Exposure of the heart and cardiac valves in women irradiated for breast cancer 1970-2009.

Purpose: To describe cardiac exposure from breast cancer radiotherapy regimens used during 1970-2009 for the development of dose-response relationships and to consider the associated radiation-risks using existing dose-response relationships. Material and methods: Radiotherapy charts for 771 women in the Netherlands selected for case control studies of heart disease after breast cancer radiotherapy were used to reconstruct 44 regimens on a typical CT-dataset. Doses were estimated for the whole heart (WH), left ventricle (LV) and cardiac valves. Results: For breast/chest wall radiotherapy average WH doses decreased during 1970-2009. For internal mammary chain (IMC) radiotherapy WH doses were highest during the 1980s and 1990s when direct anterior fields were used and reduced in the 2000s when oblique fields were introduced. Average doses varied substantially for IMC regimens (WH 2-33 Gy, LV < 1-23 Gy). For cardiac valves, at least one valve received >30 Gy from most regimens. Conclusions: Radiation-risks of IHD from breast/chest wall regimens likely reduced during 1970-2009. Direct anterior IMC regimens likely increased the risks of IHD and VHD over this time period but the use of oblique IMC fields from 2003 may have lowered these risks. These data provide a unique opportunity to develop dose-response relationships.

Adjuvant and neoadjuvant breast cancer treatments: A systematic review of their effects on mortality.

BACKGROUND: Adjuvant and neoadjuvant breast cancer treatments can reduce breast cancer mortality but may increase mortality from other causes. Information regarding treatment benefits and risks is scattered widely through the literature. To inform clinical practice we collated and reviewed the highest quality evidence. METHODS: Guidelines were searched to identify adjuvant or neoadjuvant treatment options recommended in early invasive breast cancer. For each option, systematic literature searches identified the highest-ranking evidence. For radiotherapy risks, searches for dose-response relationships and modern organ doses were also undertaken. RESULTS: Treatment options recommended in the USA and elsewhere included chemotherapy (anthracycline, taxane, platinum, capecitabine), anti-human epidermal growth factor 2 therapy (trastuzumab, pertuzumab, trastuzumab emtansine, neratinib), endocrine therapy (tamoxifen, aromatase inhibitor, ovarian ablation/suppression) and bisphosphonates. Radiotherapy options were after breast conserving surgery (whole breast, partial breast, tumour bed boost, regional nodes) and after mastectomy (chest wall, regional nodes). Treatment options were supported by randomised evidence, including > 10,000 women for eight treatment comparisons, 1,000-10,000 for fifteen and < 1,000 for one. Most treatment comparisons reduced breast cancer mortality or recurrence by 10-25%, with no increase in non-breast-cancer death. Anthracycline chemotherapy and radiotherapy increased overall non-breast-cancer mortality. Anthracycline risk was from heart disease and leukaemia. Radiation-risks were mainly from heart disease, lung cancer and oesophageal cancer, and increased with increasing heart, lung and oesophagus radiation doses respectively. Taxanes increased leukaemia risk. CONCLUSIONS: These benefits and risks inform treatment decisions for individuals and recommendations for groups of women.

Exposure of the oesophagus in breast cancer radiotherapy: A systematic review of oesophagus doses published 2010-2020.

BACKGROUND AND PURPOSE: Breast cancer radiotherapy can increase the risk of subsequent primary oesophageal cancer, with risk increasing according to oesophagus radiation dose. We describe oesophagus exposure from modern breast cancer regimens and discuss the risks of oesophageal cancer for women irradiated recently. MATERIALS AND METHODS: A systematic review was undertaken of oesophagus doses from breast cancer radiotherapy regimens published during 2010-2020. Mean and maximum oesophagus doses were described for different target regions irradiated and different radiotherapy techniques. RESULTS: In 112 published regimens from 18 countries, oesophagus doses varied with target region. For partial breast irradiation, average mean oesophagus dose was 0.2 Gy (range 0.1-0.4) in four regimens; maximum dose was not reported. For breast or chest wall radiotherapy, average oesophagus doses were mean 1.8 Gy (range 0.1-10.4) in 24 regimens and maximum 6.7 Gy (range 0.4-14.3) in seven regimens. For radiotherapy including a nodal region, average oesophagus doses were higher: mean 11.4 Gy (range <0.1-29.3) in 61 regimens and maximum 34.4 Gy (range 3.4-51.3) in 55 regimens. Average mean oesophagus doses were >10 Gy for intensity modulated nodal radiotherapy, but lower for other node techniques. CONCLUSIONS: Mean oesophagus doses from partial breast and breast/chest wall regimens were usually less than 2 Gy, hence radiation-risks will be very small. However, for radiotherapy including lymph nodes, average mean oesophagus dose of 11.4 Gy may nearly double oesophageal cancer risk. Consideration of oesophageal exposure during nodal radiotherapy planning may reduce the risks of radiation-related oesophageal cancer for women irradiated today.

