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Background and purpose: Xerostomia remains a common side effect of radiotherapy (RT) for patients with head and neck (H&N) cancer despite advancements in treatment planning and delivery. Secretory salivary gland cells express the prostate-specific membrane antigen (PSMA), and show significant uptake on PET scans using 68Ga/18F-PSMA-ligands. We aimed to objectively quantify the dose–response of salivary glands to RT using PSMA PET. Methods and materials: 28H&N cancer patients received RT with 70 Gy in 35 fractions over 7 weeks. PSMA PET/CT was acquired at baseline (BL), during treatment (DT) and at 1-&6-months post-treatment (PT1M/PT6M). Dose, BL- PT1M- and PT6M-SUV were extracted for every voxel inside each parotid (PG) and submandibular (SMG) gland. The PT1M/6M data was analysed using a generalised linear mixed effects model. Patient-reported xerostomia and DT-PSMA loss was also analysed. Results: Dose had a relative effect on BL SUV. For a population average gland (BL-SUV of 10), every 1 Gy increment, decreased the PT1M/PT6M-SUV by 1.6 %/1.6 % for PGs and by 0.9 %/1.8 % for SMGs. TD50 of the population curves was 26.5/31.3 Gy for PGs, and 22.9/27.8 Gy for SMGs at PT1M /PT6M. PSMA loss correlated well with patient-reported xerostomia at DT/PT1M (Spearman's ρ = -0.64, −0.50). Conclusion: A strong relationship was demonstrated between radiation dose and loss of secretory cells in salivary glands derived using PSMA PET/CT. The population curve could potentially be used as a dose planning objective, by maximising the predicted post-treatment SUV. BL scans could be used to further tailor this to individual patients.

Purpose To test if the relative change in FDG-PET SUVmax over the course of treatment was associated with disease progression and overall survival. Additionally, the prognostic values of other first-order PET-metric changes were investigated. Methods The study included 38 patients with stage II–III NSCLC, who underwent concurrent chemoradiotherapy. Patients received two pre-treatment FDG-PET scans and four during-treatment scans at weekly intervals. SUVmax was normalized to the start of treatment and analyzed using linear regression. Linear regression coefficients of other first order PET-metrics were grouped according to dissimilarity. Associations to patient outcome were analyzed using Cox hazard ratio. Results Twenty-eight patients satisfied the criteria for analysis. All PET-metrics demonstrated a strong linear correlation with time during treatment [median R-range: −0.87: −0.97]. No strong associations (p > 0.10) were found for the relative slope of SUVmax to patient outcomes. Other first-order metrics did correlate with outcome but the single imaging time-point maximizing the association of PET response with outcome varied per PET metric and outcome parameter. Conclusion All investigated FDG PET metrics linearly decreased during treatment. Relative change in SUVmax was not associated to patient outcome while several other first order PET-metrics were related to patient outcome. A single optimal imaging time-point could not be identified.

PurposeRespiratory-induced motion of oesophageal tumours and lymph nodes can influence positron emission tomography/computed tomography (PET/CT). The aim was to compare standard three-dimensional (3D) and motion-compensated PET/CT regarding standardized uptake value (SUV), metabolic tumour volume (MTV) and detection of lymph node metastases. MethodsThis prospective observational study (NCT02424864) included thirty-seven newly diagnosed oesophageal cancer patients. Diagnostic PET/CT was reconstructed in 3D and motion-compensated PET/CT. MTVs of the primary tumour were calculated using an automated region-growing algorithm with SUV thresholds of 2.5 (MTV2.5) and ≥50% of SUVmax (MTV50%). Blinded for reconstruction method, a nuclear medicine physician assessed all lymph nodes showing 18F-fluorodeoxyglucose uptake for their degree of suspicion. ResultsThe mean (95% CI) SUVmax of the primary tumour was 13.1(10.6-15.5) versus 13.0(10.4-15.6) for 3D and motion-compensated PET/CT, respectively. MTVs were also similar between the two techniques. Bland-Altman analysis showed mean differences between both measurements (95% limits of agreement) of 0.08(-3.60 - 3.75), -0.26(-2.34 – 1.82), 4.66(-29.61 – 38.92)cm3 and -0.95(-19.9 – 18.0)cm3 for tumour SUVmax, lymph node SUVmax, for MTV2.5 and MTV50%, respectively. Lymph nodes were classified as highly suspicious (30/34 nodes), suspicious (20/22) and dubious (66/59) for metastases on 3D/motion-compensated PET/CT. No additional lymph node metastases were found on motion-compensated PET/CT. SUVmax of the most intense lymph nodes was similar for both scans: mean (95% CI) 6.6(4.3-8.8) and 6.8(4.5-9.1) for 3D and motion-compensated, respectively.ConclusionsSUVmax of the primary oesophageal tumour and lymph nodes was comparable on 3D and motion-compensated PET/CT. The use of motion-compensated PET/CT did not improve lymph node detection. Trial registration(www.clinicaltrials.gov: NCT02424864)

Purpose We investigated in a single-center prospective trial (NCT03376386) the use of serial fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) to determine the boost dose and to guide boost segmentation in head and neck cancer. Methods and Materials Patients were eligible when treated with curative radiation therapy with or without systemic treatment for T2-4 squamous cell carcinoma of the hypopharynx, larynx, or oropharynx (20 patients in total). FDG-PET/CT scans were made at baseline and for redelineation and replanning at the end of weeks 2 and 4 of radiation therapy. The metabolically active part of the primary tumor received a 4 Gy boost on top of the 70 Gy baseline dose per partial metabolic response. The study would be considered feasible when ≥80% of adaptations were successful and no Common Terminology Criteria for Adverse Events grade ≥4 acute toxicity occurred. Results One patient received 70 Gy after complete metabolic response in week 2, and 12 patients received 78 Gy because of partial metabolic response at weeks 2 and 4. Seven patients received 74 Gy, either because of complete metabolic response at week 4 (n = 3) or a missed FDG-PET/CT (n = 4). The patients missed their FDG-PET/CT scans because they did not fast (n = 2) or at patients’ request (n = 2). In addition to the 4 missed FDG-PET/CT scans, 2 adaptive plans could not be finished successfully owing to logistical problems. In total, 85% of adaptations were completed correctly. No patient experienced grade ≥4 toxicity, and 40% had grade 3 dysphagia (tube feeding) during treatment. This decreased at 12 weeks posttreatment to 20%. Conclusions This prospective trial demonstrates the feasibility of serial FDG-PET/CT scans for dose escalation and patient selection.

