Evaluating the influence of organ motion during photon vs. proton therapy for locally advanced prostate cancer using biological models.

BACKGROUND: Proton therapy (PT) may have a normal tissue sparing potential when co-irradiating pelvic lymph nodes in patients with locally advanced prostate cancer, but may also be more sensitive towards organ motion in the pelvis. Building upon a previous study identifying motion-robust proton beam angles for pelvic irradiation, we aimed to evaluate the influence of organ motion for PT using biological models, and to compare this with contemporary photon-based RT. MATERIAL AND METHODS: Eight locally advanced prostate cancer patients with a planning CT (pCT) and 8-9 repeated CT scans (rCTs) were included. Two PT plans were created, one using two lateral opposed beams at gantry angles of 90°/270° and the other using two lateral oblique beams at 35°/325°; these were compared with volumetric modulated arc therapy (VMAT) plans. All plans were optimised on the pCT and subsequently re-calculated on each rCT (following rigid alignment on the prostate). Dose distributions in organs at risk (OARs) were evaluated using mean dose, generalized equivalent uniform doses (gEUDs) and normal tissue complication probabilities (NTCPs), while mean dose and the volume receiving 98% of the dose (V98%) were used for the targets. RESULTS: PT significantly reduced the mean dose to the OARs and a correlation was seen in the pCTs between the prostate PTV overlapping the relevant OAR and OAR NTCPs, as was also the case for the VMAT plans. The best prostate target coverage across the rCTs for the IMPT plans were seen with two lateral opposed beams, although a poor coverage of the lymph node target was apparent based on V98% compared to the VMAT plans. CONCLUSIONS: PT reduced the mean dose to normal tissues in the irradiation of pelvic lymph nodes and a strong association between the volume overlap and NTCPs in the pCTs were found.

Beam angle evaluation to improve inter-fraction motion robustness in pelvic lymph node irradiation with proton therapy.

BACKGROUND: Proton therapy dose distributions are sensitive to range variations, e.g. arising from inter-fraction organ motion. The aim of this study was to evaluate the inter-fraction motion robustness of proton beams from different beam angles in irradiation of pelvic lymph nodes (LNs). MATERIAL AND METHODS: Planning CT (pCT) and multiple repeat CT (rCT) scans of 18 prostate cancer patients were used. Considering left and right LNs separately, the average water equivalent path length (WEPL) over all ray paths in the beams eye view of the LNs were calculated for all gantry/couch angle combinations across all rCTs versus the corresponding pCT. Single beam proton plans were optimized on the pCT for all gantry angles (0° couch) and were re-calculated on all rCTs for each respective patient. WEPL and dose parameters were extracted and a statistical clustering analysis performed to identify patient sub-populations in terms of patterns in which angles were robust. RESULTS: The WEPL analysis showed a general pattern of least variation for 0° couch beam angles where three minima were found across gantry angles for the left LNs and two for the right LNs. The clustering analysis identified three patient sub-groups for the left LNs and two groups for the right LNs. The dose calculations showed similar results as the WEPL variation, e.g. for the left LNs angles around 25°-35°, 100°-110°, and 160°-170° were consistently preferable for both target and organs at risk. CONCLUSIONS: Sub-populations of patients with similar patterns of WEPL variations across beam angles were identified. The most robust angles found for WEPL variations were also confirmed by the dose/volume analysis.

Adaptive radiotherapy strategies for pelvic tumors - a systematic review of clinical implementations.