Cardiac mortality after radiotherapy, chemotherapy and endocrine therapy for breast cancer: Cohort study of 2 million women from 57 cancer registries in 22 countries.

Comparisons of patients receiving different cancer treatments reflect the effects of both treatment and patient selection. In breast cancer, however, if radiotherapy decisions are unrelated to laterality, comparisons of left-sided and right-sided cancers can demonstrate the causal effects of higher-versus-lower cardiac radiation dose. Cardiac mortality was analysed using individual patient data for 1,934,248 women with breast cancer in 22 countries. The median date of diagnosis was 1996 and the interquartile range was 1987-2002. A total of 1,018,505 women were recorded as irradiated, 223,077 as receiving chemotherapy, 317,619 as receiving endocrine therapy and 55,264 died of cardiac disease. Analyses were stratified by time since breast cancer diagnosis, age at diagnosis, calendar year of diagnosis and country. Patient-selection effects were evident for all three treatments. For radiotherapy, there was also evidence of selection according to laterality in women irradiated 1990 or later. In patients irradiated before 1990, there was no such selection and cardiac mortality was higher in left-sided than right-sided cancer (rate ratio [RR]: 1.13, 95% confidence interval 1.09-1.17). Left-versus-right cardiac mortality RRs were greater among younger women (1.46, 1.19, 1.20, 1.09 and 1.08 after cancer diagnoses at ages <40, 40-49, 50-59, 60-69 and 70+ years, 2ptrend =0.003). Left-versus-right RRs also increased with time since cancer diagnosis (1.03, 1.11, 1.19 and 1.21 during 0-4, 5-14, 15-24 and 25+ years, 2ptrend =0.002) while for women who also received chemotherapy, the left-versus-right RR was 1.42 (95% confidence interval 1.13-1.77), compared to 1.10 (1.05-1.16) for women who did not (2pdifference = 0.03). These results show that the relative increase in cardiac mortality from cardiac exposure during breast cancer radiotherapy given in the past was greater in younger women, lasted into the third decade after exposure and was greater when chemotherapy was also given.

Heart failure after treatment for breast cancer.

BACKGROUND: We aimed to develop dose-response relationships for heart failure (HF) following radiation and anthracyclines in breast cancer treatment, and to assess HF associations with trastuzumab and endocrine therapies. METHODS AND RESULTS: A case-control study was performed within a cohort of breast cancer survivors treated during 1980-2009. Cases (n = 102) had HF as first cardiovascular diagnosis and were matched 1:3 on age and date of diagnosis. Individual cardiac radiation doses were estimated, and anthracycline doses and use of trastuzumab and endocrine therapy were abstracted from oncology notes. For HF cases who received radiotherapy, the estimated median mean heart dose (MHD) was 6.8 Gy [interquartile range (IQR) 0.9-13.7]. MHD was not associated with HF risk overall [excess rate ratio (ERR) = 1%/Gy, 95% confidence interval (CI) -2 to 10]. In patients treated with anthracyclines, exposure of ≥20% of the heart to ≥20 Gy was associated with a rate ratio of 5.7 (95% CI 1.7-21.7) compared to <10% exposed to ≥20 Gy. For cases who received radiotherapy, median cumulative anthracycline dose was 247 mg/m2 (IQR 240-319). A dose-dependent increase was observed after anthracycline without trastuzumab (ERR = 1.5% per mg/m2 , 95% CI 0.5-4.1). After anthracycline and trastuzumab, the rate ratio was 34.9 (95% CI 11.1-110.1) compared to no chemotherapy. CONCLUSIONS: In absence of anthracyclines, breast cancer radiotherapy was not associated with increased HF risk. Strongly elevated HF risks were observed after treatment with anthracyclines and also after treatment with trastuzumab. The benefits of these systemic treatments usually exceed the risks of HF, but our results emphasize the need to support ongoing efforts to evaluate preventative strategies.

