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Si5345, SY88422L, LT3482, and MSK130 components Total Ionizing Dose Test Report

The purpose of this test was to characterize the SI-5345, SY88422L, LT3482 and MSK130 parameter degradation for total dose response. The components are associated with REAG ID #21-024. In the test, each device was exposed to high dose rate (HDR) irradiation using gamma radiation. Device parameters such as leakage currents, timing, and overall chip health were investigated. These devices were tested for an interstellar mission on a trajectory between 0.9 AU and 5.3 AU with a 2.5-year mission, yielding an expected overall dose of 29 krad(Si)behind 1 mm of aluminum shielding (at 95% confidence; environment and dose determined through SPENVIS). This test report gives an initial look at candidate parts. Extremely small sample sizes (only 1 or 2 devices tested) do not allow consideration of part-to-part variability. High dose rates were used despite LT3482 and MSK130 having potential enhanced low dose rate sensitivity (ELDRS). Care should be taken in interpreting results given these limitations.

Total Ionizing Dose (TID)↗

Hardened Containment Vent System Dose Considerations for FLEX

Fukushima lessons learned include adding diverse and flexible mitigation strategies, or FLEX, that will increase defense-in-depth for beyond-design-basis (BDB) scenarios to address an Extended Loss of AC Power (ELAP). FLEX and NRC order EA-13-109 require improvements to the reliability of Hardened Containment Vent Systems (HCVS) for Mark I and II boiling water reactors (BWR) for venting of the core under severe accident conditions. NEI HCVSWP-02 provides generic guidance to determine radiological dose from HCVS piping. This paper presents a more refined analysis tool and method to assess the doses from the HCVS piping resulting from a failed core during an ELAP for a representative Mark I BWR. The dose rates up to 4' from the HCVS pipe at 8 hours after ELAP and over time at 3' are provided for the different cases. HCVS pipe length can affect dose rates farther from the pipe. As expected, dose rates versus time for representative plant case 2 drop off quickly as the HCVS activity is vented out. The dose rate results show that significant protection for personnel would be required in the areas near HCVS piping during certain time frames of containment venting. Equipment in the vicinity of the vent piping should also be evaluated for impact of radiation exposure. The results for the representative plant cases are higher and lower than the scaled NEI results depending on the model assumptions, limitations and considerations which can change as the HCVS design evolves. Using the NEI paper with scaling factors may not be conservative for all applications.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗

Dose Rate Analysis of As-Loaded Spent Nuclear Fuel Casks - Paper 97

Used Nuclear Fuel Storage, Transportation and Disposal Analysis Resource and Data System (UNF-ST[and]DARDS) is a comprehensive data and calculation capability for UNF safety assessments currently being developed at Oak Ridge National Laboratory through a collaborative effort of multiple national laboratories and industry participants. The purpose of UNF-ST[and]DARDS is to provide a unified domestic UNF system of data and analysis capabilities in support of U.S. Department of Energy waste management and fuel cycle-related objectives. UNF-ST[and]DARDS is designed to provide safety assessments for UNF storage, transportation, and disposal systems based on actual characteristics of the as-loaded UNF (e.g., fuel assembly burnup, enrichment, decay time, cladding integrity, etc.). The cask-specific safety evaluations allow quantification of realistic safety margins and conditions and provide the technical basis for addressing concerns related to potential fuel failure (e.g., for high-burnup fuel). This paper describes the UNF-ST[and]DARDS methodology for calculating radiation dose rates for U.S. Nuclear Regulatory Commission (NRC) licensed casks based on actual UNF canister contents. Realistic dose rate values based on actual canister contents may be used in place of bounding dose rate values to support development of repackaging operations procedures, evaluation of radiation-related transportation risks, and communication with stakeholders. UNF-ST[and]DARDS capabilities have been recently expanded to include automated radiation source term calculations and dose rate analyses of as-loaded transportation casks. This unique capability determines realistic dose rate values based on actual canister UNF contents that may be used in radiation dose assessments to demonstrate safe transportation of commercial UNF. (authors)

