JURNAL RADIOLOGI 3.pdf

BJR 2015 The Authors. Published by the British Institute of Radiology

Received:1 February 2015

Revised:30 April 2015

Accepted:7 May 2015

doi: 10.1259/bjr.20150100

Cite this article as:Korreman SS. Image-guided radiotherapy and motion management in lung cancer. Br J Radiol 2015; 88: 20150100.

ADVANCES IN RADIOTHERAPY SPECIAL FEATURE: REVIEWARTICLE

Image-guided radiotherapy and motion management inlung cancer

S S KORREMAN, PhD

Department of Science, Systems and Models, Roskilde University, Roskilde, Denmark

Address correspondence to: Dr Stine S KorremanE-mail: [email protected]

ABSTRACT

In this review, image guidance and motion management in radiotherapy for lung cancer is discussed. Motion char-

acteristics of lung tumours and image guidance techniques to obtain motion information are elaborated. Possibilities for

management of image guidance and motion in the various steps of the treatment chain are explained, including imaging

techniques and beam delivery techniques. Clinical studies using different motion management techniques are reviewed,

and finally future directions for image guidance and motion management are outlined.

Image-guided radiotherapy (IGRT) implies the use of in-room imaging to localize the target with the aim of guidingthe treatment beam to an accurate aim. Based on the images,compensating actions may be taken to adjust for variationsfound in the images. Variations can be of both rigid and non-rigid nature, and occur on different time scales. Specic toimage guidance for radiotherapy in the lungs, is the phe-nomenon that breathing causes geometric anatomical changesto take place in the patient within the time scale of a radio-therapy fraction that are (more or less) predictable and cyclic.This phenomenon at the same time poses great challenges toimplementation of image guidance for lung radiotherapy,as well as great opportunities. Over the last approximately15 years, almost overwhelming attention has been given tothis subject in particular in the radiotherapy physics society,and great technical advances have been made, which havechanged the clinical practice of lung radiotherapy. This reviewsystematically covers both technical aspects and clinicalimplementation of various strategies for image guidance inlung radiotherapy. Focus will be given to techniques aimed atcompensating for breathing dynamics, although it should bestated now that a fully comprehensive review would be muchtoo vast to t in the space available in a single article.

BASIC CONCEPTS OF LUNG IMAGE-GUIDEDRADIOTHERAPYMotion characteristics of target, lung andnearby structuresMotion characteristics of thoracic structures have been in-vestigated and presented in a number of studies, both with

regard to the cyclic breathing motion on the short timescale of seconds and minutes, and variations on longertime scales of days and weeks.

In a previous review,1 this author has collected data froma number of early studies of motion of organs and struc-tures in the thoracoabdominal region (Table 1). Notable isthat motion takes place in all three orthogonal directionsand may be of a considerable extent up to several centi-metres, especially in the craniocaudal direction. Fortumours in the lung, motion extent and characteristics maydepend on location of the tumour, tumour size, lungfunction and whether or not the tumour is attached tostructures. Additional to this, there are cycle-to-cycle var-iations in breathing, hysteresis and changes on a longertime scale of days and weeks.

The hysteresis phenomenon is well documented in, forinstance, the classic and often cited study by Seppenwooldeet al2 (Figure 1a). In this gure, the potentially large extentof motion is conrmed, as is the occurrence of motion inall three directions, at the same time as the hysteresis isvisually illustrated by the differences between inspirationand expiration paths in the drawn trajectories.

In the recent years, several studies have investigated indetail cycle-to-cycle variation in breathing pattern, as thesevariations are crucial in relation to implementation of real-time motion management techniques. An example of sucha study is reported in Worm et al,4 where sequences of

breathing have been investigated for a series of patients un-dergoing stereotactic body radiotherapy (SBRT) for liver cancer.The study showed that the cycle-to-cycle variability had a stan-dard deviation of approximately 20% of the mean total motionextent over all cycles.

Finally, variations related to breathing take place on longer timescales as well. This was, for instance, quantied for 56 patientswith lung cancer in Sonke et al,3 as illustrated in Figure 1b usinga representation similar to that in Figure 1a. It is demonstratedby this study that breathing varies from day to day in referenceto the surrounding structures, with a mean magnitude of var-iations of 3.9mm.

From imaging for treatment planning totreatment deliveryGiven that all of the above stated variations take place in relationto target localization and motion of structures in the lung, it isalso evident that accurate radiotherapy requires images to beacquired at various stages of the radiotherapy chain and withhigh degrees of temporal and spatial resolution.

Imaging for treatment planning consists of a CT scan possiblycombined with a positron emission tomography (PET) or evena MR scan. In a standard CT scan of the thoracic region, motionof structures on time scales comparable to that of slice acqui-sition and scan acquisition introduces artefacts in the CT imageof the patient. These effects have been extensively studied,57 andalthough they are well known, they are not easily predicted oraccounted for in clinical practice for standard CT scanning. Withthe aim of minimizing artefacts stemming from motion, four-dimensional CT (4DCT) scanning is now becoming standard forimaging for treatment planning for lung cancer radiotherapy.The 4DCT scan displays the breathing motion of all structures inthe scan region as it occurs in the breathing cycles taking placeduring the scan period. Depending on the specications of thescanner and the scan settings, the image quality resulting fromsuch a scan varies, but generally, there are markedly less artefactsthan in a standard scan.

Modern CT scanners used for treatment planning scanning canbe acquired with 4DCT capability as a standard. For PET-CTscanners, four-dimensional (4D) capability may be available forthe CT part but not for the PET part. Motion has a signicantlydifferent effect in PET scans than in CT scans, because the timescale of a PET acquisition is much longer than the time scale ofthe breathing cycle. As the PET acquisition thus spans a largenumber of breathing cycles, the effect is a blurring of the signalover the motion trajectory of the target.8 A 4DPET scan con-sisting of a number of scans representing different phases ofthe breathing cycle may be produced by sorting the countsaccording to when in the breathing cycle they were recorded.9

Some scanners come with this capability, but it is not as widelyavailable and used as 4DCT scanning is.

The quality and representativeness of a 4DCT scan dependshighly on the regularity of the patients breathing. The moreirregular the breathing, the more artefacts will be present in the4DCT scan,10 and the less representative the scan can be for theT

able

1.Dynamicsofnorm

alstructureswithrespiration

Structure

Meanexcursion(m

m)(ran

ge)a

Numberof

studies

Numberof

patients

over

all

studies

repo

rted

Free

breathing

Deepbreathing

SIAP

ML

SIAP

ML

Lungs

10.3

(131.9)

6.4(024.4)

(110)

9.3(0.170)

7.8(0.518.8)

4.2(1.117.6)

762

Diaph

ragm

14.9

(2.638.2)

44.6

(3.196)

10112

Liver

12.3

(4.930.4)

(max.5.2)

(max.4.6)

38(2557)

659

Chestwall

7.3(215)

2.3(08)

(57)

16(0.737.3)

11.7

(0.564.1)

688

Heart

18.1

(1225)

2.4

220

AP,anteriorposterior;max.,maxim

um;ML,medio-lateral;SI,superiorinferior.

aThistablecontainsanoverviewoftheresultsofanumberofstudiesconcerningorganmotionwithrespiration.Foreachorgan,themeanvalue(ortherange)oftheorganexcursionoverseveral

studiesisreported,andthenumberofstudiesusedto

obtain

themeanaswellasthetotalnumberofpatients

isgiven.Thetable

isreproducedfrom

Korreman1withperm

issionfrom

IOP,and

referencesforthestudiescanbefoundthere.

