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Recommendations for implementing stereotactic radiotherapy in peripheral stage IA non-small cell lung cancer: report from the Quality Assurance Working Party of the randomised phase III ROSEL study

Recommendations for implementing stereotactic radiotherapy in peripheral stage IA non-small cell... Background: A phase III multi-centre randomised trial (ROSEL) has been initiated to establish the role of stereotactic radiotherapy in patients with operable stage IA lung cancer. Due to rapid changes in radiotherapy technology and evolving techniques for image-guided delivery, guidelines had to be developed in order to ensure uniformity in implementation of stereotactic radiotherapy in this multi-centre study. Methods/Design: A Quality Assurance Working Party was formed by radiation oncologists and clinical physicists from both academic as well as non-academic hospitals that had already implemented stereotactic radiotherapy for lung cancer. A literature survey was conducted and consensus meetings were held in which both the knowledge from the literature and clinical experience were pooled. In addition, a planning study was performed in 26 stage I patients, of which 22 were stage 1A, in order to develop and evaluate the planning guidelines. Plans were optimised according to parameters adopted from RTOG trials using both an algorithm with a simple homogeneity correction (Type A) and a more advanced algorithm (Type B). Dose conformity requirements were then formulated based on these results. Conclusion: Based on current literature and expert experience, guidelines were formulated for this phase III study of stereotactic radiotherapy versus surgery. These guidelines can serve to facilitate the design of future multi-centre clinical trials of stereotactic radiotherapy in other patient groups and aid a more uniform implementation of this technique outside clinical trials. Page 1 of 14 (page number not for citation purposes) Radiation Oncology 2009, 4:1 http://www.ro-journal.com/content/4/1/1 (both direct and indirect). In case of surgery, a lobectomy Background Until recently, conventionally fractionated high-dose should be carried out, but limited resections are accepta- radiation therapy was the preferred treatment in patients ble. Careful radiological follow-up is performed within with stage I NSCLC who were unfit to undergo surgery or the trial in patients treated by SRT, as salvage surgery or declined surgery. This is, however, a poor alternative to mediastinal radiation therapy might still be possible in surgery in operable patients as the mean reported crude case of clinical, radiological or histological evidence of local recurrence rates are as high as 40% (range 6–70%), local or hilar disease progression. resulting in a three year overall and cause-specific survival of only 34 and 39%, respectively [1]. Accreditation and dosimetry guidelines have been previ- ously developed for trials of stereotactic radiotherapy such Recently, stereotactic radiotherapy has gained much inter- as RTOG 0236 and JCOG 0403 [12-14]. However, a reas- est in the treatment of medically inoperable patients with sessment was considered necessary because a new patient stage I lung cancer, as local control rates are dramatically group was being treated with stereotactic radiotherapy, improved with this technique compared to conventional namely patients who were fit to undergo both primary fractionation. In studies where schedules with a biologi- and salvage surgery. As a result, normal tissue dose-con- cally effective dose (BED) larger than 100 Gy are used, typ- straints had to be more stringently defined in order to ical local control rates are approximately 90%. The largest minimize the risk of increased complications after salvage series were reported from Japan [2,3], United States [4] surgery. Furthermore, IGRT technology from different and the Netherlands [5], comprising experience in over vendors has been rapidly adopted at various Dutch cen- 750 patients. Onishi et al. [6] retrospectively described the tres, which had to be taken into account. The resulting results of 257 patients treated in 14 Japanese centres using guidelines include both minimum requirements that a number of different fractionation schedules and delivery must be met by each participating centre as well as recom- approaches. This Japanese study also included nearly 100 mendations for possible further improvements. They are patients who refused surgery, and the 5-year overall sur- presented here in order to facilitate the implementation of vival rate of 70.8% observed after a BED of 100 Gy among future multi-centre studies, to stimulate and improve the those patients is at least equivalent to the outcome after implementation of stereotactic techniques in clinical prac- surgery [7-9]. Currently, several phase II trials have started tice and to improve the comparability of results. in operable lung cancer patients [10] (RTOG 0618 and JCOG 0403), however, to date no prospective multi-cen- Methods tre randomized studies have been performed to compare A ROSEL Quality Assurance Working Party was formed by stereotactic radiotherapy with surgery in patients with radiation oncologists and medical physicists from both operable lung cancer. academic as well as non-academic hospitals that had already implemented stereotactic radiotherapy for lung A randomized phase III trial of Radiosurgery Or Surgery cancer. Several working party meetings were organised in for operable Early stage (stage 1A) non-small cell Lung which both the knowledge from literature and clinical cancer (ROSEL, ClinicalTrials.gov ID = NCT00687986) experience were shared and amalgamated. In support of has been opened for accrual in August 2008. The study is these meetings, a literature search was conducted by initiated by the VU medical centre Amsterdam and the searching MEDLINE with different key words and their Dutch Lung Cancer Research Group. The primary study permutations such as stereotactic radiotherapy, stage I objectives are to compare local and regional control, qual- lung cancer, treatment planning, CT scan, patient posi- ity of life and treatment costs at 2 and 5 years in patients tioning and tumour mobility. Abstract books of the who are randomized to either surgery or radiosurgery ASTRO, ASCO, AAPM and ESTRO/ECCO from 2004 to (Figure 1). Treatment costs are a primary end-point, as the 2008 were reviewed. It was recognized that there was little costs associated with surgery for stage IA in The Nether- data available in the literature about the influence of dif- lands are far higher than the present costs of stereotactic ferent planning algorithms on the planning of stereotactic radiotherapy [11]. These costs are expected to be even radiotherapy. Therefore, an additional planning study was more if the costs of post-operative revalidation and loss of performed in 22 stage IA and 4 stage 1B non-small cell economic activity are taken into account. However, lung cancer patients in order to develop and evaluate the patients treated with stereotactic radiotherapy could incur planning guidelines differentiated according to type of costs for salvage treatment if a higher incidence of local or dose calculation algorithm used. Patient characteristics regional recurrences is detected. Therefore, treatment costs and treatment planning details have been reported previ- were considered to be a relevant end-point. ously [15]. Secondary objectives include overall survival, pulmonary In brief, a four-dimensional (4D)-CT was reconstructed in function tests, quality adjusted life years and total costs ten equally spaced time bins using respiratory phase bin- Page 2 of 14 (page number not for citation purposes) Radiation Oncology 2009, 4:1 http://www.ro-journal.com/content/4/1/1 ROSEL st Figure 1udy design ROSEL study design. Page 3 of 14 (page number not for citation purposes) Radiation Oncology 2009, 4:1 http://www.ro-journal.com/content/4/1/1 ning for each patient. From these phases, a maximum (IV) contrast on dose calculations for lung patients is not intensity projection (MIP) was reconstructed [16]. The specifically studied, the influence of IV contrast in head treatment datasets were then imported in the Pinnacle and neck intensity modulated radiotherapy plans was planning system (Philips Medical Systems, Wisconsin). proven to be insignificant [25]. The slice spacing between Using the MIP dataset, an experienced radiation oncolo- reconstructed CT images should be ≤3 mm over the com- gist delineated the internal target volume (ITV). Organs at plete tumour trajectory and ≤5 mm elsewhere. The scan risk were delineated on an average-density CT reconstruc- should encompass the entire lung volume in order to cal- tion. The PTV was created by expanding the ITV with a 3 culate meaningful lung dose-volume parameters. mm margin. The treatment plans consisted of 9 equally spaced coplanar 6 MV beams which were not allowed to Target volume definition enter through the oesophagus, heart, spinal cord or con- The gross tumour volume (GTV) will generally be con- tralateral lung. The plans were inversely optimized using toured using CT pulmonary windows; however, soft tissue the direct aperture optimization module of the Pinnacle windows may be used to avoid inclusion of adjacent ves- treatment planning system with the same objectives as sels or chest wall structures within the GTV. The correct- used in the ROSEL trial. Three different plans were cre- ness of the GTV delineation should be checked in axial, ated; using an advanced (type A) dose calculation algo- sagittal and coronal views. The clinical target volume rithm, a less advanced (type B) algorithm and a plan (CTV) is assumed to be identical to the GTV, i.e. with no assuming all tissues within the body to have unit density, margin for microscopic disease added, which appears to in accordance with the RTOG study 0236 and 0618 proto- be justified by the high local control rates observed in cols [17,18]. patients undergoing careful post-treatment follow-up [26]. This approach has also been accepted in the ASTRO- In order to facilitate the clinical use of these recommenda- ACR recommendations on stereotactic radiotherapy [27]. tions, we divided the process of implementing high-dose radiotherapy into the following headings: CT scanning For PTV definition, two main treatment planning and exe- and patient positioning, target volume definition, organs cution techniques can be distinguished; planning and at risk definition, Dose calculation algorithms and frac- irradiation based on the internal target volume (ITV) con- tionation, dose prescription, coverage and constraints, cept or the time-averaged mean position of the tumour. treatment planning and treatment execution. PTV based on the ITV concept Patient positioning and CT scanning For 4D CT scans, the ITV can be derived from the union of The patient should be scanned in the treatment position GTV delineations on all breathing phases or alternatively, which should be supine with both arms raised above the from contouring on a maximum intensity projection head using an arm-rest or other fixation device. Positions (MIP) CT-dataset [28,29]. The appropriateness of the which are less comfortable for the patient should be MIP-delineation should at least be confirmed by a visual avoided so as to prevent the likelihood of uncontrolled inspection of the projected ITV contours on the CT-data- movement during scanning or treatment. Four-dimen- sets of the end-inspiration and end-expiration phase bins sional (4D) CT scanning is strongly recommended in using axial, sagittal and coronal views. In addition to the order to account for an individualised assessment and MIP contouring, the GTV should also be contoured in a incorporation of tumour motion [19-21]. Preferably 10 single phase (preferably the end-expiration phase, but no less than 6 breathing phases should be recon- because this is the most stable tumour position and the structed in order to determine the tumour movement for phase with the least breathing artefacts) in all patients in treatment planning. Using 10 phases, it was found that order to determine the GTV size. For checking the ITV con- generally the full amplitude of motion can be captured tour based on the MIP it is not necessary to delineate the [22]. Within the ROSEL trial, acquisition of a slow-CT end-inspiration and end-expiration phase bins (visual scan or multiple (at least 3) rapid planning scans covering assessment suffices). Alternatively, the ITV may be con- the entire range of tumour motion is also allowed, as 4D- structed by the union of all delineations of the GTV in all CT scanners are not widely available yet. However, target breathing phases. If only 3D CT data is available, the ITV volume delineation might be more difficult as the images, should be based on either multiple slow CT-scans cover- and thus also the tumour volume, of slow-CT scans are ing the whole tumour trajectory or an additional margin blurred [23,24]. All centres participating in the ROSEL of 3–5 mm in all directions around the CTV determined study will most likely be able to implement 4D-CT scan- on a single slow CT-scan [30]. The ITV to PTV margin is ning in the near future. Generally, intravenous contrast is primarily meant to take into account patient set-up uncer- not necessary for planning CT scans for early stage lung tainties. However, small intra-fractional variations in the cancer, but contrast-enhanced CT images may still be used tumour motion and mean position may be present. Also for dose calculations. Although the effect of intravenous inter-fractional variations may be present, but these might Page 4 of 14 (page number not for citation purposes) Radiation Oncology 2009, 4:1 http://www.ro-journal.com/content/4/1/1 be corrected for using tumour based image guided posi- located in the mid- or lower zones of the lungs, the peri- tion verification and correction [31]. In addition, small cardium and/or heart should