|Year : 2008 | Volume
| Issue : 4 | Page : 147-153
Magnitude of shift of tumor position as a function of moderated deep inspiration breath-hold: An analysis of pooled data of lung patients with active breath control in image-guided radiotherapy
KR Muralidhar1, P Narayana Murthy2, D Shanker Mahadev1, K Subramanyam1, G Sudarshan1, A Krishnam Raju1
1 Indo-American Cancer Institute and Research Center, Hyderabad, AP, India
2 Department of Physics, Nagarjuna University, Guntur, AP, India
|Date of Submission||20-Apr-2008|
|Date of Acceptance||29-May-2008|
K R Muralidhar
Indo-American Cancer Institute and Research Center, Road No: 14, Banjara Hills, Hyderabad, AP
| Abstract|| |
The purpose of this study was to evaluate the reproducibility and magnitude of shift of tumor position by using active breathing control and iView-GT for patients with lung cancer with moderate deep-inspiration breath-hold (mDIBH) technique. Eight patients with 10 lung tumors were studied. CT scans were performed in the breath-holding phase. Moderate deep-inspiration breath-hold under spirometer-based monitoring system was used. Few important bony anatomic details were delineated by the radiation oncologist. To evaluate the interbreath-hold reproducibility of the tumor position, we compared the digital reconstruction radiographs (DRRs) from planning system with the DRRs from the iView-GT in the machine room. We measured the shift in x, y, and z directions. The reproducibility was defined as the difference between the bony landmarks from the DRR of the planning system and those from the DRR of the iView-GT. The maximum shift of the tumor position was 3.2 mm, 3.0 mm, and 2.9 mm in the longitudinal, lateral, and vertical directions. In conclusion, the moderated deep-inspiration breath-hold method using a spirometer is feasible, with relatively good reproducibility of the tumor position for image-guided radiotherapy in lung cancers.
Keywords: Active breath control, digital reconstruction radiographs, image-guided radiotherapy, iView-GT
|How to cite this article:|
Muralidhar K R, Murthy P N, Mahadev D S, Subramanyam K, Sudarshan G, Raju A K. Magnitude of shift of tumor position as a function of moderated deep inspiration breath-hold: An analysis of pooled data of lung patients with active breath control in image-guided radiotherapy. J Med Phys 2008;33:147-53
|How to cite this URL:|
Muralidhar K R, Murthy P N, Mahadev D S, Subramanyam K, Sudarshan G, Raju A K. Magnitude of shift of tumor position as a function of moderated deep inspiration breath-hold: An analysis of pooled data of lung patients with active breath control in image-guided radiotherapy. J Med Phys [serial online] 2008 [cited 2013 May 25];33:147-53. Available from: http://www.jmp.org.in/text.asp?2008/33/4/147/44475
| Introduction|| |
Respiratory motion studies have tracked the movement of the tumor the host organ; radiographic fiducial markers imbedded at the tumor site; radioactive tracers targeting the tumor; and surrogate organs, such as the diaphragm, which are assumed to correlate with the tumor.
To reduce the target margin error due to respiratory motion, various respiratory motion-control treatment techniques, including gating, ,, breath holding,  or active breathing control (ABC), , are used in radiotherapy. A precise breathing-monitoring system is needed for such techniques. The most commonly used systems are as follows.
The spirometer to measure the change in the lung volume, measurement of the surface of the abdomen by tracking a reflective marker on the chest with a fixed camera ,,,, or by measuring the distance from a fixed point to the surface of the abdomen using a laser-based distance sensor  and by tracking internal markers using x-ray ,,,, or internal sensors using magnetic fields. 
