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Potential impacts of China's climate policies on energy security

Highlights: • We develop an energy security assessment framework in a 3E-integrated system model. • The potential relations between climate targets and energy security are examined. • Climate policy reduces risks of energy system in terms of main safety metrics. • The impact of emission budgets on energy diversity relies on the time scale options. • Co-benefits of energy security would improve the economics of climate policies. - Abstract: Energy security, as an indispensable constituent of economic security, has long been a top research priority, and the dynamics of energy security become particularly complicated with the involvement of climate change. In this work, we combined a one-sector integrated assessment framework with a series of well-proposed energy security metrics to extensively explore the unidirectional consistency between climate policy and energy security from the national perspective. Implementation of climate policy is generally beneficial for improving energy security. Specifically, climate policy helps to reduce the systematic risk of China's energy system according to the metrics of energy (oil) intensity, energy (oil) expenditures and per capita energy (oil) consumption independent of time scale options. As observed from the perspective of energy diversity, co-benefits arising from climate policy primarily emerge in the first half of this century, and they may gradually decline as emission constraints and the phasing out of fossil fuels are enhanced. Additionally, the macroeconomic costs required to reach China's committed carbon-peaking target might be far lower than the costs required to fulfill the emission budgets under the global 2-degree warming rise threshold. If the co-benefits of energy security are considered, the economics of climate policy is expected to significantly improve.

54 ENVIRONMENTAL SCIENCES↗

Efficient Screening of Bi–Metallic Electrocatalysts for Glycerol Valorization

Glycerol is a byproduct of biodiesel production and, as such, it is of limited economic value. By means of electrooxidation, glycerol can be used as a feedstock for scalable hydrogen production, in addition to conversion to value-added products. The development of novel and efficient catalytic electrode materials for the anodic side of the reaction is a key towards a hydrogen-based energy economy. In the present study, a computational screening protocol combining DFT, scaling relations, and microkinetic modeling allows for a rational selection of novel catalysts that can deliver efficient glycerol electrooxidation, low cost of production, and environmental sustainability. Activity and chemical selectivity towards hydrogen production on pure metal catalysts is discussed in terms of volcano-shaped plots. We find that the selectivity in the glycerol oxidation reaction is influenced by a different energy landscape when in the presence of water and best classified by a comparison of O—H and C—H bond-breaking barriers. In addition, we screened 3570 bi-metallic catalysts in the AB (L1 0 ) and A 3 B (L1 2 ) ordered structures for activity, stability, price, and toxicity. By filtering based on the criteria for toxicity, resistance to oxidation, miscibility, and price, we have identified 5 L1 0 structured catalysts (AgPd, AuPd, PtSb, CuPt, and AgPt) and 20 L1 2 catalysts (Ga 3 Ta, In 3 Ta, Ir 3 W, Ir 3 Mo, Cu 3 Pt, Ir 3 Ta, Ir 3 Re, Pd 3 Bi, Pd 3 Cu, Pd 3 W, Pd 3 Co, Pd 3 Sn, Pd 3 Mo, Pd 3 Ag, Pd 3 Ga, Pd 3 Ta, Au 3 Ru, Pd 3 In, Au 3 Ir, and Pd 3 Au) that are all predicted to show high activity. We also identify an additional 37 L1 0 and 92 L1 2 structured electrocatalysts with an anticipated medium-high activity.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Novel geometries for air-cooled condensation of ammonia-water mixtures

An analytical and experimental investigation of air-cooled condensers for small-scale ammonia-water absorption heat pumps is presented. Conventional round-tube corrugated fin design and a novel multi-pass tube array design are considered for a condenser operating at severe ambient conditions within a compact footprint. Segmental heat and mass transfer models are developed to gain a deeper understanding of the characteristics of each design. Predicted heat duties are within 5% of the measured values. The limitations of correlations to predict air-side pressure drop in corrugated fins are identified. The performance of the novel multi-pass tube array condenser was comparable to that of conventional condensers, but is determined to be air-side limited throughout length of the heat exchanger. An improved multi-pass condenser design with fins for increased air-side area is proposed using the insights gained from the modeling and experiments. In closing this design meets the heat duty requirements at severe ambient conditions, while decreasing the size of the heat exchanger by 33%.

