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Purpose Patients with urinary bladder cancer are obvious candidates for adaptive radiotherapy (ART) due to large inter-fractional variation in bladder volumes. In this study we have compared the normal tissue sparing potential of two ART strategies: daily plan selection (PlanSelect) and daily plan re-optimisation (ReOpt). Materials and methods Seven patients with bladder cancer were included in the study. For the PlanSelect strategy, a patient-specific library of three plans was generated, and the most suitable plan based on the pre-treatment cone beam CT (CBCT) was selected. For the daily ReOpt strategy, plans were re-optimised based on the CBCT from each daily fraction. Bladder contours were propagated to the CBCT scan using deformable image registration (DIR). Accumulated dose distributions for the ART strategies as well as the non-adaptive RT were calculated. Results A considerable sparing of normal tissue was achieved with both ART approaches, with ReOpt being the superior technique. Compared to non-adaptive RT, the volume receiving more than 57 Gy (corresponding to 95% of the prescribed dose) was reduced to 66% (range 48–100%) for PlanSelect and to 41% (range 33–50%) for ReOpt. Conclusion This study demonstrated a considerable normal tissue sparing potential of ART for bladder irradiation, with clearly superior results by daily adaptive re-optimisation.

Background and purpose Many dose-limiting normal tissues in radiotherapy (RT) display considerable internal motion between fractions over a course of treatment, potentially reducing the appropriateness of using planned dose distributions to predict morbidity. Accounting explicitly for rectal motion could improve the predictive power of modelling rectal morbidity. To test this, we simulated the effect of motion in two cohorts. Materials and methods The included patients (232 and 159 cases) received RT for prostate cancer to 70 and 74 Gy. Motion-inclusive dose distributions were introduced as simulations of random or systematic motion to the planned dose distributions. Six rectal morbidity endpoints were analysed. A probit model using the QUANTEC recommended parameters was also applied to the cohorts. Results The differences in associations using the planned over the motion-inclusive dose distributions were modest. Statistically significant associations were obtained with four of the endpoints, mainly at high doses (55–70 Gy), using both the planned and the motion-inclusive dose distributions, primarily when simulating random motion. The strongest associations were observed for GI toxicity and rectal bleeding (Rs = 0.12–0.21; Rs = 0.11–0.20). Applying the probit model, significant associations were found for tenesmus and rectal bleeding (Rs = 0.13, p = 0.02). Conclusion Equally strong associations with rectal morbidity were observed at high doses (>55 Gy), for the planned and the simulated dose distributions including in particular random rectal motion. Future studies should explore patient-specific descriptions of rectal motion to achieve improved predictive power.

Background. The increasing complexity of radiotherapy (RT) has motivated research into three-dimensional (3D) dosimetry. In this study we investigate the use of 3D dosimetry with polymerizing gels and optical computed tomography (optical CT) as a verification tool for complex RT: dose painting and target tracking. Materials and Methods. For the dose painting studies, two dosimeters were irradiated with a seven-field intensity modulated radiotherapy (IMRT) plan with and without dose prescription based on a hypoxia image dataset of a head and neck patient. In the tracking experiments, two dosimeters were irradiated with a volumetric modulated arc therapy (VMAT) plan with and without clinically measured prostate motion and a third with both motion and target tracking. To assess the performance, 3D gamma analyses were performed between measured and calculated stationary dose distributions. Results. Gamma pass-rates of 95.3% and 97.3% were achieved for the standard and dose-painted IMRT plans. Gamma pass-rates of 91.4% and 54.4% were obtained for the stationary and moving dosimeter, respectively, while tracking increased the pass-rate for the moving dosimeter to 90.4%. Conclusions. This study has shown that the 3D dosimetry system can reproduce and thus verify complex dose distributions, also when influenced by motion.

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.