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

Use of the portable decay gamma source feature in the R2Smesh code system for the accurate estimation of photon radiation dose fields around activated ITER components - Paper 111

The R2Smesh ('Rigorous 2-step') code system, developed by KIT for the determination of shut-down dose rate distribution on mesh grid, can be utilized to provide photon radiation dose field around activated components which are moved from the irradiation site in fusion reactor to another external location. R2Smesh couples MCNP transport calculations and FISPACT inventory calculations through suitable interfaces utilizing MCNP mesh tally capability. Neutron flux and the decay gamma source are provided with high resolution on the mesh grid superimposed to the real geometry to take into account the spatial variations of the flux and the decay gamma source distributions. This feature enables the decay gamma source distribution to be transferred from the irradiation site in the reactor to any other external location for the determination of photon flux and dose rate distributions. In this work, we applied the feature of the portable decay gamma source in R2Smesh code system to a dose rate analysis for a tunnel connecting the ITER tokamak complex building (TCB) and the hot cell facility building (HCFB). This paper presents the use of the portability feature of the decay gamma source in R2Smesh interface code system developed by KIT for a dose rate analysis of the ITER tunnel connecting TCB and HCFB. This application shows that the decay gamma source of the activated components could be transferred successfully from one coordinate system to another coordinate system and superimposed to the geometry of the components. This is very useful when the activated components need to be transported from the reactor to somewhere else for maintenance, testing or storage and the dose rate analysis is requested. Another portable feature, which could convert the 3D decay gamma source distribution generated by R2Smesh system to the MCNP 'SDEF' card source description and avoid the use of source sampling subroutine, is under consideration. With this feature, one decay gamma source result for the specific reactor components could be shared by different institutions who need to use the same decay gamma source for different analysis. (authors)

61 RADIATION PROTECTION AND DOSIMETRY↗

Effective dose rate coefficients for exposure to contaminated soil

The Oak Ridge National Laboratory Center for Radiation Protection Knowledge has undertaken calculations related to various environmental exposure scenarios. A previous paper reported the results for submersion in radioactive air and immersion in water using age-specific mathematical phantoms. This paper presents age-specific effective dose rate coefficients derived using stylized mathematical phantoms for exposure to contaminated soils. Dose rate coefficients for photon, electron, and positrons of discrete energies were calculated and folded with emissions of 1252 radionuclides addressed in ICRP Publication 107 to determine equivalent and effective dose rate coefficients. The MCNP6 radiation transport code was used for organ dose rate calculations for photons and the contribution of electrons to skin dose rate was derived using point-kernels. Bremsstrahlung and annihilation photons of positron emission were evaluated as discrete photons. As a result, the coefficients calculated in this work compare favorably to those reported in the US Federal Guidance Report 12 as well as by other authors who employed voxel phantoms for similar exposure scenarios.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

SU-E-P-55: The Reaserch of Cervical Cancer Delivered with Constant Dose Rate and Gantry Speed Arc Therapy(CDR-CAS-IMAT) On Conventional Linac

Purpose: Postoperative cervical cancer patients with large target volume and the target shape is concave, treatmented with static intensity-modulated radiotherapy (IMRT) is time consuming. The purpose of this study is to investigate using constant dose rate and gantry speed arc therapy(CDR-CAS-IMAT) on conventional linear accelrator, by comparing with the IMRT technology to evaluate the performance of CDR-CAS-IMAT on postoperative cervical cancer patients. Methods: 18 cervical cancer patients treated with IMRT on Varian 23IX were replanted using CDR-CAS-IMAT. The plans were generated on Oncentra v4.1 planning system, PTV was prescribed to 50.4 Gy in 28 fractions. Plans were evaluated based on the ability to meet the dose volume histogram. The homogeneity index (HI), conformity index (CI) of target volume, the dose of organs at risk, radiation delivery time and monitor units were also compared. SPSS 19.0 software paired T-test analysis was carried out on the two sets of data. Results: Compared with the IMRT plans PTV’s CI (t= 3.85, P =0.001), CTV’s CI, HI, D90, D95, D98, V95, V98, V100 (t=4.21, −3.18, 2.13, 4.65, 7.79, 2.29, 6.00, 2.13, p=0.001, 0.005, 0.049, 0.000, 0.000, 0.035, 0.000, 0.049), and cord D2 and rectum V40 (t=−2.65, −2.47, p= P =0.017, 0.025), and treatment time and MU (t=−36.0, −6.26, P =0.000, 0.000) were better than that of IMRT group. But the IMRT plans in terms of decreasing bladder V50, bowel V30 (t=2.14, 3.00, P =0.048, 0.008) and low dose irradiation volume were superior to that of CDR-CAS-IMAT plans. There were no significant differences in other statistical index. Conclusion: Cervical cancer patients with CDR-CAS-IMAT on Varian Clinical 23IX can get equivalent or superior dose distribution compared with the IMRT technology. IMAT have much less treatment time and MU can reduce the uncertainty factor and patient discomfort in treatment. This work was supported by the Medical Science Foundation of the health department of Hebei Province (No. 20130253)

