Bladder Volume Variation Research Articles

Evaluation of cumulative dose distributions from external beam radiation therapy using CT-to-CBCT deformable image registration (DIR) for cervical cancer patients.

To investigate dose differences between the planning CT (pCT) and dose calculated on pre-treatment verification CBCTs using DIR and dose summation for cervical cancer patients. Cervical cancer patients treated at our institution with 45Gy EBRT undergo a pCT and 5 CBCTs, once every five fractions of treatment. A free-form intensity-based DIR in MIM was performed between the pCT and each CBCT using the "Merged CBCT" feature to generate an extended FOV-CBCT (mCBCT). DIR-generated bladder and rectum contours were adjusted by a physician, and dice similarity coefficients (DSC) were calculated. After deformation, the investigated doses were (1) recalculated in Eclipse using original plan parameters (ecD), and (2) deformed from planning dose (pD) using the deformation matrix in MIM (mdD). Dose summation was performed to the first week's mCBCT. Dose distributions were compared for the bladder, rectum, and PTV in terms of percent dose difference, dose volume histograms (DVHs), and gamma analysis between the calculated doses. For the 20 patients, the mean DSC was 0.68±0.17 for bladder and 0.79±0.09 for rectum. Most patients were within 5% of pD for D2cc (19/20), Dmax (17/20), and Dmean (16/20). All patients demonstrated a percent difference>5% for bladder V45 due to variations in bladder volume from the pCT. D90 showed fewer differences with 19/20 patients within 2% of pD. Gamma rates between pD and ecD averaged 94% for bladder and 94% for rectum, while pD and mdD exhibited slightly better performance for bladder (93%) and lower for rectum (85%). Using DIR with weekly CBCT images, the MIM deformed dose (mdD) was found to be in close agreement with the Eclipse calculated dose (ecD). The proposed workflow should be used on a case-by-case basis when the weekly CBCT shows marked difference in organs-at-risk from the planning CT.

Adaptive radiotherapy for muscle invasive bladder cancer: a retrospective audit of two bladder filling protocols

BackgroundRadical radiotherapy for muscle-invasive bladder cancer (MIBC) is challenging due to large variations in bladder shape, size and volume during treatment, with drinking protocols often employed to mitigate geometric uncertainties. Utilising adaptive radiotherapy together with CBCT imaging to select a treatment plan that best fits the bladder target and reduce normal tissue irradiation is an attractive option to compensate for anatomical changes. The aim of this retrospective study was to compare a bladder empty (BE) protocol to a bladder filling (BF) protocol with regards to variations in target volumes, plan of the day (PoD) selection and plan dosimetry throughout treatment.MethodsForty patients were included in the study; twenty were treated with a BE protocol and twenty with a BF protocol to a total prescribed dose of 55 Gy in 20 fractions. Small, medium and large bladder plans were generated using three different CTV to PTV margins. Bladder (CTV) volumes were delineated on planning CTs and online pre-treatment CBCTs. Differences in CTV volumes throughout treatment, plan selection, PTV volumes and resulting dose metrics were compared for both protocols.ResultsMean bladder volume differed significantly on both the planning CTs and online pre-treatment CBCTs between the protocols (p < 0.05). Significant differences in bladder volumes were observed between the planning CT and pre-treatment CBCTs for BF (p < 0.05) but not for BE (p = 0.11). Both protocols saw a significant decrease in bladder volume between first and final treatment fractions (p < 0.05). Medium plans were preferentially selected for BE whilst when using the BF protocol the small plan was chosen most frequently. With no significant change to PTV coverage between the protocols, the volume of body receiving 25.0–45.8 Gy was found to be significantly smaller for BE patients (p < 0.05).ConclusionsThis work provides evidence in favour of a BE protocol compared to a BF protocol for radical radiotherapy for MIBC. The smaller treatment volumes observed in the BE protocol led to reduced OAR and total body doses and were also observed to be more consistent throughout the treatment course. These results highlight improvements in dosimetry for patients who undergo a BE protocol for MIBC.

Clinical Implementation of “Plan of the Day” Strategy in Definitive Radiation Therapy of Cervical Cancer: Online Adaptation to Address the Challenge of Organ Filling Reproducibility