UNLABELLED: Introdution: Variation in shape, position and treatment response of both tumor and organs at risk are major challenges for accurate dose delivery in radiotherapy. Adaptive radiotherapy (ART) has been proposed to customize the treatment to these motion/response patterns of the individual patients, but increases workload and thereby challenges clinical implementation. This paper reviews strategies and workflows for clinical and in silico implemented ART for prostate, bladder, gynecological (gyne) and ano-rectal cancers. MATERIAL AND METHODS: Initial identification of papers was based on searches in PubMed. For each tumor site, the identified papers were screened independently by two researches for selection of studies describing all processes of an ART workflow: treatment monitoring and evaluation, decision and execution of adaptations. Both brachytherapy and external beam studies were eligible for review. RESULTS: The review consisted of 43 clinical studies and 51 in silico studies. For prostate, 1219 patients were treated with offline re-planning, mainly to adapt prostate motion relative to bony anatomy. For gyne 1155 patients were treated with online brachytherapy re-planning while 25 ano-rectal cancer patients were treated with offline re-planning, all to account for tumor regression detected by magnetic resonance imaging (MRI)/computed tomography (CT). For bladder and gyne, 161 and 64 patients, respectively, were treated with library-based online plan selection to account for target volume and shape variations. The studies reported sparing of rectum (prostate and bladder cancer), bladder (ano-rectal cancer) and bowel cavity (gyne and bladder cancer) as compared to non-ART. CONCLUSION: Implementations of ART were dominated by offline re-planning and online brachytherapy re-planning strategies, although recently online plan selection workflows have increased with the availability of cone-beam CT. Advantageous dosimetric and outcome patterns using ART was documented by the studies of this review. Despite this, clinical implementations were scarce due to challenges in target/organ re-contouring and suboptimal patient selection in the ART workflows.

A method for evaluation of proton plan robustness towards inter-fractional motion applied to pelvic lymph node irradiation.

BACKGROUND: The benefit of proton therapy may be jeopardized by dose deterioration caused by water equivalent path length (WEPL) variations. In this study we introduced a method to evaluate robustness of proton therapy with respect to inter-fractional motion and applied it to irradiation of the pelvic lymph nodes (LNs) from different beam angles. Patient- versus population-specific patterns in dose deterioration were explored. MATERIAL AND METHODS: Patient data sets consisting of a planning computed tomography (pCT) as well as multiple repeat CT (rCT) scans for three patients were used, with target volumes and organs at risk (ORs) outlined in all scans. Single beam spot scanning proton plans were optimized for the left and right LN targets separately, across all possible beam angle configurations (5° angle intervals). Isotropic margins of 0, 3, 5 and 7 mm from the clinical target volume (CTV) to the planning target volume (PTV) were investigated. The optimized fluence maps for the pCT for each beam were applied onto all rCTs and the dose distributions were re-calculated. WEPL variation for each beam angle was computed by averaging over beams eye view WEPL distributions. RESULTS: Similarity in deterioration patterns were found for the investigated patients, with beam angles delivering less dose to rectum, bladder and overall normal tissue identified around 40° and around 150°-160° for the left LNs, and corresponding angles for the right LNs. These angles were also associated with low values of WEPL variation. CONCLUSION: We have established and explored a method to quantify the robustness towards inter-fractional motion of single beam proton plans treating the pelvic LNs from different beam configurations and with different CTV to PTV margins. For the patients investigated we were able to identify beam orientations that were robust to dose deterioration in the target and ORs.

Degradation of target coverage due to inter-fraction motion during intensity-modulated proton therapy of prostate and elective targets.

