Citations

AbstractBackgroundAAPM Task Group (TG) 275 was charged with developing practical, evidence‐based recommendations for physics plan and chart review clinical processes for radiation therapy. As part of this charge, and to characterize practices and clinical processes, a survey of the medical physics community was developed and conducted. Detailed analyses and trends based on the survey that exceeded TG report length constraints are presented herein.AimsThe design, development, and detailed results of the TG‐ 275 survey as well as statistical analysis and trends are described in detail. This is complementary material to the TG 275 report.Methods and materialsThe survey consisted of 100 multiple‐choice questions divided into four main sections: 1) Demographics, 2) Initial Plan Check, 3) On‐Treatment, and 4) End‐of‐Treatment Chart Check. The survey was released to all AAPM members who self‐reported working in the radiation oncology field, and it was kept open for 7 weeks. Results were summarized using descriptive statistics. To study practice differences, tests of association were performed using data grouped by four demographic questions: 1) Institution Type, 2) Average number of patients treated daily, 3) Radiation Oncology Electronic Medical Record, and 4) Perceived Culture of Safety.ResultsThe survey captured 1370 non‐duplicate entries from the United States and Canada. Differences across practices were grouped and presented based on Process‐Based and Check‐Specific questions. A risk‐based summary was created to show differences amongst the four demographic questions for checks associated with the highest risk failure modes identified by TG‐275.ConclusionThe TG‐275 survey captured a baseline of practices on initial plan, on‐treatment, and end‐of‐treatment checks across a wide variety of clinics and institutions. The results of test of association showed practice heterogeneities as a function of demographic characteristics. Survey data were successfully used to inform TG‐275 recommendations.

OBJECTIVE Patient-reported outcomes (PROs) have become the standard means to measure surgical outcomes. Insurers and policy makers are also increasingly utilizing PROs to assess the value of care and measure different aspects of a patient’s condition. For cervical myelopathy, it is currently unclear which outcome measure best reflects patient satisfaction. In this investigation, the authors evaluated patients treated for cervical myelopathy to determine which outcome questionnaires best correlate with patient satisfaction. METHODS The Quality Outcomes Database (QOD), a prospectively collected multi-institutional database, was used to retrospectively analyze patients undergoing surgery for cervical myelopathy. The North American Spine Society (NASS) satisfaction index, Neck Disability Index (NDI), numeric rating scales for neck pain (NP-NRS) and arm pain (AP-NRS), EQ-5D, and modified Japanese Orthopaedic Association (mJOA) scale were evaluated. RESULTS The analysis included 1141 patients diagnosed with myelopathy, of whom 1099 had an NASS satisfaction index recorded at any of the follow-up time points. Concomitant radiculopathy was an indication for surgery in 368 (33.5%) patients, and severe neck pain (NP-NRS ≥ 7) was present in 471 (42.8%) patients. At the 3-month follow-up, NASS patient satisfaction index scores were positively correlated with scores for the NP-NRS (r = 0.30), AP-NRS (r = 0.32), and NDI (r = 0.36) and negatively correlated with EQ-5D (r = −0.38) and mJOA (r = −0.29) scores (all p < 0.001). At the 12-month follow-up, scores for the NASS index were positively correlated with scores for the NP-NRS (r = 0.44), AP-NRS (r = 0.38), and NDI (r = 0.46) and negatively correlated with scores for the EQ-5D (r = −0.40) and mJOA (r = −0.36) (all p < 0.001). At the 24-month follow-up, NASS index scores were positively correlated with NP-NRS (r = 0.49), AP-NRS (r = 0.36), and NDI (r = 0.49) scores and negatively correlated with EQ-5D (r = −0.44) and mJOA (r = −0.38) scores (all p < 0.001). CONCLUSIONS Neck pain was highly prevalent in patients with myelopathy. Notably, improvement in neck pain–associated disability rather than improvement in myelopathy was the most prominent PRO factor for patients. This finding may reflect greater patient concern for active pain symptoms than for neurological symptoms caused by myelopathy. As commercial payers begin to examine novel remuneration strategies for surgical interventions, thoughtful analysis of PRO measurements will have increasing relevance.

