Quantifying intrafractional gastric motion using auto-segmentation on MRI: Deformation and respiratory-induced displacement compared.

BACKGROUND AND PURPOSE: For accurate pre-operative gastric radiotherapy, intrafractional changes must be taken into account. The aim of this study is to quantify local gastric deformations and compare these deformations with respiratory-induced displacement. MATERIALS AND METHODS: Coronal 2D MRI scans (15-16 min; 120 repetitions of 25-27 interleaved slices) were obtained for 18 healthy volunteers. A deep-learning network was used to auto-segment the stomach. To separate out respiratory-induced displacements, auto-segmentations were rigidly shifted in superior-inferior (SI) direction to align the centre of mass (CoM) within every slice. From these shifted auto-segmentations, 3D iso-probability surfaces (isosurfaces) were established: a reference surface for POcc  = 0.50 and 50 other isosurfaces (from POcc  = 0.01 to 0.99), with POcc indicating the probability of occupation by the stomach. For each point on the reference surface, distances to all isosurfaces were determined and a cumulative Gaussian was fitted to this probability-distance dataset to obtain a standard deviation (SDdeform ) expressing local deformation. For each volunteer, we determined median and 98th percentile of SDdeform over the reference surface and compared these with the respiratory-induced displacement SDresp , that is, the SD of all CoM shifts (paired Wilcoxon signed-rank, α = 0.05). RESULTS: Larger deformations were mostly seen in the antrum and pyloric region. Median SDdeform (range, 2.0-2.9 mm) was smaller than SDresp (2.7-8.8 mm) for each volunteer (p < 0.00001); 98th percentile of SDdeform (3.2-7.3 mm) did not significantly differ from SDresp (p = 0.13). CONCLUSION: Locally, gastric deformations can be large. Overall, however, these deformations are limited compared to respiratory-induced displacement. Therefore, unless respiratory motion is considerably reduced, the need to separately include these deformation uncertainties in the treatment margins may be limited.

Sensitivity of dose-volume indices to computation settings in high-dose-rate prostate brachytherapy treatment plan evaluation.

PURPOSE: To investigate the variation in computed dose-volume (DV) indices for high-dose-rate (HDR) prostate brachytherapy that can result from typical differences in computation settings in treatment planning systems (TPSs). METHODS: Five factors were taken into account: number of dose-calculation points, radioactive source description, interpolation between delineated contours, intersections between delineated organ contours, and organ shape at the top and bottom contour using either full or partial slice thickness. Using in-house developed software, the DV indices of the treatment plans of 26 patients were calculated with different settings, and compared to a baseline setting that closely followed the default settings of the TPS used in our medical center. Studied organs were prostate and seminal vesicles, denoted as targets, and bladder, rectum, and urethra, denoted as organs at risk (OARs), which were delineated on MRI scans with a 3.3 mm slice thickness. RESULTS: When sampling a fixed number of points in each organ, in order to achieve a width of the 95% confidence interval over all patients of the DV indices of 1% or less, only 32,000 points had to be sampled per target, but 256,000 points had to be sampled per OAR. For the remaining factors, DV indices changed up to 0.4% for rectum, 1.3% for urethra, and 2.6% for prostate. DV indices of the bladder changed especially if the high-dose-region was (partly) located at the most caudal contour, up to 8.5%, and DV indices of the vesicles changed especially if there were few delineated contours, up to 9.8%, both due to the use of full slice thickness for the top and bottom contour. CONCLUSIONS: The values of DV indices used in prostate HDR brachytherapy treatment planning are influenced by the computation settings in a TPS, especially at the most caudal part of the bladder, as well as in the seminal vesicles.

The effectiveness of 4DCT in children and adults: A pooled analysis.

