National Cancer Institute (USA), National Institutes of Health

The National Center on Sleep Disorders Research (NCSDR) of the National Heart, Lung, and Blood Institute (NHLBI) at the National Institutes of Health (NIH) hosted a two-day virtual workshop titled Big Data Approaches for Novel Mechanistic Insights on Disorders of Sleep and Circadian Rhythms on May 2nd and 3rd, 2024. The goals of this workshop were to establish a comprehensive understanding of the current state of sleep and circadian rhythms disorders research to identify opportunities to advance the field by using approaches based on artificial intelligence (AI) and machine learning (ML). The workshop showcased rapidly developing technologies for sensitive and comprehensive remote analysis of sleep and its disorders that can account for physiological, environmental and social influences, potentially leading to novel insights on long-term health consequences of sleep disorders and disparities of these health problems in specific populations.

Background Medicare Advantage (MA) plans may offer more benefits and lower costs relative to Traditional Medicare (TM), but may also provide narrower provider networks and pre-authorization requirements. We explore the impact of a cancer diagnosis on switching between MA and TM after diagnosis. Methods We used the 2015-2019 Surveillance, Epidemiology and End Results-Medicare data to examine patterns of switching between MA and TM after cancer relative to those without cancer. We used binomial generalized estimating equations to evaluate the cancer and sociodemographic characteristics of those with higher probabilities of switching. Results Among those initially enrolled in MA plans (39.27% of those with vs 40.79% without cancer), 3.76% of individuals with cancer switched to TM compared to 2.23% without cancer. For those initially enrolled in TM, 2.96% of individuals with cancer switched to MA vs 4.35% without cancer. Multivariable analyses demonstrated that, among individuals starting in MA, a cancer diagnosis was associated with a 52.02% increase in switching relative to those without cancer, whereas among those starting in TM, a cancer diagnosis was associated with a 26.90% reduction in switching. Younger individuals, males, dual-eligible, those with more comorbidities, rural-dwellers, and those living in zip codes with higher education and income levels also had higher probabilities of switching from MA to TM. Conclusions Prior to diagnosis, MA enrollment is comparable between individuals with and without cancer. However, after diagnosis, individuals with cancer have higher probability of switching from MA to TM and lower probability of switching from TM to MA.

INTRODUCTION Vincristine sulfate liposome injection (VSLI), a liposomal formulation of vincristine, may be better tolerated than standard aqueous vincristine and enable dose intensification. PROCEDURES Based on single‐agent tolerability, activity, and FDA approval in adults with acute lymphoblastic leukemia (ALL), we tested the safety and feasibility of VSLI as replacement for standard vincristine in the UK ALL R3 mitoxantrone‐based four‐drug induction (Cohort A), a three‐drug anthracycline‐free induction (Cohort B), and maintenance chemotherapy (Cohort C) in children and young adults with relapsed/refractory B‐cell ALL. RESULTS Among 29 participants with a median age of 12.4 years (range: 1.8–19.6 years), 16 received Cohort A, eight received Cohort B, and five received Cohort C therapy. Dose level 1 (DL1): 1.5 mg/m ² and dose level 2 (DL2): 2 mg/m ² of VSLI, each without a dose cap, were tested. Collectively, the median VSLI dose administered was 1.9 mg (range: 0.71–4.06 mg), and 13 (44.8%) received a dose above the standard 2 mg vincristine dose cap. Dose‐limiting toxicities (DLTs) at DL2 were seen in three patients, two in Cohort A and one in Cohort B, prompting further evaluation at DL1 for both cohorts. No DLTs were experienced at DL1. Only DL2 was tested in Cohort C—without DLT. Complete remissions were seen in 14 of 16 (87.5%) participants in Cohort A; three of eight (37.5%) in Cohort B; and one (20%) in Cohort C. VSLI with combination chemotherapy at DL1 was generally well tolerated. CONCLUSION Based on the promising response signal in this heavily pretreated population, further study of VSLI is warranted. (ClinicalTrials.gov NCT02879643)