42 ENGINEERING↗

4π Noncoplanar Stereotactic Body Radiation Therapy for Centrally Located or Larger Lung Tumors

Purpose: To investigate the dosimetric improvements in stereotactic body radiation therapy for patients with larger or central lung tumors using a highly noncoplanar 4π planning system. Methods and Materials: This study involved 12 patients with centrally located or larger lung tumors previously treated with 7- to 9-field static beam intensity modulated radiation therapy to 50 Gy. They were replanned using volumetric modulated arc therapy and 4π plans, in which a column generation method was used to optimize the beam orientation and the fluence map. Maximum doses to the heart, esophagus, trachea/bronchus, and spinal cord, as well as the 50% isodose volume, the lung volumes receiving 20, 10, and 5 Gy were minimized and compared against the clinical plans. A dose escalation study was performed to determine whether a higher prescription dose to the tumor would be achievable using 4π without violating dose limits set by the clinical plans. The deliverability of 4π plans was preliminarily tested. Results: Using 4π plans, the maximum heart, esophagus, trachea, bronchus and spinal cord doses were reduced by 32%, 72%, 37%, 44%, and 53% (P≤.001), respectively, and R{sub 50} was reduced by more than 50%. Lung V{sub 20}, V{sub 10}, and V{sub 5} were reduced by 64%, 53%, and 32% (P≤.001), respectively. The improved sparing of organs at risk was achieved while also improving planning target volume (PTV) coverage. The minimal PTV doses were increased by the 4π plans by 12% (P=.002). Consequently, escalated PTV doses of 68 to 70 Gy were achieved in all patients. Conclusions: We have shown that there is a large potential for plan quality improvement and dose escalation for patients with larger or centrally located lung tumors using noncoplanar beams with sufficient quality and quantity. Compared against the clinical volumetric modulated arc therapy and static intensity modulated radiation therapy plans, the 4π plans yielded significantly and consistently improved tumor coverage and critical organ sparing. Given the known challenges in central structure dose constraints in stereotactic body radiation therapy to the lung, 4π planning may increase efficacy and reduce toxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Phase 1 Study of Dose Escalation in Hypofractionated Proton Beam Therapy for Non-Small Cell Lung Cancer

Background: Many patients with locally advanced non-small cell lung cancer (NSCLC) cannot undergo concurrent chemotherapy because of comorbidities or poor performance status. Hypofractionated radiation regimens, if tolerable, may provide an option to these patients for effective local control. Methods and Materials: Twenty-five patients were enrolled in a phase 1 dose-escalation trial of proton beam therapy (PBT) from September 2010 through July 2012. Eligible patients had histologically documented lung cancer, thymic tumors, carcinoid tumors, or metastatic thyroid tumors. Concurrent chemotherapy was not allowed, but concurrent treatment with biologic agents was. The dose-escalation schema comprised 15 fractions of 3 Gy(relative biological effectiveness [RBE])/fraction, 3.5 Gy(RBE)/fraction, or 4 Gy(RBE)/fraction. Dose constraints were derived from biologically equivalent doses of standard fractionated treatment. Results: The median follow-up time for patients alive at the time of analysis was 13 months (range, 8-28 months). Fifteen patients received treatment to hilar or mediastinal lymph nodes. Two patients experienced dose-limiting toxicity possibly related to treatment; 1 received 3.5-Gy(RBE) fractions and experienced an in-field tracheoesophageal fistula 9 months after PBT and 1 month after bevacizumab. The other patient received 4-Gy(RBE) fractions and was hospitalized for bacterial pneumonia/radiation pneumonitis 4 months after PBT. Conclusion: Hypofractionated PBT to the thorax delivered over 3 weeks was well tolerated even with significant doses to the lungs and mediastinal structures. Phase 2/3 trials are needed to compare the efficacy of this technique with standard treatment for locally advanced NSCLC.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Dose–Volume Relationships Associated With Temporal Lobe Radiation Necrosis After Skull Base Proton Beam Therapy

