In Vivo Simvastatin and Brain Radiation in a Model of HER2 + Inflammatory Breast Cancer Brain Metastasis.

Purpose: Inhibiting HMG-CoA reductase with simvastatin prevents breast cancer metastases in preclinical models and radiosensitizes monolayer and stem-like IBC cell lines in vitro . Given the extensive use of simvastatin worldwide and its expected penetration into the brain, we examined whether regulating cholesterol with simvastatin affected IBC3 HER2+ brain metastases. Methods and Materials: Breast cancer cell lines KPL4 and MDA-IBC3 were examined in vitro for DNA repair after radiation with or without statin treatment. Brain metastasis endpoints were examined in the MDA-IBC3 brain metastasis model after ex vivo exposure to lipoproteins and after tail vein injections with and without whole-brain radiotherapy (WBR) and oral statin exposure. Results: Ex vivo preculture of MDA-IBC3 cells with very low-density lipoprotein (vLDL) enhanced the growth of colonized lesions in the brain in vivo compared with control or high-density lipoprotein (HDL), and concurrent oral simvastatin/ WBR reduced the incidence of micrometastatic lesions evaluated 10 days after WBR. However, statin, with or without WBR, did not reduce the incidence, burden, or number of macrometastatic brain lesions evaluated 5 weeks after WBR. Conclusions: Although a role for cholesterol biosynthesis is demonstrated in DNA repair and response to whole brain radiation in this model, durable in vivo efficacy of concurrent whole brain irradiation and oral statin was not demonstrated.

Condensed Matter Systems Exposed to Radiation: Multiscale Theory, Simulations, and Experiment.

This roadmap reviews the new, highly interdisciplinary research field studying the behavior of condensed matter systems exposed to radiation. The Review highlights several recent advances in the field and provides a roadmap for the development of the field over the next decade. Condensed matter systems exposed to radiation can be inorganic, organic, or biological, finite or infinite, composed of different molecular species or materials, exist in different phases, and operate under different thermodynamic conditions. Many of the key phenomena related to the behavior of irradiated systems are very similar and can be understood based on the same fundamental theoretical principles and computational approaches. The multiscale nature of such phenomena requires the quantitative description of the radiation-induced effects occurring at different spatial and temporal scales, ranging from the atomic to the macroscopic, and the interlinks between such descriptions. The multiscale nature of the effects and the similarity of their manifestation in systems of different origins necessarily bring together different disciplines, such as physics, chemistry, biology, materials science, nanoscience, and biomedical research, demonstrating the numerous interlinks and commonalities between them. This research field is highly relevant to many novel and emerging technologies and medical applications.

PTCOG Gastrointestinal Subcommittee Lower Gastrointestinal Tract Malignancies Consensus Statement.

Purpose: Radiotherapy delivery in the definitive management of lower gastrointestinal (LGI) tract malignancies is associated with substantial risk of acute and late gastrointestinal (GI), genitourinary, dermatologic, and hematologic toxicities. Advanced radiation therapy techniques such as proton beam therapy (PBT) offer optimal dosimetric sparing of critical organs at risk, achieving a more favorable therapeutic ratio compared with photon therapy. Materials and Methods: The international Particle Therapy Cooperative Group GI Subcommittee conducted a systematic literature review, from which consensus recommendations were developed on the application of PBT for LGI malignancies. Results: Eleven recommendations on clinical indications for which PBT should be considered are presented with supporting literature, and each recommendation was assessed for level of evidence and strength of recommendation. Detailed technical guidelines pertaining to simulation, treatment planning and delivery, and image guidance are also provided. Conclusion: PBT may be of significant value in select patients with LGI malignancies. Additional clinical data are needed to further elucidate the potential benefits of PBT for patients with anal cancer and rectal cancer.

EFOMP policy statement 18: Medical physics education for the non-physics healthcare professions.

