Cisplatin plus capecitabine as first-line chemotherapy for recurrent or metastatic head and neck squamous cell cancer: experience outside of a trial setting.

PURPOSE: Cisplatin/5-fluorouracil (5-FU) is an accepted palliative chemotherapy treatment for head and neck squamous cell carcinoma, improving quality of life but not overall survival. Capecitabine in place of 5-FU removes the morbidity of an infusional regime with potential benefit in patient well-being. This study looks at outcomes for cisplatin plus capecitabine (PX) outside of a trial setting. METHODS: Consecutive patients receiving this treatment in a single centre were retrospectively analysed. Cisplatin (mean dose 75 mg/m²) was given on day 1 of a 3-week cycle and capecitabine (mean dose 808 mg/m² twice daily) on days 1-14, for up to 6 cycles. RESULTS: Sixty-five patients (median age 58.6 years) received a median of 4 cycles of chemotherapy. The overall response rate was 30.7%, with a median overall survival of 7.3 months. Treatment was well tolerated with a 10.7% grade 3 and a 1.5% grade 4 neutropenia rate, with no other grade 4 toxicities. One patient died of neutropenic sepsis whilst on treatment. Twenty-seven percent of patients stopped treatment early due to chemotherapy-related side effects. CONCLUSION: PX is well tolerated outside the trial setting with outcomes similar to historical published literature. Ease of administration and benefit to patient convenience make it an attractive alternative to standard palliative treatment.

Analysis of a National Programme for Selective Internal Radiation Therapy for Colorectal Cancer Liver Metastases.

AIMS: Patients with chemotherapy-refractory colorectal cancer liver metastases have limited therapeutic options. Selective internal radiation therapy (SIRT) delivers yttrium 90 microspheres as a minimally invasive procedure. This prospective, single-arm, observational, service-evaluation study was part of National Health Service England Commissioning through Evaluation. METHODS: Patients eligible for treatment had histologically confirmed carcinoma with liver-only/liver-dominant metastases with clinical progression during or following oxaliplatin-based and irinotecan-based chemotherapy. All patients received SIRT plus standard of care. The primary outcome was overall survival; secondary outcomes included safety, progression-free survival (PFS) and liver-specific PFS (LPFS). RESULTS: Between December 2013 and March 2017, 399 patients were treated in 10 centres with a median follow-up of 14.3 months (95% confidence interval 9.2-19.4). The median overall survival was 7.6 months (95% confidence interval 6.9-8.3). The median PFS and LPFS were 3.0 months (95% confidence interval 2.8-3.1) and 3.7 months (95% confidence interval 3.2-4.3), respectively. During the follow-up period, 143 patients experienced an adverse event and 8% of the events were grade 3. CONCLUSION: Survival estimates from this pragmatic study show clinical outcomes attainable in the National Health Service comparable with previously published data. This study shows the value of a registry-based commissioning model to aid national commissioning decisions for highly specialist cancer treatments.

Salivary gland adenoid cystic carcinoma: a review of chemotherapy and molecular therapies.

Adenoid cystic carcinoma (ACC) accounts for about 1% of all head and neck malignancies. It has a tendency for a prolonged clinical course, with local recurrences and distant metastases sometimes occurring many years after presentation. Standard treatment for salivary gland ACC is surgery and post-operative radiotherapy. The aim of this review was to examine the reported efficacy of various chemotherapy regimens and molecular therapies on recurrent/metastatic salivary gland ACC. One hundred and fourteen publications were reviewed on chemotherapy as well as possible molecular targets of therapy, including KIT, epidermal growth factor receptor (EGFR), human epidermal growth receptor-2 (HER-2), oestrogen and progesterone receptors, proliferating cell nuclear antigen (PCNA), Ki-67 and the p53, bcl-2 and SOX-4 genes. Reported response rates to combination chemotherapy are low and response duration generally short lived. The response to molecular therapies is low also. More research into novel molecular targets is needed.

Radiotherapy for pleomorphic adenoma of the parotid gland.

