Framework Development: Standardizing Definition of Advanced Practice Radiation Therapy Activities for Clinical Workload Quantification.

Purpose: Advanced practice (AP) in radiation therapy (RT) is being implemented around the globe. In an effort to advance the understanding of the similarities and differences in APRT roles in Ontario, Canada, a community of practice (CoP) sought ways to provide quantitative data on the nature of APRT clinical activities and the frequency with which these activities were being executed. Methods: In 2017, a consensus building project involving 20 APRTs and 14 radiation therapy (RT) department managers in Ontario was completed to establish a mechanism to quantify APRTs' clinical impact. In Round 1 & 2, expert feedback was gathered to generate an Advanced Practice (AP) Activity List. In Round 3: 20 APRTs completed an online survey to assess the importance and applicability of each AP Activity to their role using Likert scale (0-5). A final AP Activity List & Definitions was generated. Results & discussion: Round 1: Forty-seven AP activities were identified. Round 2: 3/14 RT managers provided 145 feedback statements on Round 1 AP Activity List. The working group used RT managers' feedback to clarify AP activities and definitions, specifically merging 33 unique AP activities to create 11 inclusive AP activities and eliminating 8 activities identified from Round 1. The most inclusive AP activity created was #1 New Patient Consultation, this AP Activity is merged from 7 unique AP activities. Incorporating RT managers' feedback with the internal AP clinical workload lists from 2 Ontario cancer centres resulted in a revised AP Activity List with 20 AP inclusive activities. Round 3: 14/20 APRTs provided Likert scores on this revised list. The most applicable AP activities (mean score) were #16 Technical Consultation (4.0), #15 Contouring Target Volume (3.8) and #2 Planning Consultation (3.8); the least applicable was #18 MR Applicator Assessment (0.9). Conclusions: This is the first systematic attempt to build consensus on AP clinical activities. Non-clinical APRT activities related to research, education, innovation, and program development were not in the scope of this project. The Final AP Activity List & Definitions serves as a framework that allows standardized and continuous monitoring of AP clinical activities and impact.

Prospective evaluation of patient-reported anxiety and experiences with adaptive radiation therapy on an MR-linac.

Purpose: An integrated magnetic resonance scanner and linear accelerator (MR-linac) was implemented with daily online adaptive radiation therapy (ART). This study evaluated patient-reported experiences with their overall hospital care as well as treatment in the MR-linac environment. Methods: Patients pre-screened for MR eligibility and claustrophobia were referred to simulation on a 1.5 T MR-linac. Patient-reported experience measures were captured using two validated surveys. The 15-item MR-anxiety questionnaire (MR-AQ) was administered immediately after the first treatment to rate MR-related anxiety and relaxation. The 40-item satisfaction with cancer care questionnaire rating doctors, radiation therapists, the services and care organization and their outpatient experience was administered immediately after the last treatment using five-point Likert responses. Results were analyzed using descriptive statistics. Results: 205 patients were included in this analysis. Multiple sites were treated across the pelvis and abdomen with a median treatment time per fraction of 46 and 66 min respectively. Patients rated MR-related anxiety as "not at all" (87%), "somewhat" (11%), "moderately" (1%) and "very much so" (1%). Positive satisfaction responses ranged from 78 to 100% (median 93%) across all items. All radiation therapist-specific items were rated positively as 96-100%. The five lowest rated items (range 78-85%) were related to general provision of information, coordination, and communication. Overall hospital care was rated positively at 99%. Conclusion: In this large, single-institution prospective cohort, all patients had low MR-related anxiety and completed treatment as planned despite lengthy ART treatments with the MR-linac. Patients overall were highly satisfied with their cancer care involving ART using an MR-linac.

Clinical and dosimetric outcomes of image-guided, dose-painted radiotherapy in muscle invasive bladder cancer.