Purpose To benchmark and improve, through means of a targeted intervention, the quality of intensity modulated radiation therapy treatment planning for locally advanced head and neck cancer (HNC) in the Netherlands. The short and long-term impact of this intervention was assessed. Methods and materials A delineated computed tomography-scan of an oropharynx HNC case was sent to all 15 Dutch radiation therapy centers treating HNC. Aims for planning target volume and organ-at-risk (OAR) dosimetry were established by consensus. Each center generated a treatment plan. In a targeted intervention, OAR sparing of all plans was discussed, and centers with the best OAR sparing shared their planning strategies. Impact of the intervention was assessed by (1) short-term (half a year after intervention) replanning of the original case and (2) long-term (1 and 3 years after intervention) planning of new cases. Results Benchmarking revealed substantial difference in OAR doses. Initial mean doses were 22 Gy (range, 15-31 Gy), 35 Gy (18-49 Gy), and 37 Gy (20-46 Gy) for the contralateral parotid gland, contralateral submandibular gland, and combined swallowing structures, respectively. Replanning after targeted intervention significantly reduced mean doses and variation, but clinically relevant differences still remained: 18 Gy (14-22 Gy), 28 Gy (17-45 Gy), and 29 Gy (18-39 Gy), respectively. One and 3 years later the variation remained stable. Conclusions Despite many years of HNC intensity modulated radiation therapy experience, initial treatment plans showed surprisingly large variations. The simple targeted intervention used in this analysis improved OAR sparing, and its impact was durable; however, fairly large dose differences still continue to exist. Additional work is needed to understand these variations and to minimize them. A national radiation oncology platform can be instrumental for developing and maintaining high-quality planning protocols.

Respiratory-induced motion of oesophageal tumours and lymph nodes can influence positron-emission tomography/computed tomography (PET/CT). The aim was to compare standard three-dimensional (3D) and motion-compensated PET/CT regarding standardized uptake value (SUV), metabolic tumour volume (MTV) and detection of lymph node metastases.This prospective observational study (NCT02424864) included 37 newly diagnosed oesophageal cancer patients. Diagnostic PET/CT was reconstructed in 3D and motion-compensated PET/CT. MTVs of the primary tumour were calculated using an automated region-growing algorithm with SUV thresholds of 2.5 (MTV2.5) and ≥ 50% of SUVmax (MTV50%). Blinded for reconstruction method, a nuclear medicine physician assessed all lymph nodes showingThe mean (95% CI) SUVmax of the primary tumour was 13.1 (10.6-15.5) versus 13.0 (10.4-15.6) for 3D and motion-compensated PET/CT, respectively. MTVs were also similar between the two techniques. Bland-Altman analysis showed mean differences between both measurements (95% limits of agreement) of 0.08 (-3.60-3.75), -0.26 (-2.34-1.82), 4.66 (-29.61-38.92) cmSUVmax of the primary oesophageal tumour and lymph nodes was comparable on 3D and motion-compensated PET/CT. The use of motion-compensated PET/CT did not improve lymph node detection.

Background and purpose: External dosimetry audits are powerful quality assurance instruments for radiotherapy. The aim of this study was to implement an electron dosimetry audit based on a contemporary code of practice within the requirements for calibration laboratories performing proficiency tests. This involved the determination of suitable acceptance criteria based on thorough uncertainty analyses. Materials and methods: Subject of the audit was the determination of absorbed dose to water, Dw, and the beam quality specifier, R50,dos. Fifteen electron beams were measured in four institutes according to the Belgian-Dutch code of practice for high-energy electron beams. The expanded uncertainty (k = 2) for the Dw values was 3.6% for a Roos chamber calibrated in 60Co and 3.2% for a Roos chamber cross-calibrated against a Farmer chamber. The expanded uncertainty for the beam quality specifier, R50,dos, was 0.14 cm. The audit acceptance levels were based on the expanded uncertainties for the comparison results and estimated to be 2.4%. Results: The audit was implemented and validated successfully. All Dw audit results were satisfactory with differences in Dw values mostly smaller than 0.5% and always smaller than 1%. Except for one, differences in R50,dos were smaller than 0.2 cm and always smaller than 0.3 cm. Conclusions: An electron dosimetry audit based on absorbed dose to water and present-day requirements for calibration laboratories performing proficiency tests was successfully implemented. It proved international traceability of the participants value with an uncertainty better than 3.6% (k = 2). Keywords: Absorbed dose to water, Audit, Code of practice, Dosimetry, Electron beam, Radiation therapy

External-beam radiotherapy treatments are delivered by a linear accelerator (linac) in a series of high-energy radiation sessions over multiple days. With the increase in the incidence of cancer and the use of radiotherapy (RT), the problem of automatically scheduling RT sessions while satisfying patient preferences regarding the time of their appointments becomes increasingly relevant. While most literature focuses on timeliness of treatments, several Dutch RT centers have expressed their need to include patient preferences when scheduling appointments for irradiation sessions. In this study, we propose a mixed-integer linear programming (MILP) model that solves the problem of scheduling and sequencing RT sessions considering time window preferences given by patients. The MILP model alone is able to solve the problem to optimality, scheduling all sessions within the desired window, in reasonable time for small size instances up to 66 patients and 2 linacs per week. For larger centers, we propose a heuristic method that pre-assigns patients to linacs to decompose the problem in subproblems (clusters of linacs) before using the MILP model to solve the subproblems to optimality in a sequential manner. We test our methodology using real-world data from a large Dutch RT center (8 linacs). Results show that, combining the heuristic with the MILP model, the problem can be solved in reasonable computation time with as few as 2.8% of the sessions being scheduled outside the desired time window.

Background In radiotherapy, minimizing the time between referral and start of treatment (waiting time) is important to possibly mitigate tumor growth and avoid psychological distress in cancer patients. Radiotherapy pre-treatment workflow is driven by the scheduling of the first irradiation session, which is usually set right after consultation (pull strategy) or can alternatively be set after the pre-treatment workflow has been completed (push strategy). The objective of this study is to assess the impact of using pull and push strategies and explore alternative interventions for improving timeliness in radiotherapy. Methods Discrete-event simulation is used to model the patient flow of a large radiotherapy department of a Dutch hospital. A staff survey, interviews with managers, and historical data from 2017 are used to generate model inputs, in which fluctuations in patient inflow and resource availability are considered. Results A hybrid (40% pull / 60% push) strategy representing the current practice (baseline case) leads to 12% lower average waiting times and 48% fewer first appointment rebooks when compared to a full pull strategy, which in turn leads to 41% fewer patients breaching the waiting time targets. An additional scenario analysis performed on the baseline case showed that spreading consultation slots evenly throughout the week can provide a 21% reduction in waiting times. Conclusions A 100% pull strategy allows for more patients starting treatment within the waiting time targets than a hybrid strategy, in spite of slightly longer waiting times and more first appointment rebooks. Our algorithm can be used by radiotherapy policy makers to identify the optimal balance between push and pull strategies to ensure timely treatments while providing patient-centered care adapted to their specific conditions.

