Citations

98 Background: Prior authorization (PA) purports to control costs and ensure adherence to evidence-based guidelines but negatively impacts cancer care. Radiation oncology (RO) represents a minority of overall cancer spending yet bears a disproportionately high PA burden. Limited research exists on the effects of PA on patient outcomes and administrative workload within RO clinics. Methods: From 9/2024 to 10/2024, an online survey was open to U.S. members of the American Society for Radiation Oncology assessing experiences with PA including disposition (approval/denial/appeal including peer-to-peer [P2P] review) and perceived impact on patient care and administrative workload. Outcomes included treatment delays, changes from recommended treatment, and patient event including hospitalization, ED visits, permanent disability, or death. Descriptive statistics evaluated responses. Results: Of 736 responding radiation oncologists (16% response rate), 83% reported a rise in PA over the past three years, with 58% noting the burden has increased greatly. In the past year, 50% reported that more than half of their cases required PA, with a median approval rate of 75% and median overturn rate of 82% for denials. For more than half of their cases, nearly half of physicians (43%) noted that P2P was a futile effort to overturn PA denials due to insurance policies. Most (75%) reported that PA resulted in their practice needing to reallocate staff; 91% reported worsening burnout due to PA. P2P reviews were particularly burdensome, averaging 1.65 hours per week. A third (30%) reported that PA requirements had caused serious complications for their patients, including 7% who reported PA had contributed to patient death. Almost all (91%) reported PA-related treatment delays for some of their patients, with 58% indicating average delays of ≥5 days. Most (81%) reported that at times they had to use radiation techniques they considered less optimal due to PA, including 58% who were forced to deviate from national guidelines. The most common reasons for not appealing a PA denial were anticipated delays (73%), perceived futility based on prior PA experiences (62%), and administrative burden (45%). Conclusions: The administrative and clinical burdens associated with PA have significant implications for patient care, physician well-being, and healthcare resource allocation in RO. Treatment delays, compromised therapies, and adverse patient outcomes are commonly reported and underscore the need for PA reform to improve patient outcomes, reduce physician burnout, and improve efficiency.

Abstract In recent years, various tracking technologies that work independently of imaging systems have been proposed to automate, simplify, and enhance various tasks in the brachytherapy treatment workflow. These tasks, critical to the overall accuracy of the therapeutic dose delivery, include applicator, catheter and needle insertion guidance, and reconstruction as well as transfer tube connection in afterloading technique. Task Group 317 was established as a joint American Association of Physicists in Medicine (AAPM) and European Society for Radiotherapy and Oncology (ESTRO) committee to review: the current state‐of‐the‐art scientific literature as it pertains to tracking technology in the field of brachytherapy; the benefits and issues related to the use of the technology for automated reconstruction of brachytherapy implants, quality control (QC) tasks such as channel path and tip reconstruction, and real‐time guidance tasks; their limitations, in particular in the clinical environment and, finally, to develop recommendations related to commissioning, quality assurance (QA) and clinical use. The Task Group has looked in detail at key tracking technologies in advanced brachytherapy applications: infrared, electromagnetic, fiber optic shape sensing (fiber Bragg grating), and active radiofrequency coil tracking. For each, the performance and accuracy in well‐controlled conditions as well as in clinically relevant environments are provided. Guidelines for clinical implementations, including target accuracy and performance needed for critical tasks, are summarized. Risk‐based analysis is discussed in the context of an electromagnetic‐based tracking system used as part of a clinical trial. The report concludes with the essential elements of an effective quality management program dedicated to the advanced features enabled by the above‐described technology.

Background: Chronic nonspecific low back pain (CNLBP) is a prevalent, disabling condition worldwide. Tuina, a traditional Chinese manual therapy, has shown potential benefits, but evidence remains limited. Objective: This study evaluated the effectiveness and safety of Tuina therapy in managing CNLBP in a U.S. population. Methods: A prospective, single-blind, randomized controlled trial was conducted at Mayo Clinic Rochester campus (February 2020-April 2024). 204 participants with CNLBP were randomized into 3 groups: Tuina (N = 68), physical therapy (N = 68), or a combination of both (N = 68). Each group received 6 treatments over 2 months. The primary outcome was pain intensity (VAS); secondary outcomes included disability (ODI), quality of life (SF-36), and adverse events. Additionally, participants completed a satisfaction survey at the end of the trial. Research Electronic Data Capture (REDCap) was used for survey data collection. Data was assessed by analysis of variance (ANOVA) for the multiple repeated measurements, Kruskal-Wallis tests, while Chi-square tests, and Bonferroni correction in SAS software. Results: 185 subjects completed the study. Significant decreases in VAS, ODI, and SF-36 Overall Physical scores were found from baseline, to post treatment and follow-up in all groups ( P < .05), while there were no significant differences in VAS, ODI, or SF-36 outcomes between the Tuina group and the other 2 groups. There were 4 adverse events observed in the trial, 1 in the Physical therapy group and 3 in the Mixed group. Only 1 transient low back pain after Tuina therapy was observed in the Mixed group but did not require treatment. The high percentage of patients who received the Tuina program was extremely helpful (n = 94/126, 77.0%). The willingness to recommend was significantly higher for Tuina compared to physical therapy (Mixed group [N = 59/62, 95.2%], Tuina group [N = 57/64, 91.9%], and physical therapy group [N = 31/59, 59.6%] ( P < .05). Conclusion: Tuina therapy showed comparable benefits to physical therapy and combined treatment of both in improving pain, function, and quality of life in patients with CNLBP. With high patient satisfaction and a favorable safety profile, Tuina appears to be a safe and acceptable non-invasive treatment option. Further studies are needed to validate these findings in the future.

