Normal tissue complication probability modelling of tissue fibrosis following breast radiotherapy.

Cosmetic late effects of radiotherapy such as tissue fibrosis are increasingly regarded as being of importance. It is generally considered that the complication probability of a radiotherapy plan is dependent on the dose uniformity, and can be reduced by using better compensation to remove dose hotspots. This work aimed to model the effects of improved dose homogeneity on complication probability. The Lyman and relative seriality NTCP models were fitted to clinical fibrosis data for the breast collated from the literature. Breast outlines were obtained from a commercially available Rando phantom using the Osiris system. Multislice breast treatment plans were produced using a variety of compensation methods. Dose-volume histograms (DVHs) obtained for each treatment plan were reduced to simple numerical parameters using the equivalent uniform dose and effective volume DVH reduction methods. These parameters were input into the models to obtain complication probability predictions. The fitted model parameters were consistent with a parallel tissue architecture. Conventional clinical plans generally showed reducing complication probabilities with increasing compensation sophistication. Extremely homogenous plans representing idealized IMRT treatments showed increased complication probabilities compared to conventional planning methods, as a result of increased dose to areas receiving sub-prescription doses using conventional techniques.

A pragmatic approach to dosimetric audit in radiotherapy.

In 1993 a dosimetric audit programme was initiated by physicists from a group of hospitals in the South West UK with the aim of detecting dosimetric errors greater than 5%. The scope of this programme was developed to cover megavoltage and kilovoltage photons as well as electrons. Procedures operated within each department were also audited in situations where they could influence dosimetry. No dose discrepancies greater than 5% were detected in the course of the audits, though differences did correlate with complexity in some situations. These measurements provide an ongoing assurance that dosimetry within the participating centres is well controlled and provides a firm foundation for clinical practice.

High energy neutron treatment for pelvic cancers: study stopped because of increased mortality.

OBJECTIVE: To compare high energy fast neutron treatment with conventional megavoltage x ray treatment in the management of locally advanced pelvic carcinomas (of the cervix, bladder, prostate, and rectum). DESIGN: Randomised study from February 1986; randomisation to neutron treatment or photon treatment was unstratified and in the ratio of 3 to 1 until January 1988, when randomisation was in the ratio 1 to 1 and stratified by site of tumour. SETTING: Mersey regional radiotherapy centre at Clatterbridge Hospital, Wirral. PATIENTS: 151 patients with locally advanced, non-metastatic pelvic cancer (27 cervical, 69 of the bladder, seven prostatic, and 48 of the rectum). INTERVENTION: Randomisation to neutron treatment was stopped in February 1990. MAIN OUTCOME MEASURES: Patient survival and causes of death in relation to the development of metastatic disease and treatment related morbidity. RESULTS: In the first phase of the trial 42 patients were randomised to neutron treatment and 14 to photon treatment, and in the second phase 48 to neutron treatment and 47 to photon treatment. The relative risk of mortality for photons compared with neutrons was 0.66 (95% confidence interval 0.40 to 1.10) after adjustment for site of tumour and other important prognostic factors. Short term and long term complications were similar in both groups. CONCLUSIONS: The trial was stopped because of the increased mortality in patients with cancer of the cervix, bladder, or rectum treated with neutrons.

Advances in treatment planning dosimetry for a high energy neutron beam.

Before starting the clinical programme, a series of physical measurements were made using the Clatterbridge high energy neutron facility. These consisted of measurements made under standard conditions, e.g. with square fields, full scatter conditions and perpendicular beam incidence. Further measurements have now been performed to include various clinically relevant non-standard conditions. These included the effects of field shape, backscatter, oblique incidence, bolus and beam blocking on dose distributions.

A comparison of two methods of in vivo dosimetry for a high energy neutron beam.

Two methods of in vivo dosimetry have been compared in a high energy neutron beam. These were activation dosimetry and thermoluminescence dosimetry (TLD). Their suitability was determined by comparison with estimates of total dose, obtained using a tissue equivalent ionization chamber. Measurements were made on the central axis and a profile of a 10 x 10 cm square field and also behind a shielding block in order to simulate conditions of clinical use. The TLD system was found to provide the best estimate of total dose.

Neutron dosimetry intercomparisons between National Accelerator Centre, Université Catholique de Louvain and Clatterbridge Hospital.

Neutron dosimetry intercomparison studies have been undertaken at three neutron therapy facilities which have similar beam characteristics; viz. National Accelerator Centre, South Africa [p(66 MeV)+Be], Université Catholique de Louvain, Belgium, [p(65 MeV)+Be] and MRC Cyclotron Unit, Clatterbridge Hospital, U. K. [p(62 MeV)+Be]. The procedures followed at all centres were the same: tissue equivalent (TE) ionization chambers were first calibrated in 60Co beams and then exposed under various conditions in the respective neutron therapy beams. Measurements were made with the chambers flushed with TE gas or filled with static air. The neutron beam measurements differed by a maximum of 2.4%, whereas if only one particular type of ionization chamber is considered the spread in values is reduced to +/- 0.5%. The TE gas/air response ratios are consistent with calculated values. The results obtained are highly satisfactory and confirm that the dosimetry procedures adopted by the participating institutes conform to international standards.