Purpose Oropharynx cancer (OPC) is heterogeneous; human papillomavirus (HPV)-positive and HPV- tumors represent 2 disease entities with a different prognosis. Earlier studies investigating the prognostic value of pretreatment 18F-FDG PET in OPC are small or included patients with unknown HPV status. This study assessed the prognostic value of PET variables, in a large cohort with balanced HPV status. Methods Retrospectively, primary tumor SUVmax, SUVpeak, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were extracted from baseline FDG PET/CT of patients with OPC treated with (chemo)radiation. The Pearson correlation between the PET variables was calculated. With linear regression, the correlation between the PET variables and HPV status, age, smoking status, T stage, N stage, and American Joint Committee on Cancer stage was calculated. Univariable and multivariable Cox models analyzed local control, overall survival, and disease-free survival (DFS). Results Of 201 patients, 109 were HPV+. Metabolic tumor volume and TLG correlated (r = 0.96), as did SUVpeak and SUVmax (r = 0.97). The PET variables correlated strongest with HPV status and T stage. These two accounted for 40% of the variance of MTV and 33% of TLG. Human papillomavirus-negative tumors had a significantly higher SUVmax, SUVpeak, MTV, and TLG. In univariable analysis, all PET variables were significantly associated with local control, overall survival, and DFS. In multivariable analysis, TLG was significantly associated to DFS in patients with HPV- OPC (hazard ratio, 1.005; 95% confidence interval, 1.001-1.010; P = 0.03). However, we did not observe this in HPV+ patients. Conclusions Increased baseline TLG is associated with worse DFS in HPV- OPC and might be used as biomarker for risk stratification in these patients. Interestingly, we could not identify this association in HPV+ patients.

In 2010, the NCS (Netherlands Commission on Radiation Dosimetry) installed a subcommittee to develop guidelines for quality assurance and control for volumetric modulated arc therapy (VMAT) treatments. The report (published in 2015) has been written by Dutch medical physicists and has therefore, inevitably, a Dutch focus. This paper is a condensed version of these guidelines, the full report in English is freely available from the NCS website www.radiationdosimetry.org.After describing the transition from IMRT to VMAT, the paper addresses machine quality assurance (QA) and treatment planning system (TPS) commissioning for VMAT. The final section discusses patient specific QA issues such as the use of class solutions, measurement devices and dose evaluation methods.

As the number of people diagnosed with cancer increases, demand for radiotherapy (RT) services has been continuously growing. In RT, delays in the start of treatment have shown to increase the risk of tumor progression in various cancer types, and patients experience greater psychological distress when subject to longer waiting times. The RT process, which involves imaging and treatment planning before treatment, is subject to complexities that hamper resource planning and control. On the demand side, the amount of workload in each operation depends on the highly variable patient inflow. On the supply side, radiation therapy technologists (RTTs) have multiple skills, rotation needs and partial availability, which makes the allocation of RTTs a complex task that often leads to situations of understaffing, jeopardizing the fulfillment of the patients' waiting time standards. In this paper, we propose a stochastic mixed-integer linear programming model that optimizes the allocation of RTTs to multiple operations in RT over a set of scenarios of patient inflow. The scenarios are generated from historical patient data, and the final RTT allocation covers the workload associated with all scenarios. The goal is to maximize the (expected) number of patients completing pre-treatment within the waiting time target. Results for a case study in the RT department of the Netherlands Cancer Institute show that, on average, the number of patients able to start treatment within the maximum waiting time standards may increase from 91.3% to 97.9% for subacute patients, and from 96.3% to 100.0% for regular patients.

Advancements in functional imaging technology have allowed new possibilities in contouring of target volumes, monitoring therapy, and predicting treatment outcome in non-small cell lung cancer (NSCLC). Consequently, the role of 18F-fluorodeoxyglucose positron emission tomography (FDG PET) has expanded in the last decades from a stand-alone diagnostic tool to a versatile instrument integrated with computed tomography (CT), with a prominent role in lung cancer radiotherapy. This review outlines the most recent literature on developments in FDG PET imaging for prognostication and radiotherapy target volume delineation (TVD) in NSCLC. We also describe the challenges facing the clinical implementation of these developments and present new ideas for future research.

In locally advanced lung cancer, established baseline clinical variables show limited prognostic accuracy and 18F-fluorodeoxyglucose positron emission tomography (FDG PET) radiomics features may increase accuracy for optimal treatment selection. Their robustness and added value relative to current clinical factors are unknown. Hence, we identify robust and independent PET radiomics features that may have complementary value in predicting survival endpoints. A 4D PET dataset (n = 70) was used for assessing the repeatability (Bland-Altman analysis) and independence of PET radiomics features (Spearman rank: |ρ

Purpose The purpose of this study was to investigate if FDG-PET and DWI identify the same or different targets for dose escalation in the GTV of HN cancer patients. Additionally, the dose coverage of DWI-targets in an FDG-PET-based dose painting plan was analyzed. Materials and methods Eighteen HN cancer patients underwent FDG-PET and DWI exams, which were converted to standardized uptake value (SUV)- and apparent diffusion coefficient (ADC)-maps. The correspondence between the two imaging modalities was determined on a voxel-level using Spearman's correlation coefficient ( ρ ). Dose painting plans were optimized based on the 50% isocontour of the maximum SUV ( SUV 50%max ). Dose coverage was analyzed in three different SUV- and three different ADC-targets using the mean dose and the near-minimum and near-maximum doses. Results The average maximum SUV was 13.9 and the mean ADC was 1.17·10 −3 mm 2 /s. The average ρ between SUV and ADC was −0.2 (range: −0.6 to 0.4). The ADC-targets were only partly overlapping the SUV 50%max -target and the dose parameters were significantly smaller in the ADC-targets compared to the SUV 50%max -target. Conclusions FDG-PET and DWI contain different information, resulting in different targets. Further information about failure patterns and dose relations can be obtained by adding DWI to currently ongoing dose painting trials.

