Intrafractional motion management in external beam radiotherapy

Abstract

The recent advancements in radiotherapy technologies have made delivery of the highly conformal dose to the target volume possible. With the increasing popularity of delivering high dose per fraction in modern radiotherapy schemes such as in stereotactic body radiotherapy and stereotactic body ablative therapy, high degree of treatment precision is essential. In order to achieve this, we have to overcome the potential difficulties caused by patient instability due to immobilization problems; patient anxiety and random motion due to prolonged treatment time; tumor deformation and baseline shift during a treatment course. This is even challenging for patients receiving radiotherapy in the chest and abdominal regions because it is affected by the patient’s respiration which inevitably leads to tumor motion. Therefore, monitoring of intrafractional motion has become increasingly important in modern radiotherapy. Major intrafractional motion management strategies including integration of respiratory motion in treatment planning; breath-hold technique; forced shallow breathing with abdominal compression; respiratory gating and dynamic real-time tumor tracking have been developed. Successful intrafractional motion management is able to reduce the planning target margin and ensures planned dose delivery to the target and organs at risk. Meanwhile, the emergency of MRI-linear accelerator has facilitated radiation-free real-time monitoring of soft tissue during treatment and could be the future modality in motion management. This review article summarizes the various approaches that deal with intrafractional target, organs or patient motion with discussion of their advantages and limitations. In addition, the potential future advancements including MRI-based tumor tracking are also discussed.

Keywords

Intrafractional motion respiratory gating breath-hold tumor tracking real-time motion management

List of Abbreviations

4-D

4-dimenstional

ABC

Active breathing coordinator

Computed tomography

DIBH

Deep inspiration breath hold

DoF

Degree of freedom

DRR

Digitally reconstructed radiograph

fps

Frame per second

GTV

Gross tumor volume

IMRT

Intensity modulated radiotherapy

ITV

Internal target volume

Kilovoltage

LAD

artery Left anterior descending artery

MLC

Multi-leaf collimator

MRI

Magnetic resonance imaging

OAR

Organ at risk

OBI

On-board imager

PTV

Planning target volume

RPM

Real-time position management

SBRT

Stereotactic body radiation therapy

SBAR

Stereotactic ablative body radiation therapy

VMAT

Volumetric modulated arc therapy

1 Background

The goals of radiotherapy treatment are to deliver the sufficient radiation dose to the tumor so as to achieve adequate tumor control and low dose to the organs at risk (OARs) so as to minimize radiation-induced toxicity. With the recent advancements in radiotherapy technologies, external beam radiotherapy has been evolved to the delivery of highly conformal dose to the target volumes. These include intensity modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), stereotactic body radiation therapy (SBRT) and stereotactic ablative body radiation therapy (SBAR). In addition, hypofractionation schemes which employs higher dose per fraction and less number of fractions has become more popular and they are used to treat malignant diseases including lung, liver, pancreas, breast and prostate cancers [1 –5].

With the characteristics of delivering high dose per fraction, high degree of precision and rapid fall-off of radiation dose around the target volume in SBRT and SBAR, a high accuracy of target dose delivery is needed. Any tumor movement during treatment must be corrected so as to ensure that it receives the intended radiation dose. Dose escalation and tumor control may be limited by target or organs motion during irradiation resulted from various physiological processes. For instance, patients receiving radiotherapy treatment in the chest and abdominal regions are affected by normal breathing condition, and there is inevitable tumor motion due to respiration. In addition, the problems of patient instability due to imperfect immobilization device, patient anxiety and random motion due to prolonged treatment time, tumor deformation and baseline shift, have also been reported [6]. Tracking and monitoring of intrafractional motion has become increasingly important in modern radiotherapy.