Background: Definitive pelvic intensity-modulated radiotherapy (IMRT) in cervical cancer is susceptible to geographic miss due to daily positional and volumetric variations in target and organs at risk. Hence, despite evidence of reduced acute and late treatment-related toxicities, implementation of image-guided IMRT (IG-IMRT) with a reasonable safety margin to encompass organ motion is challenging. Materials and Methods: In this prospective, non-randomized phase II study, patients with cervical cancer FIGO (2009) stage IB2-IIIB between the ages of 18 and 65 years were treated with definitive pelvic CT-RT with a pre-specified organ (bladder and rectum) filling protocol. Reproducibility of organ filling was assessed along with the implementation of daily comprehensive adaptive IGRT, with a library of 3 IMRT (VMAT) plans with incremental expansions of CTV to PTV (Primary) margins (small 0.7 cm, adequate 1 cm and large 1.5 cm) and a backup motion robust 3DCRT plan; the appropriate plan is chosen based on pre-treatment CBCT (‘Plan of the Day’ approach). Results: Fifty patients with a median age of 49 years (IQR 45-56 years), received definitive RT (45-46Gy in 23-25 fractions to pelvis; with simultaneous integrated boost to gross nodes in 15 patients) with the said IGRT protocol. In the analysis of 1171 CBCT images (in 1184 treatment sessions), the mean planning CT and CBCT bladder volumes were 417 ccs and 373 ccs respectively. Significant inter-fractional variation in bladder volume was noted with a mean absolute dispersion of 29.5% with respect to planning CT; significant influential random factors were post-chemotherapy sessions (p=<0.001), pre-CBCT protocol duration (p= 0.001), grades of CINV (p=0.001). Significantly higher variation in bladder filling noted in patients with higher age (p=0.014) and larger planning CT bladder volume (p=<0.001). Time trend analysis of fraction-wise bladder volume revealed an absolute systemic reduction of 16.3% in bladder volume means from 1st to 5th week. Variation in rectal diameter was much less pronounced, with 19.2% mean dispersion, without any significant factors affecting it.While in 19% and 2% of sessions ‘Large’ IMRT PTV and ‘3DCRT’ were necessary to cover the primary target respectively, reduction in treated volume was possible in 43% of sessions with ‘Small’ PTV selection instead of standard ‘Adequate’ PTV (36% sessions). ‘Plan of the day’ selection had a moderate to strong correlation with non-absolute dispersion of bladder filling (Spearman's R= 0.4; p= 0.001) and a weak (but significant) correlation with grades of acute toxicities. The planned protocol was well tolerated with no radiation-induced local grade III toxicity. Conclusion: Inter-fractional variation in organ filling (especially bladder) is inevitable despite fixed pre-treatment protocol in definitive settings (intact cervix). Despite the logistical challenges; adaptive IGRT in form of ‘plan of the day’ based on incremental CTV-to-PTV margins is a relatively simple and feasible strategy to minimise geometric uncertainties in radical IG-IMRT of cervical cancer.

Early Experience with CBCT-Guided Online Adaptive Radiotherapy for Muscle Invasive Bladder Cancer.

Radiation therapy for muscle-invasive bladder cancer (MIBC) requires substantial planning target volume (PTV) margins to account for variability in bladder filling as well as other anatomic changes. We hypothesized that CBCT-guided online adaptive RT (oART) may both improve target coverage and reduce normal tissue exposure as compared to non-adaptive RT. The purpose of this study is to report the dosimetric results of our initial experience utilizing oART for treatment of MIBC. Seven patients with MIBC were treated with oART over a 1-year period. Patients were simulated with an empty bladder and were asked to void prior to each treatment. Five patients received 55 Gy in 20 fractions to a clinical target volume (CTV) expanded from the TURBT bed and 46 Gy simultaneously to the remaining bladder and for 2 patients the high dose CTV was the entire bladder. PTVs consisted of a 7mm isometric expansion of the CTV. The oART delivery process initially coregisters the daily CBCT to the treatment planning CBCT using skeletal alignment. Target volumes and organs-at-risk (OARs) were modified at each treatment session and the plan re-optimized to meet prespecified clinical goals. Target coverage and OAR dosimetric parameters for the adaptive were compared non-adaptive (scheduled) plan for each fraction using the Wilcoxon paired test of means. The adapted plan was selected for delivery for all fractions across all patients. Daily bladder volumes differed from the bladder volume at simulation by a mean of 60cc ± 66cc. At least 95% of the high dose CTV was covered by the prescription dose for 139 (99.3%) fractions with the oART plan as compared to 70 (50%) fractions with scheduled. A portion of the high dose CTV was outside of the 80% isodose line for 13 (9.3%) of scheduled fractions and was outside of the 50% isodose line for 2 (0.01%) of scheduled fractions. There were no cases of oART plans where any portion of the high dose CTV was outside of the 90% isodose line. A comparison of selected target and OAR dosimetric parameters is shown in the Table. oART treatment plans were associated with greater target coverage and less OAR exposure for all metrics. In this initial experience, oART resulted in acceptable delivered dosimetry to target volumes with a reduced PTV margin of 7mm despite considerable daily variation in bladder volume. As expected, oART plans were associated with improved target coverage and OAR dosimetry. Future patient-centered studies should explore the clinical impact of reduced margin oART for patients with MIBC.

