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Predicting objective function weights from patient anatomy in prostate IMRT treatment planning

Purpose: Intensity-modulated radiation therapy (IMRT) treatment planning typically combines multiple criteria into a single objective function by taking a weighted sum. The authors propose a statistical model that predicts objective function weights from patient anatomy for prostate IMRT treatment planning. This study provides a proof of concept for geometry-driven weight determination. Methods: A previously developed inverse optimization method (IOM) was used to generate optimal objective function weights for 24 patients using their historical treatment plans (i.e., dose distributions). These IOM weights were around 1% for each of the femoral heads, while bladder and rectum weights varied greatly between patients. A regression model was developed to predict a patient's rectum weight using the ratio of the overlap volume of the rectum and bladder with the planning target volume at a 1 cm expansion as the independent variable. The femoral head weights were fixed to 1% each and the bladder weight was calculated as one minus the rectum and femoral head weights. The model was validated using leave-one-out cross validation. Objective values and dose distributions generated through inverse planning using the predicted weights were compared to those generated using the original IOM weights, as well as an average of the IOM weights across all patients. Results: The IOM weight vectors were on average six times closer to the predicted weight vectors than to the average weight vector, usingl{sub 2} distance. Likewise, the bladder and rectum objective values achieved by the predicted weights were more similar to the objective values achieved by the IOM weights. The difference in objective value performance between the predicted and average weights was statistically significant according to a one-sided sign test. For all patients, the difference in rectum V54.3 Gy, rectum V70.0 Gy, bladder V54.3 Gy, and bladder V70.0 Gy values between the dose distributions generated by the predicted weights and IOM weights was less than 5 percentage points. Similarly, the difference in femoral head V54.3 Gy values between the two dose distributions was less than 5 percentage points for all but one patient. Conclusions: This study demonstrates a proof of concept that patient anatomy can be used to predict appropriate objective function weights for treatment planning. In the long term, such geometry-driven weights may serve as a starting point for iterative treatment plan design or may provide information about the most clinically relevant region of the Pareto surface to explore.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

SU-E-T-525: Dose Volume Histograms (DVH) Analysis and Comparison with ICRU Point Doses in MRI Guided HDR Brachytherapy for Cervical Cancer

Purpose: Brachytherapy plays a crucial role in management of cervix cancer. MRI compatible applicators have made it possible to accurately delineate gross-target-volume(GTV) and organs-at-risk(OAR) volumes, as well as directly plan, optimize and adapt dose-distribution for each insertion. We sought to compare DVH of tumor-coverage and OARs to traditional Point-A, ICRU-38 bladder and rectum point-doses for four different planning-techniques. Methods: MRI based 3D-planning was performed on Nucletron-Oncentra-TPS for 3 selected patients with varying tumor-sizes and anatomy. GTV,high-risk-clinical-target-volume(HR-CTV), intermediate-risk-clinical-target-volume(IR-CTV) and OARs: rectum, bladder, sigmoid-colon, vaginal-mucosa were delineated. Three conventionally used techniques: mg-Radium-equivalent(RaEq),equal-dwell-weights(EDW), Medical-College-of-Wisconsin proposed points-optimization (MCWO) and a manual-graphical-optimization(MGO) volume-coverage based technique were applied for each patient. Prescription was 6Gy delivered to point-A in Conventional techniques (RaEq, EDW, MCWO). For MGO, goal was to achieve 90%-coverage (D90) to HR-CTV with prescription-dose. ICRU point doses for rectum and bladder, point-A doses, DVH-doses for HR-CTV-D90,0.1cc-volume(D0.1),1ccvolume( D1),2cc-volume(D2) were collected for all plans and analyzed . Results: Mean D90 for HR-CTV normalized to MGO were 0.89,0.84,0.9,1.0 for EDW, RaEq, MCWO, MGO respectively. Mean point-A doses were 21.7% higher for MGO. Conventional techniques with Point-A prescriptions under covered HR-CTV-D90 by average of 12% as compared to MGO. Rectum, bladder and sigmoid doses were highest in MGO-plans for ICRU points as well as D0.1,D1 and D2 doses. Among conventional-techniques, rectum and bladder ICRU and DVH doses(0.1,1,2cc) were not significantly different (within 7%).Rectum D0.1 provided good estimation of ICRU-rectum-point doses (within 3.9%),rectum D0.1 were higher from 0.8 to 3.9% while bladder D0.1 overestimated the bladder ICRU point dose up to 43% for conventional-techniques.Bladder-D2 provided a good estimation of ICRU bladder point-doses(within 3.6%) for conventional-techniques. This correlation is not observed for MGO plans perhaps due to steering of isodose line, leading to unpredictable dwell-weighting. Conclusion: MRI based HDR-planning provides accurate delineation of tumor volumes and normal structures, and optimized tumor-coverage can be achieved with acceptable normal-tissue doses. This study showed that for conventional techniques D0.1 rectum dose and D2 bladder dose are good representation of ICRU-reference-point doses.

