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Colloidal structures are crucial components in biological systems and provide a vivid and seemingly infinite source of inspiration for the design of functional bio-inspired materials. They form multi-dimensional confinements and shape living matter, and transport and protect bioactive molecules in harsh biological environments such as the stomach. Recently, colloidal nanostructures based on natural antimicrobial peptides have emerged as promising alternatives to conventional antibiotics. This contribution summarizes the recent progress in the understanding and design of these bio-inspired antimicrobial nanomaterials, and discusses their advances in the form of dispersions and as surface coatings. Their potential for applications in future food and healthcare materials is also highlighted. Further, it discusses challenges in the characterization of structure and dynamics in these materials.

Purpose: To evaluate the dosimetric effects of the AeroForm TM (AirXanpders®, Palo Alto, CA) tissue expander in-situ for breast cancer patients receiving post-mastectomy radiation therapy., Methods and Materials: A film phantom (P1) was constructed by placing the metallic canister of the AeroForm on a solid water phantom with EBT3 films at five depths ranging from 2.6 mm to 66.2 mm. A breast phantom (P2), a three-dimensional printed tissue-equivalent breast with fully expanded AeroForm in-situ, was placed on a thorax phantom. A total of 21 optical luminescent dosimeters (OLSDs) were placed on the anterior skin-gas interface and the posterior chest wall-metal interface of the AeroForm. Both phantoms were imaged with a 16-bit computed tomography scanner with orthopedic metal artifact reduction. P1 was irradiated with an open field utilizing 6 MV and 15 MV photon beams at 0°, 90°, and 270°. P2 was irradiated using a volumetric modulated arc therapy plan with a 6 MV photon beam and a tangential plan with a 15 MV photon beam. All doses were calculated using Eclipse (Varian, Palo Alto, CA) with AAA and AcurosXB (AXB) algorithms., Results: The average dose differences between film measurements and AXB in the region adjacent to the canister in P1 were within 3.1% for 15 MV and 0.9% for 6 MV. Local dose differences over 10% were also observed. In the chest wall region of P2, the median dose of OLSDs in percentage of prescription dose were 108.4% (range 95.4%-113.0%) for the 15MV tangential plan and 110.4% (range 99.1%-113.8%) for the 6MV volumetric modulated arc therapy plan. In the skin-gas interface, the median dose of the OLSDs were 102.3% (range 92.7%-107.7%) for the 15 MV plan and 108.2% (range 97.8-113.5%) for the 6 MV plan. Measured doses were, in general, higher than calculated doses with AXB calculations. The AAA dose algorithms produced results with slightly larger discrepancies between measurements compared with AXB., Conclusions: The AeroForm creates significant dose uncertainties in the chest wall-metal interface. The AcurosXB dose calculation algorithm is recommended for more accurate calculations. If possible, post-mastectomy radiation therapy should be delivered after the permanent implant is in place., (© 2020 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Purpose: To present a fully automated treatment planning process for proton therapy including beam angle selection using a novel Bayesian optimization approach and previously developed constrained hierarchical fluence optimization method., Methods: We adapted our in-house automated intensity modulated radiation therapy (IMRT) treatment planning system, which is based on constrained hierarchical optimization and referred to as ECHO (expedited constrained hierarchical optimization), for proton therapy. To couple this to beam angle selection, we propose using a novel Bayesian approach. By integrating ECHO with this Bayesian beam selection approach, we obtain a fully automated treatment planning framework including beam angle selection. Bayesian optimization is a global optimization technique which only needs to search a small fraction of the search space for slowly varying objective functions (i.e., smooth functions). Expedited constrained hierarchical optimization is run for some initial beam angle candidates and the resultant treatment plan for each beam configuration is rated using a clinically relevant treatment score function. Bayesian optimization iteratively predicts the treatment score for not-yet-evaluated candidates to find the best candidate to be optimized next with ECHO. We tested this technique on five head-and-neck (HN) patients with two coplanar beams. In addition, tests were performed with two noncoplanar and three coplanar beams for two patients., Results: For the two coplanar configurations, the Bayesian optimization found the optimal beam configuration after running ECHO for, at most, 4% of all potential configurations (23 iterations) for all patients (range: 2%-4%). Compared with the beam configurations chosen by the planner, the optimal configurations reduced the mandible maximum dose by 6.6 Gy and high dose to the unspecified normal tissues by 3.8 Gy, on average. For the two noncoplanar and three coplanar beam configurations, the algorithm converged after 45 iterations (examining <1% of all potential configurations)., Conclusions: A fully automated and efficient treatment planning process for proton therapy, including beam angle optimization was developed. The algorithm automatically generates high-quality plans with optimal beam angle configuration by combining Bayesian optimization and ECHO. As the Bayesian optimization is capable of handling complex nonconvex functions, the treatment score function which is used in the algorithm to evaluate the dose distribution corresponding to each beam configuration can contain any clinically relevant metric., (© 2020 American Association of Physicists in Medicine.)