UNLABELLED: Internal target and organ motion during treatment is a challenge in radiotherapy (RT) of the prostate and the involved elective targets, with residual motion being present also following image-guidance strategies. The aim of this study was to investigate organ motion-induced dose degradations for the prostate, seminal vesicle and the pelvic lymph node when treating these targets with proton therapy, using different image-guidance and delivery strategies. MATERIAL AND METHODS: Four patients were selected from a larger series as they displayed large inter-fractional variation in bladder and rectum volume. Intensity-modulated proton therapy plans were generated using both simultaneous integrated and sequential boost delivery. For each technique, three isotropic margin expansions (in the range of 4-10 mm) were evaluated for the clinical target volume of prostate (CTV-p), seminal vesicles (CTV-sv) and lymph nodes (CTV-ln). Simulation of the dose degradations for all treatment plans were based on dose re-calculations for the 8-9 repeat CTs available for each patient, after applying rigid registrations to reproduce set-up based on either intra-prostatic fiducials or bony anatomy. RESULTS: The simulated dose received by 99% of the target volume (D(99)) and generalized equivalent dose (gEUD) showed substantial inter-patient variations. For 40% of the investigated scenarios, the patient average simulated D(99) for all targets were within 2 GyE from the planned dose. The largest difference between simulated and planned dose was seen for the CTV-sv when using SIB delivery, with an average relative reduction in D(99) of 13% and 15% for the largest margin expansion, when positioned using fiducials and bony anatomy, respectively. CONCLUSIONS: The most severe dose degradations were found for CTV-sv, but they were also evident for CTV-ln. The degradations could not be completely resolved, neither by using the largest margin expansion nor with the choice of set-up. With fiducial set-up CTV-p was robust against the inter-fraction changes.

Adaptive radiotherapy in locally advanced prostate cancer using a statistical deformable motion model.

UNLABELLED: Daily treatment plan selection from a plan library is a major adaptive radiotherapy strategy to account for individual internal anatomy variations. This strategy depends on the initial input images being representative for the variations observed later in the treatment course. Focusing on locally advanced prostate cancer, our aim was to evaluate if residual motion of the prostate (CTV-p) and the elective targets (CTV-sv, CTV-ln) can be prospectively accounted for with a statistical deformable model based on images acquired in the initial part of treatment. METHODS: Thirteen patients with locally advanced prostate cancer, each with 9-10 repeat CT scans, were included. Displacement vectors fields (DVF) obtained from contour-based deformable registration of delineations in the repeat- and planning CT scans were used to create patient-specific statistical motion models using principal component analysis (PCA). For each patient and CTV, four PCA-models were created: one with all 9-10 DVF as input in addition to models with only four, five or six DVFs as input. Simulations of target shapes from each PCA-model were used to calculate iso-coverage levels, which were converted to contours. The levels were analyzed for sensitivity and precision. RESULTS: A union of the simulated shapes was able to cover at least 97%, 97% and 95% of the volumes of the evaluated CTV shapes for PCA-models using six, five and four DVFs as input, respectively. There was a decrease in sensitivity with higher iso-coverage levels, with a sharper decline for greater target movements. Apart from having the steepest decline in sensitivity, CTV-sv also displayed the greatest influence on the number of geometries used in the PCA-model. CONCLUSIONS: PCA-based simulations of residual motion derived from four to six DVFs as input could account for the majority of the target shapes present during the latter part of the treatment. CTV-sv displayed the greatest range in both sensitivity and precision.

Intensity profile based measurement of prostate gold markers influence on 1.5 and 3T diffusion-weighted MR images.

BACKGROUND AND PURPOSE: In this study the influence of fiducial markers (FMs) on diffusion-weighted (DW) magnetic resonance images was investigated by measuring the intensity variations due to the artefact from the FM image reconstruction. MATERIAL AND METHODS: DW- and reference T1W images were acquired of an Agar-gel phantom containing two fixed cylindrical FMs, with a 1.5- and 3T MR scanner. The center of gravity (CoG) positions of the manually segmented FM artefacts (FMA) and the size of FMAs in x-, y- and z direction were measured in the two corresponding image sets, based on the intensity changes caused by the FM reconstruction. Also, a similarity measure, the Dice similarity coefficient (DSC), of the segmented FMAs in the two image sets was calculated. RESULTS: The mean shift of the CoG of the manually segmented FMAs in the phase encoding (PE) and the two orthogonal directions, respectively, was: 1.5T/3T; 0.3 ± 0.1/0.5 ± 0.3 cm and 1.5T/3T; 0.1 ± 0.1/0.1 ± 0.1 cm. The largest shift was observed in the 3T DW images for FMs aligned with the long axis orthogonal to the PE direction (0.9 ± 0.1 cm). The mean size of the FMA in the PE- and the two orthogonal directions, respectively, was: 1.5T/3T; 1.7 ± 0.5/1.3 ± 0.1 cm, and 1.5T/3T; 0.9 ± 0.3/1.0 ± 0.2 cm. The mean DSC value of the segmented artefact volumes in the DW- vs. T1W images were 21% and 5% for the 1.5- and 3.0T MR scanner, respectively. CONCLUSIONS: This study has shown that both the size and displacement of the FMAs increase in the PE direction on DW images. The larger shifts were observed for FMs positioned with the long axis orthogonal to the PE direction. Measurements obtained for different b-values gave consistent results.