Effectiveness of bladder filling control during online MR-guided adaptive radiotherapy for rectal cancer

BackgroundMagnetic resonance-guided adaptive radiotherapy (MRgART) treatment sessions at MR-Linac are time-consuming and changes in organs at risk volumes can impact the treatment dosimetry. This study aims to evaluate the feasibility to control bladder filling during the rectum MRgART online session and its effectiveness on plan dosimetry.MethodsA total of 109 online adaptive sessions of 24 rectum cancer patients treated at Unity 1.5 T MR-Linac with a short course radiotherapy (25 Gy, 5 Gy × 5) for whom the adaptive plan was optimized and recalculated online based on the daily magnetic resonance imaging (MRI) were analysed. Patients were fitted with a bladder catheter to control bladder filling; the bladder is emptied and then partially filled with a known amount of saline at the beginning and end of the online session. A first MRI ({mathrm{MRI}}_{mathrm{i}}) acquired at the beginning of the session was used for plan adaptation and the second ({mathrm{MRI}}_{mathrm{f}}) was acquired while approving the adapted plan and rigidly registered with the first to ensure the appropriateness of the isodoses on the ongoing delivery treatment. For each fraction, the time interval between the two MRIs and potential bladder changes were assessed with independent metrics, and the impact on the plan dosimetry was evaluated by comparing target and organs at risk dose volume histogram cut-off points of the plan adapted on {mathrm{MRI}}_{mathrm{i}} and recalculated on {mathrm{MRI}}_{mathrm{f}}.ResultsMedian bladder volume variations, DSC, and HD of 8.17%, 0.922, and 2.92 mm were registered within a median time of 38 min between {mathrm{MRI}}_{mathrm{i}} and {mathrm{MRI}}_{mathrm{f}}; dosimetric differences < 0.65% were registered for target coverage, and < 0.5% for bladder, small bowel and femoral heads constraints, with a p value > 0.05.ConclusionThe use of a bladder filling control procedure can help ensure the dosimetric accuracy of the online adapted treatment delivered.

Planning Target Volume Margin Determination for Volumetric Modulated Arc Therapy Planning in Cervix Cancers Using an Empty Bladder Protocol

OBJECTIVE To evaluate the planning target volume (PTV) margin and bladder volume variation of volumetric modulated arc therapy (VMAT) in cervical cancer using an empty bladder protocol. METHODS Ten patients with cervical cancer who had indications to receive whole pelvic radiotherapy and who had been identified to receive whole pelvic irradiation with a dose of 46-55.2 Gy in 23 fractions planned by VMAT were included. International Commission on Radiation Units and Measurements (ICRU) Report 83 was used to report plan parameters. The empty bladder protocol is designed for use with all patients before simulation and irradiation. From June 2020 to February 2021, 215 fractions from the 10 patients were evaluated. The ‘all fraction’ set-up errors were recorded using cone-beam computed tomography (CBCT) and were interpreted as error margins using the Van Herk Formula. RESULTS The calculated PTV margins were 0.75, 0.84, and 0.98 cm on the X, Y, and Z-axes, respectively. The median volume of the bladder before irradiation was 40.6 cc, with an interquartile range of 31.9 to 59.2 cc. The average change in bladder volume from the planning volume was 23.56%. CONCLUSIONS Using the empty bladder protocol, the clinical target volume (CTV) to PTV margin was 1 cm following the Van Herk formula. No patients experienced side effects of grade 3 or greater. The empty bladder protocol is a method which can reduce target placement error and reduce patient discomfort without causing serious side effects. KEYWORDS PTV margin, VMAT, IGRT, Cervix cancer, Empty bladder

A new target localization method for image-guided radiation therapy of prostate cancer

In imaged-guided radiation therapy (IGRT), target localization is usually done with rigid-body registration based on anatomy matching. Problems arise when the target volume can only be matched partially due to inter-fractional organ motion and deformation, resulting in deteriorated target coverage and critical structure sparing. A new target localization method is investigated in which the treatment target volume is aligned with the prescription isodose surface. Our study included 15 prostate patients previously treated with intensity-modulated radiation therapy (IMRT). Patient setup and target localization were performed using a CT-on-rails system before and after the IMRT treatment. IMRT plans were generated on the original simulation CTs (15) and the same MUs and leaf sequences were used to compute the dose distributions on post-treatment CTs (98) with the isocenter adjustments based on either anatomical structure matching or prescription isodose surface alignment. When patients were aligned with the traditional anatomy matching method, the dose to 95% of the CTV, D95, received 74.0 – 77.6 Gy and the minimum CTV dose, Dmin, was 61.9 – 71.6 Gy, respectively, in the cumulative dose distributions. The rectal dose-volume constraints were violated in 35.7% of the treatment fractions. When patients were aligned using the new localization method, the dose to 95% of the CTV, D95, received 74.0 – 78.2 Gy and the minimum CTV dose, Dmin, was 68.4 – 71.6 Gy, respectively, in the cumulative dose distributions. The rectal dose-volume constraints were violated in 17.3% of the treatment fractions. Traditional IGRT target localization based on anatomy matching is effective for population-based PTV margins but not ideal for those patients with large inter-fractional prostate rotation/deformation due to large rectal and bladder volume variation. The new method using the prescription isodose surface to align the target volume could improve the target coverage and rectal sparing for these patients, which can be implemented clinically to improve target dose delivery accuracy.

