Introduction
The main goal in radiation therapy is to deliver a prescribed dose to a target volume while minimising toxicity to adjacent healthy tissues. One potential way to decrease radiation related toxicity would be to spare more normal tissues.Reference Kitamura, Shirato and Shimizu 1 – Reference Balter, Lam and Sandler 5 The latest equipment development now allows us to use more precise and conformal techniques when delivering radiation, such as intensity modulated radiotherapy (IMRT) and intensity modulated arc therapy techniques. The introduction of these techniques demands for precise target immobilisation and localisation so there is minimal movement during treatment.Reference Litzenberg, Willoughby and Balter 6
New imaging modalities have improved localisation and setup accuracy. The possibility to acquire a cone beam computed tomography (CBCT) before treatment allows professionals to make adjustments according to the target and surrounding organs position, instead of making adjustments according to boney position (MV planar images).Reference Schweikard, Shiomi and Adler 7 – Reference Sharp, Jiang and Shimizu 16 CBCT images can be acquired before and/or after treatment delivery or even between beams. Nevertheless, that does not account for movement that may occur during treatment and organ motion is a major obstacle to reducing margins without compromising dose to the target volume.Reference Shinohara, Kassaee and Mitra 17 Camille Noel et al. studied this pre- and post-treatment CBCT acquisition as a way of predicting intrafraction movement in prostate patients. The conclusion of this study indicated that this imaging acquisition is not a good predictor of intrafraction prostate motion.Reference Noel, Parikh and Roy 18
In order to consider internal movement, various methods have been used for real-time tracking. Methods as fluoroscopy and megavoltage imaging (associated or not with gold fiducials) have the disadvantage of increasing the radiation delivered to the patient. On the other hand infrared tracking of external markers consider external movement as directly related to internal movement, but this correlation has been proven to be imperfect.Reference Schweikard, Shiomi and Adler 7 – Reference Sharp, Jiang and Shimizu 16 , Reference Gierga, Brewer and Sharp 19 – Reference Shirato, Oita and Fujita 21
The Calypso® 4D Localization System (Calypso® Medical, Seatle, WA, USA) is a wireless electromagnetic localisation system which aims to target tumours accurately before and during treatment delivery.Reference Murphy, Eidens, Vertatschitsch and Wright 22
This review provides information in order to (1) show how Calypso® 4D Localization System works, (2) to present advantages and disadvantages of this system, (3) to gather information from several clinical studies and, finally, (4) to refer Calypso® System as a tool in dynamic multileaf collimator (DMLC) studies for target motion compensation.
Materials and methods
The review was based on literature searched on B-On Platform. The key words used in this research were ‘Calypso’, ‘Transponder’, ‘Electromagnetic Localization’, ‘Electromagnetic Tracking’, ‘Target Localization’, ‘Intrafraction Motion’ and ‘DMLC’. The search provided several articles since January 2005. After reading and analysing the B-On search, a selection of references mentioned in some of these articles was made and also analysed and included in this review.
The Calypso® 4D Localization System
This system has five components: Beacon® transponders (specially created for Calypso® System), the console, the array, the optical localisation subsystem and the monitoring station.Reference Quigley, Mate and Sylvester 23
Each transponder consists of a sealed glass capsule containing a miniature electronic circuit. Transponders are 8·7 mm length and 1·85 mm in diameter and are biologically inert.Reference Litzenberg, Willoughby and Balter 6 , Reference Quigley, Mate and Sylvester 23 , Reference Li, Chetty and Enke 24 Typically, three Beacons are implanted in the patient. Only two transponders are necessary for the system to calculate translational movements. However, to have information about rotations a minimum of three transponders is needed.Reference Quigley, Mate and Sylvester 23 – Reference Willoughby, Kupelian and Pouliot 25 The transponders resonate when excited with the electromagnetic field generated by the array. Each transponder has a unique frequency response. The transponders are also color coded with their intended position, which allows them to be distinguished individually. Sensors in the array measure the magnetic field strength from each transponder and the software can calculate the location of each transponder.Reference Murphy, Eidens, Vertatschitsch and Wright 22 , Reference Quigley, Mate and Sylvester 23 , Reference King, Butler and Merrick 26 , Reference Mate, Krag, Wright and Dimmer 27
The console is inside the treatment room. It is a movable unit that gathers a power supply, a computer with the software that calculates transponders location, cables and the array.Reference Quigley, Mate and Sylvester 23
The array contains source coils, sensors and infrared targets. The source coils generate the electromagnetic fields that excite the transponders. The sensors of the array receive the resonant signals of each transponder and the infrared targets are detected by infrared cameras.Reference Murphy, Eidens, Vertatschitsch and Wright 22 , Reference Quigley, Mate and Sylvester 23 The array is positioned above the patient, with minimum beam attenuation.Reference Zou, Betancourt and Yin 28
Three infrared cameras are mounted in the treatment room so that the array position is continuously monitored. The array location yields the position of the centre of the target, with respect to the machine isocenter. This means that the system calculates the table translation movements that are necessary to have the Beacons positioned at the treatment unit according to the planning computed tomography (CT) scan. The positional information is simultaneously displayed and updated in the console as it is in the control areaReference Quigley, Mate and Sylvester 23 , Reference Li, Chetty and Enke 24 , Reference Mate, Krag, Wright and Dimmer 27 , Reference Rassian-Szegedi, Wang and Szegedi 29 (Figure 1).