Purpose: We evaluated patient and treatment parameters correlated with development of temporal lobe radiation necrosis. Methods and Materials: This was a retrospective analysis of a cohort of 66 patients treated for skull base chordoma, chondrosarcoma, adenoid cystic carcinoma, or sinonasal malignancies between 2005 and 2012, who had at least 6 months of clinical and radiographic follow-up. The median radiation dose was 75.6 Gy (relative biological effectiveness [RBE]). Analyzed factors included gender, age, hypertension, diabetes, smoking status, use of chemotherapy, and the absolute dose:volume data for both the right and left temporal lobes, considered separately. A generalized estimating equation (GEE) regression analysis evaluated potential predictors of radiation necrosis, and the median effective concentration (EC50) model estimated dose–volume parameters associated with radiation necrosis. Results: Median follow-up time was 31 months (range 6-96 months) and was 34 months in patients who were alive. The Kaplan-Meier estimate of overall survival at 3 years was 84.9%. The 3-year estimate of any grade temporal lobe radiation necrosis was 12.4%, and for grade 2 or higher radiation necrosis was 5.7%. On multivariate GEE, only dose–volume relationships were associated with the risk of radiation necrosis. In the EC50 model, all dose levels from 10 to 70 Gy (RBE) were highly correlated with radiation necrosis, with a 15% 3-year risk of any-grade temporal lobe radiation necrosis when the absolute volume of a temporal lobe receiving 60 Gy (RBE) (aV60) exceeded 5.5 cm{sup 3}, or aV70 > 1.7 cm{sup 3}. Conclusions: Dose–volume parameters are highly correlated with the risk of developing temporal lobe radiation necrosis. In this study the risk of radiation necrosis increased sharply when the temporal lobe aV60 exceeded 5.5 cm{sup 3} or aV70 > 1.7 cm{sup 3}. Treatment planning goals should include constraints on the volume of temporal lobes receiving higher dose. The EC50 model provides suggested dose–volume temporal lobe constraints for conventionally fractionated high-dose skull base radiation therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Nomograms for Prediction of Outcome With or Without Adjuvant Radiation Therapy for Patients With Endometrial Cancer: A Pooled Analysis of PORTEC-1 and PORTEC-2 Trials

Background: Postoperative radiation therapy for stage I endometrial cancer improves locoregional control but is without survival benefit. To facilitate treatment decision support for individual patients, accurate statistical models to predict locoregional relapse (LRR), distant relapse (DR), overall survival (OS), and disease-free survival (DFS) are required. Methods and Materials: Clinical trial data from the randomized Post Operative Radiation Therapy for Endometrial Cancer (PORTEC-1; N=714 patients) and PORTEC-2 (N=427 patients) trials and registered group (grade 3 and deep invasion, n=99) were pooled for analysis (N=1240). For most patients (86%) pathology review data were available; otherwise original pathology data were used. Trial variables which were clinically relevant and eligible according to data constraints were age, stage, given treatment (pelvic external beam radiation therapy (EBRT), vaginal brachytherapy (VBT), or no adjuvant treatment, FIGO histological grade, depth of invasion, and lymph-vascular invasion (LVSI). Multivariate analyses were based on Cox proportional hazards regression model. Predictors were selected based on a backward elimination scheme. Model results were expressed by the c-index (0.5-1.0; random to perfect prediction). Two validation sets (n=244 and 291 patients) were used. Results: Accuracy of the developed models was good, with training accuracies between 0.71 and 0.78. The nomograms validated well for DR (0.73), DFS (0.69), and OS (0.70), but validation was only fair for LRR (0.59). Ranking of variables as to their predictive power showed that age, tumor grade, and LVSI were highly predictive for all outcomes, and given treatment for LRR and DFS. The nomograms were able to significantly distinguish low- from high-probability patients for these outcomes. Conclusions: The nomograms are internally validated and able to accurately predict long-term outcome for endometrial cancer patients with observation, pelvic EBRT, or VBT after surgery. These models facilitate decision support in daily clinical practice and can be used for patient counseling and shared decision making, selecting patients who benefit most from adjuvant treatment, and generating new hypotheses.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Predictors of Toxicity Associated With Stereotactic Body Radiation Therapy to the Central Hepatobiliary Tract