The aim of this study was to investigate whether the stopping power ratio (SPR) of a deformable, silicone-based 3D dosimeter could be determined more accurately using dual energy (DE) CT compared to using conventional methods based on single energy (SE) CT. The use of SECT combined with the stoichiometric calibration method was therefore compared to DECT-based determination.The SPR of the dosimeter was estimated based on its Hounsfield units (HUs) in both a SECT image and a DECT image set. The stoichiometric calibration method was used for converting the HU in the SECT image to a SPR value for the dosimeter while two published SPR calibration methods for dual energy were applied on the DECT images. Finally, the SPR of the dosimeter was measured in a 60 MeV proton by quantifying the range difference with and without the dosimeter in the beam path.The SPR determined from SECT and the stoichiometric method was 1.10, compared to 1.01 with both DECT calibration methods. The measured SPR for the dosimeter material was 0.97.The SPR of the dosimeter was overestimated by 13% using the stoichiometric method and by 3% when using DECT. If the stoichiometric method should be applied for the dosimeter, the HU of the dosimeter must be manually changed in the treatment planning system in order to give a correct SPR estimate. Using a wrong SPR value will cause differences between the calculated and the delivered treatment plans.

Background and purpose Radiotherapy (RT) induced genitourinary (GU) morbidity is typically assessed by physicians as single symptoms or aggregated scores including symptoms from various domains. Here we apply a method to group patient-reported GU symptoms after RT for localized prostate cancer based on their interplay, and study how these relate to urinary bladder dose. Materials and methods Data were taken from two Scandinavian studies ( N =207/276) including men treated with external-beam RT (EBRT) to 78/70Gy (2Gy/fraction; median time-to-follow-up: 3.6–6.4y). Within and across cohorts, bladder dose–volume parameters were tested as predictors for GU symptom domains identified from two study-specific questionnaires (35 questions on frequency, incontinence, obstruction, pain, urgency, and sensory symptoms) using univariate and multivariate logistic regression analysis (MVA) with 10-fold cross-validation. Performance was evaluated using Area Under the Receiver Operating Characteristic Curve (A z ). Results For the identified Incontinence (2–5 symptoms), Obstruction (3–5 symptoms), and Urgency (2–7 symptoms) domains, MVA demonstrated that bladder doses close to the prescription doses were the strongest predictors for Obstruction (A z : 0.53–0.57) and Urgency (A z : 0.60). For Obstruction , performance increased for the across cohort analysis (A z : 0.61–0.64). Conclusions Our identified patient-reported GU symptom domains suggest that high urinary bladder doses, and increased focus on both obstruction and urgency is likely to further add to the understanding of GU tract RT responses.

Background Adaptive radiotherapy is introduced in the management of urinary bladder cancer to account for day-to-day anatomical changes. The purpose of this study was to determine whether an adaptive plan selection strategy using either the first four cone beam computed tomography scans (CBCT-based strategy) for plan creation, or the interpolation of bladder volumes on pretreatment CT scans (CT-based strategy), is better in terms of tumor control probability (TCP) and normal tissue sparing while taking the clinically applied fractionation schedules also into account. Material and methods With the CT-based strategy, a library of five plans was created. Patients received 55 Gy to the bladder tumor and 40 Gy to the non-involved bladder and lymph nodes, in 20 fractions. With the CBCT-based strategy, a library of three plans was created, and patients received 70 Gy to the tumor, 60 Gy to the bladder and 48 Gy to the lymph nodes, in 30–35 fractions. Ten patients were analyzed for each adaptive plan selection strategy. TCP was calculated applying the clinically used fractionation schedules, as well as a rescaling of the dose from 55 to 70 Gy for the CT-based strategy. For rectum and bowel, equivalent doses in 2 Gy fractions (EQD2) were calculated. Results The CBCT-based strategy resulted in a median TCP of 75%, compared to 49% for the CT-based strategy, the latter improving to 72% upon rescaling the dose to 70 Gy. A median rectum V30Gy (EQD2) of 26% [interquartile range (IQR): 8–52%] was found for the CT-based strategy, compared to 58% (IQR: 55–73%) for the CBCT-based strategy. Also the bowel doses were lower with the CT-based strategy. Conclusions Whereas the higher total bladder TCP for the CBCT-based strategy is due to prescription differences, the adaptive strategy based on CT scans results in the lowest rectum and bowel cavity doses.

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.