Stereotactic radiotherapy (SRT) in the treatment of lung tumors has been shown to have good results and low morbidity , and has been supported by various methods using immobilization devices  or coordinating systems for respiratory motion. To reduce respiratory motion during Image-guided radiotherapy (IGRT) for lung or liver tumors and improve feasibility for IGRT in elderly patients or patients with pulmonary dysfunction, we used deep-inspiration breath-hold method. Reproducibility of organ position, especially diaphragmatic motion, was verified in healthy volunteers by others.  However, the diaphragm position does not necessarily reflect the lung tumor position directly, especially for tumors in the lower lobe, due to the complexity of tumor motion in a clinical setting.  Because of this, from June 2007, we have used the '2D-2D match analysis of bony landmarks' method in IGRT for lung tumors and clinically and directly verified the interbreath-hold reproducibility of tumor position using CT scans before the treatment.
| Materials and Methods|| |
Active breath control system
It consists of the patient's respiratory system, which again consists of mouthpiece, transducer turbine, balloon valve coupler, etc.; mirror support system, patient control switch, RS-232 cable, control computer, and PC extender system transmitter [Figure 1A]. Schematic drawing of the above system is also shown in [Figure 1B].
Eight patients with lung cancer were treated with RT and were studied from March 2007 to January 2008 [Table 1]. All tumors were delivered 5 Gy per fraction at the isocenter, and the total dose was 50 Gy with 10 fractions, with a deep-inspiration breath-hold method using spirometer-based monitoring. The median age was 62 years (range, 47-82 years). Five patients were male and 3 patients were female. Six patients were diagnosed with primary lung cancers, and 2 patients had secondary lymphanode from primary. The median tumor volume was 69 cc (range, 10.33-149.13 cc). Tumor location was as follows: 2 tumors in the right upper lobe (RUL), 2 tumors in the right middle lobe (RML), 4 tumors in the right lower lobe (RLL), and 2 tumors in the left upper lobe (LUL). All tumors were peripheral lung tumors and were not adjacent to other organs, such as the chest wall or heart.
The deep-inspiration breath-hold method using spirometer-based monitoring in active breath control system
Here we describe the procedure of the active breath control method using a spirometer.
A reproducible state of maximum breath-hold (deep-inspiration breath-hold [DIBH]) is advantageous for treating thoracic tumors, because it significantly reduces respiratory tumor motion and changes internal anatomy in a way that often protects critical normal tissues. The pneumotach spirometer is a differential pressure transducer that measures air flow; a computer program integrates the signal to obtain the volume of air breathed in and out, which is displayed and recorded as a function of time. To monitor the respiratory phase and breath-holding phase, the patient breathed through a mouthpiece connected to a pneumotachometer. The other end of the pneumotachometer was attached to a spirometer to assist the breath-hold. A nose clip was used to prevent nasal breathing and ensure that the patient breathed through the mouthpiece. For patient setup, we used all-in-one (AIO) immobilization system (POCL, USA) [Figure 2]. The workstation showed the spirometry signal, yielded the respiratory tidal volume of the patient, and was able to display a flow-time curve which can show the state of inspiration, expiration, and breath-hold [Figure 3].
After a predefined volume of air (threshold volume) has passed through the spirometer, a small balloon valve inflates and occludes the tube, applying an assisted BH. The system is configurable to each individual patient or procedure, with variable threshold levels and BH durations possible. At all times, the patient is in control of the BH, via a patient control switch. This switch when depressed will initiate an ABC procedure; and if released, it will automatically open the balloon valve and allow the patient to breathe freely. Before the treatment, patients were familiarized with the procedure with training sessions. For the initial training session, a separate clinic room was used to avoid unnecessary utilization of the CT scanner facility. During this session, explanations were provided regarding the ABC procedure, and an appropriate threshold level and BH duration were determined. Threshold limit was taken as 80% of the maximum value of the deep inspiration. On an average, 20 seconds were taken as time duration for which breath was held. The patient immediately proceeded to the CT scanner, where the 3-D dataset was acquired.
CT scan procedure
The largest intra-fraction motion observed is respiratory motion. CT scans (Somatom, Siemens, USA) were performed in the breath-holding (the moderated deep inspiration) phase. Set-up was also performed at the treatment position. Images were acquired with moderate deep-inspiration breath-hold (mDIBH) during 2 to 3 BHs, depending on the BH duration and length of the scan, and were sent to three-dimensional (3D) treatment planning system (CMS XIO planning system, USA). A slice thickness of 2 mm was taken for this study.
