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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 505 records · Page 28
All sourcesNASA NTRSDOE OSTI
DOE OSTI2015

Defining the “Hostile Pelvis” for Intensity Modulated Radiation Therapy: The Impact of Anatomic Variations in Pelvic Dimensions on Dose Delivered to Target Volumes and Organs at Risk in Patients With High-Risk Prostate Cancer Treated With Whole Pelvic Radiation Therapy

Purpose: The aim of this study was to evaluate the impact of variations in pelvic dimensions on the dose delivered to the target volumes and the organs at risk (OARs) in patients with high-risk prostate cancer (PCa) to be treated with whole pelvic radiation therapy (WPRT) in an attempt to define the hostile pelvis in terms of intensity modulated radiation therapy (IMRT). Methods and Materials: In 45 men with high-risk PCa to be treated with WPRT, the target volumes and the OARs were delineated, the dose constraints for the OARs were defined, and treatment plans were generated according to the Radiation Therapy Oncology Group 0924 protocol. Six dimensions to reflect the depth, width, and height of the bony pelvis were measured, and 2 indexes were calculated from the planning computed tomographic scans. The minimum dose (D{sub min}), maximum dose (D{sub max}), and mean dose (D{sub mean}) for the target volumes and OARs and the partial volumes of each of these structures receiving a specified dose (V{sub D}) were calculated from the dose-volume histograms (DVHs). The data from the DVHs were correlated with the pelvic dimensions and indexes. Results: According to an overall hostility score (OHS) calculation, 25 patients were grouped as having a hospitable pelvis and 20 as having a hostile pelvis. Regarding the OHS grouping, the DVHs for the bladder, bowel bag, left femoral head, and right femoral head differed in favor of the hospitable pelvis group, and the DVHs for the rectum differed for a range of lower doses in favor of the hospitable pelvis group. Conclusions: Pelvimetry might be used as a guide to define the challenging anatomy or the hostile pelvis in terms of treatment planning for IMRT in patients with high-risk PCa to be treated with WPRT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Clinical and Dosimetric Predictors of Acute Severe Lymphopenia During Radiation Therapy and Concurrent Temozolomide for High-Grade Glioma

Purpose: Acute severe lymphopenia (ASL) frequently develops during radiation therapy (RT) and concurrent temozolomide (TMZ) for high-grade glioma (HGG) and is associated with decreased survival. The current study was designed to identify potential predictors of ASL, with a focus on actionable RT-specific dosimetric parameters. Methods and Materials: From January 2007 to December 2012, 183 patients with HGG were treated with RT+TMZ and had available data including total lymphocyte count (TLC) and radiation dose-volume histogram parameters. ASL was defined as TLC of <500/μL within the first 3 months from the start of RT. Stepwise logistic regression analysis was used to determine the most important predictors of ASL. Results: Fifty-three patients (29%) developed ASL. Patients with ASL had significantly worse overall survival than those without (median: 12.5 vs 20.2 months, respectively, P<.001). Stepwise logistic regression analysis identified female sex (odds ratio [OR]: 5.30; 95% confidence interval [CI]: 2.46-11.41), older age (OR: 1.05; 95% CI: 1.02-1.09), lower baseline TLC (OR: 0.92; 95% CI: 0.87-0.98), and higher brain volume receiving 25 Gy (V{sub 25Gy}) (OR: 1.03; 95% CI: 1.003-1.05) as the most significant predictors for ASL. Brain V{sub 25Gy} <56% appeared to be the optimal threshold (OR: 2.36; 95% CI: 1.11-5.01), with an ASL rate of 38% versus 20% above and below this threshold, respectively (P=.006). Conclusions: Female sex, older age, lower baseline TLC, and higher brain V{sub 25Gy} are significant predictors of ASL during RT+TMZ therapy for HGG. Maintaining the V{sub 25Gy} of brain below 56% may reduce the risk of ASL.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Assessing the Clinical Impact of Approximations in Analytical Dose Calculations for Proton Therapy

