British Journal of Radiology (2005) 78, 1069-1074
© 2005 British Institute of Radiology
doi: 10.1259/bjr/20742408
Quantification and reduction of cardiac dose in radical radiotherapy for oesophageal cancer
M Cominos, FRCR1,
M A Mosleh-Shirazi, PhD2,
D Tait, FRCR1,
A Henrys, Dip.App.Sc2 and
P Cornes, FRCR1
1 Department Clinical Oncology and 2 Department of Physics, Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT, UK
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Abstract
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Chemoradiation is increasingly used in the management of localized oesophageal cancer and has been shown in randomized controlled trials to improve overall survival. Although early toxicity of radiotherapy is well documented, this is not the case for late toxicity. As patients with oesophageal cancer have a high incidence of co-morbidities including cardiac problems, the aim of this paper was to quantify the extent of cardiac radiation and discuss the influence of beam arrangement to reduce this. Eight patients with localized oesophageal cancer treated with radical chemoradiation were selected. The mean cardiac dose and the volumes of heart receiving 30 Gy, 40 Gy and 45 Gy from the conventional two-phase technique were compared with those of single-phase 3-field and 4-field conformal beam arrangements. The 4-field arrangement reduced the mean cardiac dose by at least 3.3 Gy compared with the other two beam arrangements (p=0.01). The mean volume of heart receiving high doses between the three techniques widened as the dose increased in the range 30–45 Gy. There is no statistically significant difference in volumes receiving more than 30 Gy and 40 Gy. 65% of the cardiac volume received more than 45 Gy using a two-phase technique, compared with 57% using three fields and 26% using four fields (p<0.01). With a 4-field beam arrangement, therefore, there is a significant reduction in cardiac dose compared with the other two techniques. Cardiac toxicity and a 4-field beam arrangement should be considered when planning radical radiotherapy for localized oesophageal cancer.
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Introduction
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Oesophageal cancer is the ninth most common cancer in the UK with over 7000 new cases per year. It tends to occur in males, more often than females, between the ages of 40 years and 80 years. In 2001, 7008 people died in the UK from oesophageal cancer [1]. Smoking is a major risk factor for squamous cancer, which means that patients often have serious co-morbidities that need to be considered prior to treatment. Published 5 year survival rates from surgical series for localized oesophageal cancer range from 50% to 80% for T1 N0 M0 tumours, 10–30% for T1–2 N1 and 10–15% for T3/T4 N+ tumours [2]. Survival figures following radiotherapy as a single modality are also considered disappointing, but cases are usually medically unfit for surgery or the tumours are locally advanced. However, in a series from Manchester treating earlier lesions with radiotherapy alone, the 3 years and 5 year survival was 27% and 21%, respectively [3]. The impact of technical sophistication on outcome is hinted at by the superior results for CT planned patients. It should be remembered that the majority of the patients in the Manchester series were medically unfit for surgery.
The development of chemoradiation schedules has a sound theoretical basis, both for improving local control and suppression of systemic metastases. This potential has been demonstrated in the RTOG 85-01 trial comparing chemoradiation using 50 Gy in 25 fractions with concomittant cisplatin and 5FU (5-fluorouracil) followed by two cycles of adjuvant chemotherapy, to 64 Gy radiotherapy alone. In patients with T1–3 N0–1 M0 squamous cell or adenocarcinoma the overall 5 year survival was 26% compared with 0% with radiotherapy alone [4]. Acute toxicity was greater in the combined treatment group, but long-term toxicity was not significantly different [5]. In an Eastern Cooperative Oncology Group study 130 patients were randomized to receive 60 Gy with or without 5FU/Mitomycin C. 2- and 5-year survivals were 12% and 7% in the radiation alone arm, and 27% and 9% in the chemoradiation arm. Patients treated with chemoradiation had a longer median survival (14.8 months) compared with patients receiving radiation therapy alone (9.2 months). This difference was statistically significant [6]. At the Royal Marsden Hospital, a series of patients with locally advanced disease treated with chemoradiation in a Phase II trial looking at triple modality therapy achieved a 44.1% 2 year survival rate [7].
