Manually after-loaded 192Ir low-dose rate brachytherapy after subtotal excision and flap reconstruction of recurrent cervical lymphadenopathy from head and neck cancer.

BACKGROUND: Treatment of extensive recurrent cervical lymph node metastases from previously irradiated head and neck cancer represents a difficult clinical challenge. We report the results of an approach of maximal surgical debulking and manually after-loaded intra-operative brachytherapy. PATIENTS AND METHODS: Seventy-four procedures were carried out at the Royal Marsden Hospital between 1979 and 2003. All patients had previously been treated with radical radiotherapy or chemoradiation. Patients underwent maximal surgical debulking, followed by brachytherapy to the tumour bed with low-dose rate (192)Ir to a dose of 60 Gy to the reference isodose using the Paris system. RESULTS: Overall and disease specific survival rates were 31% and 28% at two years and 23% and 17% at five years. Corresponding Loco-regional control rates were 37% and 23%, respectively. Fifty per cent of patients developed metastatic disease within 5 years of treatment. Best results were obtained with surgical excision, brachytherapy and reconstruction of the skin defect using a vascularised myo-cutaneous flap with in-field control rates of 72% at two years and 66% at 5 years. Nine per cent of patients developed fistulae, 4% had haemorrhage and 8% wound breakdown/infection. CONCLUSIONS: Maximal surgical debulking, including removal of overlying skin, and brachytherapy to the surgical tumour bed provides high levels of local control, and can be achieved with acceptable morbidity. Only a minority of patients achieve long-term survival because of the high risk of systemic relapse.

Three weeks radiotherapy for T1 glottic cancer: the Christie and Royal Marsden Hospital Experience.

BACKGROUND AND PURPOSE: Radiotherapy for laryngeal carcinoma is conventionally given over a 6-7-week period. However, in a number of UK centres early lesions are treated over 3 weeks. We review recent results of this policy and discuss the reasons why short treatment times may be advantageous. MATERIALS AND METHODS: Two hundred patients (100 from each centre) with T1 glottic invasive squamous cell carcinoma treated with definitive radiotherapy between 1989 and 1997 were analysed. The median age was 68 years. All patients received once daily fractionation, 5 days a week to a total tumour dose of 50.0-52.5 Gy in 16 fractions over 21 days; the fraction size ranged from 3.12 to 3.28 Gy. The median follow-up period was 5 years and 10 months. RESULTS: The 5-year local control rates with radiotherapy for the whole group was 93%; there were 14 recurrences of which seven were salvaged by laryngectomy giving an ultimate local control of 96%. The 5-year overall survival was 80% and cause specific survival at 5 years was 97%. Univariate analysis revealed that T1 substaging (P=0.82) and anterior commissure involvement (P=0.47) did not significantly influence local control. A severe late radiation complication was seen in only one patient who continued to smoke heavily after treatment. There were no severe acute complications. CONCLUSIONS: Once daily radiotherapy over 3 weeks gives excellent local control in patients with T1 glottic squamous-cell carcinoma and has a low rate of severe complications. The short overall treatment time and large fraction size may be advantageous in radiotherapy of these well-differentiated tumours.

Le Fort I osteotomy and low-dose rate Ir192 brachytherapy for treatment of recurrent nasopharyngeal tumours.

BACKGROUND: Treatment of recurrent nasopharyngeal carcinoma is a difficult clinical problem. External beam re-irradiation is associated with a long-term cure in a proportion of cases but this may be associated with severe radiation injury. METHODS: Eighteen patients with post-nasal space tumours were treated between 1986 and 2001 with surgical excision and nasopharyngeal brachytherapy via a Le Fort I osteotomy approach. Low-dose rate (LDR) and high-dose rate (HDR) brachytherapy was used. Data was prospectively collected. Local control and overall survival were measured. Acute and late complications were assessed using the RTOG system. RESULTS: The overall survival was 67% at 2 years and 33.5% at 5 years. The corresponding local control rates were 42 and 31.5%, respectively. The T stage at relapse was a significant prognostic factor for local control (P=0.004) but not overall survival. Acute toxicity was mild. RTOG grade >/=3 late complications occurred in 40% of patients treated with the HDR, and 0% treated with LDR. CONCLUSIONS: The results of the Le Fort osteotomy, tumour debulking and post-operative brachytherapy gives local control rates similar to those achieved with wide-field re-irradiation. Complication rates are acceptable and are lower than that reported with other methods of radiation therapy. The surgical technique was well tolerated. HDR brachytherapy with this technique had a high complication rate. This approach is a viable option in the treatment of recurrent nasopharyngeal tumours.

Treatment of head and neck cancer with CHART and nimorazole: phase II study.

BACKGROUND AND PURPOSE: Causes of failure of radiotherapy in squamous cell carcinoma of the head and neck probably include repopulation and hypoxia. Very accelerated schedules such as continuous hyperfractionated accelerated radiation therapy (CHART) overcome the repopulation problem but allow limited time for reoxygenation, so a hypoxic-cell sensitizer may be especially beneficial. Nimorazole is the only such agent to have shown a significant effect in a randomized controlled trial in head and neck cancer. Accordingly we studied the combination of CHART and nimorazole. METHODS: Sixty-one patients with advanced stage III (21) or IV (40) squamous cell carcinoma of the head and neck unsuitable for surgery were treated in a phase II study of the combination. The radiation dose was 56.75 Gy in 36 fractions in 12 consecutive days. Nimorazole was administered orally or enterally 90 min before radiotherapy at a dose of 1.2, 0.9, and 0.6 g/m(2) with the first, second and third daily fractions, respectively. This dosage consistently yielded plasma concentrations above 30 microg/ml. RESULTS: All the patients have been followed for a minimum of 2 years since treatment. Loco-regional control at 2 years is 55%, stage III 62% and stage IV 50%. Normal tissue effects were the same as those previously seen with CHART, except for a possible slight increase in acute skin reaction. Nimorazole toxicity was somewhat greater than with once daily administration in previous studies. Grade 3 nausea or vomiting occurred in 22% of patients. Two patients developed grade 1 peripheral neuropathy, and one patient died during treatment of encephalopathy, which was probably an idiosyncratic reaction to the drug. CONCLUSIONS: Local control rates are higher than those previously seen with CHART, suggesting a positive effect of nimorazole. Further studies of hypoxia-modifying agents with accelerated radiotherapy are warranted, and nimorazole is the simplest of these.