A. Nisbet

Risk of Ischemic Heart Disease in Women after Radiotherapy for Breast Cancer

BACKGROUND Radiotherapy for breast cancer often involves some incidental exposure of the heart to ionizing radiation. The effect of this exposure on the subsequent risk of ischemic heart disease is uncertain. METHODS We conducted a population-based case-control study of major coronary events (i.e., myocardial infarction, coronary revascularization, or death from ischemic heart disease) in 2168 women who underwent radiotherapy for breast cancer between 1958 and 2001 in Sweden and Denmark; the study included 963 women with major coronary events and 1205 controls. Individual patient information was obtained from hospital records. For each woman, the mean radiation doses to the whole heart and to the left anterior descending coronary artery were estimated from her radiotherapy chart. RESULTS The overall average of the mean doses to the whole heart was 4.9 Gy (range, 0.03 to 27.72). Rates of major coronary events increased linearly with the mean dose to the heart by 7.4% per gray (95% confidence interval, 2.9 to 14.5; P<0.001), with no apparent threshold. The increase started within the first 5 years after radiotherapy and continued into the third decade after radiotherapy. The proportional increase in the rate of major coronary events per gray was similar in women with and women without cardiac risk factors at the time of radiotherapy. CONCLUSIONS Exposure of the heart to ionizing radiation during radiotherapy for breast cancer increases the subsequent rate of ischemic heart disease. The increase is proportional to the mean dose to the heart, begins within a few years after exposure, and continues for at least 20 years. Women with preexisting cardiac risk factors have greater absolute increases in risk from radiotherapy than other women. (Funded by Cancer Research UK and others.).

Volumetric modulated arc therapy: a review of current literature and clinical use in practice

Volumetric modulated arc therapy (VMAT) is a novel radiation technique, which can achieve highly conformal dose distributions with improved target volume coverage and sparing of normal tissues compared with conventional radiotherapy techniques. VMAT also has the potential to offer additional advantages, such as reduced treatment delivery time compared with conventional static field intensity modulated radiotherapy (IMRT). The clinical worldwide use of VMAT is increasing significantly. Currently the majority of published data on VMAT are limited to planning and feasibility studies, although there is emerging clinical outcome data in several tumour sites. This article aims to discuss the current use of VMAT techniques in practice and review the available data from planning and clinical outcome studies in various tumour sites including prostate, pelvis (lower gastrointestinal, gynaecological), head and neck, thoracic, central nervous system, breast and other tumour sites.

CARDIAC DOSE FROM TANGENTIAL BREAST CANCER RADIOTHERAPY IN THE YEAR 2006

PURPOSE To quantify the radiation doses received by the heart and coronary arteries from contemporary tangential breast or chest wall radiotherapy. METHODS AND MATERIALS Fifty consecutive patients with left-sided breast cancer and 5 consecutive patients with right-sided breast cancer treated at a large United Kingdom radiotherapy center during the year 2006 were selected. All patients were irradiated with 6- or 8-MV tangential beams to the breast or chest wall. For each dose plan, dose-volume histograms for the heart and left anterior descending (LAD) coronary artery were calculated. For 5 of the left-sided and all 5 right-sided patients, dose-volume histograms for the right and circumflex coronary arteries were also calculated. Detailed spatial assessment of dose to the LAD coronary artery was performed for 3 left-sided patients. RESULTS For the 50 patients given left-sided irradiation, the average mean (SD) dose was 2.3 (0.7) Gy to the heart and 7.6 (4.5) Gy to the LAD coronary artery, with the distal LAD receiving the highest doses. The right and circumflex coronary arteries received approximately 2 Gy mean dose. Part of the heart received >20 Gy in 22 left-sided patients (44%). For the 5 patients given right-sided irradiation, average mean doses to all cardiac structures were in the range 1.2 to 2 Gy. CONCLUSIONS Heart dose from left-tangential radiotherapy has decreased considerably over the past 40 years, but part of the heart still receives >20 Gy for approximately half of left-sided patients. Cardiac dose for right-sided patients was generally from scattered irradiation alone.

Cardiac doses from Swedish breast cancer radiotherapy since the 1950s.