Although acute toxicity with chemoradiation is often well documented, late toxicities are less well reported. With regards to long-term toxicity, tolerance of spinal cord and lung has traditionally influenced oesophageal radiotherapy planning, but, with improving outcomes, cardiac toxicity also needs to be considered. Information on radiation injuries following whole heart radiation come mostly from patients with Hodgkin's disease whereas partial volume information is mainly derived from patients treated post-operatively for breast cancer [8–11]. Emami et al, having reviewed available literature on normal tissue tolerance, suggest whole heart tolerance dose (TD) 5/5 (normal tissue complication probability of 5%, 5 years following radiotherapy) of 40 Gy and 60 Gy for 1/3 of the volume. TD 50/5 values (normal tissue complication probability of 50%, 5 years following radiotherapy) are mostly speculative and have been extrapolated from TD 5/5 data but estimations show TD 50/5 70 Gy for one third of the heart and 50 Gy for whole heart [12]. Pericarditis is considered as the main end-point for these figures because it is the most commonly occurring complication. However, it is often asymptomatic and of little clinical significance. In our experience with oesophageal cancer patients, the main cardiac toxicities are associated with heart failure and ischaemic heart disease as would be expected in a population with other risk factors for coronary artery disease.
The aim of this study is to quantify cardiac doses in patients undergoing radical chemoradiation for mid-to-lower oesophageal cancers and to investigate the influence of beam arrangements on cardiac dose parameters in an attempt to optimize treatment in this group of patients.
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Materials and methods
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Eight patients with mid-to-lower oesophageal tumours who had been treated with radical chemoradiation during 2000 were selected for this study. Treatment included 3 months of neo-adjuvant platinum and continuous 5FU chemotherapy followed by concomitant peripheral venous infusion (PVI) 5FU. The selection criterion was to provide a representative sample of the planning target volumes (PTVs) seen in routine clinical practice. The patients had undergone planning CT scans in a supine position with their arms above their heads, where axial 0.8 cm thick CT slices had been acquired at 1 cm intervals.
Two-phase technique
The patients were treated with a two-phase technique (2ph), both phases being CT planned according to policy at that time. Patients were treated in two phases, by a 10 MV anteroposterior-posteroanterior (AP-PA) pair followed by a 6 MV 3-field phase 2, both phasings being based on the same CT-defined PTV. Conformal treatment plans were created using the Pinnacle TPS (ADAC Laboratories, Philips Medical Systems, Milpitas, CA). Gross tumour volumes (GTVs) were localized by the findings from endoscopy, endoscopic ultrasound and diagnostic CT scans. PTVs were grown from GTVs by adding 1.5–2 cm axially (4 patients having a 1 cm margin in the posterior direction) and 3–5 cm in the superior/inferior direction. The whole of both lungs were contoured as well as the spinal cord for the length of the PTV. A 0.6 cm field penumbra margin was used from the PTV. Field shaping was performed using conformal blocks or 1 cm wide multileaf collimator (MLC) depending on the linear accelerator used. The phase 2 beam geometry for all patients included an AP beam, in addition to which six patients had two posterior oblique beams, one had two anterior oblique fields, and one right-anterior and left-posterior obliques. The AP beam was either unwedged, wedged (in the superior/inferior or left/right directions), or had an additional asymmetric boost field for the inferior portion. Density heterogeneities were accounted for on a pixel-by-pixel basis using CT data. Dose calculation was performed on a 0.3 cm x 0.3 cm x 0.3 cm grid using the collapsed-cone algorithm.
The treatments were prescribed 54 Gy in 30 fractions to 100% of the dose at the isocentre or a representative normalization point. The tolerance doses applied were 48 Gy in 1.8 Gy fractions for spinal cord and less than 20% of lung receiving in excess of 20 Gy. Table 1
summarizes the breakdown of the prescribed dose between the two phases. The reason for the differences between the patients' treatments was that the changeover time was determined on an individual patient basis depending on maximum spinal cord dose. For all but two patients, a greater dose was prescribed in phase 1 than phase 2.
The heart volume (including myocardium and the coronary arteries on its periphery but excluding the great vessels) was then outlined on Pinnacle with the help of a radiologist. As the dose–volume histograms (DVHs) for the whole treatment were required for the actual delivered doses, a composite 5-field plan comprising the beams from the two phases was created for each patient. The beam weights for the composite plans were assigned by entering the monitor units (MUs) from each individual phase. DVHs of the PTV, heart, spinal cord and lungs were computed. The mean cardiac dose and volumes of heart receiving more than 30 Gy, 40 Gy and 45 Gy were then calculated.