Purpose Four-dimensional positron emission tomography (4D PET) imaging of the thorax produces sharper images with reduced motion artifacts. Current radiation therapy planning systems, however, do not facilitate 4D plan optimization. When images are acquired in a 2-minute time slot, the signal-to-noise ratio of each 4D frame is low, compromising image quality. The purpose of this study was to implement and evaluate the construction of mid-position 3D PET scans, with motion compensated using a 4D computed tomography (CT)-derived motion model. Methods and Materials All voxels of 4D PET were registered to the time-averaged position by using a motion model derived from the 4D CT frames. After the registration the scans were summed, resulting in a motion-compensated 3D mid-position PET scan. The method was tested with a phantom dataset as well as data from 27 lung cancer patients. Results PET motion compensation using a CT-based motion model improved image quality of both phantoms and patients in terms of increased maximum SUV (SUV max ) values and decreased apparent volumes. In homogenous phantom data, a strong relationship was found between the amplitude-to-diameter ratio and the effects of the method. In heterogeneous patient data, the effect correlated better with the motion amplitude. In case of large amplitudes, motion compensation may increase SUV max up to 25% and reduce the diameter of the 50% SUV max volume by 10%. Conclusions 4D CT-based motion-compensated mid-position PET scans provide improved quantitative data in terms of uptake values and volumes at the time-averaged position, thereby facilitating more accurate radiation therapy treatment planning of pulmonary lesions.

Background The delivery of radiotherapy (RT) involves the use of rather expensive resources and multi-disciplinary staff. As the number of cancer patients receiving RT increases, timely delivery becomes increasingly difficult due to the complexities related to, among others, variable patient inflow, complex patient routing, and the joint planning of multiple resources. Operations research (OR) methods have been successfully applied to solve many logistics problems through the development of advanced analytical models for improved decision making. This paper presents the state of the art in the application of OR methods for logistics optimization in RT, at various managerial levels. Methods A literature search was performed in six databases covering several disciplines, from the medical to the technical field. Papers included in the review were published in peer-reviewed journals from 2000 to 2015. Data extraction includes the subject of research, the OR methods used in the study, the extent of implementation according to a six-stage model and the (potential) impact of the results in practice. Results From the 33 papers included in the review, 18 addressed problems related to patient scheduling (of which 12 focus on scheduling patients on linear accelerators), 8 focus on strategic decision making, 5 on resource capacity planning, and 2 on patient prioritization. Although calculating promising results, none of the papers reported a full implementation of the model with at least a thorough pre-post performance evaluation, indicating that, apart from possible reporting bias, implementation rates of OR models in RT are probably low. Conclusions The literature on OR applications in RT covers a wide range of approaches from strategic capacity management to operational scheduling levels, and shows that considerable benefits in terms of both waiting times and resource utilization are likely to be achieved. Various fields can be further developed, for instance optimizing the coordination between the available capacity of different imaging devices or developing scheduling models that consider the RT chain of operations as a whole rather than the treatment machines alone. Electronic supplementary material The online version of this article (doi:10.1186/s12911-016-0390-4) contains supplementary material, which is available to authorized users.

Purpose To evaluate the effect of different α/β and half-time of repair T ½ on the assessment of clinical treatment plans for patients with cervical cancer. Materials and methods We used EBRT and BT treatment plans of five patients, planned with MRI guided BT. We computed 3D EQD2 dose distributions of combined EBRT and BT treatments and calculated D90 of high-risk clinical target volume (HR-CTV) and D 2cc for bladder and rectum, and the ratio D 2cc (bladder)/D90(HR-CTV). BT was modelled as PDR (two applications of 32×60cGy) and HDR (two applications of 2×7Gy). We assumed a low, standard and high value for the biological parameters: HR-CTV α / β =5/10/15Gy and T ½ =0.5/1.5/2.5h; OAR α / β =2/3/4Gy; T ½ =0.5/1.5/4.5h. Results The chosen variation in modelling parameters had a much larger effect on PDR treatments than on HDR treatments, especially for OAR, thus creating larger uncertainties. The relative mean range of the ratio D 2cc (bladder)/D90(HR-CTV) is 72% for PDR and 25% for HDR. Out of the 125 modelled combinations 48 PDR plans and 23 HDR plans comply with clinical objectives. Conclusion For HDR brachytherapy, only α/β has a significant impact on reported EQD2 values, whereas for PDR both α/β and T 1/2 are important. Generally, the ratio D 2cc (bladder)/D90(HR-CTV) is more favourable for PDR, even considering the larger uncertainties in EQD2.

Purpose: A biomechanical model was constructed to give insight into pelvic organ motion as a result of bladder filling changes. Methods: The authors used finite element(FE)modeling to simulate bladder wall deformation caused by urine inflow. For ten volunteers, a series of MRI scans of the pelvic area was recorded at regular intervals of 10 min over 1 h. For the series of scans, the bladder volume gradually increased while the rectal volume was constant. The MR image with the bladder volume closest to 250 ml was selected as the reference in each volunteer. All pelvic structures were defined from the reference image including bladder wall, small bowel, prostate (male), uterus (female), rectum, pelvic bone, and the rest of the body. These structures were translated to FE meshes. Using appropriate material properties for all organs, deformations of these organs as a response to changing bladder pressure were computed. Results: The computation results showed realistic anisotropic deformation of the bladder wall: The bladder became more elongated in the cranial and anterior directions with increasing bladder volume. After fitting the volume of the computed bladder to the actual bladder volume on the test images, the computed bladder shape agreed well with the real bladder shape (overlap from 0.79 to 0.93). The average mean bladder wall prediction errors of all the volunteers were 0.31 cm average and 0.29 cm SD. Conclusions: In conclusion, a FE based mechanical bladder model shows promise for the prediction of the short-term bladder shape change using only one pelvic scan and volume change of the bladder as input. The accuracy levels achieved with this method are likely mostly limited by inaccuracies in material properties and sliding tissue between organs, which has not been modeled. This model can potentially be used to improve image-guidedradiotherapy for bladder cancer patients, i.e., by prediction short-term bladder deformation.

