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Knowledge-based planning (KBP) is increasingly implemented clinically because of its demonstrated ability to improve treatment planning efficiency and reduce plan quality variations. However, cases with large dose-volume histogram (DVH) prediction uncertainties may still need manual adjustments by the planner to achieve high plan quality.The purpose of this study is to develop a data-driven method to detect patients with high prediction uncertainties so that intentional effort is directed to these patients.We apply an anomaly detection method known as the local outlier factor (LOF) to a dataset consisting of the training set and each of the prospective patients considered, to evaluate their likelihood of being an anomaly when compared with the training cases. Features used in the LOF analysis include anatomical features and the model-generated DVH principal component scores. To test the efficacy of the proposed model, 142 prostate patients were retrieved from the clinical database and split into a training dataset of 100 patients and a test dataset of 42 patients. The outlier identification performance was quantified by the difference between the DVH prediction root-mean-squared errors (RMSE) of the identified outlier cases and that of the remaining inlier cases.With a predefined LOF threshold of 1.4, the inlier cases achieved average RMSEs of 5.0 and 6.7 for bladder and rectum, while the outlier cases have substantially higher RMSEs of 6.7 and 13.0 in comparison.We propose a method that can determine the prospective patient's outlier status. This method can be integrated into existing automated treatment planning workflows to reduce the risk of generating suboptimal treatment plans while providing an upfront alert to the treatment planner.

Purpose: High radiation doses to the heart have been correlated with poor overall survival in patients receiving radiation therapy for stage III non-small cell lung cancer (NSCLC). We built a knowledge-based planning (KBP) tool to limit the dose to the heart during creation of volumetric modulated arc therapy (VMAT) treatment plans for patients being treated to 60 Gy in 30 fractions for stage III NSCLC. Methods and Materials: A previous study at our institution retrospectively delineated intracardiac volumes and optimized VMAT treatment plans to reduce dose to these substructures and to the whole heart. Two RapidPlan (RP) KBP models were built from this cohort, 1 model using the clinical plans and a separate model using the cardiac-optimized plans. Using target volumes and 6 organs at risk (OARs), models were trained to generate treatment plans in a semiautomated process. The cardiac-sparing KBP model was tested in the same cohort used for training, and both models were tested on an external validation cohort of 30 patients. Results: Both RP models produced clinically acceptable plans in terms of target coverage, dose uniformity, and dose to OARs. Compared with the previously created cardiac-optimized plans, cardiac-sparing RPs showed significant reductions in the mean dose to the esophagus and lungs while performing similarly or better in all evaluated heart dose metrics. When comparing the 2 models, the cardiac-sparing RP showed reduced (P < .05) heart mean and maximum doses as well as volumes receiving 60 Gy, 50 Gy, and 30 Gy. Conclusions: By using a set of cardiac-optimized treatment plans for training, the proposed KBP model provided a means to reduce the dose to the heart and its substructures without the need to explicitly delineate cardiac substructures. This tool may offer reduced planning time and improved plan quality and might be used to improve patient outcomes.

We report a case of a 72-year-old woman who presented with ST-elevation myocardial infarction (STEMI). However, coronary angiography showed unobstructed arteries while echocardiography (ECHO) showed severe left ventricular (LV) apical hypokinesia with ejection fraction (EF) of 25–30%. Seven months later she presented with a transient ischaemic attack and a repeat ECHO showed a normal EF. A few months later, she was diagnosed with breast cancer and as part of staging procedure, an incidental left adrenal mass was identified. This was biochemically confirmed as phaeochromocytoma (PY) and she underwent laparoscopic adrenalectomy. PY is a rare catecholamine secreting tumour arising from adrenomedullary chromaffin cells. Excessive catecholamine-induced stimulation can present as transient, reversible cardiomyopathy similar to Takotsubo cardiomyopathy and cerebrovascular events. The diagnosis of PY is often delayed but it is important to recognize PY as a cause of reversible cardiomyopathy. Early intervention is essential to improve mortality from cardiovascular and cerebrovascular complications.

