Improved survival prediction for oropharyngeal cancer beyond TNMv8.

PURPOSE: For oropharynx squamous cell carcinoma (OPSCC) this study aimed to: (i) compare 5-year overall survival (OS) stratification by AJCC/UICC TNM versions 7 (TNMv7) and 8 (TNMv8), (ii) determine whether changes to T and N stage groupings improve prognostication and (iii) develop and validate a model incorporating additional clinical characteristics to improve 5-year OS prediction. MATERIAL AND METHODS: All OPSCC treated with curative-intent at our institution between 2011 and 2017 were included. The primary endpoint was 5-year OS. Survival curves were produced for TNMv7 and TNMv8. A three-way interaction between T, N stage and p16 status was evaluated for improved prognostication. Cox proportional hazards modelling was used to derive a new predictive model. RESULTS: Of 750 OPSCC cases, 574 (77%) were p16-positive. TNMv8 was more prognostic than TNMv7 (concordance probability estimate [CPE] ±â€¯SE = 0.72 ±â€¯0.02 vs 0.53 ±â€¯0.02). For p16-positive disease, TNMv8 discriminated stages II vs I (HR 2.32, 95% CI 1.47-3.67) and III vs II (HR 1.75, 95% CI 1.13-2.72). For p16-negative disease, TNMv7 and TNMv8 demonstrated poor hazard discrimination. Different T, N stage and p16-status combinations did not improve prognostication after adjusting for other factors (CPE = 0.79 vs 0.79, p = 0.998). A model for p16-positive and p16-negative OPSCC including additional clinical characteristics improved 5-year OS prediction beyond TNMv8 (c-index 0.76 ±â€¯0.02). CONCLUSIONS: TNMv8 is superior to TNMv7 for p16-positive OPSCC, but both performed poorly for p16-negative disease. A novel model incorporating additional clinical characteristics improved 5-year OS prediction for both p16-positive and p16-negative disease.

Transoral laser microsurgery versus radiotherapy for T2 glottic squamous cell carcinoma: a systematic review of local control outcomes.

BACKGROUND: Systematic reviews comparing treatment of early glottic cancer with transoral surgery or radiotherapy demonstrate similar oncological outcomes. Most studies of 'early-stage' laryngeal cancer include Tis, T1a, T1b and T2 cases. The data are dominated by patients with T1 and Tis tumours, although extrapolating these results and applying them for T2 cases may be inappropriate. No previous systematic reviews have focused on T2 cancers as a separate group. OBJECTIVE OF REVIEW: This review compares local control outcomes for T2 glottic squamous cell carcinoma, treated with transoral microsurgery or external beam radiotherapy. TYPE OF REVIEW: This is a systematic review of case series and comparison studies, focusing on oncological outcomes. SEARCH STRATEGY: Independent searches of MEDLINE, EMBASE and the Cochrane Database were conducted by two authors, using the search terms: laryngeal/glottic/vocal cord combined with carcinoma/cancer/tumour and laser/microsurgery or radiotherapy. Studies of adult patients treated for primary T2N0 glottic squamous cell carcinoma (SCC) with laser surgery or curative radiotherapy were included. EVALUATION METHOD: Full text of studies satisfying the inclusion criteria were reviewed with extraction of local control and survival data and laryngeal preservation rates. The primary endpoint is local control at 5 years. RESULTS: Initial searches identified 3252 studies. Following full-text review of 183 papers, 59 studies met the inclusion criteria, all level IV evidence. A total of 48 studies specified 5-year local control for 1156 patients treated with transoral laser surgery and 3191 patients treated with radiotherapy. Weighted averages of local control at 5 years demonstrated similar results: 75.81% for radiotherapy versus 77.26% for transoral laser surgery. CONCLUSIONS: The results of this review indicate no difference in 5-year local control between radiotherapy and transoral surgery for T2 glottic SCC. The data demonstrated higher rates of local failure for T2b compared with T2a cases, although outcomes were similar between laser excision and radiotherapy for each substage. Further research focusing upon functional outcomes for T2 glottic tumours is imperative to guide decision-making, ideally with subgroup analysis of T2a and T2b cases.

Surgery in head and neck cancer: United Kingdom National Multidisciplinary Guidelines.

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. Surgery is one of the key modalities used in head and neck cancer treatment. Recent advances and a greater awareness of the short- and long-term toxicities associated with non-surgical modalities and newer technologies that permit minimal access resections have led to a resurgence in surgery. This paper provides an overview of the role of surgery in head and neck cancer practice.