PURPOSE/OBJECTIVE: Definitive radiotherapy (RT) is an alternative to radical cystectomy for select patients with muscle invasive bladder cancer (MIBC); however, there is limited data on dose-painted RT approaches. We report the clinical and dosimetric outcomes of a cohort of MIBC patients treated with dose-painted RT. MATERIAL/METHODS: This was a single institution retrospective study of cT2-4N0M0 MIBC patients treated with external beam radiotherapy (EBRT) to the bladder, and sequential or concomitant boost to the tumor bed. The target delineation was guided by either intravesical injection of Lipiodol or through fusion of the pre-treatment imaging. The majority were treated with daily image-guidance. Kaplan-Meier was used to characterize overall survival (OS) and progression-free survival (PFS). Cumulative incidence function (CIF) was used to estimate local (intravesical) recurrence (LR), regional recurrence (RR) and distant metastasis (DM). Univariable and multivariable cause-specific hazard model was used to assess factors associated with LR and OS. RESULTS: 117 patients were analyzed. The median age was 73 years (range 43, 95). The median EQD2 to the boost volume was 66 Gy (range 52.1, 70). Lipiodol injection was used in 64 patients (55%), all treated with IMRT/VMAT. 95 (81%) received concurrent chemotherapy, of whom, 44 (38%) received neoadjuvant chemotherapy. The median follow-up was 37 months (IQR 16.2, 83.3). At 5-year, OS and PFS were 79% (95% CI 70.5-89.2) and 46% (95% CI 36.5-57.5). Forty-five patients had bladder relapse, of which 30 patients (67%) were at site of the tumor bed. Nine patients underwent salvage-cystectomy. Late high-grade (G3-G4) genitourinary and gastrointestinal toxicity were 3% and 1%. CONCLUSION: Partial boost RT in MIBC is associated with good local disease control and high rates of cystectomy free survival. We observed a pattern of predominantly LR in the tumor bed, supporting the use of a dose-painted approach/de-escalation strategy to the uninvolved bladder. Prospective trials are required to compare oncological and toxicity outcomes between dose-painted and homogeneous bladder RT techniques.

Practice-based training strategy for therapist-driven prostate MR-Linac adaptive radiotherapy.

Purpose: To develop a practice-based training strategy to transition from radiation oncologist to therapist-driven prostate MR-Linac adaptive radiotherapy. Methods and materials: In phase 1, 7 therapists independently contoured the prostate and organs-at-risk on T2-weighted MR images from 11 previously treated MR-Linac prostate patients. Contours were evaluated quantitatively (i.e. Dice similarity coefficient [DSC] calculated against oncologist generated online contours) and qualitatively (i.e. oncologist using a 5-point Likert scale; a score ≥ 4 was deemed a pass, a 90% pass rate was required to proceed to the next phase). Phase 2 consisted of supervised online workflow with therapists required no intervention from the oncologist on 10 total cases to advance. Phase 3 involved unsupervised therapist-driven workflow, with offline support from oncologists prior to the next fraction. Results: In phase 1, the mean DSC was 0.92 (range 0.85-0.97), and mean Likert score was 3.7 for the prostate. Five therapists did not attain a pass rate (3-5 cases with prostate contour score < 4), underwent follow-up one-on-one review, and performed contours on a further training set (n = 5). Each participant completed a median of 12 (range 10-13) cases in phase 2; of 82 cases, minor direction were required from the oncologist on 5 regarding target contouring. Radiation oncologists reviewed 179 treatment fractions in phase 3, and deemed 5 cases acceptable but with suggestions for next fraction; all other cases were accepted without suggestions. Conclusion: A training stepwise program was developed and successfully implemented to enable a therapist-driven workflow for online prostate MR-Linac adaptive radiotherapy.

The dosimetric underpinning of bladder filling criteria for prostate image-guided volumetric modulated arc therapy.

OBJECTIVES: Repeated CT simulation imaging is common at our institution due to failure to achieve acceptable bladder filling in patients undergoing prostate radiotherapy. There is operational value in re-assessing the validity of the bladder filling assessment criteria by comparing the quality of two plans optimized based on either an "Accepted" or "Rejected" bladder status. METHODS: Twenty prostate patients with repeated CT simulation imaging were included. For each patient, a VMAT plan created using the "Rejected" bladder was compared with the "Accepted" bladder plan. Then, delivered dose to bladder was estimated using ≥4 CBCTs to measure number of fractions with major bladderdose violation (>5% difference) for both plans. Bladder heights of fractions without major bladder dose violations were compared to those with a violation to determine a threshold height for bladder filling acceptability. RESULTS: Using the "Accepted" bladder plans for treatment resulted in 30/175 fractions with major dose violations. These 30 bladders were significantly shorter than those without major violation (mean 28 vs 43mm, p < 0.05). The "Rejected" bladder plans delivered a lower dose to the bladder by ≥5% than the '"Accepted" bladder plans in 59% of fractions, and the number of fractions with major dose violations was 17. CONCLUSIONS: Using a shorter bladder for plan optimization resulted in better bladder sparing during treatment and improved compliance to protocol specific bladder dose constraints. A bladder height range of 20-40 mm measured between the bladder dome and the superior aspect of the symphysis pubis is recommended for prostate radiotherapy requiring a full bladder protocol. ADVANCES IN KNOWLEDGE: Using real patient data from simulation and treatment, this study established a range of bladder height that can be measured easily in a clinical setting for assessing adequacy of bladder filling for prostate radiotherapy.