Plan robustness of simultaneous integrated boost radiotherapy of prostate and lymph nodes for different image-guidance and delivery techniques.

BACKGROUND AND PURPOSE: Uncorrelated motion of targets and large deformations of organs at risk represent challenges for image-guidance in simultaneous integrated boost (SIB) radiotherapy (RT) of pelvic tumour sites. This study aims to evaluate the robustness towards geometrical uncertainties in prostate cancer using two image-guided RT (IGRT) set-up strategies for two SIB delivery methods. Secondly, we evaluate the ability of geometrical parameters to predict when the applied margins are insufficient, resulting in target underdosage (TUD). MATERIAL AND METHODS: The study included nine patients with eight to nine repeat computed tomography (CT)-scans evenly distributed throughout their treatment course. The prostate target (CTV-p) and the lymph node target including seminal vesicles (CTV-ln/sv) were delineated in all scans. SIB treatment plans for intensity-modulated RT and volumetric modulated arc therapy were generated on the planning CT and transferred to the repeat CTs for dose re-calculation using registration based on either anatomy or intra-prostatic fiducial markers. Receiving operator characteristic analysis was used to deduce the ability of the parameters to predict TUD. RESULTS: The dosimetric differences between the two positioning strategies were small for all parameters evaluated and significant only for the dose to rectum. Anatomy based registration resulted in inferior target coverage with a larger number of TUDs, mostly seen in the seminal vesicles. For both targets the highest sensitivity and specificity of predicting TUD was seen for the relative volume and the lowest was found for the displacement vector. CONCLUSIONS: Positioning based on fiducials gave the best trade-off between coverage of the targets although resulting in the highest dose to rectum. Target underdosage occurred mostly in the seminal vesicles. For both targets, the best parameter to predict TUD was the relative volume.

Propagation of target and organ at risk contours in radiotherapy of prostate cancer using deformable image registration.

BACKGROUND: Successful deformable image registration is an essential component of both dose accumulation and plan adaptation in radiotherapy. The aim of this study was to evaluate the performance of a deformable image registration application for propagation of contours using repeat CT scans of the pelvis, a region where considerable deformations are expected. MATERIAL AND METHODS: The study involved four prostate cancer patients, each with 9-11 repeat CT scans. An oncologist contoured bladder, rectum, clinical target volume of pelvic lymph nodes (CTV-ln) and prostate (CTV-p) in all CT scans. The reference CT was retrospectively registered to the repeat CT scans with both rigid and deformable registration using a recently released commercial clinical software application. Two different diffusion-based 'demons' deformable registration algorithms were applied, differing in the amount of deformations being allowed, with algorithm A being more generous than algorithm B. The evaluation of the propagated structures included both quantitative measures and qualitative scoring. RESULTS: We found the differences between the algorithms to be most evident for bladder and rectum. An increase in mean Dice similarity coefficient relative the rigid registrations of 12% and 13% was obtained with algorithm A for bladder and rectum, compared to 2% with algorithm B. For bladder the mean sensitivity and positive predictive value was 0.92 and 0.87 with algorithm A and 0.82 and 0.83 with algorithm B. Corresponding values for rectum was 0.81 and 0.76 with algorithm A and 0.75 and 0.69 with algorithm B. This translated into 57% and 26% passing the clinical evaluation for bladder and rectum, with algorithm A, compared to 17% and 14% with algorithm B. For CTV-ln and CTV-p both algorithms performed well by all measures, e.g. with 86% of the target structures passing the clinical evaluation. CONCLUSIONS: Deformable image registration improved contour propagation in the pelvis for all organs investigated. Differences in the performance of the algorithms were seen which became more pronounced for the highly deformable organs of bladder and rectum.

