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Abstract Disclosure: R.S. Douglas: Consulting Fee; Self; Horizon Therapeutics plc, Immunovant, Viridian. S. Couch: None. S.T. Wester: Advisory Board Member; Self; Horizon Therapeutics plc. Consulting Fee; Self; Immunovant, Sling. B. Fowler: Consulting Fee; Self; Horizon Therapeutics plc. C. Liu: Other; Self; Walter Kluwer Health. P. Subramanian: Consulting Fee; Self; Gensight, Horizon Therapeutics plc, Viridian. R. Tang: Consulting Fee; Self; Viridian, Alexion, Valenza. Research Investigator; Self; Viridian, Horizon Therapeutics plc, Novartis, Immunovant, Vasaragen. Speaker; Self; Serono Speaker Journal Club. Q.T. Nguyen: None. K. Hsu: Employee; Self; Horizon Therapeutics plc. Stock Owner; Self; Horizon Therapeutics plc. M. Karon: Employee; Self; Horizon Therapeutics plc. Stock Owner; Self; Horizon Therapeutics plc. M.N. Stan: Consulting Fee; Self; Immunovant, Horizon Therapeutics plc, Sling, Genentech, ArgenX. Background: Thyroid eye disease (TED) is characterized by expansion of peri- and retro-orbital fat and muscle, often resulting in disfiguring proptosis (eye-bulging) and diplopia (double vision) which may persist chronically. Teprotumumab, an inhibitor of the insulin-like growth factor-1 receptor, demonstrated improvements in proptosis, diplopia, inflammation and quality of life in clinical trials in patients with TED history of short duration (6-13 months), and active disease (clinical activity score [CAS] ≥4). In a published study of 31 patients with CAS≤3 and TED duration >2 years, teprotumumab reduced proptosis, diplopia and inflammation.1 We have undertaken the first randomized, placebo (PBO)-controlled trial to evaluate teprotumumab in patients with chronic/inactive/low CAS TED. The trial has completed randomization with results available in May 2023. Here we report characteristics of the randomized patients. Methods: The trial (NCT04583735) is being conducted in 11 centers in the United States. Key inclusion criteria were age≥18 years, TED duration ≥2 years but <10 years and CAS≤1 in both eyes, ≥3mm proptosis from baseline and/normal for sex and race, or no progression in proptosis or diplopia or new inflammatory symptoms in the preceding year. Patients must have been euthyroid or mildly hypo/hyperthyroid, and not require surgical intervention through the trial. Patients could not have received teprotumumab previously, or steroids within 3 weeks before screening. Patients were randomized 2:1 to receive 8 infusions of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for the remaining 7 infusions) or PBO once every 3 weeks. The primary endpoint is improvement in proptosis (mm) as compared with PBO from baseline at Week 24. Other endpoints include percentage of proptosis responders (improvement of ≥2mm), diplopia responders (improvement of ≥1 grade in diplopia on the Bahn-Gorman scale, 0-3), and improvement in Graves’ Ophthalmopathy- Quality of Life (GO-QoL), all at Week 24. Adverse events (AE) and AE of special interest will be reported. Results: 62 patients were randomized. 80.6% are female, mean (SD) age was 48.7 (14.94) years. 54.8% are White, 24.2 %, Black or African American, and 12.9%, Asian. Mean (SD) TED duration was 5.2 (1.77) years. 87.1% are never/former smokers. At baseline, mean (SD) proptosis in the study eye was 24.4 (2.94) mm, and mean (SD) CAS was 0.4 (0.49). 27.4% had binocular diplopia with a mean diplopia score of 2. The mean overall GO-QoL score was 63.9 indicating similar disutility as observed in the acute trial population (previously published). Results from this 24-week trial will be presented. Conclusions: Despite a long duration of TED and low “activity”, patients enrolled in this trial have high levels of proptosis and impaired quality of life at baseline. Presentation: Saturday, June 17, 2023

Abstract Disclosure: R.S. Douglas: Consulting Fee; Self; Horizon, Immunovant, Viridian. Research Investigator; Self; Horizon. S. Couch: Research Investigator; Self; Horizon. S.T. Wester: Advisory Board Member; Self; Horizon. Consulting Fee; Self; Immunovant, Sling. Research Investigator; Self; Horizon. B.T. Fowler: Consulting Fee; Self; Horizon. Research Investigator; Self; Horizon. C. Liu: Research Investigator; Self; Horizon. Other; Self; Royalties from Wolters-Kluwer. P. Subramanian: Consulting Fee; Self; Horizon, Gensight, Viridian. Research Investigator; Self; Horizon. R. Tang: Consulting Fee; Self; Viridian, Alexion, Valenza. Research Investigator; Self; Horizon, Viridian, Novartis, Immunovant, Vasaragen. Speaker; Self; Serono Journal Club. Q.T. Nguyen: Research Investigator; Self; Horizon. R.N. Maamari: Research Investigator; Self; Horizon. K. Hsu: Employee; Self; Horizon. Stock Owner; Self; Horizon. M. Karon: Employee; Self; Horizon. Stock