D. Ash

ESTRO/EAU/EORTC recommendations on permanent seed implantation for localized prostate cancer

INTRODUCTION The last few years has seen an enormous increase in interest in the role of new transrectal ultrasound and template guided techniques for brachytherapy in localised prostate cancer. In the USA there has been a dramatic rise in the number of implants performed in the last five years. A similar rapid expansion is expected in Europe and this guidance is intended to indicate to those embarking on brachytherapy the factors which may be related to successful outcomes.

Prostate-specific antigen relapse-free survival in patients with localized prostate cancer treated by brachytherapy

Brachytherapy has become a very popular way of treating prostate cancer worldwide, and increasing attempts are being made by radiation oncologists to find the exact type of patient for whom this treatment is the most suitable. One of the largest series has come from Leeds, and the authors present the PSA relapse‐free survival in 667 patients with localised prostate cancer treated by brachytherapy in their department.

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.

Short-term morbidity and acceptability of 125iodine implantation for localized carcinoma of the prostate.

To report the short‐term morbidity and acceptability of the first 50 patients treated with the percutaneous implantation of radioactive iodine seeds for localized carcinoma of the prostate at the Cookridge Hospital.

The optical properties of skin tumours measured during superficial photodynamic therapy

Accurate measurement of light distribution in tissue can improve the knowledge of in vivo tissue optical properties, which is essential for precise dosimetry calculations during photodynamic therapy (PDT). In our application of PDT, superficial skin lesions are treated by topical administration of 5-aminolaevulinic acid followed by surface illumination using 630 nm laser light. Several small detector probes inserted under the skin surface prior to illumination record the light intensity at different depths throughout the treatment. Results from 11 patients are presented. These results indicate light distributions described by the diffusion theory for light transport in tissue. The accumulated data do not imply one specific set of optical parameters for the skin, but indicate that although the depth of light penetration is constant for all patients, the variation in skin colour is significant when performing dosimetry calculations. The average value of effective attenuation coefficient was found to be 0.359 mm−1 (±9.5%) and the coefficientk that is used to quantify the build-up of subsurface fluence rate varies between 0.12 and 8.23.

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 Johns 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.

Report on the Early Efficacy and Tolerability of I125 Permanent Prostate Brachytherapy from a UK Multi-institutional Database

AIMS To report the results of I(125) prostate brachytherapy from a central, prospectively collected database of three UK institutions. MATERIALS AND METHODS All patients treated with I(125) permanent prostate brachytherapy at the Christie Hospital, Manchester (CHM), Cookridge Hospital, Leeds (CKL) and Mount Vernon Hospital, Northwood, London (MVL) since 2003 have been prospectively registered on a detailed central database. Patient, tumour, pre- and post-implant dosimetry data have been recorded. Urinary toxicity as assessed by the International Prostate Symptom Score, catheterisation and urinary stricture rates after implant have been documented and biochemical failure determined, using both the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus and the Phoenix (nadir + 2 ng/ml) definition. RESULTS In total, 1535 patients were registered on the database between January 2003 and October 2006, including 432 from CHM, 926 from CKL and 177 from MVL, with a median follow-up of 21 months (range 1-56). Patient and tumour characteristics were similar at all centres. Pre-implant dose indices were comparable between centres, except for the V150, with median values of 51.9, 64.3 and 69.8% at CHM, CKL and MVL, respectively. Median post-implant dose parameters were lower than pre-planned constraints by up to 33.0% at each centre for all values, except at CKL where the V200 was 23.9% higher. The International Prostate Symptom Score increased from a median of 5 at baseline to 18, 6 weeks after implant, but was not significantly different to baseline values by 12 months. Nine per cent of men required catheterisation after implant for a median duration of 53 days, but urinary stricture rates remained low at 1%. Neoadjuvant hormonal manipulation was used in 228 men (15%) for downsizing and 159 (10%) for intermediate/high-risk disease. Collated biochemical failure rates were low at this point of follow-up, with actuarial 2-year ASTRO and Phoenix biochemical failure-free survival rates of 94.4 and 94.5%, respectively, consistent with other large single centre reports. When post-implant dosimetric factors were assessed for a relationship to biochemical failure, no indices consistently predicted for improved ASTRO and Phoenix biochemical failure-free survival rates. CONCLUSIONS This ongoing collaboration shows that with limited infrastructure (a single industry-sponsored data manager), a large multi-institutional database estimated to represent one-third of implants carried out in the UK during this time can be developed. Patient selection was similar across all centres and adhered to published guidelines. Early biochemical and toxicity outcomes confirm the efficacy and tolerability of I(125) prostate brachytherapy in a large cohort of patients. A further analysis is planned.

Distribution of protoporphyrin IX in Bowen's disease and basal cell carcinomas treated with topical 5-aminolaevulinic acid

We have used ultra-low light level fluorescence microscopy to examine the suggestion that the relatively poor response of human basal cell carcinomas (BCC) to topical 5-aminolaevulinic acid (ALA)-based photodynamic therapy (PDT) arises from limited drug penetration into the lesion. The distribution of ALA-induced protoporphyrin IX (PpIX) in human BCC and Bowens disease was examined and, in almost all cases, was found to be most intense in those regions of tumor immediately adjacent to the dermis. This distribution was independent of tumor type, and did not appear to be affected by tumor depth in the skin. It is suggested that ALA penetration may not limit the efficacy of ALA-PDT in the treatment of BCC. Failure of superficial ALA-based PDT in basal cell carcinoma may, instead, be related to the histological structure of this type of lesion.

An attempt to reduce skin photosensitivity in clinical photodynamic therapy using oral activated charcoal

Skin photosensitivity remains the major side-effect of current clinical photodynamic therapy using porphyrin based drugs. We have studied the usefulness of oral activated charcoal in 12 patients undergoing photodynamic therapy and a control group of patients treated without charcoal. Detailed pharmacokinetic studies were carried out and measurements of skin erythema responses to known light doses were made using a reflectance spectrophotometer in these patients. There were no significant differences with respect to the area under the curve, clearance, mean residence time or half-life of the drug between the two groups and no significant differences in reflectance values. Prolonged skin photosensitivity as assessed by reflectance spectrophotometry was confirmed up to and beyond 2 months after treatment.

The response of a rodent fibrosarcoma to superficial/interstitial photochemotherapy, chemotherapy or radiotherapy.

Growth and dose-response curves were established for a subcutaneously implanted isogenic fibrosarcoma in BD9 rats after treatment with photochemotherapy (PCT), using Photofrin II or polyhaematoporphyrin with superficial or interstitial 630 nm light, cyclophosphamide or gamma-irradiation. Tumour response to PCT increased with dose up to 200 J.cm-2 for superficial light or 200 J for interstitial light but no further response occurred after higher light doses. The maximum response after interstitial treatment was significantly greater than after superficial treatment where only a small margin of normal tissue was treated. The incidence of necrosis in the overlying skin was significantly less after interstitial than superficial light suggesting a better therapeutic ratio after interstitial than superficial PCT. Tumour response increased with the diameter of the treatment field after superficial light supporting the possibility of a tumour bed effect associated with PCT. The largest tumour that could be effectively treated with a single optical fibre was 12 mm. The dose-response curves for interstitial PCT and cyclophosphamide were similar but ionizing irradiation produced increasing tumour response throughout the range of doses used (5 to 30 Gy) and the maximum response was greater after radiotherapy than after PCT or chemotherapy suggesting that in this tumour model interstitial PCT is as effective as cyclophosphamide but less effective than radiotherapy.