Although Medical Physics educators have historically contributed to the education of the non-physics healthcare professions, their role was not studied in a systematic manner. In 2009, EFOMP set up a group to research the issue. In their first paper, the group carried out an extensive literature review regarding physics teaching for the non-physics healthcare professions. Their second paper reported the results of a pan-European survey of physics curricula delivered to the healthcare professions and a Strengths-Weaknesses-Opportunities-Threats (SWOT) audit of the role. The group's third paper presented a strategic development model for the role, based on the SWOT data. A comprehensive curriculum development model was subsequently published, whilst plans were laid to develop the present policy statement. This policy statement presents mission and vision statements for Medical Physicists teaching non-physics users of medical devices and physical agents, best practices for teaching non-physics healthcare professionals, a stepwise process for curriculum development (content, method of delivery and assessment), and summary recommendations based on the aforementioned research studies.

Absolute dosimetry for FLASH proton pencil beam scanning radiotherapy.

A paradigm shift is occurring in clinical oncology exploiting the recent discovery that short pulses of ultra-high dose rate (UHDR) radiation-FLASH radiotherapy-can significantly spare healthy tissues whilst still being at least as effective in curing cancer as radiotherapy at conventional dose rates. These properties promise reduced post-treatment complications, whilst improving patient access to proton beam radiotherapy and reducing costs. However, accurate dosimetry at UHDR is extremely complicated. This work presents measurements performed with a primary-standard proton calorimeter and derivation of the required correction factors needed to determine absolute dose for FLASH proton beam radiotherapy with an uncertainty of 0.9% (1[Formula: see text]), in line with that of conventional treatments. The establishment of a primary standard for FLASH proton radiotherapy improves accuracy and consistency of the dose delivered and is crucial for the safe implementation of clinical trials, and beyond, for this new treatment modality.

Pre-treatment analysis of non-rigid variations can assist robust intensity-modulated proton therapy plan selection for head and neck patients.

PURPOSE: To incorporate small non-rigid variations of head and neck patients into the robust evaluation of intensity-modulated proton therapy (IMPT) for the selection of robust treatment plans. METHODS: A cohort of 20 nasopharynx cancer patients with weekly kilovoltage CT (kVCT) and 15 oropharynx cancer patients with weekly cone-beam CT (CBCT) were retrospectively included. Anatomical variations between week 0/week 1 of treatment were acquired using deformable image registration (DIR) for all 35 patients and then applied to the planning CT of four patients who have kVCT scanned each week to simulate potential small non-rigid variations (sNRVs). The robust evaluations were conducted on IMPT plans with: (1) different number of beam fields from 3-field to 5-field; (2) different beam angles. The robust evaluation before treatment, including the sNRVs and setup uncertainty, referred to as sNRV+R evaluation was compared with the conventional evaluation (without sNRVs) in terms of robustness consistency with the gold standard evaluation based on weekly CT. RESULTS: Among four patients (490 scenarios), we observed a maximum difference in the sNRV+R evaluation to the nominal dose of: 9.37% dose degradation on D95 of clinical target volumes (CTVs), increase in mean dose (D mean $_{\text{mean}}$ ) of parotid 11.87 Gy, increase in max dose (D max $_{\text{max}}$ ) of brainstem 20.82 Gy. In contrast, in conventional evaluation, we observed a maximum difference to the nominal dose of: 7.58% dose degradation on D95 of the CTVs, increase in parotid D mean $_{\text{mean}}$ by 4.88 Gy, increase in brainstem D max $_{\text{max}}$ by 13.5 Gy. In the measurement of the robustness ranking consistency with the gold standard evaluation, the sNRV+R evaluation was better or equal to the conventional evaluation in 77% of cases, particularly, better on spinal cord, parotid glands, and low-risk CTV. CONCLUSION: This study demonstrated the additional dose discrepancy that sNRVs can make. The inclusion of sNRVs can be beneficial to robust evaluation, providing information on clinical uncertainties additional to the conventional rigid isocenter shift.

Ultrahigh dose rate pencil beam scanning proton dosimetry using ion chambers and a calorimeter in support of first in-human FLASH clinical trial.

