Purpose/Objective(s) There is an ongoing desire to define "value" in clinical research. ESMO-MCBS is a commonly used framework, endorsed by ESMO and used by several governments in their health technology assessments in various settings. Such value frameworks have not been validated for assessing benefit derived from radiotherapy (RT). We herein assess the applicability of the ESMO-MCBS in radiation oncology, using breast cancer as a test-case. Materials/Methods We reviewed the supportive literature used by the ASTRO Evidence-Based Guideline on Radiation Therapy for the Whole Breast for adjuvant whole breast Radiation Therapy. We delineated a pool of "core" (112 studies) and "supplemental" articles (additional 65 studies). Among these, we identified a subset of 15 randomized trials, 1 systematic review and 1 big data study. The goals of our exercise were (1) to evaluate the "scorability" of data, (2) to evaluate the reasonableness of the generated grades for clinical benefit using the current version of the ESMO-MCBS tool, and (3) to identify shortcomings in the instrument when applied to RT approaches, and suggest amendments to improve the efficacy and validity of the ESMO-MCBS tool. Results Few studies met the ESMO-MCBS criteria for crediting clinical benefit; i.e., in (1) superiority of the trials in overall survival (OS) or disease-free survival (DFS), or, (2) non-inferiority in OS or DFS with benefit in either life quality (QOL) or toxicity or reduced treatment costs as secondary end-points. OS was the primary end point in only one trial (which was a negative study). However, that study (EORTC boost trial) was practice-changing because it showed a significant improvement in local control (LC) which was a secondary outcome. Since the ESMO-MCBS does not credit local control (i.e., "local DFS"), superiority studies using this endpoint were not scoreable. Arguably, the 4 non-inferiority studies and one meta-analysis comparing hypo-fractionation with standard fractionation (that demonstrated non-inferior disease control with reduced acute and late toxicity) could be scored. Finally, reports describing cosmetic, clever technical or dosimetric advances, without verification of improved patient outcomes nor associated with clinical benefit, were not scoreable. Conclusion Currently, ESMO-MCBS does not credit LC as distinct from DFS or RFS. Since local recurrence results in a cascade of adverse events for patients, this is a clinically meaningful outcome, albeit often not always a good surrogate for OS. For consistency in research design and description of results, we propose replacing the conventional nomenclature of LC with Local-DFS (L-DFS)- a subtype of DFS most-relevant to local treatments (e.g., RT and surgery). The utility of the ESMO-MCBS in studies involving RT and surgery would be improved by incorporation of credit for statistically and clinically significant improvements in L-DFS.

Purpose:CT simulation has become an integral component of modern RT planning and therefore must be continually optimized. We evaluated the detection of small and low‐contrast regions in images obtained during CT simulation.Methods:A CT phantom containing a contrast detail modulus for detection of low‐contrast structures was used to optimize the CT reconstruction protocol for abdomen. The parameters (A) Pitch, (B) Reconstruction Filter, and (C) Rotation Time type were varied for assessment of image quality.Three factors, three levels, and nine experiments were identified. According to the Taguchi approach an L9 orthogonal array was selected. The reconstruction parameters of the CT scanner (Brilliance Big Bore), Pitch, Reconstruction Filter type, and Rotation Time, were iteratively scanned according to the orthogonal array. A Catphan 604 CT phantom was used to characterize low‐contrast resolution (CPT730 module). All CT scan images were analyzed by IMAGE‐OWL software. The objective of the study was to identify parameters that maximize the low‐contrast resolution of the images. The ANOVA and F‐tests were used to analyze results using JMP statistical software.Results:The optimal settings and predicted optimal values for low‐contrast resolution were determined. The ANOVA was used to determine the optimum combination of process parameters more accurately by investigating the relative importance of each process parameter. We determined that Pitch (61.4%) had the most significant influence on low contrast resolution, followed by the Reconstruction Filter type (29.7%). The optimal setting level is A1‐B1‐C3, 0.68 pitch, smooth filter, and gantry rotation time 1.5sec., respectively. Additional measurements were made to confirm the prediction error model is justified and the results are validated.Conclusion:These experiments have several implications for CT imaging, especially for clinical detection of small, low‐contrast lesions in liver or pancreas. In the phantom model of this study, optimal Contrast Detail Values were determined to be: 1% contrast, 2mm; 0.5% contrast, 4mm; 0.3% contrast, 7mm.