A study was made of 187 patients with parotid pleomorphic adenoma treated by radiotherapy. This followed surgery but with incomplete removal or tumor spillage. In the early years of the study radiotherapy was given by radium needle implant done usually at the time of surgery, but from the late 1960s beam-directed external radiotherapy with a head shell was used most commonly. A 3-field technique or wedge pair was the standard technique. The median age was 46 with nearly half the patients (87/187) aged between 40 and 60, and the ratio of women to men was 1.4:1 (110:77). Median follow-up for all patients was 14 years. One hundred fifteen patients had radiotherapy immediately after their first operation with a recurrence rate of 0.9% (1/115). Of the 115 there were 2 cases of radionecrosis (1 major, 1 minor), 1 case of permanent facial nerve palsy, 1 Frey Syndrome (post-gustatory sweating), and 1 salivary fistula. Seventy-two patients had radiotherapy delayed until one or more recurrences had been surgically treated. Nine (12.5%) of these developed yet further recurrence after radiotherapy. There were 2 cases of radionecrosis (1 major), 4 cases of facial nerve palsy (3 of which were complete), 16 cases (22.2%) of Frey Syndrome, and 1 case of malignant change in a parotid tumor. In addition one squamous cell carcinoma developed at the site of a needle implant 25 years later. Recurrences after radiotherapy continued beyond 20 years of follow-up. Patients having unsatisfactory surgery due to spill at operation or residual tumor left behind should have radiotherapy immediately and not delayed until local recurrence occurs because of the increased morbidity and the higher incidence of yet further recurrence.

Relative clinical influence of tumor dose versus dose per fraction on the occurrence of late normal tissue morbidity following larynx radiotherapy.

A study was made of 242 cases of T2 No glottic cancer treated by definitive radiotherapy over a 15-year period. The aim was to examine the relative influences of tumor biological dose (indicated by locoregional control) versus dose per fraction on the occurrence of late normal tissue effects; in addition, the impact of cord mobility on outcome was analyzed. The 5-year survival corrected for intercurrent deaths was 84% and local disease-free (larynx and/or nodes) survival was 76%. Using Cox regression analysis the only factor significant for local control was cord mobility (p < 0.0001) which also had an effect on overall survival (p < 0.0001); subdivision of T2 glottic staging should be reintroduced into staging classifications. It is evident that comparison of clinical results between centers is potentially prejudiced by an array of factors relating not only to fractionation differences but also variation in clinical and organizational aspects of care. Nevertheless, using other published data for comparison, it seems likely that the serious morbidity rate of 4.1% seen in this study is due in some part to the high tumor biological dose (resulting in high local control). The influence of fraction size was difficult to discern as equivalence in local control was not seen in the data chosen.

Modelling the optimal radiotherapy regime for the control of T2 laryngeal carcinoma using parameters derived from several datasets.

PURPOSE: A number of previous studies have used direct maximum-likelihood methods to derive the values of radiobiological parameters of the linear-quadratic model for head and neck tumors from large clinical datasets. Time factors for accelerated repopulation were included, along with a lag period before the start of this repopulation. This study was performed to attempt to utilise these results from clinical datasets to compare treatment regimes in common clinical use in the UK, along with other schedules used historically in a number of clinical series in North America and elsewhere, and to determine if an optimal treatment regime could be derived based on these clinical data. METHODS: The biologically-based linear-quadratic model, applied to local tumor control and late morbidity, has been used to derive theoretical optimum (maximising tumor control whilst not exceeding tolerance for late reactions) radiotherapy schedules based on daily fractions. The specific case of T2 laryngeal carcinoma was considered as this is treated primarily by radiotherapy in many centers. Parameter values for local control were taken from previous analyses of several large single-center and national datasets. A time factor and a lag period were included in the modelling. Values for the alpha/beta ratio for late morbidity were used in the range 1-4 Gy, which is compatible with the limited range of values reported in the literature for particular complications following radiotherapy for head and neck cancer. Early reactions and their consequential late morbidity were not modelled in this study, but assumed to be within tolerance. RESULTS: For treatments using daily fractions there was a broad optimum treatment time of between 3-6 weeks. The theoretical optimum depended to some extent on the value of the alpha/beta ratio for late morbidity, but in many cases was at or just beyond the end of the purported lag period of 3-4 weeks, although small values of alpha/beta between 1-2 Gy favour longer treatment times. Similar results were obtained using a range of parameter values derived from four independent clinical datasets. CONCLUSION: The mathematical modelling of this broad range of once-daily treatments for most of which differences in local control and late morbidity are essentially undetectable (< 5%) has shown how this clinically-recognised phenomenon is interpreted in terms of the combination of dose-response slopes, fractionation sensitivities and time factors for both tumor control and normal tissue morbidity. Although the conclusions are inevitably tempered by a number of caveats concerning confounding factors in different centers; for example, the use of different treatment volumes, the present analysis provides a framework with which to explore the potential value of modifications to conventional treatment schedules, such as the use of multiple fractions per day.

