Race and Ethnicity Representation in Phase 2/3 Oncology Clinical Trial Publications: A Systematic Review.

Importance: The five 1997 Office of Management and Budget races in the US include American Indian or Alaska Native, Asian, Black or African American, Native Hawaiian or Other Pacific Islander, and White, with Hispanic ethnicity. Despite the Affordable Care Act mandating Office of Management and Budget-based collecting and reporting standards, race and ethnicity publishing in medical journals is inconsistent, despite being necessary to achieve health equity. Objective: To quantify race and ethnicity reporting rates and calculate representation quotients (RQs) in published oncology clinical trials. Evidence Review: In this systematic review, PubMed and Embase were queried for phase 2/3 clinical trials of the 6 most common noncutaneous solid cancers, published between January 1, 2012, and December 31, 2022, in 4 high-impact journals. Trial characteristics were recorded. The RQs for each race and ethnicity were calculated by dividing the percent of representation in each clinical trial publication by the percent of year-matched, site-specific incident cancers in the US, compared with Kruskal-Wallis tests with Bonferroni correction (BC). Reporting was compared between journal publications and ClinicalTrials.gov. Findings: Among 1202 publications evaluated, 364 met inclusion criteria: 16 JAMA, 241 Journal of Clinical Oncology, 19 Lancet, and 88 New England Journal of Medicine. Publications included 268 209 patients (171 132 women [64%]), with a median of 356 (IQR, 131-800) patients per publication. Reported race and ethnicity included American Indian or Alaska Native in 52 (14%) publications, Asian in 196 (54%), Black or African American in 215 (59%), Hispanic in 67 (18%), Native Hawaiian or Other Pacific Islander in 28 (8%), and White in 254 (70%). Median RQ varied across race (P < .001 BC), with 1.04 (IQR, 0.09-4.77) for Asian, 0.98 (IQR, 0.86-1.06) for White, 0.42 (IQR, 0.12-0.75) for Black or African American, and 0.00 (IQR, 0.00-0.00) for both American Indian or Alaska Native and Native Hawaiian or Other Pacific Islander patients. Sensitivity analyses showed similar findings on subset analysis for US-only clinical trials. There was significantly less race and ethnicity reporting in the clinical trial publications compared with ClinicalTrials.gov documentation for American Indian or Alaska Native (14% vs 45%; P < .001 per McNemar χ2 test with continuity correction [MC]) and Native Hawaiian or Other Pacific Islander (8% vs 43%; P < .001 MC). Conclusions and Relevance: While most phase 2/3 oncology clinical trials published in high-impact journals report race and ethnicity, most did not report American Indian or Alaska Native and Native Hawaiian or Other Pacific Islander racial categories. Our findings support a call to action for consistent journal policies and transparent race and ethnicity reporting, in alignment with Affordable Care Act-concordant race and ethnicity federal reporting requirements.

Outcomes of endoscopic ultrasound-guided gallbladder drainage: A multicenter study from India (with video).