BACKGROUND: While four-dimensional computed tomography (4DCT) is extensively used in adults, reluctance remains to use 4DCT in children. Day-to-day (interfractional) variability and irregular respiration (intrafractional variability) have shown to be limiting factors of 4DCT effectiveness in adults. In order to evaluate 4DCT applicability in children, the purpose of this study is to quantify inter- and intrafractional variability of respiratory motion in children and adults. The pooled analysis enables a solid comparison to reveal if 4DCT application for planning purposes in children could be valid. METHODS/MATERIALS: We retrospectively included 90 patients (45 children and 45 adults), for whom the diaphragm was visible on abdominal/thoracic free-breathing cone beam CTs (480 pediatric, 524 adult CBCTs). For each CBCT, the cranial-caudal position of end-exhale and end-inhale positions of the right diaphragm dome were manually selected in the projection images. The difference in position between both phases defines the amplitude. Cycle time equaled inspiratory plus expiratory time. We analyzed the variability of the inter- and intrafractional respiratory-induced diaphragm motion. RESULTS: Ranges of respiratory motion characteristics were large in both children and adults (amplitude: 4-17 vs 5-24 mm, cycle time 2.1-3.9 vs 2.7-6.5 s). The mean amplitude was slightly smaller in children than in adults (10.7 vs 12.3 mm; P = 0.06). Interfractional amplitude variability was statistically significantly smaller in children than in adults (1.4 vs 2.2 mm; P = 0.00). Mean cycle time was statistically significantly shorter in children (2.9 vs 3.6 s; P = 0.00). Additionally, intrafractional cycle time variability was statistically significantly smaller in children (0.5 vs 0.7 s; P = 0.00). CONCLUSIONS: Overall variability is smaller in children than in adults, indicating that respiratory motion is more regular in children than in adults. This implies that a single pretreatment 4DCT could be a good representation of daily respiratory motion in children and will be at least equally beneficial for planning purposes as it is in adults.

How do patient characteristics and anatomical features correlate to accuracy of organ dose reconstruction for Wilms' tumor radiation treatment plans when using a surrogate patient's CT scan?

In retrospective radiation treatment (RT) dosimetry, a surrogate anatomy is often used for patients without 3D CT. To gain insight in what the crucial aspects in a surrogate anatomy are to enable accurate dose reconstruction, we investigated the relation of patient characteristics and internal anatomical features with deviations in reconstructed organ dose using surrogate patient's CT scans. Abdominal CT scans of 35 childhood cancer patients (age: 2.1-5.6 yr; 17 boys, 18 girls) undergoing RT during 2004-2016 were included. Based on whether an intact right or left kidney is present in the CT scan, two groups were formed each containing 24 patients. From each group, four CTs associated with Wilms' tumor RT plans with an anterior-posterior-posterior-anterior field setup were selected as references. For each reference, a 2D digitally reconstructed radiograph was computed from the reference CT to simulate a 2D radiographic image and dose reconstruction was performed on the other CTs in the respective group. Deviations in organ mean dose (DEmean) of the reconstructions versus the references were calculated, as were deviations in patient characteristics (i.e. age, height, weight) and in anatomical features including organ volume, location (in 3D), and spatial overlaps. Per reference, the Pearson's correlation coefficient between deviations in DEmean and patient characteristics/features were studied. Deviation in organ locations and DEmean for the liver, spleen, and right kidney were moderately correlated (R2 > 0.5) for 8/8, 5/8, and 3/4 reference plans, respectively. Deviations in organ volume or spatial overlap and DEmean for the right and left kidney were weakly correlated (0.3 < R2 < 0.5) in 4/4 and 1/4 reference plans. No correlations (R2 < 0.3) were found between deviations in age or height and DEmean. Therefore, the performance of organ dose reconstruction using surrogate patients' CT scans is primarily related to deviation in organ location, followed by volume and spatial overlap. Further, results were plan dependent.

Target tailoring and proton beam therapy to reduce small bowel dose in cervical cancer radiotherapy : A comparison of benefits.

PURPOSE: The aim of the study was to investigate the potential clinical benefit from both target tailoring by excluding the tumour-free proximal part of the uterus during image-guided adaptive radiotherapy (IGART) and improved dose conformity based on intensity-modulated proton therapy (IMPT). METHODS: The study included planning CTs from 11 previously treated patients with cervical cancer with a >4-cm tumour-free part of the proximal uterus on diagnostic magnetic resonance imaging (MRI). IGART and robustly optimised IMPT plans were generated for both conventional target volumes and for MRI-based target tailoring (where the non-invaded proximal part of the uterus was excluded), yielding four treatment plans per patient. For each plan, the V15Gy, V30Gy, V45Gy and Dmean for bladder, sigmoid, rectum and bowel bag were compared, and the normal tissue complication probability (NTCP) for ≥grade 2 acute small bowel toxicity was calculated. RESULTS: Both IMPT and MRI-based target tailoring resulted in significant reductions in V15Gy, V30Gy, V45Gy and Dmean for bladder and small bowel. IMPT reduced the NTCP for small bowel toxicity from 25% to 18%; this was further reduced to 9% when combined with MRI-based target tailoring. In four of the 11 patients (36%), NTCP reductions of >10% were estimated by IMPT, and in six of the 11 patients (55%) when combined with MRI-based target tailoring. This >10% NTCP reduction was expected if the V45Gy for bowel bag was >275 cm3 and >200 cm3, respectively, during standard IGART alone. CONCLUSIONS: In patients with cervical cancer, both proton therapy and MRI-based target tailoring lead to a significant reduction in the dose to surrounding organs at risk and small bowel toxicity.