Purpose: To identify dosimetric predictors of hepatobiliary (HB) toxicity associated with stereotactic body radiation therapy (SBRT) for liver tumors. Methods and Materials: We retrospectively reviewed 96 patients treated with SBRT for primary (53%) or metastatic (47%) liver tumors between March 2006 and November 2013. The central HB tract (cHBT) was defined by a 15-mm expansion of the portal vein from the splenic confluence to the first bifurcation of left and right portal veins. Patients were censored for toxicity upon local progression or additional liver-directed therapy. HB toxicities were graded according to Common Terminology Criteria for Adverse Events version 4.0. To compare different SBRT fractionations, doses were converted to biologically effective doses (BED) by using the standard linear quadratic model α/β = 10 (BED10). Results: Median follow-up was 12.7 months after SBRT. Median BED10 was 85.5 Gy (range: 37.5-151.2). The median number of fractions was 5 (range: 1-5), with 51 patients (53.1%) receiving 5 fractions and 29 patients (30.2%) receiving 3 fractions. In total, there were 23 (24.0%) grade 2+ and 18 (18.8%) grade 3+ HB toxicities. Nondosimetric factors predictive of grade 3+ HB toxicity included cholangiocarcinoma (CCA) histology (P<.0001), primary liver tumor (P=.0087), and biliary stent (P<.0001). Dosimetric parameters most predictive of grade 3+ HB toxicity were volume receiving above BED10 of 72 Gy (V{sub BED10}72) ≥ 21 cm{sup 3} (relative risk [RR]: 11.6, P<.0001), V{sub BED10}66 ≥ 24 cm{sup 3} (RR: 10.5, P<.0001), and mean BED10 (Dmean{sub BED10}) cHBT ≥14 Gy (RR: 9.2, P<.0001), with V{sub BED10}72 and V{sub BED10}66 corresponding to V40 and V37.7 for 5 fractions and V33.8 and V32.0 for 3 fractions, respectively. V{sub BED10}72 ≥ 21 cm{sup 3}, V{sub BED10}66 ≥ 24 cm{sup 3}, and Dmean{sub BED10} cHBT ≥14 Gy were consistently predictive of grade 3+ toxicity on multivariate analysis. Conclusions: V{sub BED10}72, V{sub BED10}66, and Dmean{sub BED10} to cHBT are associated with HB toxicity. We suggest V{sub BED10}72 < 21 cm{sup 3} (5-fraction: V40 < 21 cm{sup 3}; 3-fraction: V33.8 < 21 cm{sup 3}), V{sub BED10}66 < 24 cm{sup 3} (5-fraction: V37.7 < 24 cm{sup 3}; 3-fraction: V32 < 24 cm{sup 3}) as potential dose constraints for the cHBT when clinically indicated.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Accuracy of Routine Treatment Planning 4-Dimensional and Deep-Inspiration Breath-Hold Computed Tomography Delineation of the Left Anterior Descending Artery in Radiation Therapy

Purpose: To assess the feasibility of radiation therapy treatment planning 4-dimensional computed tomography (4DCT) and deep-inspiration breath-hold (DIBH) CT to accurately contour the left anterior descending artery (LAD), a primary indicator of radiation-induced cardiac toxicity for patients undergoing radiation therapy. Methods and Materials: Ten subjects were prospectively imaged with a cardiac-gated MRI protocol to determine cardiac motion effects, including the displacement of a region of interest comprising the LAD. A series of planar views were obtained and resampled to create a 3-dimensional (3D) volume. A 3D optical flow deformable image registration algorithm determined tissue displacement during the cardiac cycle. The measured motion was then used as a spatial boundary to characterize motion blurring of the radiologist-delineated LAD structure for a cohort of 10 consecutive patients enrolled prospectively on a breast study including 4DCT and DIBH scans. Coronary motion–induced blurring artifacts were quantified by applying an unsharp filter to accentuate the LAD structure despite the presence of motion blurring. The 4DCT maximum inhalation and exhalation respiratory phases were coregistered to determine the LAD displacement during tidal respiration, as visualized in 4DCT. Results: The average 90th percentile heart motion for the region of interest was 0.7 ± 0.1 mm (left–right [LR]), 1.3 ± 0.6 mm (superior–inferior [SI]), and 0.6 ± 0.2 mm (anterior–posterior [AP]) in the cardiac-gated MRI cohort. The average relative increase in the number of voxels comprising the LAD contour was 69.4% ± 4.5% for the DIBH. The LAD volume overestimation had the dosimetric impact of decreasing the reported mean LAD dose by 23% ± 9% on average in the DIBH. During tidal respiration the average relative LAD contour increase was 69.3% ± 5.9% and 67.9% ± 4.6% for inhalation and exhalation respiratory phases, respectively. The average 90th percentile LAD motion was 4.8 ± 1.1 mm (LR), 0.9 ± 0.4 mm (SI), and 1.9 ± 0.6 mm (AP) for the 4DCT cohort, in the absence of cardiac gating. Conclusions: An anisotropic margin of 2.7 mm (LR), 4.1 mm (SI), and 2.4 mm (AP) was quantitatively determined to account for motion blurring and patient setup error while placing minimum constraint on the plan optimization.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Dependence of Achievable Plan Quality on Treatment Technique and Planning Goal Refinement: A Head-and-Neck Intensity Modulated Radiation Therapy Application