Tracking station display: in this example the patient is positioned in (0, 0, 0) Calypso® coordinates (black line) and during the monitoring period beacons’ movements are within acceptable limits (grey zone) whenever the graph is blue, and outside acceptable limits (black zone) whenever the graph is yellow; the actual shift value for the three coordinates is on the screen left side (reproduced by kind permission of Calypso® from Calypso® System user’s manual).
Radiation therapists are in the control area monitoring the movement of the target during the treatment delivery through the observation of the data that is being displayed on the monitoring station. Visual and audio alerts warn therapists that the target has exceeded the limits established.Reference Quigley, Mate and Sylvester 23 , Reference Ogunleye, Rossi, Jani, Fox and Elder 30
AdvantagesReference Murphy, Eidens, Vertatschitsch and Wright 22 , Reference Balter, Wright and Newell 31 – Reference Henry, Wilkinson and Wylie 35
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∙ No additional ionising radiation is delivered to the patient.
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∙ The target is monitored continuously.
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∙ Real-time information is provided so that action may be taken to limit the influence of intrafraction motion.Reference Litzenberg, Balter and Hadley 33
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∙ 3D target tracking.
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∙ Not dependent on target size: the system relates to a virtual point about which the physician defined radiation volume is actually delivered.
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∙ The transponders are implanted directly into the target volume.
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∙ The implantation procedures are generally uneventful and well tolerated by the patients.Reference Quigley, Mate and Sylvester 23
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∙ Compact.
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∙ Biocompatible.
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∙ Transponders are compatible with CT imaging and, in some cases, megavoltage imaging.
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∙ Connection between Calypso® System and linear accelerator: the irradiation may stop automatically when the detected movement is superior to the threshold previously defined (available only for Varian Edge Platform).
DisadvantagesReference Quigley, Mate and Sylvester 23 , Reference Willoughby, Kupelian and Pouliot 25 , Reference Rassian-Szegedi, Wang and Szegedi 29 , Reference Ogunleye, Rossi, Jani, Fox and Elder 30 , Reference Kimple, Wallen, Pruthi and Marks 36 , Reference Shah, Kupelian, Willoughby and Meeks 37
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∙ Extra imaging may be needed to assess fully the planning target volume (PTV) and the organs at risk (OARs) – for example the system may confirm that the prostate is in the right position, but no information is given regarding the size of the bladder, an image is required to evaluate that OAR.
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∙ Need for implantation.
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∙ Calypso® manual considers a localisation volume under the array of 14×14×27 cm3 space in lateral, longitudinal and vertical directionsReference Santanam, Malinowski and Hubenshmidt 32 therefore the Beacons should be placed so that they are inside this volume during treatment.
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∙ Implanted Beacons may result in a problem when magnetic resonance imaging follow-up exams are performed: the RF transmitters in the Beacons create huge image artefacts.Reference Shah, Kupelian, Willoughby and Meeks 37
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∙ Patients with pacemakers should be handled with care.
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∙ After implantation, Beacons stay inside the patient and cannot be re-used.
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∙ Patients with certain prostheses may not be suitable candidates for this system.
Quality assurance
The accuracy of the system has been verified to submillimetre accuracy, in several laboratory and clinical studies.