Changes in biological effectiveness of the neutron beam at Clatterbridge (62 MeV p on Be) measured with cells in vitro.

Chinese hamster V79 cells have been used to assess changes in RBE of the p(62)Be neutron beam at the Clatterbridge Hospital with depth in a phantom and with use of a hydrogenous filter. The cells were exposed at depths of 2 and 12 cm and at a depth of 2 cm with a hydrogenous filter. Two groups of experimenters each conducted two experiments. The ratios of relative biological effectiveness (RBE) at a depth of 12 cm to that at 2 cm were found by the two groups to be 0.99 +/- 0.04 and 0.96 +/- 0.02 (standard errors). The effect of a polythene filter 4.5 cm thick was measured at a depth of 2 cm and the ratio of RBE with and without the filter was found by both groups to be 0.99 +/- 0.02. All the experiments suggest that there may be small effects of beam hardening by depth and filtration but these results are in marked contrast with those obtained using an in vivo system.

Changes in relative biological effectiveness with depth of the Clatterbridge neutron therapy beam.

We have measured the biological equivalence of the Clatterbridge neutron therapy beam [p(62)-Be] and the Hammersmith neutron therapy beam [d(16)-Be] using the mouse intestinal crypt assay. The ratio (NDR) of Clatterbridge neutron (n + gamma) dose relative to Hammersmith neutron dose (n + gamma) was found to be 1.2-1.13 over a dose/fraction range of 1.8-9 Gy at 2 cm deep in a Perspex phantom. It is shown that the effectiveness of the Clatterbridge beam was reduced with penetration into the phantom because of hardening of the beam to a maximum reduction of 11% at 12 cm deep in the phantom. The hardening of the beam with depth of penetration will need to be taken into account by clinicians in assessing the tumour dose and tissue tolerance. Relative biological effectiveness values for the Clatterbridge and Hammersmith neutron beams were also measured. All neutron doses for both Hammersmith and Clatterbridge beams are total doses (n + gamma) which comply with the European protocol for neutron dosimetry and include the gamma-ray component of dose.

The Clatterbridge high-energy neutron facility: dosimetry intercomparisons.

Dosimetry intercomparisons have been performed between the Clatterbridge high-energy neutron facility and the following institutions, all employing beams with similar neutron energies: Université Catholique de Louvain, Belgium; University of Washington, Seattle, USA; MD Anderson Hospital, Houston, USA; and Fermi National Accelerator Laboratory, Batavia, USA. The purpose of the intercomparison was to provide a basis for the exchange of dose-response data and to facilitate the involvement of Clatterbridge in collaborative clinical trials. Tissue-equivalent ionization chambers were used by the participants in each intercomparison to compare measurements of total (neutron plus gamma) absorbed dose in the host institution's neutron beam, following calibration of the chambers in a reference photon beam. The effects of differences in exposure standards, chamber responses in the neutron beams and protocol-dependent dosimetry factors were all investigated. It was concluded that the overall difference in the measurement of absorbed dose relative to that determined by the Clatterbridge group was less than 2%.

The Clatterbridge high-energy neutron therapy facility: specification and performance.

A new high-energy neutron therapy facility has been installed at the Douglas Cyclotron Centre, Clatterbridge Hospital, Merseyside, in order to extend the clinical trials of fast neutrons initiated by the Medical Research Council. The neutron beam is produced by bombarding a beryllium target with 62 MeV protons. The target is isocentrically mounted with the potential for 360 degrees rotation and has a fully variable collimator. This gives a range of rectilinear field sizes from 5 cm x 5 cm to 30 cm x 30 cm. Basic neutron beam data including output, field flatness, penumbra and depth-dose data have been measured. For a 10 cm x 10 cm field, the 50% depth dose occurs at 16.2 cm in water and the output is 1.63 cGy microA-1 min-1 at the depth of dose maximum. The effectiveness of the target shielding and the neutron-induced radioactivity in the treatment head have also been measured. It is concluded that the equipment meets both the design specifications and also fully satisfies criticisms of earlier neutron therapy equipment. A full radiation survey of the centre was also carried out and it was found that radiation levels are low and present no significant hazard to staff.

The Clatterbridge high-energy neutron therapy facility: measurements of beam parameters for clinical use.

Measurements have been performed on the 62 MeV proton cyclotron at the Douglas Cyclotron Centre, Clatterbridge Hospital, to determine the variation in beam parameters necessary for clinical use of the neutron therapy facility. These measurements are of total (neutron and gamma) doses, and include: depth doses for wedged and unwedged fields at various treatment distances; profile measurements and the production of associated isodose charts; calibration of the dosimetry system of the cyclotron; and determination of variations in calibration associated with changes in field size, wedge and focus-skin distance. Measurements have also been performed to estimate the degree of long-term stability of both calibration and field uniformity.