British Journal of Radiology (2004) 77, 137-142
© 2004 British Institute of Radiology
doi: 10.1259/bjr/11764177
Irradiation of the heart during tangential breast treatment: a study within the START trial
K Venables, MSc, MIPEM1,
E A Miles, BSc, DCR(T)1,
A Deighton, BSc, DCR(T)1,
E G A Aird, PhD, FIPEM2 and
P J Hoskin, FCRP, FRCR1 on behalf of the START trial management group
1 Marie Curie Research Wing and 2 Physics Department, Mount Vernon Hospital, Northwood, Middlesex HA6 2RN, UK
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Abstract
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Radiotherapy to the breast is often given as a component of the treatment for women with breast cancer. It has been shown to increase overall survival although an increase in cardiac mortality has also been noted. This study was undertaken as part of the START trial quality assurance programme to record and evaluate the cardiac dose using modern radiotherapy techniques. Departments randomizing patients into the START trial and who had CT facilities for planning breast patients were invited to take part. 62 patients were included. CT slices were taken at the level of the maximum heart depth and on the treatment field central axis. Each patient was planned in the normal way and the distributions were analysed by the quality assurance team at Mount Vernon Hospital. The maximum heart position was found to be inferior to the central axis used for breast planning for the majority of patients; mean position 2.3 cm inferior with a mean maximum heart depth of 0.55 cm. For 45% of patients the maximum heart dose was less than 50% of the prescribed dose. The study showed that the volume of irradiated cardiac tissue has decreased compared with earlier studies, and also highlighted the need to scan away from the central axis if the dose to cardiac tissue is to be assessed.
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Introduction
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Many patients with breast cancer will receive radiotherapy to the breast or chest wall as part of their treatment. Radiotherapy is associated with improved local control and more recently has been shown to improve survival [1, 2]. It is known from studies of mediastinal tumours in Hodgkin's disease that irradiation of the heart is associated with an increased risk of cardiac mortality [3]. Radiation to the heart can contribute to an increase in patient morbidity. Some early trials show an increased risk of myocardial infarction in patients receiving breast radiotherapy [4–9]. More recent studies [10–14] have found no evidence of increased cardiac mortality. The most recent overview by the Early Breast Cancer Trialist's Collaborative Group highlights a significant risk of cardiac mortality among certain groups of patients [15]. There are two possible explanations for this discrepancy:- there may be a threshold dose for inducing myocardial infarction, a value of 30 Gy has been suggested [16, 17]
- myocardial infarction may not present until the second decade after radiotherapy. This may explain the absence of cardiac events in the more recent papers [5, 9]
Modern radiotherapy techniques in the UK have tended to reduce the amount of lung and therefore the amount of heart irradiated compared with older techniques. The literature largely reports on non-current radiotherapy treatment techniques and equipment and the majority of data collected is retrospective. A prospective study to record the dose to cardiac tissue within a clinical trial setting was therefore felt to be necessary. The START trial is a multicentre trial comparing different fractionation schemes to the breast [18]. The trial has had a quality assurance team from the outset that has visited departments and documented techniques. This trial provided an opportunity for the dose to the heart and the irradiated volume of heart to be assessed in a clinical trial setting. Multiregional ethics committee approval was obtained for this substudy, which required one further CT slice in addition to those slices routinely acquired.
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Methods
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All patients were treated according to the START trial B protocol and thus received a prescribed dose at the START trial reference point in the centre of the breast of either 40 Gy in 15 fractions over 3 weeks or 50 Gy in 25 fractions over 5 weeks. All patients were treated with tangential fields using appropriate wedges. The medial field border was defined as the patient midline. Patients requiring treatment to the internal mammary chain (IMC) nodes were excluded from the trial. For patients in the cardiac study no additional cardiac shielding was used. Patients requiring radiotherapy to the left breast in departments where CT scanning to produce patient outlines was routine were eligible. In keeping with the As Low As Reasonably Achievable (ALARA) principle and to minimize the additional time required, particularly for departments with simulator-CT, it was decided to limit the number of slices requested for each patient to two. One slice at the level of the maximum heart (determined either using fluoroscopy or from a scannogram depending on the equipment) and the other the treatment field central axis. Each patient was planned according to the START trial protocol and at least the 50% and 90% isodose levels were displayed to enable analysis of the dose to the heart to be performed. Isodose distributions on these two slices were sent to the quality assurance team for analysis.
The following data were collected from each plan (2 slices):
- total area of heart
- area irradiated to doses of 50% and 90%
- area irradiated to additional dose levels if these were shown
- maximum lung depth (measured to the 50% isodose)
- maximum heart depth (measured to the 50% isodose)
- size, position and energy of the boost with an estimate of the maximum and minimum distances to the heart where applicable
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Results
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A total of 62 patients were entered into the study from five centres. 58 patients had received breast-conserving surgery; the remaining 4 had undergone a mastectomy.
