Optimal beam arrangement for pulmonary ventilation image-guided intensity-modulated radiotherapy for lung cancer
- Ruihao Wang†1,
- Shuxu Zhang†1Email author,
- Hui Yu1,
- Shengqu Lin1,
- Guoqian Zhang1,
- Rijie Tang2 and
- Bin Qi3
© Wang et al.; licensee BioMed Central Ltd. 2014
Received: 10 October 2013
Accepted: 7 August 2014
Published: 16 August 2014
The principal aim of this study was to evaluate the feasibility of incorporating four-dimensional (4D)-computed tomography (CT)-based functional information into treatment planning and to evaluate the potential benefits of individualized beam setups to better protect lung functionality in patients with non-small cell lung cancer (NSCLC).
Peak-exhale and peak-inhale CT scans were carried out in 16 patients with NSCLC treated with intensity-modulated radiotherapy (IMRT). 4D-CT-based ventilation information was generated from the two sets of CT images using deformable image registration. Four kinds of IMRT plans were generated for each patient: two anatomic plans without incorporation of ventilation information, and two functional plans with ventilation information, using either five equally spaced beams (FESB) or five manually optimized beams (FMOB). The dosimetric parameters of the plans were compared in terms of target and normal tissue structures, with special focus on dose delivered to total lung and functional lung.
In both the anatomic and functional plans, the percentages of both the functional and total lung regions irradiated at V5, V10, and V20 (percentage volume irradiated to >5, >10 and >20 Gy, respectively) were significantly lower for FMOB compared with FESB (P < 0.05), but there was no significant difference for V30 (P > 0.05). Compared with FESB, a greater degree of sparing of the functional lung was achieved in functional IMRT plans with optimal beam arrangement, without compromising target volume coverage or the irradiated volume of organs at risk, such as the spinal cord, esophagus, and heart.
Pulmonary ventilation image-guided IMRT planning with further optimization of beam arrangements improves the preservation of functional lung in patients with NSCLC.
KeywordsIntensity-modulated radiotherapy Pulmonary ventilation Four-dimensional computed tomography Plan optimization
Radiation therapy (RT) plays a significant role in the curative treatment of surgically inoperable non-small cell lung cancer (NSCLC). Radiation pneumonitis (RP) is the most common complication of RT for NSCLC, and its occurrence and severity are closely correlated with the mean lung dose, total lung volume irradiated to >20 Gy (V20), location of the tumor, pulmonary function, and simultaneous or sequential chemotherapy [1–4]. Graham et al.  showed that when the V20 was <22%, the incidence of RP within 2 years was zero; however, the incidences of RP within 2 years increased to 7%, 13%, and 36% when the V20 percentages were 22–31%, 32–40%, and >40%, respectively. This risk of RP could be reduced by up to 10% by using intensity-modulated radiotherapy (IMRT), without compromising tumor-dose delivery . Nevertheless, ways of minimizing RT-induced side effects such as RP, while continuing to achieve reasonable local control of NSCLC, remain a challenge for radiation oncologists.
Information on pulmonary function provided by perfusion and/or ventilation imaging has been shown to be important in evaluating pulmonary toxicity after RT for NSCLC [7–10]. Several techniques exist for pulmonary ventilation imaging, including single photon emission computed tomography and X-ray CT (SPECT-CT) [7, 8], hyperpolarized helium-3 magnetic resonance imaging (3He-MRI) [9, 10], and inert xenon CT (Xe-CT) . However, although all these imaging modalities can provide useful ventilation information, each has serious drawbacks, such as high cost, low resolution, long scan time and/or low accessibility .