BJR SS Korreman

2 of 12 birpublications.org/bjr Br J Radiol;88:20150100

patients breathing pattern. However, we have recently shown ina phantom study that even for highly irregular motion, a 4DCTscan will represent the target shape and trajectory at least as goodas a standard scan.11 However, the 4DCT scan will always only bean image of the motion taking place in a few breathing cycles onthat particular daya snapshot cycle image so to speak.

Although the 4DCT scan provides signicant information to theradiotherapy process of the volumetric breathing dynamics inthe patient, the snapshot nature of the image means that itcannot supply information regarding intercycle variations andvariations on time scales longer than seconds.

How the informationand lack of informationobtained ina 4DCT scan is used in the radiotherapy process depends on

the choice of motion management strategy employed, as willbe seen in the Motion management strategies section. In allcases, IGRT includes additional imaging in the treatment room inrelation to treatment fraction(s), in two, three or four dimen-sions. In two-dimensional (2D) images, mainly bony structuresare visible, especially when the megavoltage (MV) beam is usedfor imaging where the contrast is low. In kilovoltage (kV)images, soft-tissue contrast is higher, and especially when three-dimensional (3D) cone-beam CT (CBCT) imaging is used, it maybe possible to set up directly to soft-tissue structures. Semi-3Dimaging may be performed by combining information from twoorthogonal 2D images. Options for imaging in the treatmentroom do not as a standard include high-quality volumetric 4Dtechniques (at least not yet), although both 4D CBCT imagingand uoroscopic imaging are increasingly available with new

Figure 1. (a) Orthogonal projections of the trajectories of the 21 tumours on (left) the coronal (LR-CC) and (right) the sagittal

(AP-CC) plane. The tumours are displayed at the approximate position, based on the localization mentioned in the treatment chart.

Reproduced from Seppenwoolde et al.2 (b) Graphical representation of systematic (arrows) and random (ellipses) baseline

variations projected on coronal and sagittal views of a schematic bronchial tree. Colours reflect average amplitude. Reproduced

from Sonke et al3 with permission from Elsevier.

Review article: Image-guided radiotherapy and motion management in lung cancer BJR


and upgraded treatment machines. CT on rails, with a full-scaleCT scanner physically adjacent to the treatment machine canprovide in-room full-scale 4DCT imaging, although only used toa limited extent in few clinics.

An entirely different option for gaining information specicallyon the position of single points in the patient (typically in thetumour) over time, is that of implanting radiofrequency beacons,which can be monitored in real time (for instance the Calypsosystem, see the Techniques for imaging motion section).

When variations take place on the same time scale as a treatmentfraction, imaging during treatment may be relevant. This cantake place either during beam on time, or in-between beams.The purpose of imaging during treatment will either beverication for possible intervention if tolerance levels are ex-ceeded, or dynamic beam adaptation such as motion tracking.

An alternative option should be mentioned, namely that offreezing the motion rather than imaging and accounting for it,which can be achieved by employing breath-hold during imag-ing and treatment. Breath-hold is a well-known and earlytechnique used in diagnostics for achieving CT images withreduced artefacts, and CT images obtained during a breath-holdare of a better quality than those obtained in a 4DCT scanasis seen in an example in Figure 2.12,13 When employed in CTscanning for radiotherapy planning, a crucial point, however, isthe reproducibility of the breath-hold that must be mimicked inthe treatment situation, making in-room imaging (with breath-hold) even more important.14

Techniques for imaging motionA number of techniques are available for imaging in the treat-ment room as well as for treatment planning. In the treatmentroom, radiographic and uoroscopic kV imaging capabilities arenow standard for new machines. This may be either as equip-ment mounted on the linear accelerator (linac) gantry, mostly inan orthogonal geometry to the treatment MV beam, or as in-dependent units mounted in the ceiling or oor of the room inan orthogonal (or at least stereoscopic) geometry. Two orthog-onal (or stereoscopic) imaging units may be combined to givesemi-3D information, while gantry-mounted imaging units canadditionally be used for CBCT imaging, yielding true 3D images,as well as for 2D radiographic/uoroscopic imaging. For CBCTscanning, the acquisition time is long compared with thebreathing cycle time, and the image will therefore containa blurred image of the target position over several breathingcycles. Time-resolved CBCTscanning (4D CBCT) yielding a set of3D images corresponding to different phases of the breathingcycle has been developed, although it is not widely available yet.15

Visibility of lung tumours in kV images is often quite good andis sufcient for matching with digitally reconstructed radio-graphs from the treatment planning CT scan. This is especiallytrue for 3D (and 4D) CT imaging. However, for valid high-precision tumour-tracking purposes, especially in real time, it ismore optimal to implant markers for increased visibility. Whenmarkers are implanted, an added benet is that the tumour isvisible even in MV images, for instance, from the treatment beamduring beam delivery. Marker implantation carries a risk of sideeffects, depending on how the implantation is performedthe

Figure 2. CT scans of two patients with large deviations in gross target volume (GTV) between scans: conventional three-dimensional

CT (3DCT) (left), four-dimensional CT (4DCT) midventilation bin (middle) and breath-hold CT (BHCT; right). The upper row shows

images from a patient with a tumour in the right lower lobe. The delineated GTV size was 64.9, 45.2 and 34.9cm3, respectively, and the

craniocaudal (CC) tumour motion was 2.4cm. The lower row shows a patient with an apical tumour in the left lower lobe. The GTV size

was 4.2, 3.0 and 2.1 cm3, respectively, and CC tumour motion was 0.6cm. Reproduced from Persson13 with permission.

BJR SS Korreman


risk of pneumothorax for percutaneous implantation is reportedto be up to 30% including all levels of severity and up to 10% re-quiring intervention.16,17 Alternative to the percutaneous method,implantation may be performed bronchoscopically as in for in-stance reported in Harada et al.18

Common for all methods of imaging motion, is that it is oftenrelevant to monitor breathing through an external surrogatesimultaneously. This can be performed through many differenttechniquesoptical recording of reective optical markers orlight-emitting diodes positioned on the surface of the patient,spirometry for volume measurement of air owing and outof the lungs, measurement of the temperature of in- and out-owing air, with a thermocouple placed under the nose, meas-urement of pressure produced by chest expansion withpiezoelectric ceramics placed in an elastic abdominal strap,patient surface rendering by use of lasers. All these surrogatesgive respiratory cyclic signals that are one dimensional in thesense that they (mostly) only monitor a single property(pressure, temperature, ow, position) as a function of time.The surrogates reecting position (such as optical markers)have the potential of giving 3D positional information whenstereoscopic imaging of several markers is performed or in thecase of surface rendering.

A method for monitoring which gives direct information ontarget position without imaging is the implantation of radio-frequency beacons in the patientfor instance, using the Ca-lypso system. The implantation process carries the risks relatedto implantation as described previously, especially since thebeacons are quite large. The advantage is that the target positionmonitoring process becomes less complicated, since the targetposition is directly monitored without the necessity of extensiveimaging and image processing.19

MOTION MANAGEMENT STRATEGIESWhen motion is present in the treatment region of the patient,this needs to be accounted for both in treatment preparation andin treatment delivery. The past approximately 15 years of de-velopment has made it possible to do so on an individual basisand even in real time. The classic method of using the clinicaltarget volume to planning target volume (CTV-to-PTV) marginto account for all variations on a population basis can now bereplaced by more and more sophisticated individual approaches.