Impact of intrafraction changes in delivered dose of the day for prostate cancer patients treated with stereotactic body radiotherapy via MR-Linac.

Purpose: The purpose of this study is to evaluate the impact of intrafraction pelvic motion by comparing the adapted plan dose (APD) and the computed delivered dose of the day (DDOTD) for patients with prostate cancer (PCa) treated with SBRT on the MR-Linac. Methods: Twenty patients with PCa treated with MR-guided adaptive SBRT were included. A 9-field IMRT distribution was adapted based on the anatomy of the day to deliver a total prescription dose of 3000 cGy in 5 fractions to the prostate plus a 5 mm isotropic margin. Prostate, bladder, and rectum were re-contoured on the MR-image acquired during treatment delivery (MRBO). DDOTD was computed by propagating the dose from the daily adapted plan generated during treatment onto the MRBO. Results: Target coverage was met for all fractions, however, computed DDOTD was significantly less than the APD (p < 0.05). During an average treatment of 53 min, mean bladder volume increased by 116%, which led to a significant decrease in the DDOTD bladder D40% (p < 0.001). However, DDOTD to bladder 5 cc was significantly higher (p < 0.001) than APD. Rectum intrafraction changes were observed based on a volume change of -20% to 83% and presence of significant dose changes from APD to DDOTD for rectum D20% (p < 0.05) and D1cc (p < 0.0001). Conclusions: Intrafraction motion observed during prostate SBRT treatment on the MR-Linac have dosimetric impacts on both the target and organs at risk. Post-treatment computation using DDOTD may inform adaptation beyond anatomic changes in subsequent treatment fractions to best capitalize on MR-Linac technology and widen the therapeutic index of SBRT for PCa.

Case Report: MR-Guided Adaptive Radiotherapy, Some Room to Maneuver.

Background: A magnetic resonance linear accelerator (MR-Linac) provides superior soft tissue contrast to evaluate inter- and intra-fraction motion and facilitate online adaptive radiation therapy (ART). We present here an unusual case of locally advanced castrate-resistant prostate cancer treated with high-dose palliative ultra-hypofractionated radiation therapy on the MR-Linac with significant inter-fraction tumor regression. Case Presentation: The patient was a 65-year-old man diagnosed with metastatic prostate cancer to bone and pelvic lymph nodes 7 years prior. At diagnosis, he presented with a PSA of 23 ng/ml and was commenced on a luteinizing hormone-releasing hormone agonist, achieving a PSA nadir of 4.68 ng/ml at 12 months. The patient subsequently had progressive lower urinary tract symptoms, his PSA increased to 47 ng/ml, and there was a markedly enlarged pelvic mass involving the prostate with gross extra-capsular disease and invasion into the posterior bladder wall. The patient was referred for palliative radiation to the pelvic mass due to urinary symptoms, pain, and lower limb paraesthesia. Treatment was planned to be delivered on the MR-Linac with a schedule of 36 Gy over 6 weekly factions allowing for maximal target dose delivery while minimizing surrounding organs at risk (OARs) radiation exposure. Unexpectedly, the target volume had a marked 49% (453 cc to 233 cc) reduction that was accounted for in the online adaptive process. A new reference plan was generated after 3 fractions to add sacral plexus as an OAR, previously not visible due to mass encroachment. The patient reported ongoing reduction in urinary symptoms, pelvic pain, and lower limb paresthesia by the end of treatment. Conclusion: Using daily MR-guided ART, improved visualization of the changing target and OARs ensured safe dose escalation. The unexpected positive response of the target and improved patient outcomes demonstrated the added value of the MR-Linac for online adaptive radiotherapy in this setting.

Dosimetric comparison of MR-guided adaptive IMRT versus 3DOF-VMAT for prostate stereotactic radiotherapy.