PURPOSE To estimate cardiac doses from breast cancer radiotherapy in Sweden from the 1950s to the 1990s. These doses will contribute to deriving dose-response relationships for the risk of radiation-induced heart disease. MATERIALS AND METHODS The Swedish nationwide cancer register was used to identify women irradiated for breast cancer in the Stockholm area. Virtual simulation, computed tomography planning, and manual planning were used to reconstruct radiotherapy regimens. Estimates of heart and coronary artery dose were derived for each woman. RESULTS Cardiac doses were assessed in 358 women. Mean heart dose varied from <0.1 to 23.6 Gy and mean left anterior descending coronary artery dose varied from 0.1 to 46.3 Gy. Mean heart doses averaged across women irradiated in each decade for left-sided and right-sided breast cancers, respectively, were 5.1 and 1.8 Gy in the 1950s, 10.5 and 4.7 Gy in the 1970s and 3.0 and 1.9 Gy in the 1990s. CONCLUSIONS Cardiac doses from Swedish breast cancer radiotherapy increased from the 1950s to the 1970s, and then reduced substantially in the 1980s and 1990s. The wide range of doses observed should provide substantial statistical power for the estimation of dose-response relationships for radiation-induced heart disease.

Cardiac dose estimates from Danish and Swedish breast cancer radiotherapy during 1977–2001

Background and purpose To estimate target and cardiac doses from breast cancer radiotherapy in Denmark and in the Stockholm and Umeå areas of Sweden during 1977–2001. Methods Representative samples of irradiated women were identified from the databases of the Danish Breast Cancer Cooperative Group and the Swedish Nationwide Cancer Registry. Virtual simulation, computed tomography planning and manual planning were used to reconstruct radiotherapy regimens on a typical woman. Estimates of target dose and various measures of cardiac dose were derived from individual radiotherapy charts. Results Doses were estimated in 681 Danish and 130 Swedish women. Mean heart dose for individual women varied from 1.6 to 14.9 Gray in Denmark and from 1.2 to 22.1 Gray in Sweden. In Denmark, mean target doses averaged across women increased from 40.6 to 53.8 Gray during 1977–2001 but, despite this, mean heart dose averaged across women remained around 6 Gy for left-sided and 2–3 Gray for right-sided radiotherapy. In Sweden mean target dose averaged across women increased from 38.7 to 46.6 Gray during 1977–2001, while mean heart dose averaged across women decreased from 12.0 to 7.3 Gray for left-sided and from 3.6 to 3.2 Gray for right-sided radiotherapy. Temporal trends for mean biologically effective dose [BED] to the heart, mean dose to the left anterior descending coronary artery, the right coronary artery and the circumflex coronary artery were broadly similar. Conclusions Cardiac doses in Denmark were low relative to those in Sweden. In both countries, target dose increased during 1977–2001. Despite this, cardiac doses remained constant in Denmark and decreased in Sweden.

The IPEM code of practice for electron dosimetry for radiotherapy beams of initial energy from 4 to 25 MeV based on an absorbed dose to water calibration

This report contains the recommendations of the Electron Dosimetry Working Party of the UK Institute of Physics and Engineering in Medicine (IPEM). The recommendations consist of a code of practice for electron dosimetry for radiotherapy beams of initial energy from 4 to 25 MeV. The code is based on the absorbed dose to water calibration service for electron beams provided by the UK standards laboratory, the National Physical Laboratory (NPL). This supplies direct N(D,w) calibration factors, traceable to a calorimetric primary standard, at specified reference depths over a range of electron energies up to approximately 20 MeV. Electron beam quality is specified in terms of R(50,D), the depth in water along the beam central axis at which the dose is 50% of the maximum. The reference depth for any given beam at the NPL for chamber calibration and also for measurements for calibration of clinical beams is 0.6R(50.D) - 0.1 cm in water. Designated chambers are graphite-walled Farmer-type cylindrical chambers and the NACP- and Roos-type parallel-plate chambers. The practical code provides methods to determine the absorbed dose to water under reference conditions and also guidance on methods to transfer this dose to non-reference points and to other irradiation conditions. It also gives procedures and data for extending up to higher energies above the range where direct calibration factors are currently available. The practical procedures are supplemented by comprehensive appendices giving discussion of the background to the formalism and the sources and values of any data required. The electron dosimetry code improves consistency with the similar UK approach to megavoltage photon dosimetry, in use since 1990. It provides reduced uncertainties, approaching 1% standard uncertainty in optimal conditions, and a simpler formalism than previous air kerma calibration based recommendations for electron dosimetry.

A comparison of the gamma index analysis in various commercial IMRT/VMAT QA systems.