Purpose Increasing radiation dose to the heart is associated with worse survival in stage III non-small cell lung cancer. We sought to evaluate the ability of optimized volumetric modulated arc therapy (VMAT) and intensity modulated proton therapy (IMPT) to spare cardiac substructures. We also wanted to determine how a cardiac optimization treatment planning algorithm influences dose distribution to other thoracic organs at risk (OARs). Methods and Materials Cardiac substructures were retrospectively contoured for all patients with stage III non-small cell lung cancer who were treated at our institution with VMAT to 60 Gy in 2-Gy fractions. The structures included valves, atrioventricular node, coronary arteries, chambers, and great vessels. New cardiac-optimized VMAT plans were created to spare these structures while preserving planning target volume coverage and maintaining standard dose constraints to OARs. Dosimetry variables for the new cardiac-optimized VMAT plans were compared via paired t test with the original VMAT plans. IMPT plans were also created, and the cardiac-optimized VMAT plans were then similarly compared with the IMPT plans. Results Twenty-six patients who were treated from July 2013 to September 2017 were included. Compared with the original VMAT plans, statistically significant improvements were demonstrated for all cardiac structures for the new cardiac-optimized VMAT plans while maintaining or improving appropriate lung, esophagus, and spinal cord constraints and planning target volume coverage goals. Compared with cardiac-optimized VMAT, IMPT demonstrated additional statistically significant improvements for some cardiac dosimetry metrics while maintaining or improving other thoracic OAR constraints. Conclusions VMAT is now widely available, and high-quality VMAT plans that incorporate cardiac substructures into the optimization process can provide overall improvements in dose to OARs and, in particular, substantial sparing of critical cardiac structures. IMPT provides some incremental dosimetric improvements beyond cardiac-optimized VMAT, the clinical significance of which remains uncertain.

Purpose/Objective(s) Chemoradiation (CRT) followed by maintenance durvalumab is the standard of care for locally advanced non-small cell lung cancer (NSCLC) but is limited by toxicity to normal lung tissue from radiotherapy and immunotherapy1. Many lung cancer patients have heterogeneous lung function as a result of the tumor and/or pre-existing co-morbidities2. We proposed Volumetric Modulated Arc Therapy (VMAT) could be used to spare the functional parts of the lung (FL) without exceeding organs at risk (OARs) constraints or compromising tumor coverage. Materials/Methods Functional lung volumes were retrospectively contoured using 4D-CT ventilation maps for 32 patients with stage III NSCLC treated with CRT and maintenance durvalumab at a single institution from September 2017- October 2019. Functional lung volumes were created from 4D-CT data using methodology previously described3,4. Studies have shown 4D-CT ventilation maps generated from the changes in the density of lungs during the respiratory cycle correlate with pulmonary function tests and ventilation-perfusion imaging5. New VMAT plans were generated to spare the FL while also maintaining adequate planning target volume (PTV) coverage and without exceeding dose constraints to the OARs. The dosimetric values of the original plans were compared to the dosimetric values of the optimized plans using paired t-test or paired Wilcox rank-sum test as appropriate. Specifically, the PTV D95, heart mean, esophagus mean, spinal cord Dmax, as well as the FL mean, FL V5, FL V10, FL V20, and FL V30 were compared. Results Optimized plans had statically significant lower FL mean dose, FL V5, FL V10, FL V20, and FL V30 (all P values Conclusion We demonstrated the ability to optimize VMAT plans to avoid functional parts of the lung while maintaining adequate PTV coverage and meeting OAR constraints for locally advanced NSCLC. VMAT plans optimized to avoid functional lung can be created with minimal extra cost or change in treatment planning workflow as 4D-CT acquisition at time of simulation is standard practice, which is advantageous compared to other functional lung avoidance techniques, i.e., single photon emission computerized tomography (SPECT). Given already compromised lung function and risk of pulmonary toxicities from treatment, this work highlights a personalized approach to radiation treatment planning.