Encompassing treatment field marginsWhen a 4DCT scan is available for planning, there is an imme-diate potential for applying individualized treatment eld marginsto encompass the breathing motion. Two different methods fordoing this in practice have been established(1) denition of theinternal target volume (ITV) and (2) the midventilation ap-proach. Both are in use in clinical practice and have been reportedin the literature, for instance, in Sonke et al20 and in Hanna et al.21

The two methods take two quite different approaches to achievingthe same goalcalculating an adequate CTV-to-PTV margin toaccount for the breathing motion observed in the 4DCT scan.

Using the ITV approach, the all images of the 4DCT scan areoverlayed using, for instance, a maximum intensity projection of

all phases, and the combined volume of the target in all phasesof the breathing cycle is outlined as the ITV.22 The ITV is thenconsidered the gross target of irradiation ensuring full irradia-tion of the target over the entire breathing cycle. On the ITV,further margins are subsequently added to give the planningtarget volume (PTV). In relation to the image guidance per-spective, there are two advantages of the approach. At theplanning stage, residual image artefacts in the target shape andvolume in the 4DCT scan are to a large degree eliminated by theoverlay of the images of all the phases. When subsequentlyperforming in-room image guidance, matching for set-up can beperformed between the ITV in the 4DCT planning scan and thecorresponding target in the CBCT scan.23,24

In the midventilation approach, the trajectory of the target in the4DCT scan is analysed, and the phase in which the target isclosest to its mean position is identiedthis is termed themidventilation phase.25 This phase is then used for delineationand treatment planning. The motion extent of the targetthroughout breathing can be measured from the trajectory andused in the combined margin applied to the target. In this ap-proach, it is often also argued that the margin to account forbreathing motion should be calculated by quadratic addition ofthe breathing variation.26 (This is in opposition to the ITV ap-proach where the margin for breathing is de facto linearlyadded.) For the midventilation approach, image-guided set-upcan be performed by matching the target in the midventilationphase of the 4DCT scan to the target in the correspondingmidventilation phase of a 4D CBCT scan or matching can beattempted using the full motion in both scans.27

Gating and breath-hold techniquesGoing a step further in motion management, it may be relevantto utilize the knowledge of breathing motion to decrease thetreatment eld margins, especially when toxicity is a limitingfactor and/or of high concern. This can be achieved by reducingthe breathing motion of the target during irradiation, throughonly irradiating the target when it is within a limited pre-denedwindow of the breathing trajectory. The approach of turning thebeam on and off in synchronization with the breathing cycle istermed respiratory gating. An illustration of the principle ofrespiratory gating is shown in Figure 3a.

For treatment delivery, the gating phase of the breathing cycleneeds to be identied and positionally veried, and the beammust be triggered on and off accordingly for the duration of thebeam delivery. A breathing monitoring device for providing thetrigger signals is required, and there are several commerciallyavailable systems on the market for this. Breathing monitoringdevices for respiratory gating most often rely on surrogates forthe actual motion of the target, such as an external optical skinmarker or a pressure sensor, as described in the Techniques forimaging motion section.

For respiratory gating, image guidance is of utmost importanceas has been shown in Korreman et al.28 This is owing to the inertvariable degree of irregularity of breathing, and the resulting lackof predictability of breathing motion. The correspondence be-tween the breathing motion of an external surrogate and the



breathing motion of the target may change markedlytherefore,when external surrogates are used for motion monitoring, thecorrespondence between surrogate motion and target motionneeds to be established and veried on a regular basis, not onlyfrom fraction to fraction but also within each treatment fraction.If this is not performed, geographical miss may be risked, withunderdosage of the target as a result.28 Image guidance adequatefor this purpose includes 4D CBCT, respiratory correlateduoroscopy or repeated radiographs combined with suitablesoftware to establish a quantication of the target position in theimages.

In order to perform treatment planning for respiratory gating,the planning phase of the 4DCT scan appropriate for gatingcan initially be selected as the planning scan. Parameters for

choice of gating phase will typically include stability, timespent in the phase and proximity of nearby organs at risk. Forhigh stability and large fraction of time spent in the gatingwindow, end-expiration will be the phase of choice. On theother hand, dosimetric concerns for organs at risk may insome cases point to the inspiration phase as the optimal phasefor gating.29

The breath-hold approach is somewhat simpler than cyclic re-spiratory gating in several aspects, although it relies on the samebasic principle of turning the beam on and off based on targetposition (Figure 3b). The continuous detection of breathingphase as well as the potential lack of consistent correlation withsurrogate monitored motion are not issues, although targetposition still needs to be veried during breath-hold.30,31 For

Figure 3. (a) Normal breathing shown with the principle of respiratory gating of beam delivery. (b) Breathing with breath-hold

shown with the principle of beam delivery during breath-hold. For both (a, b) the horizontal lines indicate the thresholds within

which the beam can be turned on. The vertical dashed lines indicate the points in time at which the beam should be turned on and

off, respectively.

BJR SS Korreman


increased stability of breath-hold procedures, the ActiveBreathing Coordinator (Elekta AB, Stockholm, Sweden) usesa combination of a valve system shutting off air ow and a visualguidance to the patient.32 As for free breathing, breath-holdduring expiration is more stable than during inspiration, but thechoice of whether to use expiration or inspiration breath-holdwill depend not only on stability but also on dosimetric concerns.

For both respiratory gating in free breathing and breath-holdtechniques, it has been shown that reproducibility and stabilitycan be enhanced by use of patient training and coaching tech-niques, using both audio and visual guidance33,34 (see the De-cision making strategies for motion management section).

Motion trackingThe ultimate solution for accounting for target motion duringtreatment is to aim the treatment beam continuously and dy-namically at the moving target. This is also the most demandingsolution in terms of image guidance requirements.

There are several systems for motion-tracking treatment on themarket.

Since its rst use in 2002, the Synchrony system for Cyberknife(BrainLab AG, Feldkirchen, Germany) has been in clinical use inan increasing number of clinics, and several articles havereported investigations as well as clinical protocols using thesystem.3537 The Cyberknife robotic arm is programmed to movesynchronously with the breathing cycle, in a trajectory followingthe projected 3D motion of the target. The target motion is notmonitored directly, but before treatment is started, a sequence oforthogonal radiographic images is recorded from which the targetbreathing motion is derived in three dimensions. At the sametime, a mathematical correlation model between the target mo-tion and the motion of a set of external optical markers on thesurface of the patient is established. During beam on, the motionof the external optical markers is monitored and the correlationmodel is used to direct the beam at the corresponding targetpositions dynamically. Intermittent radiographic images are ac-quired throughout beam on time, to provide verication of targetposition and to update the correlation model.

The newer Vero (BrainLab AG) dynamic tracking system is inclinical use in only few clinics (only two reported inliterature38,39). The machinery is very different from that of theCyberKnife, using a gimballed treatment head mounted on anO-ring, but the principles of the tracking monitoring anddriving systems are very similar to those of the CyberKnife de-scribed above. External optical markers are placed on the patientsurface, and orthogonal uoroscopic imaging sequences areinitially used to establish a mathematical correlation modelbetween the motion of the external markers and the target.During beam on, the motion of the external markers is moni-tored and the correlation model is used to direct the beam (withpan and tilts of the gimballed head) dynamically at the modelledtarget position. During beam delivery, orthogonal radiographicimages are acquired regularly, and the images are used postbeam delivery for evaluation of the need for recalculation of thecorrelation model.