Density override in treatment planning to mitigate the dosimetric effect induced by gastrointestinal gas in esophageal cancer radiation therapy.

PURPOSE: To investigate the dosimetric effect of variable gas volume in esophageal cancer radiation therapy (RT) and whether a density override (DO) in treatment planning can effectively mitigate this dosimetric effect. MATERIAL AND METHODS: Nine patients with gastrointestinal gas pockets in the planning computed tomography (pCT) were retrospectively included. Per patient, the intensity-modulated RT (IMRT) and volumetric-modulated arc therapy (VMAT) plans associated with no DO, DO = 0.5, and DO = 1 in the gas pockets were made. Initial and follow-up gas volumes were assessed from the pCTs and cone-beam CTs (CBCTs), respectively. Fractional CTs were created based on the pCT and CBCTs to calculate the fractional doses using all six plans. We then investigated for all six plans the correlation between the gas volume difference (relative to initial gas volume) and the dose difference (relative to planned dose). We also calculated and compared the accumulated dose by summing the fractional doses using two strategies: single-plan strategy (i.e. using each of the six plans separately) and plan-selection strategy (i.e. selecting one of the three plans depending on the fractional gas volume for IMRT and VMAT planning separately). RESULTS: The dose difference was approximately linearly correlated to the gas volume difference. Underdoses of >3.5% and overdoses of >7% were found for gas volume decreases >160 mL/330 mL and increases >260 mL/370 mL for IMRT/VMAT planning, respectively. Moreover, for most patients, the single-plan strategy with the use of DO = 0.5 resulted in neither undesired underdose nor much overdose. The plan-selection strategy, however, can always ensure sufficient target coverage and minimize high dose regions to the most extent. CONCLUSIONS: The variation in gas volume during the treatment course can result in clinically undesired underdose or overdose. The DO-based plan-selection strategy can effectively mitigate the gas-induced underdose and minimize the overdose for esophageal cancer RT.

Quality assurance of the PREOPANC trial (2012-003181-40) for preoperative radiochemotherapy in pancreatic cancer : The dummy run.

BACKGROUND: The Dutch Pancreatic Cancer Group initiated the national, multicentre, controlled PREOPANC trial, randomising between preoperative radiochemotherapy and direct explorative laparotomy for patients with (borderline) resectable pancreatic cancer. The aim of this dummy run is to evaluate compliance with the radiotherapy protocol of this trial, and the quality of delineation and radiation plans. METHODS: Eleven radiation oncology departments open for accrual of patients in the PREOPANC trial were provided with all necessary information of a selected 'dummy' patient. Each institute was asked to delineate the target volumes, including gross tumour volume, internal gross tumour volume (iGTV), internal clinical target volume, and planning target volume. The institutions were also asked to provide a radiation treatment plan in accordance with the PREOPANC trial protocol. RESULTS: The range of the iGTV was 19.3-77.2 cm3 with a mean iGTV of 41.5 cm3 (standard deviation 14.8 cm3). Nine institutions made a treatment plan using an arc technique for treatment delivery, one an intensity modulated technique and one a 3-field conformal technique. All institutions reached the prescribed target coverage, without exceeding the organs at risk constraints. The institution with the 3­field conformal technique was advised to use a more sophisticated technique (e. g. volumetric modulated arc therapy) to reduce the dose to the spinal cord. CONCLUSION: All institutions showed acceptable deviations from the PREOPANC trial protocol and achieved an acceptable quality of delineation and radiation technique. All institutions were allowed to continue participation in the PREOPANC trial.

Dosimetric advantages of a clinical daily adaptive plan selection strategy compared with a non-adaptive strategy in cervical cancer radiation therapy.

BACKGROUND: Radiation therapy (RT) using a daily plan selection adaptive strategy can be applied to account for interfraction organ motion while limiting organ at risk dose. The aim of this study was to quantify the dosimetric consequences of daily plan selection compared with non-adaptive RT in cervical cancer. MATERIAL AND METHODS: Ten consecutive patients who received pelvic irradiation, planning CTs (full and empty bladder), weekly post-fraction CTs and pre-fraction CBCTs were included. Non-adaptive plans were generated based on the PTV defined using the full bladder planning CT. For the adaptive strategy, multiple PTVs were created based on both planning CTs by ITVs of the primary CTVs (i.e., GTV, cervix, corpus-uterus and upper part of the vagina) and corresponding library plans were generated. Daily CBCTs were rigidly aligned to the full bladder planning CT for plan selection. For daily plan recalculation, selected CTs based on initial similarity were deformably registered to CBCTs. Differences in daily target coverage (D98% > 95%) and in V0.5Gy, V1.5Gy, V2Gy, D50% and D2% for rectum, bladder and bowel were assessed. RESULTS: Non-adaptive RT showed inadequate primary CTV coverage in 17% of the daily fractions. Plan selection compensated for anatomical changes and improved primary CTV coverage significantly (p < 0.01) to 98%. Compared with non-adaptive RT, plan selection decreased the fraction dose to rectum and bowel indicated by significant (p < 0.01) improvements for daily V0.5Gy, V1.5Gy, V2Gy, D50% and D2%. However, daily plan selection significantly increased the bladder V1.5Gy, V2Gy, D50% and D2%. CONCLUSIONS: In cervical cancer RT, a non-adaptive strategy led to inadequate target coverage for individual patients. Daily plan selection corrected for day-to-day anatomical variations and resulted in adequate target coverage in all fractions. The dose to bowel and rectum was decreased significantly when applying adaptive RT.