Objective: The purpose of this work is to develop and validate a learning-based method to derive electron density from routine anatomical MRI for potential MRI-based SBRT treatment planning. Methods: We proposed to integrate dense block into cycle generative adversarial network (GAN) to effectively capture the relationship between the CT and MRI for CT synthesis. A cohort of 21 patients with co-registered CT and MR pairs were used to evaluate our proposed method by the leave-one-out cross-validation. Mean absolute error, peak signal-to-noise ratio and normalized cross-correlation were used to quantify the imaging differences between the synthetic CT (sCT) and CT. The accuracy of Hounsfield unit (HU) values in sCT for dose calculation was evaluated by comparing the dose distribution in sCT-based and CT-based treatment planning. Clinically relevant dose–volume histogram metrics were then extracted from the sCT-based and CT-based plans for quantitative comparison. Results: The mean absolute error, peak signal-to-noise ratio and normalized cross-correlation of the sCT were 72.87 ± 18.16 HU, 22.65 ± 3.63 dB and 0.92 ± 0.04, respectively. No significant differences were observed in the majority of the planning target volume and organ at risk dose–volume histogram metrics ( p > 0.05). The average pass rate of γ analysis was over 99% with 1%/1 mm acceptance criteria on the coronal plane that intersects with isocenter. Conclusion: The image similarity and dosimetric agreement between sCT and original CT warrant further development of an MRI-only workflow for liver stereotactic body radiation therapy. Advances in knowledge: This work is the first deep-learning-based approach to generating abdominal sCT through dense-cycle-GAN. This method can successfully generate the small bony structures such as the rib bones and is able to predict the HU values for dose calculation with comparable accuracy to reference CT images.

Purpose: To determine the utility of focal high-dose-rate brachytherapy for localized prostate cancer, we investigated the impact on target coverage and dose to organs at risk (OARs) with hemigland (HG) compared with whole-gland (WG) treatment. Methods and Materials: A total of 10 WG implants were used to generate 10 WG and 20 HG (left and right) treatment plans optimized with the inverse planning simulation annealing algorithm using Oncentra MasterPlan (Nucletron B.V., Veenendaal, The Netherlands). The standard distribution of 17-18 catheters designed for WG was used to generate HG plans. The same OARs namely bladder, rectum, and urethra contours and dose constraints were applied for HG and WG plans. The HG contour was a modification of the WG contour whereby the urethra divided the prostate into HGs. The prescription dose was 7.25 Gy×6. Evaluated dose parameters were target dose D90, V100, and V150 and D0.1 cc, D1 cc, and D2 cc to OARs. Results: The HG plans had a D90, V100, and V150 to the HG target of 112%, 97.6%, and 33.8%, respectively. The WG plans had a D90, V100, and V150 to the WG target of 108%, 98.8%, and 26.5%, respectively. The OAR D2 cc doses were significantly lower in HG vs. WG plans: rectum (53.1% vs.64.1%, p

Objectives The late effects of RT are not well reported in patients with oral tongue cancer (OTC). This study reports the incidence of late effects and factors associated with the development of late effects in OTC patients. Methods Patients with OTC treated in our institution from 2003 to 2013 were evaluated. The association between RT doses, including mandible maximum and minimum doses and total 3D maximum dose, and late toxicity, defined as development of osteoradionecrosis (ORN), percutaneous endoscopic gastrostomy (PEG) tube dependence for >6 months after treatment, and narcotic dependency >6 months posttreatment were assessed using both univariate and multivariable (MV) analysis. Results Seventy-six patients with OTC (45% males and 55% females) were treated with definitive surgical resection followed by adjuvant RT. The median follow-up was 4.3 years. Combined late toxicities were reported in 38% of patients. Thirty-four percent of the patients had narcotic dependency and, 3.9% of the patients had ORN of the mandible. Thirteen percent of patients developed PEG tube dependency that was significantly associated with a higher 3D maximum radiation dose on univariate analysis (p