Purpose: To assess the impact of approximations in current analytical dose calculation methods (ADCs) on tumor control probability (TCP) in proton therapy. Methods: Dose distributions planned with ADC were compared with delivered dose distributions as determined by Monte Carlo simulations. A total of 50 patients were investigated in this analysis with 10 patients per site for 5 treatment sites (head and neck, lung, breast, prostate, liver). Differences were evaluated using dosimetric indices based on a dose-volume histogram analysis, a γ-index analysis, and estimations of TCP. Results: We found that ADC overestimated the target doses on average by 1% to 2% for all patients considered. The mean dose, D95, D50, and D02 (the dose value covering 95%, 50% and 2% of the target volume, respectively) were predicted within 5% of the delivered dose. The γ-index passing rate for target volumes was above 96% for a 3%/3 mm criterion. Differences in TCP were up to 2%, 2.5%, 6%, 6.5%, and 11% for liver and breast, prostate, head and neck, and lung patients, respectively. Differences in normal tissue complication probabilities for bladder and anterior rectum of prostate patients were less than 3%. Conclusion: Our results indicate that current dose calculation algorithms lead to underdosage of the target by as much as 5%, resulting in differences in TCP of up to 11%. To ensure full target coverage, advanced dose calculation methods like Monte Carlo simulations may be necessary in proton therapy. Monte Carlo simulations may also be required to avoid biases resulting from systematic discrepancies in calculated dose distributions for clinical trials comparing proton therapy with conventional radiation therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Magnetic Resonance–Based Automatic Air Segmentation for Generation of Synthetic Computed Tomography Scans in the Head Region

Purpose: To incorporate a novel imaging sequence for robust air and tissue segmentation using ultrashort echo time (UTE) phase images and to implement an innovative synthetic CT (synCT) solution as a first step toward MR-only radiation therapy treatment planning for brain cancer. Methods and Materials: Ten brain cancer patients were scanned with a UTE/Dixon sequence and other clinical sequences on a 1.0 T open magnet with simulation capabilities. Bone-enhanced images were generated from a weighted combination of water/fat maps derived from Dixon images and inverted UTE images. Automated air segmentation was performed using unwrapped UTE phase maps. Segmentation accuracy was assessed by calculating segmentation errors (true-positive rate, false-positive rate, and Dice similarity indices using CT simulation (CT-SIM) as ground truth. The synCTs were generated using a voxel-based, weighted summation method incorporating T2, fluid attenuated inversion recovery (FLAIR), UTE1, and bone-enhanced images. Mean absolute error (MAE) characterized Hounsfield unit (HU) differences between synCT and CT-SIM. A dosimetry study was conducted, and differences were quantified using γ-analysis and dose-volume histogram analysis. Results: On average, true-positive rate and false-positive rate for the CT and MR-derived air masks were 80.8% ± 5.5% and 25.7% ± 6.9%, respectively. Dice similarity indices values were 0.78 ± 0.04 (range, 0.70-0.83). Full field of view MAE between synCT and CT-SIM was 147.5 ± 8.3 HU (range, 138.3-166.2 HU), with the largest errors occurring at bone–air interfaces (MAE 422.5 ± 33.4 HU for bone and 294.53 ± 90.56 HU for air). Gamma analysis revealed pass rates of 99.4% ± 0.04%, with acceptable treatment plan quality for the cohort. Conclusions: A hybrid MRI phase/magnitude UTE image processing technique was introduced that significantly improved bone and air contrast in MRI. Segmented air masks and bone-enhanced images were integrated into our synCT pipeline for brain, and results agreed well with clinical CTs, thereby supporting MR-only radiation therapy treatment planning in the brain.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Evaluation of the Risk of Grade 3 Oral and Pharyngeal Dysphagia Using Atlas-Based Method and Multivariate Analyses of Individual Patient Dose Distributions

Purpose: The study aimed to apply the atlas of complication incidence (ACI) method to patients receiving radical treatment for head and neck squamous cell carcinomas (HNSCC), to generate constraints based on dose-volume histograms (DVHs), and to identify clinical and dosimetric parameters that predict the risk of grade 3 oral mucositis (g3OM) and pharyngeal dysphagia (g3PD). Methods and Materials: Oral and pharyngeal mucosal DVHs were generated for 253 patients who received radiation (RT) or chemoradiation (CRT). They were used to produce ACI for g3OM and g3PD. Multivariate analysis (MVA) of the effect of dosimetry, clinical, and patient-related variables was performed using logistic regression and bootstrapping. Receiver operating curve (ROC) analysis was also performed, and the Youden index was used to find volume constraints that discriminated between volumes that predicted for toxicity. Results: We derived statistically significant dose-volume constraints for g3OM over the range v28 to v70. Only 3 statistically significant constraints were derived for g3PD v67, v68, and v69. On MVA, mean dose to the oral mucosa predicted for g3OM and concomitant chemotherapy and mean dose to the inferior constrictor (IC) predicted for g3PD. Conclusions: We have used the ACI method to evaluate incidences of g3OM and g3PD and ROC analysis to generate constraints to predict g3OM and g3PD derived from entire individual patient DVHs. On MVA, the strongest predictors were radiation dose (for g3OM) and concomitant chemotherapy (for g3PD).