Owner; Self; Horizon. M. Stan: Consulting Fee; Self; Septerna Inc, Third Rock Ventures LLC, Genentech, MedicXi Ventures, ArgenX US Inc, Tourmaline Bio, Lassen Therapeutics, Ortho Clinical Diagnostics, Siemens Healthcare, Tolmar Inc, OSE, Immunotherapeutics, Roivant Sciences. Research Investigator; Self; Horizon, Immunovant, ValenzaBio, Sling Therapeutics. Background: Early inflammatory thyroid eye disease (TED) gives way to chronic disease which may lead to long-term disfiguring proptosis (eye-bulging). Teprotumumab, an IGF-1 receptor inhibitor, significantly improved signs and symptoms of newly diagnosed TED (6-13 months) with active disease (clinical activity score [CAS] ≥4) in prior studies. We present data from the first randomized, placebo (PBO)-controlled trial (NCT04583735) with teprotumumab in chronic/low CAS TED, where disease has not regressed. Methods: Pts met all following criteria: ≥18 yrs, TED 2-10 yrs, inactive disease or >1 yr without progression in proptosis/diplopia/new symptoms, baseline (BL) CAS≤1, increased proptosis ≥3mm before TED or from normal, euthyroid/mildly hypo/hyperthyroid, no prior teprotumumab and no steroids within 3 wks of screen. Pts received teprotumumab or PBO once every 3 wks for 21 wks. Primary endpoint was improvement in proptosis(mm) from BL at Wk 24 vs PBO. Secondarily proptosis responders (≥2mm improvement), diplopia responders (≥1 grade improvement on Gorman scale 0-3) with resolved diplopia (grade 0) and improvement in Graves’ Ophthalmopathy-QoL (GO-QoL) visual function (VF) and appearance (AP) subscales were assessed. Treatment-emergent adverse events (TEAE) and AEs of special interest are reported. Study was solely sized/powered for proptosis. Results: 62 pts were randomized 2:1 (ITT, teprotumumab:42; PBO:20), 80.6% were female, mean(SD) age was 48.7(14.94) yrs. Mean(SD) TED duration was 5.2(1.8) yrs. 87.1% were never/former smokers. At BL, mean(SD) proptosis was 24.4(2.94) mm, mean CAS was 0.4, and 29% (teprotumumab, n=14, PBO, n=4) had diplopia with a mean score ∼2. 93%(39) of teprotumumab pts completed the study. At Wk 24, proptosis improvements from BL were significantly greater in the teprotumumab group [2.41 (0.228) mm] vs PBO [0.92(0.323) mm], P<.001. Proptosis response was observed in 26/42 (62%) of teprotumumab pts vs 5/20 (25%) of PBO, P=.01. Diplopia improvement was observed in 6/14 (43%) teprotumumab pts with resolved diplopia in 4(29%) vs 2/4(50%) in PBO and 1(25%) resolved. Significantly greater improvement from BL was observed on GO-QoL-VF for teprotumumab (8.73) vs PBO (2.41), P=.03. Change from BL on AP was 10.03 vs 7.19, P= .65. TEAEs proportions were similar: 33/41(80.5%) of teprotumumab, and 16/20(80%) of PBO pts. Hyperglycemia was reported in 6(15%) vs 2(10%) and hearing impairment in 9(22%) vs 2(10%), respectively. There were two AE discontinuations: teprotumumab (left ear conductive hearing loss with congenital anomaly) and PBO (infusion related). Conclusions: For the first time in pts with longstanding TED and low CAS/inflammation, a medical therapy, teprotumumab, produced significant improvement in proptosis as compared with PBO supporting its use regardless of TED duration or activity. The safety profile was comparable to that previously reported. Presentation: Saturday, June 17, 2023

AbstractThe American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education, and professional practice of medical physics. The AAPM has more than 8000 members and is the principal organization of medical physicists in the United States.The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the United States. Existing medical physics practice guidelines will be reviewed for the purpose of revision or renewal, as appropriate, on their fifth anniversary or sooner.Each medical physics practice guideline represents a policy statement by the AAPM, has undergone a thorough consensus process in which it has been subjected to extensive review, and requires the approval of the Professional Council. The medical physics practice guidelines recognize that the safe and effective use of diagnostic and therapeutic radiology requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guidelines and technical standards by those entities not providing these services is not authorized.The following terms are used in the AAPM practice guidelines: Must and Must Not: Used to indicate that adherence to the recommendation is considered necessary to conform to this practice guideline. While must is the term to be used in the guidelines, if an entity that adopts the guideline has shall as the preferred term, the AAPM considers that must and shall have the same meaning. Should and Should Not: Used to indicate a prudent practice to which exceptions may occasionally be made in appropriate circumstances.