be contoured as a single delineation uncertainties will exist. Thus, a minimum of 3 structure. The superior aspect (or base) for purposes of mm ITV to PTV margin is required in all dimensions, even contouring will begin at the level of the inferior aspect of if a set-up error of <3 mm can be guaranteed. On the other the aortic arch (aorto-pulmonary window) and extend hand, the ITV to PTV margin should not exceed 5 mm, as inferiorly to the apex of the heart. this would unnecessarily enlarge treated volumes. In case an institution would need to apply a larger margin, e.g. The defined ipsilateral brachial plexus originates from the because of their set-up accuracy, it is advised to first spinal nerves exiting the neural foramen on the involved improve its (set-up) technique (see also paragraph about side from around C5 to T2 [35,36]. treatment execution). For peripheral tumours in the upper lobes, the major PTV based on the mean tumour position trunks of the brachial plexus should be contoured, using As an alternative to the ITV concept, planning and irradi- the subclavian and axillary vessels as surrogates. This neu- ation based on the time-averaged mean position of the rovascular complex will be contoured starting proximally tumour has been developed [32]. In contrast to the ITV to at the bifurcation of the brachiocephalic trunk into the PTV margin discussed previously, the CTV to PTV margin jugular/subclavian veins (or carotid/subclavian arteries) needed here should take the tumour motion into account. and following along the route of the subclavian vein to However, similar to the reasoning given for the ITV to PTV the axillary vein ending after the neurovascular structures margin, a minimum margin of 3 mm should be used for cross the 2nd rib. the incorporation of the other uncertainties. The trachea and proximal bronchial tree are contoured as Organs at risk definition two separate structures using mediastinal windows on CT Dose volume criteria for organs at risk (OAR) given in a to correspond to the mucosa, submucosa and cartilage next paragraph are all constraints to the highest doses rings and airway channels associated with these structures. received by the OAR. As a consequence, the impact of dif- For this purpose, the trachea will be divided into two sec- ferences in delineation protocols between institutions is tions: the proximal trachea and the distal 2 cm of trachea. not expected to be high, as these differences are likely to The proximal trachea will be contoured as one structure, be primarily of influence on the delineations located out- and the distal 2 cm of trachea will be included in the struc- side the high dose region. However, in order to support ture identified as proximal bronchial tree (main carina, future normal tissue complication probability (NTCP) right and left main bronchi, right and left upper lobe modelling studies, the OAR delineation guidelines as used bronchi, intermedius bronchus, right middle lobe bron- in the ROSEL protocol are given below. chus, lingular bronchus, right and left lower lobe bron- chi). When 4D-CT scans are used for treatment planning, the critical OAR should be contoured on the relevant refer- Delineation of the chest wall has not been regularly per- ence reconstruction (i.e. the scan used for dose calcula- formed. Little is known about chest wall morbidity in rela- tions, see also paragraph about treatment planning). This tion to dose in stereotactic radiotherapy, and therefore can generally be performed without taking into account delineation is not mandatory within the ROSEL trial [37]. potential mobility of these organs, as current experience is However, it is recommended to delineate the chest wall in based on this type of delineations. However, extremes of case of tumours in close proximity to the chest wall. This motion of organs such as the oesophagus may influence will aid the development of NTCP models concerning the choice of beam arrangements in case of 'peripheral' chest wall toxicity. lesions located in the proximity of the mediastinum [33]. Also, patient set-up corrections due to tumour shifts lead Dose calculation algorithms and fractionation to a change in the dose given to the OAR. To avoid exces- A number of different dose fractionation schedules have sive doses to OAR, it is recommended to evaluate the been reported for lung SRT [38,39], but the optimal dose impact of such shifts on the OAR dose during treatment fractionation schedule may vary with tumour stage and planning. This might be accomplished by using Planning location. Although no randomized studies comparing dif- organ at Risk Volumes (PRV) [34]. ferent fractionation schedules have been conducted for stage I tumours, most of the clinical experience is based The spinal cord and oesophagus should be contoured on schedules with 3 fractions of 20 Gy. In RTOG study starting at least 10 cm above the superior extent of the PTV 0236, RTOG study 0618 and in the ROSEL study, this frac- and continuing on every CT slice to at least 10 cm below tionation scheme is used. In all studies, eligibility for the inferior extent of the PTV. For patients with tumours inclusion was limited to lesions located ≥ 2 cm distal to Page 5 of 14 (page number not for citation purposes) Radiation Oncology 2009, 4:1 http://www.ro-journal.com/content/4/1/1 the hilar structures. Within the ROSEL study, a more con- should be 5 fractions of 12 Gy or 5 fractions of 11 Gy. A 3 servative fractionation scheme of 5 fractions of 12 Gy is fractions of 20 Gy schedule is not allowed in combination also allowed for patients with a tumour with broad con- with type B models in the ROSEL trial, as this might lead tact to the thoracic wall or adjacent to the heart or medi- to dose levels being approximately 10% higher than the astinum. Lung function is not considered to affect the dose levels with which extensive experience has been scheduling or fractionation. The largest clinical experience gained in the VU Medical Centre Amsterdam, using a type published thus far did not exclude any patient on the basis A algorithm. These higher dose levels might lead to of poor lung function [26], and did not observe excessive increased morbidity. The fractionation of 5 times 12 Gy is lung toxicity when 'risk-adapted' SRT schemes were used still allowed with type B models since the errors of type A This is supported by 2 recent reviews [40,41]. A report by algorithms in calculating dose to the thoracic wall, heart Timmerman [42] which suggested that toxicity rates were or mediastinum are expected to be less significant. high for central tumors treated with SRT has been criti- Although this also would lead to approximately 10% cized on the grounds of the toxicity definitions used [43]. higher dose levels, the biologically effective dose for the PTV will still be well below the BED of the 3 fractions However, it is recognized that differences between calcu- schedule. There are no indications in the literature that lation algorithms in the various treatment planning sys- this would lead to an unacceptable level of morbidity. It is tems may be as high as 30% in individual cases [15]. highly recommended to include dose algorithm specifics These differences are largest for lung tumour treatment in future reports about stereotactic radiotherapy for lung plans, and generally increase with decreasing field size, tumours. If a more accurate algorithm becomes available which is especially relevant in stereotactic radiotherapy of to the authors of such articles, one should also consider stage 1A lung tumours. Thus, depending on the treatment the publication of the recalculated data. These data can be planning algorithm used, one should actually use an alter- used to improve our dose-effect models, which aid the fur- native nominal fraction dose to deliver the same actual ther improvement of stereotactic radiotherapy. dose to the patient. Unfortunately, extensive data compar- ing all the calculation algorithms that are likely to be used Dose prescription, coverage and constraints in the ROSEL study are not available. For the nominal In line with current multi-institutional trials and multiple single-centre experiences, the dose prescription should be dose fractionation schedules allowed within the ROSEL trial two main type of algorithms are distinguished based on 95% of the target volume (PTV) receiving at least [15,44]. the nominal fraction dose (e.g., 20 Gy per fraction = 60 Gy total), and 99% of the target volume (PTV) receiving a � Type A models: Models primarily based on electronic minimum of 90% of the fraction dose. The dose maxi- path length (EPL) scaling for inhomogeneity corrections. mum within the PTV should preferably not be less than Changes in lateral transport of electrons are not (well) 110% or exceed 140% of the prescribed dose, similar to modelled. The algorithms in this group are e.g. Eclipse/ the criteria formulated in RTOG protocol 0618 [18]. The ModBatho and Eclipse/ETAR from Varian, OMP/PB and location of the treatment plan normalization point, Plato/ETAR from Nucletron, PrecisePLAN from Elekta, I- which is in fact only influencing the display of the dose plan Dose/PB from BrainLAB, and XiO/Convolution from distribution, can be left to the institutions preference. CMS. RTOG trial 0236 defined a set of parameters to quantify � Type B models: Models that in an approximate way con- the conformity of the dose and PTV coverage. The same sider changes in lateral electron transport. The models in parameters were used in RTOG trial 0618 and are used this group are e.g. Pinnacle/CC from Philips Medical Sys- here. However, the ROSEL trial requires the use of inho- tems, Eclipse/AAA from Varian, OMP/CC from Nucletron, mogeneity corrections, whereas this is not allowed within I-Plan-dose with XVMC Monte-Carlo algorithm from the RTOG trials. Consequently, the dose conformity BrainLAB and XiO/Superposition from CMS. requirements in the ROSEL study differ from the RTOG recommendations. Moreover, a distinction in these values As a guideline, the fractionation schedule(s) and dose is made between type A and B algorithms, because of the constraints one wants to implement should be adapted to significant differences in calculation results between them the dose algorithm used. For example, within the ROSEL (Table 1). trial, it was decided that for type A models, a standard frac- tionation schedule of 3 fractions of 20 Gy or 3 fractions of From Figure 2 it is clear that using a type B algorithm, it is 18 Gy and a conservative fractionation schedule of 5 frac- more difficult to conform the planned dose to the PTV tions of 12 Gy or 5 fractions of 11 Gy could be allowed. than using a type A algorithm, especially for a small PTV. For type B models, the standard fractionation should be 3 This is caused by the increased influence of lateral scatter fractions of 18 Gy and the conservative fractionation disequilibrium for smaller PTV, which is modelled better Page 6 of 14 (page number not for citation purposes) Radiation Oncology 2009, 4:1 http://www.ro-journal.com/content/4/1/1 Table 1: Dose conformity requirements and definition of protocol deviations. R and R = ratio of respectively the 100% and 50% 100% 50% Prescription Isodose Volume to the PTV. D = dose maximum at 2 cm from the PTV as percentage of the prescribed dose. V = 2 cm 20 Gy Percent of lung receiving 20 Gy or more (both lungs minus GTV). Type A models (standard algorithms) R R D (%) V (%) PTV (cc) 100% 50% 2 cm 20 Gy Deviation Deviation Deviation Deviation None Minor None Minor None Minor None Minor <1.15 1.15–1.25 <8 8–10 <55 55–60 <4 4–6 0–20 <1.15 1.15–1.25 <7 7–8 <65 65–70 <6 6–8 20–40 <1.10 1.10–1.20 <6 6–6.5 <65 65–75 <8 8–10 >40 Type B models (more advanced algorithms) R R D (%) V (%) PTV (cc) 100% 50% 2 cm 20 Gy Deviation Deviation Deviation Deviation None Minor None Minor None Minor None Minor <1.25 1.25–1.40 <12 12–14 <65 65–75 <5 5–8 0–20 <1.15 1.15–1.25 <9 9–11 <70 70–80 <6 6–10 20–40 <1.10 1.10–1.20 <6 6–8 <70 70–80 <10 10–15 >40 using a type B algorithm. Thus, a less strict conformity lower than the prescribed value. The overestimation of the requirement was formulated. The difference between type dose increased with decreasing PTV size, although large B and type A or unit density calculations is even more pro- variations are observed between individual patients. For ranged nounced for the R50% values (Figure 3). Also for the dose the unit density calculations the recalculated D at 2 cm from the PTV (Figure 4) and the percentage of the between as much as 63 and 42 Gy for individual patients. lung receiving more than 20 Gy (Figure 5), it is clear that a type B algorithm will result in higher values, due to the Dose-volume constraints for OAR within the ROSEL pro- fact that the change in lateral scattering in lung tissue is tocol are given in Table 2 and differ from the ones used in taken into account much better. Again, the conformity RTOG 0236 and 0618 (for lung constraints, see previous requirements for type B algorithms were relaxed for these Table 1). A reassessment was considered necessary parameters. However, relaxation of these requirements because a new patient group will be treated with stereotac- does not result in an actual inferior patient treatment. On tic radiotherapy within the ROSEL trial, namely patients the contrary, because these more advanced algorithms who are fit to undergo both primary and salvage surgery. provide a better description of the actual dose distribu- As a result, normal tissue dose-constraints have to be tion, the user has a greater opportunity to optimize the more stringently defined in order to minimize the risk of dose distribution to the stated requirements. Therefore, increased complications after salvage surgery. Addition- the use of these more advanced algorithms is strongly ally, new constraints were formulated to be used for the 5 encouraged. Please note that the figures presented here are fraction scheme. Furthermore, the constraints are based based on the treatment plans