Balter et al. report the results for several tests focused on the accuracy of transponder localisation relative to the array. First a single transponder was positioned at locations up to 8 cm in the X and Y planes from the center position, at Z distances of 8 and 27 cm from the array. A continuous readout of the transponder positions was recorded at these positions for periods up to 20 minutes. At 8 cm distance from the array the offset after 15 minutes the readouts were +0·03, +0·05 and −0·09 mm for the X, Y and Z directions, respectively. At 27 cm distance from the array after 15 minutes the readouts were +0·19, +0·22 and −0·2 mm for the same directions, respectively.Reference Balter, Wright and Newell 31
The experiment was repeated with the beacon in 0·9% saline solution (concentration that simulates a conductivity environment compared to twice that of human tissue). At 27 cm distance from the array and 8 cm away from the centre the readouts after 20 seconds were +0·29, +0·43 and −0·33 mm for the same directions, respectively.Reference Balter, Wright and Newell 31
After concluding that the system correctly detects one beacon, the experience was repeated at 8 and 27 cm offset from the array, this time with a set of three beacons: at Z distance of 8 cm the offset was +0·17, +0·03 and +0·05 mm and at Z distance of 27 cm the offset was +0·16, +0·18 and +0·12 mm for X, Y and Z, respectively, for both measurements.Reference Balter, Wright and Newell 31
Ogunleye et al. compared Calypso® System with kV planar imaging for localisation of markers. In this case Beacons were the markers to be localised as they are detected by Calypso® System (magnetic resonance) and they are also detected in X-ray image (radio opaque).Reference Bittner, Butler and Reed 38
A stationary phantom was not aligned in the isocenter. The measured offset of the target isocenter from the correct position as indicated by the Calypso® System should be the exact opposite of the OBI shift required to move the target isocenter to the correct position. The values were compared for 30 different phantom positions. The difference between the two systems was 0·4 (δ=0·4); 0·2 (δ=0·3) and 0·4 (δ=0·3) mm in the X, Y and Z directions, respectively.Reference Bittner, Butler and Reed 38 The process was repeated with 259 prostate treatment fractions. The difference between the two systems was 0·7 (δ=0·5); 1·1 (δ=0·9) and 1·2 (δ=0·9) mm in the X, Y and Z directions, respectively.Reference Bittner, Butler and Reed 38
Action protocol for treatment intervention
The above mentioned target positioning limits are inserted into the Calypso® software according to an Action Protocol for Treatment Intervention. Several protocols have been reported.
Shinohara et al. studied five locally advanced pancreatic cancer patients with a 3 mm-action protocol. The therapists were to interrupt radiation delivery every time intrafractional motion was >3 mm.Reference Shinohara, Kassaee and Mitra 17 In a prostate study by Smith et al. the same action level was established.Reference Smith, Sawant and Santanam 39
Also in a prostate study by Su et al. a 5 mm shift as threshold was used. A re-localisation was to be performed only if the Beacon centroid drifted more than 5 mm for 25 seconds continuously.Reference Su, Zhang, Murphy and Williamson 40
One of the prone position studies was reported by Shah et al. In this study, therapists were instructed to observe the prostate gland position and intervene when the motion was larger than 3 mm. However, if the motion was transient as peristaltic movement, even if exceeding 3 mm, the therapists should not act. Also, intervention should be between beams.Reference Bittner, Butler and Reed 38
Clinical applications
The Calypso® 4D Localization System has been approved for marketing by FDA for target organ positioning and monitoring during delivery of radiation therapy in prostate cancer patients.Reference Quigley, Mate and Sylvester 23 Most recently, CE Mark approved Calypso® Anchored Beacons to be used in lung treatments as well. Several studies considering future clinical applications have been performed.
Prostate
The implantation procedures are generally uneventful and well tolerated by patients. Quigley et al. refer that 52% of patients in their study (22/42) reported symptoms after the implantation procedure. Those symptoms were not revealed, but it was referred that those were usual symptoms after similar procedures as implantation of gold fiducials.Reference Quigley, Mate and Sylvester 23 , Reference Willoughby, Kupelian and Pouliot 25 , Reference Berger, Gozzi and Steiner 34 , Reference Henry, Wilkinson and Wylie 35
It is to be mentioned that, after the implantation of fiducials, the prostate usually swells (inflammatory response). There may be a change in fiducials position when prostate swells and also when it returns back to its natural position. Litzenberg et al. reported that it is safe to acquire a planning CT scan 4 days after implantation, as any swelling appears to have resolved by then.Reference Litzenberg, Willoughby and Balter 6
Calypso® System has been a very important tool in the most recent studies of intrafraction prostate motion.Reference Kitamura, Shirato and Seppenwoolde 2 , Reference Dawson, Litzenberg and Brock 41 – Reference Xie, Djajaputra and King 43 These movements are caused not only by repeating processes such as breathing, but also because of random processes like gradual rectal distention, peristaltic motion and bladder volume. This means prostate movement is random, sporadic and patient specific, which makes the prediction of the prostate motion difficult.