Background and purpose Standard tumour control probability (TCP) models assume uniform tumour cell density across the tumour. The aim of this study was to develop an individualised TCP model by including index-tumour regions extracted form multi-parametric magnetic resonance imaging (MRI) and apparent diffusion coefficient (ADC) maps-based cell density distributions. Materials and methods ADC maps in a series of 20 prostate cancer patients were applied to estimate the initial number of cells within each voxel, using three different approaches for the relation between ADC values and cell density: a linear, a binary and a sigmoid relation. All TCP models were based on linear-quadratic cell survival curves assuming α / β =1.93Gy (consistent with a recent meta-analysis) and α set to obtain a 70% of TCP when 77Gy was delivered to the entire prostate in 35 fractions ( α =0.18Gy −1 ). Results Overall, TCP curves based on ADC maps showed larger differences between individuals than those assuming uniform cell densities. The range of the dose required to reach 50% TCP across the patient cohort was 20.1Gy, 18.7Gy and 13.2Gy using an MRI-based voxel density (linear, binary and sigmoid approach, respectively), compared to 4.1Gy using a constant density. Conclusions Inclusion of tumour-index information together with ADC maps-based cell density increases inter-patient tumour response differentiation for use in prostate cancer RT, resulting in TCP curves with a larger range in D 50% across the cohort compared with those based on uniform cell densities.

Purpose: Both temporal and thermal dependencies of the dose response have been observed in radiochromic dosimeters. As these dependencies may be influenced by the dose level, the present study investigates the temperature dependence during irradiation and the temporal change of the optical response following irradiation of radiochromic dosimeters at a range of doses. Methods: Cuvette samples of the PRESAGE Trade-Mark-Sign radiochromic dosimeter were irradiated within a dose range of 0-10 Gy at irradiation temperatures within 5-35 Degree-Sign C and postirradiation storage within 6-30 Degree-Sign C. The optical response due to irradiation was measured using a standard spectrophotometer and the data were analyzed in terms of thermal and temporal change. Results: The initial dose response was linear over the applied dose range independent of irradiation temperature. However, the optical response to a specific dose increased exponentially with irradiation temperature corresponding to an activation energy of 0.114 {+-} 0.007 eV. The temporal change in dose response after irradiation consisted of an offset, an auto-oxidation rate with activation energy 0.84 {+-} 0.03 eV, and an initial exponential increase in optical response (1.6 {+-} 0.2 eV) followed by an exponential decrease in optical response (0.98 {+-} 0.08 eV). These contributions depended on both storagemore » temperature and the dose given, leading to a nonlinear dose response with time at low storage temperatures and a high auto-oxidation rate at high storage temperatures. Conclusions: Thermal equilibration is important to the radiochromic dosimeter investigated due to an exponential change in dose response with irradiation temperature and a considerable postirradiation temporal change in response. For the dosimeter version investigated in this study, a compromise in storage temperature has to be made between increasing the nonlinearity of the dose response with time and inducing a high auto-oxidation rate.« less

Variations in bladder position, shape and volume cause uncertainties in the doses delivered to this organ during a course of radiotherapy for pelvic tumors. The purpose of this study was to evaluate the potential of dose accumulation based on repeat imaging and deformable image registration (DIR) to improve the accuracy of bladder dose assessment. For each of nine prostate cancer patients, the initial treatment plan was re-calculated on eight to nine repeat computed tomography (CT) scans. The planned bladder dose-volume histogram (DVH) parameters were compared to corresponding parameters derived from DIR-based accumulations as well as DVH summation based on dose re-calculations. It was found that the deviations between the DIR-based accumulations and the planned treatment were substantial and ranged (-0.5-2.3) Gy and (-9.4-13.5) Gy for D(2%) and D(mean), respectively, whereas the deviations between DIR-based accumulations and DVH summation were small and well within 1 Gy. For the investigated treatment scenario, DIR-based bladder dose accumulation did not result in substantial improvement of dose estimation as compared to the straightforward DVH summation. Large variations were found in individual patients between the doses from the initial treatment plan and the accumulated bladder doses. Hence, the use of repeat imaging has a potential for improved accuracy in treatment dose reporting.