_____________________________________________________________________________________________________parietal tumor localization was a predictor for a higher contralateral hippocampal dose (p=0.01). Conclusion:A substantial reduction of the dose to the contralateral hippocampus is technically feasible when VMAT is used instead of our standard 3D-CRT planning strategy.The amount of sparing that can be achieved strongly depends on the individual patient geometry.Whether this approach is able to conserve the neurocognitive status without compromising the oncological outcome for patients with glioblastoma needs to be investigated in the setting of prospective clinical trials. EP-1674Should VMAT be routinely applied to treat sacral bone metastases?V. Soyfer

Moran Artzi, Orna Aizenstein, Deborah T. Blumenthal, Felix Bokstein, Benjamin W. Corn, and Dafna Ben Bashat The Functional Brain Center, The Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, Neuro-Oncology Service, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, Institute of Radiotherapy, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

Purpose: Lung Cancer represents the major reason for mortality in the modern society. The disease is usually diagnosed in the advanced stage. External beam radiation therapy is the essential component in the treatment of stage 3 Non Small Cell and Small Cell Lung cancer patients. IMRT proved as preferred technique above conformal 3 D in term of sparing lung tissue and subsequent radiation pneumonitis. In our work we investigated the impact of innovate technique of combination of 3 D and IMRT on dose distribution in centrally located lung cancer patients. The rational of combination is based on the inability of IMRT technique to provide the oppositional fields arrangement desired in order to avoid the additional lung tissue Methods: Three treatment plans were generated for seven patients with lung cancer. For every patient 3 D conformal, IMRT and combined 3D and IMRT plans were compared for V5, V10, V20, V 30 and mean dose of the lung DVH, maximal dose to the esophagus and spinal cord Results: The DVH of the lung in three comparative plans for 3D, IMRT and combined plans for the total lung ‐GTV was as follow: V5‐63.2±8.6%, 63.9± 9.2%, 56.6± 11.4%; V10‐53.07± 10.1, 52.3± 11.2, 38.8± 9.6; V20‐27.6± 6.7, 31.1± 7.0, 20.6± 2.3; V30‐14.3±4.6, 13.36± 0.37, 14.96± 1.22 respectively. The maximal doses to esophagus was 53.21± 3.05, 54.4± 4.67, 52.3± 4.5 Gy respectively. Maximal dose to the spinal cord was 42.5± 2.9, 39.58± 1.2 and 43.7± 4.5 Gy respectively Conclusions: Combined 3 D and IMRT technique results in better lung tissue sparing comparing to other treatment plans

Purpose: Implanted fiducial markers are commonly used for high accuracy positioning of the prostate in radiation therapy. One source of error in fiducial‐based patient positioning is the rotation and deformation of the prostate. The sensitivity of fiducial‐based positioning to rotation and deformation depends upon the location of the center of mass (COM) of the fiducials relative to the COM of the prostate and on the stability of this geometric relationship throughout the treatment. This work assesses the geometric stability within the prostate of a single implanted trackable fiducial marker (Tracer, Navotek Medical Ltd.) relative to the COM of 4 gold seeds. Methods: In a multi‐site ethics committee approved clinical trial, 20 prostate radiation therapy patients were implanted with 4 gold seeds and one Tracer. CBCT imaging was performed during 5 treatment sessions to measure the locations of the implants. The locations of the Tracer and the COM of the gold seeds were compared in each treatment session, and the stability of the Tracer relative to the COM of the gold seeds from treatment to treatment was assessed. Results: The mean change in position of the Tracer relative to the COM of the gold seeds was 2mm +/− 1mm (mean +/− std) and increased with the distance between the Tracer and the COM of the gold seeds and with the amount of rotation of the prostate as estimated based on the positions of the gold seeds, as expected. Conclusions: The stability of the Tracer relative to the COM of the gold seeds was found to be similar in magnitude to the differences in positioning between any two highly accurate positioning methods. These results support the assertion that a single fiducial, placed near the COM of the prostate, can provide positioning accuracy comparable to multiple fiducials distributed around the prostate.This research was funded by Navotek Medical Ltd.