generated without recalcula- on 1 cc volumes (except for the spinal cord), to prevent an tion with a more advanced algorithm, thus representing excessive dependency on the calculation grid size in the treatment planning clinical practice within the ROSEL evaluation of these parameters. Skin dose, with the con- trial, while in the article of Schuring and Hurkmans the straint that no point within the skin should receive a dose results were presented after recalculation, thus quantify- higher than 24 Gy as dictated in RTOG 0618 is not ing the actual delivered dose differences arising from the included in Table 2, as dose calculations within this use of different algorithms [15]. To emphasize the region are often not very accurate and this dose parameter improvement that can be achieved using a more advanced is often very labour intensive to score. However, this will algorithm over a type A algorithm or a unit density calcu- be evaluated in a dummy run procedure planned before lation, the dose to the PTV after recalculation is given in trial participation for each institution. Figure 6 (reprinted with permission from Schuring and Hurkmans [15]. The figure clearly shows that The EPL Treatment planning plans (Type A algorithm) consistently overestimate the If treatment planning and irradiation are based on the ITV dose to the PTV, resulting in an average D of 48 Gy, 20% concept, the PTV incorporates the complete respiratory Page 7 of 14 (page number not for citation purposes) Radiation Oncology 2009, 4:1 http://www.ro-journal.com/content/4/1/1 1.4 Type A algorithm Type B algorithm RTOG 1.3 1.2 1.1 1.0 0.9 0 25 50 75 100 125 PTV [cm ] stage 1B tumours (with Figure 2 Ratio of Prescription Isod PTVs of ose Volum 59 cc, 85 e to the PTV (R cc, 107 cc and 1 ) from a 08 cc)total of 22 patients with stage IA tumours and 4 patients with 100% Ratio of Prescription Isodose Volume to the PTV (R ) from a total of 22 patients with stage IA tumours and 100% 4 patients with stage 1B tumours (with PTVs of 59 cc, 85 cc, 107 cc and 108 cc). tumour mobility. Several studies indicate that the use of performed by Underberg and colleagues, it was shown the ITV concept leads to the use of larger margins than that only 15% of their patients would have a clinically rel- necessary to compensate for tumour motion due to evant PTV reduction (defined as 50% or more) using gat- breathing [45-48]. This may in turn lead to the unneces- ing compared to the PTV based on the ITV concept [52]. sary exposure of relatively large volumes of organs at risk, They also showed that the PTV reduction correlated well especially for patients with very mobile tumours. How- with the tumour mobility. Thus, the abovementioned ever, Lagerwaard et al. have shown that the incidence of techniques should be primarily considered when treating toxicity is low using this concept and a risk-adapted frac- very mobile tumours or for example tumours close to the tionation schedule [26]. Therefore, the use of this concept stomach. is accepted within the ROSEL trial. However, one might want to avoid unnecessary exposure of organs at risk due It has been shown that the use of a different margin recipe to breathing motion, and four techniques can be distin- leads to a similar reduction of the PTV as gating [45,50]. guished [49]: 1) adaptation of margin recipe [32,50,40], From a patients' perspective, the use of an adapted margin 2) tumour tracking, 3) gating and 4) reduction of breath- recipe might be preferred, as gating significantly prolongs ing motion [51]. These methods are not mutually exclu- the treatment time and this, in turn, leads to significantly sive, for example, one might use abdominal compression more intra-fractional changes in tumour position [53]. in combination with the mean-position margin recipe. It Also, the use of an abdominal compression plate or active must be emphasised that introduction of these techniques breathing control device might be less comfortable for a is not needed for the majority of the patients. In a study patient. This less comfortable position might lead to Page 8 of 14 (page number not for citation purposes) R [ - ] 100% Radiation Oncology 2009, 4:1 http://www.ro-journal.com/content/4/1/1 Type A algorithm Type B Algorithm RTOG 0 25 50 75 100 125 PTV [cm ] with sta Figure 3 Ratio of 50% Prescription Is ge 1B tumours (with PTVs of 59 cc, 85 cc, 107 cc odose Volume to the PTV (R and 108 cc ) from a total of 22 p ) atients with stage IA tumours and 4 patients 50% Ratio of 50% Prescription Isodose Volume to the PTV (R ) from a total of 22 patients with stage IA tumours 50% and 4 patients with stage 1B tumours (with PTVs of 59 cc, 85 cc, 107 cc and 108 cc). increased patient movement and no data about this pos- generally thoracic wall doses are larger than with multiple sible effect is available yet. Tumour tracking by means of static beams. an external marker does not cause any patient discomfort and might be seen as a patient friendly alternative. How- For ITV based treatment plans, dose calculations can be ever, it is shown that variations in external/internal performed on the 3D CT scan reconstruction generated motion correlation are present, making their use poten- without breathing phase binning. (i.e. an average scan or tially less accurate [54,55]. The use of internal markers is untagged scan reconstruction). This has proven to be a considered more accurate, but is associated with an good approximation of 4D dose calculations if combined increased risk of pneumothorax [56]. Furthermore, gating with a type B algorithm [47,58]. and tracking are also technically challenging techniques. They can only be used on a wide scale if existing technical For mid-position based treatment plans, dose calculations problems can be solved [57]. should be either performed on the CT reconstruction phase which represents the time-averaged mean position Due to the wide penumbra of high energy (≥ 15 MV) of the tumour or on scan reconstruction generated with- beams, it is recommended to only use photon (x-ray) out breathing phase binning. beams with energies of 6–10 MV. Experience has been gained with both coplanar and non-coplanar techniques, Treatment execution with in general a 7–13 beam angles in case static beams It is advised to keep the inter-fraction interval at a mini- are used. Dynamic conformal arcs can be used, although mum of 40 hours, in line with the RTOG protocol 0618. Page 9 of 14 (page number not for citation purposes) R [ - ] 50% Radiation Oncology 2009, 4:1 http://www.ro-journal.com/content/4/1/1 Type A algorithm Type B algorithm RTOG 0 25 50 75 100 125 PTV [cm ] a Figure 4 Max nd 4 patients with sta imum dose 2 cm from ge 1B tum PTV in any direction (D ours (with PTVs of 59 cc, 85 cc, 107 cc ) as % of prescribed do and 108 cc se from a total of ) 22 patients with stage I tumours 2 cm Maximum dose 2 cm from PTV in any direction (D ) as % of prescribed dose from a total of 22 patients with 2 cm stage I tumours and 4 patients with stage 1B tumours (with PTVs of 59 cc, 85 cc, 107 cc and 108 cc). The maximum inter-fraction interval should be 4 days. an on-line set-up correction protocol based upon bony Within the ROSEL trial, the standard fractionation should anatomy should be applied. be given over 5–8 days, while the conservative fractiona- tion should be given over 10–14 days. In general, it is rec- Discussion ommended to keep the treatment time as short as possible The ROSEL trial Quality Assurance Working Party in this in order to limit possible patient movement and patient article has tried to present a broad overview of all the tech- discomfort. Longer sessions have been correlated with sig- nical aspects of stereotactic radiotherapy for early stage nificantly more inter-fractional changes in tumour posi- lung cancer. Our aim was to develop widely applicable tion [53]. guidelines in view of the number of stereotactic radiother- apy systems used at centres in The Netherlands which will Patient positioning should be determined by imaging at participate in the ROSEL trial. However, we also formu- the treatment unit itself by means of kV-CT imaging, MV- lated recommendations assuming the most advanced CT imaging or orthogonal kV imaging. It is strongly rec- technical possibilities are at ones disposal. Hopefully, ommended that the target position should be compared these recommended techniques can be implemented on a to the target position in the images used for treatment large scale in the near future. As stereotactic radiotherapy planning, and appropriate patient set-up corrections techniques are in general highly sophisticated, our paper should be applied when tumour shifts are detected [31]. cannot possibly cover all areas in detail. As many aspects As a minimum requirement within the ROSEL protocol, of implementation depend on the available equipment, we recommend that centres should familiarize themselves Page 10 of 14 (page number not for citation purposes) D [%] 2cm Radiation Oncology 2009, 4:1 http://www.ro-journal.com/content/4/1/1 Type A algorithm Type B algorithm RTOG 0 25 50 75 100 125 PTV [cm ] 4 Figure 5 Percent of lung patients with (both lungs minu stage 1B tumours (with s GTV) receiving 20 PTVs of 59 cc, 8 Gy or 5 cc, mor 107 cc a e (V nd 108 cc) ) from a total of 22 patients with stage I tumours and 20 Gy Percent of lung (both lungs minus GTV) receiving 20 Gy or more (V ) from a total of 22 patients with stage 20 Gy I tumours and 4 patients with stage 1B tumours (with PTVs of 59 cc, 85 cc, 107 cc and 108 cc). with technical details of the equipment to be used. Appro- which is highly dependent on the patient specific anat- priate quality assurance systems should also be imple- omy and in general the deviation increases with decreas- mented. A comprehensive overview of quality assurance ing target volume [15]. Therefore, relationships between issues can be found in a special edition about quality treatment outcome and dose generated from stereotactic assurance of the Int. J. Radiat. Oncol. Biol. Phys. (71S, lung cancer trials which not primarily applied type B cal- 2008). culation algorithms should be interpreted with caution. To the best of our knowledge, this is the first trial in stere- Conclusion otactic lung radiotherapy which makes a distinction in Guidelines and recommendations have been formulated dose prescription and dose to OAR criteria based on the to aid the implementation of stereotactic radiotherapy for calculation algorithm used. As was clearly shown, the early stage lung cancer patients in both individual centres dosimetric differences from the use of different algo- as in future multi-institutional trials. They are formulated rithms can be large, and it is more difficult to plan a con- such that stereotactic treatment can safely and effectively formal dose distribution using a more advanced be implemented in clinical practice in a wide variety of algorithm. Without making a distinction based on type of hospitals and treatment results become better compara- algorithm, this might lead to the incorrect assumption ble. that centres with such algorithms use less conformal tech- niques. However, it is shown that the actually delivered Competing interests dose using type A algorithms can deviate as much as 30%, The authors declare that they have no competing interests. Page 11 of 14 (page number not for citation purposes) V [%] 20% Radiation Oncology 2009, 4:1 http://www.ro-journal.com/content/4/1/1 CC plan UD plan EPL plan 0 20406080 100 120 PTV [cm ] Pinnacle 8.0 h) from a cc Figure 6 Dose to 95% of the PTV as a fu , 107 cc and 108 cc) (reprinted with permission fr total of 22 nction of patientsthe PT with stage IA V after recalculation usin om r tumours ef 20) and 4 pa g a tients with type B al gorithm ( stage 1B tumours (with Collapsed Cone ( PTVs of 59 CC) algorithm, cc, 85 Dose to 95% of the PTV as a function of the PTV after recalculation using a type B algorithm (Collapsed Cone (CC) algorithm, Pinnacle 8.0 h) from a total of 22 patients with stage IA tumours and 4 patients with stage 1B tumours (with PTVs of 59 cc, 85 cc, 107 cc and 108 cc) (reprinted with permission from ref 20). Plans were opti- mized using a type A algorithm (EPL), a unit density calculation (UD) or a type B algorithm (CC). the study, and participated in its design and coordination. Authors' contributions CH drafted the manuscript, coordinated and participated All authors read and approved the final manuscript. in the Quality Assurance Working Party designing the guidelines, and participated in performing the calcula- Acknowledgements The ROSEL study is supported by a grant from ZonMW. Grants for the tions comparing dose calculation algorithms. JC, FL, JW ROSEL radiotherapy quality assurance work from Elekta, Philips Medical and UH were all members of the Quality Assurance Work- Systems and Promis Electro-Optics are gratefully acknowledged. ing Party. DS participated in performing the calculations comparing dose calculation algorithms. SS conceived of Table 2: Dose constraints for organs at risk and definition of protocol deviations. Organ Volume (cc) Deviation given as cumulative absolute dose (Gy) 3 fraction scheme 5 fraction scheme None Minor None Minor Spinal Cord Any point 18 > 18 to 22 25 > 25 to 28 Oesophagus 1 24 > 24 to 27 27 > 27 to 28.5 Ipsilateral Brachial Plexus 1 24 > 24 to 26 27 > 27 to 29 Heart 1 24 > 24 to 26 27 > 27 to 29 Trachea and main stem bronchus 1 30 > 30 to 32 32 > 32 to 35 Page 12 of 14 (page number not for citation purposes) 95 Radiation Oncology 2009, 4:1 http://www.ro-journal.com/content/4/1/1 Patients with Medically Inoperable Stage I/II Non-Small Cell References Lung Cancer. RTOG 2007. 