Purpose: We present a method for fully automated generation of high quality robust proton treatment plans using hierarchical optimization. To fill the gap between the two common extreme robust optimization approaches, that is, stochastic and worst-case, a robust optimization approach based on the p-norm function is used whereby a single parameter, p , can be used to control the level of robustness in an intuitive way., Methods: A fully automated approach to treatment planning using Expedited Constrained Hierarchical Optimization (ECHO) is implemented in our clinic for photon treatments. ECHO strictly enforces critical (inviolable) clinical criteria as hard constraints and improves the desirable clinical criteria sequentially, as much as is feasible. We extend our in-house developed ECHO codes for proton therapy and integrate it with a new approach for robust optimization. Multiple scenarios accounting for both setup and range uncertainties are included (13scenarios), and the maximum/mean/dose-volume constraints on organs-at-risk (OARs) and target are fulfilled in all scenarios. We combine the objective functions of the individual scenarios using the p-norm function. The p-norm with a parameter p = 1 or p = ∞ result in the stochastic or the worst-case approach, respectively; an intermediate robustness level is obtained by employing p -values in-between. While the worst-case approach only focuses on the worst-case scenario(s), the p-norm approach with a large p value ( p ≈ 20 ) resembles the worst-case approach without completely neglecting other scenarios. The proposed approach is evaluated on three head-and-neck (HN) patients and one water phantom with different parameters, p ∈ 1 , 2 , 5 , 10 , 20 . The results are compared against the stochastic approach (p-norm approach with p = 1 ) and the worst-case approach, as well as the nonrobust approach (optimized solely on the nominal scenario)., Results: The proposed algorithm successfully generates automated robust proton plans on all cases. As opposed to the nonrobust plans, the robust plans have narrower dose volume histogram (DVH) bands across all 13 scenarios, and meet all hard constraints (i.e., maximum/mean/dose-volume constraints) on OARs and the target for all scenarios. The spread in the objective function values is largest for the stochastic approach ( p = 1 ) and decreases with increasing p toward the worst-case approach. Compared to the worst-case approach, the p-norm approach results in DVH bands for clinical target volume (CTV) which are closer to the prescription dose at a negligible cost in the DVH for the worst scenario, thereby improving the overall plan quality. On average, going from the worst-case approach to the p-norm approach with p = 20 , the median objective function value across all the scenarios is improved by 15% while the objective function value for the worst scenario is only degraded by 3%., Conclusion: An automated treatment planning approach for proton therapy is developed, including robustness, dose-volume constraints, and the ability to control the robustness level using the p-norm parameter p , to fit the priorities deemed most important., (© 2020 American Association of Physicists in Medicine.)

Purpose: Breast radiation therapy accounts for a significant proportion of patient volume in contemporary radiation oncology practice. In the setting of anticipated resource constraints and widespread community infection with SARS-CoV-2 during the COVID-19 pandemic, measures for balancing both infectious and oncologic risk among patients and providers must be carefully considered. Here, we present evidence-based guidelines for omitting or abbreviating breast cancer radiation therapy, where appropriate, in an effort to mitigate risk to patients and optimize resource utilization., Methods and Materials: Multidisciplinary breast cancer experts at a high-volume comprehensive cancer center convened contingency planning meetings over the early days of the COVID-19 pandemic to review the relevant literature and establish recommendations for the application of hypofractionated and abbreviated breast radiation regimens., Results: Substantial evidence exists to support omitting radiation among certain favorable risk subgroups of patients with breast cancer and for abbreviating or accelerating regimens among others. For those who require either whole-breast or postmastectomy radiation, with or without coverage of the regional lymph nodes, a growing body of literature supports various hypofractionated approaches that appear safe and effective., Conclusions: In the setting of a public health emergency with the potential to strain critical healthcare resources and place patients at risk of infection, the parsimonious application of breast radiation therapy may alleviate a significant clinical burden without compromising long-term oncologic outcomes. The judicious and personalized use of immature study data may be warranted in the setting of a competing mortality risk from this widespread pandemic., (© 2020 The Author(s).)