Single-phase technique
In order to carry out a comparison with the delivered two-phase plans, single-phase, 3-field (3F) and 4-field (4F) treatment plans were calculated on Pinnacle using the same patients, volumes, prescription points, treatment machines, shielding methods (MLC or blocks), calculation parameters and dose limitation criteria for the spinal cord and lungs as above, as well as the same requirement for PTV isodose coverage.
The aim was to compare the conventional way of optimizing oesophageal radiotherapy plans (i.e. ignoring the cardiac dose) to the proposed modern optimization criteria, which includes considering cardiac toxicity. In the conventional arm, a 3F plan normally satisfies the dose constraints so there is no real need to use further beams. Therefore, the conventional criteria were represented by a 3F plan as follows: the maximum spinal cord dose was allowed to reach the 48 Gy tolerance level in order to spare the lungs, while no effort was made to limit the heart dose. A beam geometry consisting of an AP and two posterior oblique fields was used in all cases. In the 3F plans, the posterior-oblique gantry angles were selected on a patient-by-patient basis with a view to reduce beam overlap while maintaining a separation between the posterior border of the beam and the spinal cord (to reduce cord dose). The added requirement of limiting the dose to the heart normally necessitates additional planning flexibility. This was offered by the use of a fourth field. Therefore, 4F plans were optimized while considering the heart dose as well as the spinal cord and lungs. AP, PA and lateral beams were first constructed and then a gantry rotation of up to 10° was applied to the lateral fields if that increased the distance between the posterior border of the beam and the spinal cord. The choice of beam energy was made on a patient-by-patient basis to produce the best overall dose distribution in each case. This resulted in the 3F plans consisting of 10 MV AP and 6 MV oblique fields while all beams in the 4F plans were 10 MV.
The mean cardiac doses and volumes of heart receiving more than 30 Gy, 40 Gy and 45 Gy were compared between plans. Statistical significance of differences between any two of the planning techniques was carried out on an individual patient basis using the paired two-tailed Student's t-test.
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Results
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The eight patients were aged from 59 years to 86 years. All patients had locally advanced mid-to-lower squamous cell carcinomas with tumours ranging from T2 N0 M0 to T4 N0 M0. The length of the tumours ranged from 3 cm to 11 cm. The volumes of PTV ranged from 252.2 cm3 to 678.9 cm3 (Figure 1) showing the diversity commonly seen in clinical practice. Out of these eight patients, three achieved a complete response and are still under regular follow up with no evidence of recurrence up to 3 years following completion of treatment.
Figure 1
shows the PTV and cardiac volumes in all eight cases. The overlap between the PTV and heart volumes ranged from 35.0 cm3 for Case 6 to 87.7 cm3 for Case 3. In terms of percentage heart volume, the overlap ranged from 6% for Case 6 to 14% for Case 1. Figure 2 demonstrates examples of three cases and how the volumes overlap each other.
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Figure 2. Three examples of digitally reconstructed radiographs showing the overlap of planning target volume (PTV) and cardiac volume.
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Comparing the three different treatment plans, the mean cardiac dose received was less in the 4F technique in all eight patients. The difference varied from as little as 2 Gy in Case 7 to 8 Gy in Cases 2 and 6 (Figure 3). Examining the volume of heart irradiated using different beam arrangements; there is very little difference in the volume of heart receiving more than 30 Gy (Figure 4). There is a trend, however, for less volume of heart to receive more than 40 Gy with a 4F technique, although this is not necessarily true for all eight cases (Figure 5). The difference becomes more pronounced when looking at cardiac volumes receiving more than 45 Gy (Figure 6).
In order to be able to quantify these trends in more detail, the mean cardiac dose and dose–volume data for each technique was averaged over all eight patients (see Table 2). Using the 4F technique reduced the mean cardiac dose by at least 3.3 Gy compared with the other two (p=0.01), with 3F offering a 1.1 Gy improvement over 2ph (p=0.06). It can be seen from Table 2 that the differences in the mean volume of heart receiving high doses between the three techniques widened as the dose increased in the range 30–45 Gy. At 30 Gy, there was no statistically significant difference between 4F and 3F, while 4F reduced the mean volume by 9.5 cm3 compared with 2ph (p= 0.1). There was a relatively small improvement of 8.3 cm3 from using 3F rather than 2ph at this dose level (p=0.02). At 40 Gy, 4F reduced the mean volume compared with 3F and 2ph by 125.1 cm3 and 143.8 cm3, respectively, (p<0.02), while 3F offered an 18.7 cm3 improvement over 2ph (p=0.1). At 45 Gy, the benefit from 4F compared with 3F and 2ph increased to 188.4 cm3 and 234.1 cm3, respectively, (p<0.001), while on average 45.7 cm3 of heart volume was spared this dose with 3F compared with 2ph. Although not shown here, the differences between the three methods became small again at 50 Gy, mainly due to the overlap between the PTV and heart volumes.