1. Qiao X, Tullgren O, Lax I, Sirzen F, Lewensohn R: The role of radi- 18. Timmerman RD, Galvin J, Gore E, Pass H, Edelman MJ, Kong FP: otherapy in treatment of stage I non-small cell lung cancer. RTOG 0618 A phase II trial of stereotactic body radiation Lung Cancer 2003, 41:1-11. therapy (SBRT) in the treatment of patients with operable 2. Nagata Y, Takayama K, Matsuo Y, Norihisa Y, Mizowaki T, Sakamoto stage I/II non-small cell lung cancer. RTOG 2007. T, Sakamoto M, Mitsumori M, Shibuya K, Araki N, Yano S, Hiraoka M: 19. Bosmans G, Buijsen J, Dekker A, Velders M, Boersma L, De Ruysscher Clinical outcomes of a phase I/II study of 48 Gy of stereotac- D, Minken A, Lambin P: An "in silico" clinical trial comparing tic body radiotherapy in 4 fractions for primary lung cancer free breathing, slow and respiration correlated computed using a stereotactic body frame. Int J Radiat Oncol Biol Phys 2005, tomography in lung cancer patients. Radiother Oncol 2006, 63:1427-1431. 81:73-80. 3. Onishi H, Shirato H, Nagata Y, Hiraoka M, Fujino M, Gomi K, Niibe 20. Chen GT, Kung JH, Beaudette KP: Artifacts in computed tomog- Y, Karasawa K, Hayakawa K, Takai Y, Kimura T, Takeda A, Ouchi A, raphy scanning of moving objects. Semin Radiat Oncol 2004, Hareyama M, Kokubo M, Hara R, Itami J, Yamada K, Araki T: Hypof- 14:19-26. ractionated stereotactic radiotherapy (HypoFXSRT) for 21. Keall P: 4-dimensional computed tomography imaging and stage I non-small cell lung cancer: updated results of 257 treatment planning. Semin Radiat Oncol 2004, 14:81-90. patients in a Japanese multi-institutional study. J Thorac Oncol 22. Rietzel E, Pan T, Chen GT: Four-dimensional computed tomog- 2007, 2:S94-100. raphy: image formation and clinical protocol. Med Phys 2005, 4. McGarry RC, Papiez L, Williams M, Whitford T, Timmerman RD: 32:874-889. Stereotactic body radiation therapy of early-stage non- 23. Seki S, Kunieda E, Takeda A, Nagaoka T, Deloar HM, Kawase T, small-cell lung carcinoma: phase I study. Int J Radiat Oncol Biol Fukada J, Kawaguchi O, Uematsu M, Kubo A: Differences in the Phys 2006, 63(4):1010-1015. definition of internal target volumes using slow CT alone or 5. Lagerwaard FJ, Haasbeek CJA, Smit EF, Slotman BJ, Senan S: Out- in combination with thin-slice CT under breath-holding con- come After Stereotactic Radiotherapy in 'High-Risk' ditions during the planning of stereotactic radiotherapy for Patients With Stage I Non-small Cell Lung Cancer lung cancer. Radiother Oncol 2007, 85:443-449. (NSCLC). Int J Radiat Oncol Biol Phys 2007, 69:S87-S88. 24. Wurstbauer K, Deutschmann H, Kopp P, Sedlmayer F: Radiother- 6. Onishi H, Araki T, Shirato H, Nagata Y, Hiraoka M, Gomi K, Yamas- apy planning for lung cancer: slow CTs allow the drawing of hita T, Niibe Y, Karasawa K, Hayakawa K, Takai Y, Kimura T, tighter margins. Radiother Oncol 2005, 75:165-170. Hirokawa Y, Takeda A, Ouchi A, Hareyama M, Kokubo M, Hara R, 25. Letourneau D, Finlay M, O'sullivan B, Waldron JN, Cummings BJ, Rin- Itami J, Yamada K: Stereotactic hypofractionated high-dose gash J, Kim JJ, Bayley AJ, Dawson LA: Lack of influence of intrave- irradiation for stage I nonsmall cell lung carcinoma. Cancer nous contrast on head and neck IMRT dose distributions. 2004, 101:1623-1631. Acta Oncol 2008, 47:90-94. 7. El-Sherif A, Gooding WE, Santos R, Pettiford B, Ferson PF, Fernando 26. Lagerwaard FJ, Haasbeek CJA, Smit EF, Slotman BJ, Senan S: Out- HC, Urda SJ, Luketich JD, Landreneau RJ: Outcomes of sublobar comes of Risk-Adapted Fractionated Stereotactic Radio- resection versus lobectomy for stage I non-small cell lung therapy for Stage I Non-Small-Cell Lung Cancer. Int J Radiat cancer: a 13-year analysis. Ann Thorac Surg 2006, 82:408-415. Oncol Biol Phys 2008, 70:685-692. 8. Strand TE, Rostad H, Moller B, Norstein J: Survival after resection 27. Potters L, Steinberg M, Rose C, Timmerman R, Ryu S, Hevezi JM, for primary lung cancer: a population based study of 3211 Welsh J, Mehta M, Larson DA, Janjan NA: American Society for resected patients. Thorax 2006, 61:710-715. Therapeutic Radiology and Oncology and American College 9. Rami-Porta R, Ball D, Crowley J, Giroux DJ, Jett J, Travis WD, Tsuboi of Radiology practice guideline for the performance of ster- M, Vallieres E, Goldstraw P: The IASLC Lung Cancer Staging eotactic body radiation therapy. Int J Radiat Oncol Biol Phys 2004, Project: proposals for the revision of the T descriptors in the 60:1026-1032. forthcoming (seventh) edition of the TNM classification for 28. Bradley JD, Nofal AN, El Naga IM, Lu W, Liu J, Hubenschmidt J, Low lung cancer. J Thorac Oncol 2007, 2:593-602. DA, Drzymala RE, Khullar D: Comparison of helical, maximum 10. Timmerman RD, Park C, Kavanagh BD: The North American intensity projection (MIP), and averaged intensity (AI) 4D experience with stereotactic body radiation therapy in non- CT imaging for stereotactic body radiation therapy (SBRT) small cell lung cancer. J Thorac Oncol 2007, 2:S101-S112. planning in lung cancer. Radiother Oncol 2006, 81:264-268. 11. Pasic A, Brokx HA, Vonk NA, Paul RM, Postmus PE, Sutedja TG: 29. Riegel AC, Chang JY, Vedam SS, Johnson V, Chi PC, Pan T: Cine Cost-effectiveness of early intervention: comparison Computed Tomography Without Respiratory Surrogate in between intraluminal bronchoscopic treatment and surgical Planning Stereotactic Radiotherapy for Non-Small-Cell resection for T1N0 lung cancer patients. Respiration 2004, Lung Cancer. Int J Radiat Oncol Biol Phys 2008. DOI: 10.1016/ 71:391-396. j.ijrobp.2008.04.047 12. Timmerman RD, Paulus R, Galvin J, Michalski J, Straube WL, Bradley 30. van Sornsen de Koste JR, Lagerwaard FJ, Nijssen-Visser MR, Grave- J, Fakiris A, Bezjak A, Videtic G, Choy H: Toxicity Analysis of land WJ, Senan S: Tumor location cannot predict the mobility RTOG 0236 Using Stereotactic Body Radiation Therapy to of lung tumors: a 3D analysis of data generated from multi- Treat Medically Inoperable Early Stage Lung Cancer ple CT scans. Int J Radiat Oncol Biol Phys 2003, 56:348-354. Patients. Int J Radiat Oncol Biol Phys 2007, 69:S86. 31. Sonke JJ, Lebesque J, van Herk M: Variability of four-dimensional 13. Xiao Y, Straube WL, Bosch WR, Timmerman RD, Galvin JM: Dosi- computed tomography patient models. Int J Radiat Oncol Biol metric Evaluation of Heterogeneity Corrections for RTOG Phys 2008, 70:590-598. 0236: Hypofractionated Radiotherapy of Inoperable Stage I/ 32. Wolthaus JWH, Schneider C, Sonke JJ, van Herk M, Belderbos JSA, II Non-small Cell Lung Cancer. Int J Radat Oncol Biol Phys 2007, Rossi MMG, Lebesque JV, Damen EFM: Mid-ventilation CT scan 69:S46-S47. construction from four-dimensional respiration-correlated 14. Hiraoka M, Ishikura S: A Japan clinical oncology group trial for CT scans for radiotherapy planning of lung cancer patients. stereotactic body radiation therapy of non-small cell lung Int J Radat Oncol Biol Phys 2006, 65:1560-1571. cancer. J Thorac Oncol 2007, 2:S115-S117. 33. Dieleman EM, Senan S, Vincent A, Lagerwaard FJ, Slotman BJ, van 15. Schuring D, Hurkmans CW: Developing and evaluating stereo- Sornsen de Koste JR: Four-dimensional computed tomo- tactic lung RT trials: What we should know about the influ- graphic analysis of esophageal mobility during normal respi- ence of inhomogeneity corrections on dose. Radiat Oncol 2008, ration. Int J Radiat Oncol Biol Phys 2007, 67:775-780. 3:21. 34. ICRU report 62 prescribing, recording and reporting photon 16. Underberg RW, Lagerwaard FJ, Slotman BJ, Cuijpers JP, Senan S: Use beam therapy. (Supplement to ICRU report 50) 1999, 33:1-51. of maximum intensity projections (MIP) for target volume 35. Hall WH, Guiou M, Lee NY, Dublin A, Narayan S, Vijayakumar S, generation in 4DCT scans for lung cancer. Int J Radiat Oncol Biol Purdy JA, Chen AM: Development and Validation of A Stand- Phys 2005, 63:253-260. ardized Method for Contouring THE Brachial Plexus: Pre- 17. Timmerman RD, Michalski J, Galvin J, Fowler JF, Choy H, Gore E, liminary Dosimetric Analysis Among Patients Treated with Johnstone D: RTOG 0236 : A Phase II Trial of Stereotactic IMRT for Head-and-Neck Cancer. Int J Radiat Oncol Biol Phys Body Radiation Therapy (SBRT) in the Treatment of 2008, 72;1:S385. Page 13 of 14 (page number not for citation purposes) Radiation Oncology 2009, 4:1 http://www.ro-journal.com/content/4/1/1 36. Madu CN, Quint DJ, Normolle DP, Marsh RB, Wang EY, Pierce LJ: combined with respiratory correlated image guidance. Radi- Definition of the supraclavicular and infraclavicular nodes: other Oncol 2008, 86:61-68. implications for three-dimensional CT-based conformal 55. Ionascu D, Jiang SB, Nishioka S, Shirato H, Berbeco RI: Internal- radiation therapy. Radiology 2001, 221:333-339. external correlation investigations of respiratory induced 37. Collins BT, Erickson K, Reichner CA, Collins SP, Gagnon GJ, Diet- motion of lung tumors. Med Phys 2007, 34:3893-3903. erich S, McRae DA, Zhang Y, Yousefi S, Levy E, Chang T, Jamis-Dow 56. Geraghty PR, Kee ST, McFarlane G, Razavi MK, Sze DY, Dake MD: C, Banovac F, Anderson ED: Radical stereotactic radiosurgery CT-guided transthoracic needle aspiration biopsy of pulmo- with real-time tumor motion tracking in the treatment of nary nodules: needle size and pneumothorax rate. Radiology small peripheral lung tumors. Radiat Oncol 2007, 2:39. 2003, 229:475-481. 38. Koto M, Takai Y, Ogawa Y, Matsushita H, Takeda K, Takahashi C, 57. Jiang SB: Radiotherapy of mobile tumors. Semin Radiat Oncol Britton KR, Jingu K, Takai K, Mitsuya M, Nemoto K, Yamada S: A 2006, 16:239-248. phase II study on stereotactic body radiotherapy for stage I 58. Guckenberger M, Wilbert J, Krieger T, Richter A, Baier K, Meyer J, non-small cell lung cancer. Radiother Oncol 2007, 85:429-434. Flentje M: Four-dimensional treatment planning for stereo- 39. Sinha B, McGarry RC: Stereotactic body radiotherapy for bilat- tactic body radiotherapy. Int J Radiat Oncol Biol Phys 2007, eral primary lung cancers: the Indiana university experience. 69:276-285. Int J Radiat Oncol Biol Phys 2007, 66:1120-1124. 40. Haasbeek CJ, Senan S, Smit EF, Paul MA, Slotman BJ, Lagerwaard FJ: Critical review of nonsurgical treatment options for stage I non-small cell lung cancer. Oncologist 2008, 13:309-319. 41. Brock J, Ashley S, Bedford J, Nioutsikou E, Partridge M, Brada M: Review of Hypofractionated Small Volume Radiotherapy for Early-stage Non-small Cell Lung Cancer. Clin Oncol (R Coll Radiol) 2008, 20:666-676. 42. Timmerman R, McGarry R, Yiannoutsos C, Papiez L, Tudor K, DeLuca J, Ewing M, Abdulrahman R, DesRosiers C, Williams M, Fletcher J: Excessive toxicity when treating central tumors in a phase II study of stereotactic body radiation therapy for medically inoperable early-stage lung cancer. J Clin Oncol 2006, 24:4833-4839. 43. Senan S, Haasbeek NJ, Smit EF, Lagerwaard FJ: Stereotactic radio- therapy for centrally located early-stage lung tumors. J Clin Oncol 2007, 25:464. 44. Knöös T, Wieslander E, Cozzi L, Brink C, Fogliata A, Albers D, Nys- tröm H, Lassen S: Comparison of dose calculation algorithms for treatment planning in external photon beam therapy for clinical situations. Phys Med Biol 2006, 51:5785-5807. 45. Wolthaus JW, Sonke JJ, van Herk M, Belderbos JS, Rossi MM, Leb- esque JV, Damen EM: Comparison of different strategies to use four-dimensional computed tomography in treatment plan- ning for lung cancer patients. Int J Radiat Oncol Biol Phys 2008, 70:1229-1238. 46. Guckenberger M, Krieger T, Baier K, Richter A, Polat B, Flentje M: Four Dimensional Target Volume Generation in Pulmonary Stereotactic Body Radiotherapy. Int J Radiat Oncol Biol Phys 2007, 69(1):S191. 47. Admiraal MA, Schuring D, Hurkmans CW: Dose calculations accounting for breathing motion in stereotactic lung radio- therapy based on 4D-CT and the internal target volume. Radiother Oncol 2008, 86:55-60. 48. Mutaf YD, Brinkmann DH: Optimization of internal margin to account for dosimetric effects of respiratory motion. Int J Radiat Oncol Biol Phys 2008, 70:1561-1570. 49. Giraud P, Yorke E, Jiang S, Simon L, Rosenzweig K, Mageras G: Reduction of organ motion effects in IMRT and conformal 3D radiation delivery by using gating and tracking tech- niques. Cancer Radiother 2006, 10:269-282. 50. Burnett SS, Sixel KE, Cheung PC, Hoisak JD: A study of tumor motion management in the conformal radiotherapy of lung cancer. Radiother Oncol 2008, 86:77-85. 51. Heinzerling JH, Anderson JF, Papiez L, Boike T, Chien S, Zhang G, Abdulrahman R, Timmerman R: Four-dimensional computed Publish with Bio Med Central and every tomography scan analysis of tumor and organ motion at var- scientist can read your work free of charge ying levels of abdominal compression during stereotactic treatment of lung and liver. Int J Radiat Oncol Biol Phys 2008, "BioMed Central will be the most significant development for 70:1571-1578. disseminating the results of biomedical researc h in our lifetime." 52. Underberg RWM, Lagerwaard FJ, Slotman BJ, Cuijpers JP, Senan S: Sir Paul Nurse, Cancer Research UK Benefit of respiration-gated stereotactic radiotherapy for stage I lung cancer: an analysis of 4DCT datasets. Int J Radiat Your research papers will be: Oncol Biol Phys 2005, 62:554-560. available free of charge to the entire biomedical community 53. Purdie TG, Bissonnette JP, Franks K, Bezjak A, Payne D, Sie F, Sharpe MB, Jaffray DA: Cone-beam computed tomography for on-line peer reviewed and published immediately upon acceptance image guidance of lung stereotactic radiotherapy: localiza- cited in PubMed and archived on PubMed Central tion, verification, and intrafraction tumor position. Int J Radiat Oncol Biol Phys 2007, 68:243-252. yours — you keep the copyright 54. Korreman SS, Juhler-Nottrup T, Boyer AL: Respiratory gated BioMedcentral beam delivery cannot facilitate margin reduction, unless Submit your manuscript here: http://www.biomedcentral.com/info/publishing_adv.asp Page 14 of 14 (page number not for citation purposes) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Radiation Oncology Springer Journals

Recommendations for implementing stereotactic radiotherapy in peripheral stage IA non-small cell lung cancer: report from the Quality Assurance Working Party of the randomised phase III ROSEL study

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Springer Journals
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Copyright © 2009 by Hurkmans et al; licensee BioMed Central Ltd.