INTRODUCTION: To compare the dosimetry of prostate stereotactic radiotherapy (SBRT) delivered by adaptive intensity modulated radiotherapy (A-IMRT) and 3 degree of freedom volumetric modulated arc therapy (3DOF-VMAT). METHODS & MATERIALS: Twenty-five prostate patients treated with High Dose Rate (HDR) brachytherapy followed by SBRT were included (fifteen with hydrogel spacer in place for treatment). Interfraction changes in the volume of prostate, rectum and bladder were measured. Fractional dose to these structures was estimated for A-IMRT and 3DOF-VMAT for comparison against the corresponding reference dose and between each other. RESULTS: Clinically acceptable dose was delivered to prostate in all 125 fractions through A-IMRT and 3DOF-VMAT. A-IMRT was better than 3DOF-VMAT in reducing dose to 1 cm3 of rectum. Conversely, 3DOF-VMAT was superior in sparing 50% and 20% of rectum. When comparing the reference and delivered dose, there was no significant difference for Bladder D5cm3 for either technique. However, rectum in the high dose region benefited more from A-IMRT by being irradiated to a lower than reference dose in more fractions than 3DOF-VMAT. Hydrogel spacer reduced the rectal dose and was associated with a smaller deviation from reference dose for rectum D50% for A-IMRT. CONCLUSIONS: Despite the presence of large interfraction organ volumes changes, clinically acceptable dose was delivered to the prostate by both systems. A-IMRT facilitated a greater rectal sparing from the high dose region than 3DOF-VMAT. Further reduction in rectal dose could be achieved by hydrogel spacer to displace the rectum, or by adaptation delivered by VMAT.

Clinical integration of machine learning for curative-intent radiation treatment of patients with prostate cancer.

Machine learning (ML) holds great promise for impacting healthcare delivery; however, to date most methods are tested in 'simulated' environments that cannot recapitulate factors influencing real-world clinical practice. We prospectively deployed and evaluated a random forest algorithm for therapeutic curative-intent radiation therapy (RT) treatment planning for prostate cancer in a blinded, head-to-head study with full integration into the clinical workflow. ML- and human-generated RT treatment plans were directly compared in a retrospective simulation with retesting (n = 50) and a prospective clinical deployment (n = 50) phase. Consistently throughout the study phases, treating physicians assessed ML- and human-generated RT treatment plans in a blinded manner following a priori defined standardized criteria and peer review processes, with the selected RT plan in the prospective phase delivered for patient treatment. Overall, 89% of ML-generated RT plans were considered clinically acceptable and 72% were selected over human-generated RT plans in head-to-head comparisons. RT planning using ML reduced the median time required for the entire RT planning process by 60.1% (118 to 47 h). While ML RT plan acceptability remained stable between the simulation and deployment phases (92 versus 86%), the number of ML RT plans selected for treatment was significantly reduced (83 versus 61%, respectively). These findings highlight that retrospective or simulated evaluation of ML methods, even under expert blinded review, may not be representative of algorithm acceptance in a real-world clinical setting when patient care is at stake.

Prostate or bone? Comparing the efficacy of image guidance surrogates for pelvis and prostate radiotherapy using accumulated delivered dose.

INTRODUCTION: This study assessed the impact of dosimetry to both the target and normal tissue when either bony anatomy (BA) or prostate (PRO) was used as surrogates for image guidance for pelvis and prostate radiotherapy using a dose accumulation process. METHODS: Thirty patients who were prescribed 50-54Gy to the pelvic lymph nodes (PLN) and 78Gy to the prostate/seminal vesicles were included. Daily acquired CBCTs were rigidly registered to the CT using BA and PRO to simulate two different treatment positions. The accumulated delivered dose (DAcc) of PLN, prostate, bladder and rectum for each surrogate were compared with the planned dose. Deviation from the planned dose (ΔDAcc-Plan) of >5% was considered clinically significant. RESULTS: Prostate was displaced from bony anatomy by > 5 mm in 96/755 fractions (12.7%). Deviation between the mean DAcc and the planned dose for PLN and prostate was <2% when either BA or PRO was used. No significant deviation from planned dose was observed for bladder (p > 0.2). In contrary, DAcc for rectum D50 was significantly greater than the planned dose when BA was used (Mean ΔDAcc-Plan = 6%). When examining individual patient, deviation from the planned dose for rectum D50 was clinically significant for 18 patients for BA (Range: 5-21%) and only 8 patients for PRO (Range: 5-8%). CONCLUSIONS: The use of either BA or PRO for image guidance could deliver dose to PLN and prostate with minimal deviation from the plan using existing PTV margins. However, deviation for rectum was greater when BA was used.