BACKGROUND: Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) offers a safe and minimally invasive alternative for percutaneous cholecystostomy (PCC) in acute cholecystitis patients with high-surgical risk. Additionally, EUS-GBD serves as a rescue biliary drainage in malignant distal biliary obstruction. Despite its widespread application, data within the Indian context remains sparse. This study aims to report the outcomes of EUS-GBD through the first multi-center study from India. METHODS: We retrospectively analyzed patients undergoing EUS-GBD at six tertiary care centers of India from March 2022 to November 2023. EUS-GBD was performed by free hand or over-the-guidewire technique with lumen-apposing metal stent (LAMS) or large caliber metal stent (LCMS). The primary outcome was technical success (defined as successful deployment of stent between gallbladder and stomach/duodenal lumen). The secondary outcomes were clinical success (defined as resolution of symptoms of acute cholecystitis and more than > 50% reduction in bilirubin level within two weeks in distal biliary obstruction), adverse event rate, 30-day mortality rate and 90-day reintervention rate. RESULTS: Total 29 patients (mean age 65.86 ± 12.91, 11 female) underwent EUS-GBD. The indication for EUS-GBD were acute cholecystitis (79.31%) and rescue biliary drainage for malignant distal biliary obstruction (20.69%). LAMS was deployed in 92.86%, predominantly by free-hand technique (78.57%). Technical and clinical success rates were 96.55% and 82.75%, respectively. Adverse events occurred in 27.59% patients, with severe adverse events (bile leak and bleeding) being uncommon (10%). Both 30-day mortality rate and 90-day reintervention rate were 13.79% in patients. Cholecysto-duodenal fistula facilitated cholecystoscopic intervention and stone removal in one patient and transgastric EUS-GBD did not hamper bilio-enteric anastomosis during Whipple surgery in two patients. CONCLUSION: EUS-GBD is a safe and effective technique for managing acute cholecystitis in high-risk patients and for biliary drainage in cases with malignant distal biliary obstruction.

Meta-Analysis of 5-Fraction Preoperative Radiotherapy for Soft Tissue Sarcoma.

OBJECTIVES: Studies investigating preoperative 5-fraction radiation therapy (RT) for soft tissue sarcoma (STS) are limited. We performed a meta-analysis to determine the efficacy and safety of this treatment paradigm. METHODS: This study-level meta-analysis was conducted using Bayesian methods. Statistical estimation for risk of outcome rates was conducted by posterior mean and 95% highest posterior density (HPD) intervals. Studies with 2-year local control (LC) and description of major wound complications (MWC) per the CAN-NCIC-SR2 study were included and served as the primary endpoints. Secondary endpoints included rates of acute and late toxicity. A total of 10 studies were identified and 7 met the inclusion criteria. Subgroup analyses were performed for ≥30 Gy vs <30 Gy. RESULTS: A total of 209 patients from 7 studies were included. Five studies used ≥30 Gy (n=144), and 2 studies <30 Gy (n=64). Median follow-up was 29 months (range: 21 to 57 mo). Primary tumor location was lower extremity in 68% and upper extremity in 22%. Most tumors were intermediate or high grade (95%, 160/169), and 50% (79/158) were >10 cm. The two-year LC for the entire cohort was 96.9%, and the rate of MWC was 30.6%. There was a trend toward improved LC with ≥ 30 Gy (95% HPD: 0.95 to 0.99 vs 0.84 to 0.99). There was no difference in MWC (95% HPD: 0.18 to 0.42 vs 0.17 to 0.55) or late toxicity between the groups. CONCLUSION: Preoperative 5-fraction RT for STS demonstrates excellent 2-year LC with MWC and toxicity similar to standard fractionation preoperative RT. Multi-institutional trials with a universal RT protocol are warranted.

Exhaled breath condensate contains extracellular vesicles (EVs) that carry miRNA cargos of lung tissue origin that can be selectively purified and analyzed.