Objective: Germline BRCA mutation rates in the Latina population are yet to be well described. We aimed to quantitate the rates of referral for genetic testing in qualifying women and testing completion rates in a population of women presenting for gynecologic oncology care. Results were then stratified by ethnic/racial background., Methods: Charts of new patients evaluated at a comprehensive cancer center in Southern California were reviewed. Patients qualifying for genetic testing in accordance with NCCN Guidelines version 1.2017 for breast and/or ovarian cancer genetic assessment were identified. The actual rates of prescriptions for genetic testing placed, testing completion rates, test results, as well as patients' family history were abstracted. Data were analyzed with chi-square tests., Results: Five hundred and seventy-two of 2,053 patients met testing criteria, and 256/572 (45%) were prescribed testing in accordance with the guidelines. By ethnicity, testing was prescribed in 44% of Non-Hispanic White (NHW), 44% of Latina, 46% of African-American, and 60% of Asian (p = 0.6) patients. Testing was completed in 65% of NHW, 66% of Latina, 65% of African-American, and 67% of Asian patients (p = 0.97). Completion rates were low overall: 28% of those who met testing criteria were tested (p = 0.85). Pathogenic BRCA mutations were found in 29% of NHW and 21% of Latina, 45% of African-American, and 20% of Asian patients (p = 0.4)., Conclusions: There was no difference by ethnicity in rates of testing prescription, completion, or presence of BRCA mutations. Overall, testing rates were suboptimal. BRCA mutations were found in large percentage of Latinas (21%). Further studies are underway to identify barriers to testing prescriptions and completion for Latina women., (© 2020 S. Karger AG, Basel.)

Purpose: We report on the clinical performance of a fully automated approach to treatment planning based on a Pareto optimal, constrained hierarchical optimization algorithm, named Expedited Constrained Hierarchical Optimization (ECHO)., Methods and Materials: From April 2017 to October 2018, ECHO produced 640 treated plans for 523 patients who underwent stereotactic body radiation therapy (RT) for paraspinal and other metastatic tumors. A total of 182 plans were for 24 Gy in a single fraction, 387 plans were for 27 Gy in 3 fractions, and the remainder were for other prescriptions or fractionations. Of the plans, 84.5% were for paraspinal tumors, with 69, 302, and 170 in the cervical, thoracic, and lumbosacral spine, respectively. For each case, after contouring, a template plan using 9 intensity modulated RT fields based on disease site and tumor location was sent to ECHO through an application program interface plug-in from the treatment planning system. ECHO returned a plan that satisfied all critical structure hard constraints with optimal target volume coverage and the lowest achievable normal tissue doses. Upon ECHO completion, the planner received an e-mail indicating the plan was ready for review. The plan was accepted if all clinical criteria were met. Otherwise, a limited number of parameters could be adjusted for another ECHO run., Results: The median planning target volume size was 84.3 cm 3 (range, 6.9-633.2). The median time to produce 1 ECHO plan was 63.5 minutes (range, 11-340 minutes) and was largely dependent on the field sizes. Of the cases, 79.7% required 1 run to produce a clinically accepted plan, 13.3% required 1 additional run with minimal parameter adjustments, and 7.0% required ≥2 additional runs with significant parameter modifications. All plans met or bettered the institutional clinical criteria., Conclusions: We successfully implemented automated stereotactic body RT paraspinal and other metastatic tumors planning. ECHO produced high-quality plans, improved planning efficiency and robustness, and enabled expedited treatment planning at our clinic., (© 2019 The Author(s).)

Neurologic complications following neuraxial anesthesia for cesarean delivery are rare. We present a 33-year-old parturient who developed prolonged lower extremity weakness following a single-shot subarachnoid block for cesarean delivery. After neurologic evaluation, she was diagnosed with bilateral sciatic neuropathies due to prolonged positioning for the anesthetic. We review the incidence of nerve injury associated with neuraxial anesthesia and risk factors for developing peripheral nerve injury in this context. We offer a solution to prevent this complication from occurring.