Dynamic multi-leaf collimator (MLC) tracking for a standardgantry-based linac has recently been used clinically for the rsttime,40 although not for lung cancer but prostate cancer treat-ment. MLC tracking for lung cancer is still in development.4143

In MLC tracking, the MLC leaves shaping the treatment beamare programmed to move in accordance with the target motionduring breathing. This leaf motion can be superposed onintensity-modulated radiotherapy (IMRT) or dynamic arc leafmotion.4446 In relation to the development of MLC tracking,focus is on beam delivery, and specic image guidance protocolsare not established. Development issues relate primarily to po-sitioning of the leaves and jaws. Image guidance techniquesavailable in the treatment room can be used in the trackingprocess in various ways. The standard linac does not have or-thogonal radiographic imaging capabilities, like the CyberKnifeand the Vero machines, but some rooms may have additionalradiographic imaging equipment installed, such as the BrainLabExacTrac X-ray system (BrainLab). Monitoring of the breath-ing by, for instance, an optical tracking system may additionallybe available in the treatment room. Several alternatives of director indirect motion monitoring and positional verication areinvestigated for MLC tracking implementation.4749

Finally, tracking by couch countermotion is under investigationby several groups but is not clinically implemented.50,51

Treatment planning for motion tracking can be performed eitherfor all phases of the full 4DCTscan for a 4D optimized treatmentplan44 or to a single phase for a static plan, which may besubsequently translated according to breathing motion.

Decision-making strategies for motion managementIt is still a question of heated debate, which motion managementstrategy to use for which patients. A standard or guideline fordecision-making regarding motion management has not beenestablished in the radiotherapy community, rather the com-munity is divided by different basic views on the issue.

It has been shown that the median motion extent of lungtumours is around 5mm, and only around 20% of patients withlung cancer have tumours with motion .1 cm.26,52,53 For mo-tion less than approximately 13mm, respiratory gating or mo-tion tracking can reduce treatment eld margins by ,2mm53

compared with a midventilation approach. The effects of motionmanagement on treatment eld margins are rather small ingeneral because it is only one component of random nature inthe entire uncertainty chain, and especially small for lung cancerradiotherapy because of the smeared out penumbra in the low-density lung tissue.

A cost-effectiveness decision criterion for choice of motionmanagement in treatment delivery based on motion extent alonewould therefore imply that only few patients would be eligiblefor respiratory gating or motion tracking. However, an addi-tional parameter relevant for decision-making is the dose tonearby organs at risk. Dose to organs at risk is very much de-pendent on individual features in each case, and there are noeasily quantiable simple parameters that can pre-determineeligibility for motion management. Calculation of doses to



organs at risk in the treatment planning system is doable forrespiratory gating or breath-hold techniques (where calculationscan be carried out in one single phase of breathing), but formotion-encompassing techniques and tracking techniques, cal-culation should really be performed in all phases of breathingand accumulated, and treatment planning systems do not havethat capability in full. Proximity of target to organs at risk may bea parameter indicating potential relevance of respiratory gating ortracking, but it will be a matter of individual assessment.

Regularity of breathing relates to a feasibility criterion that mayalso determine eligibility for use of motion management tech-niques in treatment delivery. The success of both respiratorygating and motion-tracking techniques rely on the ability of thepatient to breathe in a regular and predictable pattern. The moreirregular and unpredictable the pattern, the more likely themotion management is to fail, for instance, by lack of consis-tency in the correspondence between motion of the target and ofthe external motion surrogate used for driving the beam posi-tion. Also for this, there is no easily quantiable parameter toindicate adequate regularity of breathing. Training and real-timecoaching in regular breathing may increase the regularity ofbreathing for many patients.54,55

Motion management techniques that do not imply beam deliveryinterference include 4D scanning for treatment planning andrespiratory correlation of in-room imaging for localization andverication of target position. Treatment planning based on re-spiratory correlated imaging should always be applied for lungcancer. A 4DCT scan will give information on motion extent andproximity of target of organs at risk, which can be used in thedecision-making strategy for further motion management. Also,the 4DCT scan will be less prone to image artefacts of the target,enabling more accurate delineation. In-room imaging should alsoas a default be performed with inclusion of respiratory in-formation for pre-treatment set-up, as it has been demonstratedthat this gives a large potential for increasing accuracy and therebyenabling reduction of treatment eld margins.26,53,56

Obviously in each department, availability of equipment is therst parameter determining the image guidance and motionmanagement strategies used. With purchase of new equipment,importance of image guidance and motion management will beweighed, with consideration to the patient groups, work loadand performance expected for the machine operation.

CLINICAL PROTOCOLSIn this section, examples are given of high-level use of imageguidance and motion management protocols reported in recentliterature. As the literature reports mostly investigations of in-novative and experimental methods rather than general clinicalpractice, it is not easy to nd state-of-the-art protocols in literature.

A good example of routine clinical use of image guidance andmotion management for lung cancer radiotherapy with curativeintent can be found in the ofcial Danish recommendations forlung cancer radiotherapy from the Danish Oncological LungCancer Group from 2014 (www.dolg.dk/stralerekommandationer.php in Danish). In these recommendations, treatment planning

should be performed based on a 4DCT scan, in which the mag-nitude of breathing motion is estimated. Based on the CT scan,either the midventilation approach or ITV approach (or similarmethod in which breathing motion is taken into account) is usedfor margin encompassing of the breathing motion. It is suggestedthat a breath-hold CT scan is additionally acquired in order togive an artefact-free guide for tumour shape and size to aid intarget delineation. For treatment delivery, image guidance is rec-ommended on a daily basis in accordance with and supportingthe added CTV-to-PTV margin. Specic recommendations forchoice of image guidance method (2D, 3D or 4D) and actionlevels are not given, but it is implicit that the CTV-to-PTV marginmust be adequate to support the specic choice, and individuallycalculated at each clinic and for each protocol. Guidelines formargin calculation are also given, based on relevant literature.5763

In the Danish guidelines, there are no recommendations regardingrespiratory gating, breath-hold or motion tracking. None of thesetechniques are used on a routine basis, although they may be ap-plied in some clinics for specic cases where normal tissue con-straints or target dose prescription cannot otherwise be achieved.

Use of a breath-hold technique during beam delivery in clinicalpractice has been reported, for instance, in Brock et al64 at theRoyal Marsden Hospital. The Active Breathing Coordinator wasused in deep inspiration breath-hold, in order to minimize ir-radiation of lung tissue. No reduction of treatment eld marginswas applied, but the increased lung volume (mean increase of41% measured in a deep inspiration CT scan compared withvolume in a free breathing CT scan) implied reduction of therelative lung volume irradiated and presumably therefore alsoa corresponding reduction of irradiated lung tissue. Imaging fortreatment planning was performed as deep inspiration breath-hold CT scanning (free breathing CT was performed for com-parison). Repeated breath-hold CT scans showed that targetposition changed markedly between fractions, and the studyrecommends image guidance be used on a daily basis.

