Improving cardiac dosimetry: Alternative beam arrangements for intensity modulated radiation therapy planning in patients with carcinoma of the distal esophagus
Article Outline
Abstract
Purpose
Radiation for carcinoma of the distal esophagus is associated with cardiac perfusion deficits and pericardial effusion. We performed a dosimetric analysis of alternative beam arrangements for use in intensity modulated radiation therapy (IMRT) planning, seeking to lower radiation dose to the heart.
Methods and Materials
Treatment plans using 4 separate beam arrangements were generated and optimized for 12 patients. Hemispheric and butterfly beam arrangements were compared with plans with posterior and lateral beam entries. Radiotherapy was planned to 50.4 Gy in 28 fractions, using step and shoot IMRT with 6 MV photons. Mean heart dose and volumes of heart and lung receiving up to specified doses (V5-V40) were recorded. Isodose distributions were evaluated for target coverage and normal tissue exposure.
Results
IMRT plans utilizing posterior-lateral beam arrangements significantly reduced mean cardiac doses (32.5 ± 3.9 Gy, 33.3 ± 3.2 Gy vs 24.3 ± 3.7 Gy, and 23.4 ± 4.2 Gy, P < .05, paired Student t test with post hoc Bonferroni correction) as well as the total heart volumes receiving at least 20 and 30 Gy. IMRT allowed the maximum cord dose to be limited to less than 40 Gy. While both posterior-lateral beam arrangements lead to improved cardiac dosimetry, mean lung doses as well as V5 and V20 were slightly higher, although within accepted limits. Target coverage, homogeneity, and conformality were similar or improved with the use of alternative beam configurations.
Conclusions
The use of IMRT with posterior-lateral beams can significantly reduce radiation dose to cardiac structures with minimal increased dose to the lung. Future studies will assess the physiologic and clinical impact of cardiac sparing.
Introduction
Trimodality therapy for patients with esophageal cancer has improved outcomes with radiotherapy, contributing to improvements in local control and survival.1, 2 Unfortunately, these gains may come at the expense of increased toxicity. Recent work has shown that radiation for esophageal carcinoma is associated with cardiac perfusion deficits and places patients at risk for pericardial effusion.3, 4
For patients with distal esophageal tumors, proximity of dose-limiting organs, including the lung and heart, makes treatment planning and radiotherapy delivery technically challenging. The incorporation of computed tomography (CT) imaging into radiotherapy practice allowed for the depiction beam paths through individual patients' anatomy and thus optimization of beam orientations with increased conformality and normal tissue sparing. Further technological advances led to the implementation of intensity modulated radiation therapy (IMRT), providing additional flexibility to modify dose distributions and maximal normal tissue sparing.5 Dosimetric studies have demonstrated that, in comparison to 3-dimensional conformal radiation therapy, IMRT allows for greater lung sparing.6 However, in order to achieve maximal lung sparing, close attention to beam arrangements is still critical.7
While gains have been made in sparing the lung, previous reports have not demonstrated improvements in cardiac sparing.6 In the current study, we sought to reduce cardiac dose using alternative beam arrangements for IMRT planning. Treatment plans using 4 separate beam arrangements were generated and optimized for 12 patients with carcinoma of the distal esophagus.
Methods
Volume definition and treatment planning
Twelve patients treated for carcinoma of the esophagus were identified retrospectively. For planning purposes all patients had undergone 4-dimensional CT scanning to account for respiratory motion. Planning images were obtained at 2.5 mm intervals throughout the chest and upper abdomen. The gross tumor volume was delineated by the attending physician using all available resources, including fused positron emission tomographic-CT data, endoscopic reports, and diagnostic CT imaging. Clinical target volume expansions ensured coverage 3 cm superiorly, 1 cm laterally, 3 cm inferiorly, and 3 cm into the mucosa of the stomach depending on attending preference. The celiac axis was not routinely included in the target volume. The planning target volume (PTV) was generated by the addition of a 1-cm expansion to the clinical target volume. Organs at risk were outlined. Total lung excluded gross tumor volumes. There is uncertainty in the delineation of cardiac structures. For detailed guidelines on contouring the heart and individual structures, please refer to Feng et al.8 Briefly, the whole heart, including atria, ventricles, pericardium, and cardiac vessels, was contoured from the inferior aspect of the right pulmonary artery through the apex. Non-contrast planning CT scans were utilized, precluding the contouring of cardiac substructures.