PURPOSE: To provide ultrahigh dose rate (UHDR) pencil beam scanning (PBS) proton dosimetry comparison of clinically used plane-parallel ion chambers, PTW (Physikalisch-Technische Werkstaetten) Advanced Markus and IBA (Ion Beam Application) PPC05, with a proton graphite calorimeter in a support of first in-human proton FLASH clinical trial. METHODS: Absolute dose measurement intercomparison of the plane-parallel plate ion chambers and the proton graphite calorimeter was performed at 5-cm water-equivalent depth using rectangular 250-MeV single-layer treatment plans designed for the first in-human FLASH clinical trial. The dose rate for each field was designed to remain above 60 Gy/s. The ion recombination effects of the plane-parallel plate ion chambers at various bias voltages were also investigated in the range of dose rates between 5 and 60 Gy/s. Two independent model-based extrapolation methods were used to calculate the ion recombination correction factors ks to compare with the two-voltage technique from most widely used clinical protocols. RESULTS: The mean measured dose to water with the proton graphite calorimeter across all the predefined fields is 7.702 ± 0.037 Gy. The average ratio over the predefined fields of the PTW Advanced Markus chamber dose to the calorimeter reference dose is 1.002 ± 0.007, whereas the IBA PPC05 chamber shows ∼3% higher reading of 1.033 ± 0.007. The relative differences in the ks values determined from between the linear and quadratic extrapolation methods and the two-voltage technique for the PTW Advanced Markus chamber are not statistically significant, and the trends of dose rate dependence are similar. The IBA PPC05 shows a flat response in terms of ion recombination effects based on the ks values calculated using the two-voltage technique. Differences in ks values for the PPC05 between the two-voltage technique and other model-based extrapolation methods are not statistically significant at FLASH dose rates. Some of the ks values for the PPC05 that were extrapolated from the three-voltage linear method and the semiempirical model were reported less than unity possibly due to the charge multiplication effect, which was negligible compared to the volume recombination effect in FLASH dose rates. CONCLUSIONS: The absolute dose measurements of both PTW Advanced Markus and IBA PPC05 chambers are in a good agreement with the National Physical Laboratory graphite calorimeter reference dose considering overall uncertainties. Both ion chambers also demonstrate good reproducibility as well as stability as reference dosimeters in UHDR PBS proton radiotherapy. The dose rate dependency of the ion recombination effects of both ion chambers in cyclotron generated PBS proton beams is acceptable and therefore, both chambers are suitable to use in clinical practice for the range of dose rates between 5 and 60 Gy/s.

Improving workflow for adaptive proton therapy with predictive anatomical modelling: A proof of concept.

PURPOSE: To demonstrate predictive anatomical modelling for improving the clinical workflow of adaptive intensity-modulated proton therapy (IMPT) for head and neck cancer. METHODS: 10 radiotherapy patients with nasopharyngeal cancer were included in this retrospective study. Each patient had a planning CT, weekly verification CTs during radiotherapy and predicted weekly CTs from our anatomical model. Predicted CTs were used to create predicted adaptive plans in advance with the aim of maintaining clinically acceptable dosimetry. Adaption was triggered when the increase in mean dose (Dmean) to the parotid glands exceeded 3 Gy(RBE). We compared the accumulated dose of two adaptive IMPT strategies: 1) Predicted plan adaption: One adaptive plan per patient was optimised on a predicted CT triggered by replan criteria. 2) Standard replan: One adaptive plan was created reactively in response to the triggering weekly CT. RESULTS: Statistical analysis demonstrates that the accumulated dose differences between two adaptive strategies are not significant (p > 0.05) for CTVs and OARs. We observed no meaningful differences in D95 between the accumulated dose and the planned dose for the CTVs, with mean differences to the high-risk CTV of -1.20 %, -1.23 % and -1.25 % for no adaption, standard and predicted plan adaption, respectively. The accumulated parotid Dmean using predicted plan adaption is within 3 Gy(RBE) of the planned dose and 0.31 Gy(RBE) lower than the standard replan approach on average. CONCLUSION: Prediction-based replanning could potentially enable adaptive therapy to be delivered without treatment gaps or sub-optimal fractions, as can occur during a standard replanning strategy, though the benefit of using predicted plan adaption over the standard replan was not shown to be statistically significant with respect to accumulated dose in this study. Nonetheless, a predictive replan approach can offer advantages in improving clinical workflow efficiency.

Diavik Waste Rock Project: Simulation of the geochemical evolution of a large test pile using a scaled temperature and sulfide-content dependent reactive transport model.