Background and Purpose: The two main modalities to deliver high dose to the prostate and prevent high doses to neighboring organs are intensity modulated radiotherapy (IMRT) or external beam radiotherapy combined with brachytherapy. Because of the different biological effectiveness the physical dose distributions were converted to 3-dimensional linear quadratic dose at 2 Gy per fraction (EQD(2)). From the latter, cumulative EQD(2)-volume histograms were determined for comparison of the modalities. Material and methods: An IMRT plan was made on the contoured planning target volume (PTV1) and organs at risk (OAR) of 20 patients (IMRT-only). A dose of 70 Gy was prescribed on the PTV1 with a concomitant boost to a total of 76 Gy on a subvolume (PTV2). Also a 46 Gy IMRT plan was made combined with either a pulsed dose-rate (PDR) or a high dose-rate (HDR) brachytherapy boost. The EQD(2) on the PTV1 of the combined IMRT-PDR and IMRT-HDR plans were made equivalent to the EQD(2) of the 70 Gy IMRT-only plan. The alpha/beta-ratio for prostate was set to 1.5 Gy and 10 Gy. For normal tissues an alpha/beta-ratio of 3.0 Gy was taken. Several EQD(2)-volume histogram parameters were calculated for comparison and analyzed by two-way ANOVA. Results: The mean EQD(2) to 95% of the prostate volume was slightly higher for the IMRT-only plan than for the brachytherapy modalities (P

Purpose To investigate the dosimetric effect of prostate rotations and limited on-line corrections by couch rotations (⩽3°) for prostate, seminal vesicles and organs at risk. Methods For 5 patients IMRT plans were made, treating the prostate plus base of the seminal vesicles. Realistic and idealised dose distributions were considered, the latter demonstrating extreme effects for rotations and their corrections. Translation errors were assumed to be corrected on-line. For each patient 20 treatments with different rotation errors were simulated: 20 systematic errors were generated and 20 times 35 random deviations were superimposed to simulate day-to-day variations. Using a research module of PLATO-RTS treatments with rotation errors, with and without on-line corrections, were simulated. Results The largest dosimetric effect of rotation errors and corrections was found for the seminal vesicles with idealised dose distribution: coverage improved from 92.6% (range 89.9–96.0%) to 95.9% (94.7–98.1%). The gain for the idealised prostate was less: 95.9% (94.4–97.0%) to 97.5% (95.5–98.4%). For the femoral heads the dose increase could be as large as 12.2% (6.2–19.3%). Conclusions On-line correction of rotations can improve target coverage slightly. For organs at risk at a large distance from the isocentre the result can be a significant increase in dose.

In this paper the concept of using B1+ imaging as a means to validate SAR models for radiofrequency hyperthermia is presented. As in radiofrequency hyperthermia, in common clinical MR imaging which applies RF frequencies between 64 and 128 MHz, the RF field distribution inside a patient is largely determined by the dielectric distribution of the anatomy. Modern MR imaging techniques allow measurement of the RF magnetic field component B1+ making it possible to measure at high resolution the dielectric interaction of the RF field with the patient. Given these considerations, we propose to use MR imaging to verify the validity of our dielectric patient model used for SAR models of radiofrequency hyperthermia. The aim of this study was to investigate the feasibility of this concept by performing B1+ measurements and simulations on cylindrical split phantoms consisting of materials with dielectric properties similar to human tissue types. Important topics of investigation were the accuracy and sensitivity of B1+ measurements and the validity of the electric model of the MR body coil. The measurements were performed on a clinical 1.5 T MR scanner with its quadrature body coil operating at 64 MHz. It was shown that even small B1+ variations of 2 to 5% could be measured reliably in the phantom experiments. An electrical model of the transmit coil was implemented on our FDTD-based hyperthermia treatment planning platform and the RF field distributions were calculated assuming an idealized quadrature current distribution in the coil. A quantitatively good correlation between measurements and simulations was found for phantoms consisting of water and oil, while highly conductive phantoms show considerable deviations. However, assuming linear excitation for these conductive phantoms resulted in good correspondence. As an explanation it is suggested that the coil is being detuned due to the inductive nature of the conductive phantoms, breaking up the phase difference of pi/2 between the two quadrature modes. It is concluded that B1+ imaging is an accurate and sensitive method for obtaining quantitative information about the RF field in phantoms. The electrical model of the body coil is inadequate for highly conductive phantoms. It is expected that for experiments on human bodies the inductive coupling is also significant, demonstrating the need for a full resonant FDTD model of the transmit coil. This will be pursued in the near future.

Background In contemporary positron emission tomography (PET)/computed tomography (CT) scanners, PET attenuation correction is performed by means of a CT-based attenuation map. Respiratory motion can however induce offsets between the PET and CT data. Studies have demonstrated that these offsets can cause errors in quantitative PET measures. The purpose of this study is to quantify the effects of respiration-induced CT differences on the attenuation correction of pulmonary 18-fluordeoxyglucose (FDG) 3D PET/CT in a patient population and to investigate contributing factors. Methods For 32 lung cancer patients, 3D-CT, 4D-PET and 4D-CT data were acquired. The 4D FDG PET data were attenuation corrected (AC) using a free-breathing 3D-CT (3D-AC), the end-inspiration CT (EI-AC), the end-expiration CT (EE-AC) or phase-by-phase (P-AC). After reconstruction and AC, the 4D-PET data were averaged. In the 4Davg data, we measured maximum tumour standardised uptake value (SUV)max in the tumour, SUVmean in a lung volume of interest (VOI) and average SUV (SUVmean) in a muscle VOI. On the 4D-CT, we measured the lung volume differences and CT number changes between inhale and exhale in the lung VOI. Results Compared to P-AC, we found −2.3% (range −9.7% to 1.2%) lower tumour SUVmax in EI-AC and 2.0% (range −0.9% to 9.5%) higher SUVmax in EE-AC. No differences in the muscle SUV were found. The use of 3D-AC led to respiration-induced SUVmax differences up to 20% compared to the use of P-AC. SUVmean differences in the lung VOI between EI-AC and EE-AC correlated to average CT differences in this region (ρ = 0.83). SUVmax differences in the tumour correlated to the volume changes of the lungs (ρ = −0.55) and the motion amplitude of the tumour (ρ = 0.53), both as measured on the 4D-CT. Conclusions Respiration-induced CT variations in clinical data can in extreme cases lead to SUV effects larger than 10% on PET attenuation correction. These differences were case specific and correlated to differences in CT number in the lungs.