As above mentioned Calypso® manual considers a localisation volume under the array of 14×14×27 cm3 which means that patients with protuberant abdomen may not be a suitable candidate for this system. When considering the localisation volume of the system, the recommendation is that the maximum distance between the array and the beacons should be <27 cm. On the other hand Bittner et al.Reference Ogunleye, Rossi, Jani, Fox and Elder 30 and Quigley et al.Reference Quigley, Mate and Sylvester 23 assumed that this distance should not be more than 23 cm in their studies’ patient selection. The latter led to several studies in order to present the prone position as an alternative position to treat these patients with Calypso® accurately.Reference Kimple, Wallen, Pruthi and Marks 36 , Reference Bittner, Butler and Reed 38 , Reference Bittner, Butler and Reed 44 Shah et al. refer that prostate displacements larger than 3 and 5 mm were higher in the prone position by a factor of three in comparison to the supine position. Displacements larger than 10 mm occurred as often in the prone as in the supine position.
Lung
Implantation of transponders in lung has some risks. The current design of the transponders was not the most appropriate for lung implantation: although they show good to moderate short-term fixation rates, long-term fixation rates are low.Reference Mayse, Parikh and Lechleiter 45 Percutaneous implantation in the lung led to a significant rate of pneumothorax.Reference Whyte, Crownover and Murphy 46 However, bronchoscopic implantation has been safer.Reference Kupelian, Forbes and Willoughby 47 , Reference Imura, Yamazaki and Kubota 48
In the meantime, Calypso® Medical has developed a new transponder design with a stabilisation feature: Calypso® Anchored Beacon. This improved Beacon is a regular Beacon with a five-legged nitinol stability feature. These five legs are to anchor the transponder in a small diameter airway (bronchoscopic implantation).Reference Shah, Kupelian, Willoughby and Meeks 37 Mayse et al. refer that this lung transponder has 100% long-term fixation rates over 60-day period for 54 bronchoscopic implanted transponders in canine lungs.Reference Mayse, Smith and Park 49 In the European Union, the Beacons were approved to be used in lung treatments by CE Mark. The first application for lung tumour treatment was already conducted in August of this year in the Fundação Champalimaud in Lisbon, Portugal.
Pancreas
A study has been developed in The Vanderbilt Clinic, Nashville by University of Pennsylvania (2011), with five locally advanced pancreatic cancer patients (with no metastatic disease). Each patient underwent implantation of three regular Beacons. Transponder implantation was well tolerated in all patients, with minimal migration: a single transponder migrated in a patient who had intractable vomiting out of the 15 transponders implanted. To monitor the stability of the transponder placement, intertransponder distance was obtained before the start of each fraction using the Calypso® System.