The traditional method to avoid geographical miss of a moving target is to give a more generous margin to gross tumor volume (GTV), which enables to ensure the adequate tumor coverage. However, this inevitably leads to the irradiation of a relatively large volume of surrounding healthy tissue. Previous studies shown that tumor or organ motion was the greatest in the cranio-caudal direction, while left-right and antero-posterior amplitude were comparatively smaller [7 –9]. Akimoto M et al. [9] reported that tumor motion could be up to 15 to 24 mm in the cranio-caudal direction in pancreatic cancer patients and 34 mm in lung cancer patients. It is expected that effective motion tracking management will improve the accuracy of radiation delivery and allow the reduction of margin for the planning target volume (PTV); this will reduce the dose to the OARs and subsequently the radiation-induced complications.

2 Motion management approaches

There are two main approaches in motion management: passive and active. The passive approach is the conventional method that does not involve any intervention on the patient during treatment. It works by chasing the entire path of tumor motion in the localization process using 4-dimensional (4D) CT. The taking of 4DCT helps to identify the trajectory of tumor movement at different phases of the respiratory cycle and define the internal target volume (ITV) and PTV, which can encompass all possible locations of the tumor during respiration. Compared with the active monitoring approach, the passive approach produces a relatively larger PTV margin. In addition, it also cannot correct for the potential difference in tumor motion between CT-simulation and actual treatment conditions, and therefore cannot directly address the intrafractional motion problem.

The active approach can eliminate, reduce or track tumor motion during treatment. The methods developed include breath hold, forced shallow breathing with abdominal compression, respiratory gating and dynamic tumor tracking, which are discussed in the following paragraphs. A summary of the literatures which reported on the various active motion management methods are given in Table 1 and the details are discussed in the following paragraphs.

Table 1
Summary of literatures on radiotherapy motion monitoring

Technique Application Authors Comments

Deep inspiration breath hold Left breast cancer Register S et al.¹⁰, Darapu A et al.¹¹ Reduced risk of radiation associated cardiac perfusion

Pham T et al.¹², Vikström J et al.¹³ Involved use of VisionRT to reduce cardiac injury

Bruzzaniti V et al.¹⁴ Reduced mean lung dose by 16% and lung volume by 20%

Right breast cancer Rice et al.¹⁵ Reduced liver volume by 63% and dose by 46%

Breast cancer Latty D et al.¹⁹, Bergom C et al.²¹ Involved use of ABC to reduce radiation complications

Wang et al.²³ Involved use of ABC to spare heart and left anterior descending artery

Rydhög J²⁵ Involved use of ABC to reduce target margin and escalate target dose

Lung cancer Cole A et al.²² Involved use of ABC to reduce radiation complications

Abdominal compression Lung cancer Han K et al.²⁷ Reduced ITV size

Liver cancer SBRT Llacer-Moscardo C et al.²⁹ Reduced intrafractional liver motion

Pancreatic cancer Heerken et al.⁷ Reduced cranio-caudal motion by 40%

Respiratory gating Lung cancer Han K et al.²⁷ Reduced PTV size and normal tissue irradiation

Prostate &liver cancers Kitamura K et al.³³ Use of fiducial gold marker demonstrated better correlation

Lung cancer Ionascu D et al.³⁴ Use of internal fiducial marker demonstrated better correlation

Tumor tracking Phantom Burghelea et al.³⁸ Use of Vero system that kept maximum deviation < 0.6°

Oligometastases in lung &liver Depuydt et al.³⁹ Use of Vero system that reduced PTV volume in SBRT

Phantoms of chest &pelvis Wu V et al.⁴² ExacTrac reduced verification time and dose compared with OBI

MLC tracking Lung cancer Bedford J et al.⁴³ Conformal VMAT could be achieved without ITV in 4D SBRT

Cailet V et al.⁴⁵ Reduced PTV volume and OAR doses in SABR

Lung metastasis Booth J et al.⁴⁶ Reduced lung toxicity in SABR

Couch tracking Prostate cancer Nguyen D et al.⁴⁹, Wilbert J et al.⁵⁰ Achieved sub-millimetre accuracy in motion correction

MRI guidance Phantom Crijns S et al.⁵⁴, Choudhury A et al.⁵⁵ Achieved real-time reconstruction of accumulated dose and facilitated intrafractional online plan adaptation