Clinical Practice Evolvement for Post-Operative Prostate Cancer Radiotherapy-Part 1: Consistent Organs at Risk Management with Advanced Image Guidance.

Purpose: Post-operative prostate cancer patients are treated with full bladder instruction and the use of an endorectal balloon (ERB). We reassessed the efficacy of this practice based on daily image guidance and dose delivery using high-quality iterative reconstructed cone-beam CT (iCBCT). Methods: Fractional dose delivery was calculated on daily iCBCT for 314 fractions from 14 post-operative prostate patients (8 with and 6 without ERB) treated with volumetric modulated radiotherapy (VMAT). All patients were positioned using novel iCBCT during image guidance. The bladder, rectal wall, femoral heads, and prostate bed clinical tumor volume (CTV) were contoured and verified on daily iCBCT. The dose-volume parameters of the contoured organs at risk (OAR) and CTV coverage were assessed for the clinical impact of daily bladder volume variations and the use of ERB. Minimum bladder volume was studied, and a straightforward bladder instruction was explored for easy clinical adoption. Results: A “minimum bladder” contour, the overlap between the original bladder contour and a 15 mm anterior and superior expansion from prostate bed PTV, was confirmed to be effective in identifying cases that might fail a bladder constraint of V65% <60%. The average difference between the maximum and minimum bladder volumes for each patient was 277.1 mL. The daily bladder volumes varied from 62.4 to 590.7 mL and ranged from 29 to 286% of the corresponding planning bladder volume. The bladder constraint of V65% <60% was met in almost all fractions (98%). CTVs (D90%, D95%, and D98%) remained well-covered regardless of the absolute bladder volume daily variation or the presence of the endorectal balloon. Patients with an endorectal balloon showed smaller variation but a higher average maximum rectal wall dose (D0.03mL: 104.3% of the prescription) compared to patients without (103.3%). Conclusions: A “minimum bladder” contour was determined that can be easily generated and followed to ensure sufficient bladder sparing. Further analysis and validation are needed to confirm the utility of the minimal bladder contour. Accurate dose delivery can be achieved for prostate bed target coverage and OAR sparing with or without the use of ERB.

Bladder Volumes Matter: Clinical Significance of Bladder Filling in Salvage Radiotherapy for Prostate Cancer

<h3>Purpose/Objective(s)</h3> Salvage radiotherapy (SRT) is the only curative option for recurrent prostate cancer after radical prostatectomy. Urinary bladder is the major organ at risk in this setting. Different bladder filling protocols are used to reduce radiation dose to the bladder and thus limit genitourinary (GU) side effects. However, constant bladder volume is hard to maintain throughout the treatment course. A pronounced inter-fractional variation in bladder volume is a well-recognized problem in SRT. The purpose of this study was to investigate if there is a relationship between actual bladder volumes measured on daily cone-beam computer tomography (CBCT) images and GU adverse effects. <h3>Materials/Methods</h3> Consecutive patients treated with SRT at Karolinska university hospital, Sweden, in 2019-2020 (n=126) were included. Patients received either 35 × 2 Gy (n=103) or 35 × 2.2 Gy and/or pelvic lymph node irradiation (n=23) with IMRT (n=82) or four-field box-technique (n=44). All patients were treated with image-guided radiotherapy (IGRT) including daily cone-beam CT (CBCT). Bladder volumes were graded (visual analogue scale) on CBCT images (n=4410) at each treatment fraction. Internal validation of bladder volume measurements was performed in 22 patients by manually delineating bladders on daily CBCTs (n=770). Clinician-reported outcome (ClinRO) and patient-reported outcome measures (PROM) were available in 103 (83%) and 80 (66%) cases, respectively, ClinRO and PROM combined in 68 (54%) patients. Baseline bladder volumes, within-patient volume variation as well as average of 35 CBCT bladder volumes for the entire treatment course were compared between groups of patients with and without GU adverse events during 12 months of follow-up. <h3>Results</h3> Manually delineated and visually graded bladder volumes were strongly correlated (r=0.869, p<0.001). ClinRO and PROM were significantly associated (Chi-square =33.1, p<0.001). A repeated-measures ANOVA determined that mean bladder volumes did not differ across 35 CBCT measurements (p=0.16). Average actual bladder volumes were significantly smaller than baseline volumes (Wilcoxon S-R test Z=-2.68, p<0.007). Bladder volumes were significantly smaller in patients with GU adverse events compared to asymptomatic patients, measured with both ClinRO (p=0.006) and PROM (p=0.003). <h3>Conclusion</h3> In conclusion, our detailed analysis indicates that patients with GU adverse effects had significantly smaller bladder volumes during SRT. Clinical use of bladder filling protocol to increase bladder size during SRT is thus justified.