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Thoracic Vertebral Body Irradiation Contributes to Acute Hematologic Toxicity During Chemoradiation Therapy for Non-Small Cell Lung Cancer

Purpose: To determine the relationships between radiation doses to the thoracic bone marrow and declines in blood cell counts in non-small cell lung cancer (NSCLC) patients treated with chemoradiation therapy (CRT). Methods and Materials: We included 52 patients with NSCLC treated with definitive concurrent carboplatin–paclitaxel and RT. Dose-volume histogram (DVH) parameters for the thoracic vertebrae (TV), sternum, scapulae, clavicles, and ribs were assessed for associations with changes in blood counts during the course of CRT. Linear and logistic regression analyses were performed to identify associations between hematologic nadirs and DVH parameters. A DVH parameter of Vx was the percentage of the total organ volume exceeding x radiation dose. Results: Grade ≥3 hematologic toxicity including neutropenia developed in 21% (n=11), leukopenia in 42% (n=22), anemia in 6% (n=3), and throbocytopenia in 2% (n=1) of patients. Greater RT dose to the TV was associated with higher risk of grade ≥3 leukopenia across multiple DVH parameters, including TV V{sub 20} (TVV) (odds ratio [OR] 1.06; P=.025), TVV{sub 30} (OR 1.07; P=.013), and mean vertebral dose (MVD) (OR 1.13; P=.026). On multiple regression analysis, TVV{sub 30} (β = −0.004; P=.018) and TVV{sub 20} (β = −0.003; P=.048) were associated with white blood cell nadir. Additional bone marrow sites (scapulae, clavicles, and ribs) did not affect hematologic toxicity. A 20% chance of grade ≥3 leukopenia was associated with a MVD of 13.5 Gy and a TTV{sub 30} of 28%. Cutoff values to avoid grade ≥3 leukopenia were MVD ≤23.9 Gy, TVV{sub 20} ≤56.0%, and TVV{sub 30} ≤52.1%. Conclusions: Hematologic toxicity is associated with greater RT doses to the TV during CRT for NSCLC. Sparing of the TV using advanced radiation techniques may improve tolerance of CRT and result in improved tolerance of concurrent chemotherapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Effect of Dosimetric Outliers on the Performance of a Commercial Knowledge-Based Planning Solution

Purpose: RapidPlan, a commercial knowledge-based planning solution, uses a model library containing the geometry and associated dosimetry of existing plans. This model predicts achievable dosimetry for prospective patients that can be used to guide plan optimization. However, it is unknown how suboptimal model plans (outliers) influence the predictions or resulting plans. We investigated the effect of, first, removing outliers from the model (cleaning it) and subsequently adding deliberate dosimetric outliers. Methods and Materials: Clinical plans from 70 head and neck cancer patients comprised the uncleaned (UC) Model{sub UC}, from which outliers were cleaned (C) to create Model{sub C}. The last 5 to 40 patients of Model{sub C} were replanned with no attempt to spare the salivary glands. These substantial dosimetric outliers were reintroduced to the model in increments of 5, creating Model{sub 5} to Model{sub 40} (Model{sub 5-40}). These models were used to create plans for a 10-patient evaluation group. Plans from Model{sub UC} and Model{sub C}, and Model{sub C} and Model{sub 5-40} were compared on the basis of boost (B) and elective (E) target volume homogeneity indexes (HI{sub B}/HI{sub E}) and mean doses to oral cavity, composite salivary glands (comp{sub sal}) and swallowing (comp{sub swal}) structures. Results: On average, outlier removal (Model{sub C} vs Model{sub UC}) had minimal effects on HI{sub B}/HI{sub E} (0%-0.4%) and sparing of organs at risk (mean dose difference to oral cavity and comp{sub sal}/comp{sub swal} were ≤0.4 Gy). Model{sub 5-10} marginally improved comp{sub sal} sparing, whereas adding a larger number of outliers (Model{sub 20-40}) led to deteriorations in comp{sub sal} up to 3.9 Gy, on average. These increases are modest compared to the 14.9 Gy dose increases in the added outlier plans, due to the placement of optimization objectives below the inferior boundary of the dose-volume histogram-predicted range. Conclusions: Overall, dosimetric outlier removal from or addition of 5 to 10 outliers to a 70-patient model had marginal effects on resulting plan quality. Although the addition of >20 outliers deteriorated plan quality, the effect was modest. In this study, RapidPlan demonstrated robustness for moderate proportions of salivary gland dosimetric outliers.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