Purpose We performed a dosimetry analysis to determine how well the goals for clinical target volume coverage, dose homogeneity, and normal tissue dose constraints were achieved with high-dose-rate (HDR) prostate brachytherapy. Methods and Materials Cumulative dose-volume histograms for 208 consecutively treated HDR prostate brachytherapy implants were analyzed. Planning was based on ultrasound-guided catheter insertion and postoperative CT imaging; the contoured clinical target volume (CTV) was the prostate, a small margin, and the proximal seminal vesicles. Dosimetric parameters analyzed for the CTV were D90, V90, V100, V150, and V200. Dose to the urethra, bladder, bladder balloon, and rectum were evaluated by the dose to 0.1 cm 3 , 1 cm 3 , and 2 cm 3 of each organ, expressed as a percentage of the prescribed dose. Analysis was stratified according to prostate size. Results The mean prostate ultrasound volume was 38.7 ± 13.4 cm 3 (range: 11.7-108.6 cm 3 ). The mean CTV was 75.1 ± 20.6 cm 3 (range: 33.4-156.5 cm 3 ). The mean D90 was 109.2% ± 2.6% (range: 102.3%-118.4%). Ninety-three percent of observed D90 values were between 105 and 115%. The mean V90, V100, V150, and V200 were 99.9% ± 0.05%, 99.5% ± 0.8%, 25.4% ± 4.2%, and 7.8% ± 1.4%. The mean dose to 0.1 cm 3 , 1 cm 3 , and 2 cm 3 for organs at risk were: Urethra: 107.3% ± 3.0%, 101.1% ± 14.6%, and 47.9% ± 34.8%; bladder wall: 79.5% ± 5.1%, 69.8% ± 4.9%, and 64.3% ± 5.0%; bladder balloon: 70.3% ± 6.8%, 59.1% ± 6.6%, and 52.3% ± 6.2%; rectum: 76.3% ± 2.5%, 70.2% ± 3.3%, and 66.3% ± 3.8%. There was no significant difference between D90 and V100 when stratified by prostate size. Conclusions HDR brachytherapy allows the physician to consistently achieve complete prostate target coverage and maintain normal tissue dose constraints for organs at risk over a wide range of target volumes.

Due to glioblastoma's infiltrative nature, an optimal radiation therapy (RT) plan requires targeting infiltration not identified by anatomical magnetic resonance imaging (MRI). Here, high-resolution, whole-brain spectroscopic MRI (sMRI) is used to describe tumor infiltration alongside anatomical MRI and simulate the degree to which it modifies RT target planning. In 11 patients with glioblastoma, data from preRT sMRI scans were processed to give high-resolution, whole-brain metabolite maps normalized by contralateral white matter. Maps depicting choline to N-Acetylaspartate (Cho/NAA) ratios were registered to contrast-enhanced T1-weighted RT planning MRI for each patient. Volumes depicting metabolic abnormalities (1.5-, 1.75-, and 2.0-fold increases in Cho/NAA ratios) were compared with conventional target volumes and contrast-enhancing tumor at recurrence. sMRI-modified RT plans were generated to evaluate target volume coverage and organ-at-risk dose constraints. Conventional clinical target volumes and Cho/NAA abnormalities identified significantly different regions of microscopic infiltration with substantial Cho/NAA abnormalities falling outside of the conventional 60 Gy isodose line (41.1, 22.2, and 12.7 cm3, respectively). Clinical target volumes using Cho/NAA thresholds exhibited significantly higher coverage of contrast enhancement at recurrence on average (92.4%, 90.5%, and 88.6%, respectively) than conventional plans (82.5%). sMRI-based plans targeting tumor infiltration met planning objectives in all cases with no significant change in target coverage. In 2 cases, the sMRI-modified plan exhibited better coverage of contrast-enhancing tumor at recurrence than the original plan. Integration of the high-resolution, whole-brain sMRI into RT planning is feasible, resulting in RT target volumes that can effectively target tumor infiltration while adhering to conventional constraints.