Cardiac Structure Doses in Women Irradiated for Breast Cancer in the Past and Their Use in Epidemiological Studies.

PURPOSE: Incidental cardiac exposure during radiation therapy may cause heart disease. Dose-response relationships for cardiac structures (segments) may show which ones are most sensitive to radiation. Radiation-related cardiac injury can take years to develop; thus, studies need to involve women treated using 2-dimensional planning, with segment doses estimated using a typical computed tomography (CT) scan. We assessed whether such segment doses are accurate enough to use in dose-response relationships using the radiation therapy charts of women with known segment injury. We estimated interregimen and interpatient segment dose variability and segment dose correlations. METHODS AND MATERIALS: The radiation therapy charts of 470 women with cardiac segment injury after breast cancer radiation therapy were examined, and 41 regimens were identified. Regimens were reconstructed on a typical CT scan. Doses were estimated for 5 left ventricle (LV) and 10 coronary artery segments. Correlations between cardiac segments were estimated. Interpatient dose variation was assessed in 10 randomly selected CT scans for left regimens and in 5 for right regimens. RESULTS: For the typical CT scan, interregimen segment dose variation was substantial (range, LV segments <1-39 Gy; coronary artery segments <1-48 Gy). In 10 CT scans, interpatient segment dose variation was higher for segments near field borders (range, 3-47 Gy) than other segments (range, <2 Gy). Doses to different left-anterior descending coronary artery (LADCA) segments were highly correlated with each other, as were doses to different LV segments. Also, LADCA segment doses were highly correlated with doses to LV segments usually supplied by the LADCA. For individual regimens there was consistency in hotspot location and segment ranking of higher-versus-lower dose. CONCLUSIONS: The scope for developing quantitative cardiac segment dose-response relationships in patients who had 2-dimensional planning is limited because different segment doses are often highly correlated, and segment-specific dose uncertainties are not independent of each other. However, segment-specific doses may be reliably used to rank segments according to higher-versus-lower doses.

Radiation Dose-Response for Risk of Myocardial Infarction in Breast Cancer Survivors.

PURPOSE: Previous reports suggest that radiation therapy for breast cancer (BC) can cause ischemic heart disease, with the radiation-related risk increasing linearly with mean whole heart dose (MWHD). This study aimed to validate these findings in younger BC patients and to investigate additional risk factors for radiation-related myocardial infarction (MI). METHODS AND MATERIALS: A nested case-control study was conducted within a cohort of BC survivors treated during 1970 to 2009. Cases were 183 patients with MI as their first heart disease after BC. One control per case was selected and matched on age and BC diagnosis date. Information on treatment and cardiovascular risk factors was abstracted from medical and radiation charts. Cardiac doses were estimated for each woman by reconstructing her regimen using modern 3-dimensional computed tomography planning on a typical patient computed tomography scan. RESULTS: Median age at BC of cases and controls was 50.2 years (interquartile range, 45.7-54.7). Median time to MI was 13.6 years (interquartile range, 9.9-18.1). Median MWHD was 8.9 Gy (range, 0.3-35.2 Gy). MI rate increased linearly with increasing MWHD (excess rate ratio [ERR] per Gy, 6.4%; 95% confidence interval, 1.3%-16.0%). Patients receiving ≥20 Gy MWHD had a 3.4-fold (95% confidence interval, 1.5-7.6) higher MI rate than unirradiated patients. ERRs were higher for younger women, with borderline significance (ERR<45years, 24.2%/Gy; ERR≥50years, 2.5%/Gy; Pinteraction = .054). Whole heart dose-volume parameters did not modify the dose-response relationship significantly. CONCLUSIONS: MI rate after radiation for BC increases linearly with MWHD. Reductions in MWHD are expected to contribute to better cardiovascular health of BC survivors.

Cardiovascular disease incidence after internal mammary chain irradiation and anthracycline-based chemotherapy for breast cancer.