Purpose: To develop a practical workflow for retrospectively analyzing target and normal tissue dose–volume endpoints for various intensity modulated radiation therapy (IMRT) delivery techniques; to develop technique-specific planning goals to improve plan consistency and quality when feasible. Methods and Materials: A total of 165 consecutive head-and-neck patients from our patient registry were selected and retrospectively analyzed. All IMRT plans were generated using the same dose–volume guidelines for TomoTherapy (Tomo, Accuray), TrueBeam (TB, Varian) using fixed-field IMRT (TB-IMRT) or RAPIDARC (TB-RAPIDARC), or Siemens Oncor (Siemens-IMRT, Siemens). A MATLAB-based dose–volume extraction and analysis tool was developed to export dosimetric endpoints for each patient. With a fair stratification of patient cohort, the variation of achieved dosimetric endpoints was analyzed among different treatment techniques. Upon identification of statistically significant variations, technique-specific planning goals were derived from dynamically accumulated institutional data. Results: Retrospective analysis showed that although all techniques yielded comparable target coverage, the doses to the critical structures differed. The maximum cord doses were 34.1 ± 2.6, 42.7 ± 2.1, 43.3 ± 2.0, and 45.1 ± 1.6 Gy for Tomo, TB-IMRT, TB-RAPIDARC, and Siemens-IMRT plans, respectively. Analyses of variance showed significant differences for the maximum cord doses but no significant differences for other selected structures among the investigated IMRT delivery techniques. Subsequently, a refined technique-specific dose–volume guideline for maximum cord dose was derived at a confidence level of 95%. The dosimetric plans that failed the refined technique-specific planning goals were reoptimized according to the refined constraints. We observed better cord sparing with minimal variations for the target coverage and other organ at risk sparing for the Tomo cases, and higher parotid doses for C-arm linear accelerator–based IMRT and RAPIDARC plans. Conclusion: Patient registry–based processes allowed easy and systematic dosimetric assessment of treatment plan quality and consistency. Our analysis revealed the dependence of certain dosimetric endpoints on the treatment techniques. Technique-specific refinement of planning goals may lead to improvement in plan consistency and plan quality.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Volumetric Modulated Arc Therapy Planning for Primary Prostate Cancer With Selective Intraprostatic Boost Determined by {sup 18}F-Choline PET/CT

Purpose: This study evaluated expected tumor control and normal tissue toxicity for prostate volumetric modulated arc therapy (VMAT) with and without radiation boosts to an intraprostatically dominant lesion (IDL), defined by {sup 18}F-choline positron emission tomography/computed tomography (PET/CT). Methods and Materials: Thirty patients with localized prostate cancer underwent {sup 18}F-choline PET/CT before treatment. Two VMAT plans, plan{sub 79} {sub Gy} and plan{sub 100-105} {sub Gy}, were compared for each patient. The whole-prostate planning target volume (PTV{sub prostate}) prescription was 79 Gy in both plans, but plan{sub 100-105} {sub Gy} added simultaneous boost doses of 100 Gy and 105 Gy to the IDL, defined by 60% and 70% of maximum prostatic uptake on {sup 18}F-choline PET (IDL{sub suv60%} and IDL{sub suv70%}, respectively, with IDL{sub suv70%} nested inside IDL{sub suv60%} to potentially enhance tumor specificity of the maximum point dose). Plan evaluations included histopathological correspondence, isodose distributions, dose-volume histograms, tumor control probability (TCP), and normal tissue complication probability (NTCP). Results: Planning objectives and dose constraints proved feasible in 30 of 30 cases. Prostate sextant histopathology was available for 28 cases, confirming that IDL{sub suv60%} adequately covered all tumor-bearing prostate sextants in 27 cases and provided partial coverage in 1 case. Plan{sub 100-105} {sub Gy} had significantly higher TCP than plan{sub 79} {sub Gy} across all prostate regions for α/β ratios ranging from 1.5 Gy to 10 Gy (P<.001 for each case). There were no significant differences in bladder and femoral head NTCP between plans and slightly lower rectal NTCP (endpoint: grade ≥ 2 late toxicity or rectal bleeding) was found for plan{sub 100-105} {sub Gy}. Conclusions: VMAT can potentially increase the likelihood of tumor control in primary prostate cancer while observing normal tissue tolerances through simultaneous delivery of a steep radiation boost to a {sup 18}F-choline PET-defined IDL.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Shortening Delivery Times of Intensity Modulated Proton Therapy by Reducing Proton Energy Layers During Treatment Plan Optimization