A Prospective Comparison of the Effects of Interfractional Variations on Proton Therapy and Intensity Modulated Radiation Therapy for Prostate Cancer

Purpose: To quantify and compare the impact of interfractional setup and anatomic variations on proton therapy (PT) and intensity modulated radiation therapy (IMRT) for prostate cancer. Methods and Materials: Twenty patients with low-risk or intermediate-risk prostate cancer randomized to receive passive-scattering PT (n=10) and IMRT (n=10) were selected. For both modalities, clinical treatment plans included 50.4 Gy(RBE) to prostate and proximal seminal vesicles, and prostate-only boost to 79.2 Gy(RBE) in 1.8 Gy(RBE) per fraction. Implanted fiducials were used for prostate localization and endorectal balloons were used for immobilization. Patients in PT and IMRT arms received weekly computed tomography (CT) and cone beam CT (CBCT) scans, respectively. The planned dose was recalculated on each weekly image, scaled, and mapped onto the planning CT using deformable registration. The resulting accumulated dose distribution over the entire treatment course was compared with the planned dose using dose-volume histogram (DVH) and γ analysis. Results: The target conformity index remained acceptable after accumulation. The largest decrease in the average prostate D{sub 98} was 2.2 and 0.7 Gy for PT and IMRT, respectively. On average, the mean dose to bladder increased by 3.26 ± 7.51 Gy and 1.97 ± 6.84 Gy for PT and IMRT, respectively. These values were 0.74 ± 2.37 and 0.56 ± 1.90 for rectum. Differences between changes in DVH indices were not statistically significant between modalities. All volume indices remained within the protocol tolerances after accumulation. The average pass rate for the γ analysis, assuming tolerances of 3 mm and 3%, for clinical target volume, bladder, rectum, and whole patient for PT/IMRT were 100/100, 92.6/99, 99.2/100, and 97.2/99.4, respectively. Conclusion: The differences in target coverage and organs at risk dose deviations for PT and IMRT were not statistically significant under the guidelines of this protocol.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Impact of Spot Size and Beam-Shaping Devices on the Treatment Plan Quality for Pencil Beam Scanning Proton Therapy

Purpose: This study aimed to assess the clinical impact of spot size and the addition of apertures and range compensators on the treatment quality of pencil beam scanning (PBS) proton therapy and to define when PBS could improve on passive scattering proton therapy (PSPT). Methods and Materials: The patient cohort included 14 pediatric patients treated with PSPT. Six PBS plans were created and optimized for each patient using 3 spot sizes (∼12-, 5.4-, and 2.5-mm median sigma at isocenter for 90- to 230-MeV range) and adding apertures and compensators to plans with the 2 larger spots. Conformity and homogeneity indices, dose-volume histogram parameters, equivalent uniform dose (EUD), normal tissue complication probability (NTCP), and integral dose were quantified and compared with the respective PSPT plans. Results: The results clearly indicated that PBS with the largest spots does not necessarily offer a dosimetric or clinical advantage over PSPT. With comparable target coverage, the mean dose (D{sub mean}) to healthy organs was on average 6.3% larger than PSPT when using this spot size. However, adding apertures to plans with large spots improved the treatment quality by decreasing the average D{sub mean} and EUD by up to 8.6% and 3.2% of the prescribed dose, respectively. Decreasing the spot size further improved all plans, lowering the average D{sub mean} and EUD by up to 11.6% and 10.9% compared with PSPT, respectively, and eliminated the need for beam-shaping devices. The NTCP decreased with spot size and addition of apertures, with maximum reduction of 5.4% relative to PSPT. Conclusions: The added benefit of using PBS strongly depends on the delivery configurations. Facilities limited to large spot sizes (>∼8 mm median sigma at isocenter) are recommended to use apertures to reduce treatment-related toxicities, at least for complex and/or small tumors.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Long-Term Bone Marrow Suppression During Postoperative Chemotherapy in Rectal Cancer Patients After Preoperative Chemoradiation Therapy