60 APPLIED LIFE SCIENCES↗

Ultra-low-dose limited renal CT for volumetric stone surveillance: advantages over standard unenhanced CT

Purpose: To describe and validate a novel CT approach using volumetric analysis for renal stone surveillance. Materials and methods: This prospective trial consisted of a standard low-dose non-contrast CT (SLD) of the abdomen and pelvis, immediately followed by an ultra-low-dose non-contrast CT (ULD) with reconstruction limited to the kidneys. A novel dedicated software tool was applied that automates stone volume, density, and maximum linear size. Manual linear stone size was measured by a radiology fellow and urology resident for comparison. CT dose and clinical charges were considered. Results: Twenty-eight stones in 16 patients were analyzed. Mean effective dose of ULD CT was 0.57 mSv, an average 92% lower than the SLD CT dose. For SLD, mean size ± SD (range) (mm) was 7.9 ± 6.2 (2.6–30.5) for Reader 1, 7.3 ± 6 (2.4–30.7) for Reader 2, and 9.3 ± 6.4 (3.7–33.1) for the automated software. For ULD, mean size ± SD (range) (mm) was 7.3 ± 6 (2.5–30.5) for Reader 1, 7.2 ± 6.1 (2.1–30.7) for Reader 2, and 9.1 ± 6.4 (4.2–32.8) for the automated software. Automated stone diameters were larger than manual diameters for 27/28 stones (mean difference, 23%); difference was ≥ 2 mm in 30%. Average variability between manual measurements was 8.6% (SLD) and 7.8% (ULD), but was 0% for the automated technique. Our institutional charge for ULD renal CT is slightly less than renal US, and > 4× less than SLD CT. The Medicare global fee for the ULD renal CT is less than the SLD CT of the abdomen and pelvis. Conclusions: This focused stone surveillance CT protocol is lower cost and lower dose compared to the standard CT approach. Automated assessment of stone burden provides improved reproducibility over manual linear measurement and offers the advantages of 3D measurements and volumetry. We now offer and perform this protocol in routine clinical practice for stone surveillance.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Benzo[a]pyrene (BaP) metabolites predominant in human plasma following escalating oral micro-dosing with [ 14 C]-BaP