To explore international patterns of practice in the prophylaxis of radiation-induced nausea and vomiting (RINV). A web-based survey designed by investigators from several countries was sent to all oncologists currently prescribing radiotherapy in participating countries. Respondents estimated the risks of nausea and vomiting associated with 6 radiotherapy-only clinical cases modeled according to the Multinational Association of Supportive Care in Cancer (MASCC)-defined levels of emetogenic risk (1 High-risk case, 2 Moderate-risk cases, 2 Low-risk cases, 1 Minimal-risk case). Respondents recommended either prophylactic, rescue, or no anti-emetic therapy as an initial treatment approach to each case, and selected up to 3 classes of anti-emetic agents to allow them to carry out their plan (E.g., 5HT3 receptor antagonists, corticosteroids, NK-1 receptor antagonists, dopamine antagonists, pro-kinetics, anti-histamines, cannabinoids, or other). Data from countries whose surveys had closed by the time of abstract submission are presented here. Nine hundred three cumulative responses were received from 9 countries as follows: The United States of America (n = 550, 16% response rate), Canada (n = 121, 40% response rate), the Netherlands (n = 89, 36% response rate), Australia and New Zealand (n = 61, 19% response rate), Italy (n = 48, 7% response rate), Singapore (n = 15, 56% response rate), Cyprus (n = 10, 83% response rate), and Israel (n = 9, 32% response rate). The percentages of respondents by country recommending prophylactic therapy as an initial treatment approach for each case are as follows:Tabled 1CountryHigh RiskModerate Risk #1Moderate Risk #2Low Risk #1Low Risk #2Minimal RiskAustralia and New Zealand100409041355Canada98498549160Cyprus1002288506325Israel100118956440Italy98407865295Netherlands87467833224Singapore8614505707USA95297138111 Open table in a new tab Rates of RINV prophylaxis generally increased for cases of higher emetogenic risk. The greatest variability between countries was for the Moderate- and Low-risk cases. Survey responses from 6 countries are pending.

Purpose: To evaluate the relative plan quality of single‐isocenter vs. multi‐isocenter for radiosurgical treatment of multiple brain metastases Methods: Ten patients referred to stereotactic radiosurgery treatment for 2–3 lesions in the brain. Two stereotactic radiosurgery plans were generated for each patient, First Plan using static beams and arcs for multi isocenter treatment plan and a second plan with one isocenter covering all lesions using static beams All plans were generated using ergo++ software on Elekta synergy‐s with beam modulator 16×21 cm with 4mm interdigitating leaves. Plans were normalized to deliver a prescription dose to the 80% isodose‐line Results: All plans were judged clinically acceptable, and no significant differences for OAR were observed in the dosimetry parameters. Nevertheless patient with different size of lesions and proximity to OAR had a different prescription dose which lead to much higher dose at the center of the lesion in the single iso plan compare to the multi isocenter plan and still kept very tight dose cover and gradient, in some cases the maximum dose was higher by 20% and average machine on time was 43.6± 9.58% higher, respectively Conclusions: Our initial results suggest that single‐isocenter plans can be utilized to deliver conformity equivalent to that of multiple isocenter techniques. Single isocenter radiosurgery for multiple targets can be efficiently delivered, and requiring less than one‐half the beam time required for multiple isocenter set ups.

Purpose: Volumetric modulated arc therapy (VMAT) is a relatively new treatment modality characterized by variable angular dose rate arc delivery. The purpose of this study was to compare treatment plans for multileaf collimators (MLCs) with different leaf widths and different dose calculation grids, in order to determine the optimal planning quality and delivery efficiency for VMAT of GBM boost plans. Method and Materials: CT images of 10 GBM patients were used for this study on an ERGO++ Treatment planning system ((ELEKTA; Crawley, UK). Two dose grids were used. The first grid was 2mm and the second 3mm. We used the Elekta Beam Modulator (4mm leaf) and Elekta MLCi (1cm leaf). The same dose constraints and beam parameters were used for optimization. Tissue inhomogeneity corrections were applied during optimization and dose calculation. Plans were optimized such as that the CTV received 14 Gy in 7 fractions. Dose distributions to the target and normal structures were evaluated. The number of monitor units (MU) and delivery times were used to evaluate delivery efficiency. Results: The doses to the CTV, eyes, optic nerves, tracts, brain stem, pituitary gland and optic chiasm were calculated. The 3mm grid with the 4mm leaf width used 303±18 MU and 0.66±0.068 conformity index (CI). The 3mm grid with the 1cm leaf width used 274±19 MU and 0.67±0.064 CI .The 2mm grid with the 1cm leaf width used 280±25MU and 0.67±0.064CI. The 2mm grid with the lcm leaf width used 264±20MU and 0.64±0.060CI. Conclusion: Treatment plans generated with the 2mm dose grid and the 4mm leaf width seem to be optimal for both plan quality and delivery efficiency. While this study was specifically designed for the ERGO++ Treatment planning system combined with the ELEKTA linear accelerator/MLC and IMPAC R&V system, the conclusions drawn have ramifications for other environments as well.