Background and purpose Radiation-induced cancer is a serious late effect that may follow radiotherapy. A considerable uncertainty is associated with carcinogenesis from photon-based treatment, and even less established when including relative biological effectiveness (RBE) for particle therapy. The aim of this work was therefore to estimate and in particular explore relative risks (RR) of secondary cancer (SC) following particle therapy as applied in treatment of prostate cancer. Material and methods RRs of radiation-induced SC in the bladder and rectum were estimated using a bell-shaped dose–response model incorporating RBE and fractionation effects. The risks from volumetric modulated arc therapy (VMAT) were compared to intensity-modulated proton therapy (IMPT) and scanning carbon ions for ten patients. Results The mean estimated RR (95% CI) of SC for VMAT/C-ion was 1.31 (0.65–2.18) for the bladder and 0.58 (0.41–0.80) for the rectum. Corresponding values for VMAT/IMPT were 1.72 (1.06–2.37) and 1.10 (0.78–1.43). The radio-sensitivity parameter α had the strongest influence on the results with decreasing RR for increasing values of α . Conclusion Based on the wide spread in RR between patients and variations across the included parameter values, the risk profiles of the rectum and bladder were not dramatically different for the investigated radiotherapy techniques.

Lung cancer patients referred to radiotherapy (RT) often present with regional lung function deficits, and it is therefore of interest to image their lung function prior to treatment. In this study a method was developed that uses a deformable image registration (DIR) between the peak-inhale and peak-exhale phases of a thoracic four-dimensional computed tomography (4D-CT) scan to extract ventilation information. The method calculates the displacement vector fields (DVFs) resulting from the DIR using the Jacobian map approach in order to extract information regarding regional lung volume change.The DVFs resulting from DIRs were analysed to compute the Jacobian determinant of vectors in the field, thus obtaining a map of the vector gradients of the entire registered CT image, i.e. voxel-wise local volume change. Geometric and quantitative validation was achieved using images of both phantoms and patients. In the phantom studies, translations and deformations of known size and direction were introduced to validate both the DIR algorithm and the method as a whole. Furthermore, five patients underwent 4D-CT for planning of stereotactic body RT (SBRT). The patients were immobilised in a stereotactic body frame (SBF) and for each patient, two thoracic 4D-CT scans were acquired, one scan with respiration restricted by an abdominal compression plate and the other under free breathing.In the phantom studies deformation errors were found to be of the order of the expected precision of 3 mm, corresponding to the image slice distance, in lateral and vertical directions. For the longitudinal direction a more pronounced discrepancy was observed, with the algorithm predicting displacement lengths of less than half of the physically introduced deformation. Qualitatively the method performed as expected. In the patient study an inverse consistency test showed deviations of up to 5.8 mm, i.e. almost twice the image slice separation. Jacobian maps of the patient images indicated well-ventilated areas as anatomically expected.The established method provides a means of using a (commercially available) DIR algorithm to obtain a quantitative measure of local lung volume change. With further phantom and patient validation studies, quantitative maps of specific ventilation should be possible to produce and use in a clinical setting.

Background and purpose. Daily organ motion occurring during the course of radiotherapy in the pelvic region leads to uncertainties in the doses delivered to the tumour and the organs at risk. Motion patterns include both volume and shape changes, calling for deformable image registration (DIR), in approaches involving dose accumulation and adaptation. In this study, we tested the performance of a DIR application for contour propagation from the treatment planning computed tomography (pCT) to repeat cone-beam CTs (CBCTs) for a set of prostate cancer patients. Material and methods. The prostate, rectum and bladder were delineated in the pCT and in six to eight repeat CBCTs for each of five patients. The pCT contours were propagated onto the corresponding CBCT using the Multi-modality Image Registration and Segmentation application, resulting in 36 registrations. Prior to the DIR, a rigid registration was performed. The algorithm used for the DIR was based on a 'demons' algorithm and the performance of it was examined quantitatively using the Dice similarity coefficient (DSC) and qualitatively as visual slice-by-slice scoring by a radiation oncologist grading the deviations in shape and/or distance relative to the anatomy. Results. The average DSC (range) for the DIR over all scans and patients was 0.80 (0.65-0.87) for prostate, 0.77 (0.63-0.87) for rectum and 0.73 (0.34-0.91) for bladder, while the corresponding DSCs for the rigid registrations were 0.77 (0.65-0.86), 0.71 (0.55-0.82) and 0.64 (0.33-0.87). The percentage of propagated contours of good/acceptable quality was 45% for prostate; 20% for rectum and 33% for bladder. For the bladder, there was an association between the average DSC and the different scores of the qualitative evaluation. Conclusions. DIR improved the performance of pelvic organ contour propagation from the pCT to CBCTs as compared to rigid registration only. Still, a large fraction of the propagated rectum and bladder contours were unacceptable. The image quality of the CBCTs was sub-optimal and the usability of CBCTs for dose accumulation and adaptation purposes is therefore likely to benefit from improved image quality and improvements of the DIR algorithm.