Purpose: To shorten delivery times of intensity modulated proton therapy by reducing the number of energy layers in the treatment plan. Methods and Materials: We have developed an energy layer reduction method, which was implemented into our in-house-developed multicriteria treatment planning system “Erasmus-iCycle.” The method consisted of 2 components: (1) minimizing the logarithm of the total spot weight per energy layer; and (2) iteratively excluding low-weighted energy layers. The method was benchmarked by comparing a robust “time-efficient plan” (with energy layer reduction) with a robust “standard clinical plan” (without energy layer reduction) for 5 oropharyngeal cases and 5 prostate cases. Both plans of each patient had equal robust plan quality, because the worst-case dose parameters of the standard clinical plan were used as dose constraints for the time-efficient plan. Worst-case robust optimization was performed, accounting for setup errors of 3 mm and range errors of 3% + 1 mm. We evaluated the number of energy layers and the expected delivery time per fraction, assuming 30 seconds per beam direction, 10 ms per spot, and 400 Giga-protons per minute. The energy switching time was varied from 0.1 to 5 seconds. Results: The number of energy layers was on average reduced by 45% (range, 30%-56%) for the oropharyngeal cases and by 28% (range, 25%-32%) for the prostate cases. When assuming 1, 2, or 5 seconds energy switching time, the average delivery time was shortened from 3.9 to 3.0 minutes (25%), 6.0 to 4.2 minutes (32%), or 12.3 to 7.7 minutes (38%) for the oropharyngeal cases, and from 3.4 to 2.9 minutes (16%), 5.2 to 4.2 minutes (20%), or 10.6 to 8.0 minutes (24%) for the prostate cases. Conclusions: Delivery times of intensity modulated proton therapy can be reduced substantially without compromising robust plan quality. Shorter delivery times are likely to reduce treatment uncertainties and costs.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Treatment Guidelines for Preoperative Radiation Therapy for Retroperitoneal Sarcoma: Preliminary Consensus of an International Expert Panel

Purpose: Evidence for external beam radiation therapy (RT) as part of treatment for retroperitoneal sarcoma (RPS) is limited. Preoperative RT is the subject of a current randomized trial, but the results will not be available for many years. In the meantime, many practitioners use preoperative RT for RPS, and although this approach is used in practice, there are no radiation treatment guidelines. An international expert panel was convened to develop consensus treatment guidelines for preoperative RT for RPS. Methods and Materials: An expert panel of 15 academic radiation oncologists who specialize in the treatment of sarcoma was assembled. A systematic review of reports related to RT for RPS, RT for extremity sarcoma, and RT-related toxicities for organs at risk was performed. Due to the paucity of high-quality published data on the subject of RT for RPS, consensus recommendations were based largely on expert opinion derived from clinical experience and extrapolation of relevant published reports. It is intended that these clinical practice guidelines be updated as pertinent data become available. Results: Treatment guidelines for preoperative RT for RPS are presented. Conclusions: An international panel of radiation oncologists who specialize in sarcoma reached consensus guidelines for preoperative RT for RPS. Many of the recommendations are based on expert opinion because of the absence of higher level evidence and, thus, are best regarded as preliminary. We emphasize that the role of preoperative RT for RPS has not been proven, and we await data from the European Organization for Research and Treatment of Cancer (EORTC) study of preoperative radiotherapy plus surgery versus surgery alone for patients with RPS. Further data are also anticipated pertaining to normal tissue dose constraints, particularly for bowel tolerance. Nonetheless, as we await these data, the guidelines herein can be used to establish treatment uniformity to aid future assessments of efficacy and toxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Outcomes for Spine Stereotactic Body Radiation Therapy and an Analysis of Predictors of Local Recurrence