Purpose: To assess the effect of the RealEye gantry-mounted tracking system (Navotek Medical, Yokneam, Israel) on kV x-ray and Cone Beam CT (CBCT) imaging and image quality on a Varian LINAC with On-Board Imager (Varian Medical Systems, Palo Alto, CA). Although routine x-ray or CBCT imaging should not be necessary for patients being positioned with the RealEye system, it is important to assess the image quality with the system installed for cases where anatomical imaging is necessary to verify accurate patient positioning and for situations where the system is installed but not being used for the current patient. Method and Materials: kV x-ray and CBCT images were made of a quality assurance phantom with and without the RealEye system installed. Image quality in terms of artifacts, contrast, and signal-to-noise ratio was compared. Results: No significant effects on signal-to-noise ratio or contrast were associated with the RealEye system, and no discernable image artifacts were induced with the RealEye system mounted on the gantry. At a distance of 18.5 cm from isocenter the RealEye system encroaches upon the imaging field of view and then interferes somewhat with image quality. Since a 35 cm field of view is generally sufficient for patient positioning and position verification, this should not limit the use of the On-Board Imager for patient positioning with the RealEye system installed. Conclusion: The RealEye gantry-mounted tracking system does not interfere with the use of the Varian On-Board Imager and does not produce any effects on images with a field of view below 35 cm. The RealEye system therefore has no impact on the usability of the On-Board Imager for patient positioning. Conflict of Interest: Tal Shchory, David Neustadter, and Ben Corn are employees and shareholders of Navotek Medical Ltd. Research sponsored by Navotek Medical Ltd.

Conventional therapies have not been effective in the treatment of pancreatic cancer. Stereotactic body radiation therapy (SBRT) is a novel technique that is predicated on technological advances in image guidance which aspire to deliver ablative doses of irradiation. SBRT mandates a high degree of confidence in tumor localization. We recently reported the application of depleted radioactive sources (i.e., I-125 seeds that were no longer suitable for prostate brachytherapy) as fiducial markers for external irradiation of prostate cancer. Those seeds were chosen since, unlike gold seeds, they do not create artifacts on CT images are widely available in Radiation Oncology Departments. We describe, herein, the feasibility of incorporating such depleted sources in SBRT programs for pancreatic cancer. An 80-year-old woman with resectable pancreatic cancer declined to undergo resection (Whipple Procedure). Compassionate use was granted to treat with SBRT. Depleted I-125 seeds were endoscopically implanted to localize the target. Treatment delivery consisted of 3 fractions of 12 Gy after the patient was trained to use an Automatic Breathing Coordinator. The seeds were successfully implanted in the patient. The fiducials were easily visualized and target was clearly identified. No seed migration occurred. No significant artifact was encountered. No acute complications occurred. SBRT is a biologically appealing alternative for the management of pancreatic cancer. The use of depleted iodine seeds as a component of SBRT programs is not only feasible but also attractive since most radiotherapy departments have access to this resource and the seeds are easily identifiable without inducing artifact that impairs interpretation on conventional imaging modalities. We have embarked on an IRB-approved protocol to advance this approach.

Setup accuracy and exact tumor position are profoundly important for stereotactic radiation therapy. One must be wary of target movement in daily set-up. To date, most research has focused on the movement of the target in longitudinal, anterior-posterior and lateral directions. The aspects of tumor distortion, alterations in configuration and the location as a result of treatment itself, have received less attention in the literature. Published guidelines for most clinical trials require portal imaging be obtained prior to initiation of treatment and on a weekly basis thereafter. The advent of cone beam CT technology has focused the spotlight on the dynamic changes in target volume and position that are ongoing daily. When synthesized with the new realities ushered in by IMRT and SBRT (e.g., smaller margins with higher doses) one becomes cognizant of the need to continually re-asses the volume via daily imaging. A patient with lung metastases from uterine sarcoma was illustrative of the new "problem" that clinicians and physicists encounter. A woman was to be treated with SBRT to a 5.5 cm diameter lesion which was tethered to the diaphragm. This lesion was planned for treatment with three dimensional conformal techniques. Automatic Breathing Coordinator was employed to treat the lesion. A dose of 70 Gy in 2Gy/fx was prescribed. A daily cone beam CT for setup was performed prior to each treatment. After delivering 12 Gy to the target volume, the target volume responded and unexpectedly changed its location as well as its orientation. Apparently, changes in its form and/or dimension "untethered" the mass from the diaphragm and dispatched it to a new position. Accordingly, these alterations were corrected by defining a new target volume at repeat simulation. Daily setup with cone beam CT offers images of superior quality than standard MV portal imaging due to the unique ability to view soft tissues. We will argue that this is a critical step in modern radiotherapy practices which call for the precise delivery of high doses. This concept is especially applicable in providing radiation as a primary treatment of viable tumors in "moveable organs" such as lung and liver. It is unlikely that standard portal imaging would distinguish changes such as those described. As such, the clinical team risks missing the target itself when cone beam CT is not applied. Whether the new target needs to include the initial tumor bed or just the new location where the tumor resides is unknown at this time.