Data from 164 treatments was analyzed. Mean intrafractional motion was superior 7·2 mm; inferior 11·9 mm; anterior 4·9 mm; posterior 2·9 mm; left 2·2 mm; and right 3·1 mm. All these values were smaller when applied breath holding while treating (157 treatments analysed): superior 4·3 mm; anterior 2·5 mm; posterior 1·7 mm; inferior 8·1 mm; left 1·0 mm; and right 2·1 mm.Reference Shinohara, Kassaee and Mitra 17
Electromagnetic Guided Real-Time Dynamic Multileaf Collimator Tracking System
In the past few years researchers have investigated DMLC tracking possibilities.Reference Keall, Cattell and Pokhrel 50 – Reference Poulsen, Cho and Ruan 53 The goal of these investigations is to create a system able to find the target location and reposition the treatment beam to compensate for target motion. Considering this, Calypso® System can be the key tool on finding target location. To reposition the treatment beam a DMLC is used.Reference Wu, Ruan and Cho 54 – Reference Krauss, Nill, Tacke and Oelfke 56
There are some obstacles when integrating these systems. Once target movement is detected, the data stream is input to the DMLC tracking software, which generates the ideal beam aperture. Depending on the MLC, this ideal beam aperture may not be viable because of MLC physical limitations such as finite LMC leaf widths or the paired leaf structure. Another limitation is related to a finite time lag that is observed between motion detection and MLC response—system latency—which is spent in motion detection, the calculation of the new leaf positions and the time required by the MLC leaves to reach their new positions.Reference Wu, Ruan and Cho 54 – Reference Krauss, Nill, Tacke and Oelfke 56
To reduce the system latency, studies have been made on predictive algorithms to estimate future target positions.Reference Krauss, Nill, Tacke and Oelfke 56 , Reference Srivastava, Keall and Sawant 57
Wu et al. studied an algorithm capable of readjusting treatment beam for translational and also rotational intrafraction movements. They tested this integrated system with success. The system detected and adapted the treatment beam for translation and rotation movements.Reference Wu, Ruan and Cho 54
Sawant et al. refer to have built their system successfully. The system was tested on patient-derived 3D motion trajectories comprising two lung tumours and one prostate trace. Tracking accuracy was sub-2 mm for the respiratory motion and sub-1 mm for prostate motion.Reference Sawant, Smith and Venkat 55
Discussion
The Calypso® 4D Localization System is a technology based on electromagnetic transponders detection which enables precise 3D localisation and continuous tracking of tumour target. The main advantage of this system with respect to other systems continuous internal tracking with no extra ionising radiation delivered to the patient. Advantages and disadvantages should be considered when thinking of acquiring this system as well as costs and objectives on how to use the system in the clinic.
Quality assurance
Balter et al. tested the accuracy of Calypso® System when localising one and three transponders. The accuracy was higher for one transponder detection; still both tests resulted in submillimetre shift values. It was also performed a similar test in 0·9% saline solution—concentration that simulates a conductivity environment compared to twice that of human tissue. The accuracy of the system was lower, but the values were also below a millimetre, showing that transponder detection should be accurate in human body. For all these tests the accuracy decreased as the beacon(s) distance to the array increased, but the measured values kept being submillimetre.Reference Balter, Wright and Newell 31
Ogunleye et al. evaluated the difference between Calypso® and kV planar image for 30 different phantom positions: values were submillimetre. When he repeated the process with 259 more fractions the difference between the two systems was higher than 1 mm (1·2 mm in the Z direction), so values are not that small. However, OBI system uncertainty should be taken in consideration in these tests, added to Calypso® System inner uncertainty present in other studies.Reference Bittner, Butler and Reed 38
Action protocol for treatment intervention
Regarding action protocols on how to intervene when using Calypso® System to monitor a treatment several examples were presented.
The pancreatic study with the 3 mm action protocol was performed on patients treated with 3D conformal treatment using 4 fields and a 1–1·5 cm margin was added to the clinical target volume to construct a PTV_4500; there was no reference to the linac used to deliver the treatment.Reference Shinohara, Kassaee and Mitra 17 The prostate study that used this same protocol referred that IMRT treatments were analysed on 44 prostate treatment fractions of 28 patients; there was mention neither to PTV margins nor to the linac used to deliver these treatments.Reference Smith, Sawant and Santanam 39
Su et al. referred that each patient underwent 28 treatment sessions, each about 8 minutes long, but there was also no reference to the treatment plans (PTV margins, technique) or to the linac that delivered these treatments.Reference Su, Zhang, Murphy and Williamson 40
Shah et al. treated their patients in 40 sessions. The PTV margins were 3 mm posterior and 5 mm in all other directions.Reference Bittner, Butler and Reed 38
There are no studies available on the validity of these protocols. It is however to note that the treatments administered in these studies were different from clinic to clinic so it is natural that the protocols were also different. More investigation should be performed regarding action protocols and the treatments they apply to. A recommendation for a future study on action protocols could include suggestions on how Calypso® margins should be defined according to PTV margins, time of irradiation (regular or FFF beams, 3D conventional or IMRT techniques), and target localisation (natural movement of target and surrounded OARs).
Clinical applications
Concerning prostate treatments, Calypso® System has been implemented and used in several clinics. It detects prostate movements due to breathing movements, peristaltic movements and other natural processes. However, depending on the protocol being used, it may be necessary to acquire images to assess OARs position related to the PTV (such as the rectum and the bladder).
Another obstacle for prostate treatment is the transponder implantation maximum depth in tissue. Prone position has been presented as an alternative.Reference Kimple, Wallen, Pruthi and Marks 36 , Reference Bittner, Butler and Reed 38 , Reference Bittner, Butler and Reed 44 It is to refer that previous literature presents studies on the stability of prone versus supine positions.