Technique	Application	Authors	Comments
Deep inspiration breath hold	Left breast cancer	Register S et al.¹⁰, Darapu A et al.¹¹	Reduced risk of radiation associated cardiac perfusion
		Pham T et al.¹², Vikström J et al.¹³	Involved use of VisionRT to reduce cardiac injury
		Bruzzaniti V et al.¹⁴	Reduced mean lung dose by 16% and lung volume by 20%
	Right breast cancer	Rice et al.¹⁵	Reduced liver volume by 63% and dose by 46%
	Breast cancer	Latty D et al.¹⁹, Bergom C et al.²¹	Involved use of ABC to reduce radiation complications
		Wang et al.²³	Involved use of ABC to spare heart and left anterior descending artery
		Rydhög J²⁵	Involved use of ABC to reduce target margin and escalate target dose
	Lung cancer	Cole A et al.²²	Involved use of ABC to reduce radiation complications
Abdominal compression	Lung cancer	Han K et al.²⁷	Reduced ITV size
	Liver cancer SBRT	Llacer-Moscardo C et al.²⁹	Reduced intrafractional liver motion
	Pancreatic cancer	Heerken et al.⁷	Reduced cranio-caudal motion by 40%
Respiratory gating	Lung cancer	Han K et al.²⁷	Reduced PTV size and normal tissue irradiation
	Prostate &liver cancers	Kitamura K et al.³³	Use of fiducial gold marker demonstrated better correlation
	Lung cancer	Ionascu D et al.³⁴	Use of internal fiducial marker demonstrated better correlation
Tumor tracking	Phantom	Burghelea et al.³⁸	Use of Vero system that kept maximum deviation < 0.6°
	Oligometastases in lung &liver	Depuydt et al.³⁹	Use of Vero system that reduced PTV volume in SBRT
	Phantoms of chest &pelvis	Wu V et al.⁴²	ExacTrac reduced verification time and dose compared with OBI
MLC tracking	Lung cancer	Bedford J et al.⁴³	Conformal VMAT could be achieved without ITV in 4D SBRT
		Cailet V et al.⁴⁵	Reduced PTV volume and OAR doses in SABR
	Lung metastasis	Booth J et al.⁴⁶	Reduced lung toxicity in SABR
Couch tracking	Prostate cancer	Nguyen D et al.⁴⁹, Wilbert J et al.⁵⁰	Achieved sub-millimetre accuracy in motion correction
MRI guidance	Phantom	Crijns S et al.⁵⁴, Choudhury A et al.⁵⁵	Achieved real-time reconstruction of accumulated dose and facilitated intrafractional online plan adaptation

ABC = active breathing control, ITV = internal target volume, PTV = planning target volume, SBRT = stereotactic body radiotherapy, OBI = on-board imager, 4D = 4-dimensional, SABR = stereotactic ablation body radiotherapy.

3 Intrafractional motion management

3.1 Breath hold

Clinically, breath hold method is used for radiotherapy of cancers in the thoracic and upper abdominal regions. It is important for treatment that requires higher precision such as the SBRT of lung and liver cancers. Meanwhile, voluntary deep inspiration breath hold (DIBH) requires patient to voluntarily carry out a maximum inhalation and hold that level of inspiration during radiation delivery, either freely or with the help of a modified spirometer for 20 to 25 seconds. DIBH has been coupled with surface monitoring system, such as AlignRT (Vision RT Ltd, London, UK) or Real-time Position Management (RPM) (Fig. 1) (Varian Medical Systems, Palo Alto, CA) to allow an active monitoring of patient’s respiratory motion by using 3-dimensional surface tracking. AlignRT (Fig. 2) detects real-time surface image of patient, registers with the planned surface contour and calculates real-time positioning offsets, so that patient can be precisely aligned before treatment commence and monitored during treatment.

Fig.1

Real-time Position Management system.

Fig.2

AlignRT system. Diagram at right lower corner showing radiation beam coverage.