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Table 2. Mean cardiac dose and cardiac dose–volume data averaged over all patients for each technique. Percentage heart volumes are given in brackets
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Generally similar lung DVHs were produced by the three techniques. The percentage lung volumes receiving 10 Gy, 30 Gy, 40 Gy and 50 Gy from the different methods were within ±4%, ±2%, ±3% and ±1%, respectively. The lung volume receiving 20 Gy was always kept below 20% as required by the planning dose constraint. However, the 20 Gy dose was delivered to a greater volume by the 3F technique than the other two by an average of 5% (range 2–10%).
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Discussion
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The better selection of patients for radical treatment due to improved diagnostic imaging and the improvement in survival observed in the chemoradiation trials means that long-term treatment toxicity will be of increased significance. So far, little attention has been given to the effects of radiation on the heart in this setting but should be considered alongside the better-documented organs, the lung and spinal cord.
This study looked at a small number of patients in order to concentrate on the technical aspects that affect the dose of radiation the heart receives during radical treatment. These eight patients, however, seem to represent the spectrum of cases seen in clinical practice. All cases were planned conformally and were treated using a two-phase technique, which was standard at the time. It was appreciated that with this technique the cardiac doses were high and attempts were made to compare other beam arrangements in order to reduce these. The disadvantage of a two-phase technique using an AP-PA parallel pair for phase 1 is that the dose to the spinal cord tends to be relatively high compared with the PTV requiring the addition of two heavily weighted oblique beams for phase 2. Two-phase techniques are used in some departments as a means of starting treatment quickly without the routine use of conformal planning. As chemoradiation and multiple modality therapies offer the prospect of improved survival it is important to be able to assess and document the doses received by normal tissue by using conformal treatment throughout in all radical cases.
The three techniques produced similar lung and spinal cord doses as well as PTV coverage by the 95% isodose (except for the localized reduced coverage due to the neighbouring lung tissue and the influence of beam geometry on this effect [13, 14]). However, with respect to the mean cardiac dose and cardiac volumes receiving high doses of radiation, the 4F technique is superior in these cases. With a 4F beam arrangement, not only is there a reduction in cardiac doses and volumes of heart treated compared with the 3F beam arrangements, but also the isodose distribution within the PTV is more homogeneous. Compared with 4F, the 3F beam arrangement showed less uniformity of dose throughout the PTV (although still within the recommended range of –95% and +107%), which can be attributed to heavy weighting of the anterior field to ensure that lung doses were kept within specified tolerance. Influence of factors such as heart-PTV volume overlap and phase 1 prescribed dose on high cardiac dose in patients treated with the 2ph technique is of interest. MLC orientation also affects cardiac dose as the degree of shielding and ability to conform around the PTV varies depending on the direction of the leaves. The number of patients in this series, however, is too small to establish correlations given the heterogeneity of patient and planning parameters.
The largest difference in the delivered cardiac dose between the techniques studied in this paper occurred in the 30–45 Gy range. If the margins contributing to the PTV can be reduced (for instance by means of better patient immobilization, image-guided radiotherapy, respiratory gating, etc.), then the overlap volume will be reduced. That will result in a reduced cardiac dose, especially for the high doses, and the different techniques may also exhibit differences above 45 Gy.
A Japanese group recently published retrospective long-term toxicity data 5 years after definitive chemoradiation for squamous cell carcinoma of the thoracic oesophagus using 60 Gy in 30 fractions given concurrently with cisplatin and 5FU. 139 patients (aged 38–75 years) were followed up for a median of 56 months; 78 patients achieved complete response and the overall 5-year survival rate was 29%. A two-phase technique was used, treating with AP-PA fields to 40 Gy then multiple fields for phase 2 to a total dose of 60 Gy. In total, eight patients died without recurrence of their cancer due to cardiorespiratory causes which may have been due to radiation toxicity. Out of these eight patients, two patients died of cardiac failure 37 months and 38 months after starting treatment, two of an acute myocardial infarct at 30 months and 40 months, three of pneumonia and one sudden death. The most common cardiac toxicity was pericarditis with 16 patients having a Grade 2 toxicity or more between 3 months and 42 months following treatment. Other late cardiopulmonary toxicities included the development of pleural effusions in 15 patients and only 4 patients required corticosteroids due to radiation pneumonitis [15].