The Diavik Waste Rock Project (DWRP) project included four principal components focused on the development of techniques for assessing the environmental impacts of waste rock at mine sites. These components were small-volume laboratory experiments, intermediate- and large-volume field experiments, and assessment of the operational-scale waste-rock stockpiles, which facilitated characterization of waste-rock weathering at different scales. The heavily instrumented large-scale field experiments (test piles) were constructed to replicate, as closely as practicable, the temperature, water flow, and gas transport regimes of a waste-rock pile that is exposed to annual freezing and thawing cycles and to facilitate characterization of the long-term weathering of a low-sulfide waste rock. An integrated conceptual model of sulfide-bearing waste-rock weathering, developed at the small scale, was applied to assess the capacity of the conceptual model to capture the geochemical evolution of the waste rock at the large field-scale test-pile experiment. The integrated conceptual model was implemented using reactive transport code MIN3P, taking into account scale-dependent mechanisms. The test-pile mineralogy was similar to the small-scale laboratory experiments and included low-sulfide waste rock with an S content of 0.053 wt% (primarily pyrrhotite). The flow regime of the test pile was simulated using parameters measured as part of other DWRP investigations, including temporally variable infiltration estimates that represented the measured precipitation events at the site. The temporally and spatially variable temperature of the test pile was interpolated from values measured using instrumentation installed at the beginning of the experiment and was included in the simulation to refine the temperature dependence of the geochemical reactions. To allow continuous, multi-year simulation, freezing was also simulated to represent the conditions experienced at the test-pile experiment. Normalized root mean square error analysis of the large-scale field experiment simulation results indicated most parameters compare well to measured daily mass flux (i.e., the fraction of the range of annual values encompassed in the residual was less than 0.5 for SO4, Fe, Ni, Si, Ca, K, Mg, Na, and pH and 1.0 or less for all parameters except Cu). The method of using an integrated conceptual model developed from the results of humidity cell experiments to implement a mechanistic approach for assessing the primary geochemical processes of waste-rock weathering on a large scale was shown to provide reasonable results; however, the results are specific to the study site and the approach requires application to various sites under different geological and climatological conditions to facilitate further refinement.

Proton Therapy for Breast Cancer: A Consensus Statement From the Particle Therapy Cooperative Group Breast Cancer Subcommittee.

Radiation therapy plays an important role in the multidisciplinary management of breast cancer. Recent years have seen improvements in breast cancer survival and a greater appreciation of potential long-term morbidity associated with the dose and volume of irradiated organs. Proton therapy reduces the dose to nontarget structures while optimizing target coverage. However, there remain additional financial costs associated with proton therapy, despite reductions over time, and studies have yet to demonstrate that protons improve upon the treatment outcomes achieved with photon radiation therapy. There remains considerable heterogeneity in proton patient selection and techniques, and the rapid technological advances in the field have the potential to affect evidence evaluation, given the long latency period for breast cancer radiation therapy recurrence and late effects. In this consensus statement, we assess the data available to the radiation oncology community of proton therapy for breast cancer, provide expert consensus recommendations on indications and technique, and highlight ongoing trials' cost-effectiveness analyses and key areas for future research.

Heated column experiments: A proxy for investigating the effects of in situ thermal recovery operations on groundwater geochemistry.

In situ thermal recovery is utilized extensively for unconventional bitumen extraction in the Cold Lake-Beaver River (CLBR) basin in Alberta, Canada. Public health concerns have been raised over potable groundwater contamination and arsenic release adjacent to these operations within the CLBR basin, which have been linked to subsurface heating of aquifer sediments. Under localized heated conditions, As-bearing aquifer sediments have been shown to undergo water-rock interactions and release constituents at near neutral pH conditions; however, release mechanisms have yet to be conclusively reported. To investigate the hydrogeochemical processes of aquifer heating and solute transport in detail, this study applies a novel heated column design to mimic saturated aquifer materials in contact with a thermal recovery well while constraining flow and geochemical conditions. Two column experiment scenarios were considered using: 1) quartz [SiO2] sand with 0.6 wt% pyrite [FeS2]; and 2) aquifer sediments collected from the CLBR region. Heated temperature gradients between 50 °C and 90 °C were maintained within a 0.6 m section of the 3 m column with a flow rate of one pore volume per week. During heated low oxygen (<3 mg L-1) conditions, results generally show increases in pH, Al, As, B, Mn, Mo, Si and Zn concentrations within and downgradient of the column heating section. Constituent release is primarily attributed to thermal desorption from Fe oxides, clay and silicate mineral dissolution, competitive anion exchange, and increased mixing. Overall results suggest that these mechanisms are responsible for increasing constituent concentrations in groundwater adjacent to in situ thermal recovery operations.