Target delineation and data analysis
Target delineation was performed on a 3D treatment planning system. A physician delineated the target volume on the axial CT slices using lung CT window settings. Pleural indentations were included within the target. MRI and PET CT were used for delineation.
Digital reconstructed radiographs from planning system were used to compare the images taken from iView-GT for tumor position and potential motion during ABC in the treatment room using 2D-2D matching tool for bony landmark [Figure 4]. Daily patient position can be corrected based on accurate 4-D data at the time of radiation delivery. Portal images were taken five times with the same threshold that we used for scanning during one treatment delivery. This procedure was chosen to measure the reproducibility that can eliminate any external setup errors, and thus all tumor displacement would be a measure of internal motion only. The deviation was measured and displayed in graphical form, as shown in [Figure 5],[Figure 6],[Figure 7],[Figure 8],[Figure 9],[Figure 10],[Figure 11]. During an ABC procedure, a specifically designed device is utilized to reproducibly apply the same breath-holding level for each session. After a predefined volume of air (threshold volume) has passed through the spirometer, a small balloon valve will inflate and occlude the tube, applying an assisted breath-hold (BH). The system is configurable to each individual patient or procedure, with variable threshold levels and BH durations possible. For the same value of threshold, the shifts in x, y, and z directions of target were noticed and tabulated. This was done with the help of comparison of AP and lateral DRRs with 4D-CT DRRs using 2D-2D match tool in iView-GT. The treatment table was moved to match DRRs, and treatment delivery was begun.
| Results|| |
A total of 80 fractions of radiation were delivered using ABC breath-holds. Our study pertains to 40 observations taken @ 5 mDIBHs per patient in one of the treatment fractions. Up to 3.2 mm intra-fraction motion of the tumor was observed on DRR during ABC breath-holds. The maximum shifts in x, y, and z directions were 3 mm, 3.2 mm, and 2.9 mm respectively, indicating a change of tumor position over the course of treatment with breath-holds at the same phase of the respiratory cycle (mDIBH) with the same value of threshold.
| Discussion|| |
Good reproducibility of the tumor position has been reported in all kinds of breath-hold methods. Cheung et al.  reported that the inter-fraction reproducibility of the tumor position with the active breath control (ABC) device, which temporary immobilizes the patient's breathing and the average displacement of the GTV center was 0.3 mm (±1.8 mm), 1.2 mm (±2.3 mm), and 1.1 mm (±3.5 mm) in LR, AP, and CC directions respectively.
According to Cheung et al., the average (±standard deviation) displacement of GTV centers with ABC breath-hold applied was 0.3 mm ((±1.8 mm), 1.2 mm ((±2.3 mm), and 1.1 mm ((±3.5 mm) in the lateral direction, anterior-posterior direction, and superior-inferior direction respectively. 
The DIBH maneuver was found to be highly reproducible, with intrabreath-hold reproducibility of 1.0 ((±0.9) mm and interbreath-hold reproducibility of 2.5 ((±1.6) mm, as determined from diaphragm position. Patients were able to perform 10 to 13 breath-holds in one session, with comfortable breath-hold duration of 12 to 16 seconds. 
In our study, the shift in the tumor position was 3.2 mm, 3.0 mm, and 2.9 mm in CC, LR, and AP directions respectively by using the moderated deep-inspiration technique by matching bony anatomy from TPS to iView-GT-through DRRs. To derive the shift values, a model table for a single patient out of 10 patients is shown in [Table 2]. These results are similar to the results of other reports with breath-hold methods. Seppenwoolde et al.  demonstrated that the trajectory of the tumor during inhalation is different from the trajectory during exhalation, i.e., hysteresis, by analyzing the 3D motion of lung tumors during radiotherapy using a real-time tumor-tracking system, and suggested the complexity of tumor motion, especially that of tumor motion in the lower lobe. Our study suggested that our method would be effective for temporary immobilization of respiratory motion in the lower lobe and in the upper lobe.