IMRT plans were generated using a step and shoot technique and the Pinnacle planning system (Phillips Medical Systems, Andover, MA). Treatment plans using 4 separate beam arrangements were generated and optimized. Traditional beam arrangements, hemispheric (350, 30, 70, 100, and 180 degrees) and butterfly (350, 25, 130, 165, and 195 degrees), were compared with arrangements restricted to posterior and lateral beam entries (firefly: 100, 130, 180, 230, and 260 degrees and dragonfly: 70, 100, 180, 260, and 290 degrees). The prescribed dose was 50.4 Gy in 28 fractions, with the requirement that 95% of the PTV received the prescribed dose. Planning objectives placed highest priority on achieving PTV coverage with secondary objectives to avoid the lung and heart. Mean dose to normal tissues and total volumes irradiated to given dose levels were recorded.
Comparison of treatment plans
Isodose distributions were compared visually on axial, sagittal, and coronal slices to assess conformality and avoidance of normal tissues. Target coverage and normal tissue sparing were also assessed numerically by calculation of the following indices:
and
TV is the target volume, TVRI is the target volume covered by reference dose, and VRI is the volume of reference isodose.
The CN ranges from 0 to 1, with 1 being the optimum value. A lower CN, closer to 0, indicates a complete lack of irradiation of the target or a large volume of irradiation relative to the target.9 The IC1 and IC2 measure the target dose distribution variance.10 A larger number indicates greater variability target dose.
Statistics
Statistical significance was determined using the 2-tailed paired Student t test. Significance was defined as a P value ≤.05 following post-hoc Bonferroni correction to account for multiple comparisons.
Results
Traditional beam arrangements commonly employ anterior beams in order to ensure target coverage. Two traditional configurations, hemispheric and butterfly, were compared with plans designed with posterior and lateral beam entries avoiding entry directly over the heart. Typical dose distributions, as well as beam angles utilized for treatment planning, are depicted in Figure 1.
Figure 1.
Cross-sectional computed tomographic images for a single patient. Beam angles and typical dose distributions are displayed for (A) hemispheric, (B) butterfly, (C) dragonfly, and (D) firefly beam configurations.
IMRT plans utilizing posterior-lateral beam arrangements significantly reduced mean cardiac doses (Table 1, Bonferroni corrected P value <.05). While the volume of heart receiving lower doses of radiation were similar, heart volumes treated to at least 20 (V20 heart) and 30 Gy (V30 heart) were significantly reduced through the use of posterior arrangements (Fig 2). Higher dose regions were also reduced although to a lesser extent.
Table 1. Normal tissue sparing
| Organ | Technique | |||
|---|---|---|---|---|
| Hemispheric | Butterfly | Firefly | Dragonfly | |
| Heart | ||||
 Mean dose | 32.5 ± 3.9 | 33.3 ± 3.2 | 24.3 ± 3.7 a,b | 23.4 ± 4.2 a,b |
| V5 | 100 ± 1 | 98 ± 3 | 99 ± 1 | 93 ± 5 a |
| V10 | 97 ± 3 | 95 ± 4 | 88 ± 9 a | 86 ± 6 a,b |
| V20 | 83 ± 12 | 85 ± 8 | 49 ± 11 a,b | 43 ± 12 a,b |
| V30 | 56 ± 16 | 55 ± 14 | 29 ± 9 a,b | 27 ± 11 a,b |
| V40 | 27 ± 9 | 34 ± 1 | 19 ± 8 a,b | 19 ± 8 b |
| Lung | ||||
| Mean dose | 10.2 ± 2.2 | 9.8 ± 2.3 | 11.3 ± 2.8 b | 10.8 ± 2.5 b |
| V5 | 51 ± 11 | 43 ± 11 | 55 ± 14 b | 49 ± 11 b |
| V10 | 35 ± 8 | 30 ± 7 | 37 ± 10 b | 37 ± 9 b |
| V20 | 17 ± 4 | 18 ± 5 | 21 ± 6.8 | 22 ± 6 a,b |
| Spinal cord | ||||
| Maximum | 39.9 ± 4.6 | 41.1 ± 3.7 | 39.1 ± 3.2 | 38.1 ± 3.3 |
Figure 2.
Graphical depiction of cardiac sparing. (A) Dose-volume histogram (DVH) from a single representative patient. (B) Cumulative heart DVH (error bars represent the standard error of the mean). (C) Cumulative lung DVH. PTV, planning target volume.
For both patients with esophageal carcinoma and non-small cell carcinoma of the lung, a great deal of study has focused on the correlation of pneumonitis with the volume of lung irradiated. Mean pulmonary doses, as well as V20, are commonly cited predictors.11, 12 As shown in Table 1, these indices were slightly higher in comparison to the butterfly or hemispheric techniques although still clinically acceptable.
No significant differences were found with respect to target coverage (Table 2). Analysis of conformality number revealed significant differences comparing posterior-lateral beam arrangements to the butterfly technique. This is consistent with a relatively large volume of normal tissues receiving radiation in comparison to the target volume, given good target coverage. All plans achieved excellent target coverage with ≥95% of the PTV receiving at least 100% of the prescription dose as expected based on planning restrictions. Target dose uniformity showed no significant differences among all plans based on HI, IC1, and IC2.