Four-dimensional (4D) CT imaging is an exciting new form of ventilation imaging, which consists of three-dimensional (3D) CT images resolved into different phases of the breathing cycle . 4D-CT is becoming widely available and has shown great promise for treatment planning. Because 4D-CT data are relatively easy to acquire during treatment planning, calculating ventilation maps from 4D-CT data only involves additional image processing, and does not add any extra dosimetric or monetary cost to the patient. Moreover, 4D-CT ventilation imaging has higher resolution, a shorter scan time and is more accessible than other existing techniques. Previous studies have investigated the incorporation of 4D-CT ventilation imaging into RT treatment planning [8, 14–16]. For example, Castillo et al.  examined different ways of calculating ventilation from 4D-CT data to estimate local volume changes, and compared the results with those obtained clinically from SPECT ventilation. Ding et al.  explored the changes in lung ventilation after RT, and Yamamoto et al.  and Yaremko et al.  discussed the idea of designing treatment plans to avoid high-ventilation areas of the lung. However, most of these studies considered treatment planning based on fixed-beam arrangements, and to the best of our knowledge, no studies have compared the use of different beam arrangements.
The primary purpose of this study was to investigate the feasibility of combining IMRT with ventilation maps calculated from 4D-CT data, and to compare the benefits of optimal and fixed-beam arrangements in IMRT for NSCLC.
This study was approved by the Institutional Review Board (IRB) at the Affiliated Tumor Hospital of Guangzhou Medical University. Informed consent was obtained from each patient, in accordance with the IRB regulations.
NSCLC, squamous cell carcinoma
4D-CT pulmonary ventilation imaging
The Oncentra treatment planning system, version 4.1 (Nucletron V.B., Veenendaal, The Netherlands) was used to delineate the target volumes and organs at risk (OARs) and for IMRT planning and dose calculation. Both target volumes and OARs, including the spinal cord, esophagus, heart, and lungs, were contoured and approved on peak-exhale 4D-CT images by an attending physician. The gross tumor volume to clinical target volume (CTV), and CTV to planning target volume (PTV) margins were 6–8 mm and 8 mm, respectively. Planning OAR volumes were generated for the spinal cord and esophagus by adding 5.0-mm isotropic margins. In addition, functional lung regions were defined from 4D-CT ventilation images for functional planning, as described for other IMRT studies for NSCLC . In this study, regions in the top 30% for ventilation in the 4D-CT-based ventilation image were set as functional lung structures to avoid in the functional IMRT plans. Moreover, the total lung and functional lung represented the total volume and the functional part of the sum of both lungs.
IMRT planning goals and constraints
Min. dose ≥65 Gy
Max. dose ≤70 Gy
Volume receiving ≥66 Gy more than 95%
Dmean 20 Gy
Volume receiving ≥20 Gy less than 30%
Volume receiving ≥30 Gy less than 20%
Max. point dose ≤40 Gy
Volume receiving ≥40 Gy less than 100%
Volume receiving ≥45 Gy less than 67%
Volume receiving ≥60 Gy less than 33%
Volume receiving ≥55 Gy less than 35%
Max. dose ≤70 Gy
Volume receiving ≥20 Gy less than 20%
Volume receiving ≥10 Gy less than 35%
Data analysis and statistical methods
The quality of the IMRT plans was evaluated by comparing the metrics of PTVs using common dose-volume parameters such as the conformity index (CI), heterogeneity index (HI), mean dose (Dmean), and total number of monitor units (MUs). Dosimetric parameters including the percentage of lung volume receiving >5 Gy, >10 Gy, >20 Gy, and >30 Gy were calculated for the functional lung (FLV5, FLV10, FLV20, and FLV30, respectively) and total lung (TLV5, TLV10, TLV20, and TLV30, respectively). Regarding the other critical structures, the maximum dose (Dmax) delivered to the spinal cord, the Dmean and Dmax delivered to esophagus, and the V40, V45, and V60 delivered to the heart were also quantified and compared between the anatomic and functional plans with different beam arrangements.
Statistical analysis was performed using SPSS 19.0 statistical software (SPSS Inc., Chicago, IL, USA). Volumetric and dosimetric parameters for the target volumes and OARs were characterized using descriptive statistics. The dosimetric differences between the application of FESB and FMOB were evaluated for each plan and compared using paired, two tailed t-tests. A P value < 0.05 was considered statistically significant.