Proton Accelerated Partial Breast Irradiation: Clinical Outcomes at a Planned Interim Analysis of a Prospective Phase 2 Trial.

PURPOSE: To perform a planned interim analysis of acute (within 12 months) and late (after 12 months) toxicities and cosmetic outcomes after proton accelerated partial breast irradiation (APBI). METHODS AND MATERIALS: A total of 100 patients with pTis or pT1-2 N0 (≤3cm) breast cancer status after segmental mastectomy were enrolled in a single-arm phase 2 study from 2010 to 2019. The clinically determined postlumpectomy target volume, including tumor bed surgical clips and operative-cavity soft-tissue changes seen on imaging plus a radial clinical expansion, was irradiated with passively scattered proton APBI (34 Gy in 10 fractions delivered twice daily with a minimum 6-hour interfraction interval). Patients were evaluated at protocol-specific time intervals for recurrence, physician reports of cosmetic outcomes and toxicities, and patient reports of cosmetic outcomes and satisfaction with the treatment or experience. RESULTS: Median follow-up was 24 months (interquartile range [IQR], 12-43 months). Local control and overall survival were 100% at 12 and 24 months. There were no acute or late toxicities of grade 3 or higher; no patients experienced fat necrosis, fibrosis, infection, or breast shrinkage. Excellent or good cosmesis at 12 months was reported by 91% of patients and 94% of physicians; at the most recent follow-up, these were 94% and 87%, respectively. The most commonly reported late cosmetic effect was telangiectasis (17%). The total patient satisfaction rate for treatment and results at 12 and 24 months was 96% and 100%, respectively. Patients' mean time away from work was 5 days (IQR, 2-5 days), and the median out-of-pocket cost was $700 (IQR, $100-$1600). The mean left-sided heart dose was 2 cGy (range, 0.2-75 cGy), and the mean ipsilateral lung dose was 19 cGy (range, 0.2-164 cGy). CONCLUSIONS: Proton APBI is a maturing treatment option with high local control, favorable intermediate-term cosmesis, high treatment satisfaction, low treatment burden, and exceptional heart and lung sparing.

Technical Note: Simulation of dose buildup in proton pencil beams.

PURPOSE: The purpose of this study is to characterize the magnitude and depth of dose buildup in pencil beam scanning proton therapy. METHODS: We simulate the integrated depth-dose curve of realistic proton pencil beams in a water phantom using the Geant4 Monte Carlo toolkit. We independently characterize the electronic and protonic components of dose buildup as a function of proton beam energy from 40 to 400 MeV, both with and without an air gap. RESULTS: At clinical energies, electronic buildup over a distance of about 1 mm leads to a dose reduction at depth of the basal layer (0.07 mm) by up to 6% compared to if no buildup effect were present. Protonic buildup reduces the dose to the basal layer by up to 16% and has effects at depths of up to 150 mm. Secondary particles with a mass number A > 1 do not contribute to dose buildup. An air gap of 1 m has no significant effect on protonic buildup but reduces electronic buildup below 1%. CONCLUSIONS: Protonic and electronic dose buildup are relevant for accurate dosimetry in proton therapy although a realistic air gap reduces the electronic buildup to levels where it can be safely neglected. We recommend including electrons and secondary protons in Monte Carlo-based treatment planning systems down to a predicted range of 10-20 µ m in order to accurately model the dose at depths of the basal layer, no matter the size of the air gap between nozzle and patient.

Impact of varying planning parameters on proton pencil beam scanning dose distributions in four commercial treatment planning systems.