Benzo[a]pyrene (BaP) is formed by incomplete combustion of organic materials (petroleum, coal, tobacco, etc.). BaP is designated by the International Agency for Research on Cancer as a group 1 known human carcinogen; a classification supported by numerous studies in preclinical models and epidemiology studies of exposed populations. Risk assessment relies on toxicokinetic and cancer studies in rodents at doses 5–6 orders of magnitude greater than average human uptake. Using a dose–response design at environmentally relevant concentrations, this study follows uptake, metabolism, and elimination of [ 14 C]-BaP in human plasma by employing UPLC - accelerator mass spectrometry (UPLC-AMS). Volunteers were administered 25, 50, 100, and 250 ng (2.7–27 nCi) of [ 14 C]-BaP (with interceding minimum 3-week washout periods) with quantification of parent [ 14 C]-BaP and metabolites in plasma measured over 48 h. [ 14 C]-BaP median T max was 30 min with C max and area under the curve (AUC) approximating dose-dependency. Marked inter-individual variability in plasma pharmacokinetics following a 250 ng dose was seen with 7 volunteers as measured by the C max (8.99 ± 7.08 ng × mL -1 ) and AUC0-48hr (68.6 ± 64.0 fg × hr -1 × mL -1 ). Approximately 3–6% of the [ 14 C] recovered (AUC 0-48 hr ) was parent compound, demonstrating extensive metabolism following oral dosing. Metabolite profiles showed that, even at the earliest time-point (30 min), a substantial percentage of [ 14 C] in plasma was polar BaP metabolites. The best fit modeling approach identified non-compartmental apparent volume of distribution of BaP as significantly increasing as a function of dose (p = 0.004). Bay region tetrols and dihydrodiols predominated, suggesting not only was there extensive first pass metabolism but also potentially bioactivation. AMS enables the study of environmental carcinogens in humans with de minimus risk, allowing for important testing and validation of physiologically based pharmacokinetic models derived from animal data, risk assessment, and the interpretation of data from high-risk occupationally exposed populations.

59 BASIC BIOLOGICAL SCIENCES↗

Irradiation of rainbow trout at early life stages results in a proteomic legacy in adult gills. Part B; the effect of a second radiation dose, after one year, on the proteomic responses in the irradiated and non-irradiated bystander fish

Highlights: • The effects of a 2nd radiation dose at one year were investigated. • The bystander effect proteomic responses in non-irradiated fish were investigated. • The effects of a 2nd radiation dose differed to those of early life irradiation only. • Proteomic responses of irradiated fish indicated tumorigenesis or cancer progression. • Bystander effect proteomic responses were tumorigenic, detrimental or uncertain. This study extends the investigation of the legacy effects of exposure to a single radiation dose at one of four early life stages, in adult rainbow trout (Part A), by examining the effects of a second identical dose after one year; i.e. egg 48 h after fertilisation (48 h egg) + 1 year, eyed egg + 1 year, yolk sac larvae (YSL) + 1 year and first feeder + 1 year. This included the induction of a bystander effect in non-irradiated trout which had swam with the irradiated fish. The second radiation dose negated any beneficial proteomic responses following early life stage irradiation only, particularly irradiation of 48 h eggs and eyed eggs (Part A). Instead the responses after early life stage + 1 year irradiation are consistently associated with tumorigenesis, cancer progression, or are otherwise damaging: upregulation of alpha-globin 1 (YSL + 1 year and first feeders + 1 year) and downregulation of histone H1, type II keratin, malate dehydrogenase 2–2, Na/K ATPase alpha subunit isoform 1b, nucleoside diphosphate kinase (48 h egg + 1 year), electron transfer flavoprotein subunit alpha (eyed egg + 1 year), 60 S ribosomal protein L30 (YSL + 1 year) and haemoglobin subunit beta-4 (first feeder + 1 year). Most significantly the second radiation dose also negated the overwhelmingly beneficial bystander effect proteomic responses induced by trout irradiated at an early life stage only (Part A). Instead the bystander effect proteomic changes induced by trout irradiated at an early life stage and again at 1 year have been associated with uncertain, with respect to tumorigenesis, or detrimental effects; upregulation of alpha-globin 1 (YSL + 1 year and first feeder + 1 year) and downregulation of malate dehydrogenase 2–2, nucleoside diphosphate kinase (48 h egg + 1 year), transferrin precursor (eyed egg + 1 year), 60 S ribosomal protein L30 (YSL + 1 year) and serine / threonine-protein phosphatase 2 A 65 kDa (first feeder + 1 year). This difference between the bystander effect induced proteomic changes following early life stage irradiation only and early life stage + 1 year irradiation may indicate a fundamental change in the non-targeted effects of radiation following multiple exposure to radiation.