Oropharyngeal cancer: United Kingdom National Multidisciplinary Guidelines.

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. There has been significant debate in the management of oropharyngeal cancer in the last decade, especially in light of the increased incidence, clarity on the role of the human papilloma virus in this disease and the treatment responsiveness of the human papilloma virus positive cancers. This paper discusses the evidence base pertaining to the management of oropharyngeal cancer and provides recommendations on management for this group of patients receiving cancer care. Recommendations • Cross-sectional imaging is required in all cases to complete assessment and staging. (R) • Magnetic resonance imaging is recommended for primary site and computed tomography scan for neck and chest. (R) • Positron emission tomography combined with computed tomography scanning is recommended for the assessment of response after chemoradiotherapy, and has a role in assessing recurrence. (R) • Examination under anaesthetic is strongly recommended, but not mandatory. (R) • Histological diagnosis is mandatory in most cases, especially for patients receiving treatment with curative intent. (R) • Oropharyngeal carcinoma histopathology reports should be prepared according to The Royal College of Pathologists Guidelines. (G) • Human papilloma virus (HPV) testing should be carried out for all oropharyngeal squamous cell carcinomas as recommended in The Royal College of Pathologists Guidelines. (R) • Human papilloma virus testing for oropharyngeal cancer should be performed within a diagnostic service where the laboratory procedures and reporting standards are quality assured. (G) • Treatment options for T1-T2 N0 oropharyngeal squamous cell carcinoma include radical radiotherapy or transoral surgery and neck dissection (with post-operative (chemo)radiotherapy if there are adverse pathological features on histological examination). (R) • Transoral surgery is preferable to open techniques and is associated with good functional outcomes in retrospective series. (R) • If treated surgically, neck dissection should include levels II-IV and possibly level I. Level IIb can be omitted if there is no disease in level IIa. (R) • If treated with radiotherapy, levels II-IV should be included, and possibly level Ib in selected cases. (R) • Altering the modalities of treatment according to HPV status is currently controversial and should be undertaken only in clinical trials. (R) • Where possible, patients should be offered the opportunity to enrol in clinical trials in the field. (G).

Management of lateral skull base cancer: United Kingdom National Multidisciplinary Guidelines.

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. It provides recommendations on the work up and management of lateral skull base cancer based on the existing evidence base for this rare condition. Recommendations • All patients with more than one of: chronic otalgia, bloody otorrhoea, bleeding, mass, facial swelling or palsy should be biopsied. (R) • Magnetic resonance and computed tomography imaging should be performed. (R) • Patients should undergo audiological assessment. (R) • Carotid angiography is recommended in select patients. (G) • The modified Pittsburg T-staging system is recommended. (G) • The minimum operation for cancer involving the temporal bone is a lateral temporal bone resection. (R) • Facial nerve rehabilitation should be initiated at primary surgery. (G) • Anterolateral thigh free flap is the workhorse flap for lateral skull base defect reconstruction. (G) • For patients undergoing surgery for squamous cell carcinoma, at least a superficial parotidectomy and selective neck dissection should be carried out. (R).

Follow-up after treatment for head and neck cancer: United Kingdom National Multidisciplinary Guidelines.

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. In the absence of high-level evidence base for follow-up practices, the duration and frequency are often at the discretion of local centres. By reviewing the existing literature and collating experience from varying practices across the UK, this paper provides recommendations on the work up and management of lateral skull base cancer based on the existing evidence base for this rare condition. Recommendations • Patients should be followed up to a minimum of five years with a prolonged follow-up for selected patients. (G) • Patients should be followed up at least two monthly in the first two years and three to six monthly in the subsequent years. (G) • Patients should be seen in dedicated multidisciplinary head and neck oncology clinics. (G) • Patients should be followed up by dedicated multidisciplinary clinical teams. (G) • The multidisciplinary follow-up team should include clinical nurse specialists, speech and language therapists, dietitians and other allied health professionals in the role of key workers. (G) • Clinical assessment should include adequate clinical examination including fibre-optic rigid or flexible nasopharyngolaryngoscopy. (R) • Magnetic resonance imaging and positron emission tomography combined with computed tomography imaging should be used when recurrence is suspected. (R) • Narrow band imaging can be used in the follow-up in selected sites. (R) • Second primary tumours should be part of rationale of follow-up and therefore adequate screening strategies should be used to detect them. (G) • Patients should be educated with regard to the appearance and detection of recurrences. (G) • Patients with persistent pain should be investigated to exclude recurrent disease. (R) • Patients should be offered support with tobacco and alcohol cessation services. (R).