A retrospective study from Velindre Hospital in Cardiff has also quantified doses of radiotherapy received by the heart during chemoradiation as well as assessing the effect on myocardial function. Mean cardiac doses and volume of heart receiving >70% of total dose were calculated from DVHs in 15 patients treated with chemoradiation in whom pre and post radiotherapy multiple gated acquisition (MUGA) scans were available. These patients were treated with 11 weeks of neo-adjuvant chemotherapy using continuous infusion 5FU and cisplatin. Eight patients also received paclitaxel as part of a phase 2 trial. Radiotherapy was delivered in 2 phases, AP phase 1 (60% of total dose) then 3F plan phase 2 anterior and two posterior oblique to a total of 45–50 Gy. There was a reduction in ejection fraction in 12 of the 15 patients. The median ejection fraction pre-treatment was 63% and the median drop was 11% of baseline function, which was statistically significant. Median radiation doses with and without shielding blocks was 27.4 Gy and 35 Gy. This difference was statistically significant. In the two phase technique 63.8% of the volume of heart received 70% or more of the total radiation dose. The use of a 3F technique throughout would have reduced the median cardiac dose to 22.7 Gy [16]. In comparison, the median cardiac doses in the eight cases selected in this paper, using a 4F technique, ranged between 39.5 Gy and 42.0 Gy. This may be due to the smaller number of cases with possibly longer and more advanced tumours, or due to differences in margins used for PTV.
Although the Velindre study was unable to demonstrate a correlation between a decline in ejection fraction and dose of radiotherapy, we have information on cardiac damage from autopsy reports in patients treated with more than 35 Gy. The myocardium tends to develop lesions, which are characterized by patches of diffuse fibrosis resulting from injury to the endothelial cells of the myocardial capillaries [17]. This results in microvascular perfusion defects, which can be detected on single photon emission computed tomography (SPECT) scanning which has been used to assess radiation effects in patients receiving adjuvant treatment for breast cancer [18]. When radiation cardiomyopathy does occur, this can be aggravated by simultaneous or sequential radiotherapy, especially anthracyclines, which is important if one is considering neo-adjuvant chemotherapy prior to chemoradiation. Analysis of patients with Hodgkins and breast cancer, and also animal experiments, have shown that there is a dose response for pericardial and myocardial disease but there is insufficient data for ischaemic heart disease [19]. Several retrospective analyses have confirmed an increased risk of ischaemic heart disease in patients treated with mediastinal radiotherapy for Hodgkins disease [8, 9]. Relative risks for fatal cardiovascular events range from 2.2–7.2 [10]. The Early Breast Cancer Trialists' Collaborative Group after 20 years follow up showed an excess of non-breast cancer deaths due to vascular events following radiotherapy (standardized mortality ratio (SMR) 1.62). This increase in risk appeared as early as 2 years post- radiotherapy [11]. We can therefore deduce from the above data that radiotherapy to the heart results in significant toxicity, which needs to be taken into account when designing radical radiotherapy to the oesophagus.
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Conclusion
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Despite overall poor prognosis of oesophageal cancer, there is some improvement with the use of chemoradiation. In every series of multimodality therapy in the modern era, a significant minority of patients do go on to be long-term survivors. Cardiac toxicity is therefore increasingly important to consider in the treatment of oesophageal cancer, especially as patients also have risk factors of cardiac disease. Improvement of radiotherapy techniques used to treat oesophageal cancer is necessary. Conformal planning should routinely be used in this group of patients with careful consideration to long-term toxicity. A 4F technique seems to spare the heart more than other common field arrangements used. Despite this, emphasis should be made on planning each case individually as the position and length of tumour treated vary and this in turn will alter the dose normal tissues receive. Our aim is to emphasise that in these group of patients, despite their overall poor prognosis, optimum radiotherapy planning techniques should be used.
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Acknowledgments
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We would like to thank Dr Nahid Kamangari for her assistance in the localization of the cardiac volume.
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Footnotes
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Current address for M Cominos, Kent Oncology Centre, Maidstone Hospital, Hermitage Lane, Maidstone, Kent ME16 9QQ, UK. 