Background: Microfluidics is becoming increasingly of interest as a superior technique for the synthesis of nanoparticles, particularly for their use in nanomedicine. In microfluidics, small volumes of liquid reagents are rapidly mixed in a microchannel in a highly controlled manner to form nanoparticles with tunable and reproducible structure that can be tailored for drug delivery. Both polymer and lipid-based nanoparticles are utilized in nanomedicine and both are amenable to preparation by microfluidic approaches., Aim: Therefore, the purpose of this review is to collect the current state of knowledge on the microfluidic preparation of polymeric and lipid nanoparticles for pharmaceutical applications, including descriptions of the main synthesis modalities. Of special interest are the mechanisms involved in nanoparticle formation and the options for surface functionalisation to enhance cellular interactions., Conclusion: The review will conclude with the identification of key considerations for the production of polymeric and lipid nanoparticles using microfluidic approaches., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Cubosomes are highly ordered self-assembled lipid particles analogous to liposomes, but with internal liquid crystalline structure. They are receiving interest as stimuli responsive delivery particles, but their preparation typically requires high energy approaches such as sonication which is not favourable in many applications., Objective: Here we investigated the impact of microfluidic preparation on particle size distribution and internal structure of cubosomes prepared from two different lipid systems, phytantriol and glyceryl monooleate (GMO)., Methods: The impact of relative flow rates of the aqueous and organic streams, the total flow rate and temperature were investigated in a commercial microfluidic system. The particle size distribution and structure were measured using dynamic light scattering and small angle X-ray scattering respectively., Results: Phytantriol based particles were robust to different processing conditions, while cubosomes formed using GMO were more sensitive to composition both locally and globally, which reflects their preparation using other techniques., Conclusion: Thus, in summary microfluidics represents a reproducible and versatile method to prepare complex lipid particle dispersions such as cubosomes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

For left-sided postmastectomy patients requiring chest wall plus comprehensive nodal irradiation, sometimes traditional techniques such as partial wide tangents or electron/tangents combination are not feasible due to abnormal chest wall contour or heart position or unusually wide excision scar. We developed electron chest wall irradiation technique using Electron Monte Carlo (EMC) dose algorithm that will achieve heart sparing with acceptable ipsilateral lung dose, minimal contralateral lung, and breast dose. Ten left-sided postmastectomy patients with very challenging anatomy were selected for this dosimetry study. The en face electron fields were designed from a single isocenter and gantry angle with different energy beams using different cutouts that matched on the skin. Smaller energy was used in the central thin chest wall part and higher energy in the medial internal mammary nodes (IMN) area, superior part of the thick chest wall, and/or axillary nodal area. The electron fields were matched to the photon supraclavicular field in the superior region. Daily field junctions were used to feather the match lines between all the fields. Electron field dose calculations were done with Monte Carlo. Five patients' chest wall fields were planned with 6/9MeVcombination, 1 with 6/12 MeV, 2 with 9/12 MeV, 1 with 9/16 MeV, and 1 with 6/9/12 MeV. Institutional criteria of prescription dose of 50 Gy for target volumes and normal tissue dose were met with this technique in spite of the challenging anatomy. Mean heart dose averaged 3.0 Gy ± 0.8 Gy. For ipsilateral lung, V20Gy and V5Gy averaged 33.2% ± 4.5% and 64.6% ± 9.6%, respectively. For contralateral lung, V5Gy averaged 5.1% ± 5.0%. For contralateral breast, V5Gy averaged 3.3% ± 3.1%. The electron chest wall irradiation technique using EMC dose algorithm can provide adequate dose coverage to the chest wall, IMNs, and/or axillary nodes while achieving heart sparing with acceptable ipsilateral lung dose, minimal contralateral lung, and breast dose., (Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Lipid-based liquid crystalline systems based on the combination of digestible and nondigestible lipids have been proposed as potential sustained release delivery systems for oral delivery of poorly water-soluble drugs. The potential for cubic phase liquid crystal formation to induce dramatically extended gastric retention in vivo has been shown previously to strongly influence the resulting pharmacokinetics of incorporated drug. In vitro studies showing the in situ formation of cubic phase from a disordered precursor comprising a mixture of digestible and nondigestible lipids under enzymatic digestion have also recently been reported. Combining both concepts, here we show the potential for such systems to form in vivo, increasing gastric retention, and providing a sustained release effect for a model poorly water-soluble drug cinnarizine. A mixture of phytantriol and tributyrin at an 85:15 mass ratio, shown previously to form cubic phase under the influence of digestion, induced a similar pharmacokinetic profile to that in the absence of tributyrin, but completely different from tributyrin alone. The gastric retention of the formulation, assessed using micro-X-ray CT imaging, was also consistent with the pharmacokinetic behavior, where phytantriol alone and with 15% tributyrin was greater than that of tributyrin in the absence of phytantriol. Thus, the concept of precursor lipid systems that form cubic phase in situ during digestion in vivo has been demonstrated and opens new opportunities for sustained release of poorly water-soluble drugs.