The RPM system uses an infrared camera mounted on the wall of the treatment room. Surrounding the camera, there are infrared lights aiming at the same direction as the camera. A marker box with reflective dots is usually placed at the xiphoid process or the upper abdomen of the patient to act as an external surrogate to measure the breathing motion of the patient. The camera detects the infrared lights reflected by the marker box and calculates its position. When the patient breathes, a graphical sinusoidal representation of the marker position is generated as a function of time, indicating the breathing motion of the patient. Breathing training is provided for the patient in order to obtain the deep inspiration threshold. Once the required threshold zone has been reached, the patient is asked to voluntarily hold the breath and the radiation is then given.

In the treatment of breast cancer, DIBH reduces cardiac dose by increasing the distance between the heart and the chest wall. This is particularly useful for the irradiation of the internal mammary nodes in the left side breast cancer patients where the target volume is closer to the heart [10, 11]. With DIBH technique, the heart is displaced posteriorly, medially and inferiorly away from the breast and the posterior border of the tangential fields; potentially avoiding radiation-associated cardiac perfusion [11]. It has been clinically proven that DIBH, with the use of AlignRT and RPM, was an effective mean to reduce cardiac injuries and cardiac mortality in radiotherapy of left breast cancer patients [12, 13]. Furthermore, DIBH was also reported to reduce lung dose in which a reduction of at least 16% in lung mean dose and 20% in irradiated pulmonary volume were observed with the use of DIBH in left-sided breast treatment [14]. DIBH also benefits the treatment of right-sided breast cancer patients because it improves liver sparing compared to treatment under free breathing. Rice et al. reported that DIBH could displace the liver inferiorly and posteriorly away from the high dose, reducing the liver volume in the irradiated field by 63% and the mean liver dose by 46% [15]. However, there is one limitation about the system, which is the uncertainty about the accurate correlation of the external surrogate with the tumor position during the breathing process [16].

Active Breathing Coordinator^TM (ABC) (Fig. 3) (Elekta, Stockholm, Sweden) is another commercially available system that helps the patient to withhold the breath so as to freeze the motion of the target volume during irradiation. The ABC system consists of a mouthpiece connected to a spirometer with pinch valves inside. A nose clip is applied to the patient to prevent breathing through the nose and the patient breathes solely through the mouthpiece. The spirometer is connected to a computer so that the inspiration level of the patient can be visualized. A switch is given to the patient for pressing when the patient is ready for breath-hold. Breathing training is provided for the patient before the actual treatment. Once the patient has reached the required threshold, the pinch valves in the spirometer close instantly to prevent the patient from breathing. During treatment, instruction to patient is achieved by broadcasting standardized audio command via intercom or with the aid of visual feedback tools.

Fig.3

Active Breathing Coordinator system.

After the required breath-hold time of about 20–25 seconds, the valves will open automatically to allow the patient to breathe normally through the mouthpiece again. The ABC system is interlocked with the linear accelerator so that the delivery of breath hold treatment can be automatic [17]. This method can be applied to the treatment of most thoracic cancers including lung cancer patients who may have difficulty to carry out breath hold by themselves. A feasibility study has reported that the duration and reproducibility of breath hold using ABC were possible in lung cancer patients without significant problems [18].

Furthermore, ABC was reported to effectively reduce target movement induced by respiratory motion and show major dosimetric improvement to OARs resulting in reduction of radiation-induced complications [19 –22]. Wang et al. demonstrated significant dose reduction to the heart and the left anterior descending (LAD) artery using the ABC system, which could potentially reduce the cardiac risks [23]. In addition, ABC system was also reported to provide good intrafractional and interfractional reproducibility of the chest wall and tracheal bifurcation [24] and facilitate potential reduction of margin to target volume and dose escalation compared with free-breathing [25].

According to Lu et al. [26], substantial intrafractional motions of more than 3 mm were observed in 26.3% of liver cancer patients and in 46.7% of lung cancer patients. Breath hold technique can eliminate such motions and effectively reduce the treatment planning margins. Because of this, it is more commonly used for SBRT of lung and liver cancer cases in which a relatively small PTV can be achieved.