Probabilistic treatment planning for pancreatic cancer treatment: prospective incorporation of respiratory motion shows only limited dosimetric benefit.

BACKGROUND: We introduced a probabilistic treatment planning approach that prospectively incorporates respiratory-induced motion in the treatment plan optimization. The aim of this study was to determine the potential dosimetric benefit by comparing this approach to the use of an internal target volume (ITV). MATERIAL AND METHOD: We retrospectively compared the probabilistic respiratory motion-incorporated (RMI) approach to the ITV approach for 18 pancreatic cancer patients, for seven simulated respiratory amplitudes from 5 to 50 mm in the superior-inferior (SI) direction. For each plan, we assessed the target coverage (required: D98%≥95% of 50 Gy prescribed dose). For the RMI plans, we investigated whether target coverage was robust against daily variations in respiratory amplitude. We determined the distance between the clinical target volume and the 30 Gy isodose line (i.e. dose gradient steepness) in the SI direction. To investigate the clinical benefit of the RMI approach, we created for each patient an ITV and RMI treatment plan for the three-dimensional (3D) respiratory amplitudes observed on their pretreatment 4D computed tomography (4DCT). We determined Dmean, V30Gy, V40Gy and V50Gy for the duodenum. RESULTS: All treatment plans yielded good target coverage. The RMI plans were robust against respiratory amplitude variations up to 10 mm, as D98% remained ≥95%. We observed steeper dose gradients compared to the ITV approach, with a mean decrease from 25.9 to 19.2 mm for a motion amplitude of 50 mm. For the 4DCT motion amplitudes, the RMI approach resulted in a mean decrease of 0.43 Gy, 1.1 cm3, 1.4 cm3 and 0.9 cm3 for the Dmean, V30Gy, V40Gy and V50Gy of the duodenum, respectively. CONCLUSION: The probabilistic treatment planning approach yielded significantly steeper dose gradients and therefore significantly lower dose to surrounding healthy tissues than the ITV approach. However, the observed dosimetric gain for clinically observed respiratory motion amplitudes for this patient group was limited.

Interfractional renal and diaphragmatic position variation during radiotherapy in children and adults: is there a difference?

BACKGROUND: Pediatric safety margins are generally based on data from adult studies; however, adult-based margins might be too large for children. The aim of this study was to quantify and compare interfractional organ position variation in children and adults. MATERIAL AND METHODS: For 35 children and 35 adults treated with thoracic/abdominal irradiation, 850 (range 5-30 per patient) retrospectively collected cone beam CT images were registered to the reference CT that was used for radiation treatment planning purposes. Renal position variation was assessed in three orthogonal directions and summarized as 3D vector lengths. Diaphragmatic position variation was assessed in the cranio-caudal (CC) direction only. We calculated means and SDs to estimate group systematic (Σ) and random errors (σ) of organ position variation. Finally, we investigated possible correlations between organ position variation and patients' height. RESULTS: Interfractional organ position variation was different in children and adults. Median 3D right and left kidney vector lengths were significantly smaller in children than in adults (2.8, 2.9 mm vs. 5.6, 5.2 mm, respectively; p < .05). Generally, the pediatric Σ and σ were significantly smaller than in adults (p < .007). Overall and within both subgroups, organ position variation and patients' height were only negligibly correlated. CONCLUSIONS: Interfractional renal and diaphragmatic position variation in children is smaller than in adults indicating that pediatric margins should be defined differently from adult margins. Underlying mechanisms and other components of geometrical uncertainties need further investigation to explain differences and to appropriately define pediatric safety margins.

Addition of MRI for CT-based pancreatic tumor delineation: a feasibility study.