54 ENVIRONMENTAL SCIENCES↗

Projected Second Tumor Risk and Dose to Neurocognitive Structures After Proton Versus Photon Radiotherapy for Benign Meningioma

Purpose: To calculated projected second tumor rates and dose to organs at risk (OAR) in patients with benign intracranial meningioma (BM), according to dosimetric comparisons between proton radiotherapy (PRT) and photon radiotherapy (XRT) treatment plans. Methods and Materials: Ten patients with BM treated at Massachusetts General Hospital during 2006-2010 with PRT were replanned with XRT (intensity-modulated or three-dimensional conformal radiotherapy), optimizing dose to the tumor while sparing OAR. Total dose was 54 Gy in 1.8 Gy per fraction for all plans. We calculated equivalent uniform doses, normal tissue complication probabilities, and whole brain-based estimates of excess risk of radiation-associated intracranial second tumors. Results: Excess risk of second tumors was significantly lower among PRT compared with XRT plans (1.3 vs. 2.8 per 10,000 patients per year, p < 0.002). Mean equivalent uniform doses were lower among PRT plans for the whole brain (19.0 vs. 22.8 Gy, p < 0.0001), brainstem (23.8 vs. 35.2 Gy, p = 0.004), hippocampi (left, 13.5 vs. 25.6 Gy, p < 0.0001; right, 7.6 vs. 21.8 Gy, p = 0.001), temporal lobes (left, 25.8 vs. 34.6 Gy, p = 0.007; right, 25.8 vs. 32.9 Gy, p = 0.008), pituitary gland (29.2 vs. 37.0 Gy, p = 0.047), optic nerves (left, 28.5 vs. 33.8 Gy, p = 0.04; right, 25.1 vs. 31.1 Gy, p = 0.07), and cochleas (left, 12.2 vs. 15.8 Gy, p = 0.39; right,1.5 vs. 8.8 Gy, p = 0.01). Mean normal tissue complication probability was <1% for all structures and not significantly different between PRT and XRT plans. Conclusions: Compared with XRT, PRT for BM decreases the risk of RT-associated second tumors by half and delivers significantly lower doses to neurocognitive and critical structures of vision and hearing.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Long-Term Outcomes After High-Dose Postprostatectomy Salvage Radiation Treatment

Purpose: To review the impact of high-dose radiotherapy (RT) in the postprostatectomy salvage setting on long-term biochemical control and distant metastases-free survival, and to identify clinical and pathologic predictors of outcomes. Methods and Materials: During 1988-2007, 285 consecutive patients were treated with salvage RT (SRT) after radical prostatectomy. All patients were treated with either three-dimensional conformal RT or intensity-modulated RT. Two hundred seventy patients (95%) were treated to a dose {>=}66 Gy, of whom 205 (72%) received doses {>=}70 Gy. Eighty-seven patients (31%) received androgen-deprivation therapy as a component of their salvage treatment. All clinical and pathologic records were reviewed to identify treatment risk factors and response. Results: The median follow-up time after SRT was 60 months. Seven-year actuarial prostate-specific antigen (PSA) relapse-free survival and distant metastases-free survival were 37% and 77%, respectively. Independent predictors of biochemical recurrence were vascular invasion (p < 0.01), negative surgical margins (p < 0.01), presalvage PSA level >0.4 ng/mL (p < 0.01), androgen-deprivation therapy (p = 0.03), Gleason score {>=}7 (p = 0.02), and seminal vesicle involvement (p = 0.05). Salvage RT dose {>=}70 Gy was not associated with improvement in biochemical control. A doubling time <3 months was the only independent predictor of metastatic disease (p < 0.01). There was a trend suggesting benefit of SRT dose {>=}70 Gy in preventing clinical local failure in patients with radiographically visible local disease at time of SRT (7 years: 90% vs. 79.1%, p = 0.07). Conclusion: Salvage RT provides effective long-term biochemical control and freedom from metastasis in selected patients presenting with detectable PSA after prostatectomy. Androgen-deprivation therapy was associated with improvement in biochemical progression-free survival. Clinical local failures were rare but occurred most commonly in patients with greater burden of disease at time of SRT as reflected by either radiographic imaging or a greater PSA level. Salvage radiation doses {>=}70 Gy may ultimately be most beneficial in these patients, but this needs to be further studied.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Relative Importance of Hip and Sacral Pain Among Long-Term Gynecological Cancer Survivors Treated With Pelvic Radiotherapy and Their Relationships to Mean Absorbed Doses

