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Ewing sarcoma (EwS) is a rare bone and soft tissue malignancy driven by chromosomal translocations encoding chimeric transcription factors, such as EWSR1-FLI1, that bind GGAA motifs forming novel enhancers that alter nearby expression. We propose that germline microsatellite variation at the 6p25.1 EwS susceptibility locus could impact downstream gene expression and EwS biology. We performed targeted long-read sequencing of EwS blood DNA to characterize variation and genomic features important for EWSR1-FLI1 binding. We identified 50 microsatellite alleles at 6p25.1 and observed that EwS-affected individuals had longer alleles (>135 bp) with more GGAA repeats. The 6p25.1 GGAA microsatellite showed chromatin features of an EWSR1-FLI1 enhancer and regulated expression of RREB1, a transcription factor associated with RAS/MAPK signaling. RREB1 knockdown reduced proliferation and clonogenic potential and reduced expression of cell cycle and DNA replication genes. Our integrative analysis at 6p25.1 details increased binding of longer GGAA microsatellite alleles with acquired EWSR-FLI1 to promote Ewing sarcomagenesis by RREB1-mediated proliferation.

PurposeThe Federal Aviation Administration quantifies hazardous attitudes (HAs) among pilots using a scale. HAs have been linked to aviation risk. We assessed the influence of HAs and other factors in treatment decision making in radiation oncology (RO).Methods and materialsAn anonymous survey was sent to 809 radiation oncologists in US cities housing the top 25 cancer centers. The survey included an HA scale adapted for RO and presented 9 cases assessing risk-tolerant radiation therapy prescribing habits and compliance with the American Society for Radiation Oncology's Choosing Wisely recommendations. Demographic and treatment decision data were dichotomized to identify factors associated with prescribing habits using univariable and multivariable (MVA) logistic regression analyses.ResultsA total of 139 responses (17.1%) were received, and 103 were eligible for analysis. Among respondents, 40% were female, ages were evenly distributed, and 83% were in academics. Median scores for all attitudes (macho, anti-authority, worry, resignation, and impulsivity) were below the aviation thresholds for hazard and data from surgical specialties. On MVA, responders >50 years old with >5 years' experience were 4.45 times more likely to recommend risk-tolerant radiation (P = .016). Macho attitude was negatively associated with Choosing Wisely compliant treatments (odds ratio [OR], 0.12; P = .001). Physicians who reported having previously retreated the supraclavicular fossa without complication were more likely to recommend retreatment in medically unfit patients if they felt the complication was avoided owing to careful planning (OR, 5.2; P = .008).ConclusionsTo our knowledge, this represents the first study analyzing physician attitudes in RO and their effect on self-reported treatment decisions. This work suggests that attitude may be among the factors that influence risk-tolerant prescribing practices and compliance with Choosing Wisely rec

Background: Studies evaluating the association between peripheral blood leukocyte telomere length (LTL) and testicular germ cell tumor (TGCT) risk have produced conflicting results. Methods: Using available genotype data from the Testicular Cancer Consortium (TECAC), polygenic risk score and Mendelian randomization analyses of genetic variants previously associated with LTL were used to assess potential etiologic associations between telomere length and TGCT risk. Results: Genetically inferred telomere length was not associated with TGCT risk among 2,049 cases and 6,921 controls with individual-level genotype data (OR, 1.02; 95% confidence interval, 0.97-1.07). Mendelian randomization analyses using summary statistic data further indicated no evidence for an association between telomere length and TGCT risk among all available TECAC participants (3,558 cases and 13,971 controls). Conclusions: Our analyses in the largest molecular genetic testicular cancer study to date provide no evidence for an association between genetically inferred peripheral blood LTL and TGCT risk. Impact: The lack of evidence for an overall association indicates that peripheral blood LTL is likely not a strong biomarker for TGCT risk.

ObjectivesTo develop a training program designed to meet the specific needs of medical physicists as they transition into a clinical role with direct patient care responsibilities.Materials and methodsThe training program was designed in collaboration with the faculty at the UC San Diego School of Medicine and incorporates training techniques that have been shown to be effective in improving communication skills. The program emphasizes experiential, practice-based learning over didactic presentations.ResultsThe training program is comprised of 5 components: 1) a 1-day Clinician-Patient Communication Workshop run by the UC San Diego School of Medicine, 2) Communication Strategies for Radiation Oncology, which consists of two, 2-hour sessions designed to provide trainees with patient communication skills that are specific to patient interactions in radiation oncology, 3) Simulated Patient Interactions, in which trainees perform mock physicist-patient consults with trained patient actors, 4) Faculty-Observed Patient Consults, and 5) a Case-Based Treatment Toxicity Course. A competency assessment mechanism was also developed to provide a clear set of objectives and to guide trainer feedback. [Correction added after first online publication on November 7, 2018: The phrase ", which consists of two, 2-hour" was added above.] CONCLUSIONS: The training program that we have developed incorporates an array of established education techniques and provides a comprehensive, accessible, means of improving medical physicists' patient communication skills.