Purpose/Objective(s): To quantify ensuing bone marrow (BM) suppression during postoperative chemotherapy resulting from preoperative chemoradiation (CRT) therapy for rectal cancer. Methods and Materials: We retrospectively evaluated 35 patients treated with preoperative CRT followed by postoperative 5-Fluorouracil and oxaliplatin (OxF) chemotherapy for locally advanced rectal cancer. The pelvic bone marrow (PBM) was divided into ilium (IBM), lower pelvis (LPBM), and lumbosacrum (LSBM). Dose volume histograms (DVH) measured the mean doses and percentage of BM volume receiving between 5-40 Gy (i.e.: PBM-V5, LPBM-V5). The Wilcoxon signed rank tests evaluated the differences in absolute hematologic nadirs during neoadjuvant vs. adjuvant treatment. Logistic regressions evaluated the association between dosimetric parameters and ≥ grade 3 hematologic toxicity (HT3) and hematologic event (HE) defined as ≥ grade 2 HT and a dose reduction in OxF. Receiver Operator Characteristic (ROC) curves were constructed to determine optimal threshold values leading to HT3. Results: During OxF chemotherapy, 40.0% (n=14) and 48% (n=17) of rectal cancer patients experienced HT3 and HE, respectively. On multivariable logistic regression, increasing pelvic mean dose (PMD) and lower pelvis mean dose (LPMD) along with increasing PBM-V (25-40), LPBM-V25, and LPBM-V40 were significantly associated with HT3 and/or HE during postoperative chemotherapy. Exceeding ≥36.6 Gy to the PMD and ≥32.6 Gy to the LPMD strongly correlated with causing HT3 during postoperative chemotherapy. Conclusions: Neoadjuvant RT for rectal cancer has lasting effects on the pelvic BM, which are demonstrable during adjuvant OxF. Sparing of the BM during preoperative CRT can aid in reducing significant hematologic adverse events and aid in tolerance of postoperative chemotherapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Fractionated Boron Neutron Capture Therapy in Locally Recurrent Head and Neck Cancer: A Prospective Phase I/II Trial

Purpose: To investigate the efficacy and safety of fractionated boron neutron capture therapy (BNCT) for recurrent head and neck (H&N) cancer after photon radiation therapy. Methods and Materials: In this prospective phase 1/2 trial, 2-fraction BNCT with intravenous L-boronophenylalanine (L-BPA, 400 mg/kg) was administered at a 28-day interval. Before each fraction, fluorine-18-labeled-BPA–positron emission tomography was conducted to determine the tumor/normal tissue ratio of an individual tumor. The prescription dose (D80) of 20 Gy-Eq per fraction was selected to cover 80% of the gross tumor volume by using a dose volume histogram, while minimizing the volume of oral mucosa receiving >10 Gy-Eq. Tumor responses and adverse effects were assessed using the Response Evaluation Criteria in Solid Tumors v1.1 and the Common Terminology Criteria for Adverse Events v3.0, respectively. Results: Seventeen patients with a previous cumulative radiation dose of 63-165 Gy were enrolled. All but 2 participants received 2 fractions of BNCT. The median tumor/normal tissue ratio was 3.4 for the first fraction and 2.5 for the second, whereas the median D80 for the first and second fraction was 19.8 and 14.6 Gy-Eq, respectively. After a median follow-up period of 19.7 months (range, 5.2-52 mo), 6 participants exhibited a complete response and 6 exhibited a partial response. Regarding acute toxicity, 5 participants showed grade 3 mucositis and 1 participant showed grade 4 laryngeal edema and carotid hemorrhage. Regarding late toxicity, 2 participants exhibited grade 3 cranial neuropathy. Four of six participants (67%) receiving total D80 > 40 Gy-Eq had a complete response. Two-year overall survival was 47%. Two-year locoregional control was 28%. Conclusions: Our results suggested that 2-fraction BNCT with adaptive dose prescription was effective and safe in locally recurrent H&N cancer. Modifications to our protocol may yield more satisfactory results in the future.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Robust Proton Pencil Beam Scanning Treatment Planning for Rectal Cancer Radiation Therapy