Subcranial craniofacial resection for advanced sinonasal malignant tumours involving the anterior skull base.

BACKGROUND: The subcranial approach is a modification of traditional craniofacial resection. It provides similar broad access to the anterior skull base, but with lower mortality and morbidity. It has been the surgical technique of choice at our institution since 2006 for treating advanced stage sinonasal tumours (American Joint Committee on Cancer stage III or above). This paper reports our experience and outcomes. METHOD AND RESULTS: Eighteen patients underwent subcranial craniofacial resection over a seven-year period, this being combined with a second adjunctive procedure in 89 per cent of cases. Forty per cent of patients required reconstruction of the primary defect. No peri-operative deaths occurred. One patient had a transient cerebrospinal fluid leak. The major complication rate was 33 per cent, of which 67 per cent were directly related to soft tissue reconstruction. Tumour recurrence rate was 17 per cent and the five-year disease-free survival estimate was 40 per cent. CONCLUSION: The subcranial approach is a safe and effective technique that may be used to successfully treat advanced sinonasal malignancies with anterior skull base extension.

The prognostic significance of the biomarker p16 in oropharyngeal squamous cell carcinoma.

AIMS: There is an increasing incidence of human papillomavirus (HPV)-positive oropharyngeal squamous cell cancers (OPSCC) mostly associated with favourable outcomes. p16 immunohistochemistry is a surrogate marker for HPV positivity in OPSCC. The prognostic strength of p16 over traditional prognostic factors is not fully characterised. In this study, we evaluated the clinical and demographic differences between p16-positive and -negative OPSCC and characterised its prognostic strength versus traditional prognostic factors. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded blocks and clinical information from 217 OPSCC patients, treated with radiotherapy (alone or in combination with other therapies) between 2000 and 2010 were collected retrospectively. Immunohistochemistry for p16 protein was carried out; cancer-specific survival (CSS), recurrence-free survival (RFS) and locoregional control (LRC) were calculated for both univariate and multivariate analyses. RESULTS: Ninety-two per cent of the OPSCC originated from tonsil and tongue base sites, 61% were p16 positive. Patients with p16-positive OPSCC were younger (P < 0.0001), with lower alcohol (P = 0.0002) and tobacco (P = 0.0001) exposure. The tumours were less differentiated (P = 0.0069), had a lower T stage (P = 0.0027), higher nodal status (P = 0.014) and higher American Joint Committee on Cancer (AJCC) prognostic group (P = 0.0036). AJCC prognostic group was significant for RFS (P = 0.0096) and CSS (P = 0.018) in patients with p16-negative OPSCC, but not those with p16-positive tumours (P = 0.30 and 0.54). Other significant factors for CSS and RFS in univariate analysis were: pretreatment haemoglobin (P < 0.0001 and <0.0001), chemoradiotherapy (P = 0.005 and 0.03) and P16 status (P < 0.0001 and 0.0001). In multivariate analysis, p16 positivity was the strongest independent prognostic variable for both CSS, RFS and LRC (P < 0.0001, hazard ratio 4.15; 95% confidence interval 2.43-7.08), (P < 0.0001, hazard ratio 6.15; 95% confidence interval 3.57-10.61) and (P = 0.001, hazard ratio 3.74; confidence interval 1.76-7.95). CONCLUSION: This study shows that p16 is the single most important prognostic variable in OPSCC, surpassing traditional prognostic factors for both CSS and RFS. Furthermore, disease stage has no prognostic significance in p16-positive patients, highlighting the need for routine p16 assessment in OPSCC.

Transoral laser surgery versus radiotherapy for tumour stage 1a or 1b glottic squamous cell carcinoma: systematic review of local control outcomes.