Impact of high dose volumetric CT on PTV margin reduction in VMAT prostate radiotherapy.

The aim of the study is to determine PTV margin for inter-observer variability in the volumetric modulated arc therapy (VMAT) prostate radiotherapy with high-dose volumetric CT (HDVCT) and conventional helical CT (CCT) for planning. Secondly to investigate the impact of geometric (PTV expansion) and dosimetric (conformity) imperfection of planning process on the PTV margin analysis. Prostate gland of ten patients were scanned with CCT and HDVCT techniques consecutively on a 320 slice volumetric CT scanner with wide field detector of 16 cm. Five radiation oncologists delineated CTV of the prostate. VMAT plans were developed with PTV margin of 4 mm and 6 mm (totaling 200 plans) and target coverage of each plan was evaluated on the target volume in agreement determined by shared voxels with three or more from 5 observers. Dosimetry on 200 VMAT plans showed that PTV margin for inter-observer variability were 6 mm and 4 mm for CCT and HDVCT techniques, respectively. It is about 3 mm smaller than our estimation from the previous study (8.8 mm and 7.3 mm) based on the inter-observer variability. This difference is mainly due to the accuracy of PTV volume expansion and limited dose conformity to guarantee target coverage. PTVs were measured 2 mm larger on average than the assigned margin. Planning iso-dose volume was found to be 2 mm larger than PTV. Regardless these limitations, enhanced image quality of HDVCT reduces PTV margin by 2 mm compared to CCT. PTV reduction of 2 mm potentially leads to 15% reduction in D30% of rectal and bladder wall maintaining the same target coverage. Inter-observer variability remains a source of systematic uncertainty. HDVCT for treatment planning demonstrated reduction of the uncertainty and the PTV margin by 2 mm. It is important to consider the over-expanded PTV volume and generous iso-dose volume after optimization in the process of radiotherapy planning in the determination of PTV margin.

Quantification of interobserver variability in image registration using cone beam CT for partial bladder radiotherapy-a comparison between lipiodol and bladder wall surface.

OBJECTIVE:: The use of lipiodol or bladder wall surface (BWS) for image guidance has improved the treatment quality for partial bladder irradiation. Currently, this procedure is manually performed by different users. This study assessed the interobserver variability of using image guidance for partial bladder irradiation. METHODS:: 7 observers were prospectively recruited to manually register 5 cone beam CTs (CBCT) from each of 20 bladder cancer patients with lipiodol injected for tumor demarcation. Lipiodol and BWS were used to register the CBCT to pre-treatment reference images, and displacement values in three directions were collected. Mean difference among observers and the 95% limit of agreement were calculated to measure interobserver variability. Margin required and the resultant treatment volume were compared between the surrogates. RESULTS:: A total of 4200 displacement values were collected for analysis. Lipiodol was superior to BWS, with a mean difference among observers of <2 mm and a 95% limit of agreement of <5 mm in all directions. Of the three directions, greatest variability was observed in the superior-inferior direction for both surrogates, hence requiring a larger margin than the other two directions. After applying the corresponding margin, the mean volume of BWS-planning target volume was calculated to be significantly larger than lipiodol-planning target volume (166 cm3vs 134 cm3, p < 0.05). CONCLUSIONS:: The use of lipiodol achieved a higher interobserver agreement than BWS. A larger margin in the superior-inferior direction is recommended due to greater interobserver variability observed in this direction for both surrogates. ADVANCES IN KNOWLEDGE:: The uncertainty associated with the image registration by multiple observers for bladder image-guided radiotherapy is quantified for two surrogates.

Comparison of 3 image-guided adaptive strategies for bladder locoregional radiotherapy.