A brief description of the techniques used is given in Table 1
. The mean position for the maximum heart depth was 2.3 cm inferior to the central axis with a range of 8 cm inferior to 5 cm superior as shown in Figure 1. No significant differences were found between the departments using different techniques, however there was a trend for the maximum heart to appear more inferior to the central axis in centre A than in the other centres.
The mean maximum heart depth was 0.55 cm with a standard deviation of 0.55. There was no apparent difference between mastectomy and lumpectomy patients, though the sample size for mastectomy patients was very small. The maximum heart depths for each of the patients are shown in Figure 2. The area of heart receiving 50% and 90% of the prescribed dose is shown in Figure 3. The mean heart area on the central axis slice irradiated to >50% of the prescribed dose was 0.7 cm2 (range 0 to 7 cm2). In 39 of the 62 patients no significant dose greater than 50% of the prescribed dose was seen in cardiac tissue on the central axis slice (significant dose was defined as an area >2 cm2 in line with ICRU 29 [19]). The corresponding figures for the 90% isodose were mean irradiated area 0.28 cm2 (range 0 to 4 cm2) with 50 of the 62 patients having no significant area receiving greater than 90% of the prescribed dose on the central slice. Figure 4 shows a dose–area histogram for the maximum heart slice. In this graph the irradiated area has been divided by the approximate area of the heart on that slice to give a percentage irradiated.
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Figure 2. Maximum heart depth, measured from the 50% isodose to the maximum intrusion of the heart into the radiotherapy field.
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Figure 4. Dose–area histograms for patients in the START Cardiac study, calculated for the maximum heart slice. Each line represents the upper bound of the histogram for a single patient.
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There was a weak correlation between the maximum lung depth (taken as the maximum lung depth on either the maximum cardiac slice or the central axis slice) and the maximum heart depth (measured from the maximum cardiac slice). This is shown in Figure 5 (r=0.37), the 95% confidence interval for the correlation coefficient was wide (0.13 to 0.57).
Of the patients who had breast conserving surgery, 41 received a boost to the tumour bed, 40 given with electrons energies ranging from 6 MeV to 18 MeV (mode 10 MeV), 1 was given using orthovoltage, energy 250 kV. Two patients had a boost where the electron energy was such that there may have been a small contribution in dose to the surface of the heart. In both these cases the depth of the heart below the skin surface was less than 3 cm.
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Discussion
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In the current study, 22 (35%) of the patients did not have any heart receiving greater than 50% of the prescribed dose and a further 17 had less than 2 cm2. For many patients the heart was excluded from the radiation field. It is difficult to quantify doses outside of the radiation field as they rely on the planning system accuracy. The audit visits for the START trial showed that doses outside the field could be inaccurate by up to a factor of 2, thus it is difficult to compare the low dose areas between departments. This is in contrast to the paper by Fuller [6], where all patients received doses in excess of 40 Gy to the left anterior descending artery, indicating that at least part of the heart must have been included in the radiation field. Janjan et al [20] also investigated cardiac doses for a typical patient and found doses in excess of 45 Gy to the left ventricle. Current practice in the UK has moved to minimize the volume of both the heart and the lung included in tangential breast fields, by changing the position of the medial or lateral border. Although Fuller used modern techniques, the position of the field borders were such that larger volumes of heart and lung were included. Three similar studies were found in the literature, two of these were for small cohorts of patients, 26 patients (Canney) and Fuller (14 patients in each of 2 subgroups) [6, 21]. The third study of 100 patients [22] was performed in Sweden, the medial border of the tangential fields appeared to be further across the midline than is common in the UK although there was no attempt to cover the internal mammary lymph nodes. This would lead to a different irradiated heart volume. The introduction of wide bore CT scanners and 3D planning methods has allowed the inclusion of cardiac tissue in breast radiotherapy treatment to be assessed both in terms of the volume included in the treatment field and the dose to which it is exposed.
Canney et al investigated the amount of heart irradiated for two different patient positions [21]. He found a reduction in the amount of heart in the field when the patients were treated on a breast board with the ipsilateral arm above the head, compared with the arm at 90°. The trend for patients in centre A to have the maximum heart positioned further from the central axis may reflect the fact that the arm position used at this centre is above the head rather than at right angles to the patient. This centre routinely took five CT slices spaced evenly throughout the volume. One of these slices may have been used to define the maximum heart rather than taking an additional slice.
The position of the maximum heart intrusion into the radiotherapy field was found to be inferior to the central axis in the majority of cases. Thus it may appear to be outside the treatment field when only the central axis slice is viewed. The area of heart irradiated and the location of the maximum intrusion into the radiotherapy field will depend on a number of factors including the patient's anatomy, the treatment position (flat or on an angled board and arms above head or at right angles to the body) and the position of the field borders. Traditionally the whole of the excision scar has been included in the planning target volume (PTV) for mastectomy patients. In some cases this has led to the lateral border being placed more posteriorly. This was not seen in the small cohort of patients in this study which suggests either that excision scars were smaller, or that the whole of the scar was not included in the PTV. The area of irradiated cardiac tissue in all patients in this study was small.