PO-1415 Inter-fraction error analyses and rectal and bladder volume variations using CBCT in prostate cancer

PO-1415 Inter-fraction error analyses and rectal and bladder volume variations using CBCT in prostate cancer

Bladder volume variation in hypofractionated prostate radiotherapy.

234 Background: A full bladder for prostate radiotherapy treatment limits overall dose to the bladder and displaces bowel from high dose regions. There is currently no clear consensus on optimum bladder volume for prostate radiotherapy. Inconsistent bladder volumes can cause dosimetric uncertainty, distress, treatment delay and negative toxicity outcomes for patients. To identify potential ways to improve bladder filling consistency we retrospectively analysed bladder volume variation over the course of patients’ treatment and its relationship to various patient and treatment factors. Methods: We included all patients treated with 60gy in 20 fractions to the prostate only over a 1-year period. Standard fractionation, palliative, post-operative, and whole pelvis treatment regimens were excluded from our study. Patient, tumour, and treatment characteristics were collected retrospectively. We recorded patient reported IPSS scores that were completed pre and post treatment. Daily bladder volumes were recorded from cone beam CT (CBCT) retrospectively for a subset of 34 patients and included in correlative analyses with various treatment and patient factors. Results: 69 men were included in this study with a mean planning CT bladder volume of 272ml (79-574). Patients were divided into large ( &gt; 180ml) and small subgroups (N = 46 vs 23). Smaller bladders resulted in a greater post treatment IPSS score (10.2 vs 7.7 (p = 0.2)) and greater change in IPSS (+3.3 vs +1.4 (p = 0.23). The variation of daily bladder volumes as measured by the standard deviation was positively associated with planning CT volume (p &lt; 0.05), variation in daily treatment time (p &lt; 0.05) and urinary symptoms (p = 0.29). Greater discordances between planning CT time and mean radiotherapy time resulted in a greater average difference between CBCT bladder volume and planning CT volume (p = 0.16). There were no appreciable seasonal or diurnal associations for all recorded bladder volumes. Conclusions: Smaller bladder volumes at planning CT are associated with increased urinary symptoms whereas larger volumes undergo more daily variation. This data suggests an optimal planning bladder volume of 200-400ml to minimise on treatment variation. This is the first study to demonstrate a relationship between variation in daily treatment times and daily bladder variation. Synchronisation of planning CT time with patient treatment time preference will enable patients to better replicate planning CT bladder volumes. This, along with several other areas for improvement highlighted by this study have formed the basis for a prospective single centre pilot study.

Dosimetric Impact of Inter-Fraction Anatomical Changes in Carbon Ion Boost Treatment for High-Risk Prostate Cancer (AIRC IG 14300).

Rectum and bladder volumes play an important role in the dose distribution reproducibility in prostate cancer adenocarcinoma (PCa) radiotherapy, especially for particle therapy, where density variation can strongly affect the dose distribution. We investigated the reliability and reproducibility of our image-guided radiotherapy (IGRT) and treatment planning protocol for carbon ion radiotherapy (CIRT) within the phase II mixed beam study (AIRC IG 14300) for the treatment of high-risk PCa. In order to calculate the daily dose distribution, a set of synthetic computed tomography (sCT) images was generated from the cone beam computed tomography (CBCT) images acquired in each treatment session. Planning target volume (PTV) together with rectum and bladder volume variation was evaluated with sCT dose-volume histogram (DVH) metric deviations from the planning values. The correlations between the bladder and rectum volumes, and the corresponding DVH metrics, were also assessed. No significant difference in the bladder, rectum, and PTV median volumes between the planning computed tomography (pCT) and the sCT was found. In addition, no significant difference was assessed when comparing the average DVHs and median DVH metrics between pCT and sCT. Dose deviations determined by bladder and rectum filling variations demonstrated that dose distributions were reproducible in terms of both target coverage and organs at risk (OARs) sparing.

