Citations

Abstract Background Burnout is a work‐related syndrome characterized by increased levels of emotional exhaustion (EE) and depersonalization (DP) along with decreased levels of personal achievement. In the healthcare setting, higher burnout levels have been associated with negative impacts on personnel, an increased risk of errors, and a decrease in the quality of delivered care. Purpose The purpose of this study was to assess the prevalence of burnout among medical physicists working in the United States. Additionally, the impact of personal and organizational features on burnout risk was examined. Methods The anonymous survey was distributed to 1962 full members of the American Association of Physicists in Medicine. The survey consisted of seven demographic questions, the validated Maslach Burnout Inventory (MBI), and an organizational assessment tool. Burnout risk was evaluated using two different scoring methods. Inferential statistics were employed to examine the relationship between burnout and personal features, such as practiced sub‐specialty, and organizational features, including the respondent's assigned facility safety score. Results A total of 337 responses were received, and 59.9% of medical physicist participants scored high on at least one burnout domain. A statistically significant association was found between the EE and DP burnout domains and personal factors, including working as a therapy medical physicist, working longer hours, and a moderate or significant impact on work‐related feelings due to the COVID‐19 pandemic. A statistically significant relationship was identified between all three burnout domains and the respondent's assigned facility safety score. Amongst therapy physicists, an inverse relationship was observed between all three burnout domains and both the teamwork and staffing constructs, as well as the open communication and punitive concerns construct. Conclusions Medical physicists in the United States are experiencing significant levels of burnout. Importantly, this study identified a link between quantitative burnout scores and facility safety, stressing the importance of addressing burnout.

Abstract The establishment of guidelines and curriculum standards for medical physics residency training is a critical component of setting expectations and competencies for the profession. Since the last publication of these standards, residency training has become integrated into the eligibility criteria for most medical physics certification bodies. The rapid growth of medical physics requires periodic review of the curriculum to remove outdated approaches, update established knowledge, and add emerging technologies. The goal of this document is to provide a reference standard for residency training program directors, training mentors, and residents to guide creation and/or optimization of their program's curriculum. The document is intentionally forward‐looking to capture emerging technological advances including hybrid diagnostic and therapeutic delivery systems and applications of image processing. This document is an update of the current residency training curriculum. Version history of residency training guidelines Publication Title Date 2013 Essentials and Guidelines for Clinical Medical Physics Residency Training Programs—AAPM Report No. 249 2006 Essentials and Guidelines for Hospital‐Based Medical Physics Residency Training Programs—Report No. 90 1992 Essentials and Guidelines for Hospital‐Based Medical Physics Residency Training Programs—Report No. 36 The Work Group on Periodic Review of Medical Physics Residency Training (WGMPRT) would like to acknowledge the authors of past versions of this document as they form the basis for this update. It is the sincere hope of the WGMPRT that this report will continue to be used by the medical physics community to guide training in the profession.

Atopic dermatitis affects 20% to 25% of children and has significant impact on quality of life of patients and families. Recent studies of the pathogenesis of AD highlight the interplay between a defective skin barrier, immune dysfunction, and the cutaneous microbiome. Standard of care for AD treatment includes topical corticosteroids for active disease and moisturization to repair the barrier defect. Emerging treatments include dupilumab and Janus kinase (JAK) inhibitors. Reduction of triggers and proactive treatment with topical corticosteroids and/or topical calcineurin inhibitors can reduce flares. Treatment plans should be clear and as simple as possible to maximize adherence.