331 cases of clinically node-negative supraglottic carcinoma of the larynx: a study of a modest size fixed field radiotherapy approach.

PURPOSE: For node-negative supraglottic carcinoma of the larynx, radiotherapy with surgery in reserve commonly provides very good results in terms of both local control and survival, while preserving function. However uncertainty exists over the treatment of the node-negative neck. Elective whole neck radiotherapy, while effective, may be associated with significant morbidity. The purpose of this study was to examine our practice of treating a modest size, fixed field to a high biologically effective dose and compare it with the patterns of recurrence from other centers that use different dose/volume approaches. METHODS AND MATERIALS: Over a 10-year period 331 patients with node-negative supraglottic carcinoma of the larynx were treated with radiotherapy at the Christie Hospital Manchester. Patients were treated with doses of 50-55 Gy in 16 fractions over 3 weeks. Data were collected retrospectively for local and regional control, survival, and morbidity. RESULTS: Overall local control, after surgical salvage in 17 cases, was 79% (T1-92%, T2-81%, T3-67%, T4-73%). Overall regional lymph node control, after surgical salvage in 13 cases, was 84% (T1-91%, T2-88%, T3-81%, T4-72%). Five-year crude survival was 50%, but after correcting for intercurrent deaths was 70% (T1-83%, T2-78%, T3-53%, T4-61%). Serious morbidity requiring surgery was seen in 7 cases (2.1%) and was related to prescribed dose (50 Gy-0%, 52.5 Gy-1. 3%, 55 Gy-3.4%). DISCUSSION: Our results confirm that treating a modest size, fixed field to a high biologically effective dose is highly effective. It enables preservation of the larynx in most cases, with acceptable regional control and no loss of survival compared to whole neck radiotherapy regimes.

Similar decreases in local tumor control are calculated for treatment protraction and for interruptions in the radiotherapy of carcinoma of the larynx in four centers.

PURPOSE: Data on patients with cancer of the larynx are analyzed using statistical models to estimate the effect of gaps in the treatment time on the local control of the tumor. METHODS AND MATERIALS: Patients from four centers, Edinburgh, Glasgow, Manchester, and Toronto, with carcinoma of the larynx and treated by radiotherapy were followed up and the disease-free period recorded. In all centers the end point was control of the primary tumor after irradiation alone. The local control rates at > or = 2 years, Pc, were analyzed by log linear models, and Cox proportional hazard models were used to model the disease-free period. RESULTS: T stage, nodal involvement, and site of the tumor were important determinants of the disease-free interval, as was the radiation schedule used. Elongation of the treatment time by 1 day, or a gap of 1 day, was associated with a decrease in Pc of 0.68% per day for Pc = 0.80, with a 95% confidence interval of (0.28, 1.08)%. An increase of 5 days was associated with a 3.5% reduction in Pc from 0.80 to 0.77. At Pc = 0.60 an increase of 5 days was associated with an 7.9% decrease in Pc. The time factor in the Linear Quadratic model, gamma/alpha, was estimated as 0.89 Gy/day, 95% confidence interval (0.35, 1.43) Gy/day. CONCLUSIONS: Any gaps (public holidays are the majority) in the treatment schedule have the same deleterious effect on the disease free period as an increase in the prescribed treatment time. For a schedule, where dose and fraction number are specified, any gap in treatment is potentially damaging.

Amoxycillin-clavulanic acid combination in bronchopulmonary infection due to beta-lactamase-producing Branhamella catarrhalis. Preliminary report.

Since 1978 we have taken an interest in lower respiratory tract infections associated with Branhamella catarrhalis in Christchurch, New Zealand. In a preliminary trial, 20 patients with bronchopulmonary infection caused by beta-lactamase-producing B. catarrhalis were treated with a combination tablet of amoxycillin 500 mg and clavulanic acid 125 mg ('Augmentin') 3 times daily for 5 days. Sputum cultures were negative for B. catarrhalis within 3 days in all patients. Two of 7 patients whose sputum cultures were positive for this organism at a review 2 to 4 weeks later were successfully treated with a further course of amoxycillin/clavulanic acid.

Radical external beam radiotherapy for 333 squamous carcinomas of the oral cavity--evaluation of late morbidity and a watch policy for the clinically negative neck.