Objectives: The development and evaluation of percutaneous thrombectomy devices for pulmonary embolism (PE) pose a need for standardized large in vivo models with representative anatomical and physiological conditions and clots analogs. In this study, we present a swine model of PE model employing human-derived clot analogs. Material and Methods: Baseline angiographic and physiological pressure measurements were obtained in six adult Yorkshire pigs (45–65 kg) and results were benchmarked for interspecies comparison with published human data using fluoroscopic examinations, intra-arterial pressure measurements, and histologic studies. Then, clot analogs were created ex vivo employing banked human blood and a subset incubated in iodinated contrast for fluoroscopic visualization. Clot analogs were then embolized via a femoral venous access and angiographic/physiological consequences were evaluated. Results: The main, right, and left pulmonary artery diameters were 24 ± 1.1 mm, 16.5 ± 0.8 mm, and 12.6 ± 1.2 mm, respectively. The angle between the main pulmonary artery at the bifurcation point was approximately 90–95°. The clot analogs were heterogeneous and had increased fibrin content along the clot length. The overall composition was 96.63% red blood cell (RBC)/3.37% fibrin in the initial section, 48.85% RBC/51.15% fibrin in the intermediate section, and 3.44% RBC/96.56% fibrin in the final section. Embolization of the clot analogs resulted in distal occlusion of the right and left pulmonary arteries. Conclusions: This swine model coupled with clot analog is able to accurately mimic human anatomical and physiological conditions in PE making it feasible for the evaluation of pulmonary thrombectomy devices.

Abstract Background DICER1 alterations are associated with intracranial tumors in the pediatric population, including pineoblastoma, pituitary blastoma, and the recently described “primary DICER1-associated CNS sarcoma” (DCS). DCS is an extremely aggressive tumor with a distinct methylation signature and a high frequency of co-occurring mutations. However, little is known about its treatment approach and the genomic changes occurring after exposure to chemoradiotherapy. Methods We collected clinical, histological, and molecular data from eight young adults with DCS. Genomic analysis was performed by Next-generation Sequencing (NGS). Subsequently, an additional germline variants analysis was completed. In addition, an NGS analysis on post-progression tumor tissue or liquid biopsy was performed when available. Multiple clinicopathological characteristics, treatment variables, and survival outcomes were assessed. Results Median age was 20 years. Most lesions were supratentorial. Histology was classified as fusiform cell sarcomas (50%), undifferentiated (unclassified) sarcoma (37.5%), and chondrosarcoma (12.5%). Germline pathogenic DICER1 variants were present in two patients, 75% of cases had more than one somatic alteration in DICER1, and the most frequent commutation was TP53. Seven patients were treated with surgery, Ifosfamide, Cisplatin, and Etoposide (ICE) chemotherapy and radiotherapy. The objective response was 75%, and the median time to progression (TTP) was 14.5 months. At progression, the most common mutations were in KRAS and NF1. Overall survival was 30.8 months. Conclusions DCS is an aggressive tumor with limited therapeutic options that requires a comprehensive diagnostic approach, including molecular characterization. Most cases had mutations in TP53, NF1, and PTEN, and most alterations at progression were related to MAPK, RAS and PI3K signaling pathways.

Background: Despite the well-established potent benefit of mechanical thrombectomy (MT) for large vessel occlusion (LVO) stroke, access to MT has not been studied globally. We conducted a worldwide survey of countries on 6 continents to define MT access (MTA), the disparities in MTA, and its determinants on a global scale. Methods: Our survey was conducted in 75 countries through the Mission Thrombectomy 2020+ global network between November 22, 2020, and February 28, 2021. The primary end points were the current annual MTA, MT operator availability, and MT center availability. MTA was defined as the estimated proportion of patients with LVO receiving MT in a given region annually. The availability metrics were defined as ([current MT operators×50/current annual number of estimated thrombectomy-eligible LVOs]×100 = MT operator availability) and ([current MT centers×150/current annual number of estimated thrombectomy-eligible LVOs]×100= MT center availability). The metrics used optimal MT volume per operator as 50 and an optimal MT volume per center as 150. Multivariable-adjusted generalized linear models were used to evaluate factors associated with MTA. Results: We received 887 responses from 67 countries. The median global MTA was 2.79% (interquartile range, 0.70–11.74). MTA was <1.0% for 18 (27%) countries and 0 for 7 (10%) countries. There was a 460-fold disparity between the highest and lowest nonzero MTA regions and low-income countries had 88% lower MTA compared with high-income countries. The global MT operator availability was 16.5% of optimal and the MT center availability was 20.8% of optimal. On multivariable regression, country income level (low or lower–middle versus high: odds ratio, 0.08 [95% CI, 0.04–0.12]), MT operator availability (odds ratio, 3.35 [95% CI, 2.07–5.42]), MT center availability (odds ratio, 2.86 [95% CI, 1.84–4.48]), and presence of prehospital acute stroke bypass protocol (odds ratio, 4.00 [95% CI, 1.70–9.42]) were significantly associated with increased odds of MTA. Conclusions: Access to MT on a global level is extremely low, with enormous disparities between countries by income level. The significant determinants of MT access are the country’s per capita gross national income, prehospital LVO triage policy, and MT operator and center availability.