Purpose: To investigate, in a treatment plan design and robustness study, whether proton pencil beam scanning (PBS) has the potential to offer advantages, relative to interfraction uncertainties, over photon volumetric modulated arc therapy (VMAT) in a locally advanced rectal cancer patient population. Methods and Materials: Ten patients received a planning CT scan, followed by an average of 4 weekly offline CT verification CT scans, which were rigidly co-registered to the planning CT. Clinical PBS plans were generated on the planning CT, using a single-field uniform-dose technique with single-posterior and parallel-opposed (LAT) fields geometries. The VMAT plans were generated on the planning CT using 2 6-MV, 220° coplanar arcs. Clinical plans were forward-calculated on verification CTs to assess robustness relative to anatomic changes. Setup errors were assessed by forward-calculating clinical plans with a ±5-mm (left–right, anterior–posterior, superior–inferior) isocenter shift on the planning CT. Differences in clinical target volume and organ at risk dose–volume histogram (DHV) indicators between plans were tested for significance using an appropriate Wilcoxon test (P<.05). Results: Dosimetrically, PBS plans were statistically different from VMAT plans, showing greater organ at risk sparing. However, the bladder was statistically identical among LAT and VMAT plans. The clinical target volume coverage was statistically identical among all plans. The robustness test found that all DVH indicators for PBS and VMAT plans were robust, except the LAT's genitalia (V5, V35). The verification CT plans showed that all DVH indicators were robust. Conclusions: Pencil beam scanning plans were found to be as robust as VMAT plans relative to interfractional changes during treatment when posterior beam angles and appropriate range margins are used. Pencil beam scanning dosimetric gains in the bowel (V15, V20) over VMAT suggest that using PBS to treat rectal cancer may reduce radiation treatment–related toxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Five-Year Biochemical Results, Toxicity, and Patient-Reported Quality of Life After Delivery of Dose-Escalated Image Guided Proton Therapy for Prostate Cancer

Purpose: To report clinical outcomes in patients treated with image guided proton therapy (PT) for localized prostate cancer. Methods and Materials: The medical records of 1327 men were reviewed. Each man was enrolled on an outcomes tracking study. Dual enrollment on a prospective clinical trial was allowed. Each patient was treated for localized prostate cancer with PT at our institution between 2006 and 2010. Ninety-eight percent of patients received 78 Gy (radiobiological equivalent [RBE]) or higher; 18% received androgen deprivation therapy (ADT). The 5-year freedom from biochemical progression (FFBP), distant metastasis-free survival, and cause-specific survival rates are reported for each risk group. Data on patient-reported quality of life and high-grade toxicities were prospectively collected and reported. A multivariate analysis was performed to identify clinical predictors of biochemical failure and urologic toxicity. Results: The median follow-up time was 5.5 years. The 5-year FFBP rates were 99%, 94%, and 74% in low-risk, intermediate-risk, and high-risk patients, respectively. The actuarial 5-year rates of late grade 3+ Common Terminology Criteria for Adverse Events, version 4.0, gastrointestinal (GI) and genitourinary (GU) toxicity were 0.6% and 2.9%, respectively. Multivariate analysis showed a significant correlation between grade 3+ GU toxicity and pretreatment prostate reductive procedures (P<.0001), prostate volume (P=.0085), pretreatment α-blockers (P=.0067), diabetes (P=.0195), and dose–volume histogram parameters (P=.0208). The median International Prostate Symptom Scores pretreatment scores and scores at 5 years after treatment were 7 and 7, respectively. The mean Expanded Prostate Cancer Index Composite (EPIC) scores significantly declined for sexual summary for patients not receiving ADT (from 67 to 53) between baseline and 5 years. Conclusions: Image guided PT provided excellent biochemical control rates for patients with localized prostate cancer. The actuarial rates of high-grade toxicity were low after PT. From pretreatment to 5 years of follow-up, a significant decline was found only in mean EPIC sexual summary scores. Prospective clinical studies are needed to determine the comparative effectiveness of PT and other radiation treatment strategies.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Stochastic Predictions of Cell Kill During Stereotactic Ablative Radiation Therapy: Do Hypoxia and Reoxygenation Really Matter?