PO-1518 Effect of bladder filling protocols on bladder volume variation in the age of adaptive radiotherapy

PO-1518 Effect of bladder filling protocols on bladder volume variation in the age of adaptive radiotherapy

Moving organ toxicity management in radiation therapy with simple fuzzy logic

The aim of present work is to estimate and manage real time toxicity of moving organ bladder in deciding level of damage using a simple fuzzy logic method. The target and bladder inter-treatment motions are considered in radiation therapy of prostate cancer in the present study. Materials and methods: The prostate target and nearby critical structures like bladder varies due to physiological behaviour during the course of radiation therapy treatment. The total displacement errors of prostate target shift ranging from 0-5 mm s.d. was considered in this study while maintain tumor dose conformity. The Mamdani-type Fuzzy Inference System (FIS) was applied for determine biological acceptable margin using TCP and NTCP parameters. The bladder volume variations with weekly analysis of cone beam CT (CBCT) were considered. Using irradiated volume-risk relationship in planning, the overlapped risk volumes were estimated. Fuzzy rules and membership function were used basis on setup errors, asymmetrical nature of organ motion and limitations of normal tissue toxicity in margin formulations. Results and discussion: The prostate target motion management was in a good consistent with conventional margin formulations at 5 mm s.d. displacement error range to maintain conformity index (CI) of target. With application of conventional margins of target volume, the sub-volumes of critical organs such as bladder and corresponding its NTCP values were fuzzified using inter treatment volume variations of critical organs. The risk factor (RF) of critical organs were qualitatively assessed with for each fractional volume of irradiated to total volume and relevant NTCP values. Conclusion: A simple fuzzy logic may be suitable to estimate critical moving organs toxicity like bladder biologically. Using proposed simple and fast method, there is interplay between volume-risk relationship and NTCP of OARs to management of normal-tissue risk level of radiation therapy.

Assessment of an ultrasound bladder scanner in prostate radiotherapy: A validation study and analysis of bladder filling variability.

During prostate radiotherapy treatment, it is important to ensure the position of the bladder and prostate is consistent between treatments. The aim of this study was to provide a quantitative basis for incorporating ultrasound bladder volume estimates into local practice for prostate radiotherapy. Agreement between bladder volume estimates obtained using computed tomography (CT) and ultrasound was assessed. Analysis of bladder volumes between planning and treatment scans was used to quantify expected variations in bladder volume over the course of radiotherapy. Dose-volume statistics were estimated and compared to planned dose constraints to propose a target bladder volume and tolerance. Bladder volume measurements were obtained from 19 radiotherapy patients using ultrasound and CT. Ultrasound underestimated bladder volume compared to CT with a mean bias of -28 ± 30 ml. Pre-treatment (planning) bladder volumes varied from 71 to 383 ml with a mean of 200 ml. Treatment bladder volumes reduced by more than half in 9% of patients during the course of their treatment, potentially leading to a 30% increase in mean bladder dose. Patients with pre-treatment bladder volumes < 200 ml were most likely to exhibit differences in bladder volume, resulting in 'out of tolerance' increases in dose. A pragmatic individualised drinking protocol, aimed at achieving a minimum ultrasound bladder volume of 200 ml at planning CT, may be beneficial to reproducibility in radiotherapy treatment. Ultrasound measurements prior to treatment should ideally confirm that bladder volume is at least half the volume measured at planning.

Analysis of the Influence of Peripheral Anatomical Changes for CBCT-Guided Prostate Cancer Radiotherapy.

Purpose:To analyze the influence of the bladder and rectum filling and the body contour changes on the prostate target dose.Methods:A total of 190 cone-beam CT (CBCT) image data sets from 16 patients with prostate cancer were used in this study. Dose reconstruction was performed on the virtual CT generated by the deformable planning CT. Then, the effects of the bladder filling, rectal filling, and the patient’s body contour changes of the PCTV1 (the prostate area, B1) and PCTV2 (the seminal vesicle area, B2) on the target dose were analyzed. Correlation analysis was performed for the ratio of bladder and rectal volume variation and the variation of the bladder and rectal dose.Results:The mean Dice coefficients of B1, B2, bladder, and rectum were 0.979, 0.975, 0.888 and 0.827, respectively, and the mean Hausdorff distances were 0.633, 1.505, 2.075, and 1.533, respectively. With the maximum volume variations of 142.04 ml for the bladder and 40.50 ml for the rectum, the changes of V100, V95, D2, and D98 were 1.739 ± 1.762 (%), 0.066 ± 0.169 (%), 0.562 ± 0.442 (%), and 0.496 ± 0.479 (%) in PCTV1 and 1.686 ± 1.051 (%), 0.240 ± 0.215 (%), 1.123 ± 0.925 (%), and 0.924 ± 0.662 (%) in PCTV2, respectively. With a 10% increase in the volume of the bladder and rectum, the V75, V70, and V65 of rectum increased at 0.73 (%), 0.71 (%), and 1.18 (%), and the V75, V70, and V65 of bladder changed at −0.21 (%), −0.32 (%), and −0.39 (%), respectively.Conclusion:Significant correlations were observed between the volume variation and the dose variation of the bladder and rectum. However, when a bladder and rectal filling protocol was adopted, the target dose coverage can be effectively ensured based on CBCT guidance to correct the prostate target position.