BACKGROUND: Improved breast cancer (BC) survival and evidence showing beneficial effects of internal mammary chain (IMC) irradiation underscore the importance of studying late cardiovascular effects of BC treatment. METHODS: We assessed cardiovascular disease (CVD) incidence in 14,645 Dutch BC patients aged <62 years, treated during 1970-2009. Analyses included proportional hazards models and general population comparisons. RESULTS: CVD rate-ratio for left-versus-right breast irradiation without IMC was 1.11 (95% CI 0.93-1.32). Compared to right-sided breast irradiation only, IMC irradiation (interquartile range mean heart doses 9-17 Gy) was associated with increases in CVD rate overall, ischaemic heart disease (IHD), heart failure (HF) and valvular heart disease (hazard ratios (HRs): 1.6-2.4). IHD risk remained increased until at least 20 years after treatment. Anthracycline-based chemotherapy was associated with an increased HF rate (HR = 4.18, 95% CI 3.07-5.69), emerging <5 years and remaining increased at least 10-15 years after treatment. IMC irradiation combined with anthracycline-based chemotherapy was associated with substantially increased HF rate (HR = 9.23 95% CI 6.01-14.18), compared to neither IMC irradiation nor anthracycline-based chemotherapy. CONCLUSIONS: Women treated with anthracycline-based chemotherapy and IMC irradiation (in an older era) with considerable mean heart dose exposure have substantially increased incidence of several CVDs. Screening may be appropriate for some BC patient groups.

Exposure of the lungs in breast cancer radiotherapy: A systematic review of lung doses published 2010-2015.

BACKGROUND AND PURPOSE: We report a systematic review of lung radiation doses from breast cancer radiotherapy. METHODS AND MATERIALS: Studies describing breast cancer radiotherapy regimens published during 2010-2015 and reporting lung dose were included. Doses were compared between different countries, anatomical regions irradiated, techniques and use of breathing adaptation. RESULTS: 471 regimens from 32 countries were identified. The average mean ipsilateral lung dose (MLDipsi) was 9.0 Gy. MLDipsi for supine radiotherapy with no breathing adaption was 8.4 Gy for whole breast/chest wall (WB/CW) radiotherapy, 11.2 Gy when the axilla/supraclavicular fossa was irradiated, and 14.0 Gy with the addition of internal mammary chain irradiation; breathing adaptation reduced MLDipsi by 1 Gy, 2 Gy and 3 Gy respectively (p < 0.005). For WB/CW radiotherapy, MLDipsi was lowest for tangents in prone (1.2 Gy) or lateral decubitus (0.8 Gy) positions. The highest MLDipsi was for IMRT in supine position (9.4 Gy). The average mean contralateral lung dose (MLDcont) for WB/CW radiotherapy was higher for IMRT (3.0 Gy) than for tangents (0.8 Gy). CONCLUSIONS: Lung doses from breast cancer radiotherapy varied substantially worldwide, even between studies describing similar regimens. Lymph node inclusion and IMRT use increased exposure, while breathing adaptation and prone/lateral decubitus positioning reduced it.

A cardiac contouring atlas for radiotherapy.

BACKGROUND AND PURPOSE: The heart is a complex anatomical organ and contouring the cardiac substructures is challenging. This study presents a reproducible method for contouring left ventricular and coronary arterial segments on radiotherapy CT-planning scans. MATERIAL AND METHODS: Segments were defined from cardiology models and agreed by two cardiologists. Reference atlas contours were delineated and written guidelines prepared. Six radiation oncologists tested the atlas. Spatial variation was assessed using the DICE similarity coefficient (DSC) and the directed Hausdorff average distance (d→H,avg). The effect of spatial variation on doses was assessed using six different breast cancer regimens. RESULTS: The atlas enabled contouring of 15 cardiac segments. Inter-observer contour overlap (mean DSC) was 0.60-0.73 for five left ventricular segments and 0.10-0.53 for ten coronary arterial segments. Inter-observer contour separation (mean d→H,avg) was 1.5-2.2mm for left ventricular segments and 1.3-5.1mm for coronary artery segments. This spatial variation resulted in <1Gy dose variation for most regimens and segments, but 1.2-21.8Gy variation for segments close to a field edge. CONCLUSIONS: This cardiac atlas enables reproducible contouring of segments of the left ventricle and main coronary arteries to facilitate future studies relating cardiac radiation doses to clinical outcomes.