Lung diseases, including lung cancer, are rising causes of global mortality. Despite novel imaging technologies and the development of biomarker assays, the detection of lung cancer remains a significant challenge. However, the lung communicates directly with the external environment and releases aerosolized droplets during normal tidal respiration, which can be collected, stored and analzsed as exhaled breath condensate (EBC). A few studies have suggested that EBC contains extracellular vesicles (EVs) whose microRNA (miRNA) cargos may be useful for evaluating different lung conditions, but the cellular origin of these EVs remains unknown. In this study, we used nanoparticle tracking, transmission electron microscopy, Western blot analyses and super resolution nanoimaging (ONi) to detect and validate the identity of exhaled EVs (exh-EVs). Using our customizable antibody-purification assay, EV-CATCHER, we initially determined that exh-EVs can be selectively enriched from EBC using antibodies against three tetraspanins (CD9, CD63 and CD81). Using ONi we also revealed that some exh-EVs harbour lung-specific proteins expressed in bronchiolar Clara cells (Clara Cell Secretory Protein [CCSP]) and Alveolar Type II cells (Surfactant protein C [SFTPC]). When conducting miRNA next generation sequencing (NGS) of airway samples collected at five different anatomic levels (i.e., mouth rinse, mouth wash, bronchial brush, bronchoalveolar lavage [BAL] and EBC) from 18 subjects, we determined that miRNA profiles of exh-EVs clustered closely to those of BAL EVs but not to those of other airway samples. When comparing the miRNA profiles of EVs purified from matched BAL and EBC samples with our three tetraspanins EV-CATCHER assay, we captured significant miRNA expression differences associated with smoking, asthma and lung tumor status of our subjects, which were also reproducibly detected in EVs selectively purified with our anti-CCSP/SFTPC EV-CATCHER assay from the same samples, but that confirmed their lung tissue origin. Our findings underscore that enriching exh-EV subpopulations from EBC allows non-invasive sampling of EVs produced by lung tissues.

Role of simulation-based training and assessment to improve brachytherapy competency among radiation oncology residents.

Simulation is a technique used in healthcare to replicate clinical scenarios and improve patient safety, efficacy, and efficiency. Simulation-based medical education facilitates training and assessment in healthcare without increasing risk to patients, supported by ample evidence from surgical/procedural specialties. Simulation in radiation oncology has been leveraged to an extent, with successful examples of both screen-based and hands-on simulators that have improved confidence and performance in trainees. In the current era, evidence substantiates a significant deficit in brachytherapy procedure education, with radiation oncology residents reporting low confidence in this procedural skill, largely attributable to insufficient caseloads at some centers. Simulation-based medical education can facilitate structured training and competency-based assessment in brachytherapy skills. This review discusses existing advances and future directions in brachytherapy simulation, using examples from simulation in surgical specialties.

Same day discharge colon surgery: is it financially worth it?

AIM: Same day discharge (SDD) for colorectal surgery shows increasing promise in the era of enhanced recovery after surgery protocols and minimally invasive surgery. It has become increasingly relevant due to the constraints posed by the COVID-19 pandemic. The aim of this study was to compare SDD and postoperative day 1 (POD1) discharge to understand the clinical outcomes and financial impact on factors such as cost, charge, revenue, contribution margin and readmission. METHOD: A retrospective review of colectomies was performed at a single institution over a 2-year period (n = 143). Two populations were identified: SDD (n = 51) and POD1 (n = 92). Patients were selected by International Statistical Classification of Diseases and Related Health Problems-10 (ICD-10) and Diagnosis Related Grouper (DRG) codes. RESULTS: There was a statistically significant difference favouring SDD in total hospital cost (p < 0.0001), average direct costs (p < 0.0001) and average charges (p < 0.0016). SDD average hospital costs were $8699 (values in USD throughout) compared with $11 652 for POD 1 (p < 0.0001), and average SDD hospital charges were $85 506 compared with $97 008 for POD1 (p < 0.0016). The net revenue for SDD was $22 319 while for POD1 it was $26 173 (p = 0.14). Upon comparison of contribution margins (SDD $13 620 vs. POD1 $14 522), the difference was not statistically significant (p = 0.73). There were no identified statistically significant differences in operating room time, robotic console time, readmission rates or surgical complications. CONCLUSIONS: Amidst the pandemic-related constraints, we found that SDD was associated with lower hospital costs and comparable contribution margins compared with POD1. Additionally, the study was unable to identify any significant difference between operating time, readmissions, and surgical complications when performing SDD.

Social Media Posts About Carpal Tunnel Release: A Cross-Sectional Analysis of Patient and Surgeon Perspectives.