Despite there are potential dosimetric benefits in breath-hold techniques, their clinical implementation is not without difficulty. DIBH and ABC are not totally patient-friendly; and they require training of patients for the specified breathing pattern. It is mainly suitable for patients with satisfactory respiratory function. The setup procedures of the whole system are complex and time-consuming. Patients of older age or poorer general condition may not show good compliance to the procedure. As a result, workload of the therapists and the treatment setup and delivery time will be increased. Because of this, proper patient selection is a pre-requisite in the success of the treatment.

3.2 Abdominal compression

Abdominal compression is achieved through the application of abdominal compression belt or custom abdominal corset by applying pressure to patient’s abdomen so as to limit diaphragm excursion [7]. The system forces the patient to maintain shallow breathing and limits the magnitude of diaphragmatic motion in the supero-inferior direction. This will reduce the associated tumor motion and subsequently the size of ITV [27]. Commercial products including the Anzai Belt (Anzai Medical, Shinagawa, Japan), BodyFIX (Elekta, Stockholm, Sweden) and Neofrakt corset (Spronken Orthopedics, Genk, Belgium) (Fig. 4) are available. Clinically, these products are used in SBRT of abdominal region such as pancreatic and liver cancers. Abdominal compression belt has the advantages of simple implementation with minimal technological requirement and allows continuous irradiation [28].

Fig.4

Abdominal compression by (A) Anzai Belt, (B) BodyFIX, (C) Neofrakt corset.

The benefits of abdominal compression have been reported in several studies. Llacer-Moscardo et al. revealed that the discrepancy in liver position due to intrafractional motion was significantly reduced by using compression belt in liver SBRT [29] and Heerkens et al. stated that tumor motion in cranio-caudal direction was reduced by almost 40% with the use of custom abdominal corset in radiotherapy of pancreatic cancer patients [7]. However, there are limitations in abdominal compression devices that make it still less widely used. For instance, the compression belt is uncomfortable and challenging for patients with poor lung function, claustrophobia or obesity problems. Furthermore, it may cause unpredictable and irregular breathing pattern and lead to unsatisfactory results [22]. The ability of compression belt to reduce target motion also varies among patients and depends greatly on the site of treatment [30].

3.3 Respiratory gating

Respiratory gating exploits the periodic nature of breathing cycle and delivers radiation only at designated period of individual cycle. With real-time monitoring, gating can be performed with patient breathing freely or constrained when combined with other motion management strategies. Radiation beam is only activated at specific phases of breathing cycle when the target moves in the distinctively predefined window. Position and width of the gating window depend prominently on individual tumor motion behavior, and are determined by observing patient’s respiratory motion using either external surrogate or internal fiducial markers [31].

Gating window is usually selected with minimal estimated tumor motion and maximal lung volume, which are the exhale and inhale phases of a breathing cycle respectively. Time spent by the signal within the gate to overall treatment time is used as a measure for the efficiency of the system and referred as duty cycle. At gated treatment, patient’s breathing motion is monitored throughout the treatment session with internal fiducial markers to indicate tumor position, or external surrogates to indicate respiration signals, or patient’s breathing pattern by optical imaging of patient’s surface anatomy [22] (Fig. 5).

Fig.5

Respiratory gating.

Currently, two major approaches are being employed for gated treatment in clinical practice. One approach is using external surrogate, such as patient putting on a jacket or vest with reflective markers (Fig. 6) or holding a box with reflective markers in-place on patient skin using elastic belt. Potential tumor motion is represented by external surrogate, monitored through imaging detection system with a frequency depending on the system used. Motion of the external surrogate is presumed to be closely correlated with the internal tumor motion. The other approach is implanting fiducial markers such as gold fiducials or ceramic markers close to the tumor by surgical method.

Fig.6

External surrogate by putting reflective markers on a jacket.

Gated treatment usually lengthens the overall treatment time because the radiation is delivered in an intermittent manner. In addition, the outcome of gated treatment is patient dependent; patients with comparatively stable breathing and considerably larger intrafraction tumor motion will benefit most from gating since a significant reduction of PTV and normal tissue irradiation can be specified [27].