Purpose: To simulate stereotactic ablative radiation therapy on hypoxic and well-oxygenated in silico tumors, incorporating probabilistic parameter distributions and linear-quadratic versus linear-quadratic-cubic methodology and the evaluation of optimal fractionation schemes using biological effective dose (BED{sub α/β=10} {sub or} {sub 3}) comparisons. Methods and Materials: A temporal tumor growth and radiation therapy algorithm simulated high-dose external beam radiation therapy using stochastic methods. Realistic biological proliferative cellular hierarchy and pO{sub 2} histograms were incorporated into the 10{sup 8}-cell tumor model, with randomized radiation therapy applied during continual cell proliferation and volume-based gradual tumor reoxygenation. Dose fractions ranged from 6-35 Gy, with predictive outcomes presented in terms of the total doses (converted to BED) required to eliminate all cells that could potentially regenerate the tumor. Results: Well-oxygenated tumor control BED{sub 10} outcomes were not significantly different for high-dose versus conventional radiation therapy (BED{sub 10}: 79-84 Gy; Equivalent Dose in 2 Gy fractions with α/β of 10: 66-70 Gy); however, total treatment times decreased from 7 down to 1-3 weeks. For hypoxic tumors, an additional 28 Gy (51 Gy BED{sub 10}) was required, with BED{sub 10} increasing with dose per fraction due to wasted dose in the final fraction. Fractions of 9 Gy compromised well for total treatment time and BED, with BED{sub 10}:BED{sub 3} of 84:176 Gy for oxic and 132:278 Gy for non-reoxygenating hypoxic tumors. Initial doses of 12 Gy followed by 6 Gy further increased the therapeutic ratio. When delivering ≥9 Gy per fraction, applying reoxygenation and/or linear-quadratic-cubic cell survival both affected tumor control doses by a significant 1-2 fractions. Conclusions: The complex temporal dynamics of tumor oxygenation combined with probabilistic cell kinetics in the modeling of radiation therapy requires sophisticated stochastic modeling to predict tumor cell kill. For stereotactic ablative radiation therapy, high doses in the first week followed by doses that are more moderate may be beneficial because a high percentage of hypoxic cells could be eradicated early while keeping the required BED{sub 10} relatively low and BED{sub 3} toxicity to tolerable levels.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Comparison of Dose Distributions With TG-43 and Collapsed Cone Convolution Algorithms Applied to Accelerated Partial Breast Irradiation Patient Plans

Purpose: To compare the treatment plans for accelerated partial breast irradiation calculated by the new commercially available collapsed cone convolution (CCC) and current standard TG-43–based algorithms for 50 patients treated at our institution with either a Strut-Adjusted Volume Implant (SAVI) or Contura device. Methods and Materials: We recalculated target coverage, volume of highly dosed normal tissue, and dose to organs at risk (ribs, skin, and lung) with each algorithm. For 1 case an artificial air pocket was added to simulate 10% nonconformance. We performed a Wilcoxon signed rank test to determine the median differences in the clinical indices V90, V95, V100, V150, V200, and highest-dosed 0.1 cm{sup 3} and 1.0 cm{sup 3} of rib, skin, and lung between the two algorithms. Results: The CCC algorithm calculated lower values on average for all dose-volume histogram parameters. Across the entire patient cohort, the median difference in the clinical indices calculated by the 2 algorithms was <10% for dose to organs at risk, <5% for target volume coverage (V90, V95, and V100), and <4 cm{sup 3} for dose to normal breast tissue (V150 and V200). No discernable difference was seen in the nonconformance case. Conclusions: We found that on average over our patient population CCC calculated (<10%) lower doses than TG-43. These results should inform clinicians as they prepare for the transition to heterogeneous dose calculation algorithms and determine whether clinical tolerance limits warrant modification.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Functional Data Analysis Applied to Modeling of Severe Acute Mucositis and Dysphagia Resulting From Head and Neck Radiation Therapy

Purpose: Current normal tissue complication probability modeling using logistic regression suffers from bias and high uncertainty in the presence of highly correlated radiation therapy (RT) dose data. This hinders robust estimates of dose-response associations and, hence, optimal normal tissue–sparing strategies from being elucidated. Using functional data analysis (FDA) to reduce the dimensionality of the dose data could overcome this limitation. Methods and Materials: FDA was applied to modeling of severe acute mucositis and dysphagia resulting from head and neck RT. Functional partial least squares regression (FPLS) and functional principal component analysis were used for dimensionality reduction of the dose-volume histogram data. The reduced dose data were input into functional logistic regression models (functional partial least squares–logistic regression [FPLS-LR] and functional principal component–logistic regression [FPC-LR]) along with clinical data. This approach was compared with penalized logistic regression (PLR) in terms of predictive performance and the significance of treatment covariate–response associations, assessed using bootstrapping. Results: The area under the receiver operating characteristic curve for the PLR, FPC-LR, and FPLS-LR models was 0.65, 0.69, and 0.67, respectively, for mucositis (internal validation) and 0.81, 0.83, and 0.83, respectively, for dysphagia (external validation). The calibration slopes/intercepts for the PLR, FPC-LR, and FPLS-LR models were 1.6/−0.67, 0.45/0.47, and 0.40/0.49, respectively, for mucositis (internal validation) and 2.5/−0.96, 0.79/−0.04, and 0.79/0.00, respectively, for dysphagia (external validation). The bootstrapped odds ratios indicated significant associations between RT dose and severe toxicity in the mucositis and dysphagia FDA models. Cisplatin was significantly associated with severe dysphagia in the FDA models. None of the covariates was significantly associated with severe toxicity in the PLR models. Dose levels greater than approximately 1.0 Gy/fraction were most strongly associated with severe acute mucositis and dysphagia in the FDA models. Conclusions: FPLS and functional principal component analysis marginally improved predictive performance compared with PLR and provided robust dose-response associations. FDA is recommended for use in normal tissue complication probability modeling.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Spot-Scanning Proton Arc (SPArc) Therapy: The First Robust and Delivery-Efficient Spot-Scanning Proton Arc Therapy