Inter- and Intra-Fractional Target Changes During Stereotactic Body Radiotherapy to the Prostate Bed With an Endorectal Balloon

Mature toxicity outcomes from the first phase I trial using stereotactic body radiotherapy (SBRT) to the prostate bed for recurrent prostate cancer have been recently reported. From that study, we herein report inter- and intra-fractional positional changes in the clinical target volume (CTV) and rectum with the use of an endorectal balloon. Prostate bed SBRT was delivered over 5 fractions in escalating doses of 35, 40, and 45 Gy. Three fiducial markers were planted in the CTV volume. A subset of 10 patients on the trial received both pre- and post-treatment CBCT for each fraction and were the subject of this analysis. An endorectal balloon was placed during both simulation and daily treatments. Patients were instructed to maintain a full bladder. On pre-treatment CBCT we localized to the anterior surface of the balloon to align the anterior rectal wall and CTV. Inter-fractional variation was measured using registrations based on pelvic anatomy. Intra-fractional changes in balloon position were assessed with soft-tissue registration. The t-test was used to evaluate the significance of correlation coefficient with significance level set at 0.05. The average daily air-filled balloon volume (±standard deviation) was 77.0±5.0 cc (range: 60.6 cc – 88.5 cc), and the average pre-treatment bladder volume was 235.0±109.7 cc. Compared to the planning CT, the pre-treatment bladder volume changed by -35.0±87.9 cc (range: -227.1 – 123.1 cc). Relative to the planning positions, the anterior rectal wall had an average inter-fractional shift of -1.6±5.6 mm (range: -15.2 – 7.5 mm) in the antero-posterior (AP) direction at the mid-section of the balloon (negative value: shifts posteriorly), with ≥ 3mm shift in 66% of total fractions. Correlation between daily bladder volume variations and anterior rectum position variations in the AP direction was statistically significant (Pearson’s correlation coefficient = 0.76, p = 0.02). The average time between the pre- and post-treatment CBCT scans was 9.8±4.0 minutes (range: 6 – 29 minutes). The post-treatment bladder volume increased significantly (p < 0.01) by an average of 58.9±51.6 cc. The balloon volume changed by <5% in each treatment. The center-of-mass of the balloon had average intra-fractional variation of 0.3±0.8 mm in the left-right (LR) direction (range: -1.3 – 2.5 mm), -0.9±2.4 mm in the AP direction (range: -11.0 – 3.0 mm), and -1.7±2.2 mm in the superoinferior (SI) direction (range: -10.9 – 0.7 mm) (negative value: shift anteriorly). No correlation was seen between increased bladder volume and intrafractional AP shifts, since the majority of greater than 3 mm shifts were attributed to one patient. Although not statistically significant, we observed higher than expected intrafractional AP and SI shifts. Our future phase II trial will incorporate larger margins to account for this finding.

Dosimetric evaluation of image-guided radiation therapy for prostate cancer

The aim of this study was to investigate the dosimetric accuracy of imaged-guided radiation therapy for prostate patients using the in-room computed tomography (CT) target localization technique. A Siemens CT-on-rails system was used for patient setup and target localization for intensity-modulated radiation therapy (IMRT) of prostate cancer. Fifteen previously treated prostate patients were included in this retrospective study. CT-on-Rails scans were performed before and after the IMRT treatment under local IRB approval. A total of 15 original simulation CT scans and 98 post-treatment CT scans were contoured by the same oncologist to delineate the prostate target, bladder, and rectum. IMRT plans were generated on the original simulation CTs and the same MUs and leaf sequences were used to compute the dose distributions using post-treatment CTs. Varian Velocity deformable registration was used for the summation of the fractional doses and the cumulative doses were compared with the planned doses. For the 15 patients investigated, the mean isocenter shift was up to 4.0 mm in the left-right direction, 5.9 mm in the anterior-posterior direction and 5.6 mm in the superior-inferior direction due to interfractional organ motion. The mean rectal volume varied from 0.6 to 1.73 times and the mean bladder volume varied from 0.59 to 3.65 times between simulation and the end of treatment. The prescription dose to 95% of the PTV, Dp, was set to 76 Gy for all treatment plans. The dose to 95% of the clinical treatment volume (CTV), D95, was 74.0 to 77.6 Gy and the minimum CTV dose, Dmin, was 61.0 to 71.6 Gy, respectively, in the cumulative dose distributions. Detailed analyses showed that 7.1% of the treatment fractions had cold spots (< 85% of Dp) in the peripheral CTV, leading to Dmin < 64 Gy in the cumulative dose distributions for 4 patients. The rectal dose-volume constraints were violated in 35.7% of the treatment fractions while the bladder dose was much improved in 82.7% of the treatment fractions. The current IGRT procedure for patient setup and target localization using rigid-body registration based on contour/anatomy matching is effective for population-based PTV margins. For a small group of patients, specific PTV margins and/or real-time target monitoring/tracking will be necessary due to significant prostate deformation/rotation caused by inter- and intrafractional bladder and rectal volume variation.