60 APPLIED LIFE SCIENCES↗

SU-F-BRD-01: A Logistic Regression Model to Predict Objective Function Weights in Prostate Cancer IMRT

Purpose: To develop a statistical model that predicts optimization objective function weights from patient geometry for intensity-modulation radiotherapy (IMRT) of prostate cancer. Methods: A previously developed inverse optimization method (IOM) is applied retrospectively to determine optimal weights for 51 treated patients. We use an overlap volume ratio (OVR) of bladder and rectum for different PTV expansions in order to quantify patient geometry in explanatory variables. Using the optimal weights as ground truth, we develop and train a logistic regression (LR) model to predict the rectum weight and thus the bladder weight. Post hoc, we fix the weights of the left femoral head, right femoral head, and an artificial structure that encourages conformity to the population average while normalizing the bladder and rectum weights accordingly. The population average of objective function weights is used for comparison. Results: The OVR at 0.7cm was found to be the most predictive of the rectum weights. The LR model performance is statistically significant when compared to the population average over a range of clinical metrics including bladder/rectum V53Gy, bladder/rectum V70Gy, and mean voxel dose to the bladder, rectum, CTV, and PTV. On average, the LR model predicted bladder and rectum weights that are both 63% closer to the optimal weights compared to the population average. The treatment plans resulting from the LR weights have, on average, a rectum V70Gy that is 35% closer to the clinical plan and a bladder V70Gy that is 43% closer. Similar results are seen for bladder V54Gy and rectum V54Gy. Conclusion: Statistical modelling from patient anatomy can be used to determine objective function weights in IMRT for prostate cancer. Our method allows the treatment planners to begin the personalization process from an informed starting point, which may lead to more consistent clinical plans and reduce overall planning time.

60 APPLIED LIFE SCIENCES↗

Radiobiologically optimized couch shift: A new localization paradigm using cone-beam CT for prostate radiotherapy

Purpose: To present a novel positioning strategy which optimizes radiation delivery by utilizing radiobiological response knowledge and evaluate its use during prostate external beam radiotherapy. Methods: Five patients with low or intermediate risk prostate cancer were evaluated retrospectively in this IRB-approved study. For each patient, a VMAT plan with one 358° arc was generated on the planning CT (PCT) to deliver 78 Gy in 39 fractions. Five representative pretreatment cone beam CTs (CBCT) were selected for each patient. The CBCT images were registered to PCT by a human observer, which consisted of an initial automated registration with three degrees-of-freedom, followed by manual adjustment for agreement at the prostate/rectal wall interface. To determine the optimal treatment position for each CBCT, a search was performed centering on the observer-matched position (OM-position) utilizing a score function based on radiobiological and dosimetric indices (EUD{sub prostate}, D99{sub prostate}, NTCP{sub rectum}, and NTCP{sub bladder}) for the prostate, rectum, and bladder. We termed the optimal treatment position the radiobiologically optimized couch shift position (ROCS-position). Results: The dosimetric indices, averaged over the five patients’ treatment plans, were (mean ± SD) 79.5 ± 0.3 Gy (EUD{sub prostate}), 78.2 ± 0.4 Gy (D99{sub prostate}), 11.1% ± 2.7% (NTCP{sub rectum}), and 46.9% ± 7.6% (NTCP{sub bladder}). The corresponding values from CBCT at the OM-positions were 79.5 ± 0.6 Gy (EUD{sub prostate}), 77.8 ± 0.7 Gy (D99{sub prostate}), 12.1% ± 5.6% (NTCP{sub rectum}), and 51.6% ± 15.2% (NTCP{sub bladder}), respectively. In comparison, from CBCT at the ROCS-positions, the dosimetric indices were 79.5 ± 0.6 Gy (EUD{sub prostate}), 77.3 ± 0.6 Gy (D99{sub prostate}), 8.0% ± 3.3% (NTCP{sub rectum}), and 46.9% ± 15.7% (NTCP{sub bladder}). Excessive NTCP{sub rectum} was observed on Patient 5 (19.5% ± 6.6%) corresponding to localization at OM-position, compared to the planned value of 11.7%. This was mitigated with radiobiologically optimized localization, resulting in a reduced NTCP{sub rectum} value of 11.3% ± 3.5%. Overall, the treatment position optimization resulted in similar target dose coverage with reduced risk to rectum. Conclusions: These encouraging results illustrate the potential advantage of applying radiobiologically optimized correction for online image-guided radiotherapy of prostate patients.