We have to pay more attention to the patient-training sessions and monitoring of respiratory motion during treatment. The advantage of our method is feasibility in many patients and adaptability by many institutions because patients are able to hold their breath more comfortably at the deep-inspiration phase. One more advantage of this study is single-time CT with ABC is sufficient instead of taking CT scan 4 to 5 times to study the intrafraction movement of the tumor. In our experience, this method is very much feasible for elderly patients also.
We calculated geometric uncertainties of the tumor position from our results. There have been many reports focused on the geometric uncertainties of the setup. ,,, However, there are few reports focused on the geometric uncertainties of internal organs or tumor motion.
Stroom et al. and Kutcher et al. calculated the geometric uncertainties in radiotherapy due to internal organ motion and external setup deviations. Both deviations consist of a systematic component, which is the same for each fraction of the treatment; as well as a random component, which varies from day to day. ,
Stroom et al.  calculated the geometric uncertainties of lung cancer patients. In this study, systematic deviations were 2 mm, 3 mm, and 3 mm in LR, AP, and CC directions respectively, and random deviations were 4 mm, 5 mm, and 5 mm in LR, AP, and CC directions respectively. However, it was considered meaningful to obtain the reproducibility of the tumor position (x, y, z vectors), as well as systematic and random motion deviations by our breath-hold method; and we believe that the internal margin of the interbreath-hold reproducibility of lung tumor position would be within almost 5 mm in vector for the treatment planning of IGRT or SRT due to the relatively good reproducibility of our method.
| Conclusion|| |
Even though we are using very sophisticated instruments like active breathe control systems to control the moving targets, there are still some intrafraction variations in the position of the tumor. Daily tumor targeting of lung cancers is feasible with the help of DRRs from planning system when compared with DRRs from iView-GT. Much accuracy is needed when we go for hypo-fractionation. Due to these reasons, we studied the intrafraction variations by using mDIBH in a single fraction 5 times on 8 patients. In our study, we have taken the DRRs of the bony anatomy as reference. We compared the DRRs from the TPS to the DRRs from the iView-GT in selected gating phase. Our data demonstrate good intrafraction reproducibility of lung tumor position using ABC with same value of threshold limit.
A patient cannot inhale the same amount of air every time even though the threshold value is kept the same. As the volume of inhalation is different for different durations, the maximum shift observed is less than 4 mm. For maximum difference of inhaling volume, there is a need for observing the shift. The results that were obtained were closer with other authors' results that compared TPS data to the iView-GT data by using soft tissues, external markers. and internal permanent markers. If this shift is less than the permissible level, we can continue treatment; otherwise, new session of mDIBH should start. Also, a margin of 5 mm has to be given while contouring itself for compensating the magnitude of the shift of tumor position with respect to mDIBH. This procedure will enable us to provide better and more accurate treatment.
Finally, we can conclude that the moderated deep-inspiration breath-hold method using a spirometer is feasible, with relatively good reproducibility of the tumor position for image-guided radiotherapy in lung cancers.