Abstract Purpose While immunotherapy has transformed treatment in multiple solid tumors, its efficacy in high-grade glioma remains limited. Understanding the molecular and clinical factors that influence glioma’s response to immunotherapy is essential to improving outcomes. Methods We identified patients with recurrent glioblastoma or astrocytoma, IDH-mutant grade 4, who had been treated with checkpoint inhibitor (CPI), virus therapy, or cell therapy and determined the association between their molecular, clinical, and demographic characteristics and survival outcomes. Results We identified 66 patients, 57 glioblastoma and 9 astrocytoma, IDH-mutant grade 4; 38 were treated with CPI, 22 with virus therapy, and 6 with cell therapy. PIK3CA mutation was associated with shorter PFS and OS (p = 0.022, 0.073, respectively) among all patients and a shorter OS among CPI-treated patients (p = 0.004). Tumor tissue without the mutation had less PD-1 expression in CD3+/CD8 + T cells. In CPI-treated patients, IDH1/2 mutation was associated with a shorter OS (p = 0.002), and mutations in RB1 and TERT promoter were associated with a shorter PFS (p-value = 0.00056, 0.022, respectively). Length of CPI therapy of more than 6 months was associated with increased PFS and OS (p = 0.048, 0.062, respectively), while steroid use at baseline was associated with a shorter OS (p = 0.00023). Multifocal disease was associated with shorter PFS and OS durations (p = 0.0017, 0.0013, respectively) among all patients. Conclusions In high-grade glioma, PIK3CA, IDH1/2, RB1, and TERT promoter mutations may be associated with a poor response to immunotherapy. Our results may provide the rationale for clinical trials combining PI3K and IDH inhibitors with CPI in high-grade glioma.

Abstract Glioblastoma (GBM) remains the most common and lethal adult malignant primary brain cancer with few treatment options. A significant issue hindering GBM therapeutic development is intratumor heterogeneity. GBM tumors contain neoplastic cells within a spectrum of different transcriptional states. Identifying effective therapeutics requires a platform that predicts the differential sensitivity and resistance of these states to various treatments. Here, we developed a novel framework, ISOSCELES ( I nferred cell S ensitivity O perating on the integration of S ingle- C ell E xpression and L 1000 E xpression S ignatures), to quantify the cellular drug sensitivity and resistance landscape. Using single-cell RNA sequencing of newly diagnosed and recurrent GBM tumors, we identified compounds from the LINCS L1000 database with transcriptional response signatures selectively discordant with distinct GBM cell states. We validated the significance of these findings in vitro, ex vivo, and in vivo , and identified a novel combination of an OLIG2 inhibitor and Depatux-M for GBM. Our studies suggest that ISOSCELES identifies cell states sensitive and resistant to targeted therapies in GBM and that it can be applied to identify new synergistic combinations. Highlights Integration of GBM single-cell RNA sequencing data with L1000-derived drug response signatures facilitates clustering of tumor cells and small molecules on cell-drug connectivity. Cell-drug connectivity predicts the identities of drug-sensitive and resistant cell states. In silico perturbation analysis using cell-drug connectivity predicts drug-induced changes in the cell-drug connectivity landscape in vivo. In silico perturbation analysis to predict drug-induced changes in the tumor cell-drug connectivity landscape predicts drug combinations that synergize in vivo to extend survival.

ABSTRACT Objective There is limited consensus on endoscopic skull base surgery (ESBS) reconstruction principles. This study aims to generate comprehensive themes regarding ESBS reconstruction by pooling the experiences of ESBS experts, with comparison to a literature review of current published evidence. Methods Structured qualitative interviews of ESBS experts regarding postoperative management and reconstruction of various defect locations were conducted. Results A total of 68 experts comprising 40 academic teams across 13 countries with an average of 18 years of ESBS experience were included. We propose 10 stepwise algorithms for common skull base reconstruction scenarios based on these expert interviews. When available, the nasoseptal flap is used for all high_flow cerebrospinal leak defects. Multilayered reconstruction is favored at all anatomical subsites with increasing number of layers for increasing defect size and complexity. Heterogeneity exists in terms of inlay technique and materials, free grafting versus various pedicled flap options for low‐flow defects or in the absence of a nasal septum, nasal packing, tissue sealant, lumbar drain use, and postoperative management. Commonalities and discrepancies between experts were summarized. Conclusion Skull base reconstruction and post‐ESBS management is highly complex with a wide variety of practice patterns and expert strategies. Further research of higher quality evidence is warranted to identify optimal management patterns, though the current work aims to inform surgeons on these controversial areas by drawing from numerous experiences.