BACKGROUND: Previous literature reviews comparing transoral laser surgery versus radiotherapy for glottic carcinoma treatment have analysed 'early stage' disease as one group. The current review aimed to assess local control outcomes, comparing these two treatment modalities, specifically for either tumour stage 1a or stage 1b lesions. METHODS: The three authors conducted independent, structured literature searches. Simple weighted means were calculated. RESULTS: Thirty-six publications were analysed. Three-year local control rates for tumour stage 1a tumours were 88.9 per cent for transoral laser surgery (n = 1308) and 89.3 per cent for radiotherapy (n = 2405). For tumour stage 1b tumours, the local control rates were 76.8 per cent for transoral laser surgery (n = 194) and 86.2 per cent for radiotherapy (n = 492). CONCLUSION: From this analysis of level four evidence, there was no demonstrable difference in local control rates for tumour stage 1a glottic squamous cell carcinoma treated by transoral laser surgery or radiotherapy. There was a trend towards improved local control of tumour stage 1b tumours treated with radiotherapy, but this finding was based on a limited number of published outcomes (n = 194).

Nasopharyngeal carcinoma: a retrospective review of demographics, treatment and patient outcome in a single centre.

AIMS: Nasopharyngeal cancer (NPC) is relatively uncommon, especially in the Western world. We report our single institution experience of 20 years of data in 128 patients with NPC, including responses to different treatment modalities and outcomes by histological subtype. MATERIALS AND METHODS: NPC patients presenting from 1992 to 2005 were located on the cancer registry database. Demographic data included age, gender, length of presenting symptoms and stage. World Health Organization classification (2005) was used for histological subtyping. The date of recurrence and survival outcomes were analysed using Kaplan-Meier curves. RESULTS: Presentation data were analysed from 128 patients; the survival analysis included 123 patients. The median age at presentation was 57.7 years. Stage III and IV presentation rates were 34 and 38%, respectively. The most common presenting symptom was a palpable neck lump (55%) and the median duration of symptoms was 16 weeks. Forty-eight patients received radiotherapy alone and 75 received chemoradiotherapy. The median overall survival in chemoradiotherapy patients was 80.3 months versus 28.5 months with radiotherapy alone (P = 0.003). A significant difference was also seen with recurrence-free survival (RFS) (P = 0.017). Type 1 keratinising carcinoma had a significantly worse overall survival (P = 0.04) and a similar but non-statistically significant trend was seen for RFS (P = 0.051). The multivariate analysis for overall survival showed that histological subtype (hazard ratio 2.7, 95% confidence interval 1.3-5.5, P = 0.034), age (hazard ratio 2.3, 95% confidence interval 1.1-4.9, P = 0.018) and N stage (hazard ratio 3.7, 95% confidence interval 1.4-9.4, P = 0.024) were prognostic factors. CONCLUSIONS: We present the first large-scale, single-centre retrospective review of NPC in a UK-based population. Demographic data were similar to that in other Western populations, with a significantly worse survival outcome in the keratinising group. Further prospective study of outcome in Western populations accounting for newer radiotherapy techniques such as intensity-modulated radiotherapy and dose escalation, particularly in the keratinising population who were more likely to present with an isolated local recurrence, is recommended.

Lack of prognostic effect of carbonic anhydrase-9, hypoxia inducible factor-1α and bcl-2 in 286 patients with early squamous cell carcinoma of the glottic larynx treated with radiotherapy.

AIMS: To evaluate the prognostic significance of potential tumour markers of hypoxia and apoptosis in early squamous cell carcinoma of the glottic larynx managed with radiotherapy. MATERIALS AND METHODS: In total, 382 patients with T1 and T2 squamous cell carcinoma of the glottic larynx (vocal cords) received radical radiotherapy (50-55 Gy, in 16 fractions in 98% of cases). Pre-treatment haemoglobin was available for 328 patients; biopsy samples were available for 286. Immunohistochemistry was carried out for carbonic anhydrase-9 (CA-9), hypoxia inducible factor-1α (HIF-1α) and Bcl-2. RESULTS: At 5 years, locoregional control was achieved in 88.2%, cancer-specific survival in 95.0% and overall survival in 78.7%. Adverse prognostic factors for locoregional tumour recurrence were pre-treatment haemoglobin <13.0 g/dl (P = 0.035, Log rank test; sensitivity 0.28, specificity 0.84) and stage T2 rather than T1 (P = 0.002). The effect of haemoglobin level on locoregional control was not significant when stratified by the median of 14.2 g/dl (P = 0.43) or as a continuous variable (P = 0.59). High CA-9 (P = 0.11), HIF-1α (P = 0.67) and Bcl-2 (P = 0.77) expression had no prognostic significance. CONCLUSIONS: High CA-9, HIF-1α and Bcl-2 do not add to the prognostic significance of tumour stage and lower haemoglobin in predicting failure of local control in early glottic larynx squamous cell carcinoma managed with radiotherapy. The effect of haemoglobin was not strong enough to be useful as a prognostic biomarker.