Purpose: We determined prostate perfusion in 18 patients with locally advanced prostate carcinoma treated with a combination of external beam irradiation and regional (10) or interstitial (8) hyperthermia.Materials and Methods: Perfusion values were calculated from temperature elevations due to constant applied power and from transient temperature measurements after a change in applied power. Student’s t test was used for comparing perfusion values with time and in the 2 groups.Results: At the start of regional hyperthermia treatment mean estimated perfusion plus or minus standard deviation was 10 ± 8 ml./100 gm. per minute. At the end of treatment mean perfusion was increased to 14 ± 2 ml./100 gm. per minute (p

In epidemiologic research radiation-associated late effects after childhood cancer are usually analyzed without considering fraction dose. According to radiobiological principles, fraction dose is an important determinant of late effects. We aim to provide the rationale for using equivalent dose in 2-Gy fractions (EQD2 α/β ) as the measure of choice rather than total physical dose as prescribed according to the clinical protocol. Between 1966 and 1996, 597 (43.8 %) children in our cohort of 1,362 5-year childhood cancer survivors (CCS) received radiotherapy before the age of 18 years as part of their primary cancer treatment. Detailed information from individual patients’ charts was collected and physical doses were converted into the EQD2 α/β , which includes total dose, fraction dose, and the tissue-specific α/β ratio. The use of EQD2 α/β is illustrated in examples studies describing different analyses using EQD2 α/β and physical dose. Radiotherapy information was obtained for 510 (85.4 %) CCS. Multivariable analyses rendered different risk estimates for total body irradiation in EQD2 α/β -based vs. physical-dose-based models. For other radiotherapy regimens, risk estimates were similar. Using the total physical dose is not adequate for advanced analyses of radiation-associated late effects in CCS. Therefore, it is advised that for future studies the EQD2 α/β is used, because the EQD2 α/β incorporates the fraction dose, and the tissue-specific α/β ratio. Furthermore, it enables comparisons across fractionation regimens and allows for summing doses delivered by various contemporary and future radiation modalities. Risk estimates of radiation-associated side effects expressed in EQD2 α/β provide more precise, clinically relevant information for cancer survivor screening guidelines.

The purpose of this study was to develop a method to use amplitude binned 4D-CT (A-4D-CT) data for the construction of mid-position CT data and to compare the results with data created from phase-binned 4D-CT (P-4D-CT) data. For the latter purpose we have developed two measures which describe the regularity of the 4D data and we have tried to correlate these measures with the regularity of the external respiration signal. 4D-CT data was acquired for 27 patients on a combined PET-CT scanner. The 4D data were reconstructed twice, using phase and amplitude binning. The 4D frames of each dataset were registered using a quadrature-based optical flow method. After registration the deformation vector field was repositioned to the mid-position. Since amplitude-binned 4D data does not provide temporal information, we corrected the mid-position for the occupancy of the bins. We quantified the differences between the two mid-position datasets in terms of tumour offset and amplitude differences. Furthermore, we measured the standard deviation of the image intensity over the respiration after registration (sigma(registration)) and the regularity of the deformation vector field ((Delta vertical bar J vertical bar) over bar) to quantify the quality of the 4D-CT data. These measures were correlated to the regularity of the external respiration signal (sigma(signal)). The two irregularity measures, (Delta vertical bar J vertical bar) over bar and sigma(registration), were dependent on each other (p and sigma(registration) and large decreases led to visible quality improvements in the mid-position data. The quantity of artefact decrease was correlated to the irregularity of the external respiratory signal. The average tumour offset between the phase and amplitude binned midposition without occupancy correction was 0.42 mm in the caudal direction (10.6% of the amplitude). After correction this was reduced to 0.16 mm in caudal direction (4.1% of the amplitude). Similar relative offsets were found at the diaphragm. We have devised a method to use amplitude binned 4D-CT to construct motion model and generate a mid-position planning CT for radiotherapy treatment purposes. We have decimated the systematic offset of this midposition model with a motion model derived from P-4D-CT. We found that the A-4D-CT led to a decrease of local artefacts and that this decrease was correlated to the irregularity of the external respiration signal

Purpose and background The purpose was to validate the accuracy of motion models derived from deformable registration from four-dimensional computed tomography (4DCT) and breath-hold contrast enhanced computed tomography (BHCCT) scans for liver SBRT. Additionally, the image quality of the time averaged mid-position (MidP) CT constructed using the detected motion model was assessed. Materials and methods 4DCT and BHCCT liver scans of 11 patients were acquired with 1 or 2 fiducial markers. Using parametric sampling the markers were digitally removed. Phase-based optical flow was used to register the 4D frames and the BHCCT, and create MidP data. We compared the deformable registration of the markerless scans with the actual displacement of the markers to assess registration accuracy. The noise levels of the MidP scans were compared to those of the 4DCT and BHCCT data. Results We found an average misregistration of 1.8 mm (±0.5 mm). The constructed MidPCT scan contained around three times less noise than the original 4D scan. The residual error between the MidPCT and the BHCCT was 3.0 mm (±0.9 mm). Conclusions High precision deformable image registration of 4DCT and BHCCT liver cancer patients was achieved and used to create motion compensated MidPCT scans, with increased contrast-to-noise (CNR) levels. This improved visualisation of tumours and anatomy, facilitates radiotherapy treatment planning.

With daily portal images and repeated CT scans from 20 patients with gold markers (GM) an adaptive margin radiotherapy strategy (AMRT) was simulated and compared to traditional bony anatomy (BA) and standard GM verification protocols. AMRT is comparable with BA. GM protocols are superior.

A biomechanical model was constructed to give insight into pelvic organ motion as a result of bladder filling changes.The authors used finite element (FE) modeling to simulate bladder wall deformation caused by urine inflow. For ten volunteers, a series of MRI scans of the pelvic area was recorded at regular intervals of 10 min over 1 h. For the series of scans, the bladder volume gradually increased while the rectal volume was constant. The MR image with the bladder volume closest to 250 ml was selected as the reference in each volunteer. All pelvic structures were defined from the reference image including bladder wall, small bowel, prostate (male), uterus (female), rectum, pelvic bone, and the rest of the body. These structures were translated to FE meshes. Using appropriate material properties for all organs, deformations of these organs as a response to changing bladder pressure were computed.The computation results showed realistic anisotropic deformation of the bladder wall: The bladder became more elongated in the cranial and anterior directions with increasing bladder volume. After fitting the volume of the computed bladder to the actual bladder volume on the test images, the computed bladder shape agreed well with the real bladder shape (overlap from 0.79 to 0.93). The average mean bladder wall prediction errors of all the volunteers were 0.31 cm average and 0.29 cm SD.In conclusion, a FE based mechanical bladder model shows promise for the prediction of the short-term bladder shape change using only one pelvic scan and volume change of the bladder as input. The accuracy levels achieved with this method are likely mostly limited by inaccuracies in material properties and sliding tissue between organs, which has not been modeled. This model can potentially be used to improve image-guided radiotherapy for bladder cancer patients, i.e., by prediction short-term bladder deformation.