Thyroid nodules are one of the most commonly encountered conditions in clinical endocrinology. Most thyroid nodules are of epithelial origin. However, primary thyroid mesenchymal tumors (TMTs), arising from the mesenchymal tissue, are being increasingly recognized. More than 20 different forms of benign and malignant TMTs have been described in the literature. Thyroid schwannoma is an extremely rare type of TMT, with only a few cases reported to date, accounting for less than 1% of all schwannomas. It primarily affects adults, with no significant sex predilection, and is often discovered incidentally during evaluation for thyroid nodules. Due to its rarity, the clinical presentation and natural history remain poorly understood, underscoring the importance of histopathological examination for accurate diagnosis and management. We describe a case of a patient with thyroid schwannoma who was diagnosed and managed at our center, contributing valuable insights to the limited body of knowledge on this rare entity. This is followed by a detailed description of the clinical features, diagnosis, and management of thyroid schwannomas.

Gastrointestinal Stromal Tumors (GISTs) have seen significant advancements in their diagnosis and management, driven by targeted therapeutic development and molecular testing. The identification of mutations in genes such as KIT and PDGFRA has transformed treatment approaches, particularly through targeted therapies like imatinib, which have improved patient outcomes. This review explores the critical role of genomic testing in GIST, highlighting its importance in accurate diagnosis, treatment planning, and long‐term surveillance for KIT/PDGFRA negative, SDH‐deficient GISTs. SDH‐deficient GISTs arise from mutations or epigenetic changes affecting the succinate dehydrogenase complex. The complexity of SDH‐deficient GISTs, including their association with hereditary syndromes such as Hereditary Paraganglioma‐Pheochromocytoma and/or hypermethylation of the SDHC promoter, underscores the need for comprehensive germline testing. Despite the availability of guidelines, variability exists in genomic testing recommendations across different regions, necessitating a unified approach. This review proposes a simplified algorithm for the genomic workup of GIST, and suggests all individuals with SDH‐deficient GIST, regardless of germline testing result, require monitoring for additional SDHx‐related tumors, given the lack of widely available methylation and full gene SDHA analysis.

Background and aims: Hepatotoxicity is a known risk of oral and intravenous methotrexate (MTX), but whether intrathecal (IT) administration causes hepatotoxicity remains unknown. We aimed to explore whether IT-MTX causes acute hepatoxicity. Methods: Retrospective single-centre analysis of all patients treated with IT-MTX from 2000 to 2020. We compared liver enzymes (LE) at baseline (within 7 days before IT-MTX) to post-MTX (within 7 days after IT-MTX). LE elevation was defined as ≥ 50% increase in LE from baseline and greater than upper limit of normal. Drug-induced liver injury (DILI) was defined based on established criteria. Results: A total of 270 patients (184 adults and 86 paediatric) received IT-MTX and had available LE data. Aminotransferase elevation was seen post-MTX in 107 (40%) patients, of whom 96 (36%) had ALT and 68 (25%) had AST elevation. DILI occurred in 16 (6%) patients. Aminotransferases peaked a median of 4 (3-5) days post-MTX, returning near baseline by day 7. Paediatric patients had higher incidence of aminotransferase elevations and DILI than adults (ALT 51% vs. 28%; AST 41% vs. 18%; DILI 11% vs. 3%; p < 0.01 for all). No significant predictors of LE elevation or DILI were identified, and no patient developed liver failure. The severity of ALT elevation after the first IT-MTX dose did not predict severity of a subsequent dose. Conclusion: Acute transient aminotransferase elevation is common after IT-MTX, especially in paediatric patients. Only a fraction of patients developed DILI, which was self-limited with no sensitisation or liver failure.

We conducted a multi-center, open-label, randomized phase II study to assess the efficacy of Nivolumab as maintenance therapy for patients with AML in first complete remission (CR) or CR with incomplete hematologic recovery (CRi) who were not candidates for SCT. Patients were stratified and randomized to Observation (Obs) or Nivolumab (Nivo, 3mg/kg IV every 2 weeks for 46 doses). The primary endpoint was progression-free survival (PFS) defined as time to disease relapse or death due to any reason. Secondary endpoints included overall survival (OS), and evaluation of adverse events following Nivolumab administration. Eighty patients were enrolled with median duration of follow-up of 24 months (33 months among survivors). PFS was 13.2 months in the Nivolumab arm (95% CI: 8.5-21.8) and 10.9 months in the Observation arm (5.4-14.9 months). Overall PFS curves were not statistically significantly different ((Nivo/Obs)= 0.92; 95% CI: 0.54, 1.56; one-sided p = 0.38). The median OS was 53.9 months in the Nivolumab arm and 30.9 months in the Observation arm. Cox regression model HR (Nivo/Obs)= 0.78; 95% CI: 0.40, 1.51; p=0.23 (one-sided). There were more adverse events (AEs) of any type (regardless of attribution) on the Nivolumab arm; 27 (71%) patients on the Nivolumab arm had a grade 3 or higher AE compared to 5 patients (12%) on the Observation arm (p<0.001). Nivolumab maintenance after AML chemotherapy failed to improve the PFS and OS in this randomized Phase II study. There were increased AEs and SAEs with nivolumab, but these AEs and SAEs were expected and manageable. ClinicalTrials.gov ID NCT02275533