OBJECTIVE Return to work (RTW) is an important surgical outcome for patients who are employed, yet a significant number of patients with cervical spondylotic myelopathy (CSM) who are employed undergo cervical spine surgery and fail to RTW. In this study, the authors investigated factors associated with failure to RTW in the CSM population who underwent cervical spine surgery and who were considered to have a good surgical outcome yet failed to RTW. METHODS This study retrospectively analyzed prospectively collected data from the cervical myelopathy module of a national spine registry, the Quality Outcomes Database. The CSM data set of the Quality Outcomes Database was queried for patients who were employed at the time of surgery and planned to RTW postoperatively. Distinct multivariable logistic regression models were fitted with 3-month RTW as an outcome for the overall population to identify risk factors for failure to RTW. Good outcomes were defined as patients who had no adverse events (readmissions or complications), who had achieved 30% improvement in Neck Disability Index score, and who were satisfied (North American Spine Society satisfaction score of 1 or 2) at 3 months postsurgery. RESULTS Of the 409 patients who underwent surgery, 80% (n = 327) did RTW at 3 months after surgery. At 3 months, 56.9% of patients met the criteria for a good surgical outcome, and patients with a good outcome were more likely to RTW (88.1% vs 69.2%, p < 0.01). Of patients with a good outcome, 11.9% failed to RTW at 3 months. Risk factors for failing to RTW despite a good outcome included preoperative short-term disability or leave status (OR 3.03 [95% CI 1.66–7.90], p = 0.02); a higher baseline Neck Disability Index score (OR 1.41 [95% CI 1.09–1.84], p < 0.01); and higher neck pain score at 3 months postoperatively (OR 0.81 [95% CI 0.66–0.99], p = 0.04). CONCLUSIONS Most patients with CSM who undergo spine surgery reenter the workforce within 3 months from surgery, with RTW rates being higher among patients who experience good outcomes. Among patients with good outcomes who were employed, failure to RTW was associated with being on preoperative short-term disability or leave status prior to surgery as well as higher neck pain scores at baseline and at 3 months postoperatively.