| References|| |
|1.||Tada T, Minakuchi K, Fujioka T, Sakurai M, Koda M, Kawase I, et al. Lung cancer: Intermittent irradiation synchronized with respiratory motion-results of a pilot study. Radiology 1998;207:779-83. [PUBMED] [FULLTEXT]|
|2.||Kubo HD, Len PM, Minohara S, Mostafavi H. Breathing synchronized radiotherapy program at the University of California Davis Cancer Center. Med Phys 2000;27:346-53. [PUBMED] |
|3.||Wagman R, Yorke E, Ford E, Giraud P, Mageras G, Minsky B, et al. Respiratory gating for liver tumors: Use in dose escalation. Int J Radiat Oncol Biol Phys 2003;55:659-68. [PUBMED] [FULLTEXT]|
|4.||Hanley J, Debois MM, Mah D, Mageras GS, Raben A, Rosenzweig K, et al. Deep inspiration breath-hold technique for lung tumors: The potential value of target immobilization and reduced lung density in dose escalation. Int J Radiat Oncol Biol Phys 1999;45:603-11. [PUBMED] [FULLTEXT]|
|5.||Wong JW, Sharpe MB, Jaffray DA, Kini VR, Robertson JM, Stromberg JS, et al. The use of active breathing control-ABC to reduce margin for breathing motion. Int J Radiat Oncol Biol Phys 1999;44:911-9. [PUBMED] [FULLTEXT]|
|6.||Dawson LA, Brock KK, Kazanjian S, Fitch D, McGinn CJ, Lawrence TS, et al. The reproducibility of organ position using active breathing control-ABC during liver radiotherapy. Int J Radiat Oncol Biol Phys 2001;51:1410-21. [PUBMED] [FULLTEXT]|
|7.||Mageras GS, Yorke E, Rosenzweig K, Braban L, Keatley E, Ford E, et al. Fluoroscopic evaluation of diaphragmatic motion reduction with a respiratory gated radiotherapy system. J Appl Clin Med Phys 2001;2:191-200. [PUBMED] |
|8.||Wagman R, Yorke E, Ford E, Giraud P, Mageras G, Minsky B, et al. Respiratory gating for liver tumors: Use in dose escalation. Int J Radiat Oncol Biol Phys 2003;55:659-68. [PUBMED] [FULLTEXT]|
|9.||Nehmeh SA, Erdi YE, Ling CC, Rosenzweig KE, Squire OD, Braban LE, et al. Effect of respiratory gating on reducing lung motion artifacts in PET imaging of lung cancer. Med Phys 2002;29:366-71. [PUBMED] |
|10.||Hugo GD, Agazaryan N, Solberg TD. An evaluation of gating window size, delivery method and composite field dosimetry of respiratory-gated IMRT. Med Phys 2002;29:2517-25. [PUBMED] |
|11.||Shimizu S, Shirato H, Ogura S, Akita-Dosaka H, Kitamura K, Nishioka T, et al. Detecting of lung tumor movement in real-time tumor-tracking radiotherapy. Int J Radiat Oncol Biol Phys 2001;51:304-10. [PUBMED] [FULLTEXT]|
|12.||Shirato H, Shimizu S, Kunieda T, Kitamura K, van Herk M, Kagei K, et al. Physical aspects of a real-time tumor-treacking system for gated radiotherapy. Int J Radiat Oncol Biol Phys 2000;48:1187-95. [PUBMED] [FULLTEXT]|
|13.||Harada T, Shirato H, Ogura S, Oizumi S, Yamazaki K, Shimizu S, et al. Real-time tumor-tracking radiation therapy for lung carcinoma by the aid of insertion of a gold marker using bronchofiberscopy. Cancer 2002;95:1720-7. [PUBMED] [FULLTEXT]|
|14.||Seppenwoolde Y, Shirato H, Kitamura K, Shimizu S, van Herk M, Lebesque JV, et al. Precise and real-time measurement of 3D tumor motion in lung due to breathing and heatbeat, measured during radiotherapy. Int J Radiat Oncol Biol Phys 2002;53:822-33. [PUBMED] [FULLTEXT]|
|15.||Shirato H, Shimizu S, Kitamura K, Nishioka T, Kagei K, Hashimoto S, et al. Four-dimensional treatment planning and fluoroscopic real time tumor tracking radiotherapy for moving tumor. Int J Radiat Oncol Biol Phys 2000;48:435-42. [PUBMED] [FULLTEXT]|
|16.||Seiler PG, Blattmann H, Kirsch S, Muench RK, Schilling C. A novel tracking technique for the continuous precise measurement of tumor position in conformal radiotherapy. Phys Med Biol 2000;45:103-10. |