Abstract The 21st Century Cures Act Final Rule (Final Rule) increases patient access to their health records but raises concerns about distress and misunderstanding of automatically released results and documentation. Little is known about genetic counselors' (GCs') experiences with the Final Rule. In Fall 2023, we conducted a cross‐sectional survey of US GCs about the Final Rule's perceived impact on practice and assessed if being the ordering versus non‐ordering provider for genetic testing affected perceptions of Final Rule‐related changes. GCs ( n = 102) reported demographic and workplace characteristics, institutional policy changes, workflow changes, and perceived patient harms and benefits due to the Final Rule. To compare ordering and non‐ordering providers, we conducted Fisher's exact tests for categorical variables and trend tests for ordinal variables. Open‐response questions elicited examples of positive and negative patient impacts, the effects of patient characteristics, and practice changes in response to the Final Rule. Twenty‐seven GCs were ordering providers and 66 were non‐ordering providers. Relative to ordering providers, non‐ordering providers expressed stronger agreement with statements indicating concern about the emotional impact on patients reviewing results or notes without support ( p = 0.002, 33% vs. 51% strongly agree), patients misunderstanding or misinterpreting results ( p = 0.025, 44% vs. 70% strongly agree), and patients contacting the inappropriate party to discuss results ( p = 0.023, 19% vs. 48% strongly agree). Agreement with the statement “patients have more knowledge/context/questions at our disclosure session due to previous results review” also differed by ordering provider status ( p = 0.007). In open responses, GCs expressed concerns about patients' strong emotional reactions, patients misinterpreting results, workflow disruptions, and widening health disparities. Benefits included patients' ability to be reassured, informed, or empowered earlier; ease of sharing health information; more efficient workflow due to the automatic release of results. These results emphasize the importance of clear communication within health systems and between patients and providers.

Abstract Rational: Talc pleurodesis is an effective intervention for preventing recurrent pleural effusions and pneumothoraces, particularly in non-surgical candidates. Due to its efficacy and safety, it is recommended as the most effective sclerosant for pleurodesis. However, in some cases, the initial pleurodesis fails, necessitating a repeat procedure. The efficacy of repeat talc pleurodesis after an initial failure is an area that requires further exploration. This study explores the safety and efficacy of repeat talc pleurodesis among patients who did not respond to the initial intervention. Methods: This retrospective study analyzed hospitalized patients who underwent 4g talc slurry pleurodesis from 2019 to 2024, focusing on demographics, comorbidities, initial pleurodesis failure, and recurrence rates. Pleurodesis failure was identified by lung sliding, recurrent effusion, or pneumothorax during the same hospitalization. The primary outcome was recurrence post-discharge, assessed by pleural effusion or pneumothorax within 180 days post-repeat pleurodesis. Results: This study included 94 patients (52.1% male, 47.9% female) with a mean age of 67.6. Among them, 79 (84%) received a single 4g dose of talc, while 15 (16%) received multiple 4g talc doses for initial pleurodesis. Recurrence occurred in 20 (25.3%) of the single-dose group and 1 (6.7%) of the multiple-dose group within 180 days, though the difference was not statistically significant (p=0.112). Recurrence-free rates were 93.6% at 30 days, 85.1% at 90 days, and 77.7% at 180 days. Of the 20 patients with recurrence after a single 4g dose of talc, 8 (40%) underwent repeat pleurodesis, with only one recurrence requiring surgical intervention. Additionally, there was no recurrence after repeat talc pleurodesis in the one patient with recurrence after receiving multiple 4g talc doses for initial pleurodesis. No associations were found between recurrence rates and factors like gender (p=0.213) or comorbidities (emphysema, COPD, lung malignancy). Chest pain was a common complaint, but no cases of respiratory distress were reported post-pleurodesis. Conclusion: The efficacy of initial talc pleurodesis (77.7%-93.6%) in this cohort aligns with existing literature. Multiple-dose talc pleurodesis effectively prevented recurrence in 93.3% of patients, with no reported respiratory distress. Additionally, repeat talc pleurodesis was successful in 87.5% of those with recurrence after an initial single 4g dose. These findings support multiple-dose talc pleurodesis and repeat talc pleurodesis as safe and effective options for preventing recurrence post-initial failure and post-repeat talc pleurodesis, respectively. Although no significant recurrence predictors were identified, future research could focus on patient-specific factors to enhance treatment selection and optimize outcomes.