Clinical use of 4D CBCT for daily set-up imaging has beenreported for SBRT for lung tumours [early stage non-small-celllung cancer (NSCLC)] at the Netherlands Cancer Institute inSonke et al.20 Patients were routinely scanned using 4DCTscanning, and treatment planning was carried out using themidventilation approach. Patients individual PTV margins werecalculated based on the individual magnitude of breathingmotion. On each treatment day, 4D CBCT was used to matchthe midventilation target position from the planning 4DCT scanto the mean position of the breathing motion on the treatmentday. No motion management was used during beam deliveryexcept the motion-encompassing margin. Signicant reductionsof PTV margins were applied compared with the margins thatwould have been necessary with no motion management inimage guidance. In a subsequent article by Peulen et al,65 clinicaloutcome for this protocol (with a slightly larger PTV margin) isreported at 98% local control and 67% overall survival at 2 years.

Clinical use of motion tracking for lung cancer has beenreported using both the CyberKnife66,67 and the Vero38,39 sys-tems. The CyberKnife motion-tracking system has been in

BJR SS Korreman


clinical use since 2005, and clinical outcome results are reportedin the referenced literature for lung cancer treatment (Stage 1NSCLC). In these reported results, standard 3D CT scanning wasused for treatment planning, and the treatment beams wererigidly translated according to the monitored motion. Imageguidance was performed according to the protocol described inthe Motion tracking section. Local control and overall survival at2 years was reported to be 96% and 62%, respectively. Clinicaluse of the Vero system has only recently been commenced. Inthe rst reported study, treatment planning was carried out inthe expiration phase of a 4DCT scan, and image guidance wasperformed according to the protocol described in the Motiontracking section. Owing to the early stage of implementation ofthis technique, outcome results are not yet available, but it is tobe expected that results comparable to those of the CyberKnifesystem motion tracking can be achieved.

PERSPECTIVES AND FUTURE DIRECTIONSSpecial issues for proton therapyMotion management for proton therapy is a special issue, whichhas been covered in a number of papers (see, for instance, Huiet al,68 Lu et al69 and Zhao et al;70 Bert and Durante;71 and Winket al72). The challenge of proton therapy for moving targets isspecically that the effects of motion on target coverage and ir-radiation of adjacent structures is potentially much larger than forphoton irradiation. For protons, the position of the narrow Braggpeak is highly dependent on the beam energy and on the amountand density of tissue penetrated by the beam during its travelthrough the patient. Motion in the patient anatomy that changesthe conguration of structures with different densities cantherefore have a potentially large impact on the dose distribution.The effects depend on whether passive scattering proton beams orspot scanning beams are used, where the respiratory motion ofthe target may interfere with the scanning motion of the protonbeam creating interplay effects changing the dose depositionpattern markedly.73 There are studies showing varying degree ofeffects for both passive beams and scanning beams.74,75 In gen-eral, it can be said that image guidance needs to be at least ascomprehensive for proton therapy as for photon therapy, and insome cases, safe implementation of proton therapy requires moreextensive image guidance schemes than does proton therapy, ineffect limiting the implementation of proton therapy for lung.

Dose painting and motionThe delivery of heterogeneous dose distributions based onfunctional imaging with high spatial resolution and large dosegradients within the target volume is termed dose painting. The

high spatial resolution and large dose gradients add to the ne-cessity of high accuracy in both pre-treatment imaging and dosedelivery. Uncertainties in the treatment chain have detrimentaleffects on the correspondence between deposited dose and thedose prescription map, as has been shown in, for instance,Korreman et al.76 A clinical multicentre Phase II trial is presentlyrunning for a very simple dose painting strategy, applying a doseboost volume within the target to the high uptake (.50%standardized uptake value) volume from a uorine-18 u-deoxyglucose PET scan.77 The protocol involves a midventilationapproach to treatment planning, use of patient-specic treat-ment eld margins and set up in the treatment room usingimage guidance with institutional policies. As there are only twodose levels in the protocol and not high degree of heterogeneity,it is expected that this provides sufcient accuracy.

New technological developments and increasingstandardization of four-dimensional imagingAn interesting new technological development that has beenemerging in the recent years is that of the combined treatmentmachine with MRI, the MRIdian by ViewRay78 or various ver-sions of the MR-linac7981 (although the MR-linac is not yet inclinical use). MRI has superior soft-tissue contrast comparedwith imaging using ionizing radiation and can be performedsimultaneously with beam delivery. The potential of using thisfor image guidance for lung cancer in the treatment room arepromising,82,83 and may well constitute the next large step indevelopment of image-guided radiotherapy.

The existing imaging technology using CT and PET scanners aswell as in-room electronic portal imaging devices is being con-tinuously developed with respect to both hardware and softwareto provide images of higher and higher quality and resolution, inboth 2D, 3D and 4D. Examples of hardware developments aredual-energy CT scanning; time-of-ight PET scanning; com-bined uses of CT, MR and PET; and rened lters for detec-tors.84 As these technologies are rened so is the softwarefollowing them, and their use will to a larger and larger extentbecome standard. The eld of 4D imaging has been in fast de-velopment since 2000 and has changed the eld of radiotherapyfor lung cancer, as described in this review. Many issues continueto challenge the clinical implementation, and research and de-velopment is ongoing (see, for instance, the summary of the 4Dtreatment planning workshop 2013 in Knopf et al85), however,radiotherapy including 4D image guidance (and dynamic beamdelivery) has become standard in many clinics, and its dissem-ination in clinical practice will continue.

REFERENCES

1. Korreman SS. Motion in radiotherapy: pho-

ton therapy. Phys Med Biol 2012; 57:

R16191. doi: 10.1088/0031-9155/57/23/

R161

2. 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

heartbeat, measured during radiotherapy. Int

J Radiat Oncol Biol Phys 2002; 53: 82234.

doi: 10.1016/S0360-3016(02)02803-1

3. Sonke JJ, Lebesque J, van Herk M. Variability

of four-dimensional computed tomography

patient models. Int J Radiat Oncol Biol Phys

2008; 70: 5908. doi: 10.1016/j.

ijrobp.2007.08.067

4. Worm ES, Hyer M, Fledelius W, Hansen AT,

Poulsen PR. Variations in magnitude and

directionality of respiratory target motion

throughout full treatment courses of stereo-

tactic body radiotherapy for tumors in the



liver. Acta Oncol 2013; 52: 143744. doi:

10.3109/0284186X.2013.813638

5. Shirato H, Shimizu S, Kitamura K, Nishioka

T, Kagei K, Hashimoto S, et al. Four-

dimensional treatment planning and uoro-

scopic real-time tumor tracking radiotherapy

for moving tumor. Int J Radiat Oncol Biol

Phys 2000; 48: 43542. doi: 10.1016/S0360-

3016(00)00625-8

6. Chen GT, Kung JH, Beaudette KP. Artifacts in

computed tomography scanning of moving

objects. Semin Radiat Oncol 2004; 14: 1926.

doi: 10.1053/j.semradonc.2003.10.004

7. Persson GF, Nygaard DE, Brink C, Jahn JW,

Munck af Rosenschold P, Specht L, et al.

Deviations in delineated GTV caused by

artefacts in 4DCT. Radiother Oncol 2010; 96:

616. doi: 10.1016/j.radonc.2010.04.019

8. 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: 36671. doi: 10.1118/1.1448824

9. Nehmeh SA, Erdi YE, Rosenzweig KE,

Schoder H, Larson SM, Squire OD, et al.

Reduction of respiratory motion artifacts in

PET imaging of lung cancer by respiratory

correlated dynamic PET: methodology and

comparison with respiratory gated PET.

J Nucl Med 2003; 44: 16448.