Stereotactic body radiotherapy (SBRT) is often the preferred treatment for the advanced liver tumours which owing to tumour distribution, size and multi-focality are out of range of surgical resection or radiofrequency ablation. However, only a minority of patients with liver tumours may be candidates for conventional SBRT because of the limited radiation tolerance of normal liver, intestine and other normal tissues. Due to the favourable depth-dose characteristics of protons, intensity-modulated proton therapy (IMPT) may be a superior alternative to photon-based SBRT. The purpose of this treatment planning study was therefore to investigate the potential sparing of normal liver by IMPT compared to photon-based intensity-modulated radiotherapy (IMRT) for solitary liver tumours.Ten patients with solitary liver metastasis treated at our institution with multi-field SBRT were retrospectively re-planned with IMRT and proton pencil beam scanning techniques. For the proton plans, two to three coplanar fields were used in contrast to five to six coplanar and non-coplanar photon fields. The same planning objectives were used for both techniques. A risk adapted dose prescription to the PTV surface of 12.5-16.75 Gy × 3 was used.The spared liver volume for IMPT was higher compared to IMRT in all 10 patients. At the highest prescription dose level, the median liver volume receiving less than 15 Gy was 1411 cm(3) for IMPT and 955 cm(3) for IMRT (p0.005); also the mean liver dose was lower with IMPT compared to IMRT (median 9.1 Gy vs. 20.0 Gy; p0.005). All IMPT and IMRT plans met the V(D15 Gy)700 cm(3) constraint. For the D(mean) ≤ 15 Gy constraint, nine of 10 cases could be treated at the highest dose level using IMPT whereas with IMRT, only two cases met this constraint at the highest dose level and six at the lowest dose level.A considerable sparing of normal liver tissue can be obtained using proton-based SBRT for solitary liver tumours.

PURPOSE The dose response of radiochromic dosimeters is based on radiation-induced chemical reactions and is thus likely to be thermally influenced. In this study we have therefore investigated the temperature dependence of the dose response for such dosimeters, regarding both irradiation and storage conditions. METHODS Dosimeter samples in cuvettes were irradiated to 5 Gy. The temperature for the different cuvettes during irradiation and post-irradiation storage was varied in the range of 3-30 degrees C in order to quantify the temperature dependence of the dosimeter response. The optical properties of the dosimeter samples were measured using a spectrophotometer before irradiation as well as at several times after irradiation to quantify the temporal variation of dose response (expressed as the optical density change induced by irradiation) as a function of storage temperature. RESULTS The measurements show considerable temperature dependencies of dose response both during irradiation and storage. Fit to an Arrhenius equation revealed an activation energy of 1.4 +/- 0.2 eV for the variation in irradiation temperature, indicating a contribution from a thermally activated process. Variation in dose response at different storage temperatures showed an exponential increase with time followed by a decrease in optical density. Exponential Arrhenius fits to rate constants gave activation energies of 1.7 +/- 0.2 eV for the increase in dose response and 2.3 +/- 0.5 eV for the subsequent decrease, in this case dominated by thermally activated processes. CONCLUSIONS Due to the exponential dependencies, stabilization of the dosimeter during irradiation at low temperatures (e.g., 5 degrees C) is preferable in clinical use to optimize the accuracy of the dose response. In addition, a low storage temperature is recommended in order to minimize the post-irradiation temporal change in dose response and thereby increase the post-irradiation stability of the dosimeter. The measurements in this study show that if the observed temperature and temporal dependencies are not considered, this could potentially deteriorate the accuracy of the dosimeter.