BACKGROUND AND PURPOSE: The aims of this study were to examine local control/morbidity for all cases and a 'watch policy' for the node-negative neck. PATIENTS/METHODS: 333 patients with squamous cell carcinoma of the oral cavity were treated with a short radical radiotherapy regime to the primary site and involved lymph node groups at the Christie Hospital, Manchester, between 1980 and 1987. Only 10 of 278 node-negative patients received elective neck node irradiation. RESULTS: Actuarial cancer-free survival and local control rates at 5 years for the whole group were 55% and 61%, respectively. Control at the primary site was adversely related to increasing T-stage, node positivity and bone involvement at presentation. Osteonecrosis was seen in 14 (5.9%) of 237 cases without bone involvement at presentation. Taking all patients, late morbidity (non-healing soft tissue injury or bone necrosis) was seen in 45 patients (13.6%) at a median time of 21 months from treatment. The factors contributing to late morbidity were: (1) bone involvement at presentation, (2) synchronous MTX chemotherapy, (3) the contribution of scattered radiation from elective neck treatment, (4) increasing radiation dose, (5) increasing target volume for doses less than 55 Gy and (6) dental extractions. Eighty-four (31%) patients who were initially node-negative developed disease in the untreated neck during follow-up. Salvage neck dissections controlled neck disease in half of the node-only recurrences (21/42 cases). CONCLUSION: These results have influenced our treatment policy, with lowering of the primary tumour dose in some cases and addition of elective neck irradiation for T2-T4 No patients.

The effect of increasing the treatment time beyond three weeks on the control of T2 and T3 laryngeal cancer using radiotherapy.

Local control of cancer by radiotherapy may be prejudiced by accelerated tumour clonogen repopulation particularly during protracted treatment schedules. A series of 496 cases of T2 and T3 larynx cancer treated here by radiotherapy has been studied to examine the impact on local control of treatment durations ranging from 9 to 41 days. Data were analysed using a linear-quadratic formulation describing the fractionation sensitivity, with the incorporation of a parameter relating to treatment time. Using combined T2 and T3 data, the increase in dose required to maintain a constant local control (the time factor) was between 0.5 and 0.6 Gy per day. These values are similar to those reported for 4 weeks or more in the literature. Also, the calculated dose to control 50% of tumours, given over the standard Christie duration of 21 days, was on the line projected back from literature data over 28-66 days. The present data are consistent with the presence of such a time factor following a lag phase of not more than 3 weeks after starting radiotherapy. Hence, further consideration should be given to using shorter overall treatment times in radiotherapy for head and neck cancer.

Radical radiotherapy for carcinoma of the oesophagus: an effective alternative to surgery.

BACKGROUND AND PURPOSE: Despite advances in operative and postoperative care, long term survival rates following radical oesophagectomy are poor. Surgery remains the mainstay of radical treatment despite various series reporting similar results for treatment with radiotherapy, in particular in the upper third of the oesophagus. We have studied a cohort of patients treated with definitive radiotherapy to examine the influence on survival of changes in diagnostic scanning and radiotherapy computer planning as well as various patient and disease related prognostic factors. PATIENTS AND METHODS: From 1985 to 1994, 101 patients with clinically localised carcinoma of the oesophagus were treated at the Christie Hospital with definitive radiotherapy. This included 11 patients with oesophageal adenocarcinoma. Diagnostic and planning techniques changed over the period studied, with increasing use of both diagnostic and radiotherapy planning CT scanning. Radiotherapy doses ranged from 45 to 52.5 Gy in 15 or 16 fractions over 3 weeks. RESULTS: The 3- and 5-year survival figures were 27% and 21%, respectively, corrected for intercurrent deaths. Survival was better for adenocarcinoma than squamous cell carcinoma, though not statistically significantly. The only significant prognostic factor (P = 0.01) was the use of diagnostic CT scanning (42% versus 13% 5-year survival with or without diagnostic CT scanning, respectively) which was associated with an increase in field size. Radiotherapy was well tolerated with no acute mortality or significant morbidity. Late stenosis requiring oesophageal was seen in five of 20 patients surviving 3 years or more. CONCLUSIONS: Survival following well planned radiotherapy is an effective alternative to surgery for both squamous cell and adenocarcinoma. Advances in staging and three-dimensional planning and the use of multimodality treatment may further improve survival.