Purpose A new platform for brachytherapy called electronic brachytherapy (EBT) has been developed, which uses a miniature X-ray source to generate low-energy radiation. A retrospective study of adverse events and clinical outcomes in patients treated with EBT to the vaginal cuff, either as monotherapy or in combination with external beam radiation therapy (EBRT), was conducted. Methods and Materials Medical records were reviewed from 16 patients treated with postoperative EBT for endometrial ( n = 13) or cervical cancer ( n = 3) between February 2009 and November 2010. Patients received either intracavitary vaginal EBT alone or EBT in combination with EBRT. The radiobiologic effectiveness of EBT was assumed to be one. Results Median follow-up was 20.5 months (range, 7–36 months). When EBT was used alone ( n = 5), the median dose per fraction, number of fractions, and total dose delivered were: 6 Gy (range, 5.5–6.2 Gy), 5 fractions (range, 5–6), and 30 Gy (range, 30–34 Gy), respectively. When EBT was combined with EBRT, the EBT component median dose per fraction, number of fractions, and total dose delivered were: 5 Gy (range, 4.5–7 Gy), 2 fractions (range, 2–4), and 14 Gy (range, 9–20 Gy), respectively. The median EBRT dose was 45 Gy (range, 45–49.2 Gy). Our local control rate, locoregional (pelvic) control rate, and overall survival rate were 94%, 94%, and 88%, respectively. Of the 16 patients, 4 patients reported Grade 2 or greater toxicity (25%); however, there were no Grade 4–5 adverse events. Gynecologic, genitourinary, and gastrointestinal adverse events accounted for 57% ( n = 4), 43% ( n = 3), and 0% ( n = 0) of all Grade 2 or greater side effects. No Grade 2 or higher toxicities were noted in patients treated with EBT alone. Conclusion EBT is an acceptable means of delivering postoperative vaginal brachytherapy and appears comparable with other methods; as the sole method of treatment, the toxicity rates of EBT are low.

255 Background: To determine potential benefits of focal brachytherapy, we investigated target coverage and magnitude of decreased dose to organs at risk (OARs) with hemigland (HG) compared to whole gland (WG) high dose rate brachytherapy. Methods: 10 WG implants were used to generate 10 WG and 20 HG (left and right) treatment plans using Inverse Planning Simulation Annealing in Oncentra Masterplan (Nucletron). The same distribution of 17-18 catheters was used for WG and HG plans. The same dose constraints were used for all plans (D90 100-115%, V100 97-100%, V1500.1cc 0.1cc < 95%, and Urethra D0.1cc 90, V100, and V150 were calculated for HG and WG, along with D0.1cc, D1cc, D2cc, and Davg to OARs. We estimated mean difference and 95% confidence intervals for outcome measures. Bonferroni correction was used to adjust for bias due to multiple comparisons. Statistical analyses were conducted using SAS 9.2 (SAS Institute, Cary, NC), with a significance level set at p=0.003. Results: Compared to WG, HG was associated with a higher D90 (108 vs 112%, p < 0.0001), lower V100 (98.8 vs 97.6%, p = 0.0001), and higher V150 (26.5 vs 33.8%, p = 0.0001). WG therapy resulted in higher tissue doses to OARs. Mean values for the rectum were D0.1cc (76.0 vs 71.2%, p=.0027), D1cc (68.4 vs 59.0%, p2cc (64.1 vs 53.1%, pavg (27.5 vs 20.5%, p0.1cc (83.8 vs 82.2%, p=0.0925), D1cc (73.4 vs 64.0%, p2cc (67.5 vs 55.9%, pavg (22.1 vs 16.2%, p0.1cc (106.5 vs 97.7, p1cc (103.1 vs 82.9%, p2cc (95.2 vs 69.3%, pavg (73.5 vs 57.2%, p Conclusions: The catheter distribution used for WG may not be ideal for HG as a higher D90 and V150 was noted. HG plans decreased Davg to the rectum, bladder, and urethra by a difference of 7.0, 5.9, and 16.3%. Further research is warranted to determine whether further dose reductions can be achieved and are clinically meaningful.