Purpose: Volumetric modulated arc therapy (VMAT) includes features such as a variable dose rate and gantry speed in addition to the beam modulation achieved with multileaf collimator (MLC) motion patterns employed in intensity modulated radiotherapy. Three tests have previously been proposed for the evaluation of the performance of VMAT delivery. In order to enable a convenient and accurate routine machine quality control (QC) program, the present study proposes tolerance levels for these tests based on a department-wide implementation of an electronic portal imaging device (EPID)-based QC. Methods: Three different VMAT tests--a picket fence (PF) test, a dose rate versus gantry speed (DRGS) test, and a dose rate versus MLC leaf speed (DRMLC) test--were performed on nine accelerators using two different EPIDs (aS1000 and aS500, Varian Medical Systems). All tests were repeated six times for each accelerator. The images were analyzed using an in-house-developed software. For the PF test, the positions and widths of individual MLC leaf gaps were compared to the mean value. In the DRGS and DRMLC tests, different combinations of dose rate, gantry speed, and MLC leaf speed were used to deliver identical doses to separate parts of the EPID. The tests were evaluated by looking for deviationsmore » in the constancy of the measured dose for the preset combinations of dose rate, gantry speed, and MLC leaf speed. Results: For the PF test, a 0.3 mm tolerance level was suggested for the positioning of the MLC leaves. The tolerance level for the gap width was 0.5 mm. For the DRGS and DRMLC tests, a 3% tolerance level was proposed. Conclusions: With the adapted levels of tolerance for an EPID-based approach, the PF, the DRGS, and the DRMLC tests offer a convenient and accurate machine QC program for linear accelerators used for VMAT.« less

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.

This and the preceding issue of Acta Oncologica contain several papers adding to our understanding, and ability to predict, normal tissue morbidity in individual patients treated with radiotherapy ...

The urinary bladder shows considerable individual variation in shape and position during a course of radiotherapy (RT). In this study we have developed and compared three different adaptive RT (ART) strategies for bladder cancer involving daily cone beam CT (CBCT) imaging and plan selection. Material and methods. Ten patients treated for bladder cancer had daily CBCTs acquired that were registered online using bony anatomy registration. Seven patients received intensity modulated RT (IMRT) with a simultaneous integrated boost (SIB) technique to the bladder and pelvic lymph nodes. Three patients received treatment to the bladder only. Retrospectively, we compared three ART strategies that were all based on daily selection of the most suitable plan from a library consisting of three IMRT-plans corresponding to a small, medium and large target volume. ART method A utilised population-based margins while methods B and C used the bladder as seen on CBCTscans from the fi rst week of treatment; method B without delineation of the bladder on CBCT and method C with delineation of the bladder. Total dose distributions were calculated using the planning CT. For each patient, we calculated ratios of the dose volume histograms (DVHs) for the three ART strategies relative to non-adaptive therapy. Results. The interpatient variation was large for all three ART strategies. The mean ratios of the volumes receiving 57 Gy or more (corresponding to 95% of prescribed dose) for methods A, B and C were 0.66 (SD: 0.11), 0.67 (SD: 0.13) and 0.67 (SD: 0.16) respectively when compared to the non-adaptive plan. Conclusion. When using any of the ART strategies, it is possible to reduce signifi cantly the volumes receiving high doses compared to the use of a standard non-adaptive plan. The differences in dose volume parameters between the three methods were small compared with the differences from the standard plan.

There is growing clinical evidence that functional imaging is useful for target volume definition and early assessment of tumour response to external beam radiotherapy. A subject that has perhaps received less attention, but is no less promising, is the application of functional imaging to the prediction or measurement of radiation adverse effects in normal tissues. In this manuscript, we review the current published literature describing the use of positron emission tomography (PET), four-dimensional computed tomography (4D-CT), single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) to study normal tissue function in the context of radiotherapy to the lung, liver and head & neck. Published results to date demonstrate that functional imaging can be used to preferentially avoid normal tissues not easily identifiable on solely anatomical images. It is also a potentially very powerful tool for the early detection of radiotherapy-induced normal tissue adverse effects and could provide valuable data for building predictive models of outcome. However, one of the major challenges to building useful predictive models is that, to date, there are very little data available with combined images of normal function, 3D delivered radiation dose and clinical outcomes. Prospective data collection through well-constructed studies which use established morbidity scores is clearly a priority if significant progress is to be made in this area.