Abstract Rationale: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer. They are also associated with life-threatening immune-related adverse events (irAEs), including the rare, poorly understood, and potentially fatal triad of myasthenia gravis, myocarditis, and myositis(triple M syndrome). We aimed to describe the management, intensive care unit (ICU)utilization, and outcomes of patients with irAEs with a specific focus on triple M syndrome. Methods: We conducted a retrospective chart review of patients with irAEs admitted to three quaternary care hospitals between December 2018 and 2023. We aimed to collect data on demographics, cancer type, treatment, ICU resource utilization, and outcomes including mortality. Results: Over this 5-year period, 140 patients were admitted for irAEs. Forty-nine percent were male, median age was 73 (IQR 64-80) years, 7% were of African American or Asian descent, and 32%required ICU admission. Median ICU and hospital length of stay (LOS) were 1.5 (IQR 0.7-2.9)and 7.2 (IQR 4.1-13.4) days, respectively. Among ICU patients, 14/140 (10%) had myositis,22/140 (16%) myocarditis, and 9/140 (6.4%) myasthenia gravis. Triple-M syndrome was diagnosed in 7/140 (5%) patients, including 3 with metastatic melanoma, 2 with genitourinary malignancies, 1 with metastatic lung and 1 with colon cancer. Four had received pembrolizumab and 3 nivolumab. Median ICU and hospital LOS were 3 (IQR 1-6) and 10 (IQR 8-21) days in this group. Three patients required mechanical ventilation, one required tracheostomy, and one required vasopressor support. Triple-M management included corticosteroids, IVIG, pyridostigmine, mycophenolate mofetil, and rituximab. Patients with triple-M syndrome were significantly older than other patients with ICI toxicity (P <0.009) and had higher mortality (57%vs 25%, p = 0.07). Patients discharged from the ICU had a median survival of 67 (IQR 26-201)days. Conclusions: Patients with irAEs frequently require ICU level of support with significant morbidity and mortality, especially with triple M syndrome. Clinicians should always consider the possibility of triple-M syndrome in patients with multiple irAEs as symptoms can be subtle and easily overlooked. Corticosteroids remain the primary treatment of irAEs and can be combined with other immunosuppressive agents such as infliximab, anti-thymocyte globulin, or pyridostigmine. Unfortunately, mortality due to triple-M syndrome remains high underscoring the importance of early recognition and prompt multidisciplinary management of these toxicities.

Abstract Rationale: Hematopoietic cell transplantation (HCT) risk scores have seen minimal updates over the past 20 years, despite advancements in clinical practice. Pulmonary function test (PFT) thresholds, initially based on NHANES reference equations, now have alternative reference standards from the Global Lung Function Initiative (GLI) 2012 and GLI-Global, which may reclassify patients and affect outcomes. This study investigates the impact of GLI reclassification on outcomes in HCT, comparing traditional fixed thresholds with continuous (z-score) risk assessment models. Methods: A retrospective review of 3,120 adult patients who underwent autologous HCT at MD Anderson Cancer Center from 1999 to 2015 was conducted. Primary endpoints were ICU admission, mechanical ventilation (IMV), and survival within 120 days post-transplant. PFT measures (FEV1, FVC, DLCO) were calculated using GLI-2012 and GLI-Global reference equations, analyzed both continuously (z-scores) and categorically by ATS/ERS guidelines. Cox proportional hazards and logistic regression models were employed, with AUROC comparisons to evaluate predictive performance. Results: The cohort had a mean age of 49 years (SD 14), with 41% female and 77% White. Of the 3,120 patients included in the study, the cohort consisted of 77% White, 5.4% Black, 3.3% Asian, and 14% identifying as other ethnicities. At 120 days, mortality was 1% (n=41), ICU admission 5% (n=169), and IMV 2% (n=70). Continuous DLCO was associated with a lower risk of mortality (HR: 0.75; p=0.03), ICU admission (OR: 0.83; p=0.01), and IMV (OR: 0.80; p=0.02). GLI-Global's FEV1 z-scores were also significant for mortality (HR: 0.70; p=0.01), ICU admission (OR: 0.74; p<0.0001), and IMV (OR: 0.70; p=0.0003). Categorical analyses showed significant mortality reduction with normal DLCO (HR: 0.46; p=0.01) and ICU admission reduction with normal FEV1 GLI-2012 (OR: 0.63; p=0.02). Reclassification by race, as shown in Figure 1, indicated that race-specific equations overestimated PFT values in Black patients and underestimated them in Asian patients. Conclusion: Reclassification by GLI reference equations, particularly using continuous z-scores, significantly influences post-HCT outcomes, suggesting that continuous assessment may improve risk stratification. Including race does not improve the model's performance. These findings support integrating updated PFT references and continuous risk models into HCT prognostic tools for enhanced clinical decision-making.