Definitive radiotherapy for 114 cases of T3N0 glottic carcinoma: influence of dose-volume parameters on outcome.

BACKGROUND AND PURPOSE: Assuming that the dose-response curve for T3N0M0 glottic carcinoma is steep and that the rate of occult lymph node metastases is low, it should be possible to employ high biological tumour doses to modest target volumes and thereby maximise laryngeal control without compromising final neck control. Within the constraints of a retrospective study we aim to examine this policy with respect to local control, incidence of nodal relapse and late complications. MATERIALS AND METHODS: One hundred and fourteen patients with T3N0M0 glottic carcinoma who received a 3-week schedule of radical radiotherapy between 1986 and 1994 were analysed. The median age was 67 years (range, 34-85 years) and the median follow-up for living patients was 4.8 years (1.9-8.9 years). There were no strict selection criteria for those patients treated with radiotherapy. RESULTS: The 5-year overall survival was 54%. The 5-year local control with radiotherapy and the ultimate loco-regional control following salvage laryngectomy were 68 and 80%, respectively. Nine patients (8%) suffered a regional nodal relapse but only three of these (3% overall) occurred in the absence of local failure. Four patients (3.5%) developed serious late complications requiring surgical intervention (three received 55 Gy and one 52.5 Gy). CONCLUSIONS: It is possible to employ maximum tolerable doses to specific target volumes and thereby exploit the dose response demonstrated and minimise major late effects. The use of modest target volumes resulted in only 3% of patients requiring surgery that might have been avoided had prophylactic neck irradiation been employed.

Influence of radiotherapy treatment time on control of laryngeal cancer: comparisons between centres in Manchester, UK and Toronto, Canada.

A comparison has been made of the influence of treatment time on tumour control rates for 496 (T2 and T3) larynx cancer cases in Manchester, UK and 1001 (T1-T4) cases in Toronto, Canada. Both series of patients were treated in fairly short overall times, commonly 3 weeks in Manchester and 4-5 weeks in Toronto. All the tumour control data were analysed using the same method to obtain values of fitted dose, fractionation and time parameters. The analysis showed the following. (a) Differences between the total combined (T2 + T3) data sets from the two centres, fitted using direct analysis and the LQ model incorporating a parameter for overall treatment time, were not significant (p = 0.17) and close similarity in control rates was observed using treatment regimens common to both series. (b) The Manchester series over 9-41 days and the Toronto series over 14-84 days are both consistent in showing for (T2 + T3) tumours the presence of a mean time factor of 0.6-0.8 Gy/day required to abrogate the decrease in tumour control concomitant with an increase in overall treatment time from the minimum the maximum employed in each series. (c) When a parameter was included in the model to test for the possible presence of a lag period before the time factor became operative, the lag was not significant for the Toronto data, in contrast to a significant lag for the Manchester data alone (T2 + T3 data).(ABSTRACT TRUNCATED AT 250 WORDS)

Radiotherapy for carcinoma of the posterior pharyngeal wall.

Posterior pharyngeal carcinoma has an extremely poor prognosis regardless of the method of treatment. The purpose of this study was to assess the local control and survival in patients with carcinoma of the posterior pharyngeal wall treated with definitive radiotherapy and to determine prognostic factors which may be relevant to the current UICC staging classification. Between January 1991 and December 1995, 22 patients with a mean age of 60 years (range 44-82) received definitive radiotherapy, using a homogeneous technique, for carcinoma of the posterior pharyngeal wall. The median follow-up was 42 months (range 25-66). The overall 3-year survival and local control for the whole group was 50% and 73% respectively. Patients with early stage (T1 and T2) disease had a significantly better overall 3-year survival rate of 77% compared to 11% for patients with advanced stage (T3 and T4) disease (p=0.0010). Similarly, patients with early stage disease had a significantly improved 3-year local control rate compared to patients with more advanced stage disease (92% and 44% respectively, p=0.0080). Patients with node positive disease had an inferior survival rate of 29% compared to 60% for those with node negative disease though the difference did not reach statistical significance. In addition only one patient with initial node negative disease had isolated nodal relapse. There was no significant late morbidity. For patients with early stage disease we have obtained local control and survival rates comparable to other groups with a once daily, short fractionation radiotherapy scheme but with reduced morbidity. In late stage disease altered fractionation schemes should be considered in order to achieve better local control and survival. Isolated nodal relapse was not a significant problem in this cohort of patients. Outcome correlates with primary tumour size and this is reflected in the current UICC staging classification.

