National survey of radiotherapy fractionation practice in 2003.

AIMS: To document UK practice in radiotherapy fractionation. METHODS: All radiotherapy centres in the UK participated in a 1-week audit from 29 September 2003. Fractionation data were collected for all patients starting external beam radiotherapy. This included 2498 patients who were prescribed 32 547 fractions. RESULTS: For the radical treatment of non-skin malignancy (n = 708), the prescribed dose ranged from a single fraction of 8 Gy for total-body irradiation to 75 Gy in 43 fractions for prostate cancer. Postoperative treatment for breast cancer was dominated by three regimens: 40 Gy in 15 fractions; 45 Gy in 20 fractions; and 50 Gy in 25 fractions. Palliative treatment was given in a single fraction to 393 patients (36%) with doses of up to 15 Gy. Three hundred and ninety patients (36%) received four to seven fractions delivering 20-25 Gy. Only 89 patients (8%) received more than 10 fractions with palliative intent but used 29% of such fractions. In the treatment of bone metastases, the most common prescriptions were 8-10 Gy in a single fraction and 20 Gy in five fractions. CONCLUSION: UK radiotherapy practice has become more uniform and moved closer to practice in North America and Europe over the past 15 years. For radical radiotherapy, 54% of prescriptions were for a fraction size of 1.8-2.0 Gy but the distribution was bi-modal and 20% of patients were prescribed fraction sizes of 2.7-3.0 Gy. Evidence-based practice now supports hypo-fractionated palliative treatment favouring single fractions for bone metastases and one or two fractions for many patients with advanced lung cancer. Two fractions are advised for some patients with brain metastasis. If these guidelines had been applied uniformly, then the number of treatments prescribed for palliation could have fallen by 36% from 5197 to 3313. This would have represented a 6% reduction in the overall radiotherapy workload. Not all patients are suitable for such hypo-fractionated treatments, but this is an area in which resource use can be improved. In the postoperative management of breast cancer, a change in practice to use 15 fractions uniformly would reduce overall radiotherapy workload by 4%. By contrast, a change to 25 fractions would increase overall workload by 7%.

Iridium-192 implantation for node-negative carcinoma of the penis: the Cookridge Hospital experience.

Carcinoma of the penis is a rare tumour of the male urogenital tract, which may be treated by using several modalities. We present a single-centre experience of iridium-192 implantation. From 1980 to 1997, 31 patients with node-negative penile cancer were treated with an iridium-192 implant to the penis. A retrospective analysis of the case notes was made. Survival curves were estimated by the Kaplan-Meier method. The median age at treatment was 61.5 years. Twenty-seven patients presented with Jackson Stage I disease and four with Stage II disease. They were treated with an iridium-192 implant to the penis after biopsy (n = 25) or tumour excision (n = 6), with a 'watch and wait' policy for inguinal nodes. Four patients did not complete their implantation treatment and had additional external beam radiotherapy. The median follow-up was 61.5 months. The primary tumour was controlled in 25 of 31 patients (80.6%) by the implant. In all but one patient with primary relapse, surgical salvage was successful, although one patient died of septicaemia 3 weeks after surgery. Nodes were the initial site of relapse in seven patients, with associated relapse in the primary in one. The actuarial 5-year survival rates were as follows: overall survival 69.0 %, disease-specific survival (corrected for intercurrent deaths) 85.4%, relapse-free survival 57.8% and local relapse-free survival 75.6%. One patient underwent amputation for necrosis and 11 of 25 patients (44%) who achieved penile conservation required dilatation for urethral stenosis. In conclusion, iridium-192 implantation is a successful method of treatment for penile cancer in terms of local control, with preservation of function in the majority of patients. In those who do relapse at the primary site, surgical salvage is usually possible.

Erythroplasia of Queyrat treated by topical aminolaevulinic acid photodynamic therapy.

Erythroplasia of Queyrat (EQ) is an intraepithelial carcinoma in situ affecting the mucosal surfaces of the penis, with a significant risk of invasion and metastasis. Treatment is often difficult and is associated with significant recurrence rates. Topical 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) combines a photosensitizer precursor and visible light to produce a photodynamic effect. It has been used successfully to treat benign, premalignant and malignant skin diseases. We present four patients with EQ who have been treated by topical ALA PDT. Of two patients with limited disease one has achieved a long-term complete response (36 months) and the other developed a recurrence at 18 months after a complete response. Two further patients with more extensive disease achieved a significant improvement, allowing easier treatment by laser vaporization. Although topical ALA PDT offers the advantages of tumour specificity, preservation of function and a good cosmetic result, more extensive EQ appears less responsive to this new therapeutic modality using current treatment parameters.

An alternative and more cost effective method of delivery of radiotherapy in age related macular degeneration.