ObjectivesTo develop a training program designed to meet the specific needs of medical physicists as they transition into a clinical role with direct patient care responsibilities.Materials and methodsThe training program was designed in collaboration with the faculty at the UC San Diego School of Medicine and incorporates training techniques that have been shown to be effective in improving communication skills. The program emphasizes experiential, practice-based learning over didactic presentations.ResultsThe training program is comprised of 5 components: 1) a 1-day Clinician-Patient Communication Workshop run by the UC San Diego School of Medicine, 2) Communication Strategies for Radiation Oncology, which consists of two, 2-hour sessions designed to provide trainees with patient communication skills that are specific to patient interactions in radiation oncology, 3) Simulated Patient Interactions, in which trainees perform mock physicist-patient consults with trained patient actors, 4) Faculty-Observed Patient Consults, and 5) a Case-Based Treatment Toxicity Course. A competency assessment mechanism was also developed to provide a clear set of objectives and to guide trainer feedback. [Correction added after first online publication on November 7, 2018: The phrase ", which consists of two, 2-hour" was added above.] CONCLUSIONS: The training program that we have developed incorporates an array of established education techniques and provides a comprehensive, accessible, means of improving medical physicists' patient communication skills.

PurposeTo provide insight into the types of questions asked to medical physicists by patients during one-on-one physicist-patient consults at one institution.Materials and methodsMedical physicists trained in patient communication techniques met with patients to provide an overview of the treatment planning and delivery processes, discuss the patient's treatment plan, and answer any technical questions. From August 2016 to December 2019, 152 physicist-patient consults were conducted. In the initial months of the study (August 2016-December 2017), following each physicist-patient consult, all patient questions were documented by the physicists. For the remaining time period (January 2018-December 2019), any newly encountered questions were periodically added to the list. The questions were compiled into a comprehensive list and organized into categories.ResultsThere were a total of 88 unique patient questions. These questions fit into four topical categories. Fifty-four questions (61.4%) were in the "Treatment Planning and Delivery Questions" category, 15 questions (17.1%) were in the "General Radiation Questions or Concerns" category, 13 questions (14.8%) were in the "Safety and Quality Assurance Questions" category, and 6 questions (6.8%) were in the "Medical Questions" category. Overall, patients were primarily concerned about how radiation works, the treatment planning and delivery processes, and what is being done to keep them safe throughout their treatment.ConclusionPhysicist-patient consults provided an opportunity to address the technical aspects of radiation therapy with patients in greater detail. The fact that patient questions could be conveniently grouped into only four topical categories indicates that it may be straightforward for other medical physicists to prepare for effectively addressing technical questions during physicist-patient consults.

PurposeTo provide insight into the types of questions asked to medical physicists by patients during one-on-one physicist-patient consults at one institution.Materials and methodsMedical physicists trained in patient communication techniques met with patients to provide an overview of the treatment planning and delivery processes, discuss the patient's treatment plan, and answer any technical questions. From August 2016 to December 2019, 152 physicist-patient consults were conducted. In the initial months of the study (August 2016-December 2017), following each physicist-patient consult, all patient questions were documented by the physicists. For the remaining time period (January 2018-December 2019), any newly encountered questions were periodically added to the list. The questions were compiled into a comprehensive list and organized into categories.ResultsThere were a total of 88 unique patient questions. These questions fit into four topical categories. Fifty-four questions (61.4%) were in the "Treatment Planning and Delivery Questions" category, 15 questions (17.1%) were in the "General Radiation Questions or Concerns" category, 13 questions (14.8%) were in the "Safety and Quality Assurance Questions" category, and 6 questions (6.8%) were in the "Medical Questions" category. Overall, patients were primarily concerned about how radiation works, the treatment planning and delivery processes, and what is being done to keep them safe throughout their treatment.ConclusionPhysicist-patient consults provided an opportunity to address the technical aspects of radiation therapy with patients in greater detail. The fact that patient questions could be conveniently grouped into only four topical categories indicates that it may be straightforward for other medical physicists to prepare for effectively addressing technical questions during physicist-patient consults.

PurposeWe propose a novel compensator-based IMRT system designed to provide a simple, reliable, and cost-effective adjunct technology, with the goal of expanding global access to advanced radiotherapy techniques. The system would employ easily reusable tungsten bead compensators that operate independent of a gantry (e.g., mounted in a ring around the patient). Thereby the system can be retrofitted to existing linac and cobalt teletherapy units. This study explores the quality of treatment plans from the proposed system and the dependence on associated design parameters.MethodsWe considered 60 Co-based plans as the most challenging scenario for dosimetry and benchmarked them against clinical MLC-based plans delivered on a linac. Treatment planning was performed in the Pinnacle treatment planning system with commissioning based on Monte Carlo simulations of compensated beams. 60 Co-compensator IMRT plans were generated for five patients with head-and-neck cancer and five with gynecological cancer and compared to respective IMRT plans using a 6 MV linac beam with an MLC. The dependence of dosimetric endpoints on compensator resolution, thickness, position, and number of beams was assessed. Dosimetric accuracy was validated by Monte Carlo simulations of dose distribution in a water phantom from beams with the IMRT plan compensators.ResultsThe 60 Co-compensator plans had on average equivalent PTV coverage and somewhat inferior OAR sparing compared to the 6 MV-MLC plans, but the differences in dosimetric endpoints were clinically acceptable. Calculated treatment times for head-and-neck plans were 7.6 ± 2.0 min vs 3.9 ± 0.8 min (6 MV-MLC vs 60 Co-compensator) and for gynecological plans were 8.7 ± 3.1 min vs 4.3 ± 0.4 min. Plan quality was insensitive to most design parameters over much of the ranges studied, with no degradation found when the compensator resolution was finer than 6 mm, maximum thickness at least 2 tenth-value-layers, and more than five beams were used. So