We report our experience of establishing planning objectives to achieve dose coverage, conformity, and dose falloff for spine stereotactic body radiation therapy (SBRT) plans. Patients with spine lesions were treated using SBRT in our institution since September 2009. Since September 2011, we established the following planning objectives for our SBRT spine plans in addition to the cord dose constraints: (1) dose coverage—prescription dose (PD) to cover at least 95% planning target volume (PTV) and 90% PD to cover at least 99% PTV; (2) conformity index (CI)—ratio of prescription isodose volume (PIV) to the PTV < 1.2; (3) dose falloff—ratio of 50% PIV to the PTV (R(50%)); (4) and maximum dose in percentage of PD at 2 cm from PTV in any direction (D(2cm)) to follow Radiation Therapy Oncology Group (RTOG) 0915. We have retrospectively reviewed 66 separate spine lesions treated between September 2009 and December 2012 (31 treated before September 2011 [group 1] and 35 treated after [group 2]). The χ(2) test was used to examine the difference in parameters between groups. The PTV V(100% PD) ≥ 95% objective was met in 29.0% of group 1 vs 91.4% of group 2 (p < 0.01) plans. The PTV V(90% PD) ≥ 99% objective was met in 38.7% of group 1 vs 88.6% of group 2 (p < 0.01) plans. Overall, 4 plans in group 1 had CI > 1.2 vs none in group 2 (p = 0.04). For D(2cm), 48.3% plans yielded a minor violation of the objectives and 16.1% a major violation for group 1, whereas 17.1% exhibited a minor violation and 2.9% a major violation for group 2 (p < 0.01). Spine SBRT plans can be improved on dose coverage, conformity, and dose falloff employing a combination of RTOG spine and lung SBRT protocol planning objectives., (Copyright © 2015 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Background: A viable tubal pregnancy is an extremely rare occurrence with an increased risk of fetal as well as maternal morbidity and mortality. We report a third trimester tubal pregnancy occurring after an interval tubal ligation., Case: A 43-year-old woman, gravida 2 para 1, presented at 29 weeks' gestation with an asymptomatic extrauterine pregnancy and was managed expectantly in the antepartum unit. At 33 weeks the fetus was delivered for worsening umbilical artery velocimetry. Despite aggressive resuscitative efforts, the neonate did not survive., Conclusion: In managing an advanced extrauterine pregnancy, imaging with MRI may help diagnose and confirm suspicion raised by ultrasonography and may aid in presurgical planning and management. This case illustrates the diagnostic challenge and high neonatal mortality of an advanced tubal pregnancy.

Objectives: To explore whether disparities in age and sex in access to kidney transplantation (KT) originate at the time of prereferral discussions about KT., Design: Cross-sectional survey., Setting: Outpatient dialysis centers in Maryland (n = 26)., Participants: Individuals who had recently initiated hemodialysis treatment (N = 416)., Measurements: Participants reported whether medical professionals (nephrologist, primary medical doctor, dialysis staff) and social group members (significant other, family member, friend) discussed KT with them and, when applicable, rated the tone of discussions. Relative risks were estimated using modified Poisson regression., Results: Participants aged 65 and older were much less likely than those who were younger to have had discussions with medical professionals (44.5% vs 74.8%, P < .001) or social group members (47.3% vs 63.1%, P = .005). Irrespective of sex and independent of race, health-related factors, and dialysis-related characteristics, older adults were more likely not to have had discussions with medical professionals (relative risk (RR) = 1.13, 95% confidence interval (CI) = 1.03-1.24, for each 5-year increase in age through 65; RR = 1.28, 95% CI = 1.14-1.42, for each 5-year increase in age beyond 65). Irrespective of age, women were more likely (RR = 1.45, 95% CI = 1.12-1.89) not to have had discussions with medical professionals. For each 5-year increase in age, men (RR = 1.04, 95% CI = 0.99-1.10) and women (RR = 1.17, 95% CI = 1.10-1.24) were more likely not to have discussions with social group members. Of those who had discussions with medical professionals or social group members, older participants described these discussions as less encouraging (all P < .01)., Conclusion: Older adults and women undergoing hemodialysis are less likely than younger adults and men to have discussions about KT as a treatment option, supporting a need for better clinical guidelines and education for these individuals, their social network, and their providers., (© 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.)