An evaluation of current services available for people diagnosed with head and neck cancer in the UK (2009-2010).

AIMS: To evaluate current care and service provision for people with head and neck cancer in the UK. MATERIALS AND METHODS: Self-report questionnaires for cancer networks, clinical leads of oncology units and leads for multidisciplinary teams (MDTs) were designed. These questionnaires were based on a previous survey. Questionnaires were sent out between 2009 and 2010. RESULTS: Questionnaires were received from all networks (n = 37), most oncology units (48 of 53) and most MDTs (51 of 63). Care for people with head and neck cancer is increasingly being provided by a centralised MDT. The membership of these teams varies; facilities available for team meetings are fit for purpose in most cases. MDTs are meeting frequently (weekly meetings in 96%) and discussing on average 18 cases at each meeting (95% confidence interval 15-21 cases). Most oncologists have access to all common anti-cancer drugs and most have access to all forms of radiotherapy. Intensity-modulated radiotherapy is not yet available in some oncology units (28%). A small number of units have only one oncologist (13%). Despite audit and research being part of the rationale for MDT working, regular discussion of morbidity and mortality is unusual (40%) and use of a database to record decisions is not universal. Only seven centres record decisions into the Data for Head and Neck Oncology database. Reported recruitment to studies is generally low (<2% of cases enrolled in studies in 62%). CONCLUSIONS: Head and neck cancer care is increasingly provided through a centralised MDT. Increased resources and further changes in practice are required to implement current National Health Service cancer policy. Teams need to improve recording of their decision-making, discuss morbidity and mortality and support recruitment to clinical studies.

Outcomes following pharyngolaryngectomy reconstruction with the anterolateral thigh (ALT) free flap.

We retrospectively reviewed 15 cases of pharyngolaryngectomy for advanced laryngeal carcinoma reconstructed with the anterolateral thigh (ALT) free flap. Thirteen patients had primary surgery and adjuvant treatment (radiotherapy or chemoradiotherapy), and two had salvage surgery. Thirteen had stage III or IV disease, and eight had cervical nodal extracapsular spread. In this series all the flaps survived, and at median follow-up of 14.5 months (range 3.7-31.2), 12 of the 15 patients were alive. One patient developed a chronic pharyngocutaneous fistula, and five required repeat balloon dilatations for late pharyngeal strictures. Six patients enjoyed restoration of full oral intake, seven were able to take a soft diet, and two were dependent on feeding by percutaneous endoscopic gastrostomy. Four patients developed adequate tracheo-oesophageal speech, and one successfully developed oesophageal speech. In this series many of the surgical problems associated with pharyngolaryngectomy reconstruction were addressed successfully by the ALT, but late dysphagia remained troublesome in an appreciable minority. While adjuvant radiotherapy could have contributed to this, future innovations will focus on the reduction of late strictures.

Functional results of pharyngo-laryngectomy and total laryngectomy: a comparison.

OBJECTIVE: To compare the key functional results (regarding swallowing and voice rehabilitation) in patients treated by pharyngo-laryngectomy with flap reconstruction, versus standard, wide-field, total laryngectomy. METHOD: We studied 97 patients who had undergone total laryngectomy and pharyngo-laryngectomy with flap reconstruction. The main outcome measures were swallowing (i.e. solid food, soft diet, fluid or enteral feeding) and fluent voice development. RESULTS: There were 79 men and 18 women, with follow up of one to 19 years. Voice (p = 0.037) and swallowing (p = 0.041) results were significantly worse after circumferential pharyngo-laryngectomy than after non-circumferential pharyngo-laryngectomy. There was no significant difference in voice (p = 0.23) or swallowing (p = 0.655) results, comparing total laryngectomy and non-circumferential pharyngo-laryngectomy. The presence of a post-operative fistula significantly influenced voice (p = 0.001) and swallowing (p = 0.009) outcomes. CONCLUSION: The additional measures involved in pharyngo-laryngectomy do not confer any functional disadvantage, compared with total laryngectomy, but only if the procedure is non-circumferential. Functional results of circumferential pharyngo-laryngectomy are worse than those of both non-circumferential pharyngo-laryngectomy and total laryngectomy. If oncologically possible and safe, it is better to keep a pharyngo-laryngectomy non-circumferential.

Thyroid lymphoma: acute presentation and long-term outcome.