Germ cell tumours confined to the supra-clavicular fossa: a report of two cases.

Two cases of germ cell tumours in males presenting as a left supra-clavicular mass, with no evidence of disease in other sites, are reported. Biopsy showed seminoma in one case and teratoma in the other. Supra-clavicular germ cell tumour as an isolated finding after intensive investigations has not previously been reported.

Carcinoma of the hard palate treated with radiotherapy: a retrospective review of 31 cases.

There are few studies reporting the results of radical radiotherapy for carcinoma of the hard palate. We have examined our results of patients treated within a single institution, and assessed survival, local control and morbidity. A retrospective analysis was made on 31 patients with hard palate carcinoma treated with external beam radiotherapy at the Christie Hospital between 1990 and 1997. Twenty-six patients received radiotherapy alone and five were treated for post-operative positive surgical margins. The 5-year actuarial survival rate was 55%. The actuarial 5-year local control rate was 53%, rising up to 69% after salvage surgery. Survival was 48% for squamous cell carcinomas and 63% for salivary gland carcinomas, the difference was not significant. The only significant predictor of local control was T-stage, with 80% 5-year local control of T1-2 lesions and 24% control of T3-4 lesions. N-stage was the only significant factor predicting for survival. Radiation necrosis occurred in one patient. Radical radiotherapy for carcinoma of the hard palate is safe and well tolerated. It is an effective treatment for both squamous cell carcinoma and salivary gland carcinoma.

Submandibular gland carcinoma; an audit of local control and survival following adjuvant radiotherapy.

Carcinoma of the submandibular gland is a rare diagnosis, accounting for less than 2% of cases of salivary gland tumours. We have examined the treatment and outcome of a total of 30 patients treated with radiotherapy at the Christie Hospital, Manchester between 1980 and 1993. In most cases this followed radical surgery, though 12 patients were referred following either incomplete excision or biopsy only. Adenoid-cystic histology accounted for 19 cases (63%). Standard radiotherapy was delivered using a beam directed technique to treat the whole submandibular compartment. Doses prescribed were most commonly from 50 to 55 Gy in 16 fractions over three weeks. Cancer specific survival was 79% and 57% at 5 and 10 yr respectively, the continued fall at 10 yr reflected late recurrence seen in patients with adenoid-cystic histology. Local control was 85% and 73%, respectively. Nine of twelve patients with incomplete excision or biopsy only had local control with radiotherapy. Six patients developed lung metastases, all of whom had adenoid-cystic histology. Radiotherapy was well-tolerated acutely, and only one patient experienced osteoradionecrosis requiring surgical intervention. The incidence of adenoid-cystic carcinoma is higher in the submandibular than the parotid gland. This typically results in late recurrence, and a high incidence of lung metastases and this was confirmed in our study. However, overall survival was very similar to that of parotid carcinoma.

Radical radiotherapy for carcinoma of the vulva.

A study was made of 58 patients with carcinoma of the vulva treated by radical radiotherapy between 1965 and 1982. The choice of treatment technique was influenced by site and extent of disease as well as the general condition of the patient. The crude 5-year survival was 26% (15/58). Local control was achieved in 40% of cases and was associated with tumour size of 4 cm or less. Radionecrosis occurred in nine cases but none of these required surgical intervention. Surgery remains the treatment of choice for carcinoma of the vulva. This report emphasizes that radical radiotherapy has a curative potential in those cases considered unsuitable for surgery and that the necrosis type and rate are within the limits of acceptable morbidity.

Radical radiotherapy for 28 cases of mucosal melanoma in the nasal cavity and sinuses.

Mucosal melanoma is rare and is traditionally treated by radical surgery. A retrospective survey was made of 28 cases of malignant mucosal melanoma of the nasal cavity and paranasal sinuses treated by definitive radiotherapy. Initial complete regression was observed in 22 out of 28 cases (79%). Absolute local control by radiotherapy alone was achieved in 17 out of 28 cases (61%) but follow-up was limited in many cases by early death due to metastatic disease; actuarial local disease-free survival was 49% at 3 years. The approach of radical radiotherapy for melanoma of this site can be justified on the basis of the local control achieved, low treatment morbidity in patients who are typically elderly and the propensity to disseminated disease. Doses of radiotherapy required to achieve local control need to be radical; the influence of dose per fraction is uncertain.