Purpose: To investigate the relative importance of patient-reported hip and sacral pain after pelvic radiotherapy (RT) for gynecological cancer and its relationship to the absorbed doses in these organs. Methods and Materials: We used data from a population-based study that included 650 long-term gynecological cancer survivors treated with pelvic RT in the Gothenburg and Stockholm areas in Sweden with a median follow-up of 6 years (range, 2-15) and 344 population controls. Symptoms were assessed through a study-specific postal questionnaire. We also analyzed the hip and sacral dose-volume histogram data for 358 of the survivors. Results: Of the survivors, one in three reported having or having had hip pain after completing RT. Daily pain when walking was four times as common among the survivors compared to controls. Symptoms increased in frequency with a mean absorbed dose >37.5 Gy. Also, two in five survivors reported pain in the sacrum. Sacral pain also affected their walking ability and tended to increase with a mean absorbed dose >42.5 Gy. Conclusions: Long-term survivors of gynecological cancer treated with pelvic RT experience hip and sacral pain when walking. The mean absorbed dose was significantly related to hip pain and was borderline significantly related to sacral pain. Keeping the total mean absorbed hip dose below 37.5 Gy during treatment might lower the occurrence of long-lasting pain. In relation to the controls, the survivors had a lower occurrence of pain and pain-related symptoms from the hips and sacrum compared with what has previously been reported for the pubic bone.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Esophageal Toxicity From High-Dose, Single-Fraction Paraspinal Stereotactic Radiosurgery

Purpose: To report the esophageal toxicity from single-fraction paraspinal stereotactic radiosurgery (SRS) and identify dosimetric and clinical risk factors for toxicity. Methods and Materials: A total of 204 spinal metastases abutting the esophagus (182 patients) were treated with high-dose single-fraction SRS during 2003-2010. Toxicity was scored using the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 4.0. Dose-volume histograms were combined to generate a comprehensive atlas of complication incidence that identifies risk factors for toxicity. Correlation of dose-volume factors with esophageal toxicity was assessed using Fisher's exact test and logistic regression. Clinical factors were correlated with toxicity. Results: The median dose to the planning treatment volume was 24 Gy. Median follow-up was 12 months (range, 3-81). There were 31 (15%) acute and 24 (12%) late esophageal toxicities. The rate of grade {>=}3 acute or late toxicity was 6.8% (14 patients). Fisher's exact test resulted in significant median splits for grade {>=}3 toxicity at V12 = 3.78 cm{sup 3} (relative risk [RR] 3.7, P=.05), V15 = 1.87 cm{sup 3} (RR 13, P=.0013), V20 = 0.11 cm{sup 3} (RR 6, P=0.01), and V22 = 0.0 cm{sup 3} (RR 13, P=.0013). The median split for D2.5 cm{sup 3} (14.02 Gy) was also a significant predictor of toxicity (RR 6; P=.01). A highly significant logistic regression model was generated on the basis of D2.5 cm{sup 3}. One hundred percent (n = 7) of grade {>=}4 toxicities were associated with radiation recall reactions after doxorubicin or gemcitabine chemotherapy or iatrogenic manipulation of the irradiated esophagus. Conclusions: High-dose, single-fraction paraspinal SRS has a low rate of grade {>=}3 esophageal toxicity. Severe esophageal toxicity is minimized with careful attention to esophageal doses during treatment planning. Iatrogenic manipulation of the irradiated esophagus and systemic agents classically associated with radiation recall reactions are associated with development of grade {>=}4 toxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Intensity Modulated Radiation Therapy With Dose Painting to Treat Rhabdomyosarcoma