To determine accurately the radiation dose to the heart, a full set of CT scans of the patient would need to be performed. This was not felt to be appropriate in the current study for the reasons stated earlier. The area of heart irradiated was closely correlated with the maximum heart depth (correlation coefficient 0.94). Maximum heart depth has previously been shown by Hurkmans et al to be correlated with irradiated heart volume [23].
Figure 6 suggests that there may be differences between departments in the proportion of patients where the heart is excluded from the radiation field. It is not known whether this is due to patient positioning or re-assessment of field borders.
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Figure 6. Area of heart irradiated at different centres. At centre D, a larger proportion of patients have greater than 2 cm in the heart than at the other centres.
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The weak correlation between heart and lung depth is in agreement with the work by Das et al [24] who also found a weak correlation.
Hurkmans et al [23] suggested there was a rapidly increasing normal tissue complication probability (NTCP) with maximum heart depths of above 2 cm. No patient in this study had more than 2 cm heart in the treatment field and the majority had less than 1 cm, which would correspond to a normal tissue complication probability of less than 1%. All departments positioned the patients on an inclined plane using either breast boards or a foam wedge.
A threshold dose of 30 Gy for cardiac effects has been suggested [15, 17]. 20 of the 62 patients received doses in excess of this to an area greater than 2 cm2. For the patients in this study only small volumes of the heart were irradiated to doses in excess of this value, corresponding to a small increased risk. Of the 20 patients 7 had maximum heart depths of less than 1 cm, only 4 had maximum heart depths between 1.5 cm and 2 cm corresponding to an NTCP of between 1% and 2% according to Hurkmans.
The size of the study was limited by the number of centres with CT facilities who were able to put patients into the trial. All centres participating were in trial B that closed to recruitment in October 2001. The cause of death is collected within the main START trial and thus cardiac mortality data will be available in time, however, the study was not powered to investigate associations between cardiac mortality and dose of radiotherapy to the heart or volume of heart irradiated.
For patients who are though to be at a high risk of cardiac mortality, including those on anthracycline chemotherapy regimens, even the low doses described in this study may be unacceptable. For these patients a number of options are emerging which further reduce the dose to the heart including:
- inserting a small shielding block into the tangential field
- intensity-modulated radiotherapy [25]
- breathing control in which patients hold their breath for periods of 15 s to 20 s. In some patients this has been found to exclude the heart from the field [26, 27]
Only the first of these options is currently widely available in the UK. The data collected in this study indicate that only a minority of patients will benefit from these techniques.
It is not known whether the cardiac mortality is due to irradiation of the cardiac tissue itself, or whether the dose to the main coronary arteries is more important. McEniery [28] found a narrowing of the left main coronary artery in patients with angiographically proven coronary artery disease following chest irradiation. In these patients the mean dose was 42±7 Gy. No attempt was made to assess the dose to the arteries in this study.
The majority of patients in the study were from four centres. The techniques used at these centres are widely used throughout the UK but may not reflect clinical practice in all centres. This study did not record adjustment of field borders in cases where the clinician would want to minimize the amount of lung and cardiac tissue in the radiation field.
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Conclusion
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The introduction of wide bore CT scanners and CT simulators has allowed the extent of inclusion of cardiac tissue in breast radiotherapy to be assessed. This study has demonstrated that the dose to cardiac tissue using modern techniques is generally low with only small areas of the heart receiving doses in excess of 50% of the prescribed dose.
To estimate the maximum dose to the heart, departments who have the facilities may wish to consider taking an extra slice at the position of the maximum heart inclusion in the tangential fields in order to document the dose to this organ.
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Acknowledgments
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We are grateful to the staff at the following hospitals for putting patients into this study: Mount Vernon Centre for Cancer treatment, Northwood; North Staffordshire Royal Infirmary, Stoke; Oldchurch Hospital, Romford; Southend Hospital, Essex; Weston Park Hospital, Sheffield.
On behalf of the START trial management group: Edwin Aird, Jane Barrett, Peter Barrett-Lee, Judith Bliss, Jackie Brown, John Dewar, Jane Dobbs, Jo Haviland, Penny Hopwood, Peter Hoskin, Pat Lawton, Brian Magee, Judith Mills, David Morgan, Roger Owen, Eileen Parkin (RAGE Observer), Joyce Pritchard (RAGE Observer), Val Speechely, David Spooner, Mark Sydenham, Karen Venables, Elizabeth Winfield, John Yarnold.
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Footnotes
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The START Trial is funded jointly by the Medical Research Council, the Cancer Research Campaign and the UK Department of Health. It was developed under the auspices of the UKCCCR Breast Cancer Subcommittee. 
Received for publication January 27, 2003.
Accepted for publication August 29, 2003.
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References
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Abstract
Introduction