60 APPLIED LIFE SCIENCES↗

Is Dose Deformation–Invariance Hypothesis Verified in Prostate IGRT?

Purpose: To assess dose uncertainties resulting from the dose deformation–invariance hypothesis in prostate cone beam computed tomography (CT)–based image guided radiation therapy (IGRT), namely to evaluate whether rigidly propagated planned dose distribution enables good estimation of fraction dose distributions. Methods and Materials: Twenty patients underwent a CT scan for planning intensity modulated radiation therapy–IGRT delivering 80 Gy to the prostate, followed by weekly CT scans. Two methods were used to obtain the dose distributions on the weekly CT scans: (1) recalculating the dose using the original treatment plan; and (2) rigidly propagating the planned dose distribution. The cumulative doses were then estimated in the organs at risk for each dose distribution by deformable image registration. The differences between recalculated and propagated doses were finally calculated for the fraction and the cumulative dose distributions, by use of per-voxel and dose-volume histogram (DVH) metrics. Results: For the fraction dose, the mean per-voxel absolute dose difference was <1 Gy for 98% and 95% of the fractions for the rectum and bladder, respectively. The maximum dose difference within 1 voxel reached, however, 7.4 Gy in the bladder and 8.0 Gy in the rectum. The mean dose differences were correlated with gas volume for the rectum and patient external contour variations for the bladder. The mean absolute differences for the considered volume receiving greater than or equal to dose x (V{sub x}) of the DVH were between 0.37% and 0.70% for the rectum and between 0.53% and 1.22% for the bladder. For the cumulative dose, the mean differences in the DVH were between 0.23% and 1.11% for the rectum and between 0.55% and 1.66% for the bladder. The largest dose difference was 6.86%, for bladder V{sub 80Gy}. The mean dose differences were <1.1 Gy for the rectum and <1 Gy for the bladder. Conclusions: The deformation–invariance hypothesis was corroborated for the organs at risk in prostate IGRT except in cases of a large disappearance or appearance of rectal gas for the rectum and large external contour variations for the bladder.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

SU-E-T-129: Are Knowledge-Based Planning Dose Estimates Valid for Distensible Organs?

Purpose: Knowledge-based planning programs have become available to assist treatment planning in radiation therapy. Such programs can be used to generate estimated DVHs and planning constraints for organs at risk (OARs), based upon a model generated from previous plans. These estimates are based upon the planning CT scan. However, for distensible OARs like the bladder and rectum, daily variations in volume may make the dose estimates invalid. The purpose of this study is to determine whether knowledge-based DVH dose estimates may be valid for distensible OARs. Methods: The Varian RapidPlan™ knowledge-based planning module was used to generate OAR dose estimates and planning objectives for 10 prostate cases previously planned with VMAT, and final plans were calculated for each. Five weekly setup CBCT scans of each patient were then downloaded and contoured (assuming no change in size and shape of the target volume), and rectum and bladder DVHs were recalculated for each scan. Dose volumes were then compared at 75, 60,and 40 Gy for the bladder and rectum between the planning scan and the CBCTs. Results: Plan doses and estimates matched well at all dose points., Volumes of the rectum and bladder varied widely between planning CT and the CBCTs, ranging from 0.46 to 2.42 for the bladder and 0.71 to 2.18 for the rectum, causing relative dose volumes to vary between planning CT and CBCT, but absolute dose volumes were more consistent. The overall ratio of CBCT/plan dose volumes was 1.02 ±0.27 for rectum and 0.98 ±0.20 for bladder in these patients. Conclusion: Knowledge-based planning dose volume estimates for distensible OARs are still valid, in absolute volume terms, between treatment planning scans and CBCT’s taken during daily treatment. Further analysis of the data is being undertaken to determine how differences depend upon rectum and bladder filling state. This work has been supported by Varian Medical Systems.

60 APPLIED LIFE SCIENCES↗

SU-F-J-11: Radiobiologically Optimized Patient Localization During Prostate External Beam Localization