The experimental dose ranges influence the LETd dependency of the proton minimum RBE (RBEmin).

Cell experiments have shown the proton relative biological effectiveness (RBE) to vary with dose and linear energy transfer (LET), which has led to development of variable RBE models. The RBE is normally estimated from two independent functions, the RBEmax and RBEmin, describing the extreme RBE at low and high doses. While there is consensus that RBEmax increases with increasing LET, the RBEmin is not uniformly defined and its dependency on LET is deviating. In this work, we analysed this dependency and its sensitivity to variations of the experimental dose range. We performed a literature search to find data from existing monoenergetic proton cell survival experiments with (α/ß) x values below 5 Gy and dose averaged LET (LETd) values below 20 keV µm-1. From the experiments the doses and their corresponding survival data were extracted. Based on these data, multiple restricted databases were generated by sequential exclusion of low dose data in the experiments followed by a linear-quadratic (LQ) fit. The quadratic component from the LQ-fit was used to estimate RBEmin. The LETd dependency of RBEmin was determined by fitting a linear function to the RBEmin values estimated from the restricted databases. Our analysis showed the LETd dependency of RBEmin to be significantly influenced by the experimental dose range. By including experiments with doses below 1 Gy in the database, we found that RBEmin increased with increasing LETd. By excluding the low dose experiments in our database, the RBEmin became constant for all LETd values. For an LETd value of 5 keV µm-1, a restricted database including the data with the lowest doses gave an RBEmin of 1.4 ± 0.1, while databases with only high dose data (>2 Gy) gave an RBEmin of 1.0 ± 0.1. None of our restricted databases gave a decreasing RBEmin with increasing LETd. Our study showed that RBEmin has a small yet significant dependency on LETd for tissues with low (α/ß) x ratio. The LETd dependency of RBEmin varied substantially with the experimental dose range. Including experiments with high minimum dose in RBE models may lead to underestimation of the RBE.

On-line dose-guidance to account for inter-fractional motion during proton therapy.

BACKGROUND AND PURPOSE: Proton therapy (PT) of extra-cranial tumour sites is challenged by density changes caused by inter-fractional organ motion. In this study we investigate on-line dose-guided PT (DGPT) to account inter-fractional target motion, exemplified by internal motion in the pelvis. MATERIALS AND METHODS: On-line DGPT involved re-calculating dose distributions with the isocenter shifted up to 15 mm from the position corresponding to conventional soft-tissue based image-guided PT (IGPT). The method was applied to patient models with simulated prostate/seminal vesicle target motion of ±3, ±5 and ±10 mm along the three cardinal axes. Treatment plans were created using either two lateral (gantry angles of 90°/270°) or two lateral oblique fields (gantry angles of 35°/325°). Target coverage and normal tissue doses from DGPT were compared to both soft-tissue and bony anatomy based IGPT. RESULTS: DGPT improved the dose distributions relative to soft-tissue based IGPT for 39 of 90 simulation scenarios using lateral fields and for 50 of 90 scenarios using lateral oblique fields. The greatest benefits of DGPT were seen for large motion, e.g. a median target coverage improvement of 13% was found for 10 mm anterior motion with lateral fields. DGPT also improved the dose distribution in comparison to bony anatomy IGPT in all cases. The best strategy was often to move the fields back towards the original target position prior to the simulated target motion. CONCLUSION: DGPT has the potential to better account for large inter-fractional organ motion in the pelvis than IGPT.