BACKGROUND: Social media provides an increasingly popular, unfiltered source of perspectives on healthcare. The objective of this study is to characterize the landscape of social media posts regarding carpal tunnel release (CTR). METHODS: Content was queried from Instagram between February 2, 2019 to August 12, 2021 using the hashtags #carpaltunnelrelease and #carpaltunnelsurgery. The 1500 most-liked posts were analyzed. Poster demographics including age, gender, region, and symptom qualities and post characteristics including type, number, timing relative to surgery, tone, and satisfaction were collected. Categorical variables were compared utilizing chi-squared test. Univariate and multivariate regression were performed. RESULTS: The most popular post types included single photo (55.2%), multiple photos (18.8%), or single video (18.2%). Of all, 70.6% posts had fewer than 50 "likes." Patients accounted for 51.8% of posts, followed by surgeons (13.3%), other health care providers (11.7%), and physical therapists (8.8%). Women (66.7%) outnumbered men (33.3%). Fifty-five percent of posts were domestic. Posts mostly depicted postoperative care (85.6%). The most frequently mentioned symptoms were pain, burning, numbness, and tingling. Of all posts, 45.1% had a positive tone, 49.1% neutral, and 5.7% negative. Univariate analysis revealed that posters who were patients, underwent open CTR, and were female were more likely to post negative sentiments. CONCLUSIONS: Most posts regarding CTR are from patients, are postoperative, and are positive or neutral. Although rare, negative posts were more likely to originate from posters who are patients, female, or underwent open CTR. With this information, surgeons will be better prepared to address patient concerns, set patient expectations, and enter the social media themselves.

Social Media Posts About Distal Radius Fracture: A Cross-Sectional Analysis of Patient and Provider Perspectives.

BACKGROUND: Social media offers a popular, unfiltered source of patient and provider perspectives on health care. This study investigated the characteristics of social media posts referencing distal radius fracture (DRF). METHODS: Content was queried from Instagram from February 06, 2019, to December 08, 2021, using the hashtags "#distalradiusfracture" and "#wristfracture." The 1500 most-liked posts were analyzed. Poster demographics including age, gender, region, laterality, and treatment type and post characteristics including post type, number, content, timing relative to treatment, tone, and satisfaction were examined. Variables were compared using χ2 tests. Univariate, multivariate, and stepwise regression were performed. RESULTS: The most popular post formats were single photo (44.5%), multiple photos (32.3%), and single video (13.9%). Patients (40.3%) were the most common poster followed by surgeons (33.4%). Men (48.7%) and women (51.3) were evenly represented. Of the total posts, 87.7% depicted the post-treatment phase of care; 54.8% of posts depicted operative management, while 26.6% depicted non-operative management; and 73.7% of posts were positive in tone, 18.7% neutral, and 7.6% negative. Univariate analysis demonstrated that posters who were patients, friends/family of patients, female, and posts with >100 "likes" were more likely to share negative tones. Multivariate and stepwise regression were consistent with the above. CONCLUSION: Most posts regarding DRF originate from patients, are post-treatment, and are positive. Negative tone is associated with posts from patients, family/friends of patients, female posters, and posts with >100 likes. With this information, surgeons will be better prepared to address patient concerns, manage expectations, and actively participate in social media themselves.

Neoadjuvant Reirradiation for Radiation Therapy-Associated Angiosarcoma of the Breast.