AIMS/BACKGROUND: In the past 5 years there has been a dramatic increase in the use of radiotherapy to treat subfoveal neovascular membranes (NVMs) in both Europe and the USA despite the high cost. An alternative, more cost effective method of delivery using x ray simulation and bite block head fixation is described. METHOD: 15 patients were recruited with classic subfoveal NVMs. Head fixation was achieved with a customised Perspex mask for eight patients and a bite block for seven. An x ray simulator was used to check the field of irradiation. No computerised tomography (CT) was performed. All patients received a total dose of 13.3 Gy ionising radiation. Visual acuities were charted before and after treatment over a 24 month period. RESULTS: After 24 months, 5/8 (67%) in the mask group showed stable visual acuities (less than two line change on Snellen chart) compared with 3/7 (43%) in the bite block group. This difference may be attributed to a variation in the pretreatment visual acuities in the two groups. From several studies it has been estimated that 24 months after diagnosis 28% untreated individuals would have stable vision compared with 53% patients in this study. CONCLUSIONS: These results compare favourably with other studies and show that teletherapy can be safe and effective form of treatment for subfoveal NVMs. The authors have described an alternative method of head fixation and shown that CT scanning is not essential. This method of delivery is considerably less costly than that traditionally used and may allow greater numbers of patients to benefit from radiotherapy treatment.

Large patches of Bowen's disease treated by topical aminolaevulinic acid photodynamic therapy.

Large patches of Bowen's disease (intraepidermal carcinoma in situ) can be difficult to treat by conventional methods. Photodynamic therapy (PDT) uses the combination of a photosensitizer, which preferentially accumulates in malignant cells, and photoactivation by visible light to kill the malignant cells. 5-aminolaevulinic acid (ALA) PDT uses excess exogenous ALA, which produces, via the haem synthesis pathway, a build up of the photosensitizer protoporphyrin IX. We describe the use of topical ALA PDT to treat three patients with three especially large patches of Bowen's disease. Following two treatments all three lesions achieved a complete clinical and histological response with a good cosmetic result. ALA PDT is a simple, effective and well tolerated treatment for large patches of Bowen's disease.

Continuous, pulsed or single acute irradiation of a transplanted rodent tumour model.

BACKGROUND: Recent advances in remote afterloading pulsed mode brachytherapy have provided a much needed tool for the radiation oncologist. It has the versatility of optimised physical dose distribution along with improved staff radiation protection and patient nursing. PURPOSE: This preliminary study was designed to explore the radiobiological equivalence between conventional continuous low dose rate tumour irradiation (CLDR) and the new technique of pulsed dose irradiation (PDR). MATERIALS AND METHODS: Subcutaneous isogenic sarcomas transplanted in female John's Strain Wistar rats were irradiated locally with acute, pulsed or continuous interstitial low dose-rate exposures at 9-11 mm mean diameter. RESULTS: As expected, single acute doses (5-40 Gy) were more effective (P < 0.01) in achieving tumour growth delay (1.4 days/Gy) than CLDR exposure (4-51 Gy) over 24-48 h (0.93 days/Gy). However, PDR treatment (8 hourly fractions/day) at high dose-rate (8-48Gy) over 8-72 h was significantly (P = 0.01) more effective (1.66 days/Gy) than CLDR but not acute exposures. CONCLUSIONS: These data suggest that, clinically a significantly improved therapeutic ratio may also be achievable with pulsed high dose rate brachytherapy, and that further radiobiological studies with in-vivo tumour models are needed.

Replacement of hairpin and loop implants by optimised straight line sources.

Remote after loading is desirable for all forms of brachytherapy but is difficult in the oral cavity because the tight curvature at the top of implanted loops impedes passage of the source. For this reason we investigated differential loading of straight catheters to simulate a conventional loop or hairpin. Using a pulsed brachytherapy remote after loader the top four dwell positions of straight catheters were given two to four times the dwell time of other source positions. This raised the reference isodose to cover the surface mucosa without significantly changing either the total volume treated or the volume receiving > 150% of reference dose when compared with conventional loop implants of equivalent source length and separation. This optimised straight line implant should therefore be amenable to remote afterloading and have similar dose/volume characteristics to loops.

Seven-year follow-up on 334 patients treated by breast conserving surgery and short course radical postoperative radiotherapy: a report of the Yorkshire Breast Cancer Group.

A total of 334 patients have been entered into a prospective protocol of breast conserving treatment, which consisted of clinically complete excision, axillary dissection, and radical postoperative radiotherapy given in 20 fractions over 4 weeks. After 7 years' follow-up, 22 patients (6.6%) have had an isolated local recurrence and 24 (7.2%) a local recurrence associated with metastic disease. Cosmetic assessment shows that patients are more satisfied with the result than their treating consultants, and that 81% have scored themselves as having an excellent or very good result more than 5 years after treatment.

Extrapulmonary small cell cancer.

Extrapulmonary small cell cancer is rare, but it occurs in a wide variety of sites, where it has a behaviour quite different from the tumours normally found at those sites. Prognosis is generally poor, but combined modality treatment with combination chemotherapy can often achieve useful palliation and, occasionally, long term remission and cure.

Superficial photodynamic therapy with topical 5-aminolaevulinic acid for superficial primary and secondary skin cancer.