BACKGROUND: Thyroid lymphomas are relatively uncommon. This study aimed to analyse our experience of thyroid lymphoma management and outcome. MATERIALS AND METHODS: A retrospective case note analysis of 63 patients treated in the previous 13 years was conducted. RESULTS: The five-year survival rate was 68 per cent, with most patients dying of their lymphoma. This is at odds with the British Thyroid Association statement that the prognosis of this condition is 'generally excellent'. The only presenting symptom found to be significantly associated with prognosis was dysphagia (p = 0.001). Dual modality treatment provided a significantly better outcome than single modality treatment (p = 0.014). Thyroid lymphoma can present to the head and neck surgeon 'in extremis'; however, it can respond rapidly to appropriate treatment. CONCLUSION: The outcome of thyroid lymphoma seems unrelated to the acuteness of its presentation. Thyroid surgery has no role other than for diagnosis. However, 51 per cent of the study patients underwent some form of thyroidectomy, indicating the need to implement better diagnostic pathways.

The small-nucleolar RNAs commonly used for microRNA normalisation correlate with tumour pathology and prognosis.

BACKGROUND: To investigate small-nucleolar RNAs (snoRNAs) as reference genes when measuring miRNA expression in tumour samples, given emerging evidence for their role in cancer. METHODS: Four snoRNAs, commonly used for normalisation, RNU44, RNU48, RNU43 and RNU6B, and miRNA known to be associated with pathological factors, were measured by real-time polymerase chain reaction in two patient series: 219 breast cancer and 46 head and neck squamous cell carcinoma (HNSCC). SnoRNA and miRNA were then correlated with clinicopathological features and prognosis. RESULTS: Small-nucleolar RNA expression was as variable as miRNA expression (miR-21, miR-210, miR-10b). Normalising miRNA PCR expression data to these recommended snoRNAs introduced bias in associations between miRNA and pathology or outcome. Low snoRNA expression correlated with markers of aggressive pathology. Low levels of RNU44 were associated with a poor prognosis. RNU44 is an intronic gene in a cluster of highly conserved snoRNAs in the growth arrest specific 5 (GAS5) transcript, which is normally upregulated to arrest cell growth under stress. Low-tumour GAS5 expression was associated with a poor prognosis. RNU48 and RNU43 were also identified as intronic snoRNAs within genes that are dysregulated in cancer. CONCLUSION: Small-nucleolar RNAs are important in cancer prognosis, and their use as reference genes can introduce bias when determining miRNA expression.

Synchronous chemoradiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck using capecitabine: a single-centre, open-label, single-group phase II study.

AIM: To evaluate the efficacy of concurrent oral capecitabine with accelerated hypofractionated radical radiotherapy in locally advanced squamous cell carcinoma of the head and neck (SCCHN). MATERIALS AND METHODS: Between 2001 and 2004, 50 patients with stage III/IV SCCHN (0 to 2 performance status) were enrolled into this study. The capecitabine dose was between 450 and 550 mg/m(2) twice daily, continuously for 28 days. The radiotherapy dose was 5500 cGy in 20 fractions over 4 weeks. No intensity-modulated radiation was used. We evaluated the complete response rate, toxicity, locoregional control, overall survival, disease-free survival and cancer-specific survival. RESULTS: The median age was 55 (range 38-76) years; 72% had stage IV disease. The median follow-up was 6 years on the 30 surviving patients. Eighty-two per cent of patients completed the course of capecitabine and 94% completed prescribed radiotherapy. There were no treatment-related deaths, grade 3/4 haematological or renal toxicity. Five patients developed drug-related grade 3/4 acute toxicity (cardiac, skin, bowel); 47 developed grade 3/4 mucositis from chemoradiotherapy. Twenty-two (44%) patients required tube feeding and the tube dependency rate at 1 year was 6%. The complete response rate at 3 months was 90% (45/50 patients). Relapse occurred in 17/50 (34%) patients by 5 years. The locoregional control, overall survival, cancer-specific survival and disease-free survival rates at 3 years were 78, 72, 82 and 62%, respectively, and at 5 years were 72, 64, 75 and 56%, respectively. CONCLUSION: This schedule of synchronous capecitabine for locally advanced SCCHN is well tolerated. The local control in this series compares favourably with other synchronous chemoradiotherapy reports. Chronic dysphagia and tube dependence is uncommon with this approach. Capecitabine as targeted therapy given with each fraction of radiotherapy and administered orally may have significant advantages over intravenous, 3 weekly cisplatin.