Dose and Fractionation in Radiation Therapy of Curative Intent for Non-Small Cell Lung Cancer: Meta-Analysis of Randomized Trials.

PURPOSE: The optimum dose and fractionation in radiation therapy of curative intent for non-small cell lung cancer remains uncertain. We undertook a published data meta-analysis of randomized trials to examine whether radiation therapy regimens with higher time-corrected biologically equivalent doses resulted in longer survival, either when given alone or when given with chemotherapy. METHODS AND MATERIALS: Eligible studies were randomized comparisons of 2 or more radiation therapy regimens, with other treatments identical. Median survival ratios were calculated for each comparison and pooled. RESULTS: 3795 patients in 25 randomized comparisons of radiation therapy dose were studied. The median survival ratio, higher versus lower corrected dose, was 1.13 (95% confidence interval [CI] 1.04-1.22) when radiation therapy was given alone and 0.83 (95% CI 0.71-0.97) when it was given with concurrent chemotherapy (P for difference=.001). In comparisons of radiation therapy given alone, the survival benefit increased with increasing dose difference between randomized treatment arms (P for trend=.004). The benefit increased with increasing dose in the lower-dose arm (P for trend=.01) without reaching a level beyond which no further survival benefit was achieved. The survival benefit did not differ significantly between randomized comparisons where the higher-dose arm was hyperfractionated and those where it was not. There was heterogeneity in the median survival ratio by geographic region (P<.001), average age at randomization (P<.001), and year trial started (P for trend=.004), but not for proportion of patients with squamous cell carcinoma (P=.2). CONCLUSIONS: In trials with concurrent chemotherapy, higher radiation therapy doses resulted in poorer survival, possibly caused, at least in part, by high levels of toxicity. Where radiation therapy was given without chemotherapy, progressively higher radiation therapy doses resulted in progressively longer survival, and no upper dose level was found above which there was no further benefit. These findings support the consideration of further radiation therapy dose escalation trials, making use of modern treatment methods to reduce toxicity.

Uncertainties in estimating heart doses from 2D-tangential breast cancer radiotherapy.

BACKGROUND AND PURPOSE: We evaluated the accuracy of three methods of estimating radiation dose to the heart from two-dimensional tangential radiotherapy for breast cancer, as used in Denmark during 1982-2002. MATERIAL AND METHODS: Three tangential radiotherapy regimens were reconstructed using CT-based planning scans for 40 patients with left-sided and 10 with right-sided breast cancer. Setup errors and organ motion were simulated using estimated uncertainties. For left-sided patients, mean heart dose was related to maximum heart distance in the medial field. RESULTS: For left-sided breast cancer, mean heart dose estimated from individual CT-scans varied from <1Gy to >8Gy, and maximum dose from 5 to 50Gy for all three regimens, so that estimates based only on regimen had substantial uncertainty. When maximum heart distance was taken into account, the uncertainty was reduced and was comparable to the uncertainty of estimates based on individual CT-scans. For right-sided breast cancer patients, mean heart dose based on individual CT-scans was always <1Gy and maximum dose always <5Gy for all three regimens. CONCLUSIONS: The use of stored individual simulator films provides a method for estimating heart doses in left-tangential radiotherapy for breast cancer that is almost as accurate as estimates based on individual CT-scans.

Exposure of the Heart in Breast Cancer Radiation Therapy: A Systematic Review of Heart Doses Published During 2003 to 2013.