Comparison of PTV parameters between different plans
Mean dose (Gy)
Comparison of dosimetric parameters for total and functional lung between anatomic and functional plan for the same beam setups
Comparison of dosimetric parameters for total lung between different beam arrangements
Comparison of dosimetric parameters for functional lung between different beam arrangements
Comparison of dosimetric parameters for OARs between different beam arrangements
Current RT planning aimed at limiting lung toxicity assumes a uniform distribution of pulmonary function, and fails to take account of spatial and temporal patterns. Previous studies demonstrated that the incidence and seriousness of RP were positively correlated with total radiation dose to the lungs . Clarification of the relationship between radiation dose and changes in pulmonary function may help to predict and reduce RT-induced pulmonary toxicity. Decreasing the radiation dose to functional lung areas and directing the rays to the parts with perfusion/ventilation defects may help to protect highly functional lung regions and thus reduce the incidence and seriousness of RP .
Lung function can be evaluated by functional imaging modalities such as SPECT, PET/CT and 3He-MRI. However, these imaging modalities are not yet widely available in China, and their routine application in clinical practice would be associated with a long scan time and high costs to patients. We therefore assessed the value of acquiring functional information using the newly-reported 4D-CT-based ventilation imaging, which has the advantage that ventilation images can be calculated using only an additional processing step (i.e., DIR).
The results of this study showed that 4D-CT-based ventilation information could be used to reduce the radiation dose to the highly functional areas of the lung, assessed by FLV5–20, compared with anatomic planning alone, which was consistent with the results reported in previous published papers [15, 16]. Moreover, our findings indicated that both anatomic and functional treatment plans using FMOB could reduce the functional lung regions exposed to lower doses (FLV5–20), without compromising target volume coverage, compared with FESB. In addition to the observed improvements in dose-volume parameters of the functional lung, this study also identified dosimetric improvements in the low-dose zones of total lung, especially in terms of improved V20 volume. These results were compatible with that of a recent study investigating functional IMRT treatment planning using 4D-CT images . Functional plans using an optimal beam arrangement aimed at preserving the functional lung did not compromise the DVHs of OARs, such as the spinal cord, esophagus, and heart, which may be an additional important clinical factor. These results also demonstrated that this technique could be applied safely to RT treatments for patients with NSCLC, without exceeding the dose-volume tolerances of OARs.
Although significant dosimetric improvements were observed in the lower-dose regions of functional and total lung, the clinical relevance of these improvements in terms of reducing the risk of RT-induced pulmonary toxicity remains unclear. There is currently insufficient outcome data to confirm the correlation between functional lung dose-volume parameters and pulmonary toxicity endpoints, and further studies are needed to determine if dosimetric reductions to functional lung will translate into clinical benefits for NSCLC patients.
Although, several existing studies have validated the 4D-CT-based ventilation imaging modality [23, 24], its regional physiologic accuracy has not been validated in patients. In addition, temporal changes in regional ventilation to a segment of lung previously impaired by compression from a local tumor might occur during the course of RT. A possible explanation of these changes is that the shrinkage of lung tumor volume in response to IMRT treatment may result in increased ventilation as a result of reopening of the airways .
Ongoing studies aim to address the above issues by long-term follow-up of a preliminary patient cohort with known functional lung dose-volume parameters. The physiologic accuracy of 4D-CT-based ventilation imaging will be assessed in these patients by quantifying the impact of temporal changes in ventilation during the course of RT and evaluating pulmonary function and morbidity outcomes after radical RT.
In conclusion, this study demonstrated the feasibility of functional treatment planning using 4D-CT-based pulmonary ventilation information to identify structures to avoid. The results further indicated the dosimetric benefit of optimal beam arrangement compared with fixed-beam arrangement in IMRT treatment planning, in terms of preserving functional lung at lower radiation doses in patients with NSCLC.