The rectum is a major dose-limiting organ at risk (OR) in radiotherapy (RT) of prostate cancer. Methods to predict adverse effects in the rectum are therefore important but their precision often limited, not the least by the internal motion of this organ. In this study late rectal morbidity is investigated in relation to the internal motion of the rectum by applying the 'Planning organ at Risk Volume' (PRV) concept.Late rectal morbidity was analysed in 242 prostate cancer patients treated to 70 Gy with conformal RT to either the prostate, the prostate and seminal vesicles or the whole pelvis (initial 50 Gy only). Late rectal morbidity was classified by the late gastro-intestinal (GI) RTOG toxicity scoring system. Cumulative dose-volume histograms (DVHs) were derived for the rectum OR and six rectum PRVs i.e. the OR expanded with six different margins (narrow/intermediate/wide in anterior direction or in both anterior and posterior direction). The difference in rectum dose-volume parameters between patients with Grade 0-1 vs. Grade 2 or higher morbidity was investigated by logistic regression and permutation tests.Late Grade 2 or higher morbidity was observed in 25 of 242 (10%) patients. The logistic regression analysis and the permutation tests reached significance (p ≤ 0.05) for only one dose level of the rectum OR (40 Gy). For the PRVs, several dose levels were found to be significant (p-value range: 0.01-0.046), most pronounced for the PRV with narrow margins of 6 mm anterior and 5 mm posterior with five intermediate (38-42 Gy) and ten high (62-71 Gy) dose levels.The statistical methods applied displayed consistently a small though significant difference in DVH parameters between patients with vs. without Grade 2 or higher late rectal morbidity for intermediate and high dose levels. The difference became most evident when using a PRV with narrow margins.

Purpose Modern radiotherapy (RT) protocols for prostate cancer often involve the use of narrow margins and image-based monitoring of rectum/bladder fill status. These protocols have allowed safe prostate dose escalation, maintaining acceptable levels for organs at risk (bladder and rectum). However, daily cone-beam CT (CBCT) image-guided RT has demonstrated considerable bladder volume variation throughout treatment, which suggests dose delivered may vary. By using CBCT-based parametrized 2D dose surface maps (DSM) of the inferior bladder, this study aims to evaluate bladder volume impact on bladder DSMs during high-precision RT for prostate cancer. Methods Seven prostate cancer patients treated using daily CBCT-based image-guided VMAT/IMRT were included in this study (81.0 Gy prescription dose). Planning CT and RT delivery adhered to a full bladder/empty rectum protocol, where daily CBCTs were used for patient realignment and to assess bladder/rectum filling status. Fourteen CBCTs per patient were rigidly registered to the planning CT using recorded treatment shifts, and the bladder was manually contoured on each CBCT. Contours were validated by the responsible radiation oncologist. For the planning CT and each CBCT, bladder wall dose was digitally projected onto 1024x1024 DSMs using orthographic ray-traced surface dose sampling. Bladder wall volumetric meshes were generated from contours using restricted Delaunay triangulation. Surface dose was sampled at ray-wall intersections, sub-pixel sampling was used to improve image quality, and rays were oriented parallel to the prostate-bladder center-of-mass connecting line. DSM dose distributions were compared between planned and delivered. Correlation with bladder volume variations was evaluated. Results Bladder volumes varied considerably during RT (15–42%), with slightly larger volumes at planning compared to treatment (p = 0.16). Differences at the central part of the DSM ranged between 1% and 7%. Overall, delivered doses were lower at the central part of the DSM compared to planned (range: −5.4 to 0.9 Gy). Plan-vs-delivery mean dose differences were slightly correlated with bladder volume differences (Rs = 0.55, p = 0.3). Conclusions No significant variations were observed in delivered doses at the interior part of the bladder although considerable bladder volume changes occurred during the RT course. The generally smaller treatment bladder volume possibly explains lower dose delivered to the inferior bladder sector.