PURPOSE: Radiation-associated angiosarcoma of the breast (RAASB) is a rare side effect after breast radiation and has been associated with poor outcomes. At this time, there is no consensus regarding management of RAASB, and the role of reirradiation remains controversial. We present our modern institutional outcomes in managing RAASB with incorporation of neoadjuvant hyperfractionated reirradiation. METHODS AND MATERIALS: Patients identified were treated between 2016 and 2020 with inclusion of any histologically proven RAASB without metastatic disease at diagnosis, while excluding those with a history of radiation therapy outside of the breast/chest wall or other sarcoma histologies. Major wound complications were defined as requiring wound care and/or wound vacuum or return to the operating room for wound repair at any time after surgery. RESULTS: Eight patients were identified, and the median follow-up was 34 months. Median time to RAASB development was 8 years from initial radiation therapy. With respect to RAASB management, all underwent surgery and neoadjuvant reirradiation therapy, and all but 1 patient received taxol-based chemotherapy. At last follow-up, 7 patients remained free of disease, and 1 patient died with distant disease. With respect to acute toxicity after reirradiation, all patients developed at least acute grade 2 toxicities. Five of the 8 patients developed a major wound complication. CONCLUSIONS: Our institutional analysis suggests excellent local control and survival outcomes for RAASB treated with neoadjuvant hyperfractionated reirradiation, surgery, and taxol-based chemotherapy. However, major wound complications represent a major challenge with this approach. Future studies should consider how best to improve the therapeutic ratio while maintaining high rates of local control and survival.

Comparison of partial-breast irradiation and intraoperative radiation to whole-breast irradiation in early-stage breast cancer patients: a Kaplan-Meier-derived patient data meta-analysis.

PURPOSE: Partial breast irradiation (PBI) and intraoperative radiation (IORT) represent alternatives to whole breast irradiation (WBI) following breast conserving surgery. However, data is mixed regarding outcomes. We therefore performed a pooled analysis of Kaplan-Meier-derived patient data from randomized trials to evaluate the hypothesis that PBI and IORT have comparable long-term rates of ipsilateral breast tumor recurrence as WBI. METHODS: In February, 2023, PubMed, EMBASE and Cochrane Central were systematically searched for randomized phase 3 trials of early-stage breast cancer patients undergoing breast-conserving surgery with PBI or IORT as compared to WBI. Time-to-event outcomes of interest included ipsilateral breast tumor recurrence (IBTR), overall survival (OS) and distant disease-free survival (DDFS). Statistical analysis was performed with R Statistical Software. RESULTS: Eleven randomized trials comprising 15,460 patients were included; 7,675 (49.6%) patients were treated with standard or moderately hypofractionated WBI, 5,413 (35%) with PBI and 2,372 (15.3%) with IORT. Median follow-up was 9 years. PBI demonstrated comparable IBTR risk compared with WBI (HR 1.20; 95% CI 0.95-1.52; p = 0.12) with no differences in OS (HR 1.02; 95% CI 0.90-1.16; p = 0.70) or DDFS (HR 1.15; 95% CI 0.81-1.64; p = 0.43). In contrast, patients treated with IORT had a higher IBTR risk (HR 1.46; 95% CI 1.23-1.72; p < 0.01) compared with WBI with no difference in OS (HR 0.98; 95% CI 0.84-1.14; p = 0.81) or DDFS (HR 0.91; 95% CI 0.76-1.09; p = 0.31). CONCLUSION: For patients with early-stage breast cancer following breast-conserving surgery, PBI demonstrated no difference in IBTR as compared to WBI while IORT was inferior to WBI with respect to IBTR.

Five Fraction Accelerated Partial Breast Irradiation Versus Intraoperative Radiation Therapy for Early-Stage Breast Cancer.

PURPOSE/OBJECTIVE(S): Accelerated partial breast irradiation (PBI) delivered in 5 fractions with intensity modulated radiation therapy (IMRT) has been shown to have comparable clinical outcomes to whole breast irradiation with reduced toxicity profiles. In contrast, intraoperative radiation therapy (IORT) offers patients the potential to complete adjuvant radiation therapy in a single treatment. While early data were promising, concerns exist regarding long-term rates of local recurrence after IORT. We present a comparison of 5 fraction PBI versus IORT. MATERIALS/METHODS: We performed a retrospective review of 473 patients with early-stage breast cancer treated at a single institution from 2011 to 2021 with 258 receiving PBI and 215 receiving IORT. PBI patients received 30 Gy in 5 fractions delivered with IMRT. IORT patients received 20 Gy in 1 fraction prescribed to the applicator surface at surgery using the low-energy TARGIT technique. RESULTS: Mean age was 71 years old (IQR:67-74) for IORT patients and 67 years old (IQR:62-72) for PBI patients. Median follow up was 5.7 years (IQR:4.2-7.0) for IORT patients and 2.4 years (IQR:1.8-3.3) for PBI patients (P < .001). Recurrence at any time (locoregional and distant) was seen in 7.9% (n = 17) of patients receiving IORT as compared to 0.8% (n = 2) of patients receiving PBI. IORT was associated with reduced rates of locoregional relapse free survival at 5 years (93.6% vs. 99.4%, P = .05) with no difference in overall survival(92.8% vs. 95.1%, P = .99). CONCLUSION: Low-energy TARGIT IORT was associated with higher rates of locoregional recurrence compared to PBI. These outcomes, consistent with other series and current guidelines, suggest a limited role for low-energy IORT as monotherapy.