Purpose: To evaluate the effect of gold marker (GM)-based position correction on the cumulative dose in the anorectal wall compared with traditional bony anatomy (BA)-based correction, taking into account changes in anorectal shape and position. Methods and Materials: A total of 20 consecutive prostate cancer patients, treated with curative external beam radiotherapy, were included. Four fiducial GMs were implanted in the prostate. Positioning was verified according to the shift in BA and GMs on daily electronic portal images. Position corrections were determined using on- and off-line position verification protocols according to the position of the GMs (GM-on and GM-off) and BA (BA-off). For all patients, intensity-modulated radiotherapy plans were made for the GM (8-mm planning target volume margin) and BA (10-mm planning target volume margin) protocols. The dose distribution was recomputed on 11 repeat computed tomography scans to estimate the accumulated dose to the prostate and anorectal wall while considering internal organ motion. Results: The dose that is at least received by 99% of the prostate was, on average, acceptable for all protocols. The individual patient data showed the best coverage for both GM protocols, with >95% of the prescribed dose for all patients. The anorectal wall dose was significantly lower for the GM protocols. The dose that is at least received by 30% of the rectal wall was, on average, 54.6 Gy for GM-on, 54.1 Gy for GM-off, and 58.9 Gy for BA-off (p

To evaluate the effect of different α/β and half-time of repair T(½) on the assessment of clinical treatment plans for patients with cervical cancer.We used EBRT and BT treatment plans of five patients, planned with MRI guided BT. We computed 3D EQD2 dose distributions of combined EBRT and BT treatments and calculated D90 of high-risk clinical target volume (HR-CTV) and D(2cc) for bladder and rectum, and the ratio D(2cc)(bladder)/D90(HR-CTV). BT was modelled as PDR (two applications of 32×60cGy) and HDR (two applications of 2×7Gy). We assumed a low, standard and high value for the biological parameters: HR-CTV α/β=5/10/15Gy and T(½)=0.5/1.5/2.5h; OAR α/β=2/3/4Gy; T(½)=0.5/1.5/4.5h.The chosen variation in modelling parameters had a much larger effect on PDR treatments than on HDR treatments, especially for OAR, thus creating larger uncertainties. The relative mean range of the ratio D(2cc)(bladder)/D90(HR-CTV) is 72% for PDR and 25% for HDR. Out of the 125 modelled combinations 48 PDR plans and 23 HDR plans comply with clinical objectives.For HDR brachytherapy, only α/β has a significant impact on reported EQD2 values, whereas for PDR both α/β and T(½) are important. Generally, the ratio D(2cc)(bladder)/D90(HR-CTV) is more favourable for PDR, even considering the larger uncertainties in EQD2.

Purpose: To analyse the therapeutic effect and toxicity of re-irradiation (re-RT) combined with hyperthermia ( HT) following resection or clinically complete remission (CR) of persistent locoregional recurrent breast cancer in previously irradiated area. Methods and materials: Between 1988 and 2001, 78 patients with high risk recurrent breast cancer underwent elective re-RT and HT. All patients received extensive previous treatments, including surgery and high-dose irradiation (>= 50Gy). Most had received one or more lines of systemic therapy; 44% had been treated for >= one previous locoregional recurrences. At start of re-RT + HT there was no macroscopically detectable tumour following surgery (96%) or chemotherapy (CT). Re-RT typically consisted of eight fractions of 4Gy, given twice weekly. Hyperthermia was added once a week. Results: After a median follow up of 64.2 months, three-year survival was 66%. Three- and five-year local control rates were 78% and 65%. Acute grade 3 toxicity occurred in 32% of patients. The risk of late >= grade 3 toxicity was 40% after three years. Time interval to the current recurrence was found to be most predictive for local control in univariate and multivariate analysis. The extensiveness of current surgery was the most relevant treatment related factor associated with toxicity. Conclusions: For patients experiencing local recurrence in a previously radiated area, re-irradiation plus hyperthermia following minimisation of tumour burden leads to a high rate of local control, albeit with significant toxicity. The latter might be reduced by a more fractionated re-RT schedule

Background The application of lipiodol injections as markers around bladder tumors combined with the use of CBCT for image guidance enables daily on-line position correction based on the position of the bladder tumor. However, this might introduce the risk of underdosing the pelvic lymph nodes. In this study several correction strategies were compared. Methods For this study set-up errors and tumor displacements for ten complete treatments were generated; both were based on the data of 10 bladder cancer patients. Besides, two IMRT plans were made for 20 patients, one for the elective field and a boost plan for the tumor. For each patient 10 complete treatments were simulated. For each treatment the dose was calculated without position correction (option 1), correction on bony anatomy (option 2), on tumor only (option 3) and separately on bone for the elective field (option 4). For each method we analyzed the D99% for the tumor, bladder and lymph nodes and the V95% for the small intestines, rectum, healthy part of the bladder and femoral heads. Results CTV coverage was significantly lower with options 1 and 2. With option 3 the tumor coverage was not significantly different from the treatment plan. The ΔD99% (D99%, option n - D99%, treatment plan) for option 4 was small, but significant. For the lymph nodes the results from option 1 differed not significantly from the treatment plan. The median ΔD99% of the other options were small, but significant. ΔD99% for PTVbladder was small for options 1, 2 and 4, but decreased up to -8.5 Gy when option 3 was applied. Option 4 is the only method where the difference with the treatment plan never exceeds 2 Gy. The V95% for the rectum, femoral heads and small intestines was small in the treatment plan and this remained so after applying the correction options, indicating that no additional hot spots occurred. Conclusions Applying independent position correction on bone for the elective field and on tumor for the boost separately gives on average the best target coverage, without introducing additional hot spots in the healthy tissue.

Purpose To compare two methods of DVH parameter determination for combined external beam and brachytherapy treatment of cervical cancer. Materials and methods Clinical treatment plans from five patients were used in this study. We simulated two applications given with PDR (32×60cGy per application, given hourly) or HDR (4×7Gy in two applications; each application of two fractions of 7Gy, given within 17h) standard and optimised treatment plans, all combined with IMRT (25×1.8Gy). Additionally, we simulated an external beam (EBRT) boost to pathological lymph nodes or the parametrium (7×2Gy). We determined D90 of the high-risk CTV (HR-CTV) and D 2cc of bladder and rectum in EQD2 in two ways. (1) ‘Parameter adding': assuming a uniform contribution of the EBRT dose distribution and adding the values of DVH parameters for the two brachytherapy insertions, and (2) ‘distributions adding': summing 3D biological dose distributions of IMRT and brachytherapy plans and subsequently determining the values of the DVH parameters. We took α/β=10Gy for HR-CTV, α/β=3Gy otherwise and half-time of repair 1.5h. Results Without EBRT boost, ‘parameter adding' yielded a good approximation. With an EBRT boost to lymph nodes, the total D90 HR-CTV was underestimated by 2.6 (SD 1.3)% for PDR and 2.8 (SD 1.4)% for HDR. This was even worse with a parametrium boost: 9.1 (SD 6.2)% for PDR and 9.9 (SD 6.2)% for HDR. Conclusion Without an EBRT boost ‘parameter adding', as proposed by the GEC-ESTRO, yielded accurate results for the values for DVH parameters. If an EBRT boost is given ‘distributions adding' should be considered.