Purpose Multi-parametric MRI (mp-MRI) is being introduced in radiotherapy (RT) of prostate cancer for tumour delineation in focal boosting strategies. It has been shown that the apparent diffusion coefficient (ADC) from diffusion weighted MRI (DW-MRI) may reflect cell density. Apart from tumour volume and cell densities, tumour hypoxia is also an important determinant of RT response. In this study we investigate the patterns of ADC and haemodynamic maps, and the relations between them, inside the index lesion. Methods ADC and perfusion maps from 10 prostate cancer patients were used, with the prostate and index lesion delineated by an experienced uro-radiologist. Associations between different ADC and perfusion histogram parameters inside the index lesion were evaluated with the Pearson’s correlation coefficient (PCC). In the voxel-wise analysis, scatter plots of ADC vs perfusion were analysed for voxels in the index lesion, again with the associations quantified with the PCC. Voxels that were in the lower quartile of both ADC and the forward transport rate constant ( K trans ) were assumed to be poorly oxygenated. Results ADC and the extravascular-extracellular volume fraction ( V e ) were overall lower inside the index lesion than outside. The opposite was observed for K trans that was higher inside the index lesion than outside. In the distribution analysis, the maximum K trans was significantly correlated with the maximum ADC (rho = 0.85). At the voxel level inside the index lesion, significant inverse correlation between ADC and K trans and significant positive correlation between ADC and V e were observed for nine of ten patients. According to our definition, 8% of the index lesion was poorly oxygenated. Conclusions A general negative correlation was seen in the index lesion between ADC and K trans while a general positive correlation was seen in the index lesion for ADC vs. V e . A method of estimating poor oxygenation in the index lesion was developed, based on diffusion and haemodynamic maps.

Udgivelsesdato: 2008-Apr-1 PURPOSE: To investigate the incidence, time course, and relation to irradiated volumes of late morbidity after three-dimensional conformal radiation therapy (RT) for prostate cancer. METHODS AND MATERIALS: From January 2000 to December 2001, a total of 247 patients with prostate cancer received a target dose of 70 Gy using conformal RT. Forty-eight patients (20%) received irradiation to the prostate only (Group P), 154 patients (62%) received irradiation to the prostate and seminal vesicles (Group PSV), and 45 patients (18%) received modified pelvic fields (Group MPF). Androgen deprivation was given to 86% of patients. Median follow-up was 62 months. Late gastrointestinal (GI) and genitourinary (GU) morbidity were recorded according to the Radiation Therapy Oncology Group scoring system. RESULTS: We observed 9%, 7%, and 25% Grade 2 or higher GI morbidity and 36%, 30%, and 21% Grade 2 or higher GU morbidity in Groups P, PSV, and MPF, respectively. In multivariate analyses, age and treatment group were independent predictors for the incidence of late Grade 2 or higher GI morbidity, whereas age and urinary symptoms before treatment were independent predictors for late Grade 2 or higher GU morbidity. Acute side effects predicted for late effects. The rectum dose-volume histogram parameters correlated with the incidence of late Grade 2 or higher GI morbidity, especially the fractional volume receiving more than 40-43 Gy. At 5 years of follow-up, the rate of Grade 2 late GI morbidity was only 1.4%, and Grade 2 or higher GU morbidity was 10.6%. CONCLUSIONS: The data presented here show that late GI morbidity after prostate RT is low and subsides with time.

PURPOSE: The use of marker-based on-line image guided radiotherapy for prostate cancer has considerably reduced the treatment margins to sub-cm. In this study we have quantified the residual set-up errors remaining after isocenter correction, studied their development during beam delivery and estimated their impact on margins. METHODS AND MATERIALS: After initial on-line patient set-up based on orthogonal kV x-ray images of implanted fiducial markers, continuous electronic portal imaging was performed during treatment delivery in 10 of 39 treatment sessions for 20 prostate cancer patients. The cranio-caudal (CC) position of the centre-of-mass of the three markers was found using a threshold technique on every single image frame for all patients, typically 12-14 images for 5 treatment beams in every fraction. The CC prostate position was determined relative to its initial position at treatment onset and relative to its planned position within the field aperture. These results allowed determination of the CC intrafraction prostate motion and the intrafraction progression of the geometrical CC error, respectively. RESULTS: At treatment onset the standard deviation (SD) of the set-up error was 1.0mm in the lateral direction and 1.5mm in the cranio-caudal (CC) direction. It did not depend significantly on the duration of the set-up procedure (mean: 3.0 min, span 1.2-14.6 min). The distribution of CC prostate positions relative to the position at treatment onset broadened from 0 to 1.4mm during the treatment session, while the corresponding CC setup error distribution broadened from 1.5 to 1.9 mm. This broadening means that the necessary CC setup margin increased by around 1mm during the treatment fraction. CONCLUSIONS: Large differences in the intrafraction CC prostate motion patterns were found, however, intrafraction motion only results in a modest additional CC set-up margin of around 1mm relative to the margins needed for the residual set-up error at treatment start.