The objective of this study was to compare the dosimetric differences of a population-based planning target volume (PTV) approach and 3 proposed adaptive strategies: plan of the day (POD), patient-specific PTV (PS-PTV), and daily reoptimization (ReOpt). Bladder patients (n = 10) were planned and treated to 46 Gy in 23 fractions with a full bladder in supine position by the standard strategy using a population-based PTV. For each patient, the adaptive strategy was executed retrospectively as follows: (1) POD-multiple distributions of various PTV sizes were generated, and the appropriate distribution based on the bladder of the day was selected for each fraction; (2) PS-PTV-population-based PTV was used for the first 5 fractions and a new PTV derived using information from these fractions was used to deliver the remaining 18 fractions; and (3) ReOpt-distribution was reoptimized for each fraction based on the bladder of the day. Daily dose was computed on all cone beam computed tomographies (CBCTs) and deformed back to the planning computed tomography (CT) for dose summation afterward. V95_Accu, the volume receiving an accumulated delivered dose of 43.7 Gy (95% prescription dose), was measured for comparison. Mean V95_Accu (cm3) values were 1410 (standard deviation [SD]: 227), 1212 (SD: 186), 1236 (SD: 199), and 1101 (SD: 180) for standard, POD, PS-PTV, and ReOpt, respectively. All adaptive strategies significantly reduced the irradiated volume, with ReOpt demonstrating the greatest reduction compared with the standard (- 25%), followed by PS-PTV (- 16%) and POD (- 12%). The difference in the magnitude of reduction between ReOpt and the other 2 strategies reached statistical significance (p = 0.0006). ReOpt is the best adaptive strategy at reducing the irradiated volume because of its frequent adaptation based on the daily geometry of the bladder. The need to adapt only once renders PS-PTV to be the best alternative adaptive strategy.

Efficient and Effective Personalization of PTV Margins During Radiation Therapy for Bladder Cancer.

INTRODUCTION: The magnitude of bladder filling variation during bladder cancer radiation therapy varies considerably between patients. Population-based approaches for planning target volume (PTV) margin calculation may be suboptimal for this disease site, and a strategy for personalizing PTV margins for each patient may be particularly beneficial. The purpose of this study was to identify the optimal number and sampling pattern of cone beam CT image data sets that are required when generating personalized PTV margins for whole bladder (WB) and partial bladder (PB) radiation therapy. METHODS AND MATERIALS: Personalized PTV margins were generated for 24 bladder cancer patients (15 WB and 9 PB) using nine experimental strategies that varied in the number and pattern of images incorporated into the margin generation process. These PTVs were compared to the standard-of-care (SoC) PTV at our institution (15 daily fractions included) using PTV volume (cohort-based and individual patient ranking), superior and posterior expansion, and clinical target volume (CTV) coverage. RESULTS: For WB CTV, strategies ES4 (first five fractions), ES7 (every other fraction), and ES8 (first 10 fractions), provided CTV coverage equivalent to, or better than the SoC (first 15 fractions). Of these three strategies, ES4 resulted in the smallest superior and posterior borders, the smallest volume and the lowest intrapatient volume ranking, all achieved with the smallest number of fractions. For the PB CTV, strategies ES4 (first five fractions), ES7 (every other fraction), ES8 (first 10 fractions), and ES9 (last 10 fractions), provided CTV coverage equivalent to, or better than SoC (first 15 fractions). There were no statistically significant differences in the superior and posterior borders between these strategies, but ES4 resulted in the smallest volume and the lowest intrapatient volume ranking, all achieved with the smallest number of fractions. CONCLUSIONS: This study suggests that using contours from images taken during the first five daily fractions generated a personalized "patient-specific" PTV that provided CTV coverage equivalent to the 15-fraction SoC but decreased the irradiated volume, reduced delineation workload, and reduced the superior and posterior borders for WB. It is now the SoC for whole and PB radiation therapy at our institution.

Evaluation of resource burden for bladder adaptive strategies: A timing study.

INTRODUCTION: Interfraction bladder motion is substantial and therefore many different adaptive radiotherapy approaches have been developed to accommodate that motion. Previous studies comparing the efficacy of those adaptive strategies have demonstrated that reoptimization (ReOpt) was dosimetrically superior when compared to Plan of the Day (POD) and Patient-specific PTV (PS-PTV). However, the feasibility of clinical implementation is dependent upon assessment of the resource burden. This study assessed and compared the resource burden of three adaptive strategies. METHODS: Using the planning CT and all daily CBCTs of 10 bladder patients, the following adaptive strategies were simulated offline to deliver 46 Gy in 23 fractions: POD, PS-PTV and ReOpt. Additional activities required to execute these strategies compared to a nonadaptive approach were identified and categorized. Time consumed for the execution of each strategy was measured for a single, experienced observer. RESULTS: The time (minutes) consumed to execute the additional activities for PS-PTV, POD and ReOpt was 14.4, 49.1 and 248.5, respectively. In addition to a significantly shorter time spent, all activities associated with PS-PTV were categorized as those that could be performed without the presence of the patient or a treatment room. On the other hand, ReOpt was the most time intensive and all activities were categorized as those that could lead to increasing patient's time in the treatment room and decreasing capacity. CONCLUSIONS: Although ReOpt was preferred with respect to improving dosimetry, the heavy resource burden it incurred could be a deterrent for clinical implementation. PS-PTV was the least resource-intensive strategy.