The external surrogates for respiratory chest motion can be provided from commercial available systems including the RPM (Varian Medical Systems, Palo Alto, CA), and the AlignRT (VisionRT, London, UK) which uses 3-dimenional surface imaging approach. As mentioned before, the RPM system uses a marker box placed on the surface of the chest wall, which is relatively simple and convenient to use. Cautious has to be taken not to impede the motion by treatment accessories or patient’s clothing. One important assumption of this gating method is that the internal target motion is precisely correlated to the external surrogate, and the correlation remains unchanged intrafractionally. Based on this assumption, tumor motion can be truly represented by external surrogates and predicted by using the external respiratory signal [32].

Internal markers approach allows real time visualization of target and surrounding tissue and the tumor position can be monitored directly by fluoroscopic imaging [22]. Several studies reported that the use of internal markers gave better tumor-surrogate correlation than the external surrogate method [33, 34]. However, there are some limitations in this method. For instance, patient has to undergo an operation, which is relatively invasive. In addition, there are fixation issues and migration problems of fiducial markers in the tissues. Detachment or dislocation of fiducial markers over time is not unusual and this may lead to possible change of geometric relationship between the markers and tumor [35]. In order to minimize this problem, there have been suggestions to perform continuous monitoring of the marker-tumor relationship during treatment [30]. In addition, the use of computer-optimized gating parameters could further improve the gating accuracy and reduce the PTV margin [32].

Another consideration in gated treatment is the residual tumor motion, which refers to the tumor motion occurred within the “gated window”. Substantial fluctuations of magnitude of more than 300% have been observed in residual tumor motion within the same fraction of treatment [36]. Although respiratory gating reduced the total tumor motion, residual tumor motion was found to be arbitrary and unpredictable. Because of this, caution should be taken so as to choose an optimal gate width for individual patients.

3.4 Motion tracking

An ideal intrafractional motion tracking system should be able to accurately and efficiently locate the moving tumor/target during treatment and feeds back to the system to make appropriate adjustment of the radiation beam. It can be classified in to tumor tracking, multi-leaf collimator (MLC) tracking and couch tracking.

3.5 Tumor tracking

Tumor tracking refers to the continuous detection of the changing position of tumor, target or its correlated surrogates. Many clinical systems are equipped with real-time x-ray to perform dynamic tumor localization. They include CyberKnife (Accuray, Sunnyvale, CA), Vero^® system (Mitsubishi Heavy Industries, Tokyo, Japan and Brainlab, Feldkirchen, Germany) and ExacTrac^® (Brainlab, Feldkirchen, Germany).

CyberKnife consists of a compact linear accelerator mounted on a robotic arm which enables movements in all directions, and a 6 degree of freedom (DoF) treatment couch (RoboCouch). Imaging system of the CyberKnife consists of two diagnostic x-ray sources and two amorphous silicon detector cameras that image patient at 45° orthogonal angles. The imaging system generates real-time images during treatment and compared against the digital reconstructed radiographs (DRRs) generated from the planning CT. At the same time, the RoboCouch adjusts its position accordingly to the signals generated from the imaging matching result [37]. The system can continuously track intrafraction tumor motion at different anatomical sites with the use of external or internal surrogates. During treatment, the actual tumor trajectories are reflected by the motion signals from the surrogates, measured and fed to a correlation function which then estimates the true tumor position [31].

The Vero^® system integrates imaging and positioning capabilities in a treatment system. It performs treatment with dual-diagnostic x-ray for simultaneous stereo imaging and 6DoF patient positioning during treatment. In addition, with the built-in stereo fluoroscopic facility, it allows real-time imaging of moving targets. The Vero^® system is mainly used for treatment of thoracic and pelvic cancers using the hypofractionation schemes [26]. An evaluation performed by Burghelea et al. reported that the Vero^® system was capable of following complex gantry ring trajectories using the orthogonal x-ray fluoroscopic imaging with maximum deviation below 0.6° during dynamic wave arc delivery [38]. Another study by Depuydt et al. revealed that PTV volume reduction was achieved with the use of real-time tumor tracking solution in Vero^® treatment for respiratory correlated SBRT [39].