Purpose: To examine local control and patterns of failure in rhabdomyosarcoma patients treated with intensity modulated radiation therapy (RT) with dose painting (DP-IMRT). Patients and Methods: A total of 41 patients underwent DP-IMRT with chemotherapy for definitive treatment. Nineteen also underwent surgery with or without intraoperative RT. Fifty-six percent had alveolar histologic features. The median interval from beginning chemotherapy to RT was 17 weeks (range, 4-25). Very young children who underwent second-look procedures with or without intraoperative RT received reduced doses of 24-36 Gy in 1.4-1.8-Gy fractions. Young adults received 50.4 Gy to the primary tumor and lower doses of 36 Gy in 1.8-Gy fractions to at-risk lymph node chains. Results: With 22 months of median follow-up, the actuarial local control rate was 90%. Patients aged {<=}7 years who received reduced overall and fractional doses had 100% local control, and young adults had 79% (P=.07) local control. Three local failures were identified in young adults whose primary target volumes had received 50.4 Gy in 1.8-Gy fractions. Conclusions: DP-IMRT with lower fractional and cumulative doses is feasible for very young children after second-look procedures with or without intraoperative RT. DP-IMRT is also feasible in adolescents and young adults with aggressive disease who would benefit from prophylactic RT to high-risk lymph node chains, although dose escalation might be warranted for improved local control. With limited follow-up, it appears that DP-IMRT produces local control rates comparable to those of sequential IMRT in patients with rhabdomyosarcoma.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Impact of Internal Metallic Ports in Temporary Tissue Expanders on Postmastectomy Radiation Dose Distribution

Purpose: Temporary tissue expanders (TTE) with an internal magnetic metal port (IMP) have been increasingly used for breast reconstruction in post-mastectomy patients who receive radiation therapy (XRT). We evaluated XRT plans of patients with IMP to determine its effect on XRT dose distribution. Methods and Materials: Original treatment plans with CT simulation scans of 24 consecutive patients who received XRT (ORI), planned without heterogeneity corrections, to a reconstructed breast containing an IMP were used. Two additional treatment plans were then generated: one treatment plan with the IMP assigned the electron density of the rare earth magnet, nickel plated neodymium-iron-boron (HET), and a second treatment plan with the IMP assigned a CT value of 1 to simulate a homogeneous breast without an IMP (BRS). All plans were prescribed 50 Gy to the reconstructed breast (CTV). Results: CTV coverage by 50 Gy was significantly lower in the HET (mean 87.7% CTV) than in either the ORI (mean 99.7% CTV, P<.001) or BRS plans (mean 95.0% CTV, P<.001). The effect of the port was more pronounced on CT slices containing the IMP with prescription dose coverage of the CTV being less in the HET than in either ORI (mean difference 33.6%, P<.01) or BRS plans (mean difference 30.1%, P<.001). HET had a less homogeneous and conformal dose distribution than BRS or ORI. Conclusion: IMPs increase dose heterogeneity and reduce dose to the breast CTV through attenuation of the beam. For optimal XRT treatment, heterogeneity corrections should be used in XRT planning for patients with TTE with IMP, as the IMP impacts dose distribution.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Dose and Spatial Effects in Long-Distance Radiation Signaling In Vivo: Implications for Abscopal Tumorigenesis

Purpose: To investigate the dose and spatial dependence of abscopal radiation effects occurring in vivo in the mouse, along with their tumorigenic potential in the central nervous system (CNS) of a radiosensitive mouse model. Methods and Materials: Patched1 (Ptch1){sup +/−} mice, carrying a germ-line heterozygous inactivating mutation in the Ptch1 gene and uniquely susceptible to radiation damage in neonatal cerebellum, were exposed directly to ionizing radiation (1, 2, or 3 Gy of x-rays) or treated in a variety of partial-body irradiation protocols, in which the animals' head was fully protected by suitable lead cylinders while the rest of the body was exposed to x-rays in full or in part. Apoptotic cell death was measured in directly irradiated and shielded cerebellum shortly after irradiation, and tumor development was monitored in lifetime groups. The same endpoints were measured using different shielding geometries in mice irradiated with 3 or 10 Gy of x-rays. Results: Although dose-dependent cell death was observed in off-target cerebellum for all doses and shielding conditions tested, a conspicuous lack of abscopal response for CNS tumorigenesis was evident at the lowest dose of 1 Gy. By changing the amount of exposed body volume, the shielding geometry could also significantly modulate tumorigenesis depending on dose. Conclusions: We conclude that interplay between radiation dose and exposed tissue volume plays a critical role in nontargeted effects occurring in mouse CNS under conditions relevant to humans. These findings may help understanding the mechanisms of long-range radiation signaling in harmful effects, including carcinogenesis, occurring in off-target tissues.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Predictive Models for Regional Hepatic Function Based on 99mTc-IDA SPECT and Local Radiation Dose for Physiologic Adaptive Radiation Therapy