CBCT evaluation of inter- and intra-fraction motions during prostate stereotactic body radiotherapy: a technical note

BackgroundIn most clinical trials, gold fiducial markers are implanted in the prostate to tune the table position before each radiation beam. Yet, it is unclear if a cone-beam computed tomography (CBCT) should be performed before each beam to monitor a possible variation of the organs at risk (OARs) fullness, especially in case of recto-prostatic spacer implantation. The present study aimed at assessing the inter- and intra-fraction movements of prostate, bladder and rectum in patients implanted with a hyaluronic acid spacer and undergoing prostate stereotactic body radiotherapy (SBRT).MethodsData about consecutive patients undergoing prostate SBRT were prospectively collected between 2015 and 2019. Inter-and intra-fraction prostate displacements and volume variation of organs at risk (OARs) were assessed with CBCTs.ResultsEight patients were included. They underwent prostate SBRT (37.5Gy, 5 fractions of 7.5Gy) guided by prostate gold fiducial markers. Inter-fraction variation of the bladder volume was insignificant. Intra-fraction mean increase of the bladder volume was modest (29 cc) but significant (p < 0.001). Both inter- and intra-fraction variations of the rectum volume were insignificant but for one patient. He had no rectal toxicity. The magnitude of table displacement necessary to match the prostate gold fiducial marker frequently exceeded the CTV/PTV margins (0.4 cm) before the first (35%) and the second arc (15%). Inter- and intra-fraction bladder and rectum volume variations did not correlate with prostate displacement.ConclusionMajor prostate position variations were reported. In-room kV fiducial imaging before each arc seems mandatory. Intra-fraction imaging of the OARs appears unnecessary. We suggest that only one CBCT is needed before the first arc.Trial registrationNCT02361515, February 11th, 2015.

To analyse target volume variations during SIB-IMRT of squamous cell carcinoma of uterine cervix

AbstractPurpose:To assess volume variations in target site due to changes in bladder filling and rectal content including air bubbles during simultaneous-integrated boost intensity-modulated radiotherapy (SIB-IMRT) of patients suffering from squamous cell carcinoma of uterine cervix.Materials and methods:A total of ten patients of squamous cell carcinoma of uterine cervix were enrolled in this analysis. All patients were planned to undergo SIB-IMRT using 10 MV beam. Planning target volume of the tumour (PTVtumour) and PTVnodal were prescribed with 5,040 and 4,500 cGy doses, respectively. During planning, PTVtumour V95%, PTVnodal V95% and organs at risk (OARs) (bladder, rectum, femoral heads and small bowel) volumes were measured from initial CT planning scans taken with full bladder. CT scans were acquired once in a week over a treatment period of 5·5 weeks. Intra-treatment scans with full bladder were then fused with the planning scans to determine variations in the target volume and the OAR volume. Changes in radiation dose to the PTVtumour and the PTVnodal were also assessed by comparing intra-treatment scans with the planning (first) scans.Results:All patients showed intra-treatment bladder volume larger than the planning bladder volume. Difference between planning bladder and intra-treatment bladder volumes ranged from 4·5 to 49%. Rectal volume varied from 17 to 60 cc. A wide variation between planning and intra-treatment air volumes was found in most of the patients. When comparing initial and inter-fraction air volumes, the maximum difference was 366·67%. Due to bladder and rectal volume variations, PTVtumour V95% and PTVnodal V95% doses did not remain constant throughout the treatment. The maximum discrepancy between intra-treatment PTVtumour dose and planning PTVtumour dose was 12·15%. The maximum difference between planning and inter-fraction PTV V95% was 48·28%. PTVnodal dose observed from scan taken in last week of treatment was 12·87% less than planning PTVnodal dose analysed from planning CT scan. Maximum difference in planning and inter-fraction PTVnodal V95% was 57·78%.Conclusion:Inconsistent bladder and rectal volumes had a significant impact on target volume and dosage during an entire course of SIB-IMRT. For radiotherapy of gynaecological malignancies, data on variations in PTV should be acquired on daily basis to target radiation dose to the tumour site with accuracy.