Purpose: To investigate the stability of a novel type of markers used in partial bladder tumor irradiation and tumor deformation as indicated by the markers. Materials and Methods: In 15 patients with solitary bladder cancer, lipiodol was injected in the bladder wall during flexible cystoscopy to identify the tumor. A planning CT scan was made, followed by daily cone-beam CT (CBCT) scans during treatment. To study the accuracy of using these markers for image guidance, uncertainties U1 and U2 were calculated, which were defined as the difference between submask registration (covering single marker) and the average of all submask registrations and the difference between the submask registration and the general mask registration (including all markers), respectively. Finally, to study tumor deformation, the relative movement of each marker pair was correlated with the relative bladder volume (RBV). Results: The analyzed patients had 2.3 marker injections on average. The lipiodol spot size was 0.72 +/- 1.1 cm(3). The intensity of spots in both CT and CBCT was significantly higher than the surrounding bladder tissue. The uncertainties U1 and U2 were comparable, and the uncertainties in left-right direction (0.14-0.19 cm) were smaller than those in cranial-caudal and anterior-posterior directions (0.19-0.32 cm). The relative marker movement of within-zone marker pairs was much smaller (and has less dependence on the RBV) than across-zones marker pairs. Conclusions: Lipiodol markers are a feasible method to track bladder tumor by using online CBCT. Tumor deformation is observed, especially for tumors that cross the defined bladder zones. (C) 2010 Elsevier Inc

In high-field MRI severe problems with respect to B(1) (+) uniformity and specific absorption rate (SAR) deposition pose a great challenge to whole-body imaging. In this study the potential of a phased array transmit coil is investigated to simultaneously reduce B(1) (+) nonuniformity and SAR deposition. This was tested by performing electromagnetic simulations of a phased array TEM coil operating at 128 MHz loaded with two different homogeneous elliptical phantoms and four dielectric patient models. It was shown that the wave interference of a circularly polarized RF field with an ellipse and a pelvis produces largely identical B(1) (+) and electric field patterns. Especially for obese patients, this results in large B(1) (+) nonuniformity and global areas with elevated SAR deposition. It is demonstrated that a phased array transmit coil can reduce these phenomena. The technique was especially successful in suppressing SAR hotspots with a decrease up to 50%. The application of optimized settings for an ellipse to the patient models leads to comparable results as obtained with the patient-specific optimizations. This suggests that generic phase/amplitude port settings are possible, requiring no preinformation about patient-specific RF fields. Such a scheme would, due to its simultaneous B(1) (+) homogenization and extra SAR margin, have many benefits for whole-body imaging at 3 T.

A clip forceps was developed which can insert markers at the border of a bladder tumour through a rigid cystoscope. This technique proved to be simple and safe and is of help for delineation of the target volume during CT simulation for focal boost irradiation of bladder cancer. (c) 2007 Elsevier Ireland Ltd. All rights reserved

In this study, MR B(+)(1) imaging is employed to experimentally verify the validity of FDTD simulations of electromagnetic field patterns in human anatomies. Measurements and FDTD simulations of the B(+)(1) field induced by a 3 T MR body coil in a human corpse were performed. It was found that MR B(+)(1) imaging is a sensitive method to measure the radiofrequency (RF) magnetic field inside a human anatomy with a precision of approximately 3.5%. A good correlation was found between the B(+)(1) measurements and FDTD simulations. The measured B(+)(1) pattern for a human pelvis consisted of a global, diagonal modulation pattern plus local B(+)(1) heterogeneties. It is believed that these local B(+)(1) field variations are the result of peaks in the induced electric currents, which could not be resolved by the FDTD simulations on a 5 mm(3) simulation grid. The findings from this study demonstrate that B(+)(1) imaging is a valuable experimental technique to gain more knowledge about the dielectric interaction of RF fields with the human anatomy.

The application of thermal modelling for hyperthermia and thermal ablation is severely hampered by lack of information about perfusion and vasculature. However, recently, with the advent of sophisticated angiography and dynamic contrast enhanced (DCE) imaging techniques, it has become possible to image small vessels and blood perfusion bringing the ultimate goal of patient specific thermal modelling closer within reach. In this study dynamic contrast enhanced multi-slice CT imaging techniques are employed to investigate the feasibility of this concept for regional hyperthermia treatment of the prostate. The results are retrospectively compared with clinical thermometry data of a patient group from an earlier trial. Furthermore, the role of the prostate vasculature in the establishment of the prostate temperature distribution is studied. Quantitative 3D perfusion maps of the prostate were constructed for five patients using a distributed-parameter tracer kinetics model to analyse dynamic CT data. CT angiography was applied to construct a discrete vessel model of the pelvis. Additionally, a discrete vessel model of the prostate vasculature was constructed of a prostate taken from a human corpse. Three thermal modelling schemes with increasing inclusion of the patient specific physiological information were used to simulate the temperature distribution of the prostate during regional hyperthermia. Prostate perfusion was found to be heterogeneous and T3 prostate carcinomas are often characterized by a strongly elevated tumour perfusion (up to 70-80 ml 100 g(-1) min(-1)). This elevated tumour perfusion leads to 1-2 degrees C lower tumour temperatures than thermal simulations based on a homogeneous prostate perfusion. Furthermore, the comparison has shown that the simulations with the measured perfusion maps result in consistently lower prostate temperatures than clinically achieved. The simulations with the discrete vessel model indicate that significant pre-heating takes place in the prostate capsule vasculature which forms a possible explanation for the discrepancy. Pre-heating in the larger pelvic vessels is very moderate, approximately 0.1-0.3 degrees C. In conclusion, perfusion imaging provides important input for thermal modelling and can be used to obtain a lower limit on the prostate and tumour temperature in regional hyperthermia. However, it is not sufficient to calculate in detail the prostate temperature distribution in individual patients. The prostate vasculature plays such a crucial role that a patient specific discrete vessel model of the prostate vasculature is required.