Evaluation of high dose volumetric CT to reduce inter-observer delineation variability and PTV margins for prostate cancer radiotherapy.

PURPOSE: The aim was to determine whether the enhanced soft tissue contrast provided by high-dose volumetric CT (HDVCT) can reduce inter-observer variability in delineating prostate compared to helical conventional CT (CCT) scans and 3T MRI scans for patients undergoing radical prostate cancer radiotherapy. Secondly, to quantify the potential PTV reduction with decreased inter-observer variability. MATERIALS AND METHODS: A 320 slice volumetric CT scanner was used. The wide-detector coverage of 16cm enabled volumetric image acquisition of prostate gland in one rotation. Three imaging studies were performed on ten patients. CCT and HDVCT were performed consecutively at the same coordinate system followed by MRI. Five radiation oncologists delineated the prostate. RESULTS: The inter-observer variability is 2.0±0.6, 1.9±0.4 and 1.8±0.4mm for CCT, HDVCT and MR respectively with the maximum at the apex region. Comparing inter-observer difference variability between CCT and HDVCT with MR indicates that observers have larger variations in contouring using CCT than HDVCT especially at apex. Jaccard index of HDVCT is significantly higher than CCT with a mean difference of 0.03 (p=0.011). Both MRI and HDVCT provide the opportunity for a 2mm PTV margin reduction at the apex compared to CCT. CONCLUSION: Inter-observer variability in delineation remains an important source of systematic error. HDCTV for treatment planning reduces this error without recourse to MRI and permits a PTV reduction of 2mm at the apex. The margins required to account for residual error with any imaging modality are still greater than are used in typical current practice.

The effect of bowel preparation regime on interfraction rectal filling variation during image guided radiotherapy for prostate cancer.

BACKGROUND: This study aimed to investigate the tolerability and impact of milk of magnesia (MoM) on interfraction rectal filling during prostate cancer radiotherapy. METHODS: Two groups were retrospectively identified, each consisting of 40 patients with prostate cancer treated with radiotherapy to prostate+/-seminal vesicles, with daily image-guidance in 78Gy/39fractions/8 weeks. The first-group followed anti-flatulence diet with MoM started 3-days prior to planning-CT and continued during radiotherapy, while the second-group followed the same anti-flatulence diet only. The rectum between upper and lower limit of the clinical target volume (CTV) was delineated on planning-CT and on weekly cone-beam-CT (CBCT). Rectal filling was assessed by measurement of anterio-posterior diameter of the rectum at the superior and mid levels of CTV, rectal volume (RV), and average cross-sectional rectal area (CSA; RV/length). RESULTS: Overall 720 images (80 planning-CT and 640 CBCT images) from 80 patients were analyzed. Using linear mixed models, and after adjusting for baseline values at the time of planning-CT to test the differences in rectal dimensions between both groups over the 8-week treatment period, there were no significant differences in RV (p = 0.4), CSA (p = 0.5), anterio-posterior diameter of rectum at superior (p = 0.4) or mid level of CTV (p = 0.4). In the non-MoM group; 22.5% of patients had diarrhea compared to 60% in the MoM group, while 40% discontinued use of MoM by end of radiotherapy. CONCLUSION: The addition of MoM to antiflatulence diet did not reduce the interfraction variation in rectal filling but caused diarrhea in a substantial proportion of patients who then discontinued its use.

Adaptive Radiotherapy for Bladder Cancer-A Systematic Review.