Intraoperative Radiation Therapy for Early-Stage Breast Cancer: Updated Outcomes from a Single-Institution Experience.

BACKGROUND: Increasingly, data have supported the use of partial-breast irradiation (PBI) for low-risk patients after breast-conserving surgery, with techniques allowing for completion of treatment in 1-3 weeks. Intraoperative radiation therapy (IORT) is an alternative to PBI. Our institution had used low-energy photon IORT (TARGIT) for more than a decade. The initial results demonstrated a 2% local recurrence rate with a short follow-up period of 2 years. This report presents updated outcomes during with 5-year follow-up. METHODS: A review of an institutional review board (IRB)-approved institutional registry was performed. The review identified 215 patients with early-stage breast cancer (stages 0-IIA) who received IORT. At the time of surgery, IORT was delivered with 20 Gy in a single fraction, with 5.1% (n = 11) of patients receiving additional whole-breast irradiation (WBI). RESULTS: The mean age at diagnosis was 71 years (range, 49-98 years), and the median follow-up was 5.7 years (interquartile range [IQR], 4.2-7.0 years). Of the 215 patients, 2.8% (n = 6) had ductal carcinoma in situ (DCIS), 90.7% (n = 195) had T1 disease, and 6.5% (n = 14) had T2 disease. Endocrine therapy was prescribed for 79% and chemotherapy for 1.4% of the patients. The 5-year rates were 5.3% for local recurrence, 6.4% for locoregional recurrence, and 2.7% for distant metastases. At 5 years, 93% of the patients were alive. CONCLUSIONS: The 5-year outcomes with TARGIT IORT demonstrated high rates of local recurrence, exceeding those seen with alternative modern approaches. The local recurrence outcomes with IORT are more consistent with studies omitting radiation following breast-conserving surgery, using endocrine therapy alone. Consistent with current guidelines and previous data, TARGIT IORT should not be used as monotherapy outside prospective clinical trials.

Axillary Treatment and Chronic Breast Cancer-Related Lymphedema: Implications for Prospective Surveillance and Intervention From a Randomized Controlled Trial.