Purpose: To present a novel positioning strategy which optimizes radiation delivery with radiobiological response knowledge, and to evaluate its application during prostate external beam radiotherapy. Methods: Ten patients with low or intermediate risk prostate cancer were evaluated retrospectively in this IRB-approved study. For each patient, a VMAT plan was generated on the planning CT (PCT) to deliver 78 Gy in 39 fractions with PTV = prostate + 7 mm margin, except for 5mm in the posterior direction. Five representative pretreatment CBCT images were selected for each patient, and prostate, rectum, and bladder were delineated on all CBCT images. Each CBCT was auto-registered to the corresponding PCT. Starting from this auto-matched position (AM-position), a search for optimal treatment position was performed utilizing a score function based on radiobiological and dosimetric indices (D98-DTV, NTCP-rectum, and NTCP-bladder) for the daily target volume (DTV), rectum, and bladder. DTV was defined as prostate + 4 mm margin to account for intra-fraction motion as well as contouring variability on CBCT. We termed the optimal treatment position the radiobiologically optimized couch shift position (ROCS-position). Results: The indices, averaged over the 10 patients’ treatment plans, were (mean±SD): 77.7±0.2 Gy (D98-PTV), 12.3±2.7% (NTCP-rectum), and 53.2±11.2% (NTCP-bladder). The corresponding values calculated on all 50 CBCT images at the AM-positions were 72.9±11.3 Gy (D98-DTV), 15.8±6.4% (NTCP-rectum), and 53.0±21.1% (NTCP-bladder), respectively. In comparison, calculated on CBCT at the ROCS-positions, the indices were 77.0±2.1 Gy (D98-DTV), 12.1±5.7% (NTCP-rectum), and 60.7±16.4% (NTCP-bladder). Compared to autoregistration, ROCS-optimization recovered dose coverage to target volume and lowered the risk to rectum. Moreover, NTCPrectum for one patient remained high after ROCS-optimization and therefore could potentially benefit from adaptive planning. Conclusion: These encouraging results illustrate the potential utility of applying radiobiologically optimized correction for online image-guided radiotherapy of prostate patients.

60 APPLIED LIFE SCIENCES↗

SU-F-T-35: Optimization of Bladder and Rectal Doses Using a Multi-Lumen Intracavitary Applicator for Gynecological Brachytherapy

Purpose: Radiation dose delivery for endometrial cancer using HDR techniques is limited by dose to bladder and rectum. A dosimetric study was performed using Varian Capri vaginal brachytherapy applicator to determine the optimal channel configuration which minimizes dose to bladder and rectum, while providing good target coverage. Methods: A total of 17 patients, 63 plans clinically delivered, and 252 simulated plans using Varian BrachyVision planning system were generated to investigate optimal channel configuration which results in minimum dose to bladder and rectum while providing adequate target coverage. The Capri applicator consists of 13 lumens arranged in two concentric rings, one central lumen and six lumens per ring. Manual dose shaping is invariably required to lower the dose to critical organs. Three-dimensional plans were simulated for 4 channel arrangements, all 13 channels, channel 12 o’clock (close to bladder) and 6 o’clock (close to rectum) deactivated, central channel deactivated, and central channel in addition to 12 o’clock and 6 o’clock deactivated. A relationship between V100, the volume that receives the prescribed dose, and the amount of curie-seconds required to deliver it, was established. Results: Using all 13 channels results in maximum dose to bladder and rectum. Deactivating central channel in addition to 12 o’clock and 6 o’clock resulted in minimizing bladder and rectum doses but compromised target coverage. The relationship between V100, the volume that receives the prescribed dose, and the curie seconds was found to be linear. Conclusion: Deactivating channels 12 o’clock and 6 o’clock was shown to be the optimal configuration leading to minimum dose to bladder and rectum without compromising target coverage. The linear relationship between V100 and the curie- seconds can be used as a verification parameter.

60 APPLIED LIFE SCIENCES↗

Automated generation of IMRT treatment plans for prostate cancer patients with metal hip prostheses: Comparison of different planning strategies

Purpose: To compare IMRT planning strategies for prostate cancer patients with metal hip prostheses.Methods: All plans were generated fully automatically (i.e., no human trial-and-error interactions) using iCycle, the authors' in-house developed algorithm for multicriterial selection of beam angles and optimization of fluence profiles, allowing objective comparison of planning strategies. For 18 prostate cancer patients (eight with bilateral hip prostheses, ten with a right-sided unilateral prosthesis), two planning strategies were evaluated: (i) full exclusion of beams containing beamlets that would deliver dose to the target after passing a prosthesis (IMRT{sub remove}) and (ii) exclusion of those beamlets only (IMRT{sub cut}). Plans with optimized coplanar and noncoplanar beam arrangements were generated. Differences in PTV coverage and sparing of organs at risk (OARs) were quantified. The impact of beam number on plan quality was evaluated.Results: Especially for patients with bilateral hip prostheses, IMRT{sub cut} significantly improved rectum and bladder sparing compared to IMRT{sub remove}. For 9-beam coplanar plans, rectum V{sub 60Gy} reduced by 17.5%{+-} 15.0% (maximum 37.4%, p= 0.036) and rectum D{sub mean} by 9.4%{+-} 7.8% (maximum 19.8%, p= 0.036). Further improvements in OAR sparing were achievable by using noncoplanar beam setups, reducing rectum V{sub 60Gy} by another 4.6%{+-} 4.9% (p= 0.012) for noncoplanar 9-beam IMRT{sub cut} plans. Large reductions in rectum dose delivery were also observed when increasing the number of beam directions in the plans. For bilateral implants, the rectum V{sub 60Gy} was 37.3%{+-} 12.1% for coplanar 7-beam plans and reduced on average by 13.5% (maximum 30.1%, p= 0.012) for 15 directions.Conclusions: iCycle was able to automatically generate high quality plans for prostate cancer patients with prostheses. Excluding only beamlets that passed through the prostheses (IMRT{sub cut} strategy) significantly improved OAR sparing. Noncoplanar beam arrangements and, to a larger extent, increasing the number of treatment beams further improved plan quality.