Beta-2 microglobulin (B2M) is a component of the major histocompatibility complex (MHC) class I molecule and has been studied as a biomarker of kidney function, cardiovascular diseases and mortality. Little is known about the genes influencing its levels directly or through glomerular filtration rate (GFR). We conducted a genome-wide association study of plasma B2M levels in 6738 European Americans from the Atherosclerosis Risk in Communities study to identify novel loci for B2M and assessed its association with known estimated GFR (eGFR) loci. We identified 2 genome-wide significant loci. One was in the human leukocyte antigen (HLA) region on chromosome 6 (lowest p value = 1.8 × 10(-23) for rs9264638). At this locus, 6 index SNPs accounted for 3.2 % of log(B2M) variance, and their association with B2M could largely be explained by imputed classical alleles of the MHC class I genes: HLA-A, HLA-B, or HLA-C. The index SNPs at this locus were not associated with eGFR based on serum creatinine (eGFRcr). The other locus of B2M was on chromosome 12 (rs3184504 at SH2B3, beta = 0.02, p value = 3.1 × 10(-8)), which was previously implicated as an eGFR locus. In conclusion, although B2M is known to be a component of MHC class I molecule, the association between HLA class I alleles and plasma B2M levels in a community-based population is novel. The identification of the two novel loci for B2M extends our understanding of its metabolism and informs its use as a kidney filtration biomarker.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.

Intensity modulated radiotherapy (IMRT) has become an effective tool for cancer treatment with radiation. However, even expert radiation planners still need to spend a substantial amount of time adjusting IMRT optimization parameters in order to get a clinically acceptable plan. We demonstrate that the relationship between patient geometry and radiation intensity distributions can be automatically inferred using a variety of machine learning techniques in the case of two-field breast IMRT. Our experiments show that given a small number of human-expert-generated clinically acceptable plans, the machine learning predictions produce equally acceptable plans in a matter of seconds. The machine learning approach has the potential for greater benefits in sites where the IMRT planning process is more challenging or tedious.

Intensity-modulated radiation therapy can be conveniently delivered with a multileaf collimator. With this method, the entire field is not delivered at once, but rather it is composed of many subfields defined by the leaf positions as a function of beam on time. At any given instant, only these subfields are delivered. During treatment, if the organ moves, part of the volume may move in or out of these subfields. Due to this interplay between organ motion and leaf motion the delivered dose may be different from what was planned. In this work, we present a method that calculates the effects of organ motion on delivered dose. The direction of organ motion may be parallel or perpendicular to the leaf motion, and the effect can be calculated for a single fraction or for multiple fractions. Three breast patients and four lung patients were included in this study,with the amplitude of the organ motion varying from +/- 3.5 mm to +/- 10 mm, and the period varying from 4 to 8 seconds. Calculations were made for these patients with and without organ motion, and results were examined in terms of isodose distribution and dose volume histograms. Each calculation was repeated ten times in order to estimate the statistical uncertainties. For selected patients, calculations were also made with conventional treatment technique. The effects of organ motion on conventional techniques were compared relative to that on IMRT techniques. For breast treatment, the effect of organ motion primarily broadened the penumbra at the posterior field edge. The dose in the rest of the treatment volume was not significantly affected. For lung treatment, the effect also broadened the penumbra and degraded the coverage of the planning target volume (PTV). However, the coverage of the clinical target volume (CTV) was not much affected, provided the PTV margin was adequate. The same effects were observed for both IMRT and conventional treatment techniques. For the IMRT technique, the standard deviations of ten samples of a 30-fraction calculation were very small for all patients, implying that over a typical treatment course of 30 fractions, the delivered dose was very close to the expected value. Hence, under typical clinical conditions, the effect of organ motion on delivered dose can be calculated without considering the interplay between the organ motion and the leaf motion. It can be calculated as the weighted average of the dose distribution without organ motion with the distribution of organ motion. Since the effects of organ motion on dose were comparable for both IMRT and conventional techniques, the PTV margin should remain the same for both techniques.