Abstract BRCA-associated homologous recombination deficiency (HRD) is present in ~ 50% of high-grade serous carcinomas (HGSC) and predicts sensitivity to platinum-based therapy. However, there is little understanding of why some patients with BRCA-deficient tumors experience unexpectedly poor outcomes. We profiled 154 tumors, enriched for patients with BRCA-deficient tumors that experienced short overall survival (≤ 3 years, n = 42), using whole-genome, transcriptome, and methylation analyses. All but one BRCA-deficient tumor exceeded an accepted HRD genomic scarring threshold. However, patients with BRCA1-deficient HGSC with a more elevated HRD score survived significantly longer. Patients with BRCA2-deficient HGSC and loss of NF1 survived twice as long as those without NF1 loss, whereas PIK3CA or RAD21 amplification defined BRCA2-deficient HGSC with exceptionally short survival. BRCA1-deficient tumors in short survivors had evidence of immunosuppressive c-kit signaling and EMT. In a large HGSC cohort (n = 1,389) including 282 individuals with pathogenic germline BRCA variants (gBRCApv), the location of the mutation within functional domains stratified clinical outcomes. Notably, residual disease after primary surgery had limited prognostic effect in gBRCApv-carriers compared to non-carriers. Our findings indicate that tumor HR proficiency in the context of therapy response and survival is not a binary property, and highlight genomic and immune modifiers of outcomes in BRCA-deficient HGSC.

With the first series of PRRX1 -rearranged tumors published in 2019, the spectrum of these so-called fibroblastic tumors has been expanded. Since then, several smaller case series have been published; however, our understanding of them continues to be quite limited given their rarity. We herein studied 18 additional cases, the largest series to date. Eighteen tumors present in 9 male, 8 female, and 1 nonbinary patient with a median age of 35 years (range: 11 to 70 y) and involved the neck (5), the chest region (4), thigh (3), back (1), shoulder (1), forehead (1), lower leg (1), axilla (1), and the parapharyngeal region (1). Clinical follow-up (9/18 tumors; 50%; median: 10 mo; range: 4 to 40 mo) showed consistent indolent behavior without local recurrences or distant metastases. On morphology, these tumors were characterized by well-circumscription and distinctive peripheral crescent-shaped vessels. They were composed of uniform spindle and round cells growing in short fascicles within often densely hyalinized collagen lacking significant mitotic activity, necrosis, or cytologic atypia. Immunohistochemically, about half of the tested tumors expressed focal to rarely diffuse S100 with occasional co-expression of SOX10. Interestingly, almost half of the tested cases also showed complete loss of RB expression. All but 1 tumor harbored a PRRX1::NCOA1 fusion, while 1 case harbored a novel PRRX1::EP300 fusion. We herein provide additional data on these exceptionally uncommon tumors, expand their molecular spectrum, and compare them to their close morphologic mimics to aid in accurate diagnosis and avoid confusion with potentially more aggressive neoplasms.

Key Points Increased protein expression of tissue inhibitor of metalloproteinase-3, glypican 6, synuclein γ , apolipoprotein A-4, and Ecto-5′-nucleotidase was observed in old adults compared with young adults. In old adults, overexpressed proteins were enriched in mitochondrial processes while under expressed proteins enriched in RNA metabolism. Validated differentially expressed proteins were not significantly correlated with kidney pathology after adjusting for age. Background Kidney aging is characterized by a loss of glomeruli, predominantly in the superficial cortex, with a resultant decline in GFR and an increased risk of various kidney-related diseases. The early molecular alterations in glomeruli associated with the aging process are not well studied. Methods We combined laser capture microdissection and mass spectrometry–based unbiased proteomic analysis of nonsclerosed, nonischemic glomeruli in the superficial cortex from young and old adults who underwent a radical nephrectomy for a tumor to understand the age-related molecular changes in glomeruli. Twenty-four young and 30 old adults were used for the discovery dataset, and the significant differentially expressed proteins were further validated using an independent set comprising six young and eight old adults. Results Kidneys from old adults had lower eGFR, less kidney parenchyma on computed tomography imaging, and more glomerulosclerosis and arteriosclerosis on histology. Quantitative proteomic analysis of nonsclerosed, nonischemic glomeruli identified increased expression of tissue inhibitor of metalloproteinase-3, glypican 6, synuclein γ , apolipoprotein A-4, and Ecto-5′-nucleotidase in old adults that were further validated in an independent set. Pathway analysis indicated that proteins with increased expression in old adults were enriched in mitochondrial translational processes, aerobic respiration, and TCA cycle, whereas proteins with decreased expression in old adults were enriched in mRNA splicing, mRNA processing, and nonsense mediated decay. Furthermore, validated differentially expressed proteins did not show any significant correlation with the kidney pathology independent of age group. Conclusions Overall, this study identified proteins that are specifically associated with the aging process in otherwise normal-appearing glomeruli.