61 RADIATION PROTECTION AND DOSIMETRY↗

SU-E-J-14: A Novel Approach to Evaluate the Dosimetric Effect of Rectal Variation During Image Guided Prostate Radiotherapy

Purpose: Deformable registration establishes the spatial correspondence back to the reference image in order to accumulate dose. However, in prostate radiotherapy the changing shape and volume of the rectum present a challenge to accurate deformable registration and consequently calculation of delivered dose. We explored an alternative approach to calculating accumulated dose to the rectum, independent of deformable registration. Methods: This study was performed on three patients who received online image-guided radiotherapy (IGRT) with daily CBCT (XVI-system,Elekta) and target localization using intraprostatic fiducials. On each CBCT, the rectum was manually contoured and bulk density assignments were made allowing dose to be calculated for each fraction. Dose-surface maps (DSM) were generated (MATLAB,Mathworks,Natick,MA) by considering the rectum as a cylinder and sampling the dose at 21-equispaced points on each CT slice. The cylinder was “cut” at the posterior-most position on each CT and unfolded to generate a DSM. These were normalised in the longitudinal direction by interpolation creating maps of 21×21 pixels. A DSM was produced for each CBCT and the dose was accumulated. Results: The mean accumulated delivered rectal surface dose was on average 7.5(+/−3.5)% lower than the planned dose. The dose difference maps consistently show that the greatest variation in dose between planned and delivered dose is away from where the rectal surface is adjacent to the prostate. Conclusion: Estimation of dose accumulation using DSM provides an alternative method for determining actual delivered dose to the rectum. The dose difference is greatest in areas away from the region where the rectal surface abuts the prostate, the region where set-up is verified. The change in size and shape of the rectum was shown to resultin a change in the accumulated dose compared to the planned dose and this will have an impact on determining the relationships between dose delivered and toxicity. We acknowledge funding from CRUK and acknowledge NHS funding to the NIHR Biomedical Research Centre for Cancer. Patients were treated within the CHHiP IGRT sub-study (CRUK/06/016, ISRCTN:97182923) funded by CRUK. RayStation was used under an evaluation agreement with RaySearch Laboratories AB.

60 APPLIED LIFE SCIENCES↗

SU-F-J-122: Rectal Sparing Reproducibility in Prostate Cancer Patients Treated with Hydrogel Spacer and Proton Therapy

Purpose: Rectal hydrogel spacer has been shown to improve rectal sparing in prostate radiotherapy. The purpose of this study was to determine the reproducibility of rectal sparing throughout treatment in patients undergoing proton therapy. Methods: At our facility, prostate cancer patients are treated with pencil beam scanning proton therapy, utilizing an endorectal balloon (ERB) or rectal spacer hydrogel (Gel) “SpaceOAR” implant. All patients were treated with a full bladder and empty rectum (low residue diet and stool softeners). A quality assurance CT (QACT) was performed periodically throughout treatment to ensure rectal filling consistency and sparing in 41 patients treated with Gel. The treatment planning (TP) dose was calculated on each QACT and the rectum V90%, V75%, V65%, V50%, and V40% were recorded. QACT scans were acquired on day 0, week 1, week 3, and week 5. Results: 144 QACT scans were analyzed, each patient receiving 3–4 QACTs. Rectum V90% was within +/−1% of the TP dose in 70% of the QACTs and within +/−5% in 95% of scans. From previous data analyses, our ERB rectum V90% average is 6%. This value was used as an upper threshold for the Gel QACT analysis. 5 of the 41 patients (12%), corresponding to 7 QACTs, had a rectum V90% that exceeded 6% on one or more QACTs. However, the average rectal V90% measured over multiple QACTs never exceeded 6%. 55% of the QACTs had a rectum volume within 5cc of the TPCT volume, 68% were within 10cc. Conclusion: In this study, we have shown that a majority of our prostate patients can maintain consistent rectal sparing when treated with a hydrogel spacer. QACT rectal V90% exceeding our threshold was most often related to increased rectal filling and gas, which was addressed with improved dietary compliance and the intensification of stool softeners or laxatives.