Subject
Medicine & Public Health; Oncology; Radiotherapy
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1748-717X
DOI
10.1186/1748-717X-4-1
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19138400
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Abstract

Background: A phase III multi-centre randomised trial (ROSEL) has been initiated to establish the role of stereotactic radiotherapy in patients with operable stage IA lung cancer. Due to rapid changes in radiotherapy technology and evolving techniques for image-guided delivery, guidelines had to be developed in order to ensure uniformity in implementation of stereotactic radiotherapy in this multi-centre study. Methods/Design: A Quality Assurance Working Party was formed by radiation oncologists and clinical physicists from both academic as well as non-academic hospitals that had already implemented stereotactic radiotherapy for lung cancer. A literature survey was conducted and consensus meetings were held in which both the knowledge from the literature and clinical experience were pooled. In addition, a planning study was performed in 26 stage I patients, of which 22 were stage 1A, in order to develop and evaluate the planning guidelines. Plans were optimised according to parameters adopted from RTOG trials using both an algorithm with a simple homogeneity correction (Type A) and a more advanced algorithm (Type B). Dose conformity requirements were then formulated based on these results. Conclusion: Based on current literature and expert experience, guidelines were formulated for this phase III study of stereotactic radiotherapy versus surgery. These guidelines can serve to facilitate the design of future multi-centre clinical trials of stereotactic radiotherapy in other patient groups and aid a more uniform implementation of this technique outside clinical trials. Page 1 of 14 (page number not for citation purposes) Radiation Oncology 2009, 4:1 http://www.ro-journal.com/content/4/1/1 (both direct and indirect). In case of surgery, a lobectomy Background Until recently, conventionally fractionated high-dose should be carried out, but limited resections are accepta- radiation therapy was the preferred treatment in patients ble. Careful radiological follow-up is performed within with stage I NSCLC who were unfit to undergo surgery or the trial in patients treated by SRT, as salvage surgery or declined surgery. This is, however, a poor alternative to mediastinal radiation therapy might still be possible in surgery in operable patients as the mean reported crude case of clinical, radiological or histological evidence of local recurrence rates are as high as 40% (range 6–70%), local or hilar disease progression. resulting in a three year overall and cause-specific survival of only 34 and 39%, respectively [1]. Accreditation and dosimetry guidelines have been previ- ously developed for trials of stereotactic radiotherapy such Recently, stereotactic radiotherapy has gained much inter- as RTOG 0236 and JCOG 0403 [12-14]. However, a reas- est in the treatment of medically inoperable patients with sessment was considered necessary because a new patient stage I lung cancer, as local control rates are dramatically group was being treated with stereotactic radiotherapy, improved with this technique compared to conventional namely patients who were fit to undergo both primary fractionation. In studies where schedules with a biologi- and salvage surgery. As a result, normal tissue dose-con- cally effective dose (BED) larger than 100 Gy are used, typ- straints had to be more stringently defined in order to ical local control rates are approximately 90%. The largest minimize the risk of increased complications after salvage series were reported from Japan [2,3], United States [4] surgery. Furthermore, IGRT technology from different and the Netherlands [5], comprising experience in over vendors has been rapidly adopted at various Dutch cen- 750 patients. Onishi et al. [6] retrospectively described the tres, which had to be taken into account. The resulting results of 257 patients treated in 14 Japanese centres using guidelines include both minimum requirements that a number of different fractionation schedules and delivery must be met by each participating centre as well as recom- approaches. This Japanese study also included nearly 100 mendations for possible further improvements. They are patients who refused surgery, and the 5-year overall sur- presented here in order to facilitate the implementation of vival rate of 70.8% observed after a BED of 100 Gy among future multi-centre studies, to stimulate and improve the those patients is at least equivalent to the outcome after implementation of stereotactic techniques in clinical prac- surgery [7-9]. Currently, several phase II trials have started tice and to improve the comparability of results. in operable lung cancer patients [10] (RTOG 0618 and JCOG 0403), however, to date no prospective multi-cen- Methods tre randomized studies have been performed to compare A ROSEL Quality Assurance Working Party was formed by stereotactic radiotherapy with surgery in patients with radiation oncologists and medical physicists from both operable lung cancer. academic as well as non-academic hospitals that had already implemented stereotactic radiotherapy for lung A randomized phase III trial of Radiosurgery Or Surgery cancer. Several working party meetings were organised in for operable Early stage (stage 1A) non-small cell Lung which both the knowledge from literature and clinical cancer (ROSEL, ClinicalTrials.gov ID = NCT00687986) experience were shared and amalgamated. In support of has been opened for accrual in August 2008. The study is these meetings, a literature search was conducted by initiated by the VU medical centre Amsterdam and the searching MEDLINE with different key words and their Dutch Lung Cancer Research Group. The primary study permutations such as stereotactic radiotherapy, stage I objectives are to compare local and regional control, qual- lung cancer, treatment planning, CT scan, patient posi- ity of life and treatment costs at 2 and 5 years in patients tioning and tumour mobility. Abstract books of the who are randomized to either surgery or radiosurgery ASTRO, ASCO, AAPM and ESTRO/ECCO from 2004 to (Figure 1). Treatment costs are a primary end-point, as the 2008 were reviewed. It was recognized that there was little costs associated with surgery for stage IA in The Nether- data available in the literature about the influence of dif- lands are far higher than the present costs of stereotactic ferent planning algorithms on the planning of stereotactic radiotherapy [11]. These costs are expected to be even radiotherapy. Therefore, an additional planning study was more if the costs of post-operative revalidation and loss of performed in 22 stage IA and 4 stage 1B non-small cell economic activity are taken into account. However, lung cancer patients in order to develop and evaluate the patients treated with stereotactic radiotherapy could incur planning guidelines differentiated according to type of costs for salvage treatment if a higher incidence of local or dose calculation algorithm used. Patient characteristics regional recurrences is detected. Therefore, treatment costs and treatment planning details have been reported previ- were considered to be a relevant end-point. ously [15]. Secondary objectives include overall survival, pulmonary In brief, a four-dimensional (4D)-CT was reconstructed in function tests, quality adjusted life years and total costs ten equally spaced time bins using respiratory phase bin- Page 2 of 14 (page number not for citation purposes) Radiation Oncology 2009, 4:1 http://www.ro-journal.com/content/4/1/1 ROSEL st Figure 1udy design ROSEL study design. Page 3 of 14 (page number not for citation purposes) Radiation Oncology 2009, 4:1 http://www.ro-journal.com/content/4/1/1 ning for each patient. From these phases, a maximum (IV) contrast on dose calculations for lung patients is not intensity projection (MIP) was reconstructed [16]. The specifically studied, the influence of IV contrast in head treatment datasets were then imported in the Pinnacle and neck intensity modulated radiotherapy plans was planning system (Philips Medical Systems, Wisconsin). proven to be insignificant [25]. The slice spacing between Using the MIP dataset, an experienced radiation oncolo- reconstructed CT images should be ≤3 mm over the com- gist delineated the internal target volume (ITV). Organs at plete tumour trajectory and ≤5 mm elsewhere. The scan risk were delineated on an average-density CT reconstruc- should encompass the entire lung volume in order to cal- tion. The PTV was created by expanding the ITV with a 3 culate meaningful lung dose-volume parameters. mm margin. The treatment plans consisted of 9 equally spaced coplanar 6 MV beams which were not allowed to Target volume definition enter through the oesophagus, heart, spinal cord or con- The gross tumour volume (GTV) will generally be con- tralateral lung. The plans were inversely optimized using toured using CT pulmonary windows; however, soft tissue the direct aperture optimization module of the Pinnacle windows may be used to avoid inclusion of adjacent ves- treatment planning system with the same objectives as sels or chest wall structures within the GTV. The correct- used in the ROSEL trial. Three different plans were cre- ness of the GTV delineation should be checked in axial, ated; using an advanced (type A) dose calculation algo- sagittal and coronal views. The clinical target volume rithm, a less advanced (type B) algorithm and a plan (CTV) is assumed to be identical to the GTV, i.e. with no assuming all tissues within the body to have unit density, margin for microscopic disease added, which appears to in accordance with the RTOG study 0236 and 0618 proto- be justified by the high local control rates observed in cols [17,18]. patients undergoing careful post-treatment follow-up [26]. This approach has also been accepted in the ASTRO- In order to facilitate the clinical use of these recommenda- ACR recommendations on stereotactic radiotherapy [27]. tions, we divided the process of implementing high-dose radiotherapy into the following headings: CT scanning For PTV definition, two main treatment planning and exe- and patient positioning, target volume definition, organs cution techniques can be distinguished; planning and at risk definition, Dose calculation algorithms and frac- irradiation based on the internal target volume (ITV) con- tionation, dose prescription, coverage and constraints, cept or the time-averaged mean position of the tumour. treatment planning and treatment execution. PTV based on the ITV concept Patient positioning and CT scanning For 4D CT scans, the ITV can be derived from the union of The patient should be scanned in the treatment position GTV delineations on all breathing phases or alternatively, which should be supine with both arms raised above the from contouring on a maximum intensity projection head using an arm-rest or other fixation device. Positions (MIP) CT-dataset [28,29]. The appropriateness of the which are less comfortable for the patient should be MIP-delineation should at least be confirmed by a visual avoided so as to prevent the likelihood of uncontrolled inspection of the projected ITV contours on the CT-data- movement during scanning or treatment. Four-dimen- sets of the end-inspiration and end-expiration phase bins sional (4D) CT scanning is strongly recommended in using axial, sagittal and coronal views. In addition to the order to account for an individualised assessment and MIP contouring, the GTV should also be contoured in a incorporation of tumour motion [19-21]. Preferably 10 single phase (preferably the end-expiration phase, but no less than 6 breathing phases should be recon- because this is the most stable tumour position and the structed in order to determine the tumour movement for phase with the least breathing artefacts) in all patients in treatment planning. Using 10 phases, it was found that order to determine the GTV size. For checking the ITV con- generally the full amplitude of motion can be captured tour based on the MIP it is not necessary to delineate the [22]. Within the ROSEL trial, acquisition of a slow-CT end-inspiration and end-expiration phase bins (visual scan or multiple (at least 3) rapid planning scans covering assessment suffices). Alternatively, the ITV may be con- the entire range of tumour motion is also allowed, as 4D- structed by the union of all delineations of the GTV in all CT scanners are not widely available yet. However, target breathing phases. If only 3D CT data is available, the ITV volume delineation might be more difficult as the images, should be based on either multiple slow CT-scans cover- and thus also the tumour volume, of slow-CT scans are ing the whole tumour trajectory or an additional margin blurred [23,24]. All centres participating in the ROSEL of 3–5 mm in all directions around the CTV determined study will most likely be able to implement 4D-CT scan- on a single slow CT-scan [30]. The ITV to PTV margin is ning in the near future. Generally, intravenous contrast is primarily meant to take into account patient set-up uncer- not necessary for planning CT scans for early stage lung tainties. However, small intra-fractional variations in the cancer, but contrast-enhanced CT images may still be used tumour motion and mean position may be present. Also for dose calculations. Although the effect of intravenous inter-fractional variations may be present, but these might Page 4 of 14 (page number not for citation purposes) Radiation Oncology 2009, 4:1 http://www.ro-journal.com/content/4/1/1 be corrected for using tumour based image guided posi- located in the mid- or lower zones of the lungs, the peri- tion verification and correction [31]. In addition, small