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: 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.

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.

Purpose: To examine the daily patient set‐up positioning error vs. the radiation technologist rank, by deriving it from the XVI image fusion correction values. Method and Materials: A set of 5 prostate, 5 head & neck and 4 lung cancer patients had been taken for this comparison. All of the patients were treated in IMRT Step & Shoot technique. For each patient the following data was extracted: (1) 10 XVI scans randomly picked and three parameters were taken, the table shift in 3 axis: longtitudal, lateral, vertical. (2) The names of the radiation technologists correlating to the date of the XVI scan. Three intervals of fusion correction were defined: 2–3 [mm], 3–5 [mm], greater then 5 [mm]. Radiation technologists were ranked by compiling a set of categories such as: chronological time at work, overall assessment of the institute senior staff in a scale of 1–5 (1‐High Rank; 5‐Low Rank). Results: There is a definitive match between the value of the correction and the number of corrections in total per patient and the radiation technologist rank. Radiation technologists that were ranked 4 or 5 constitute most of the fusion corrections above 3 and 5 [mm] in patients positioning. A combination pair of radiation technologists that were ranked as 4 or 5 increased the correction in two forms: (1) more then one axis was corrected (2) the value of the correction was high. A combination pair of a median rank and high rank radiation technologist yielded better results then a pair of a median rank and low rank radiation technologist. Conclusion: This work clearly indicates the on‐going strive for the education of the technical staff, as a vital link in patient positioning which leads to administrating the correct dose to a patient, in an accurate treatment modality such as IMRT.

Purpose: To examine the robustness of a gantry mounted radioactive tracking system in 6MV and 10MV clinical radiation therapy environments. Method and Materials: The gantry‐mounted tracking system was installed in several radiation therapy treatment rooms. Total dose equivalent to 20 treatment sessions was delivered at 6MV or 10MV in a few fractions (within 1 hour) to a phantom containing a radioactive marker (Ir192). During irradiation the tracking system was operating and system parameters were recorded before, during and immediately after irradiation. Recorded data was analyzed to assess system performance and the accumulated effects of radiation on the system. The radioactive marker location measured by the tracking system was monitored during and after irradiation to test for accuracy and stability. The spectra of the signals from the radioactive marker before and after irradiation were compared to see if any shift in spectrum is observed. After 10MV irradiation, background signal level was monitored to analyze the halflives of the isotopes resulting from neutron activation. Results: There was no significant change in signal spectrum after irradiation and no cumulative influence on system performance was observed. Tracking is temporarily interrupted during 10MV irradiation and is resumed within a few seconds after irradiation despite the increased background noise resulting from neutron activation which decays with a half life of approximately 105 seconds. At 6MV, the system maintains tracking accuracy and performance throughout irradiation despite an increased background noise level. The system adjusts to the changes in background noise level at the beginning and end of irradiation in under 3 seconds. Conclusion: The radioactive tracking system is robust in the radiation environment. There is no observable effect or malfunction after exposure to radiation. The system is capable of tracking a radioactive marker during irradiation at 6MV. Conflict of Interest: Research sponsored by Navotek Medical Ltd.

Background: Treatment of arterio‐venous malformations (AVM) of the brain can be a challenge due to the complexity of location, size and their proximity to the cerebral vascular circulation. stereotactic radiosurgery (SRS) recent advanced in catheter technique and new embolization materials, in particular Onyx have increased the success rate of total and near‐total obliteration. The use of Onyx cause distortion of the MRI and CT images and there for has to be considering in any radiation treatment planning. Methods and Material: Between 12/2006 and 12/2008 we treated 13 AVM patients after Onyx immobilization with SRS. A bottle with 1.5ml of onyx been irradiate to find and define the absorption of it per mm of thickness, after doing that we contor the onyx and the projected area in the planning system and apply a homeginity correction to virtual organ that been draw. a pinpoint chamber been used for relative measurement because of the size of the bottle. Results: In particular larger Onyx embolized AVMs showed significant imaging artefacts especially on CT, which rendered this imaging modality useless for planning purposes. The absorption of the onyx with thickness of about 15mm was up to 5.6% higher compare to a 15mm of bolous without the onyx. Conclusion: The use of Onyx caused significant image artefact on MR and more so on CT. this results shows the importance of the correction that need to apply manually in the planning system. For patient with a large area and volume of onyx, this results shows the crucial of the correction that must be applied, if not a dose calculation can be completely wrong especially for radiosurgery patients, who prescribed high dose in single fraction to a completely healthy brain.