60 APPLIED LIFE SCIENCES↗

MRI-Based Radiotherapy Planning to Reduce Rectal Dose in Excess of Tolerance

Background and Purpose. Chronic rectal toxicity significantly decreases the quality of life for men who receive radiotherapy for prostate cancer. The most significant predictor of rectal toxicity is rectal dose-volume exceeding tolerance. To minimize the volume of rectum in the high dose field, it is essential to accurately define the prostate-rectum interface. This can be challenging to do by computed tomography (CT) imaging alone. The current study was undertaken to formally demonstrate in a clinical trial setting that image-guided intensity-modulated radiation therapy (IG-IMRT) planning using magnetic resonance imaging (MRI) can reduce the volume of rectum exceeding 70 Gy, a validated metric that predicts the risk of late rectal toxicity. Materials and Methods. This prospective single-arm study enrolled 15 men treated with IG-IMRT for localized prostate cancer. All participants received a dedicated 3 Tesla MRI examination of the prostate in addition to a pelvic CT examination for treatment planning. Two volumetric modulated arc therapy (VMAT) plans with a prescription dose of 79.2 Gy were designed using identical constraints based on CT- and MRI-defined consensus volumes. The volume of rectum exposed to 70 Gy or more was compared using the Wilcoxon paired signed rank test. Results. For CT-based treatment plans, the median volume of rectum receiving 70 Gy or more was 9.3 cubic centimeters (cc) (IQR 7.0 to 10.2) compared with 4.9 cc (IQR 4.1 to 7.8) for MRI-based plans. This resulted in a median volume reduction of 2.1 cc (IQR 0.5 to 5.3, P < .001). Conclusions. Using MRI to plan prostate IG-IMRT to a dose of 79.2 Gy reduces the volume of rectum receiving radiation dose in excess of tolerance (70 Gy or more) and should be considered in men who are at high risk for late rectal toxicity and are not good candidates for other rectal sparing techniques such as hydrogel spacer. This trial is registered with NCT02470910.

Schmidt, Daniel R.↗

Dosimetric Consequences of Interobserver Variability in Delineating the Organs at Risk in Gynecologic Interstitial Brachytherapy

Purpose: To investigate the dosimetric variability associated with interobserver organ-at-risk delineation differences on computed tomography in patients undergoing gynecologic interstitial brachytherapy. Methods and Materials: The rectum, bladder, and sigmoid of 14 patients treated with gynecologic interstitial brachytherapy were retrospectively contoured by 13 physicians. Geometric variability was calculated using κ statistics, conformity index (CI{sub gen}), and coefficient of variation (CV) of volumes contoured across physicians. Dosimetric variability of the single-fraction D{sub 0.1cc} and D{sub 2cc} was assessed through CV across physicians, and the standard deviation of the total EQD2 (equivalent dose in 2 Gy per fraction) brachytherapy dose (SD{sup TOT}) was calculated. Results: The population mean ± 1 standard deviation of κ, CI{sub gen}, and volume CV were, respectively: 0.77 ± 0.06, 0.70 ± 0.08, and 20% ± 6% for bladder; 0.74 ± 06, 0.67 ± 0.08, and 20% ± 5% for rectum; and 0.33 ± 0.20, 0.26 ± 0.17, and 82% ± 42% for sigmoid. Dosimetric variability was as follows: for bladder, CV = 31% ± 19% (SD{sup TOT} = 72 ± 64 Gy) for D{sub 0.1cc} and CV = 16% ± 10% (SD{sup TOT} = 9 ± 6 Gy) for D{sub 2cc}; for rectum, CV = 11% ± 5% (SD{sup TOT} = 16 ± 17 Gy) for D{sub 0.1cc} and CV = 7% ± 2% (SD{sup TOT} = 4 ± 3 Gy) for D{sub 2cc}; for sigmoid, CV = 39% ± 28% (SD{sup TOT} = 12 ± 18 Gy) for D{sub 0.1cc} and CV = 34% ± 19% (SD{sup TOT} = 4 ± 4 Gy) for D{sub 2cc.} Conclusions: Delineation of bladder and rectum by 13 physicians demonstrated substantial geometric agreement and resulted in good dosimetric agreement for all dose-volume histogram parameters except bladder D{sub 0.1cc.} Small delineation differences in high-dose regions by the posterior bladder wall may explain these results. The delineation of sigmoid showed fair geometric agreement. The higher dosimetric variability for sigmoid compared with rectum and bladder did not correlate with higher variability in the total brachytherapy dose but rather may be due to the sigmoid being positioned in low-dose regions in the cases analyzed in this study.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Multifield optimization intensity-modulated proton therapy (MFO-IMPT) for prostate cancer: Robustness analysis through simulation of rotational and translational alignment errors