PURPOSE: To assess the effect of additional magnetic resonance imaging (MRI) alongside the planning computed tomography (CT) scan on target volume delineation in pancreatic cancer patients. MATERIAL AND METHODS: Eight observers (radiation oncologists) from six institutions delineated the gross tumor volume (GTV) on 3DCT, and internal GTV (iGTV) on 4DCT of four pancreatic cancer patients, while MRI was available in a second window (CT + MRI). Variations in volume, generalized conformity index (CIgen), and overall observer variation, expressed as standard deviation (SD) of the distances between delineated surfaces, were analyzed. CIgen is a measure of overlap of the delineated iGTVs (1 = full overlap, 0 = no overlap). Results were compared with those from an earlier study that assessed the interobserver variation by the same observers on the same patients on CT without MRI (CT-only). RESULTS: The maximum ratios between delineated volumes within a patient were 6.1 and 22.4 for the GTV (3DCT) and iGTV (4DCT), respectively. The average (root-mean-square) overall observer variations were SD = 0.41 cm (GTV) and SD = 0.73 cm (iGTV). The mean CIgen was 0.36 for GTV and 0.37 for iGTV. When compared to the iGTV delineated on CT-only, the mean volumes of the iGTV on CT + MRI were significantly smaller (32%, Wilcoxon signed-rank, p < .0005). The median volumes of the iGTV on CT + MRI were included for 97% and 92% in the median volumes of the iGTV on CT. Furthermore, CT + MRI showed smaller overall observer variations (root-mean-square SD = 0.59 cm) in six out of eight delineated structures compared to CT-only (root-mean-square SD = 0.72 cm). However, large local observer variations remained close to biliary stents and pathological lymph nodes, indicating issues with instructions and instruction compliance. CONCLUSIONS: The availability of MRI images during target delineation of pancreatic cancer on 3DCT and 4DCT resulted in smaller target volumes and reduced the interobserver variation in six out of eight delineated structures.

Dosimetric effects of anatomical changes during fractionated photon radiation therapy in pancreatic cancer patients.

Pancreatic tumors show large interfractional position variation. In addition, changes in gastrointestinal gas volumes and body contour take place over the course of radiation therapy. We aimed to quantify the effect of these anatomical changes on target dose coverage, for the clinically used fiducial marker-based patient position verification and, for comparison, also for simulated bony anatomy-based position verification. Nine consecutive patients were included in this retrospective study. To enable fraction dose calculations on cone-beam CT (CBCT), the planning CT was deformably registered to each CBCT (13-15 per patient); gas volumes visible on CBCT were copied to the deformed CT. Fraction doses were calculated for the clinically used 10 MV VMAT treatment plan (with for the planning target volume (PTV): D98% = 95%), according to fiducial marker-based and bony anatomy-based image registrations. Dose distributions were rigidly summed to yield the accumulated dose. To evaluate target dose coverage, we defined an iCTV+5 mm volume, i.e., the internal clinical target volume (iCTV) expanded with a 5 mm margin to account for remaining uncertainties including delineation uncertainties. We analyzed D98% , Dmean , and D2% for iCTV+5 mm and PTV (i.e., iCTV plus 10 mm margin). We found that for fiducial marker-based registration, differences between fraction doses and planned dose were minimal. For bony anatomy-based registration, fraction doses differed considerably, resulting in large differences between planned and accumulated dose for some patients, up to a decrease in D98% of the iCTV+5 mm from 95.9% to 85.8%. Our study shows that fractionated photon irradiation of pancreatic tumors is robust against variations in body contour and gastrointestinal gas, with dose coverage only mildly affected. However, as a result of interfractional tumor position variations, target dose coverage can severely decline when using bony anatomy for patient position verification. Therefore, the use of intratumoral fiducial marker-based daily position verification is essential in pancreatic cancer patients.

Considerable pancreatic tumor motion during breath-holding.

BACKGROUND: Breath-holding (BH) is often used to reduce abdominal organ motion during radiotherapy. However, for inhale BH, abdominal tumor motion during BH has not yet been investigated. The aim of this study was to quantify tumor motion during inhale BH and tumor position variations between consecutive inhale BHs in pancreatic cancer patients. MATERIAL AND METHODS: Twelve patients with intratumoral fiducials were included and asked to perform three consecutive 30-second inhale BHs on each of three measurement days. During BH, lateral fluoroscopic movies were obtained and a two-dimensional (2D) image correlation algorithm was used to track the fiducials and the diaphragm, yielding the tumor and diaphragm motion during each BH. The tumor position variation between consecutive BHs was obtained from the difference in initial tumor position between consecutive BHs on a single measurement day. RESULTS: We observed tumor motion during BH with a mean absolute maximum displacement over all BHs of 4.2 mm (range 1.0-11.0 mm) in inferior-superior (IS) direction and 2.7 mm (range 0.5-8.0 mm) in anterior-posterior (AP) direction. We found only a moderate correlation between tumor and diaphragm motion in the IS direction (Pearson's correlation coefficient |r|>0.6 in 45 of 76 BHs). The mean tumor position variation between consecutive BHs was 0.2 [standard deviation (SD) 1.7] mm in the inferior direction and 0.5 (SD 0.8) mm in the anterior direction. CONCLUSION: We observed substantial pancreatic tumor motion during BH as well as considerable position variation between consecutive BHs on a single day. We recommend further quantifying these uncertainties before introducing breath-hold during radiation treatment of pancreatic cancer patients. Also, the diaphragm cannot be used as a surrogate for pancreatic tumor motion.