Between January 1991 and December 1992 a phase I trial of superficial photodynamic therapy (PDT) using topical application of 5-aminolaevulinic acid (ALA) was undertaken to treat Bowen's disease, superficial basal cell carcinomas (BCCs) and metastatic skin secondaries from breast (adenocarcinoma) or pinna (squamous cell carcinoma). Promising results were obtained with 36 areas of Bowen's disease, with a complete response rate of 89% at a median follow-up of 18 months. The treatment of BCCs was less successful, with 50% complete responses in 16 lesions at a median follow-up of 17 months. Metastatic nodules responded poorly. The treatment was well tolerated and discomfort during light irradiation could be reduced by prior application of 'Emla' cream. Lesions wept for 1-2 weeks following treatment and healed over a period of approximately 2 months. For large areas of Bowen's disease, particularly in anatomically difficult areas and in elderly patients, PDT using ALA may constitute a single simple alternative outpatient treatment to existing therapies. Further work is required to improve the results with BCCs.

Interstitial photodynamic therapy. Clinical experience with diffusing fibres in the treatment of cutaneous and subcutaneous tumours.

Interstitial photodynamic therapy has a number of potential advantages over superficial treatment. We have treated 50 subcutaneous and cutaneous tumours interstitially, in nine patients. An additional 22 tumours in the same patients, were treated by superficial PDT. Patients received 1.5-2.0 mg kg-1 of polyhaematoporphyrin and 72 h later underwent treatment using a copper vapour dye laser producing red light at 630 nm. All interstitial treatments were delivered using cylindrical diffusing fibres and a wide range of light doses (5-1500 J cm-3). The complete response rate for all tumours treated interstitially was 52%, rising to 81% in those patients who received 2.0 mg kg-1 PHP and light doses in excess of 500 J cm-3. The overall incidence of skin necrosis was 32% and was 79% in those treated with light doses of greater than 500 J cm-3. The incidence of skin necrosis with interstitial PDT is lower than that seen with superficial photodynamic therapy but higher volumetric light doses are required to produce tumour complete responses. All treatments were well tolerated and volumes of tumour up to 60 cm3 were successfully treated. The penetration depth of 630 nm light in human breast cancer tissue was determined as 4 mm. Little true tumour tissue selectivity was detected by analysis of porphyrin levels in biopsy material.

New drugs and future developments in photodynamic therapy.

New photosensitizing drugs are becoming available which should improve on some of the disadvantages of haematoporphyrin derivates for photodynamic therapy (PDT). The main features are shorter duration of systemic photosensitisation, activation by longer and more penetrating light and better tumour to normal tissue drug uptake ratios. These drugs together with better understanding of in vivo light dosimetry promise to improve both results and clinical acceptability for PDT in future studies.

Assessment of palliative chemotherapy: a step beyond response.

In summary, tumour response is a useful index of cytotoxic activity, but is of limited value in the assessment of benefit to the patient following treatment with cytotoxic drugs. Survival is a similarly inappropriate endpoint to assess the clinical benefits of palliative cytotoxic therapy. The widespread introduction of QL assessment as a primary outcome measure in cancer therapy will enhance our understanding of the value of a wide range of established cancer treatments, not only that of palliative chemotherapy, but also surgery and radiotherapy.

Interstitial brachytherapy: past-present-future.

This article summarizes and reviews the development of brachytherapy from 1930 to 1990. Its purpose is to highlight the immense contribution made to its underlying science and clinical practice by Dr. Frank Ellis, who has been personally involved with it, in theory and in practice, for that whole half-century. A remarkable achievement in itself, but so much the more when it is seen beside his contributions to other aspects of radiation in the service of man. The early use of solid sources leads on to a discussion of manual afterloading and iridium. This leads on to a quick survey of the development of dosimetry. Thereafter clinical indications are briefly discussed and some published results tabulated. Lastly, some pointers to possible future development and benefits are discussed. Mention is also made of some continuing unresolved problems where new work could help to establish the most appropriate use of brachytherapy.

Radiotherapy after conservative surgery for breast cancer: selective use of iridium-192 wire boost to tumour bed in high risk patients.

The results of treatment for 51 patients referred for radiotherapy after local excision of an 'early' breast carcinoma are reviewed. The patients were considered to be at particularly high risk of local recurrence due to the presence of one or more adverse histological features, most commonly microscopic involvement of resection margins. The patients received a course of whole-breast irradiation (40 Gy in 15 fractions over 3 weeks) but instead of following this with a routine photon or electron tumour-bed boost (15 Gy in five fractions) these patients received an iridium-192 wire implant, giving a tumour-bed boost of 25 Gy over approximately 3 days. After a median follow-up of 38 months, five patients have recurred locally within the breast, giving an actuarial breast recurrence-free survival of 87.8% at 8 years. Four patients have died of metastatic breast cancer, none of whom had uncontrolled local disease. Cosmesis was good or excellent in 76% of cases. The presence of microscopic tumour at resection margins or other adverse histological features is not, therefore, necessarily an indication for further surgery, as a good level of local control can still be achieved with radiotherapy providing a relatively high-dose tumour-bed boost is employed using an iridium-192 wire implant.