Exploration and application of phenomenological RBE models for proton therapy.

The relative biological effectiveness (RBE) of protons varies with multiple physical and biological factors. Phenomenological RBE models have been developed to include such factors in the estimation of a variable RBE, in contrast to the clinically applied constant RBE of 1.1. In this study, eleven published phenomenological RBE models and two plan-based models were explored and applied to simulated patient cases. All models were analysed with respect to the distribution and range of linear energy transfer (LET) and reference radiation fractionation sensitivity ((α/ß) x ) of their respective experimental databases. Proton therapy plans for a spread-out Bragg peak in water and three patient cases (prostate adenocarcinoma, pituitary adenoma and thoracic sarcoma) were optimised using an RBE of 1.1 in the Eclipse™ treatment planning system prior to recalculation and modelling in the FLUKA Monte Carlo code. Model estimated dose-volume parameters for the planning target volumes (PTVs) and organs at risk (OAR) were compared. The experimental in vitro databases for the various models differed greatly in the range of (α/ß) x values and dose-averaged LET (LETd). There were significant variations between the model estimations, which arose from fundamental differences in the database definitions and model assumptions. The greatest variations appeared in organs with low (α/ß) x and high LETd, e.g. biological doses given to late responding OARs located distal to the target in the treatment field. In general, the variation in maximum dose (D2%) was larger than the variation in mean dose and other dose metrics, with D2% of the left optic nerve ((α/ß) x = 2.1 Gy) in the pituitary adenoma case showing the greatest discrepancies between models: 28-52 Gy(RBE), while D2% for RBE1.1 was 30 Gy(RBE). For all patient cases, the estimated mean RBE to the PTV was in the range 1.09-1.29 ((α/ß) x = 1.5/3.1/10.6 Gy). There were considerable variations between the estimations of RBE and RBE-weighted doses from the different models. These variations were a consequence of fundamental differences in experimental databases, model assumptions and regression techniques. The results from the implementation of RBE models in dose planning studies should be evaluated in light of these deviations.

Statistical motion modelling for robust evaluation of clinically delivered accumulated dose distributions after curative radiotherapy of locally advanced prostate cancer.

BACKGROUND AND PURPOSE: Planned doses are used as surrogate for the actually delivered dose in radiotherapy. We have estimated the delivered dose in a dose-escalation trial of locally advanced prostate cancer by statistical dose-accumulation and by DVH-summation, and compared to planned dose. MATERIALS AND METHOD: Prescribed dose-escalation to the prostate was 67.5 Gy/25fr., corresponding to 81GyEQD2 assuming α/ß = 1.5. The 21 patients had three targets (i.e. CTV67.5 + 2 mm, CTV60 + 5 mm, CTV50 + 10 mm) irradiated by a simultaneous-integrated-boost technique. Analysis was based on 213 CT scans and 5-years of follow-up. For statistical dose-accumulation, we modelled 10000 possible treatment courses based on planned dose and deformation-vector-fields from contour-based registration. For DVH-summation we recalculated dose on repeat-CTs and estimated median D98%/EUD. Groups with/without disease recurrence were compared. RESULTS: Discrepancies between planned and accumulated dose were mostly seen for CTV67.5, where under-dosage was found at different locations in the prostate in 12/21 patients. Delivered dose-escalation (D98%) was on average 73.9GyEQD2 (range: 68.3-78.7GyEQD2). No significant difference in accumulated-D98% was found in patients with (n = 8) and without (n = 13) recurrence (p > 0.05). Average D98%/EUD with statistical dose-accumulation vs DVH-summation was significantly different in CTV60, CTV50, rectum and bladder but not in CTV67.5. CONCLUSION: The planned dose escalation was not received by more than half-of-the patients. Robustness of the prostate target (CTV67.5) should therefore be better prioritized in these patients given the low toxicity profile. Estimates of delivered dose were less conservative for dose-accumulation due to interaction of random organ motion with the dose matrix.