Purpose: To investigate local control, survival outcomes, and predictors of local relapse for patients treated with spine stereotactic body radiation therapy. Methods and Materials: We reviewed the records of 332 spinal metastases consecutively treated with stereotactic body radiation therapy between 2002 and 2012. The median follow-up for all living patients was 33 months (range, 0-111 months). Endpoints were overall survival and local control (LC); recurrences were classified as either in-field or marginal. Results: The 1-year actuarial LC and overall survival rates were 88% and 64%, respectively. Patients with local relapses had poorer dosimetric coverage of the gross tumor volume (GTV) compared with patients without recurrence (minimum dose [Dmin] biologically equivalent dose [BED] 23.9 vs 35.1 Gy, P<.001; D98 BED 41.8 vs 48.1 Gy, P=.001; D95 BED 47.2 vs 50.5 Gy, P=.004). Furthermore, patients with marginal recurrences had poorer prescription coverage of the GTV (86% vs 93%, P=.01) compared with those with in-field recurrences, potentially because of more upfront spinal canal disease (78% vs 24%, P=.001). Using a Cox regression univariate analysis, patients with a GTV BED Dmin ≥33.4 Gy (median dose) (equivalent to 14 Gy in 1 fraction) had a significantly higher 1-year LC rate (94% vs 80%, P=.001) compared with patients with a lower GTV BED Dmin; this factor was the only significant variable on multivariate Cox analysis associated with LC (P=.001, hazard ratio 0.29, 95% confidence interval 0.14-0.60) and also was the only variable significant in a separate competing risk multivariate model (P=.001, hazard ratio 0.30, 95% confidence interval 0.15-0.62). Conclusions: Stereotactic body radiation therapy offers durable control for spinal metastases, but there is a subset of patients that recur locally. Patients with local relapse had significantly poorer tumor coverage, which was likely attributable to treatment planning directives that prioritized the spinal cord constraints over tumor coverage. When possible, we recommend maintaining a GTV Dmin above 14 Gy in 1 fraction and 21 Gy in 3 fractions.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Trajectory Modulated Arc Therapy: A Fully Dynamic Delivery With Synchronized Couch and Gantry Motion Significantly Improves Dosimetric Indices Correlated With Poor Cosmesis in Accelerated Partial Breast Irradiation

Purpose: To develop planning and delivery capabilities for linear accelerator–based nonisocentric trajectory modulated arc therapy (TMAT) and to evaluate the benefit of TMAT for accelerated partial breast irradiation (APBI) with the patient in prone position. Methods and Materials: An optimization algorithm for volumetrically modulated arc therapy (VMAT) was generalized to allow for user-defined nonisocentric TMAT trajectories combining couch rotations and translations. After optimization, XML scripts were automatically generated to program and subsequently deliver the TMAT plans. For 10 breast patients in the prone position, TMAT and 6-field noncoplanar intensity modulated radiation therapy (IMRT) plans were generated under equivalent objectives and constraints. These plans were compared with regard to whole breast tissue volume receiving more than 100%, 80%, 50%, and 20% of the prescription dose. Results: For TMAT APBI, nonisocentric collision-free horizontal arcs with large angular span (251.5 ± 7.9°) were optimized and delivered with delivery time of ∼4.5 minutes. Percentage changes of whole breast tissue volume receiving more than 100%, 80%, 50%, and 20% of the prescription dose for TMAT relative to IMRT were −10.81% ± 6.91%, −27.81% ± 7.39%, −14.82% ± 9.67%, and 39.40% ± 10.53% (P≤.01). Conclusions: This is a first demonstration of end-to-end planning and delivery implementation of a fully dynamic APBI TMAT. Compared with IMRT, TMAT resulted in marked reduction of the breast tissue volume irradiated at high doses.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Impact of Fractionation and Dose in a Multivariate Model for Radiation-Induced Chest Wall Pain