LBA490 Background: Biliary tract cancers (BTCs) are a heterogeneous group of malignancies with a dismal prognosis. Gemcitabine-based regimens are the standard of care in advanced disease, but median overall survival (OS) is roughly 12 months. The addition of albumin-bound paclitaxel to gemcitabine and cisplatin (GAP) demonstrated promising efficacy in a 60 patient, single-arm phase II study (Shroff et al, JAMA Oncol 2019), with observed median OS of 19.2 months. Methods: SWOG 1815 is a randomized, open-label, phase III trial comparing GAP to gemcitabine/cisplatin (GC). The study included newly diagnosed advanced BTC patients (pts), randomized 2:1 to GAP vs. GC. GAP included gemcitabine at 800 mg/m2, cisplatin at 25 mg/m2 and albumin-bound paclitaxel at 100 mg/m2 on days 1 and 8 of a 21-day cycle. GC included standard dosing of gemcitabine at 1000 mg/m2 and cisplatin at 25 mg/m2 on days 1 and 8 of a 21-day cycle. Pts were treated until progression. The primary endpoint was overall survival (OS) with a target hazard ratio of 0.7 with 90% power and a 1-sided alpha of 0.025; randomization was stratified by disease site (intrahepatic cholangiocarcinoma [CCA] vs gallbladder adenocarcinoma [GBC] vs extrahepatic CCA), disease stage (locally advanced vs metastatic), and Zubrod PS 0 vs 1. Results: Of 441 eligible pts randomized, 55% were female. 67% of patients had intrahepatic CCA, 16% had GBC and 17% had extrahepatic CCA. Most pts had metastases (73%). Median OS with GAP vs. GC was 14 vs. 12.7 mo respectively (HR 0.93, 95% CI 0.74-1.19, p=0.58), ORR (confirmed and unconfirmed) 34% vs 25% (p=0.11) and median PFS 8.2 vs 6.4 mo (HR 0.92, 95% CI 0.72-1.16, p=0.47), respectively. Grade 3 and 4 treatment related adverse events (TRAEs) in ≥10% of pts for GAP and GC were anemia, neutropenia, and thrombocytopenia. GAP had more ≥ grade 3 hematologic AEs compared to the GC arm (60% vs. 45%, p=0.003). Discontinuation due to toxicity was at 24% vs 19% (p=0.26) with GAP vs GC. In exploratory subset analyses, GAP vs GC improved OS in pts with locally advanced disease (medians 19.2 vs 13.7 mo; HR 0.67, 95% CI 0.42-1.06, p=0.09) and in GBC pts (medians 17.0 vs 9.3 mo; HR 0.74, 95% CI 0.41-1.35, p=0.33). ORR for GAP vs GC in GBC was 50% vs 24% (p=0.09) and for locally advanced disease 28 vs 21% p=0.74. Conclusions: SWOG 1815 did not result in a statistically significant improvement in median OS with GAP vs. GC. The GAP regimen had higher rates of TRAEs without a statistically significant difference in discontinuation rates. Pts with locally advanced disease and GBC may benefit from the use of GAP. Further analyses are ongoing to understand potential benefit of GAP in subsets of BTC pts. Funding: NIH/National Cancer Institute grants CA180888, CA180819, CA180820, CA180821, and CA180868; and in part by Celgene Corporation, Summit, NJ (subsidiary of Bristol Myer Squibb). Clinical trial information: NCT#03768414 .