Current address for P Cornes, Bristol Oncology Centre, Horfield Road, Bristol BS2 8ED, UK.
Received for publication July 27, 2004.
Revision received May 3, 2005.
Accepted for publication May 12, 2005.
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References
|
|---|
- http://www.cancerresearchuk.org/aboutcancer/statistics/[Accessed June 2004].
- Enzinger PC, Mayer RJ. Esophageal cancer. N Engl J Med 2003;349:2241–52.[Free Full Text]
- Sykes AJ, Burt PA, Slevin NJ, Stout R, Marrs JE. Radical radiotherapy for carcinoma of the oesophagus: an effective alternative to surgery. Radiother Oncol 1998;48:15–21.[CrossRef][Medline]
- al-Sarraf M, Martz K, Herskovic A, Leichman L, Brindle JS, Vaitkevicius VK, et al. Progress report of combined chemoradiotherapy versus radiotherapy alone in patients with esophageal cancer: an intergroup study. J Clin Oncol 1997;15:277–84.[Abstract/Free Full Text]
- Cooper JS, Guo MD, Herskovic A, Macdonald JS, Martenson JA Jr, Al-Sarraf M, et al. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group. JAMA 1999;281:1623–7.[Abstract/Free Full Text]
- Smith TJ, Ryan LM, Douglass HO Jr, Haller DG, Dayal Y, Kirkwood J, et al. Combined chemoradiotherapy vs. radiotherapy alone for early stage squamous cell carcinoma of the esophagus: a study of the Eastern Cooperative Oncology Group. Int J Radiat Oncol Biol Phys 1998;42:269–76.[CrossRef][Medline]
- Waters JS, Tait D, Cunningham D, Padhani AR, Hill ME, Falk S, et al. A multicentre phase II trial of primary chemotherapy with cisplatin and protracted venous infusion 5-fluorouracil followed by chemoradiation in patients with carcinoma of the oesophagus. Ann Oncol 2002;13:1763–70.[Abstract/Free Full Text]
- Boivin JF, Hutchison GB, Lubin JH, Mauch P. Coronary artery disease mortality in patients treated for Hodgkin's disease. Cancer 1992;69:1241–7.[Medline]
- Hancock SL, Donaldson SS, Hoppe RT. Cardiac disease following treatment of Hodgkin's disease in children and adolescents. J Clin Oncol 1993;11:1208–15.[Abstract/Free Full Text]
- Adams MJ, Hardenbergh PH, Constine LS, Lipshultz SE. Radiation-associated cardiovascular disease. Crit Rev Oncol Hematol 2003;45:55–75.[Medline]
- Early Breast Cancer Trialists' Collaborative Group. Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomized trials. Lancet 2000;355:1757–70.[CrossRef][Medline]
- Emami B, Lyman J, Brown A, Coia L, Goitein M, Munzenrider JE, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 1991;21:109–22.[Medline]
- Irvine C, Morgan A, Crellin A, Nisbet A, Beange I. The clinical implications of the collapsed cone planning algorithm. Clin Oncol (R Coll Radiol) 2004;16:148–54.
- De Jaeger K, Hoogeman MS, Engelsman M, Seppenwoolde Y, Damen EM, Mijnheer BJ, et al. Incorporating an improved dose-calculation algorithm in conformal radiotherapy of lung cancer: re-evaluation of dose in normal lung tissue. Radiother Oncol 2003;69:1–10.[Medline]
- Satoshi I, Keiji N, Atushi O, Narikazu B. Long-term toxicity after definitive chemoradiotherapy for squamous cell carcinoma of the thoracic esophagus. J Clin Oncol 2003;21:2697–702.[Abstract/Free Full Text]
- Mukherjee S, Aston D, Minettt M, Brewster AE, Crosby TDL. The significance of cardiac doses received during chemoradiation of oesophageal and gastro-oesophageal junctional cancers. Clin Oncol (R Coll Radiol) 2003;15:115–20.
- Stewart JR, Fajardo LF, Gillette SM, Constine LS. Radiation injury to the heart. Int J Radiat Oncol Biol Phys 1995;31:1205–11.[CrossRef][Medline]
- Seddon B, Cook A, Gothard L, Salmon E, Latus K, Underwood SR, et al. Detection of defects in myocardial perfusion imaging in patients with early breast cancer treated with radiotherapy. Radiother Oncol 2002;64:53–63.[CrossRef][Medline]
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Abstract
Introduction