PURPOSE: The PREVENT randomized trial assessed progression to chronic breast cancer-related lymphedema (cBCRL) after intervention triggered by bioimpedance spectroscopy (BIS) or tape measurement (TM). This secondary analysis identifies cBCRL risk factors on the basis of axillary treatment. METHODS: Between June 2014 and September 2018, 881 patients received sentinel node biopsy (SNB; n = 651), SNB + regional node irradiation (RNI; n = 58), axillary lymph node dissection (ALND; n = 85), or ALND + RNI (n = 87). The primary outcome was the 3-year cBCRL rate requiring complex decongestive physiotherapy (CDP). RESULTS: After a median follow-up of 32.8 months (IQR, 21-34.3), 69 of 881 patients (7.8%) developed cBCRL. For TM, 43 of 438 (9.8%) developed cBCRL versus 26 of 443 (5.9%) for BIS (P = .028). The 3-year actuarial risk of cBCRL was 4.4% (95% CI, 2.7 to 6.1), 4.2% (95% CI, 0 to 9.8), 25.8% (95% CI, 15.8 to 35.8), and 26% (95% CI, 15.3 to 36.7). Rural residence increased the risk in all groups. For SNB, neither RNI (SNB, 4.1% v SNB + RNI, 3.4%) nor taxane (4.4%) increased cBCRL, but risk was higher for patients with a BMI of ≥30 (6.3%). For SNB + RNI, taxane use (5.7%) or supraclavicular fossa (SCF) radiation (5.0%) increased cBCRL. For ALND patients, BMI ≥25 or chemotherapy increased cBCRL. For ALND + RNI, most patients received SCF radiation and taxanes, so no additional risk factors emerged. CONCLUSION: The extent of axillary treatment is a significant risk factor for cBCRL. Increasing BMI, rurality, SCF radiation, and taxane chemotherapy also increase risk. These results have implications for a proposed risk-based lymphedema screening, early intervention, and treatment program.

Discovery of LNP1892: A Precision Calcimimetic for the Treatment of Secondary Hyperparathyroidism.

The calcium sensing receptor (CaSR) plays an important role in maintaining calcium homeostasis. The use of calcimimetic cinacalcet has been established to activate CaSR and normalize hypercalcemia. However, cinacalcet has limitations due to its high cLogP and pKa. A systematic optimization of cinacalcet to reduce its cLogP and pKa yielded compound 23a (LNP1892). Compound 23a showed excellent potency and a favorable pharmacokinetics profile, and lacked the liabilities of cinacalcet, making it a highly differentiated precision calcimimetic. In adenine-diet-induced chronic kidney disease (CKD) models, 23a demonstrated robust and dose-dependent efficacy, as measured by plasma parathyroid hormone (PTH) levels. It also showed an excellent safety profile in animal studies. Phase 1 clinical trials with 23a in healthy volunteers confirmed its excellent safety, tolerability, and effectiveness in lowering PTH levels in a dose-dependent manner, without causing symptomatic hypocalcaemia. Encouraged by these promising results, LNP1892 was taken to a Phase 2 study in CKD patients.

Consensus recommendations in the management of Ewing sarcoma from the National Ewing Sarcoma Tumor Board.

Ewing sarcoma (ES) is a malignant tumor of bone and soft tissue that most often occurs in adolescents and young adults. Despite an international coordinated approach, several nuances, discrepancies, and debates remain in defining the standard of care for treating ES. In this review, the authors leverage the expertise assembled by formation of the National Ewing Sarcoma Tumor Board, a multi-institution, multidisciplinary virtual tumor board that meets monthly to discuss complicated and challenging cases of ES. This report is focused on select topics that apply to the management of patients with newly diagnosed ES. The specific topics covered include indications for bone marrow aspirate and biopsy for initial evaluation compared with fluorodeoxyglucose-positron emission tomography, the role of interval compressed chemotherapy in patients aged 18 years and older, the role of adding ifosfamide/etoposide to vincristine/doxorubicin/cyclophosphamide for patients with metastatic disease, the data on and role of high-dose chemotherapy with autologous stem cell transplantation, maintenance therapy, and whole-lung irradiation. The data referenced are often limited to subgroup analyses and/or compiled from multiple sources. Although not intended to replace the clinical judgement of treating physicians, the guidelines are intended to provide clarity and recommendations for the upfront management of patients with ES. PLAIN LANGUAGE SUMMARY: Ewing sarcoma is a malignant tumor of bone and soft tissue that most often occurs in adolescents and young adults. For this review, the authors used the experience of the National Ewing Sarcoma Tumor Board, a multi-institution, multidisciplinary virtual tumor board that meets monthly to discuss complicated and challenging cases of Ewing sarcoma. Although not intended to replace the clinical judgement of treating physicians, the guidelines will focus on the development of consensus statements for the upfront management of patients with Ewing sarcoma.