Abstract Background: Adjuvant oral tamoxifen (TAM) benefits women with DCIS, but toxicity concerns have limited its acceptance. Transdermal therapy with 4-hydroxy tamoxifen (4-OHT) gel applied to the breast skin is a possible solution. Previous pilot data suggest equivalent anti-proliferative efficacy of TAM and 4-OHT gel, but minimal systemic exposure with transdermal therapy. We report a prospective double blinded randomized phase 2 trial comparing TAM to 4-OHT gel in women with DCIS. Methods: 107 women with estrogen receptor positive (≥10%) DCIS were randomized to TAM (20 mg/day + placebo gel) or 4-OHT gel (2mg 4-OHT gel/breast, bilaterally + oral placebo), for 4-10 weeks prior to surgery. The primary endpoint was reduction in DCIS Ki67 labeling index (LI). Secondary endpoints included the 12-gene DCIS Score assay (Exact Sciences), breast tissue and plasma concentrations of 4-OHT and endoxifen, TAM-responsive circulating proteins, and patient reported symptoms (Breast Eight Symptom Scale). We estimated that 80 evaluable participants would provide 80.5% power to establish non-inferiority of 4-OHT, defined as relative Ki67-LI decline &gt;35% and absolute decline &gt;2.6%, with one-sided 𝛼=0.10. Non-inferiority of 4-OHT gel for Ki67-LI reduction was tested using an ANCOVA model. Statistical comparisons within- and between-arms were calculated with paired t-test and Welch Two Sample t-test, respectively. Results: 72 of 87 women adhered to the protocol, and were evaluable for the primary endpoint (39 TAM and 33 4-OHT gel). Mean treatment duration was 47 days for TAM and 44 days for 4-OHT gel (p=0.2). The median absolute decline in Ki67 labeling index was significant in the oral TAM (-3.7%, p&lt; 0.001) but not in 4-OHT gel arm (-1.3%, p=0.2) (p=0.002). Ki67 results following menopausal stratification also favored the TAM arm: (-1.3%; p=0.06 in 37 premenopausal women and -3.7%; p=0.02 in 35 postmenopausal women). Similarly, DCIS score showed a significantly greater reduction in the TAM (-14, p&lt; 0.001) but not in the 4-OHT gel arm (-4, p=0.1). Tissue 4-OHT concentrations were non-significantly higher in the TAM arm and were similar between superficial and deep sampling locations (superficial 6.1 and 4.2 ng/g for TAM and 4-OHT gel, respectively, p= 0.55; deep 5.7 and 3.8 ng/g, respectively, p= 0.06), whereas plasma 4-OHT concentration was markedly lower in the gel group (2 ng/mL and 0.24 ng/mL for TAM and 4-OHT gel, respectively, P &lt; 0.001). Endoxifen was abundant in plasma (11 ng/mL) and deep tissue (13 ng/g) of the TAM arm, but present in trace amounts in the 4-OHT gel arm (undetectable in plasma and 0.31 ng/g in tissue; p &lt; 0.001). Circulating TAM responsive markers (insulin like growth factor 1, sex hormone binding globulin, von Willebrand factor, and protein S total) and vasomotor symptoms were significantly and unfavorably modulated by TAM, but not by 4-OHT gel therapy. Conclusions: The non-inferiority of transdermal 4-OHT gel to Tam in terms of anti-proliferative effect in DCIS lesions was not demonstrated at the doses used for this study. DCIS Score analysis gave similar results. Tissue 4-OHT concentration in 4-OHT gel and Tam-treated subjects was roughly similar. However, endoxifen exposure was higher with oral TAM therapy and may partially explain the observed differences in major endpoints. In future studies, use of higher 4-OHT gel doses, longer duration of treatment, or different formulation may overcome these. Citation Format: Oukseub Lee, Xinlei Mi, Yanfei Xu, Luis Blanco, Azza M. Akasha, Kelly Benante, Shanshan Zhang, Carissa LaBoy, Thomas Helland, Melissa Pilewskie, Amy Degnim, Zahraa Al-Hilli, Amanda L. Amin, E Shelley Hwang, Joseph M. Guenther, Simon Steinar Hustad, Demirkan B. Gursel, Masha Kocherginsky, Gunnar Mellgren, Eileen Dimond, Marjorie Perloff, Brandy M. Heckman-Stoddard, Seema Khan. PD15-12 A pre-surgical window trial of oral tamoxifen versus transdermal 4-hydroxytamoxifen gel in women with estrogen receptor positive duct carcinoma in situ (DCIS) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD15-12.

AbstractBackgroundRenal medullary carcinoma (RMC) is a diagnostically challenging, aggressive primary renal malignancy associated with abysmal survival. Delays in diagnosis contribute to most patients having diffusely metastatic disease at the time of initial presentation.MethodsWe present the case of a 13‐year‐old African American male with sickle cell trait who presented with a renal mass and hematuria. Evaluation included imaging, fluid cultures, and cytologic assessment.ResultsPatient was diagnosed with RMC based on cytologic assessment of sub‐centimeter fluid collections aspirated from the left kidney at the time of cortical biopsy for suspected renal mass. The additional fluid aspiration in conjunction with renal biopsy was an atypical but crucial step in early diagnosis.ConclusionCytomorphologic evaluation of fluid biospecimens is not currently part of the standard work‐up for patients with renal masses but, when available, can provide crucial information that reduces time to diagnosis. Prompt symptom recognition and treatment initiation may improve patient outcomes.

Abstract Over the past years, several arthroscopic fixation procedures have been adopted for fractures of the greater tuberosity. Although they offer advantages over open approaches, especially for avulsion‐type fixation, split‐type fractures are usually treated with open reduction and internal fixation. However, suture constructs can result in a more reliable fixation system for multifragment or osteoporotic split‐type fractures. Currently, the use of arthroscopic techniques in these more complex fractures is questionable due to inherent limitations of anatomic reduction and stability concerns. The authors report a technically simple and reproducible arthroscopic procedure based on anatomic, morphologic, and biomechanical concepts, which offers advantages over traditional open approaches or double‐row arthroscopic techniques in the treatment of most split‐type greater tuberosity fractures. Technique Video video See video under supplementary data.