A phenomenological biological dose model for proton therapy based on linear energy transfer spectra.

PURPOSE: The relative biological effectiveness (RBE) of protons varies with the radiation quality, quantified by the linear energy transfer (LET). Most phenomenological models employ a linear dependency of the dose-averaged LET (LETd ) to calculate the biological dose. However, several experiments have indicated a possible non-linear trend. Our aim was to investigate if biological dose models including non-linear LET dependencies should be considered, by introducing a LET spectrum based dose model. METHOD: The RBE-LET relationship was investigated by fitting of polynomials from 1st to 5th degree to a database of 85 data points from aerobic in vitro experiments. We included both unweighted and weighted regression, the latter taking into account experimental uncertainties. Statistical testing was performed to decide whether higher degree polynomials provided better fits to the data as compared to lower degrees. The newly developed models were compared to three published LETd based models for a simulated spread out Bragg peak (SOBP) scenario. RESULTS: The statistical analysis of the weighted regression analysis favored a non-linear RBE-LET relationship, with the quartic polynomial found to best represent the experimental data (P = 0.010). The results of the unweighted regression analysis were on the borderline of statistical significance for non-linear functions (P = 0.053), and with the current database a linear dependency could not be rejected. For the SOBP scenario, the weighted non-linear model estimated a similar mean RBE value (1.14) compared to the three established models (1.13-1.17). The unweighted model calculated a considerably higher RBE value (1.22). CONCLUSION: The analysis indicated that non-linear models could give a better representation of the RBE-LET relationship. However, this is not decisive, as inclusion of the experimental uncertainties in the regression analysis had a significant impact on the determination and ranking of the models. As differences between the models were observed for the SOBP scenario, both non-linear LET spectrum- and linear LETd based models should be further evaluated in clinically realistic scenarios.

Treatment simulations with a statistical deformable motion model to evaluate margins for multiple targets in radiotherapy for high-risk prostate cancer.

BACKGROUND AND PURPOSE: Deformation and correlated target motion remain challenges for margin recipes in radiotherapy (RT). This study presents a statistical deformable motion model for multiple targets and applies it to margin evaluations for locally advanced prostate cancer i.e. RT of the prostate (CTV-p), seminal vesicles (CTV-sv) and pelvic lymph nodes (CTV-ln). MATERIAL AND METHODS: The 19 patients included in this study, all had 7-10 repeat CT-scans available that were rigidly aligned with the planning CT-scan using intra-prostatic implanted markers, followed by deformable registrations. The displacement vectors from the deformable registrations were used to create patient-specific statistical motion models. The models were applied in treatment simulations to determine probabilities for adequate target coverage, e.g. by establishing distributions of the accumulated dose to 99% of the target volumes (D99) for various CTV-PTV expansions in the planning-CTs. RESULTS: The method allowed for estimation of the expected accumulated dose and its variance of different DVH parameters for each patient. Simulations of inter-fractional motion resulted in 7, 10, and 18 patients with an average D99 >95% of the prescribed dose for CTV-p expansions of 3mm, 4mm and 5mm, respectively. For CTV-sv and CTV-ln, expansions of 3mm, 5mm and 7 mm resulted in 1, 11 and 15 vs. 8, 18 and 18 patients respectively with an average D99 >95% of the prescription. CONCLUSIONS: Treatment simulations of target motion revealed large individual differences in accumulated dose mainly for CTV-sv, demanding the largest margins whereas those required for CTV-p and CTV-ln were comparable.

Advances in radiotherapy: from 2D to 4D.

Imaging techniques are increasingly integrated into modern radiotherapy (RT). Multimodal imaging is used to define the target for RT planning and imaging technology is also being integrated into linear accelerators, with the purpose to ensure delivery of radiation with high geometric accuracy. The integration of imaging in RT calls for a stronger collaboration between diagnostic radiologists and the professions involved in RT.