PURPOSE: In pencil beam scanning proton therapy, target coverage is achieved by scanning the pencil beam laterally in the x- and y-directions and delivering spots of dose to positions at a given radiological depth (layer). Dose is delivered to the spots on different layers by pencil beams of different energy until the entire volume has been irradiated. The aim of this study is to investigate the implementation of proton planning parameters (spot spacing, layer spacing and margins) in four commercial proton treatment planning systems (TPSs): Eclipse, Pinnacle3 , RayStation and XiO. MATERIALS AND METHODS: Using identical beam data in each TPS, plans were created on uniform material synthetic phantoms with cubic targets. The following parameters were systematically varied in each TPS to observe their different implementations: spot spacing, layer spacing and margin. Additionally, plans were created in Eclipse to investigate the impact of these parameters on plan delivery and optimal values are suggested. RESULTS: It was found that all systems except Eclipse use a variable layer spacing per beam, based on the Bragg peak width of each energy layer. It is recommended that if this cannot be used, then a constant value of 5 mm will ensure good dose homogeneity. Only RayStation varies the spot spacing according to the variable spot size with depth. If a constant spot spacing is to be used, a value of 5 mm is recommended as a good compromise between dose homogeneity, plan robustness and planning time. It was found that both Pinnacle3 and RayStation position spots outside of the defined volume (target plus margin). CONCLUSIONS: All four systems are capable of delivering uniform dose distributions to simple targets, but their implementation of the various planning parameters is different. In this paper comparisons are made between the four systems and recommendations are made as to the values that will provide the best compromise in dose homogeneity and planning time.

Radiation-Drug Combinations to Improve Clinical Outcomes and Reduce Normal Tissue Toxicities: Current Challenges and New Approaches: Report of the Symposium Held at the 63rd Annual Meeting of the Radiation Research Society, 15-18 October 2017; Cancun, Mexico.

The National Cancer Institute's (NCI) Radiation Research Program (RRP) is endeavoring to increase the relevance of preclinical research to improve outcomes of radiation therapy for cancer patients. These efforts include conducting symposia, workshops and educational sessions at annual meetings of professional societies, including the American Association of Physicists in Medicine, American Society of Radiation Oncology, Radiation Research Society (RRS), Radiosurgery Society, Society of Nuclear Medicine and Molecular Imaging, Society for Immunotherapy of Cancer and the American Association of Immunology. A symposium entitled "Radiation-Drug Combinations to Improve Clinical Outcomes and Reduce Normal Tissue Toxicities" was conducted by the NCI's RRP during the 63rd Annual Meeting of the RRS on October 16, 2017 in Cancun, Mexico. In this symposium, discussions were held to address the challenges in developing radiation-drug combinations, optimal approaches with scientific evidence to replace standard-of-care, approaches to reduce normal tissue toxicities and enhance post-treatment quality-of-life and recent advances in antibody-drug conjugates. The symposium included two broad overview talks followed by two talks illustrating examples of radiation-drug combinations under development. The overview talks identified the essential preclinical infrastructure necessary to accelerate progress in the development of evidence and important challenges in the translation of drug combinations to the clinic from the laboratory. Also addressed, in the example talks (in light of the suggested guidelines and identified challenges), were the development and translation of novel antibody drug conjugates as well as repurposing of drugs to improve efficacy and reduce normal tissue toxicities. Participation among a cross section of clinicians, scientists and scholars-in-training alike who work in this focused area highlighted the importance of continued discussions to identify and address complex challenges in this emerging area in radiation oncology.

Analysis of geometric variation of neck node levels during image-guided radiotherapy for nasopharyngeal carcinoma: recommended planning margins.