ExacTrac^® (Fig. 7) is an x-ray based patient position monitoring system incorporated to a linear accelerator that detects intrafractional tumor motion. It consists of two kV x-ray units mounted with the beams passing through the center of treatment region at 45° from one another. Images can be taken and reviewed during radiation treatment and automatic matching is performed using the built-in verification programme. This instantaneous x-ray imaging with 6D fusion provides positioning information and reduces the possibility of geographical miss of the target due to patient motion or internal anatomy shift. Any deviations in tumor position can be corrected automatically and instantaneously via the robotic 6DoF treatment couch system. ExactTac^® has been reported to be useful for evaluating setup uncertainties and determining setup margin [40]. Oh et al. reported that in the treatment of intracranial SRS, the setup discrepancy in residual setup errors between ExacTrac^® and cone beam was very mild [41]. Compared with on-board imaging, ExacTrac^® could reduce the verification time and organ dose, and it was relatively more effective in the pelvic region when compared with the head and neck region [42].

Fig.7

ExacTrac system. Diagram at right lower corner showing image matching and the result.

3.6 MLC tracking

MLC tracking involves the use of real-time imaging, respiratory modelling and predictive algorithms to anticipate motion patterns and correlate dose delivery in linear accelerator (e.g. TrueBeam, Varian Medical System, Palo Alto, CA). The goal of MLC tracking is to reposition radiation beam dynamically to follow tumor motion during irradiation, to correct for tumor position discrepancy resulted from intrafraction motion. To accomplish this, the system must be able to detect tumor position in real-time, compensate for the time delay in beam-positioning response and reposition the beam. When tumor position signal is received and processed, the MLC aperture will be reconfigured in near real-time to compensate the detected or predicted motion by a specific algorithm. Instead of adding an internal margin to the clinical target volume to create an ITV, MLC are used to follow the target and consequently allow better sparing of adjacent normal tissues [43, 44]. The impact of MLC tracking depends on the magnitude of tumor motion; patients with larger tumor motion will be benefit from larger reductions in target volume and subsequent reductions in OARs doses.

Previous studies reported that both PTV size and dose to normal tissue could be reduced using MLC tracking when compared with ITV-based planning in SBRT of lung cancer patients [43 , 46]. To enhance MLC tracking efficacy, Murtaza et al. suggested the use of rotating collimator instead of fixed collimator VMAT treatment [47]. In addition, the application of MLC tracking in VMAT can be effectively accomplished without the requirement of an internal target margin provided the system latency is less than 150 ms [43].

A challenge to dynamic MLC tracking is time delay compensation. Treatment system latencies including image acquisition, image processing, communication delay and control system processing have been reported [32]. To compensate the time delay predicament, use of predictive algorithms was suggested. By applying breathing predictions models with a range of adaptive filters, tumor position can be predicted with up to 80% accuracy in the presence of a 200 ms system time delay [48].

3.7 Couch tracking

Couch tracking compensates tumor motion by adjusting the couch position via a 6DoF robotic system (e.g. PerfectPitch 6DoF, Varian Medical System, Palo Alto, CA) which is based on the continuous tracking of tumor motion by real-time image guidance system and computer algorithm to calculate the necessary couch movement [31]. In clinical practice, couch tracking is integrated with tumor-localization signal feedback system, such as electromagnetic beacon transponder in Calypso^TM (Varian Medical System, Palo Alto, CA) to re-align the treatment couch position in response to tumor motion [6]. The Calypso^TM system mainly applies to treatment of prostate cancer in which three tiny Beacon^® transponders are inserted in the prostate gland and communicate with the Calypso^TM system through a detection plate using radiofrequency waves during treatment.