Table 2. Comparison of target coverage parameters
| Index | Technique | |||
|---|---|---|---|---|
| Hemispheric | Butterfly | Firefly | Dragonfly | |
| CN100% | 0.82 ± 0.07 a | 0.70 ± 0.06 b,c,d | 0.81 ± 0.06 a | 0.81 ± 0.04 a |
| HI | 0.22 ± 0.07 | 0.21 ± 0.07 | 0.27 ± 0.11 | 0.25 ± 0.09 |
| IC1 | 0.26 ± 0.10 | 0.24 ± 0.09 | 0.34 ± 0.19 | 0.31 ± 0.13 |
| IC2 | 0.05 ± 0.02 | 0.04 ± 0.02 | 0.04 ± 0.02 | 0.04 ± 0.02 |
| Dmin | 44.0 ± 2.6 | 44.7 ± 2.9 | 42.4 ± 4.5 | 42.5 ± 2.8 |
| Dmax | 55.1 ± 1.3 | 55.1 ± 1.2 | 56.0 ± 1.9 | 55.2 ± 1.9 |
| V90% | 99.9 ± 0.1 | 99.9 ± 0.1 | 99.8 ± 0.3 | 99.8 ± 0.2 |
| V95% | 99.4 ± 0.6 | 99.7 ± 0.3 | 99.4 ± 0.7 | 99.4 ± 0.5 |
| V100% | 95.4 ± 3.2 | 96.9 ± 0.6 | 96.9 ± 0.5 | 96.2 ± 0.7 |
Discussion
The effects of radiation on pulmonary function have been studied extensively for patients with thoracic malignancies. For patients with esophageal carcinoma, radiation dose to the normal lung correlates with postoperative pulmonary complications.13 In contrast, the impact of radiation dose on cardiac function is less well known. Traditionally, the heart has been viewed as a radiation resistant organ with long-term complications, including coronary artery disease, valvular disease, conduction abnormalities, pericardial effusion, and cardiomyopathies arising years following radiotherapy. These late effects have been most extensively studied among survivors of Hodgkin's lymphoma and patients treated for left-sided breast cancers. Recent studies of patients with esophageal carcinoma suggest the volume of the heart receiving 30 Gy may predict the development of pericardial effusion.3, 4 Gated myocardial perfusion imaging has shown that prior to surgical intervention patients treated with concurrent chemo-irradiation have perfusion deficits, which correspond with radiation isodose lines.3 Intriguingly, emerging evidence suggests that cardiac irradiation may also have sub-acute effects. In animal studies, heart irradiation increases the incidence of pneumonitis.14 This is also supported by early clinical studies.15 The development of early physiologic dysfunction following irradiation may be of special importance for patients treated with trimodality therapy as it may increase the risk of operative morbidity and mortality.
With improved outcomes for patients with carcinoma of the esophagus using trimodality therapy, more patients are surviving to see therapy-induced complications. The improved sparing of normal tissues has led to the routine use of IMRT for treatment of thoracic malignancies at many institutions. However, dose-volume constraints continue to evolve. The relation of both early and late sequelae associated with radiation to the heart is particularly uncertain. However, based on first principles, it is wise to utilize technology as best as possible to spare normal tissues from excess radiation. Here we demonstrate significant improvements with the simple use of alternative beam arrangements for IMRT for esophageal malignancies. The present study did not consider non-IMRT plans, with either fixed fields or arcs. It is possible that such conformal plans would yield acceptable dosimetric plans. Further, the differences among the IMRT plans shown may or may not persist with non-IMRT beams. Future studies will determine the physiologic and clinical significance of cardiac sparing while developing dosimetric constraints for use in planning.
References
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- Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol. 2008;26:1086–1092
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- . A conformation number to quantify the degree of conformality in brachytherapy and external beam irradiation: application to the prostate. Int J Radiat Oncol Biol Phys. 1997;37:731–736
- Report of a study on IMRT planning strategies for ethmoid sinus cancer. Strahlenther Onkol. 2002;178:572–576
- A nomogram to predict radiation pneumonitis, derived from a combined analysis of RTOG 9311 and institutional data. Int J Radiat Oncol Biol Phys. 2007;69:985–992
- Clinical dose-volume histogram analysis for pneumonitis after 3D treatment for non-small cell lung cancer (NSCLC). Int J Radiat Oncol Biol Phys. 1999;45:323–329
- Investigation of clinical and dosimetric factors associated with postoperative pulmonary complications in esophageal cancer patients treated with concurrent chemoradiotherapy followed by surgery. Int J Radiat Oncol Biol Phys. 2006;64:692–699
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Conflicts of interest: None.
PII: S1879-8500(11)00161-5
doi:10.1016/j.prro.2011.04.007
© 2012 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.