Dosimetric advantages of proton therapy compared with photon therapy using an adaptive strategy in cervical cancer.

Background Image-guided adaptive proton therapy (IGAPT) can potentially be applied to take into account interfraction motion while limiting organ at risk (OAR) dose in cervical cancer radiation therapy (RT). In this study, the potential dosimetric advantages of IGAPT compared with photon-based image-guided adaptive RT (IGART) were investigated. Material and methods For 13 cervical cancer patients, full and empty bladder planning computed tomography (CT) images and weekly CTs were acquired. Based on both primary clinical target volumes (pCTVs) [i.e. gross tumor volume (GTV), cervix, corpus-uterus and upper part of the vagina] on planning CTs, the pretreatment observed full range primary internal target volume (pITV) was interpolated to derive pITV subranges. Given corresponding ITVs (i.e. pITVs including lymph nodes), patient-specific photon and proton plan libraries were generated. Using all weekly CTs, IGART and IGAPT treatments were simulated by selecting library plans and recalculating the dose. For each recalculated IGART and IGAPT fraction, CTV (i.e. pCTV including lymph nodes) coverage was assessed and differences in fractionated substitutes of dose-volume histogram (DVH) parameters (V15Gy, V30Gy, V45Gy, Dmean, D2cc) for bladder, bowel and rectum were tested for significance (Wilcoxon signed-rank test). Also, differences in toxicity-related DVH parameters (rectum V30Gy, bowel V45Gy) were approximated based on accumulated dose distributions. Results In 92% (96%) of all recalculated IGAPT (IGART) fractions adequate CTV coverage (V95% >98%) was obtained. All dose parameters for bladder, bowel and rectum, except the fractionated substitute for rectum V45Gy, were improved using IGAPT. Also, IGAPT reduced the mean dose to bowel, bladder and rectum significantly (p < 0.01). In addition, an average decrease of rectum V30Gy and bowel V45Gy indicated reductions in toxicity probabilities when using IGAPT. Conclusion This study demonstrates the feasibility of IGAPT in cervical cancer using a plan-library based plan-of-the-day approach. Compared to photon-based IGART, IGAPT maintains target coverage while significant dose reductions for the bladder, bowel and rectum can be achieved.

Thermoradiotherapy planning: Integration in routine clinical practice.

Planning of combined radiotherapy and hyperthermia treatments should be performed taking the synergistic action between the two modalities into account. This work evaluates the available experimental data on cytotoxicity of combined radiotherapy and hyperthermia treatment and the requirements for integration of hyperthermia and radiotherapy treatment planning into a single planning platform. The underlying synergistic mechanisms of hyperthermia include inhibiting DNA repair, selective killing of radioresistant hypoxic tumour tissue and increased radiosensitivity by enhanced tissue perfusion. Each of these mechanisms displays different dose-effect relations, different optimal time intervals and different optimal sequences between radiotherapy and hyperthermia. Radiosensitisation can be modelled using the linear-quadratic (LQ) model to account for DNA repair inhibition by hyperthermia. In a recent study, an LQ model-based thermoradiotherapy planning (TRTP) system was used to demonstrate that dose escalation by hyperthermia is equivalent to ∼10 Gy for prostate cancer patients treated with radiotherapy. The first step for more reliable TRTP is further expansion of the data set of LQ parameters for normally oxygenated normal and tumour tissue valid over the temperature range used clinically and for the relevant time intervals between radiotherapy and hyperthermia. The next step is to model the effect of hyperthermia in hypoxic tumour cells including the physiological response to hyperthermia and the resulting reoxygenation. Thermoradiotherapy planning is feasible and a necessity for an optimal clinical application of hyperthermia combined with radiotherapy in individual patients.

Quantification of delineation errors of the gross tumor volume on magnetic resonance imaging in uterine cervical cancer using pathology data and deformation correction.