10. Clements N, Kron T, Franich R, Dunn L,

Roxby P, Aarons Y, et al. The effect of

irregular breathing patterns on internal target

volumes in four-dimensional CT and cone-

beam CT images in the context of stereotactic

lung radiotherapy. Med Phys 2013; 40:

021904. doi: 10.1118/1.4773310

11. Aznar MC, Persson GF, Kofoed IM, Nygaard

DE, Korreman SS. Irregular breathing during

4DCT scanning of lung cancer patients: is the

midventilation approach robust? Phys Med

2014; 30: 6975. doi: 10.1016/j.

ejmp.2013.03.003

12. Persson GF, Nygaard DE, Munck Af

Rosenschold P, Richter Vogelius I, Josipovic

M, Specht L, et al. Artifacts in conventional

computed tomography (CT) and free

breathing four-dimensional CT induce un-

certainty in gross tumor volume determina-

tion. Int J Radiat Oncol Biol Phys 2011; 80:

157380. doi: 10.1016/j.ijrobp.2010.10.036

13. Persson GF. Uncertainties in target denition

for radiotherapy of peripheral lung tumours.

PhD thesis. Copenhagen, Denmark: Univer-

sity of Copenhagen; 2011.

14. Weiss E, Robertson SP, Mukhopadhyay N,

Hugo GD. Tumor, lymph node, and lymph

node-to-tumor displacements over a radio-

therapy series: analysis of interfraction and

intrafraction variations using active breathing

control (ABC) in lung cancer. Int J Radiat

Oncol Biol Phys 2012; 82: e63945. doi:

10.1016/j.ijrobp.2011.08.021

15. Sonke JJ, Zijp L, Remeijer P, van Herk M.

Respiratory correlated cone beam CT. Med

Phys 2005; 32: 117686. doi: 10.1118/

1.1869074

16. Trumm CG, Haussler SM, Muacevic A, Stahl

R, Stintzing S, Paprottka PM, et al. CT

uoroscopy-guided percutaneous ducial

marker placement for CyberKnife stereotactic

radiosurgery: technical results and compli-

cations in 222 consecutive procedures. J Vasc

Interv Radiol 2014; 25: 7608. doi: 10.1016/j.

jvir.2014.01.004

17. Patel A, Khalsa B, Lord B, Sandrasegaran K,

Lall C. Planting the seeds of success: CT-

guided gold seed ducial marker placement

to guide robotic radiosurgery. J Med Imaging

Radiat Oncol 2013; 57: 20711. doi: 10.1111/

j.1754-9485.2012.02445.x

18. 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 bronchoberscopy. Cancer

2002; 95: 17207. doi: 10.1002/cncr.10856

19. Shah AP, Kupelian PA, Waghorn BJ,

Willoughby TR, Rineer JM, Maon RR,

et al. Real-time tumor tracking in the

lung using an electromagnetic tracking

system. Int J Radiat Oncol Biol Phys 2013;

86: 47783. doi: 10.1016/j.ijrobp.2012.12.030

20. Sonke JJ, Rossi M, Wolthaus J, van Herk M,

Damen E, Belderbos J. Frameless stereotactic

body radiotherapy for lung cancer using

four-dimensional cone beam CT guidance.

Int J Radiat Oncol Biol Phys 2009; 74: 56774.

doi: 10.1016/j.ijrobp.2008.08.004

21. Hanna GG, van Sornsen de Koste JR, Dahele

MR, Carson KJ, Haasbeek CJ, Migchielsen R,

et al. Dening target volumes for stereotactic

ablative radiotherapy of early-stage lung

tumours: a comparison of three-dimensional

18F-uorodeoxyglucose positron emission

tomography and four-dimensional computed

tomography. Clin Oncol (R Coll Radiol) 2012;

24: e7180. doi: 10.1016/j.clon.2012.03.002

22. Underberg RW, Lagerwaard FJ, Slotman BJ,

Cuijpers JP, Senan S. Use of maximum

intensity projections (MIP) for target volume

generation in 4DCT scans for lung cancer. Int

J Radiat Oncol Biol Phys 2005; 63: 25360.

doi: 10.1016/j.ijrobp.2005.05.045

23. Yin FF, Wang Z, Yoo S, Wu QJ, Kirkpatrick J,

Larrier N, et al. Integration of cone-beam CT

in stereotactic body radiation therapy. Tech-

nol Cancer Res Treat 2008; 7: 1339. doi:

10.1177/153303460800700206

24. Knap MM, Hoffmann L, Nordsmark M,

Vestergaard A. Daily cone-beam computed

tomography used to determine tumour

shrinkage and localisation in lung cancer

patients. Acta Oncol 2010; 49: 107784. doi:

10.3109/0284186X.2010.498434

25. Wolthaus JW, Schneider C, Sonke JJ, van

Herk M, BelderbosJS, Rossi MM, et al. Mid-

ventilation CT scan construction from four-

dimensional respiration-correlated CT scans

for radiotherapy planning of lung cancer

patients. Int J Radiat Oncol Biol Phys 2006;

65: 156071. doi: 10.1016/j.ijrobp.2006.04.031

26. Wolthaus JW, Sonke JJ, van Herk M,

Belderbos JS, Rossi MM, Lebesque JV, et al.

Comparison of different strategies to use

four-dimensional computed tomography in

treatment planning for lung cancer patients.

Int J Radiat Oncol Biol Phys 2008; 70:

122938. doi: 10.1016/j.ijrobp.2007.11.042

27. Sweeney RA, Seubert B, Stark S, Homann V,

Muller G, Flentje M, et al. Accuracy and

inter-observer variability of 3D versus 4D

cone-beam CT based image-guidance in

SBRT for lung tumors. Radiat Oncol 2012; 7:

81. doi: 10.1186/1748-717X-7-81

28. Korreman SS, Juhler-Nttrup T, Boyer AL.

Respiratory gated beam delivery cannot

facilitate margin reduction, unless combined

with respiratory correlated image guidance.

Radiother Oncol 2008; 86: 618. doi: 10.1016/

j.radonc.2007.10.038

29. Giraud P, Morvan E, Claude L, Mornex F,

Le Pechoux C, Bachaud JM, et al. Respiratory

gating techniques for optimization of

lung cancer radiotherapy. J Thorac Oncol

2011; 6: 205868. doi: 10.1097/

JTO.0b013e3182307ec2

30. Kimura T, Murakami Y, Kenjo M, Kaneyasu

Y, Wadasaki K, Ito K, et al. Interbreath-hold

reproducibility of lung tumour position and

reduction of the internal target volume using

a voluntary breath-hold method with spi-

rometer during stereotactic radiotherapy for

lung tumours. Br J Radiol 2007; 80: 35561.

doi: 10.1259/bjr/31008031

31. Josipovic M, Aznar MC, Persson GF. Deep

inspiration breath hold radiotherapy of lung

cancer: the good, the bad and the ugly case.

Acta Oncol 2014; 53: 14468. doi: 10.3109/

0284186X.2014.922216

32. 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: 143742. doi: 10.1016/j.

ijrobp.2003.08.006

33. George R, Chung TD, Vedam SS,

Ramakrishnan V, Mohan R, Weiss E, et al.

Audio-visual biofeedback for respiratory-

gated radiotherapy: impact of audio instruc-

tion and audio-visual biofeedback on

respiratory-gated radiotherapy. Int J Radiat

BJR SS Korreman


Oncol Biol Phys 2006; 65: 92433. doi:

10.1016/j.ijrobp.2006.02.035

34. Damkjr SM, Aznar MC, Pedersen AN,

Vogelius IR, Bangsgaard JP, Josipovic M.