Purpose: To present a novel robust and delivery-efficient spot-scanning proton arc (SPArc) therapy technique. Methods and Materials: A SPArc optimization algorithm was developed that integrates control point resampling, energy layer redistribution, energy layer filtration, and energy layer resampling. The feasibility of such a technique was evaluated using sample patients: 1 patient with locally advanced head and neck oropharyngeal cancer with bilateral lymph node coverage, and 1 with a nonmobile lung cancer. Plan quality, robustness, and total estimated delivery time were compared with the robust optimized multifield step-and-shoot arc plan without SPArc optimization (Arc{sub multi-field}) and the standard robust optimized intensity modulated proton therapy (IMPT) plan. Dose-volume histograms of target and organs at risk were analyzed, taking into account the setup and range uncertainties. Total delivery time was calculated on the basis of a 360° gantry room with 1 revolutions per minute gantry rotation speed, 2-millisecond spot switching time, 1-nA beam current, 0.01 minimum spot monitor unit, and energy layer switching time of 0.5 to 4 seconds. Results: The SPArc plan showed potential dosimetric advantages for both clinical sample cases. Compared with IMPT, SPArc delivered 8% and 14% less integral dose for oropharyngeal and lung cancer cases, respectively. Furthermore, evaluating the lung cancer plan compared with IMPT, it was evident that the maximum skin dose, the mean lung dose, and the maximum dose to ribs were reduced by 60%, 15%, and 35%, respectively, whereas the conformity index was improved from 7.6 (IMPT) to 4.0 (SPArc). The total treatment delivery time for lung and oropharyngeal cancer patients was reduced by 55% to 60% and 56% to 67%, respectively, when compared with Arc{sub multi-field} plans. Conclusion: The SPArc plan is the first robust and delivery-efficient proton spot-scanning arc therapy technique, which could potentially be implemented into routine clinical practice.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Consensus Contouring Guidelines for Postoperative Stereotactic Body Radiation Therapy for Metastatic Solid Tumor Malignancies to the Spine

Purpose: To develop consensus contouring guidelines for postoperative stereotactic body radiation therapy (SBRT) for spinal metastases. Methods and Materials: Ten spine SBRT specialists representing 10 international centers independently contoured the clinical target volume (CTV), planning target volume (PTV), spinal cord, and spinal cord planning organ at risk volume (PRV) for 10 representative clinical scenarios in postoperative spine SBRT for metastatic solid tumor malignancies. Contours were imported into the Computational Environment for Radiotherapy Research. Agreement between physicians was calculated with an expectation minimization algorithm using simultaneous truth and performance level estimation with κ statistics. Target volume definition guidelines were established by finding optimized confidence level consensus contours using histogram agreement analyses. Results: Nine expert radiation oncologists and 1 neurosurgeon completed contours for all 10 cases. The mean sensitivity and specificity were 0.79 (range, 0.71-0.89) and 0.94 (range, 0.90-0.99) for the CTV and 0.79 (range, 0.70-0.95) and 0.92 (range, 0.87-0.99) for the PTV), respectively. Mean κ agreement, which demonstrates the probability that contours agree by chance alone, was 0.58 (range, 0.43-0.70) for CTV and 0.58 (range, 0.37-0.76) for PTV (P<.001 for all cases). Optimized consensus contours were established for all patients with 80% confidence interval. Recommendations for CTV include treatment of the entire preoperative extent of bony and epidural disease, plus immediately adjacent bony anatomic compartments at risk of microscopic disease extension. In particular, a “donut-shaped” CTV was consistently applied in cases of preoperative circumferential epidural extension, regardless of extent of residual epidural extension. Otherwise more conformal anatomic-based CTVs were determined and described. Spinal instrumentation was consistently excluded from the CTV. Conclusions: We provide consensus contouring guidelines for common scenarios in postoperative SBRT for spinal metastases. These consensus guidelines are subject to clinical validation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