BACKGROUND: To safely optimize target volumes using magnetic resonance imaging (MRI) for uterine cervical cancer radiation therapy, MRI findings need to be validated. The aim of this study was to correlate pre-operatively acquired MRI and surgical specimen imaging for uterine cervical cancer patients using deformable image registration and quantify gross tumor volume (GTV) delineation discrepancies. MATERIAL AND METHODS: For 16 retrospectively selected early-stage uterine cervical cancer patients, the cervix-uterus structure, uterine cavity and the GTV were delineated on 2D pathology photos after macroscopic intersection and corresponding pre-operatively acquired T2-weighted 2D sagittal MR images. Segmentations of pathology photos and MR images were simultaneously registered using a three-step multi-image registration strategy. The registration outcome was evaluated by the Dice similarity coefficient (DSC) and the surface distance error (SDE). In addition, GTV expansions within the cervix-uterus structure needed to obtain 95% GTV coverage were determined. RESULTS: After three-step multi-image registration, the median DSC and median SDE were 0.98 and 0.4 mm (cervix-uterus) and 0.90 and 0.4 mm (uterine cavity), respectively. The average SDE around the GTV was 0.7 mm (range, 0.1 mm - 2.6 mm). An underestimation of MRI-based GTV delineations was found when no margin was applied, indicated by a mean GTV coverage of 61%. To obtain 95% GTV coverage for 90% of the patients, a minimum 12.0 mm margin around MRI-based GTVs was needed. CONCLUSION: The presented three-step multi-image registration strategy was suitable and accurate to correlate MRI and pathology data for uterine cervical cancer patients. To cover the pathology-based GTV, a margin of at least 12.0 mm around GTV delineations on T2-weighted MRI is needed.

Differences in respiratory-induced pancreatic tumor motion between 4D treatment planning CT and daily cone beam CT, measured using intratumoral fiducials.

BACKGROUND: In radiotherapy, the magnitude of respiratory-induced tumor motion is often measured using a single four-dimensional computed tomography (4DCT). This magnitude is required to determine the internal target volume. The aim of this study was to compare the magnitude of respiratory-induced motion of pancreatic tumors on a single 4DCT with the motion on daily cone beam CT (CBCT) scans during a 3-5-week fractionated radiotherapy scheme. In addition, we investigated changes in the respiratory motion during the treatment course. MATERIAL AND METHODS: The mean peak-to-peak motion (i.e. magnitude of motion) of pancreatic tumors was measured for 18 patients using intratumoral gold fiducials visible on CBCT scans made prior to each treatment fraction (10-27 CBCTs per patient; 401 CBCTs in total). For each patient, these magnitudes were compared to the magnitude measured on 4DCT. Possible time trends were investigated by applying linear fits to the tumor motion determined from daily CBCTs as a function of treatment day. RESULTS: We found a significant (p ≤ 0.01) difference between motion magnitude on 4DCT and on CBCT in superior-inferior, anterior-posterior and left-right direction, in 13, 9 and 12 of 18 patients, respectively. In the anterior- posterior and left-right direction no fractions had a difference ≥ 5 mm. In the superior-inferior direction the difference was ≥ 5 mm for 17% of the 401 fractions. In this direction, a significant (p ≤ 0.05) time trend in tumor motion was observed in 4 of 18 patients, but all trends were small (- 0.17-0.10 mm/day) and did not explain the large differences in motion magnitude between 4DCT and CBCT. CONCLUSION: A single measurement of the respiratory-induced motion magnitude of pancreatic tumors using 4DCT is often not representative for the magnitude during daily treatment over a 3-5-week radiotherapy scheme. For this patient group it may be beneficial to introduce breath-hold to eliminate respiratory-induced tumor motion.

Stomach Motion and Deformation: Implications for Preoperative Gastric Cancer Radiation Therapy.