Several studies indicated that there is more interfraction movement when the patient is in prone position.Reference Bayley, Catton and Haycocks 58 , Reference Weber, Nouet, Rouzaud and Miralbell 59 Considering that positioning the patient using Calypso® System already corrects interfraction motion, it makes sense to analyse intrafraction motion in prostate in both positions.
At Cancer Center of Irvine it was decided to treat prostate in supine position after a local study was performed in 15 patients by Wilder et al.Reference Wilder, Chittenden and Mesa 60 The study evaluated intrafraction movement in supine and prone position and position preference of the patients. The study was performed in patients with gold seeds implanted. Anteroposterior and lateral kV planar images were acquired to evaluate intrafraction movement. Mean values were 0·6 (δ=0·9), 1·6 (δ=1·8) and 1·7 (δ=1·4) mm in the supine position and 1·0 (δ=1·2), 2·2 (δ=2·0) and 2·1 (δ=1·2) in the prone position in the X, Y and Z directions, respectively. There was no significant difference in the intrafraction prostate motion of the two positions and 80% of the patients were more comfortable in the supine position.
Kitamura et al. analysed intrafraction motion using a real-time tumour-tracking system that uses two fluoroscopic images acquired 30 times per second and software that is able to detect gold markers position. Mean values for ten patients were 0·1 (δ=0·1), 0·3 (δ=0·2) and 0·3 (δ=0·4) mm in the supine position and 0·5 (δ=0·4), 1·4 (δ=0·5) and 1·6 (δ=0·4) in the prone position in the X, Y and Z directions, respectively. It was concluded that internal organ motion is less frequent in the supine position than in the pro position.Reference Kitamura, Shirato and Seppenwoolde 61
The decision on the patient position for prostate treatment lies in each radiotherapy department. On one hand supine position is more comfortable for the patient, and several studies indicate less inter- and intrafraction motion in this position; on the other hand a department that has Calypso® System available may consider that prone position is an appropriate alternative to treat large prostate patients so those movements can be detected and can be corrected by technicians.
It is of note that none of this studies compared supine and prone positions rotation shifts. More investigation should be performed in this area.
Clinical application of the Calypso® System in tumours other than prostate has not been approved in United States yet, and CE Mark approval for lung treatments with Anchored Beacons in EU is still very recent. Therefore, no published clinical results on this application are available yet, but it is understandable the advantage of the use of transponders in regions of significant target movement.
Electromagnetic Guided Real-Time Dynamic Multileaf Collimator Tracking System
In the near future, a few integrated systems have been created and tested in phantoms, with success for tracking target position. The integration of Calypso® 4D Localization System and DMLC is being developed in order to achieve an Electromagnetic Guided Real-Time Dynamic Multileaf Collimator Tracking System. Still, these algorithms have taken into account only the target position, OARs positions are not considered, yet.
Conclusion
The Calypso® 4D Localization System allows real-time localisation and monitoring of the target, with no ionising radiation additional administration. It is a very important tool in prostate cancer treatment. More studies are currently being developed.
Further research has to be performed: (1) prostate studies involving a larger cohort of patients, (2) clinical application in clinical sites other than the prostate and prostate bed, (3) the effect of the system on hypofractionated treatments, (4) studies involving rotational movement corrections besides translational movement corrections and (5) investigation and implementation of more advance prediction algorithms for DMLC systems.
Improvements and integrations are also expected in the future, such as (1) phantoms dedicated to Calypso® and/or DMLC tracking system studies, (2) integration of Calypso® System with linear accelerator, (3) integration of Calypso® System with robotic couch (6D) and (4) improvements in software design and speed of processing hardware allowing the clinical use of Calypso+DMLC integrated system into achieving adaptive radiotherapy.
Acknowledgements
The authors thank the staff of the Radiotherapy Department at Centro Clínico Champalimaud for their personal encouragement and Dr Andrew Macann for helping with English language revision.
Financial support
No monetary costs were involved in this review. Any cost related to publication is supported by the primary author herself.
Source of Support
This review was proposed in the master course Radiations applied to Health Technologies— Radiation Therapy, at Escola Superior de Tecnologias da Saúde de Lisboa. Revision of the review was kindly made by Sandra Vieira and Dalila Mateus, who have worked with Calypso, and also by Prof. Margarida Eiras.
Conflicts of Interest
None.