INTRODUCTION: Radiotherapy has been offered as a multimodality treatment for bladder cancer patients. Due to the significant variation of bladder volume observed throughout the course of treatment, large margins in the range of 20-30 mm have been used, unnecessarily irradiating a large volume of normal tissue. With the capability of visualizing soft tissue in cone beam computed tomography, there is opportunity to modify or to adapt the plan based on the variation observed during the course of treatment for quality improvement. METHODS: A literature search was conducted in May 2016, with the aim of examining the adaptive strategies that have been developed for bladder cancer and assessing the efficacy in improving treatment quality. Among the 18 identified publications, three adaptive strategies were reported: plan of the day, patient-specific planning target volume, and daily reoptimisation. RESULTS: Overall, any of the adaptive strategies achieved a significant improvement in reducing the irradiated volume compared with the nonadaptive approach, outweighing the additional resource required for its execution. CONCLUSION: The amount and the type of resource required vary from strategy to strategy, suggesting the need for the individual institution to assess feasibility based on the existing infrastructure to identify the most appropriate strategy for implementation.

Planned versus 'delivered' bladder dose reconstructed using solid and hollow organ models during prostate cancer IMRT.

BACKGROUND AND PURPOSE: All studies to date have evaluated the dosimetric effect of bladder deformation using an organ model that includes the dose to the urine. This research reconstructed bladder dose using both hollow and solid organ models, to determine if dose/volume differences exist. MATERIALS AND METHODS: 35 prostate IMRT patients were selected, who had received 78Gy in 39 fractions and full bladder instructions. Biomechanical modelling and finite element analysis were used to reconstruct bladder dose (solid and hollow organ model) using every third CBCT throughout the treatment course. RESULTS: Reconstructed dose (ReconDose) was 11.3Gy greater than planned dose (planDose) with a hollow bladder model (p<0.001) and 12.3Gy greater with a solid bladder model (p<0.0001). Median reconstructed volumes within the 30Gy, 65Gy and 78Gy isodoses were 3-4 times larger with the solid organ model (p<0.0001). The difference between planning bladder volume and median treatment volume was associated with the difference between the planDose and reconDose below 78Gy (R(2)>0.61). CONCLUSIONS: Substantial differences exist between planned and reconstructed bladder dose, associated with the differences in bladder filling between planning and treatment. Dose reconstructed using a solid bladder model over-reports the volume of bladder within key isodose levels and overestimates the differences between planned and reconstructed dose. Dose reconstruction with a hollow organ model is recommended if the goal is to associate that dose with toxicity.

Impact of image registration surrogates on the planning target volume geometry for bladder radiation therapy.

PURPOSE: The use of Lipiodol and cone beam computed tomography (CT) has facilitated the generation of patient-specific planning target volumes (PTV) to reduce irradiation of normal tissue. However, injecting Lipiodol to demarcate the target volume is an invasive procedure. Center of bladder (COB) and bladder wall surface (BWS) encompassed by the clinical target volume (CTV) are proposed to be the alternative noninvasive surrogates. This study examines the impact of using these 3 surrogates for image registration on the resultant geometry of patient-specific PTVs. METHODS AND MATERIALS: Twenty bladder cancer patients who had Lipiodol injection before planning CT were included. Lipiodol, CTV, and bladder were delineated on the planning CT. In addition, CTVs were delineated on 5 cone beam CT scans from each patient. Cone beam CT scans were registered to planning CT using Lipiodol, COB, and BWS to generate Lipiodol-PTV, COB-PTV, and BWS-PTV. Using Lipiodol as the reference, the difference in the 2-dimensional/3-dimensional displacement values and the geometry of the resultant PTVs were quantified. RESULTS: A total of 1200 displacement values and 60 volumes were included for analysis. The overall median and standard deviation (SD) of the 3-dimensional displacement (mm) measured by Lipiodol, BWS, and COB are 25 (SD, 15), 24 (SD, 14), and 21 (SD, 15), respectively. Lipiodol-PTV has the smallest mean volume, followed by BWS-PTV and COB-PTV. BWS-PTV was more geometrically similar to Lipiodol-PTV when compared with COB-PTV. Six of 20 COB-PTVs who had CTV located at either the dome or the base of the bladder were larger than the corresponding Lipiodol-PTV by more than 20%. CONCLUSION: Lipiodol is the optimal image registration surrogate for partial bladder radiation therapy. However, for patients who are contraindicated for Lipiodol injection, BWS is the preferred noninvasive surrogate because the derived PTV has a smaller geometric variation from the Lipiodol-PTV when compared with COB, especially when the CTV was located at the dome or the base of the bladder.