PURPOSE: Selection and development of image guided strategies for preoperative gastric radiation therapy requires quantitative knowledge of the various sources of anatomic changes of the stomach. This study aims to investigate the magnitude of interfractional and intrafractional stomach motion and deformation using fiducial markers and 4-dimensional (4D) imaging. METHODS AND MATERIALS: Fourteen patients who underwent preoperative gastric cancer radiation therapy received 2 to 6 fiducial markers distributed throughout the stomach (total of 54 markers) and additional imaging (ie, 1 planning 4D computed tomography [pCT], 20-25 pretreatment 4D cone beam [CB] CTs, 4-5 posttreatment 4D CBCTs). Marker coordinates on all end-exhale (EE) and end-inhale (EI) scans were obtained after a bony anatomy match. Interfractional marker displacements (ie, between EE pCT and all EE CBCTs) were evaluated for 5 anatomic regions (ie, cardia, small curvature, proximal and distal large curvature, and pylorus). Motion was defined as displacement of the center-of-mass of available markers (COMstomach), deformation as the average difference in marker-pair distances. Interfractional (ie, between EE pCT and all EE CBCTs), respiratory (between EE and EI pCT and CBCTs), and pre-post (pre- and posttreatment EE CBCTs) motion and deformation were quantified. RESULTS: The interfractional marker displacement varied per anatomic region and direction, with systematic and random errors ranging from 1.6-8.8 mm and 2.2-8.2 mm, respectively. Respiratory motion varied per patient (median, 3-dimensional [3D] amplitude 5.2-20.0 mm) and day (interquartile range, 0.8-4.2 mm). Regarding COMstomach motion, respiratory motion was larger than interfractional motion (median, 10.9 vs 8.9 mm; P < .0001; Wilcoxon rank-sum), which was larger than pre-post motion (3.6 mm; P < .0001). Interfractional deformations (median, 5.8 mm) were significantly larger than pre-post deformations (2.6 mm; P < .0001), which were larger than respiratory deformation (1.8 mm; P < .0001). CONCLUSIONS: The demonstrated sizable stomach motions and deformations during radiation therapy stress the need for generous nonuniform planning target volume margins for preoperative gastric cancer radiation therapy. These margins can be decreased by daily image guidance and adaptive radiation therapy.

Virtual unenhanced dual-energy computed tomography for photon radiotherapy: The effect on dose distribution and cone-beam computed tomography based position verification.

Background and Purpose: Virtual Unenhanced images (VUE) from contrast-enhanced dual-energy computed tomography (DECT) eliminate manual suppression of contrast-enhanced structures (CES) or pre-contrast scans. CT intensity decreases in high-density structures outside the CES following VUE algorithm application. This study assesses VUE's impact on the radiotherapy workflow of gynecological tumors, comparing dose distribution and cone-beam CT-based (CBCT) position verification to contrast-enhanced CT (CECT) images. Materials and Methods: A total of 14 gynecological patients with contrast-enhanced CT simulation were included. Two CT images were reconstructed: CECT and VUE. Volumetric Modulated Arc Therapy (VMAT) plans generated on CECT were recalculated on VUE using both the CECT lookup table (LUT) and a dedicated VUE LUT. Gamma analysis assessed 3D dose distributions. CECT and VUE images were retrospectively registered to daily CBCT using Chamfer matching algorithm.. Results: Planning target volume (PTV) dose agreement with CECT was within 0.35% for D2%, Dmean, and D98%. Organs at risk (OARs) D2% agreed within 0.36%. A dedicated VUE LUT lead to smaller dose differences, achieving a 100% gamma pass rate for all subjects. VUE imaging showed similar translations and rotations to CECT, with significant but minor translation differences (<0.02 cm). VUE-based registration outperformed CECT. In 24% of CBCT-CECT registrations, inadequate registration was observed due to contrast-related issues, while corresponding VUE images achieved clinically acceptable registrations. Conclusions: VUE imaging in the radiotherapy workflow is feasible, showing comparable dose distributions and improved CBCT registration results compared to CECT. VUE enables automated bone registration, limiting inter-observer variation in the Image-Guided Radiation Therapy (IGRT) process.

Improved tumour control probability with MRI-based prostate brachytherapy treatment planning.

BACKGROUND: Due to improved visibility on MRI, contouring of the prostate is improved compared to CT. The aim of this study was to quantify the benefits of using MRI for treatment planning as compared to CT-based planning for temporary implant prostate brachytherapy. MATERIAL AND METHODS: CT and MRI image data of 13 patients were used to delineate the prostate and organs at risk (OARs) and to reconstruct the implanted catheters (typically 12). An experienced treatment planner created plans on the CT-based structure sets (CT-plan) and on the MRI-based structure sets (MRI-plan). Then, active dwell-positions and weights of the CT-plans were transferred to the MRI-based structure sets (CT-plan(MRI-contours)) and resulting dosimetric parameters and tumour control probabilities (TCPs) were studied. RESULTS: For the CT-plan(MRI-contours) a statistically significant lower target coverage was detected: mean V100 was 95.1% as opposed to 98.3% for the original plans (p < 0.01). Planning on CT caused cold-spots that influence the TCP. MRI-based planning improved the TCPs by 6-10%, depending on the parameters of the radiobiological model used for TCP calculation. Basing the treatment plan on either CT- or MRI-delineations does not influence plan quality. CONCLUSION: Evaluation of CT-based treatment planning by transferring the plan to MRI reveals underdosage of the prostate, especially at the base side. Planning on MRI can prevent cold-spots in the tumour and improves the TCP.