This consensus document for the performance of cardiovascular computed tomography (CCT) to guide intervention in the right ventricular outflow tract (RVOT) in patients with congenital heart disease (CHD) was developed collaboratively by pediatric and adult interventionalists, surgeons, and cardiac imagers with expertise specific to this patient subset. The document summarizes definitions of RVOT dysfunction as assessed by multimodality imaging techniques and reviews existing consensus statements and guideline documents pertaining to indications for intervention. In the context of this background information, recommendations for CCT scan acquisition and a standardized approach for reporting prior to surgical or transcatheter pulmonary valve replacement are proposed and presented. It is the first Imaging for Intervention collaboration for CHD patients and encompasses imaging and reporting recommendations prior to both surgical and percutaneous pulmonary valve replacement.

The purpose of this study was to compare external workloads between collegiate men’s (MLAX) and women’s lacrosse (WLAX) matches and examine positional differences across the season. Athletes (MLAX: n = 10; WLAX: n = 13) wore a global positional system device during all matches. External load metrics included in the analysis were total distance (TD), sprint distance (SD), accelerations (>3 m/s2), sprint efforts, player load per minute (PL/min), top speed, and distances spent in various speed zones. WLAX had higher TD (p = 0.001), SD (p < 0.001), distances in SZs 2–5 (p < 0.001), PL (p < 0.001), and sprint efforts (p < 0.001) compared to MLAX. However, MLAX performed more acceleration (p < 0.001) and deceleration (p < 0.001) efforts. WLAX midfielders (M) and defenders (D) reached higher top speeds and performed more accelerations than attackers (p < 0.001). Midfielders covered the greatest distance at high speeds (p = 0.011) and the smallest distance at low speeds (<0.001) for WLAX. For MLAX, midfielders performed the highest SDs, top speeds, accelerations, decelerations, and distances in higher speed zones (p < 0.001) compared to attackers and defenders. Results indicate that there are significant gender and positional differences in external workload demands during match play, specifically for volume- and intensity-derived workload parameters, between men’s and women’s lacrosse. Therefore, sports performance coaches should create gender- and position-specific conditioning programs to prepare athletes for match demands.

PURPOSE Increased awareness of the distinct tumor biology for adolescents and young adults (AYAs) with cancer has led to improvement in outcomes for this population. However, in cholangiocarcinoma (CCA), a paucity of data exist on the AYA population. To our knowledge, we present the largest study to date on AYA disease biology, treatment patterns, and survival outcomes in CCA. METHODS A multi-institutional cohort of patients with CCA diagnosed with intrahepatic cholangiocarcinoma (ICC) or extrahepatic cholangiocarcinoma (ECC) was used for analysis. Retrospective chart review was conducted on patients who were 50 years old and younger (young; n = 124) and older than 50 years (older; n = 723). RESULTS Among 1,039 patients screened, 847 patients met eligibility (72% ICC, 28% ECC). Young patients had a larger median tumor size at resection compared with older patients (4.2 v 3.6 cm; P = .048), more commonly had N1 disease (65% v 43%; P = .040), and were more likely to receive adjuvant therapy (odds ratio, 4.0; 95% CI, 1.64 to 9.74). Tumors of young patients were more likely to harbor an FGFR2 fusion, BRAF mutation, or ATM mutation ( P < .05 for each). Young patients were more likely to receive palliative systemic therapy (96% v 69%; P < .001), targeted therapy (23% v 8%; P < .001), and treatment on a clinical trial (31% v 19%; P = .004). Among patients who presented with advanced disease, young patients had a higher median overall survival compared with their older counterparts (17.7 v 13.5 months; 95% CI, 12.6 to 22.6 v 11.4 to 14.8; P = .049). CONCLUSION Young patients with CCA had more advanced disease at resection, more commonly received both adjuvant and palliative therapies, and demonstrated improved survival compared with older patients. Given the low clinical trial enrollment and poor outcomes among some AYA cancer populations, data to the contrary in CCA are highly encouraging.