Background: Radiation treatment of spinal and paraspinal tumors has been limited by the tolerance of the spinal cord. With new treatment technologies, like IMRT and extracranial SRS, higher radiation dose can be delivered to the target with the capability of sparing sensitive normal structure. This study is comparing the most advanced radiation techniques (IMRT and SBRT) for spinal tumor treatment. Methods: 12 patients were treated for 13 spinal lesions; the treated lesions included metastases and primary spinal tumors in all spinal segments. Treatment indications were tumor control and pain palliation. All patients had been treated with SRS. We retrospectively compared the SRS and IMRT treatment plan. SRS was planned using the 3Dline, (ERGO++, Elekta) for direct treatment planning. For IMRT planning we used CMS Xio software (CMS, St. Louis, MO). A dose-volume histogram for the peripheral tissue and organ at risk around the target generated and evaluate. The IMRT plan had to meet the same tumor coverage as the srs. The SRS plan were transferred to the XiO planning system and recomputed in order to eliminate algorithm accuracy performance difference. Results: The median target volume was 8.1 cc (4.1–12.5cc). The SRS plan showed lower median target dose (5.3%, range 3–31%) and lower median dose (27.9%, range 6.6–27.2%) to critical structures (spinal cord, kidneys). The IMRT plan showed higher peripheral dose volume exposure for of 30.3%, 49.4% and 62.7% for the 10%, 20% and 30%, respectively, of overall exposed tissue volume. The planning and quality assurance duration for SRS was on average 75 minutes and for the IMRT plan 480 minutes. Conclusion: SRS technique showed a higher and faster gradient fall off reflected by a more conformal tumor coverage and less exposure to normal tissue. SRS was less time consuming for planning and quality assurance compared to the IMRT.

Although chemoradiation was viewed as the standard of care in the adjuvant management of gastric cancer since the publication of INT 0116, a more recent phase III trial (MAGIC) did not include radiotherapy in the randomization schema. The subtext of the latter trial (i.e., that radiation may be expendable in this disease) mandates that future prospective studies utilizing radiotherapy optimize its application. We therefore set out to determine whether IMRT could improve upon our published 3-D conformal approach for treatment to the stomach and draining nodes. A total of 10 patients with adenocarcinoma of the stomach were treated with adjuvant chemoradiotherapy using a non-coplanar four-field arrangement (Soyfer et al., IJROBP 2007;69:364-369). In each case, parallel planning using an IMRT approach was carried out for comparative purposes. Two beam arrangements were evaluated: Beam arrangement 1: gantry angles 0° 53° 107° 158° 204° 255° 306°. Beam arrangement 2: gantry angles 30° 90° 315° 345° and gantry angle 320°/couch 30° gantry angle 35°/couch 312°. The plans generated were subsequently assessed for target volume coverage and dose deposition in adjacent critical organs. Dose-volume histograms (DVHs) were generated for the CTV, kidneys, spine, and liver. The comparative study of the CTVs revealed satisfactory coverage by the 95% isodose envelope with either treatment approach (IMRT or 3D). The liver, spine and right kidney showed marginal benefit from the IMRT approach. In the left kidney, the mean dose dropped from 33 Gy in the conformal plan to 13 Gy in the IMRT plan. IMRT offers marginal benefits in the adjuvant treatment of gastric cancer and should only be offered to the small subset of patients with risk factors for kidney disease or pre-existing nephropathy.

Purpose: In radiation therapy there is a need to accurately know the location of the target in real time. A novel radioactive tracking technology is being developed to answer this need. The technology consists of a radioactive non‐migrating implanted fiducial marker and a linac mounted tracking device. This study measured the static and dynamic accuracy of the new tracking technology in a clinical radiation therapy environment. Method and Materials: The tracking device was installed on an Elekta Synergy® linac gantry. The radioactive marker was located in a tissue equivalent phantom. Actual marker location was measured using a Microscribe G2 coordinate measuring machine (CMM) arm (certified spatial accuracy of 0.38 mm). The marker was attached to the tip of the CMM arm and its location was measured simultaneously by the CMM and the tracking system. Static accuracy was measured at multiple locations covering a 12cm cube centered at the linac iso‐center. The measurements were repeated at multiple gantry angles. Dynamic accuracy was measured with the marker located inside a breathing phantom. Results: The mean localization error for the static source was less than 0.7mm throughout the tested region at all measured gantry angles. The mean real time tracking error for the dynamic source within the breathing phantom was less than 1mm. Conclusion: The novel radioactive tracking technology has the potential to be useful in accurate target localization and real time monitoring for radiation therapy. Conflict of Interest: Research sponsored by Navotek Medical Ltd.