Reduced lung dose and improved inspiration

level reproducibility in visually guided DIBH

compared to audio coached EIG radiotherapy

for breast cancer patients. Acta Oncol 2013;

52: 145863. doi: 10.3109/

0284186X.2013.813073

35. Nioutsikou E, Seppenwoolde Y, Symonds-

Tayler JR, Heijmen B, Evans P, Webb S.

Dosimetric investigation of lung tumor

motion compensation with a robotic re-

spiratory tracking system: an experimental

study. Med Phys 2008; 35: 123240. doi:

10.1118/1.2842074

36. Brown WT, Wu X, Fayad F, Fowler JF, Garcia

S, Monterroso MI, et al. Application of

robotic stereotactic radiotherapy to periph-

eral stage I non-small cell lung cancer with

curative intent. Clin Oncol (R Coll Radiol)

2009; 21: 62331. doi: 10.1016/j.

clon.2009.06.006

37. Pepin EW, Wu H, Zhang Y, Lord B.

Correlation and prediction uncertainties in

the cyberknife synchrony respiratory tracking

system. Med Phys 2011; 38: 403644. doi:

10.1118/1.3596527

38. Depuydt T, Poels K, Verellen D, Engels B,

Collen C, Buleteanu M, et al. Treating

patients with real-time tumor tracking using

the Vero gimbaled linac system: implemen-

tation and rst review. Radiother Oncol 2014;

112: 34351. doi: 10.1016/j.

radonc.2014.05.017

39. Solberg TD, Medin PM, Ramirez E, Ding C,

Foster RD, Yordy J. Commissioning and initial

stereotactic ablative radiotherapy experience

with Vero. J Appl Clin Med Phys 2014; 15: 4685.

doi: 10.1120/jacmp.v15i2.4685

40. Falk M, Pommer T, Keall P, Korreman S,

Persson G, Poulsen P, et al. Motion man-

agement during IMAT treatment of mobile

lung tumorsa comparison of MLC tracking

and gated delivery. Med Phys 2014; 41:

101707. doi: 10.1118/1.4896024

41. Falk M, Munck af Rosenschold P, Keall P,

Cattell H, Cho BC, Poulsen P, et al. Real-time

dynamic MLC tracking for inversely opti-

mized arc radiotherapy. Radiother Oncol

2010; 94: 21823. doi: 10.1016/j.

radonc.2009.12.022

42. Pommer T, Falk M, Poulsen PR, Keall PJ,

OBrien RT, Munck af Rosenschold P. The

impact of leaf width and plan complexity on

DMLC tracking of prostate intensity modu-

lated arc therapy. Med Phys 2013; 40: 111717.

doi: 10.1118/1.4824434

43. Fast MF, Nill S, Bedford JL, Oelfke U.

Dynamic tumor tracking using the Elekta

Agility MLC.Med Phys 2014; 41: 111719. doi:

10.1118/1.4899175

44. Suh Y, Sawant A, Venkat R, Keall PJ. Four-

dimensional IMRT treatment planning using

a DMLC motion-tracking algorithm. Phys

Med Biol 2009; 54: 382135. doi: 10.1088/

0031-9155/54/12/014

45. Zimmerman J, Korreman S, Persson G,

Cattell H, Svatos M, Sawant A, et al. DMLC

motion tracking of moving targets for in-

tensity modulated arc therapy treatment:

a feasibility study. Acta Oncol 2009; 48:

24550. doi: 10.1080/02841860802266722

46. Gui M, Feng Y, Yi B, Dhople AA, Yu C. Four-

dimensional intensity-modulated radiation

therapy planning for dynamic tracking using

a direct aperture deformation (DAD)

method. Med Phys 2010; 37: 196675. doi:

10.1118/1.3319498

47. Korreman S, Mostafavi H, Le QT, Boyer A.

Comparison of respiratory surrogates for

gated lung radiotherapy without internal

ducials. Acta Oncol 2006; 45: 93542. doi:

10.1080/02841860600917161

48. Xu Q, Hamilton RJ, Schowengerdt RA,

Alexander B, Jiang SB. Lung tumor tracking

in uoroscopic video based on optical ow.

Med Phys 2008; 35: 53519. doi: 10.1118/

1.3002323

49. Poulsen PR, Cho B, Keall PJ. A method to

estimate mean position, motion magnitude,

motion correlation, and trajectory of a tumor

from cone-beam CT projections for image-

guided radiotherapy. Int J Radiat Oncol Biol

Phys 2008; 72: 158796. doi: 10.1016/j.

ijrobp.2008.07.037

50. Menten MJ, Guckenberger M, Herrmann C,

Krau A, Nill S, Oelfke U, et al. Comparison

of a multileaf collimator tracking system and

a robotic treatment couch tracking system for

organ motion compensation during radio-

therapy. Med Phys 2012; 39: 703241. doi:

10.1118/1.4761868

51. DSouza WD, Naqvi SA, Yu CX. Real-time

intra-fraction-motion tracking using the

treatment couch: a feasibility study. Phys Med

Biol 2005; 50: 402133. doi: 10.1088/0031-

9155/50/17/007

52. Keall PJ, Mageras GS, Balter JM, Emery RS,

Forster KM, Jiang SB, et al. The manage-

ment of respiratory motion in radiation

oncology report of AAPM Task Group 76.

Med Phys 2006; 33: 3874900. doi: 10.1118/

1.2349696

53. Korreman S, Persson G, Nygaard D, Brink C,

Juhler-Nottrup T. Respiration-correlated im-

age guidance is the most important radio-

therapy motion management strategy for

most lung cancer patients. Int J Radiat Oncol

Biol Phys 2012; 83: 133843. doi: 10.1016/j.

ijrobp.2011.09.010

54. Haasbeek CJ, Spoelstra FO, Lagerwaard FJ,

van Sornsen de Koste JR, Cuijpers JP,

Slotman BJ, et al. Impact of audio-coaching

on the position of lung tumors. Int J Radiat


10.1016/j.ijrobp.2007.11.061

55. Goossens S, Senny F, Lee JA, Janssens G,

Geets X. Assessment of tumor motion re-

producibility with audio-visual coaching

through successive 4D CT sessions. J Appl

Clin Med Phys 2014; 15: 4332. doi: 10.1120/

jacmp.v15i1.4332

56. Grills IS, Hugo G, Kestin LL, Galerani AP,

Chao KK, Wloch J, et al. Image-guided

radiotherapy via daily online cone-beam CT

substantially reduces margin requirements

for stereotactic lung radiotherapy. Int J

Radiat Oncol Biol Phys 2008; 70: 104556.

doi: 10.1016/j.ijrobp.2007.07.2352

57. van Herk M, Remeijer P, Rasch C, Lebesque

JV. The probability of correct target dosage:

dose-population histograms for deriving

treatment margins in radiotherapy. Int J


58. Steenbakkers RJ, Duppen JC, Fitton I,

Deurloo KE, Zijp LJ, Comans EF, et al.

Reduction of observer variation using

matched CT-PET for lung cancer delineation:

a three-dimensional analysis. Int J Radiat


10.1016/j.ijrobp.2005.06.034

59. Persson GF, Nygaard DE, Hollensen C,

Munck af Rosenschold P, Mouritsen LS, Due

AK, et al. Interobserver delineation variation

in lung tumour stereotactic body radiother-

apy. Br J Radiol 2012; 85: e65460. doi:

10.1259/bjr/76424694

60. Nielsen TB, Hansen VN, Westberg J, Hansen

O, Brink C. A dual centre study of setup

accuracy for thoracic patients based on cone-

beam CT data. Radiother Oncol 2012; 102:

2816. doi: 10.1016/j.radonc.2011.11.012

61. Josipovic M, Persson GF, Logadottir A,

Smulders B, Westmann G, Bangsgaard JP.