PURPOSE To investigate the variability of the global gamma index (γ) analysis in various commercial IMRT/VMAT QA systems and to assess the impact of measurement with low resolution detector arrays on γ. MATERIALS Five commercial QA systems (PTW 2D-Array, Scandidos Delta4, SunNuclear ArcCHECK, Varian EPID, and Gafchromic EBT2 film) were investigated. The response of γ analysis to deliberately introduced errors in pelvis and head & neck IMRT and RapidArc™ plans was evaluated in each system. A theoretical γ was calculated in each commercial QA system software (PTW Verisoft, Delta4 software, SNC Patient, Varian Portal Dosimetry and IBA OmniPro, respectively), using treatment planning system resolution virtual measurements and compared to an independent calculation. Error-induced plans were measured on a linear accelerator and were evaluated against the error-free dose distribution calculated using Varian Eclipse™ in the relevant phantom CT scan. In all cases, global γ was used with a 20% threshold relative to a point selected in a high dose and low gradient region. The γ based on measurement was compared against the theoretical to evaluate the response of each system. RESULTS There was statistically good agreement between the predicted γ based on the virtual measurements from each software (concordance correlation coefficient, ρc>0.92) relative to the independent prediction in all cases. For the actual measured data, the agreement with the predicted γ reduces with tightening passing criteria and the variability between the different systems increases. This indicates that the detector array configuration and resolution have greater impact on the experimental calculation of γ due to under-sampling of the dose distribution, blurring effects, noise, or a combination. CONCLUSIONS It is important to understand the response and limitations of the gamma index analysis combined with the equipment in use. For the same pass-rate criteria, different devices and software combinations exhibit varying levels of agreement with the predicted γ analysis.

Review of doped silica glass optical fibre: Their TL properties and potential applications in radiation therapy dosimetry

Review is made of dosimetric studies of Ge-doped SiO(2) telecommunication fibre as a 1-D thermoluminescence (TL) system for therapeutic applications. To-date, the response of these fibres has been investigated for UV sources, superficial X-ray beam therapy facilities, a synchrotron microbeam facility, electron linear accelerators, protons, neutrons and alpha particles, covering the energy range from a few eV to several MeV. Dosimetric characteristics include, reproducibility, fading, dose response, reciprocity between TL yield and dose-rate and energy dependence. The fibres produce a flat response to fixed photon and electron doses to within better than 3% of the mean TL distribution. Irradiated Ge-doped SiO(2) optical fibres show limited signal fading, with an average loss of TL signal of ~0.4% per day. In terms of dose response, Ge-doped SiO(2) optical fibres have been shown to provide linearity to x and electron doses, from a fraction of 1 Gy up to 2 kGy. The dosimeters have also been used in measuring photoelectron generation from iodinated contrast media; TL yields being some 60% greater in the presence of iodine than in its absence. The review is accompanied by previously unpublished data.

A dosimetric intercomparison of electron beams in UK radiotherapy centres.

A dosimetry intercomparison has been carried out for all 52 radiotherapy centres in the UK which possess electron treatment facilities. The intercomparison was carried out on one treatment unit in each centre and for three energies across the range of available energies. The position of the depth of maximum dose for a standard field size was independently determined and a subsequent beam calibration made. The factor to convert the reading on a calibrated ionization chamber to absorbed dose in an electron beam is energy dependent, and hence to carry out an independent calibration measurement also requires the beam energy to be determined. In addition a quantitative measure of the difference in the calibration chains between the intercomparison equipment and the host departments field instrument was carried out. In order to provide a follow-up to the initial IPSM national photon intercomparison, a photon beam calibration was measured in one photon beam in each centre. For 156 electron beam measurements, a mean ratio of intercomparison measured dose to locally measured dose of 0.994 was obtained with a standard deviation of 1.8%. For the 52 photon beam measurements, a mean ratio of intercomparison measured dose to locally measured dose of 1.003 was obtained with a standard deviation of 1.0%.

Viscosity changes in hyaluronic acid: irradiation and rheological studies.

Hyaluronic acid (HA) is a significant component of the extracellular matrix (ECM), particular interest being shown herein in synovial fluid. The present study aims to investigate the degrading effects of X-ray radiation on HA at radiotherapy doses. Measurements of viscosity and shear stresses on HA solutions have been made at different shear rates using various types of viscometer for different concentrations in the range 0.01-1% w/v of HA. The HA has been subjected to doses of 6 MV photon radiation ranging from 0 to 20 Gy, the major emphasis being on doses below 5 Gy. It is found that there is a dose-dependent relationship between viscosity and shear rate, viscosity reducing with radiation dose, this being related to polymer scissions via the action of radiation-induced free radicals. The dependency appears to become weaker at higher concentrations, possibly due to the contribution to viscosity from polymer entanglement becoming dominant over that from mean molecular weight. Present results, for HA solutions in the concentration range 0.01% to 1% w/v, show reduced viscosity with dose over the range 0-4 Gy, the latter covering the dose regime of interest in fractionated radiotherapy. The work also shows agreement with previous Raman microspectrometry findings by others, the possible bond alterations being defined by comparison with available published data.