cardium and/or heart should be contoured as a single delineation uncertainties will exist. Thus, a minimum of 3 structure. The superior aspect (or base) for purposes of mm ITV to PTV margin is required in all dimensions, even contouring will begin at the level of the inferior aspect of if a set-up error of <3 mm can be guaranteed. On the other the aortic arch (aorto-pulmonary window) and extend hand, the ITV to PTV margin should not exceed 5 mm, as inferiorly to the apex of the heart. this would unnecessarily enlarge treated volumes. In case an institution would need to apply a larger margin, e.g. The defined ipsilateral brachial plexus originates from the because of their set-up accuracy, it is advised to first spinal nerves exiting the neural foramen on the involved improve its (set-up) technique (see also paragraph about side from around C5 to T2 [35,36]. treatment execution). For peripheral tumours in the upper lobes, the major PTV based on the mean tumour position trunks of the brachial plexus should be contoured, using As an alternative to the ITV concept, planning and irradi- the subclavian and axillary vessels as surrogates. This neu- ation based on the time-averaged mean position of the rovascular complex will be contoured starting proximally tumour has been developed [32]. In contrast to the ITV to at the bifurcation of the brachiocephalic trunk into the PTV margin discussed previously, the CTV to PTV margin jugular/subclavian veins (or carotid/subclavian arteries) needed here should take the tumour motion into account. and following along the route of the subclavian vein to However, similar to the reasoning given for the ITV to PTV the axillary vein ending after the neurovascular structures margin, a minimum margin of 3 mm should be used for cross the 2nd rib. the incorporation of the other uncertainties. The trachea and proximal bronchial tree are contoured as Organs at risk definition two separate structures using mediastinal windows on CT Dose volume criteria for organs at risk (OAR) given in a to correspond to the mucosa, submucosa and cartilage next paragraph are all constraints to the highest doses rings and airway channels associated with these structures. received by the OAR. As a consequence, the impact of dif- For this purpose, the trachea will be divided into two sec- ferences in delineation protocols between institutions is tions: the proximal trachea and the distal 2 cm of trachea. not expected to be high, as these differences are likely to The proximal trachea will be contoured as one structure, be primarily of influence on the delineations located out- and the distal 2 cm of trachea will be included in the struc- side the high dose region. However, in order to support ture identified as proximal bronchial tree (main carina, future normal tissue complication probability (NTCP) right and left main bronchi, right and left upper lobe modelling studies, the OAR delineation guidelines as used bronchi, intermedius bronchus, right middle lobe bron- in the ROSEL protocol are given below. chus, lingular bronchus, right and left lower lobe bron- chi). When 4D-CT scans are used for treatment planning, the critical OAR should be contoured on the relevant refer- Delineation of the chest wall has not been regularly per- ence reconstruction (i.e. the scan used for dose calcula- formed. Little is known about chest wall morbidity in rela- tions, see also paragraph about treatment planning). This tion to dose in stereotactic radiotherapy, and therefore can generally be performed without taking into account delineation is not mandatory within the ROSEL trial [37]. potential mobility of these organs, as current experience is However, it is recommended to delineate the chest wall in based on this type of delineations. However, extremes of case of tumours in close proximity to the chest wall. This motion of organs such as the oesophagus may influence will aid the development of NTCP models concerning the choice of beam arrangements in case of 'peripheral' chest wall toxicity. lesions located in the proximity of the mediastinum [33]. Also, patient set-up corrections due to tumour shifts lead Dose calculation algorithms and fractionation to a change in the dose given to the OAR. To avoid exces- A number of different dose fractionation schedules have sive doses to OAR, it is recommended to evaluate the been reported for lung SRT [38,39], but the optimal dose impact of such shifts on the OAR dose during treatment fractionation schedule may vary with tumour stage and planning. This might be accomplished by using Planning location. Although no randomized studies comparing dif- organ at Risk Volumes (PRV) [34]. ferent fractionation schedules have been conducted for stage I tumours, most of the clinical experience is based The spinal cord and oesophagus should be contoured on schedules with 3 fractions of 20 Gy. In RTOG study starting at least 10 cm above the superior extent of the PTV 0236, RTOG study 0618 and in the ROSEL study, this frac- and continuing on every CT slice to at least 10 cm below tionation scheme is used. In all studies, eligibility for the inferior extent of the PTV. For patients with tumours inclusion was limited to lesions located ≥ 2 cm distal to Page 5 of 14 (page number not for citation purposes) Radiation Oncology 2009, 4:1 http://www.ro-journal.com/content/4/1/1 the hilar structures. Within the ROSEL study, a more con- should be 5 fractions of 12 Gy or 5 fractions of 11 Gy. A 3 servative fractionation scheme of 5 fractions of 12 Gy is fractions of 20 Gy schedule is not allowed in combination also allowed for patients with a tumour with broad con- with type B models in the ROSEL trial, as this might lead tact to the thoracic wall or adjacent to the heart or medi- to dose levels being approximately 10% higher than the astinum. Lung function is not considered to affect the dose levels with which extensive experience has been scheduling or fractionation. The largest clinical experience gained in the VU Medical Centre Amsterdam, using a type published thus far did not exclude any patient on the basis A algorithm. These higher dose levels might lead to of poor lung function [26], and did not observe excessive increased morbidity. The fractionation of 5 times 12 Gy is lung toxicity when 'risk-adapted' SRT schemes were used still allowed with type B models since the errors of type A This is supported by 2 recent reviews [40,41]. A report by algorithms in calculating dose to the thoracic wall, heart Timmerman [42] which suggested that toxicity rates were or mediastinum are expected to be less significant. high for central tumors treated with SRT has been criti- Although this also would lead to approximately 10% cized on the grounds of the toxicity definitions used [43]. higher dose levels, the biologically effective dose for the PTV will still be well below the BED of the 3 fractions However, it is recognized that differences between calcu- schedule. There are no indications in the literature that lation algorithms in the various treatment planning sys- this would lead to an unacceptable level of morbidity. It is tems may be as high as 30% in individual cases [15]. highly recommended to include dose algorithm specifics These differences are largest for lung tumour treatment in future reports about stereotactic radiotherapy for lung plans, and generally increase with decreasing field size, tumours. If a more accurate algorithm becomes available which is especially relevant in stereotactic radiotherapy of to the authors of such articles, one should also consider stage 1A lung tumours. Thus, depending on the treatment the publication of the recalculated data. These data can be planning algorithm used, one should actually use an alter- used to improve our dose-effect models, which aid the fur- native nominal fraction dose to deliver the same actual ther improvement of stereotactic radiotherapy. dose to the patient. Unfortunately, extensive data compar- ing all the calculation algorithms that are likely to be used Dose prescription, coverage and constraints in the ROSEL study are not available. For the nominal In line with current multi-institutional trials and multiple single-centre experiences, the dose prescription should be dose fractionation schedules allowed within the ROSEL trial two main type of algorithms are distinguished based on 95% of the target volume (PTV) receiving at least [15,44]. the nominal fraction dose (e.g., 20 Gy per fraction = 60 Gy total), and 99% of the target volume (PTV) receiving a � Type A models: Models primarily based on electronic minimum of 90% of the fraction dose. The dose maxi- path length (EPL) scaling for inhomogeneity corrections. mum within the PTV should preferably not be less than Changes in lateral transport of electrons are not (well) 110% or exceed 140% of the prescribed dose, similar to modelled. The algorithms in this group are e.g. Eclipse/ the criteria formulated in RTOG protocol 0618 [18]. The ModBatho and Eclipse/ETAR from Varian, OMP/PB and location of the treatment plan normalization point, Plato/ETAR from Nucletron, PrecisePLAN from Elekta, I- which is in fact only influencing the display of the dose plan Dose/PB from BrainLAB, and XiO/Convolution from distribution, can be left to the institutions preference. CMS. RTOG trial 0236 defined a set of parameters to quantify � Type B models: Models that in an approximate way con- the conformity of the dose and PTV coverage. The same sider changes in lateral electron transport. The models in parameters were used in RTOG trial 0618 and are used this group are e.g. Pinnacle/CC from Philips Medical Sys- here. However, the ROSEL trial requires the use of inho- tems, Eclipse/AAA from Varian, OMP/CC from Nucletron, mogeneity corrections, whereas this is not allowed within I-Plan-dose with XVMC Monte-Carlo algorithm from the RTOG trials. Consequently, the dose conformity BrainLAB and XiO/Superposition from CMS. requirements in the ROSEL study differ from the RTOG recommendations. Moreover, a distinction in these values As a guideline, the fractionation schedule(s) and dose is made between type A and B algorithms, because of the constraints one wants to implement should be adapted to significant differences in calculation results between them the dose algorithm used. For example, within the ROSEL (Table 1). trial, it was decided that for type A models, a standard frac- tionation schedule of 3 fractions of 20 Gy or 3 fractions of From Figure 2 it is clear that using a type B algorithm, it is 18 Gy and a conservative fractionation schedule of 5 frac- more difficult to conform the planned dose to the PTV tions of 12 Gy or 5 fractions of 11 Gy could be allowed. than using a type A algorithm, especially for a small PTV. For type B models, the standard fractionation should be 3 This is caused by the increased influence of lateral scatter fractions of 18 Gy and the conservative fractionation disequilibrium for smaller PTV, which is modelled better Page 6 of 14 (page number not for citation purposes) Radiation Oncology 2009, 4:1 http://www.ro-journal.com/content/4/1/1 Table 1: Dose conformity requirements and definition of protocol deviations. R and R = ratio of respectively the 100% and 50% 100% 50% Prescription Isodose Volume to the PTV. D = dose maximum at 2 cm from the PTV as percentage of the prescribed dose. V = 2 cm 20 Gy Percent of lung receiving 20 Gy or more (both lungs minus GTV). Type A models (standard algorithms) R R D (%) V (%) PTV (cc) 100% 50% 2 cm 20 Gy Deviation Deviation Deviation Deviation None Minor None Minor None Minor None Minor <1.15 1.15–1.25 <8 8–10 <55 55–60 <4 4–6 0–20 <1.15 1.15–1.25 <7 7–8 <65 65–70 <6 6–8 20–40 <1.10 1.10–1.20 <6 6–6.5 <65 65–75 <8 8–10 >40 Type B models (more advanced algorithms) R R D (%) V (%) PTV (cc) 100% 50% 2 cm 20 Gy Deviation Deviation Deviation Deviation None Minor None Minor None Minor None Minor <1.25 1.25–1.40 <12 12–14 <65 65–75 <5 5–8 0–20 <1.15 1.15–1.25 <9 9–11 <70 70–80 <6 6–10 20–40 <1.10 1.10–1.20 <6 6–8 <70 70–80 <10 10–15 >40 using a type B algorithm. Thus, a less strict conformity lower than the prescribed value. The overestimation of the requirement was formulated. The difference between type dose increased with decreasing PTV size, although large B and type A or unit density calculations is even more pro- variations are observed between individual patients. For ranged nounced for the R50% values (Figure 3). Also for the dose the unit density calculations the recalculated D at 2 cm from the PTV (Figure 4) and the percentage of the between as much as 63 and 42 Gy for individual patients. lung receiving more than 20 Gy (Figure 5), it is clear that a type B algorithm will result in higher values, due to the Dose-volume constraints for OAR within the ROSEL pro- fact that the change in lateral scattering in lung tissue is tocol are given in Table 2 and differ from the ones used in taken into account much better. Again, the conformity RTOG 0236 and 0618 (for lung constraints, see previous requirements for type B algorithms were relaxed for these Table 1). A reassessment was considered necessary parameters. However, relaxation of these requirements because a new patient group will be treated with stereotac- does not result in an actual inferior patient treatment. On tic radiotherapy within the ROSEL trial, namely patients the contrary, because these more advanced algorithms who are fit to undergo both primary and salvage surgery. provide a better description of the actual dose distribu- As a result, normal tissue dose-constraints have to be tion, the user has a greater opportunity to optimize the more stringently defined in order to minimize the risk of dose distribution to the stated requirements. Therefore, increased complications after salvage surgery. Addition- the use of these more advanced algorithms is strongly ally, new constraints were formulated to be used for the 5 encouraged. Please