Purpose: High-dose radiation therapy (RT) for intrahepatic cancer is limited by the development of liver injury. This study investigated whether regional hepatic function assessed before and during the course of RT using 99mTc-labeled iminodiacetic acid (IDA) single photon emission computed tomography (SPECT) could predict regional liver function reserve after RT. Methods and Materials: Fourteen patients treated with RT for intrahepatic cancers underwent dynamic 99mTc-IDA SPECT scans before RT, during, and 1 month after completion of RT. Indocyanine green (ICG) tests, a measure of overall liver function, were performed within 1 day of each scan. Three-dimensional volumetric hepatic extraction fraction (HEF) images of the liver were estimated by deconvolution analysis. After coregistration of the CT/SPECT and the treatment planning CT, HEF dose–response functions during and after RT were generated. The volumetric mean of the HEFs in the whole liver was correlated with ICG clearance time. Three models, dose, priori, and adaptive models, were developed using multivariate linear regression to assess whether the regional HEFs measured before and during RT helped predict regional hepatic function after RT. Results: The mean of the volumetric liver HEFs was significantly correlated with ICG clearance half-life time (r=−0.80, P<.0001), for all time points. Linear correlations between local doses and regional HEFs 1 month after RT were significant in 12 patients. In the priori model, regional HEF after RT was predicted by the planned dose and regional HEF assessed before RT (R=0.71, P<.0001). In the adaptive model, regional HEF after RT was predicted by regional HEF reassessed during RT and the remaining planned local dose (R=0.83, P<.0001). Conclusions: 99mTc-IDA SPECT obtained during RT could be used to assess regional hepatic function and helped predict post-RT regional liver function reserve. This could support individualized adaptive radiation treatment strategies to maximize tumor control and minimize the risk of liver damage.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Patterns of Local Recurrence and Dose Fractionation of Adjuvant Radiation Therapy in 462 Patients With Soft Tissue Sarcoma of Extremity and Trunk Wall

Purpose: To study the impact of dose fractionation of adjuvant radiation therapy (RT) on local recurrence (LR) and the relation of LR to radiation fields. Methods and Materials: LR rates were analyzed in 462 adult patients with soft tissue sarcoma who underwent surgical excision and adjuvant RT at five Scandinavian sarcoma centers from 1998 to 2009. Medical records were reviewed for dose fractionation parameters and to determine the location of the LR relative to the radiation portals. Results: Fifty-five of 462 patients developed a LR (11.9%). Negative prognostic factors included intralesional surgical margin (hazard ratio [HR]: 7.83, 95% confidence interval [CI]: 3.08-20.0), high malignancy grade (HR: 5.82, 95% CI: 1.31-25.8), age at diagnosis (HR per 10 years: 1.27, 95% CI: 1.03-1.56), and malignant peripheral nerve sheath tumor histological subtype (HR: 6.66, 95% CI: 2.56-17.3). RT dose was tailored to margin status. No correlation between RT dose and LR rate was found in multiple Cox regression analysis. The majority (65%) of LRs occurred within the primary RT volume. Conclusions: No significant dose–response effect of adjuvant RT was demonstrated. Interestingly, patients given 45-Gy accelerated RT (1.8 Gy twice daily/2.5 weeks) had the best local outcome. A total dose of 50 Gy in 25 fractions seemed adequate following wide margin surgery. The risk of LR was associated with histopathologic subtype, which should be included in the treatment algorithm of adjuvant RT in soft tissue sarcoma.

62 RADIOLOGY AND NUCLEAR MEDICINE↗