PURPOSE: Breast cancer radiation therapy cures many women, but where the heart is exposed, it can cause heart disease. We report a systematic review of heart doses from breast cancer radiation therapy that were published during 2003 to 2013. METHODS AND MATERIALS: Eligible studies were those reporting whole-heart dose (ie, dose averaged over the whole heart). Analyses considered the arithmetic mean of the whole-heart doses for the CT plans for each regimen in each study. We termed this "mean heart dose." RESULTS: In left-sided breast cancer, mean heart dose averaged over all 398 regimens reported in 149 studies from 28 countries was 5.4 Gy (range, <0.1-28.6 Gy). In regimens that did not include the internal mammary chain (IMC), average mean heart dose was 4.2 Gy and varied with the target tissues irradiated. The lowest average mean heart doses were from tangential radiation therapy with either breathing control (1.3 Gy; range, 0.4-2.5 Gy) or treatment in the lateral decubitus position (1.2 Gy; range, 0.8-1.7 Gy), or from proton radiation therapy (0.5 Gy; range, 0.1-0.8 Gy). For intensity modulated radiation therapy mean heart dose was 5.6 Gy (range, <0.1-23.0 Gy). Where the IMC was irradiated, average mean heart dose was around 8 Gy and varied little according to which other targets were irradiated. Proton radiation therapy delivered the lowest average mean heart dose (2.6 Gy, range, 1.0-6.0 Gy), and tangential radiation therapy with a separate IMC field the highest (9.2 Gy, range, 1.9-21.0 Gy). In right-sided breast cancer, the average mean heart dose was 3.3 Gy based on 45 regimens in 23 studies. CONCLUSIONS: Recent estimates of typical heart doses from left breast cancer radiation therapy vary widely between studies, even for apparently similar regimens. Maneuvers to reduce heart dose in left tangential radiation therapy were successful. Proton radiation therapy delivered the lowest doses. Inclusion of the IMC doubled typical heart dose.

Inter-observer variation in delineation of the heart and left anterior descending coronary artery in radiotherapy for breast cancer: a multi-centre study from Denmark and the UK.

BACKGROUND AND PURPOSE: To determine the extent of inter-observer variation in delineation of the heart and left anterior descending coronary artery (LADCA) and its impact on estimated doses. METHODS AND MATERIALS: Nine observers from five centres delineated the heart and LADCA on fifteen patients receiving left breast radiotherapy. The delineations were carried out twice, first without guidelines and then with a set of common guidelines. RESULTS: For the heart, most spatial variation in delineation was near the base of the heart whereas for the LADCA most variation was in its length at the apex of the heart. Common guidelines reduced the spatial variation for the heart and the length of the LAD, but increased the variation in the anterior-posterior/right-left plane. The coefficients of variation (CV) in the estimated doses to the heart were: mean dose 7.5% without and 3.6% with guidelines, maximum dose 8.7% without and 4.0% with guidelines. The CVs in the estimated doses to the LADCA were: mean dose 27% without and 29% with guidelines, maximum dose 39% without and 31% with guidelines. CONCLUSIONS: For the heart, there was little inter-observer variation in the estimated dose, especially when guidelines were used. In contrast, for the LADCA there was substantial variation in the estimated dose, which was not reduced with guidelines.

Incidence of heart disease in 35,000 women treated with radiotherapy for breast cancer in Denmark and Sweden.

PURPOSE: To study incidence of radiation-related heart disease in a large population of breast cancer patients followed for up to 30 years. MATERIAL AND METHODS: 72,134 women diagnosed with breast cancer in Denmark or Sweden during 1976-2006 and followed prospectively. Radiation-related risk was studied by comparing women with left-sided and right-sided tumours. RESULTS: 34,825 women (48%) received radiotherapy. Among unirradiated women tumour laterality had little relevance to heart disease. Among irradiated women mean dose to the whole heart was 6.3 Gy for left-sided tumours and 2.7 Gy for right-sided tumours. Mortality was similar in irradiated women with left-sided and right-sided tumours, but incidence ratios, left-sided versus right-sided, were raised: acute myocardial infarction 1.22 (95% CI 1.06-1.42), angina 1.25 (1.05-1.49), pericarditis 1.61 (1.06-2.43), valvular heart disease 1.54 (1.11-2.13). Incidence ratios for all heart disease were as high for women irradiated since 1990 (1.09 [1.00-1.19]) as for women irradiated during 1976-1989 (1.08 [0.99-1.17]), and were higher for women diagnosed with ischaemic heart disease prior to breast cancer than for other women (1.58 [1.19-2.10] versus 1.08 [1.01-1.15], p for difference=0.01). CONCLUSIONS: Breast cancer radiotherapy has, at least until recently, increased the risk of developing ischaemic heart disease, pericarditis and valvular disease. Women with ischaemic heart disease before breast cancer diagnosis may have incurred higher risks than others.

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.

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 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.