|17.||Onishi H, Araki T, Shirato H, Nagata Y, Hiraoka M, Gomi K, et al. Stereotactic hypofractionated high-dose irradiation for stage I non-small cell lung carcinoma: Clinical outcomes in 245 subjects in a Japanese multi-institutional study. Cancer 2004;101:1623-31. [PUBMED] [FULLTEXT]|
|18.||Uematsu M, Shioda A, Suda A, Fukui T, Ozcki Y, Hama Y, et al. Computed tomography-guided frameless stereotactic radiotherapy for stage I non-small-cell lung cancer:a 5-year experience. Int J Radiat Oncol Biol Phys 2001;51:666-70. |
|19.||Negoro Y, Nagata Y, Aoki T, Mizowaki T, Araki N, Takayami K, et al. The effectiveness of an immobilization device in conformal radiotherapy for lung tumor: Reduction of respiratory tumor movement and evaluation of the daily setup accuracy. Int J Radiat Oncol Biol Phys 2001;50:889-98. |
|20.||Kimura T, Hirokawa Y, Murakami Y, Tsujimura M, Nakashima T, Ohno Y, et al. Reproducibility of organ position using voluntary breath-hold method with spirometer for extracranial stereotactic radiotherapy. Int J Radiat Oncol Biol Phys 2004;60:1307-13. [PUBMED] [FULLTEXT]|
|21.||Seppenwoolde Y, Shirato H, Kitamura K, Shimizu S, Herk M, Lebesque JV, et al. Precise and real-time measurement of 3D tumour motion in lung due to breathing and heartbeat, measured during radiotherapy. Int J Radiat Oncol Biol Phys 2002;53:822-3. [PUBMED] [FULLTEXT]|
|22.||Cheung PC, Sixel KC, Tirona R, Ung RC. Reproducibility of lung tumor position and reduction of lung mass within the planning target volume using active breathing control (ABC). Int J Radiat Oncol Biol Phys 2003;23:1437-42. |
|23.||Cheung PC, Sixel KE, Tirona R, Ung YC. Reproducibility of lung tumor position and reduction of lung mass within the planning target volume using active breathing control (ABC). Int J Radiat Oncol Biol Phys 2003;57:1437-42. [PUBMED] [FULLTEXT]|
|24.||Hanley J, Debois MM, Mah D, Mageras GS, Raben A, Rosenzweig K, et al. Deep inspiration breath-hold technique for lung tumors: The potential value of target immobilization and reduced lung density in dose escalation. Int J Radiat Oncol Biol Phys 1999;45:603-11. [PUBMED] [FULLTEXT]|
|25.||Bijhold J, Lebesque JV, Hart AA, Vijlbrief RE. Maximizing setup accuracy using portal images as applied to a conformal boost technique for prostatic cancer. Radiother Oncol 1992;24:261-71. [PUBMED] |
|26.||Onimaru R, Shirato H, Aoyama H, Kitamura K, Seki T, Hida K, et al. Calculation of rotational setup error using the real-time tracking radiation therapy (RTRT) system and its application to the treatment of spinal schwannoma. Int J Radiat Oncol Biol Phys 2002;54:939-47. |
|27.||Boer HC, Koste JR, Senan S, Visset AG, Heijmen BJ. Analysis and reduction of 3D systematic and random setup errors during the simulation and treatment of lung cancer patients with CT-based external beam radiotherapy dose planning. Int J Radiat Oncol Biol Phys 2001;49:857-68. |
|28.||Samuelsson A, Mercke C, Johansson KA. Systematic set-up errors for IMRT in the head and neck region: Effect on dose distribution. Radiothear Oncol 2003;66:303-11. |
|29.||Stroom JC, Boer HC, Huizehga H, Visset AG. Inclusion of geometrical uncertainties in radiotherapy treatment planning by means of coverage probability. Int J Radiat Oncol Biol Phys 1999;43:905-19. |
|30.||Kutcher GJ, Mageras GS, Leibel SA. Control, correction, and modeling of setup errors and organ motion. Semin Radiat Oncol 1995;5:134-45. |
[Figure 1A], [Figure 1B], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11]
[Table 1], [Table 2]
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