In order to reduce radiation therapy setup time and radiation exposure for prostate cancer patients, fiducial markers have been used with orthogonal X-ray imaging or 3-dimensional tracking as a substitute for soft tissue volume imaging for accurate patient positioning. Generally, investigators have used 3 fiducials, as 3 points are sufficient to determine the translation and rotation of a rigid body, thereby providing the same organ translation and rotation data as volume imaging. However, the prostate is not a rigid body, and organ deformation may interfere with the accurate measurement of organ rotation based on 3 fiducials. In this study, we assess the accuracy with which prostate rotation can be measured using 3 fiducials in the presence of organ deformation. A simulation was performed based on common fiducial locations and typical intermarker distance variations reported in the literature. The simulated fiducial locations were the left and right sides at mid-gland and near the apex, with an average intermarker distance of 23 mm. Organ deformation was simulated such that the intermarker distances had a standard deviation of 1 mm. When prostate rotation was calculated based on the coordinates of the fiducials, a fictitious organ rotation was measured as a result of organ deformation. The standard deviations of the fictitious rotations ranged from 1.5° to 3.3° and the maximum fictitious rotation was 10°. Our simulation indicates that organ deformation can induce errors in the fiducial-based measurement of prostate rotation which are similar in magnitude to the measured prostate rotations reported in the literature. These findings call into question the reliability of previous findings on prostate rotation. Further study is needed to determine the nature and magnitude of prostate deformation and rotation as well as the accuracy of fiducial-based rotation measurements to determine if fiducial-based measurement of prostate rotation can be considered reliable.

Position accuracy has long been an essential and challenging issue in radiation oncology. With more localized treatment modalities becoming more popular, like IMRT, Body Radiosurgery, etc., the demand for accurate and quick localization has increased and many image guided systems have been introduced to the market (i.e., Cone Beam CT, Orthogonal X-rays, Optical tracking, Ultrasound). All of them require substantial pre-treatment setup time and sometimes physician analysis. A need for a fast, accurate, and objective target localization system has been recognized. This is extremely important for targets which are not attached to bones (like prostate) and one cannot rely on bony anatomy for localization. The system used is a set of detectors attached to a linac gantry and a radioactive fiducial seed implanted in the target. The active isotope in the seed is a 50 μCi 192Ir. The detector system does not interfere with the gantry and collimator movements and the reduction in clearance is about the same as for any external MMLC system (about 8 cm). The target was localized with the system and then a cone beam CT was performed to check the localization accuracy. Localization and accuracy measurement was performed six times. The test was performed using a tissue equivalent body phantom. The mean positioning accuracy of the system was 0.3 mm, with std. of 0.16 mm. The localization was real time and the entire process took less then one minute (including repositioning, not including the CBCT which will not be a part of the clinical system). The radioactive tracking system is a fast, accurate and objective system which is appropriate for real time localization and positioning in radiation therapy. It has great potential utility for rapid and accurate beam positioning and for localization of both targets and critical normal tissues.

Purpose: Verification of SRS treatment plans was a challenge in the early beginning of stereotactic radio surgery. The large amount of dose deposited in a single fraction through a small collimator or MMLC was a cause of sleepless nights for many physicists. The traditional way was using a “hand calculation”. In some cases a special measurement in phantom was performed (while the patient was in the SRS ring). This work suggests a quick and accurate way using a standard TPS. Method and Materials: The original treatment plans were developed on the Ergo ++ treatment planning system ver. 1.6 for the 6X beam on a Beam Modulator (4mm leaves). All the plans were calculated with heterogeneity corrections turned on. For the purpose of “hand calculation” we used the built‐in second calculation in the Ergo system (the system provides an automatic and independent MU calculation mechanism). For the comparison we used the XIO software version 4.3.3. The beam was carefully modeled and commissioned on both systems for small field sizes. A total number of 20 plans were compared. The transfer was done using DICOM RT protocol. Results: The match between the calculation results on both 3D systems was excellent (in most cases less then 1% discrepancy). The 1D system showed larger errors (3–4% on head cases), which do not exist when we turned the heterogeneity corrections off. The DVH's and isodoses also showed very good agreement. The transfer and recalculation took about 15 minutes per plan. Conclusion: Using a full second 3D calculation on a separate TPS is a fast and accurate way to check SRS plans. It is usually available in most departments and it justifies the effort (if needed) of some extra modeling for small field sizes. “Hand calculation” is much less accurate, especially when inhomogeneities are present.