To evaluate the dosimetric consequences of rotational and translational alignment errors in patients receiving intensity-modulated proton therapy with multifield optimization (MFO-IMPT) for prostate cancer. Ten control patients with localized prostate cancer underwent treatment planning for MFO-IMPT. Rotational and translation errors were simulated along each of 3 axes: anterior-posterior (A-P), superior-inferior (S-I), and left-right. Clinical target-volume (CTV) coverage remained high with all alignment errors simulated. Rotational errors did not result in significant rectum or bladder dose perturbations. Translational errors resulted in larger dose perturbations to the bladder and rectum. Perturbations in rectum and bladder doses were minimal for rotational errors and larger for translational errors. Rectum V45 and V70 increased most with A-P misalignment, whereas bladder V45 and V70 changed most with S-I misalignment. The bladder and rectum V45 and V70 remained acceptable even with extreme alignment errors. Even with S-I and A-P translational errors of up to 5 mm, the dosimetric profile of MFO-IMPT remained favorable. MFO-IMPT for localized prostate cancer results in robust coverage of the CTV without clinically meaningful dose perturbations to normal tissue despite extreme rotational and translational alignment errors.

61 RADIATION PROTECTION AND DOSIMETRY↗

The importance of prostate bed tilt during postprostatectomy intensity-modulated radiotherapy

Variations in rectal and bladder filling can create a tilt of the prostate bed, which generates the potential for a geographic miss during postprostatectomy radiotherapy. The aim of this study is to assess the effect that bladder and rectum filling has on planning target volume angle, to determine a method to assess prostate bed tilt leading to potential geographic miss, and to discuss possible implementation issues. The cone-beam computed tomography images (n = 377) of 40 patients who received postprostatectomy radiotherapy with intensity-modulated radiotherapy were reviewed. The amount of tilt in the prostate bed was defined as the angle change between 2 surgical clips, one in the upper prostate bed and another in the lower. A potential geographic miss was defined as movement of any clip of more than 1 cm in any direction or 0.5 cm posteriorly when aligned to bone anatomy. Variations in bladder and rectum size were correlated with the degree of prostate bed tilt, and the rate of potential geographic miss was determined. A possible clinical use of prostate bed tilt was then assessed for different imaging techniques. A tilt of more than 10° was seen in 20.2% of images, which resulted in a 57.9% geographic miss rate of the superior clip. When tilt remained within 10°, there was only a 9% rate of geographic miss. Potential geographic miss of the inferior surgical clip was rare, occurring in only 1.9% of all images reviewed. The most common occurrence when the prostate bed tilt increased by more than 10° was a smaller bladder and larger rectum (6.4% of all images). The most common occurrence when the prostate bed tilt decreased by more than 10° was a larger bladder and smaller rectum (1.3% of all images). Significant prostate bed tilt (>± 10°) occurred in more than 20% of images, creating a 58% rate of geographic miss. Greatest prostate bed tilt occurred when the bladder size increased or reduced by more than 2 cm or the superior rectum size increased by more than 1.5 cm or reduced by more than 1 cm from the planned size. Using prostate bed tilt could be an effective measurement for assessing potential geographic miss on orthogonal images if volumetric imaging is unavailable.

61 RADIATION PROTECTION AND DOSIMETRY↗

SU-E-T-634: Analysis of Volume Based GYN HDR Brachytherapy Plans for Dose Calculation to Organs At Risk(OAR)

Purpose: We have analyzed the dose volume histogram of 140 CT based HDR brachytherapy plans and evaluated the dose received to OAR ; rectum, bladder and sigmoid colon based on recommendations from ICRU and Image guided brachytherapy working group for cervical cancer . Methods: Our treatment protocol consist of XRT to whole pelvis with 45 Gy at 1.8Gy/fraction followed by 30 Gy at 6 Gy per fraction by HDR brachytherapy in 2 weeks . The CT compatible tandem and ovoid applicators were used and stabilized with radio opaque packing material. The patient was stabilized using special re-locatable implant table and stirrups for reproducibility of the geometry during treatment. The CT scan images were taken at 3mm slice thickness and exported to the treatment planning computer. The OAR structures, bladder, rectum and sigmoid colon were outlined on the images along with the applicators. The prescription dose was targeted to A left and A right as defined in Manchester system and optimized on geometry . The dosimetry was compared on all plans using the parameter Ci.sec.cGy-1 . Using the Dose Volume Histogram (DVH) obtained from the plans the doses to rectum, sigmoid colon and bladder for ICRU defined points and 2cc volume were analyzed and reported. The following criteria were used for limiting the tolerance dose by volume (D2cc) were calculated. The rectum and sigmoid colon doses were limited to <75Gy. The bladder dose was limited to < 90Gy from both XRT and HDR brachytherapy. Results: The average total (XRT+HDRBT) BED values to prescription volume was 120 Gy. Dose 2cc to rectum was 70Gy +/− 17Gy, dose to 2cc bladder was 82+/−32 Gy. The average Ci.sec.cGy-1 calculated for the HDR plans was 6.99 +/− 0.5 Conclusion: The image based treatment planning enabled to evaluati volume based dose to critical structures for clinical interpretation.