BACKGROUND: To quantify the geometrical changes of each neck nodal level (NNL) and estimate the geometric planning target volume (PTV) margin during image-guided radiotherapy (IGRT) for nasopharyngeal cancer (NPC). METHODS: Twenty patients with locally advanced NPC underwent one planning computed tomography (CTplan) and 6 weekly repeat CT (CTrep) scans during chemoradiotherapy. Each CTrep was rigidly registered to the CTplan. All the NNLs were manually delineated in each transverse CT section. When comparing the NNL in CTrep with CTplan, their volumes, displacement of the center of the mass, and the shortest perpendicular distance (SPD) were automatically calculated. This was followed by calculation of the systematic and random errors, overlapping index (OI), and dice similarity coefficient (DSC). With PTVs isotropically expanded from NNL by 1, 2, 3, 4, and 5 mm, they were compared with NNL itself; OI >0.95 was defined as the acceptable geometrical coverage. The Mann-Whitney test was used for statistical analysis. RESULTS: All volumes, OI, and DSC of the NNLs (not including level IA) showed a linear decrease over time throughout the treatment course. The volume of NNLs decreased by 1-6% in the first week and 10-21% in the sixth week. The mean SPD was 1.3-1.7 and 1.9-3.5 mm in the first and sixth week respectively. The DSCs for nodal level IB, II, III, and IV were >0.7 and that of level V was <0.7 throughout the treatment course. For level IA and VI, DSC was <0.7 after the 2nd week. To maintain the OI >0.95, 2-5 mm was needed to expand the different NNLs. CONCLUSIONS: The geometrical changes of each NNL are substantial and the necessary margin of 2-5 mm depended on individual NNL is needed to maintain geometrical coverage throughout the course of IGRT for NPC.

Proton Partial Breast Irradiation: Detailed Description of Acute Clinico-Radiologic Effects.

Introduction: Accelerated partial breast irradiation (APBI) with protons results in a very different acute effect profile than standard whole breast irradiation. We reviewed our initial experience with proton APBI and felt that a detailed description of these effects were needed to permit a common tool to compare experience with this developing technology. Methods: Sixty sequential patients treated with proton APBI on a prospective protocol were evaluated and 43 patients with a minimum six-month follow-up underwent detailed photographic and radiologic analysis. The tumorectomy cavity plus an additional 1.5 cm clinical target volume (CTV) was treated with two or three passively-scattered proton beams to a dose of 34 Gy in 10 fractions in one week. Photographs were taken at the end of radiation, at two weeks, six weeks, and every six months thereafter. Mammography was obtained at six months after radiation and annually thereafter. All visual changes were categorized using the smallest meaningful gradations in findings and are demonstrated herein. All treatment-related mammographic findings are reported. Findings: Visual and mammographic findings showed a clear time-dependent relationship and significant variation between individuals. Peak skin reaction occurred at two to six weeks after completion of therapy. At two weeks most patients had either no visible effects and patchy erythema involving <50% of the treated skin (60%). At six weeks most patients had either patchy erythema involving <50% of the overlying skin (33%) or patchy erythema involving >50% of the treated skin (28%). Only one patient developed any moist desquamation. At six months most patients had no visible skin changes (57%) or a small, circular area of mild hyperpigmentation (33%). Mammographic changes seen at six months were regional skin thickening (40%), residual seroma (14%), localized retraction (26%), and fat necrosis (2%). A subcategorized variant on the CTCAE 4.0 was developed to foster granular recording of these findings.

Modeling short-term concentration fluctuations of semi-volatile pollutants in the soil-plant-atmosphere system.

Temperature changes can drive cycling of semi-volatile pollutants between different environmental compartments (e.g. atmosphere, soil, plants). To evaluate the impact of daily temperature changes on atmospheric concentration fluctuations we employed a physically based model coupling soil, plants and the atmosphere, which accounts for heat transport, effective gas diffusion, sorption and biodegradation in the soil as well as eddy diffusion and photochemical oxidation in the atmospheric boundary layer of varying heights. The model results suggest that temperature-driven re-volatilization and uptake in soils cannot fully explain significant diurnal concentration fluctuations of atmospheric pollutants as for example observed for polychlorinated biphenyls (PCBs). This holds even for relatively low water contents (high gas diffusivity) and high sorption capacity of the topsoil (high organic carbon content and high pollutant concentration in the topsoil). Observed concentration fluctuations, however, can be easily matched if a rapidly-exchanging environmental compartment, such as a plant layer, is introduced. At elevated temperatures, plants release organic pollutants, which are rapidly distributed in the atmosphere by eddy diffusion. For photosensitive compounds, e.g. some polycyclic aromatic hydrocarbons (PAHs), decreasing atmospheric concentrations would be expected during daytime for the bare soil scenario. This decline is buffered by a plant layer, which acts as a ground-level reservoir. The modeling results emphasize the importance of a rapidly-exchanging compartment above ground to explain short-term atmospheric concentration fluctuations.