note that the figures presented here are fraction scheme. Furthermore, the constraints are based based on the treatment plans generated without recalcula- on 1 cc volumes (except for the spinal cord), to prevent an tion with a more advanced algorithm, thus representing excessive dependency on the calculation grid size in the treatment planning clinical practice within the ROSEL evaluation of these parameters. Skin dose, with the con- trial, while in the article of Schuring and Hurkmans the straint that no point within the skin should receive a dose results were presented after recalculation, thus quantify- higher than 24 Gy as dictated in RTOG 0618 is not ing the actual delivered dose differences arising from the included in Table 2, as dose calculations within this use of different algorithms [15]. To emphasize the region are often not very accurate and this dose parameter improvement that can be achieved using a more advanced is often very labour intensive to score. However, this will algorithm over a type A algorithm or a unit density calcu- be evaluated in a dummy run procedure planned before lation, the dose to the PTV after recalculation is given in trial participation for each institution. Figure 6 (reprinted with permission from Schuring and Hurkmans [15]. The figure clearly shows that The EPL Treatment planning plans (Type A algorithm) consistently overestimate the If treatment planning and irradiation are based on the ITV dose to the PTV, resulting in an average D of 48 Gy, 20% concept, the PTV incorporates the complete respiratory Page 7 of 14 (page number not for citation purposes) Radiation Oncology 2009, 4:1 http://www.ro-journal.com/content/4/1/1 1.4 Type A algorithm Type B algorithm RTOG 1.3 1.2 1.1 1.0 0.9 0 25 50 75 100 125 PTV [cm ] stage 1B tumours (with Figure 2 Ratio of Prescription Isod PTVs of ose Volum 59 cc, 85 e to the PTV (R cc, 107 cc and 1 ) from a 08 cc)total of 22 patients with stage IA tumours and 4 patients with 100% Ratio of Prescription Isodose Volume to the PTV (R ) from a total of 22 patients with stage IA tumours and 100% 4 patients with stage 1B tumours (with PTVs of 59 cc, 85 cc, 107 cc and 108 cc). tumour mobility. Several studies indicate that the use of performed by Underberg and colleagues, it was shown the ITV concept leads to the use of larger margins than that only 15% of their patients would have a clinically rel- necessary to compensate for tumour motion due to evant PTV reduction (defined as 50% or more) using gat- breathing [45-48]. This may in turn lead to the unneces- ing compared to the PTV based on the ITV concept [52]. sary exposure of relatively large volumes of organs at risk, They also showed that the PTV reduction correlated well especially for patients with very mobile tumours. How- with the tumour mobility. Thus, the abovementioned ever, Lagerwaard et al. have shown that the incidence of techniques should be primarily considered when treating toxicity is low using this concept and a risk-adapted frac- very mobile tumours or for example tumours close to the tionation schedule [26]. Therefore, the use of this concept stomach. is accepted within the ROSEL trial. However, one might want to avoid unnecessary exposure of organs at risk due It has been shown that the use of a different margin recipe to breathing motion, and four techniques can be distin- leads to a similar reduction of the PTV as gating [45,50]. guished [49]: 1) adaptation of margin recipe [32,50,40], From a patients' perspective, the use of an adapted margin 2) tumour tracking, 3) gating and 4) reduction of breath- recipe might be preferred, as gating significantly prolongs ing motion [51]. These methods are not mutually exclu- the treatment time and this, in turn, leads to significantly sive, for example, one might use abdominal compression more intra-fractional changes in tumour position [53]. in combination with the mean-position margin recipe. It Also, the use of an abdominal compression plate or active must be emphasised that introduction of these techniques breathing control device might be less comfortable for a is not needed for the majority of the patients. In a study patient. This less comfortable position might lead to Page 8 of 14 (page number not for citation purposes) R [ - ] 100% Radiation Oncology 2009, 4:1 http://www.ro-journal.com/content/4/1/1 Type A algorithm Type B Algorithm RTOG 0 25 50 75 100 125 PTV [cm ] with sta Figure 3 Ratio of 50% Prescription Is ge 1B tumours (with PTVs of 59 cc, 85 cc, 107 cc odose Volume to the PTV (R and 108 cc ) from a total of 22 p ) atients with stage IA tumours and 4 patients 50% Ratio of 50% Prescription Isodose Volume to the PTV (R ) from a total of 22 patients with stage IA tumours 50% and 4 patients with stage 1B tumours (with PTVs of 59 cc, 85 cc, 107 cc and 108 cc). increased patient movement and no data about this pos- generally thoracic wall doses are larger than with multiple sible effect is available yet. Tumour tracking by means of static beams. an external marker does not cause any patient discomfort and might be seen as a patient friendly alternative. How- For ITV based treatment plans, dose calculations can be ever, it is shown that variations in external/internal performed on the 3D CT scan reconstruction generated motion correlation are present, making their use poten- without breathing phase binning. (i.e. an average scan or tially less accurate [54,55]. The use of internal markers is untagged scan reconstruction). This has proven to be a considered more accurate, but is associated with an good approximation of 4D dose calculations if combined increased risk of pneumothorax [56]. Furthermore, gating with a type B algorithm [47,58]. and tracking are also technically challenging techniques. They can only be used on a wide scale if existing technical For mid-position based treatment plans, dose calculations problems can be solved [57]. should be either performed on the CT reconstruction phase which represents the time-averaged mean position Due to the wide penumbra of high energy (≥ 15 MV) of the tumour or on scan reconstruction generated with- beams, it is recommended to only use photon (x-ray) out breathing phase binning. beams with energies of 6–10 MV. Experience has been gained with both coplanar and non-coplanar techniques, Treatment execution with in general a 7–13 beam angles in case static beams It is advised to keep the inter-fraction interval at a mini- are used. Dynamic conformal arcs can be used, although mum of 40 hours, in line with the RTOG protocol 0618. Page 9 of 14 (page number not for citation purposes) R [ - ] 50% Radiation Oncology 2009, 4:1 http://www.ro-journal.com/content/4/1/1 Type A algorithm Type B algorithm RTOG 0 25 50 75 100 125 PTV [cm ] a Figure 4 Max nd 4 patients with sta imum dose 2 cm from ge 1B tum PTV in any direction (D ours (with PTVs of 59 cc, 85 cc, 107 cc ) as % of prescribed do and 108 cc se from a total of ) 22 patients with stage I tumours 2 cm Maximum dose 2 cm from PTV in any direction (D ) as % of prescribed dose from a total of 22 patients with 2 cm stage I tumours and 4 patients with stage 1B tumours (with PTVs of 59 cc, 85 cc, 107 cc and 108 cc). The maximum inter-fraction interval should be 4 days. an on-line set-up correction protocol based upon bony Within the ROSEL trial, the standard fractionation should anatomy should be applied. be given over 5–8 days, while the conservative fractiona- tion should be given over 10–14 days. In general, it is rec- Discussion ommended to keep the treatment time as short as possible The ROSEL trial Quality Assurance Working Party in this in order to limit possible patient movement and patient article has tried to present a broad overview of all the tech- discomfort. Longer sessions have been correlated with sig- nical aspects of stereotactic radiotherapy for early stage nificantly more inter-fractional changes in tumour posi- lung cancer. Our aim was to develop widely applicable tion [53]. guidelines in view of the number of stereotactic radiother- apy systems used at centres in The Netherlands which will Patient positioning should be determined by imaging at participate in the ROSEL trial. However, we also formu- the treatment unit itself by means of kV-CT imaging, MV- lated recommendations assuming the most advanced CT imaging or orthogonal kV imaging. It is strongly rec- technical possibilities are at ones disposal. Hopefully, ommended that the target position should be compared these recommended techniques can be implemented on a to the target position in the images used for treatment large scale in the near future. As stereotactic radiotherapy planning, and appropriate patient set-up corrections techniques are in general highly sophisticated, our paper should be applied when tumour shifts are detected [31]. cannot possibly cover all areas in detail. As many aspects As a minimum requirement within the ROSEL protocol, of implementation depend on the available equipment, we recommend that centres should familiarize themselves Page 10 of 14 (page number not for citation purposes) D [%] 2cm Radiation Oncology 2009, 4:1 http://www.ro-journal.com/content/4/1/1 Type A algorithm Type B algorithm RTOG 0 25 50 75 100 125 PTV [cm ] 4 Figure 5 Percent of lung patients with (both lungs minu stage 1B tumours (with s GTV) receiving 20 PTVs of 59 cc, 8 Gy or 5 cc, mor 107 cc a e (V nd 108 cc) ) from a total of 22 patients with stage I tumours and 20 Gy Percent of lung (both lungs minus GTV) receiving 20 Gy or more (V ) from a total of 22 patients with stage 20 Gy I tumours and 4 patients with stage 1B tumours (with PTVs of 59 cc, 85 cc, 107 cc and 108 cc). with technical details of the equipment to be used. Appro- which is highly dependent on the patient specific anat- priate quality assurance systems should also be imple- omy and in general the deviation increases with decreas- mented. A comprehensive overview of quality assurance ing target volume [15]. Therefore, relationships between issues can be found in a special edition about quality treatment outcome and dose generated from stereotactic assurance of the Int. J. Radiat. Oncol. Biol. Phys. (71S, lung cancer trials which not primarily applied type B cal- 2008). culation algorithms should be interpreted with caution. To the best of our knowledge, this is the first trial in stere- Conclusion otactic lung radiotherapy which makes a distinction in Guidelines and recommendations have been formulated dose prescription and dose to OAR criteria based on the to aid the implementation of stereotactic radiotherapy for calculation algorithm used. As was clearly shown, the early stage lung cancer patients in both individual centres dosimetric differences from the use of different algo- as in future multi-institutional trials. They are formulated rithms can be large, and it is more difficult to plan a con- such that stereotactic treatment can safely and effectively formal dose distribution using a more advanced be implemented in clinical practice in a wide variety of algorithm. Without making a distinction based on type of hospitals and treatment results become better compara- algorithm, this might lead to the incorrect assumption ble. that centres with such algorithms use less conformal tech- niques. However, it is shown that the actually delivered Competing interests dose using type A algorithms can deviate as much as 30%, The authors declare that they have no competing interests. Page 11 of 14 (page number not for citation purposes) V [%] 20% Radiation Oncology 2009, 4:1 http://www.ro-journal.com/content/4/1/1 CC plan UD plan EPL plan 0 20406080 100 120 PTV [cm ] Pinnacle 8.0 h) from a cc Figure 6 Dose to 95% of the PTV as a fu , 107 cc and 108 cc) (reprinted with permission fr total of 22 nction of patientsthe PT with stage IA V after recalculation usin om r tumours ef 20) and 4 pa g a tients with type B al gorithm ( stage 1B tumours (with Collapsed Cone ( PTVs of 59 CC) algorithm, cc, 85 Dose to 95% of the PTV as a function of the PTV after recalculation using a type B algorithm (Collapsed Cone (CC) algorithm, Pinnacle 8.0 h) from a total of 22 patients with stage IA tumours and 4 patients with stage 1B tumours (with PTVs of 59 cc, 85 cc, 107 cc and 108 cc) (reprinted with permission from ref 20). Plans were opti- mized using a type A algorithm (EPL), a unit density calculation (UD) or a type B algorithm (CC). the study, and participated in its design and coordination. Authors' contributions CH drafted the manuscript, coordinated and participated All authors read and approved the final manuscript. in the Quality Assurance Working Party designing the guidelines, and participated in performing the calcula- Acknowledgements The ROSEL study is supported by a grant from ZonMW. Grants for the tions comparing dose calculation algorithms. JC, FL, JW ROSEL radiotherapy quality assurance work from Elekta, Philips Medical and UH were all members of the Quality Assurance Work- Systems and Promis Electro-Optics are gratefully acknowledged. ing Party. DS participated in performing the calculations comparing dose calculation algorithms. SS conceived of Table 2: Dose constraints for organs at risk and definition of protocol deviations. Organ Volume (cc) Deviation given as cumulative absolute dose (Gy) 3 fraction scheme 5 fraction scheme None Minor None Minor Spinal Cord Any point 18 > 18 to 22 25 > 25 to 28 Oesophagus 1 24 > 24 to 27 27 > 27 to 28.5 Ipsilateral Brachial Plexus 1 24 > 24 to 26 27 > 27 to 29 Heart 1 24 > 24 to 26 27 > 27 to 29 Trachea and main stem bronchus 1 30 > 30 to 32 32 > 32 to 35 Page 12 of 14 (page number not for citation purposes) 95 Radiation Oncology 2009, 4:1 http://www.ro-journal.com/content/4/1/1 Patients with Medically Inoperable Stage I/II Non-Small Cell References Lung Cancer. RTOG 2007. 