This study was partially supported by a National Natural Scientific Foundation of China grant (81170078), a Guangdong Provincial Science and Technology Agency grant (2011B031800111), and a Guangzhou Municipal Science and Technology Agency grant (2011 J4300131).
- Mazeron R, Etienne-Mastroianni B, Perol D, Arpin D, Vincent M, Falchero L, Martel-Lafay I, Carrie C, Claude L: Predictive factors of late radiation fibrosis: a prospective study in non-small cell lung cancer. Int J Radiat Oncol Biol Phys 2010, 77: 38-43.View ArticlePubMedGoogle Scholar
- Ding X, Ji W, Li J, Zhang X, Wang L: Radiation recall pneumonitis induced by chemotherapy after thoracic radiotherapy for lung cancer. Radiat Oncol 2011, 6: 24.PubMed CentralView ArticlePubMedGoogle Scholar
- Mehta V: Radiation pneumonitis and pulmonary fibrosis in non-small-cell lung cancer: pulmonary function, prediction, and prevention. Int J Radiat Oncol Biol Phys 2005, 63: 5-24.View ArticlePubMedGoogle Scholar
- Park YH, Kim JS: Predictors of radiation pneumonitis and pulmonary function changes after concurrent chemoradiotherapy of non-small cell lung cancer. Radiat Oncol J 2013, 31: 34-40.PubMed CentralView ArticlePubMedGoogle Scholar
- Graham MV, Purdy JA, Emami B, Harms W, Bosch W, Lockett MA, Perez CA: 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.View ArticlePubMedGoogle Scholar
- Murshed H, Liu HH, Liao Z, Barker JL, Wang X, Tucker SL, Chandra A, Guerrero T, Stevens C, Chang JY, Jeter M, Cox JD, Komaki R, Mohan R: Dose and volume reduction for normal lung using intensity-modulated radiotherapy for advanced-stage non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2004,58(4):1258-1267.View ArticlePubMedGoogle Scholar
- Shioyama Y, Jang SY, Liu HH, Guerrero T, Wang X, Gayed IW, Erwin WD, Liao Z, Chang JY, Jeter M, Yaremko BP, Borghero YO, Cox JD, Komaki R, Mohan R: Preserving functional lung using perfusion imaging and intensity-modulated radiation therapy for advanced-stage non-small cell lung cancer. Int J Radiat Oncol Biol Phys 2007, 68: 1349-1358.View ArticlePubMedGoogle Scholar
- Castillo R, Castillo E, Martinez J, Guerrero T: Ventilation from four-dimensional computed tomography: density versus Jacobian methods. Phys Med Biol 2010, 55: 4661-4685.View ArticlePubMedGoogle Scholar
- van Beek EJR, Wild JM, Kauczor H-U, Schreiber W, Mugler JP, de Lange EE: Functional MRI of the lung using hyperpolarized 3-helium gas. J Magn Reson Imaging 2004, 20: 540-554.View ArticlePubMedGoogle Scholar
- Fain S, Schiebler ML, McCormack DG, Parraga G: Imaging of lung function using hyperpolarized helium-3 magnetic resonance imaging: Review of current and emerging translational methods and applications. J Magn Reson Imaging 2010, 32: 1398-1408.PubMed CentralView ArticlePubMedGoogle Scholar
- Gur D, Shabason L, Borovetz HS, Herbert DL, Reece GJ, Kennedy WH, Serago C: Regional Pulmonary Ventilation Measurements by Xenon Enhanced Dynamic Computed Tomography: An Update. J Comput Assist Tomog 1981, 5: 678-683.View ArticleGoogle Scholar
- Yamamoto T, Kabus S, Klinder T, Lorenz C, von Berg J, Blaffert T, Loo BW Jr, Keall PJ: Investigation of four-dimensional computed tomography-based pulmonary ventilation imaging in patients with emphysematous lung regions. Phys Med Biol 2011, 56: 2279-2298.View ArticlePubMedGoogle Scholar