Translational and rotational intra- and inter-

fractional errors in patient and target posi-

tion during a short course of frameless

stereotactic body radiotherapy. Acta Oncol

2012; 51: 61017. doi: 10.3109/

0284186X.2011.626448

62. Gottlieb KL, Hansen CR, Hansen O,

Westberg J, Brink C. Investigation of respi-

ration induced intra- and inter-fractional

tumour motion using a standard Cone

Beam CT. Acta Oncol 2010; 49: 11928.

doi: 10.3109/0284186X.2010.498834

63. Ottosson W, Baker M, Hedman M, Behrens

CF, Sjostrom D. Evaluation of setup accuracy

for NSCLC patients; studying the impact of

different types of cone-beam CT matches

based on whole thorax, columna vertebralis,



and GTV. Acta Oncol 2010; 49: 118491. doi:

10.3109/0284186X.2010.500303

64. Brock J, McNair HA, Panakis N, Symonds-

Tayler R, Evans PM, Brada M. The use of the

active breathing coordinator throughout

radical non-small-cell lung cancer (NSCLC)

radiotherapy. Int J Radiat Oncol Biol Phys

2011; 81: 36975. doi: 10.1016/j.

ijrobp.2010.05.038

65. Peulen H, Belderbos J, Rossi M, Sonke JJ.

Mid-ventilation based PTV margins in Ste-

reotactic Body Radiotherapy (SBRT): a clini-

cal evaluation. Radiother Oncol 2014; 110:

51116. doi: 10.1016/j.radonc.2014.01.010

66. van der Voort van Zyp NC, Prevost JB,

Hoogeman MS, Prevost J, van der Holt B,

Levendag PC, et al. Stereotactic radiotherapy

with real-time tumor tracking for non-small

cell lung cancer: clinical outcome. Radiother

Oncol 2009; 91: 296300. doi: 10.1016/j.

radonc.2009.02.011

67. Ahn SH, Han MS, Yoon JH, Jeon SY, Kim

CH, Yoo HJ, et al. Treatment of stage I non-

small cell lung cancer with CyberKnife,

image-guided robotic stereotactic radiosur-

gery. Oncol Rep 2009; 21: 6936.

68. Hui Z, Zhang X, Starkschall G, Li Y, Mohan

R, Komaki R, et al. Effects of interfractional

motion and anatomic changes on proton

therapy dose distribution in lung cancer. Int J


doi: 10.1016/j.ijrobp.2008.03.007

69. Lu HM, Brett R, Sharp G, Safai S, Jiang S,

Flanz J, et al. A respiratory-gated treatment

system for proton therapy. Med Phys 2007;

34: 32738. doi: 10.1118/1.2756602

70. Zhao L, Sandison GA, Farr JB, Hsi WC, Li

XA. Dosimetric impact of intrafraction

motion for compensator-based proton ther-

apy of lung cancer. Phys Med Biol 2008; 53:

334364. doi: 10.1088/0031-9155/53/12/019

71. Bert C, Durante M. Motion in radiotherapy:

particle therapy. Phys Med Biol 2011; 56:

R11344. doi: 10.1088/0031-9155/56/16/R01

72. Wink KC, Roelofs E, Solberg T, Lin L,

Simone CB 2nd, Jakobi A, et al. Particle

therapy for non-small cell lung tumors:

where do we stand? A systematic review of

the literature. Front Oncol 2014; 4: 292. doi:

10.3389/fonc.2014.00292

73. Paganetti H, Jiang H, Tromov A. 4D Monte

Carlo simulation of proton beam scanning:

modelling of variations in time and space to

study the interplay between scanning pattern

and time-dependent patient geometry. Phys

Med Biol 2005; 50: 98390. doi: 10.1088/

0031-9155/50/5/020

74. Matney J, Park PC, Bluett J, Chen YP, Liu W,

Court LE, et al. Effects of respiratory motion

on passively scattered proton therapy versus

intensity modulated photon therapy for stage

III lung cancer: are proton plans more

sensitive to breathing motion? Int J Radiat


10.1016/j.ijrobp.2013.07.007

75. Dowdell S, Grassberger C, Sharp GC,

Paganetti H. Interplay effects in proton

scanning for lung: a 4D Monte Carlo study

assessing the impact of tumor and beam

delivery parameters. Phys Med Biol 2013; 58:

413756. doi: 10.1088/0031-9155/58/12/4137

76. Korreman SS, Ulrich S, Bowen S, Deveau M,

Bentzen SM, Jeraj R. Feasibility of dose painting

using volumetric modulated arc optimization

and delivery. Acta Oncol 2010; 49: 96471. doi:

10.3109/0284186X.2010.498440

77. van Elmpt W, De Ruysscher D, van der Salm

A, Lakeman A, van der Stoep J, Emans D,

et al. The PET-boost randomised phase II

dose-escalation trial in non-small cell lung

cancer. Radiother Oncol 2012; 104: 6771.

doi: 10.1016/j.radonc.2012.03.005

78. Mutic S, Dempsey JF. The ViewRay system:

magnetic resonance-guided and controlled

radiotherapy. Semin Radiat Oncol 2014; 24:

1969. doi: 10.1016/j.

semradonc.2014.02.008

79. Keall PJ, Barton M, Crozier S. The Australian

magnetic resonance imaging-linac program.

Semin Radiat Oncol 2014; 24: 2036. doi:

10.1016/j.semradonc.2014.02.015

80. Fallone BG. The rotating biplanar linac-

magnetic resonance imaging system. Semin

Radiat Oncol 2014; 24: 2002. doi: 10.1016/j.

semradonc.2014.02.011

81. Raaymakers BW, Lagendijk JJ, Overweg J,

Kok JG, Raaijmakers AJ, Kerkhof EM, et al.

Integrating a 1.5 T MRI scanner with a 6 MV

accelerator: proof of concept. Phys Med Biol

2009; 54: N22937. doi: 10.1088/0031-9155/

54/12/N01

82. Shi X, Diwanji T, Mooney KE, Lin J,

Feigenberg S, DSouza WD, et al. Evaluation

of template matching for tumor motion

management with cine-MR images in lung

cancer patients. Med Phys 2014; 41: 052304.

doi: 10.1118/1.4870978

83. Yun J, Wachowicz K, Mackenzie M, Rathee S,

Robinson D, Fallone BG. First demonstration

of intrafractional tumor-tracked irradiation

using 2D phantom MR images on a pro-

totype linac-MR. Med Phys 2013; 40: 051718.

doi: 10.1118/1.4802735

84. Stankovic U, van Herk M, Ploeger LS, Sonke

JJ. Improved image quality of cone beam CT

scans for radiotherapy image guidance using

ber-interspaced antiscatter grid. Med Phys

2014; 41: 061910. doi: 10.1118/1.4875978

85. Knopf A, Nill S, Yohannes I, Graeff C,

Dowdell S, Kurz C, et al. Challenges of

radiotherapy: report on the 4D treatment

planning workshop 2013. Phys Med 2014; 30:

80915. doi: 10.1016/j.ejmp.2014.07.341

BJR SS Korreman


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