1. Qiao X, Tullgren O, Lax I, Sirzen F, Lewensohn R: The role of radi- 18. Timmerman RD, Galvin J, Gore E, Pass H, Edelman MJ, Kong FP: otherapy in treatment of stage I non-small cell lung cancer. RTOG 0618 A phase II trial of stereotactic body radiation Lung Cancer 2003, 41:1-11. therapy (SBRT) in the treatment of patients with operable 2. Nagata Y, Takayama K, Matsuo Y, Norihisa Y, Mizowaki T, Sakamoto stage I/II non-small cell lung cancer. RTOG 2007. T, Sakamoto M, Mitsumori M, Shibuya K, Araki N, Yano S, Hiraoka M: 19. Bosmans G, Buijsen J, Dekker A, Velders M, Boersma L, De Ruysscher Clinical outcomes of a phase I/II study of 48 Gy of stereotac- D, Minken A, Lambin P: An "in silico" clinical trial comparing tic body radiotherapy in 4 fractions for primary lung cancer free breathing, slow and respiration correlated computed using a stereotactic body frame. Int J Radiat Oncol Biol Phys 2005, tomography in lung cancer patients. Radiother Oncol 2006, 63:1427-1431. 81:73-80. 3. Onishi H, Shirato H, Nagata Y, Hiraoka M, Fujino M, Gomi K, Niibe 20. Chen GT, Kung JH, Beaudette KP: Artifacts in computed tomog- Y, Karasawa K, Hayakawa K, Takai Y, Kimura T, Takeda A, Ouchi A, raphy scanning of moving objects. Semin Radiat Oncol 2004, Hareyama M, Kokubo M, Hara R, Itami J, Yamada K, Araki T: Hypof- 14:19-26. ractionated stereotactic radiotherapy (HypoFXSRT) for 21. Keall P: 4-dimensional computed tomography imaging and stage I non-small cell lung cancer: updated results of 257 treatment planning. Semin Radiat Oncol 2004, 14:81-90. patients in a Japanese multi-institutional study. J Thorac Oncol 22. Rietzel E, Pan T, Chen GT: Four-dimensional computed tomog- 2007, 2:S94-100. raphy: image formation and clinical protocol. Med Phys 2005, 4. McGarry RC, Papiez L, Williams M, Whitford T, Timmerman RD: 32:874-889. Stereotactic body radiation therapy of early-stage non- 23. Seki S, Kunieda E, Takeda A, Nagaoka T, Deloar HM, Kawase T, small-cell lung carcinoma: phase I study. Int J Radiat Oncol Biol Fukada J, Kawaguchi O, Uematsu M, Kubo A: Differences in the Phys 2006, 63(4):1010-1015. definition of internal target volumes using slow CT alone or 5. Lagerwaard FJ, Haasbeek CJA, Smit EF, Slotman BJ, Senan S: Out- in combination with thin-slice CT under breath-holding con- come After Stereotactic Radiotherapy in 'High-Risk' ditions during the planning of stereotactic radiotherapy for Patients With Stage I Non-small Cell Lung Cancer lung cancer. Radiother Oncol 2007, 85:443-449. (NSCLC). Int J Radiat Oncol Biol Phys 2007, 69:S87-S88. 24. Wurstbauer K, Deutschmann H, Kopp P, Sedlmayer F: Radiother- 6. Onishi H, Araki T, Shirato H, Nagata Y, Hiraoka M, Gomi K, Yamas- apy planning for lung cancer: slow CTs allow the drawing of hita T, Niibe Y, Karasawa K, Hayakawa K, Takai Y, Kimura T, tighter margins. Radiother Oncol 2005, 75:165-170. Hirokawa Y, Takeda A, Ouchi A, Hareyama M, Kokubo M, Hara R, 25. Letourneau D, Finlay M, O'sullivan B, Waldron JN, Cummings BJ, Rin- Itami J, Yamada K: Stereotactic hypofractionated high-dose gash J, Kim JJ, Bayley AJ, Dawson LA: Lack of influence of intrave- irradiation for stage I nonsmall cell lung carcinoma. Cancer nous contrast on head and neck IMRT dose distributions. 2004, 101:1623-1631. Acta Oncol 2008, 47:90-94. 7. El-Sherif A, Gooding WE, Santos R, Pettiford B, Ferson PF, Fernando 26. Lagerwaard FJ, Haasbeek CJA, Smit EF, Slotman BJ, Senan S: Out- HC, Urda SJ, Luketich JD, Landreneau RJ: Outcomes of sublobar comes of Risk-Adapted Fractionated Stereotactic Radio- resection versus lobectomy for stage I non-small cell lung therapy for Stage I Non-Small-Cell Lung Cancer. Int J Radiat cancer: a 13-year analysis. Ann Thorac Surg 2006, 82:408-415. Oncol Biol Phys 2008, 70:685-692. 8. Strand TE, Rostad H, Moller B, Norstein J: Survival after resection 27. Potters L, Steinberg M, Rose C, Timmerman R, Ryu S, Hevezi JM, for primary lung cancer: a population based study of 3211 Welsh J, Mehta M, Larson DA, Janjan NA: American Society for resected patients. Thorax 2006, 61:710-715. Therapeutic Radiology and Oncology and American College 9. Rami-Porta R, Ball D, Crowley J, Giroux DJ, Jett J, Travis WD, Tsuboi of Radiology practice guideline for the performance of ster- M, Vallieres E, Goldstraw P: The IASLC Lung Cancer Staging eotactic body radiation therapy. Int J Radiat Oncol Biol Phys 2004, Project: proposals for the revision of the T descriptors in the 60:1026-1032. forthcoming (seventh) edition of the TNM classification for 28. Bradley JD, Nofal AN, El Naga IM, Lu W, Liu J, Hubenschmidt J, Low lung cancer. J Thorac Oncol 2007, 2:593-602. DA, Drzymala RE, Khullar D: Comparison of helical, maximum 10. Timmerman RD, Park C, Kavanagh BD: The North American intensity projection (MIP), and averaged intensity (AI) 4D experience with stereotactic body radiation therapy in non- CT imaging for stereotactic body radiation therapy (SBRT) small cell lung cancer. J Thorac Oncol 2007, 2:S101-S112. planning in lung cancer. Radiother Oncol 2006, 81:264-268. 11. Pasic A, Brokx HA, Vonk NA, Paul RM, Postmus PE, Sutedja TG: 29. Riegel AC, Chang JY, Vedam SS, Johnson V, Chi PC, Pan T: Cine Cost-effectiveness of early intervention: comparison Computed Tomography Without Respiratory Surrogate in between intraluminal bronchoscopic treatment and surgical Planning Stereotactic Radiotherapy for Non-Small-Cell resection for T1N0 lung cancer patients. Respiration 2004, Lung Cancer. Int J Radiat Oncol Biol Phys 2008. DOI: 10.1016/ 71:391-396. j.ijrobp.2008.04.047 12. Timmerman RD, Paulus R, Galvin J, Michalski J, Straube WL, Bradley 30. van Sornsen de Koste JR, Lagerwaard FJ, Nijssen-Visser MR, Grave- J, Fakiris A, Bezjak A, Videtic G, Choy H: Toxicity Analysis of land WJ, Senan S: Tumor location cannot predict the mobility RTOG 0236 Using Stereotactic Body Radiation Therapy to of lung tumors: a 3D analysis of data generated from multi- Treat Medically Inoperable Early Stage Lung Cancer ple CT scans. Int J Radiat Oncol Biol Phys 2003, 56:348-354. Patients. Int J Radiat Oncol Biol Phys 2007, 69:S86. 31. Sonke JJ, Lebesque J, van Herk M: Variability of four-dimensional 13. Xiao Y, Straube WL, Bosch WR, Timmerman RD, Galvin JM: Dosi- computed tomography patient models. Int J Radiat Oncol Biol metric Evaluation of Heterogeneity Corrections for RTOG Phys 2008, 70:590-598. 0236: Hypofractionated Radiotherapy of Inoperable Stage I/ 32. Wolthaus JWH, Schneider C, Sonke JJ, van Herk M, Belderbos JSA, II Non-small Cell Lung Cancer. Int J Radat Oncol Biol Phys 2007, Rossi MMG, Lebesque JV, Damen EFM: Mid-ventilation CT scan 69:S46-S47. construction from four-dimensional respiration-correlated 14. Hiraoka M, Ishikura S: A Japan clinical oncology group trial for CT scans for radiotherapy planning of lung cancer patients. stereotactic body radiation therapy of non-small cell lung Int J Radat Oncol Biol Phys 2006, 65:1560-1571. cancer. J Thorac Oncol 2007, 2:S115-S117. 33. Dieleman EM, Senan S, Vincent A, Lagerwaard FJ, Slotman BJ, van 15. Schuring D, Hurkmans CW: Developing and evaluating stereo- Sornsen de Koste JR: Four-dimensional computed tomo- tactic lung RT trials: What we should know about the influ- graphic analysis of esophageal mobility during normal respi- ence of inhomogeneity corrections on dose. Radiat Oncol 2008, ration. Int J Radiat Oncol Biol Phys 2007, 67:775-780. 3:21. 34. ICRU report 62 prescribing, recording and reporting photon 16. Underberg RW, Lagerwaard FJ, Slotman BJ, Cuijpers JP, Senan S: Use beam therapy. (Supplement to ICRU report 50) 1999, 33:1-51. of maximum intensity projections (MIP) for target volume 35. Hall WH, Guiou M, Lee NY, Dublin A, Narayan S, Vijayakumar S, generation in 4DCT scans for lung cancer. Int J Radiat Oncol Biol Purdy JA, Chen AM: Development and Validation of A Stand- Phys 2005, 63:253-260. ardized Method for Contouring THE Brachial Plexus: Pre- 17. Timmerman RD, Michalski J, Galvin J, Fowler JF, Choy H, Gore E, liminary Dosimetric Analysis Among Patients Treated with Johnstone D: RTOG 0236 : A Phase II Trial of Stereotactic IMRT for Head-and-Neck Cancer. Int J Radiat Oncol Biol Phys Body Radiation Therapy (SBRT) in the Treatment of 2008, 72;1:S385. Page 13 of 14 (page number not for citation purposes) Radiation Oncology 2009, 4:1 http://www.ro-journal.com/content/4/1/1 36. Madu CN, Quint DJ, Normolle DP, Marsh RB, Wang EY, Pierce LJ: combined with respiratory correlated image guidance. Radi- Definition of the supraclavicular and infraclavicular nodes: other Oncol 2008, 86:61-68. implications for three-dimensional CT-based conformal 55. Ionascu D, Jiang SB, Nishioka S, Shirato H, Berbeco RI: Internal- radiation therapy. Radiology 2001, 221:333-339. external correlation investigations of respiratory induced 37. Collins BT, Erickson K, Reichner CA, Collins SP, Gagnon GJ, Diet- motion of lung tumors. Med Phys 2007, 34:3893-3903. erich S, McRae DA, Zhang Y, Yousefi S, Levy E, Chang T, Jamis-Dow 56. Geraghty PR, Kee ST, McFarlane G, Razavi MK, Sze DY, Dake MD: C, Banovac F, Anderson ED: Radical stereotactic radiosurgery CT-guided transthoracic needle aspiration biopsy of pulmo- with real-time tumor motion tracking in the treatment of nary nodules: needle size and pneumothorax rate. Radiology small peripheral lung tumors. Radiat Oncol 2007, 2:39. 2003, 229:475-481. 38. Koto M, Takai Y, Ogawa Y, Matsushita H, Takeda K, Takahashi C, 57. Jiang SB: Radiotherapy of mobile tumors. Semin Radiat Oncol Britton KR, Jingu K, Takai K, Mitsuya M, Nemoto K, Yamada S: A 2006, 16:239-248. phase II study on stereotactic body radiotherapy for stage I 58. Guckenberger M, Wilbert J, Krieger T, Richter A, Baier K, Meyer J, non-small cell lung cancer. Radiother Oncol 2007, 85:429-434. Flentje M: Four-dimensional treatment planning for stereo- 39. Sinha B, McGarry RC: Stereotactic body radiotherapy for bilat- tactic body radiotherapy. Int J Radiat Oncol Biol Phys 2007, eral primary lung cancers: the Indiana university experience. 69:276-285. Int J Radiat Oncol Biol Phys 2007, 66:1120-1124. 40. Haasbeek CJ, Senan S, Smit EF, Paul MA, Slotman BJ, Lagerwaard FJ: Critical review of nonsurgical treatment options for stage I non-small cell lung cancer. Oncologist 2008, 13:309-319. 41. Brock J, Ashley S, Bedford J, Nioutsikou E, Partridge M, Brada M: Review of Hypofractionated Small Volume Radiotherapy for Early-stage Non-small Cell Lung Cancer. Clin Oncol (R Coll Radiol) 2008, 20:666-676. 42. Timmerman R, McGarry R, Yiannoutsos C, Papiez L, Tudor K, DeLuca J, Ewing M, Abdulrahman R, DesRosiers C, Williams M, Fletcher J: Excessive toxicity when treating central tumors in a phase II study of stereotactic body radiation therapy for medically inoperable early-stage lung cancer. J Clin Oncol 2006, 24:4833-4839. 43. Senan S, Haasbeek NJ, Smit EF, Lagerwaard FJ: Stereotactic radio- therapy for centrally located early-stage lung tumors. J Clin Oncol 2007, 25:464. 44. Knöös T, Wieslander E, Cozzi L, Brink C, Fogliata A, Albers D, Nys- tröm H, Lassen S: Comparison of dose calculation algorithms for treatment planning in external photon beam therapy for clinical situations. Phys Med Biol 2006, 51:5785-5807. 45. Wolthaus JW, Sonke JJ, van Herk M, Belderbos JS, Rossi MM, Leb- esque JV, Damen EM: Comparison of different strategies to use four-dimensional computed tomography in treatment plan- ning for lung cancer patients. Int J Radiat Oncol Biol Phys 2008, 70:1229-1238. 46. Guckenberger M, Krieger T, Baier K, Richter A, Polat B, Flentje M: Four Dimensional Target Volume Generation in Pulmonary Stereotactic Body Radiotherapy. Int J Radiat Oncol Biol Phys 2007, 69(1):S191. 47. Admiraal MA, Schuring D, Hurkmans CW: Dose calculations accounting for breathing motion in stereotactic lung radio- therapy based on 4D-CT and the internal target volume. Radiother Oncol 2008, 86:55-60. 48. Mutaf YD, Brinkmann DH: Optimization of internal margin to account for dosimetric effects of respiratory motion. Int J Radiat Oncol Biol Phys 2008, 70:1561-1570. 49. Giraud P, Yorke E, Jiang S, Simon L, Rosenzweig K, Mageras G: Reduction of organ motion effects in IMRT and conformal 3D radiation delivery by using gating and tracking tech- niques. Cancer Radiother 2006, 10:269-282. 50. Burnett SS, Sixel KE, Cheung PC, Hoisak JD: A study of tumor motion management in the conformal radiotherapy of lung cancer. Radiother Oncol 2008, 86:77-85. 51. Heinzerling JH, Anderson JF, Papiez L, Boike T, Chien S, Zhang G, Abdulrahman R, Timmerman R: Four-dimensional computed Publish with Bio Med Central and every tomography scan analysis of tumor and organ motion at var- scientist can read your work free of charge ying levels of abdominal compression during stereotactic treatment of lung and liver. Int J Radiat Oncol Biol Phys 2008, "BioMed Central will be the most significant development for 70:1571-1578. disseminating the results of biomedical researc h in our lifetime." 52. Underberg RWM, Lagerwaard FJ, Slotman BJ, Cuijpers JP, Senan S: Sir Paul Nurse, Cancer Research UK Benefit of respiration-gated stereotactic radiotherapy for stage I lung cancer: an analysis of 4DCT datasets. Int J Radiat Your research papers will be: Oncol Biol Phys 2005, 62:554-560. available free of charge to the entire biomedical community 53. Purdie TG, Bissonnette JP, Franks K, Bezjak A, Payne D, Sie F, Sharpe MB, Jaffray DA: Cone-beam computed tomography for on-line peer reviewed and published immediately upon acceptance image guidance of lung stereotactic radiotherapy: localiza- cited in PubMed and archived on PubMed Central tion, verification, and intrafraction tumor position. Int J Radiat Oncol Biol Phys 2007, 68:243-252. yours — you keep the copyright 54. Korreman SS, Juhler-Nottrup T, Boyer AL: Respiratory gated BioMedcentral beam delivery cannot facilitate margin reduction, unless Submit your manuscript here: http://www.biomedcentral.com/info/publishing_adv.asp Page 14 of 14 (page number not for citation purposes)

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Published: Jan 12, 2009

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