Couch tracking can be performed in either single direction or concurrently in all 6DoF along the x, y, z, pitch, roll and yaw directions. Commercially available robotic couch systems include the HexaPOD Couch (Elekta, Stockholm, Sweden), the PerfectPitch Couch (Varian Medical System, Palo Alto, CA) and the RoboCouch (Accuray, Sunnyvale, CA). All of them are equipped with robotic alignment couch with 6DoF. Sub-millimeter accuracy in motion correction has been reported when couch tracking was integrated with kilovoltage intrafaction monitoring system in SBRT of prostate cancer [49, 50].

Compared with breath hold and gating, dynamic tumor tracking allows tracking of tumor motion close to real-time, reduces patient discomfort and patient participation such as breath-holding, and allows continuous treatment [27]. Because of these, it offers a relatively shorter treatment time.

3.8 MRI-guided treatment

MRI provides enhanced soft-tissue contrast compared to CT for target and organ delineation, and better organ and tumor visualization. This saves the use of internal markers as surrogates during the tracking process, and therefore eliminates the possibility of inconsistent correlation between the surrogates and the tumor motion. With the recent release of MRI-linear accelerators (i.e. Unity, Elekta, Stockholm, Sweden) that equip with the cine acquisition techniques, such as the Balanced Steady-State Free Precession (BSSFP) sequences, it is able to generate movie-like images to reveal intrafractional motion during the delivery of radiation [51]. The cine mode of MRI is able to directly detect real-time motion and deformation of tumor and OARs due to breathing, bowel movement, bowel gas, rectal and bladder filling. All of them can be visualized during the delivery of radiotherapy [51 –53]. This implies that MRI guided radiotherapy provides effective tumor tracking environment and is superior in detecting soft tissue tumors. Sagittal MR images can be generated at a rate of 4fps, i.e. 4 images per second. This feature is superior to other real-time imaging systems, which can only take periodic x-ray images for positional verification. Furthermore, MRI-linear accelerator can also support gated treatment in which the moving soft tissue tumor can be viewed directly without the need of fiducial markers. Radiation will be switched on when the tumor moves into the pre-defined boundary decided by the oncologist. Crijns et al. studied on the gating application of MRI-linear accelerator and reported that real-time on-line reconstruction of the accumulated dose could be performed using time- resolved position information, which facilitated intrafactional plan adaptation [54].

Apart from the superiority of MRI over x-ray in tracking soft tissue tumors, it does not deliver extra radiation dose to patient as in the cases of x-ray imaging or cone beam CT. Other potential advantages of MR-guided treatment include provision of daily online adaptive treatment plan optimization and reduction of treatment margins [55]. It is expected that with the advantages over other imaging modalities and the progressive maturity of the associated technology, MRI would be the most effective modalities for tumor motion management in future.

4 Conclusions

Managing of moving target has been a challenge in external beam radiotherapy. Various solutions including the breath hold and tumor tracking approaches coupled with the development of sophisticated devices have been recently introduced to solve this problem. The use of breath hold approach is useful for irradiation of tumors in the chest and abdominal regions. However, its effectiveness depends on the condition and participation of the patients. Tumor tracking requires the support of imaging tools and sophisticated algorithms that are integrated with the treatment machine. Currently, x-ray is the most commonly used imaging modality, however, it is expected that MRI, with its superiority in image quality and real-time soft tissue imaging, may overtake x-ray and become the most effective modality in future. With the introduction of MRI-linear accelerator, on-line adaptation and respiratory modelling, current motion management strategies can further be enhanced, treatment margins can be reduced and radiation-associated toxicity can be minimized.

Declarations

Ethics approval

Not applicable

Consent for publication

Not applicable

Availability of data and materials

Materials in the manuscript are available by contacting the author at htvinuw@polyu.edu.hk.

Competing interests

There is no financial or non-financial competing interest for all authors

Funding

Nil

Authors’ contributions

Vincent WC Wu: Design of manuscript outline, literature search, final editing

Amanda PL NG: Search of literatures, organization of materials, draft of manuscript

Emily KW Cheung: Search of literatures, organization of materials

Footnotes

Acknowledgments

Nil

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