- Rietzel E, Pan T, Chen GTY: Four-dimensional computed tomography: Image formation and clinical protocol. Med Phys 2005, 32: 874-889.View ArticlePubMedGoogle Scholar
- Ding K, Bayouth JE, Buatti JM, Christensen GE, Reinhardt JM: 4DCT-based measurement of changes in pulmonary function following a course of radiation therapy. Med Phys 2010, 37: 1261-1272.PubMed CentralView ArticlePubMedGoogle Scholar
- Yamamoto T, Kabus S, von Berg J, Lorenz C, Keall PJ: Impact of four-dimensional computed tomography pulmonary ventilation imaging-based functional avoidance for lung cancer radiotherapy. Int J Radiat Oncol Biol Phys 2011, 79: 279-288.View ArticlePubMedGoogle Scholar
- Yaremko BP, Guerrero TM, Noyola-Martinez J, Guerra R, Lege DG, Nguyen LT, Balter PA, Cox JD, Komaki R: Reduction of normal lung irradiation in locally advanced non-small-cell lung cancer patients, using ventilation images for functional avoidance. Int J Radiat Oncol Biol Phys 2007, 68: 562-571.PubMed CentralView ArticlePubMedGoogle Scholar
- Yu H, Zhang SX, Wang RH, Zhang GQ, Tan JM: The feasibility of mapping dose distribution of 4DCT images with deformable image registration in lung. Biomed Mater Eng 2014, 24: 145-153.PubMedGoogle Scholar
- Sorzano CO, Thévenaz P, Unser M: Elastic registration of biological images using vector-spline regularization. IEEE Trans Biomed Eng 2005, 52: 652-663.View ArticlePubMedGoogle Scholar
- Reinhardt JM, Ding K, Cao K, Christensen GE, Hoffman EA, Bodas SV: Registration-based estimates of local lung tissue expansion compared to xenon CT measures of specific ventilation. Med Image Anal 2008, 12: 752-763.PubMed CentralView ArticlePubMedGoogle Scholar
- Kim M, Lee J, Ha B, Lee R, Lee KJ, Suh HS: Factors predicting radiation pneumonitis in locally advanced non-small cell lung cancer. Radiat Oncol J 2011,29(3):181-190.PubMed CentralView ArticlePubMedGoogle Scholar
- Yin Y, Chen JH, Li BS, Liu TH, Lu J, Bai T, Dong XL, Yu JM: Protection of lung function by introducing single photon emission computed tomography lung perfusion image into radiotherapy plan of lung cancer. Chin med J (Engl) 2009, 122: 509-513.Google Scholar
- Huang TC, Hsiao CY, Chien CR, Liang JA, Shih TC, Zhang GG: IMRT treatment plans and functional planning with functional lung imaging from 4D-CT for thoracic cancer patients. Radiat Oncol 2013, 8: 3.PubMed CentralView ArticlePubMedGoogle Scholar
- Guerrero T, Sanders K, Castillo E, Zhang Y, Bidaut L, Pan T, Komaki R: Dynamic ventilation imaging from four-dimensional computed tomography. Phys Med Biol 2006, 51: 777-791.View ArticlePubMedGoogle Scholar
- Guerrero T, Sanders K, Noyola-Martinez J, Castillo E, Zhang Y, Tapia R, Guerra R, Borghero Y, Komaki R: Quantification of regional ventilation from treatment planning CT. Int J Radiat Oncol Biol Phys 2005, 62: 630-634.View ArticlePubMedGoogle Scholar
- Seppenwoolde Y, Muller SH, Theuws JC, Baas P, Belderbos JS, Boersma LJ, Lebesque JV: Radiation dose-effect relations and local recovery in perfusion for patients with non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2000, 47: 681-690.View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.