Purpose: To determine the role of patient/tumor characteristics, radiation dose, and fractionation using the linear-quadratic (LQ) model to predict stereotactic body radiation therapy–induced grade ≥2 chest wall pain (CWP2) in a larger series and develop clinically useful constraints for patients treated with different fraction numbers. Methods and Materials: A total of 316 lung tumors in 295 patients were treated with stereotactic body radiation therapy in 3 to 5 fractions to 39 to 60 Gy. Absolute dose–absolute volume chest wall (CW) histograms were acquired. The raw dose-volume histograms (α/β = ∞ Gy) were converted via the LQ model to equivalent doses in 2-Gy fractions (normalized total dose, NTD) with α/β from 0 to 25 Gy in 0.1-Gy steps. The Cox proportional hazards (CPH) model was used in univariate and multivariate models to identify and assess CWP2 exposed to a given physical and NTD. Results: The median follow-up was 15.4 months, and the median time to development of CWP2 was 7.4 months. On a univariate CPH model, prescription dose, prescription dose per fraction, number of fractions, D83cc, distance of tumor to CW, and body mass index were all statistically significant for the development of CWP2. Linear-quadratic correction improved the CPH model significance over the physical dose. The best-fit α/β was 2.1 Gy, and the physical dose (α/β = ∞ Gy) was outside the upper 95% confidence limit. With α/β = 2.1 Gy, V{sub NTD99Gy} was most significant, with median V{sub NTD99Gy} = 31.5 cm{sup 3} (hazard ratio 3.87, P<.001). Conclusion: There were several predictive factors for the development of CWP2. The LQ-adjusted doses using the best-fit α/β = 2.1 Gy is a better predictor of CWP2 than the physical dose. To aid dosimetrists, we have calculated the physical dose equivalent corresponding to V{sub NTD99Gy} = 31.5 cm{sup 3} for the 3- to 5-fraction groups.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

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↗

Stereotactic Body Radiation Therapy Boost After Concurrent Chemoradiation for Locally Advanced Non-Small Cell Lung Cancer: A Phase 1 Dose Escalation Study

Purpose: Stereotactic body radiation therapy (SBRT) boost to primary and nodal disease after chemoradiation has potential to improve outcomes for advanced non-small cell lung cancer (NSCLC). A dose escalation study was initiated to evaluate the maximum tolerated dose (MTD). Methods and Materials: Eligible patients received chemoradiation to a dose of 50.4 Gy in 28 fractions and had primary and nodal volumes appropriate for SBRT boost (<120 cc and <60 cc, respectively). SBRT was delivered in 2 fractions after chemoradiation. Dose was escalated from 16 to 28 Gy in 2 Gy/fraction increments, resulting in 4 dose cohorts. MTD was defined when ≥2 of 6 patients per cohort experienced any treatment-related grade 3 to 5 toxicity within 4 weeks of treatment or the maximum dose was reached. Late toxicity, disease control, and survival were also evaluated. Results: Twelve patients (3 per dose level) underwent treatment. All treatment plans met predetermined dose-volume constraints. The mean age was 64 years. Most patients had stage III disease (92%) and were medically inoperable (92%). The maximum dose level was reached with no grade 3 to 5 acute toxicities. At a median follow-up time of 16 months, 1-year local-regional control (LRC) was 78%. LRC was 50% at <24 Gy and 100% at ≥24 Gy (P=.02). Overall survival at 1 year was 67%. Late toxicity (grade 3-5) was seen in only 1 patient who experienced fatal bronchopulmonary hemorrhage (grade 5). There were no predetermined dose constraints for the proximal bronchial-vascular tree (PBV) in this study. This patient's 4-cc PBV dose was substantially higher than that received by other patients in all 4 cohorts and was associated with the toxicity observed: 20.3 Gy (P<.05) and 73.5 Gy (P=.07) for SBRT boost and total treatment, respectively. Conclusions: SBRT boost to both primary and nodal disease after chemoradiation is feasible and well tolerated. Local control rates are encouraging, especially at doses ≥24 Gy in 2 fractions. Toxicity at the PBV is a concern but potentially can be avoided with strict dose-volume constraints.

62 RADIOLOGY AND NUCLEAR MEDICINE↗