60 APPLIED LIFE SCIENCES↗

Models for predicting objective function weights in prostate cancer IMRT

Purpose: To develop and evaluate the clinical applicability of advanced machine learning models that simultaneously predict multiple optimization objective function weights from patient geometry for intensity-modulated radiation therapy of prostate cancer. Methods: A previously developed inverse optimization method was applied retrospectively to determine optimal objective function weights for 315 treated patients. The authors used an overlap volume ratio (OV) of bladder and rectum for different PTV expansions and overlap volume histogram slopes (OVSR and OVSB for the rectum and bladder, respectively) as explanatory variables that quantify patient geometry. Using the optimal weights as ground truth, the authors trained and applied three prediction models: logistic regression (LR), multinomial logistic regression (MLR), and weighted K-nearest neighbor (KNN). The population average of the optimal objective function weights was also calculated. Results: The OV at 0.4 cm and OVSR at 0.1 cm features were found to be the most predictive of the weights. The authors observed comparable performance (i.e., no statistically significant difference) between LR, MLR, and KNN methodologies, with LR appearing to perform the best. All three machine learning models outperformed the population average by a statistically significant amount over a range of clinical metrics including bladder/rectum V53Gy, bladder/rectum V70Gy, and dose to the bladder, rectum, CTV, and PTV. When comparing the weights directly, the LR model predicted bladder and rectum weights that had, on average, a 73% and 74% relative improvement over the population average weights, respectively. The treatment plans resulting from the LR weights had, on average, a rectum V70Gy that was 35% closer to the clinical plan and a bladder V70Gy that was 29% closer, compared to the population average weights. Similar results were observed for all other clinical metrics. Conclusions: The authors demonstrated that the KNN and MLR weight prediction methodologies perform comparably to the LR model and can produce clinical quality treatment plans by simultaneously predicting multiple weights that capture trade-offs associated with sparing multiple OARs.

60 APPLIED LIFE SCIENCES↗

SU-E-J-39: Dosimetric Benefit of Implanted Marker-Based CBCT Setup for Definitive Prostatic Radiotherapy

Purpose Daily setup for definitive prostatic radiotherapy is challenged by suboptimal visibility of the prostate boundary and daily variation of rectum shape and position. For patients with improved bowel preparation, we conducted a dosimetric comparison between prostate implanted marker (IM)-based daily setup and anterior rectal wall (ARW)-based setup, with the hypothesis that the former leads to adequate target coverage with better rectal sparing. Methods Five IMRT/VMAT prostate cases with implanted markers were selected for analysis. Daily CBCT showed improvement of the rectal volume compared to planning CT. For each patient, the prostate and rectum were contoured on three CBCT images (fraction 5/15/25) with subsequent physician review. The CBCTs were then registered to a planning CT using IM-based registration. The deviation of ARW positions from planning CT to CBCT were analyzed at various sup-inf levels (−1.8 cm to 1.8 cm from level of prostate center). To estimate the potential dosimetric impact from ARW-based setup, the treatment plans were recalculated using A-P shifts ranging from −1mm to +6mm. Clinically important rectum DVH values including Dmax, D3cc and Dmean were computed. Results For the studied patients, we observed on average 32% rectum volume reduction from planning CT to CBCT. As a Results, the ARW on average shifts posteriorly by −1mm to +5mm, depending on the sup-inf level of observation, with larger shifts observed at more superior levels. Recalculation shows that when ARW shifts 1mm posteriorly, ARW-based CBCT setup leads to a 1.0%, 4.2%, and 3.2% increase in rectum Dmax, D3cc, and Dmean, respectively, compared to IM-based setup. The dosimetric deviations increase to 4.7%, 25.8% and 24.7% when ARW shifts 6mm posteriorly. No significant prostate-only dose difference was observed. Conclusion For patients with improved bowel preparation, IM-based CBCT setup leads to accurate prostate coverage along with significantly lower rectal dose, compared to ARW-based setup.

60 APPLIED LIFE SCIENCES↗