Background & Aims: The CpG island methylator phenotype (CIMP) is one of the mechanisms involved in colorectal carcinogenesis (CRC). Although CIMP is probably the cause of high-frequency microsatellite instability (MSI-H) sporadic CRCs, its role in microsatellite stable (MSS) tumors is debated. The majority of MSS CRCs demonstrate chromosomal instability (CIN) with frequent loss of heterozygosity (LOH) at key tumor suppressor genes. We hypothesized that the majority of sporadic CRCs without CIN would be associated with CIMP. Methods: We tested 126 sporadic CRCs for MSI and LOH and categorized tumors into MSI, LOH, or MSI−/LOH− subgroups. Methylation status was evaluated using 6 CIMP-related markers (MINT1, MINT2, MINT31, p16INK4α, p14ARF, and hMLH1) and 6 tumor suppressor genes (PTEN, TIMP3, RUNX3, HIC1, APC, and RARβ2). BRAF V600E mutation analysis was performed using allele-specific polymerase chain reaction and DNA sequencing. Results: We observed frequent methylation at all 12 loci in all CRCs. BRAF V600E mutations correlated with the MSI (P < .0001) and MSI−/LOH− (P = .03) subgroups. MSI and MSI−/LOH− tumors exhibited more promoter methylation than CRCs with LOH (P < .0001). We also found an inverse correlation between the frequencies of methylation and LOH (ρ = −0.36; P < .0001). Conclusions: The associations between methylation frequencies at CIMP-related markers and MSI or MSI−/LOH− sporadic CRCs suggest that the majority of these tumors evolve through CIMP. These findings suggest that CIN and CIMP represent 2 independent and inversely related mechanisms of genetic and epigenetic instability in sporadic CRCs and confirm that MSI cancers arise as a consequence of CIMP.

Purpose: The goals of this study were to evaluate the difference in target dose uniformity and dose distribution through mean DVH and OAR analysis for a given PTV. Dosimetric analysis were also extended to compare sparing of normal tissue and critical structures between two treatment planning techniques. Methods and Material: The ADAC Pinnacle inverse planning system was used to generate conventional IMRT inverse plans for a few head & neck patients. These plans were then compared with treatment plans generated using the IMAT software package manufactured by 3D line USA Medical System Corp. Using axial CT for the same patients, targets, and numerous critical structures were delineated and “best” plans were developed in each environment. In IMAT planning, continuous and dynamically shaped arcs were planned through aperture optimization and leaf sequencing. The dose delivery was accomplished through a specially designed MICRO DMLC with 3 mm leaf width and double focus focalization. Results: For IMRT plans, 5 or 7 co-planar arcs were used and treatment plans were generally optimized using a predefined set of dose objectives, penalties, min and max dose and percentage of volume required. The IMAT plans were designed with typically two co-planar arcs of 180 degrees around the patient with similar dosimetry objective parameters. The percentage coverage for V95 in targets 1&2 were 94.9 ± 2.8 and 95.1 ± 2.1 for IMRT and 98.4 ± 2.6 & 98.1 ± 2.8 for IMAT respectively. Sparing of critical structures was generally better in IMAT, a detail of which will be presented at the meeting. Conclusions: In the IMAT technique with direct aperture optimization, dose distribution within the target was found to be better by 8%. Superior critical structure sparing was achieved as compared with similar plan using IMRT technique. The IMAT technique may be considered as an alternative to tomotherapy.

Purpose: Direct water measurements of small fields in general and small SRS collimators in specific have been a long known problem. The typical ion chambers, which are used with 3D water phantoms have a volume of about 0.125cc, which is not suitable for measuring small fields. The recently introduce Exradin A16 chamber, with a volume of 0.007cc was designed to overcome the problem by allowing accurate measurements of small fields in water. The purpose of this work is to validate the suitability of this chamber for small fields water measurements. Method and Materials: In order to evaluate the suitability of the A16, depth dose curves and a set of profiles were taken with this ionization chamber using SRS collimators ranging from 1cm to 4cm in diameter, in steps of 0.25cm increment. The scans were then compared with film dosimetry of the same collimators and Monte‐Carlo simulations. The films used were the Kodak XDR extended range films in Perspex phantom, which were scanned and analyzed using the Vidar 16 scanner and the RIT software. The Monte‐Carlo simulation was done using the BEAMnrc code. For the larger collimators (2.5cm and up) a set of water measurement were performed also using the standard Wellhoffer chambers (0.125cc) Results: The result showed excellent matching between all evaluations media (water measurements with the A16 and the standard chamber, film dosimetry and Monte‐Carlo simulation). The only discrepancy was with deeper depths in the films, which was due to the phantom used. Conclusion: The A16 is suitable and should be used for small field water measurements.