oral and Maxillofacial Surgery, The Dental School University of Newcastle upon Tyne, Newcastle upon Tyne, UK The northeast of England has a high incidence of oral cancer (12.2 per 100.000). In England and Wales there is a distinct north/south gradient for oral cancer incidence, with higher rates in the north. The aim was to pro®le a group of patients presenting with oral cancer in terms of referral source, previous contact with health care professionals and details relating to risk factors. This was a prospective questionnaire study involving 100 consecutive patients attending a multidisciplinary head and neck oncology clinic in Newcastle upon Tyne. Responses were analysed both qualitatively and quantitatively. The age distribution was 34±95 years; the median age was 67 years. The male to female ratio was 2.7:1. In terms of dental attendance, 64% did not attend for regular dental check-ups, but the majority (86%) in this study were referred by their dental practitioners. Eighteen per cent of these patients had experienced periods of unemployment lasting for more than 6 months. Some authorities state that material deprivation, in which unemployment may play a major role, is a risk factor in its own right and independent of the others. The smoking and alcohol drinking histories were broadly as expected, with 80% of the sample being smokers and 91% drinking alcohol to some degree. Fifty-eight per cent of the patients drank more than 20 units per week. Behaviour changes were monitored after diagnosis and/or treatment, with only a minority continuing their smoking/drinking habit (10% in the case of smoking, and 32% in the case of alcohol). Sixteen per

cent of the patients were not aware pre-diagnosis that oral cancer existed as a disease entity while 56% of the remainder had no idea of the risk factors. Patient education is still apparently lacking, both in terms of the existence of the disease and its risk factors, with attendant implications for behaviour. Behaviour changes after diagnosis indicate that patient education may improve risk factor behaviour. Dental practitioners can be a signi®cant referral source. There is a strong argument for case-control studies (now being undertaken) to separate established risk factors and deprivation.

Long-Term Outcome of Patients with Locally Advanced Thyroid Carcinoma J. Powles, L. Vini, R. A'Hern, C. Harmer and P. Rhys-Evans, Head, Neck and Thyroid Unit, Royal Marsden Hospital, London, UK This was a retrospective study to assess the long-term outcome of patients with locally advanced (pT4) differentiated thyroid carcinoma. Of 1404 patients with differentiated thyroid carcinoma treated at the Royal Marsden Hospital over the last 60 years, we identi®ed 255 who had locally advanced tumours at diagnosis (pT4); 94 were male and 161 female (M:F = 1:1.71), with a mean age at diagnosis of 56 years (range 7±85). Most patients (85%) presented with a thyroid nodule or a palpable neck node. The mean follow-up was 21 years (range 1±60). There were 193 papillary, 52 follicular and 10 Hurthle cell carcinomas; 48% of all tumours were well differentiated and 25% poorly differentiated. One hundred and forty-eight patients were recorded as having involved lymph nodes; 76 were ipsilateral (N1a), and distant metastases were found in 46 (most commonly in lungs and bones). Initial management included total thyroidectomy in 138 patients, lobectomy/hemithyroidectomy in 59 and biopsy/ enucleation in 59. A modi®ed radical neck dissection was performed in 50 patients, while 54 underwent simple nodal excision. Radioactive iodine was administered to 197 patients, with 31 receiving an ablative dose and the rest receiving more than one dose (cumulative activity 8.5±24 (GBq). External beam radiotherapy was given to 109 patients. Local recurrence (thyroid bed, neck nodes or mediastinum) occurred in 69 patients and was managed by further surgery, radioiodine or external beam radiotherapy. Overall cause-speci®c survival at 10, 20 and 30 years was 60%, 45% and 45% respectively. Age at diagnosis, grade, presence of distant metastases, radioiodine therapy and extent of surgery were found to be independent prognostic factors for survival, while external beam radiotherapy was a signi®cant prognostic factor for local control. Locally advanced differentiated thyroid carcinoma is associated

with aggressive tumour behaviour and should be managed with total thyroidectomy and selective neck dissection (if involved), followed by radioactive iodine. Radiotherapy should also be considered, especially in older patients, to reduce the risk of local recurrence.

Collecting Data for Head and Neck Cancer: A Simple Approach A. Ahmed-Shuaib1, P. Andrews2 and M. G. Dilkes3, 1,2Department of ENT/Head and Neck Surgery, Whipps Cross Hospital and 3 Department of ENT/Head and Neck Surgery, Whipps Cross and St Bartholomew's Hospital, London, UK The departments of ENT/Head and Neck Surgery at Whipps Cross and St Bartholomew's Hospitals have used the BAHNO guidelines for the collection of a head and neck cancer dataset and developed them into the ENT CareCode1 system. This is a `clinician-lead' barcode-driven system. Data are entered electronically through scanning customized barcode templates. The barcode templates incorporate clinical data, including TNM staging, treatment, outcome and quality of life measurements, which are guided by the BAHNO National Minimum Dataset (NMDS) guidelines. This system involves entering demographic data onto a computer prior to the clinic, which generates a unique barcode label for each patient. A hand-held barcode scanner is then used in the clinic to enter data by scanning the individual customized barcode templates already mentioned. The data captured are simply transferred to a computer by a `docking station' for the barcode scanner. Errors of data capture are checked on the `error report' sheet that is generated automatically from the downloaded data and corrected at this stage with subsequent automatic and accurate updating of the Windows relational database. The relational database allows accurate analysis of any parameters that are questioned and retrieval of these data can be either through the keyboard or a touch screen, or, in the future, via a voice-activated system. The advantages over conventional keyboard data entry are that this system allows data to be entered in a quick, highly ef®cient, uncomplicated way, as well as being captured in real time. The average time for data entry for an uncomplicated follow-up patient is less than 1 minute; for new patients, up to 20 separate data entries can be input within 2 minutes. The ENT CareCode system promotes the collection of accurate and comprehensive data, which is pivotal to clinical governance. The NMDS is a prerequisite in head and neck oncology and we should now be looking at systems such as this that allow us to ful®l these requirements.

Abstracts

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