Background Neomorphic isocitrate dehydrogenase (IDH) mutations lead to the accumulation of 2‐hydroxyglutarate (2‐HG), an oncometabolite implicated in tumor progression via inhibitory effects on alpha‐ketoglutarate. Moreover, mutant IDH–dependent accumulation of 2‐HG results in homologous recombination deficiency (HRD), which preclinically renders tumors sensitive to poly(adenosine diphosphate ribose) polymerase inhibitors. Here, the results of the cholangiocarcinoma (CCA) arm of the National Cancer Institute (NCI) 10129 olaparib in IDH‐mutant solid tumors basket trial are reported. Methods Olaparib 300 mg twice daily was evaluated in an open‐label, phase 2 clinical trial for treatment‐refractory IDH‐mutant solid tumors. Patients in the IDH‐mutant CCA arm enrolled in two cohorts: (1) IDH inhibitor (IDHi) pretreated and (2) IDHi untreated, with a primary end point of overall response rate. Results NCI 10129 enrolled 30 patients with IDH‐mutant CCA with no objective responses seen, and recruitment was closed early. Median progression‐free survival (PFS) was 2.4 months (95% CI, 1.9 to 6.5 months) and median overall survival was 12.9 months (95% CI, 6.3 months to not reached). Eight patients (27%) had clinical benefit (CB), with a PFS of ≥6 months. Patients with CB had lower baseline 2‐HG levels compared to those without CB (1.4 vs. 5.9 µmol/L; p = .01). Conclusions Olaparib does not have sufficient single‐agent activity to warrant further development in IDH‐mutant CCA. However, a subgroup of patients demonstrated CB, and exploratory analysis revealed this subgroup to be enriched for lower baseline 2‐HG levels. Future clinical trials leveraging the HRD properties of IDH mutations are warranted with enhanced patient selection and novel combination therapies.

Background CD4 ⁺ T-cell lymphocytopenia and immune dysfunction are factors that drive the onset and persistence of Kaposi sarcoma (KS) in people with (PWH) and without HIV. Standard chemotherapy agents for KS can contribute to increasing CD4 ⁺ T cell lymphocytopenia. IL-7 is a cytokine that is essential in T-cell development, proliferation and homeostasis. In PWH, IL-7 administration leads to increased numbers of circulating central memory and naïve T-cell phenotypes. Methods In this multicenter phase I study with a 3+3 dose escalation design, participants with KS with or without HIV received up to four intramuscular injections of IL-7 (NT-I7) every 9 weeks. The primary endpoint of the study was to evaluate safety over three escalating dose levels (DL) of NT-I7 (DL1:480 µg/kg, DL2: 960 µg/kg and DL3: 1200 µg/kg) and identify a maximum tolerated dose. Secondary endpoints included evaluation of antitumor activity per the modified AIDS Clinical Trials Group Criteria and assessment of the effect of NT-I7 on the kinetics of CD4 ⁺ and CD8 ⁺ T-cells. Results Eight cisgender male participants (five with HIV infection) were enrolled. Six participants were treated at DL1, and two were treated at DL2. The study was closed to accrual after enrolment of the second participant on DL2 due to termination of study funding. Four of the eight participants (three in DL1 and one in DL2) completed all four doses of the NT-I7. With regard to treatment-emergent adverse events (AEs), all participants had <grade 2 AEs, which included injection site reaction and alanine aminotransferase increase. Injection site reaction was a dose-limiting toxicity in one participant at DL1. The overall KS objective response rate to NT-I7 was 42.9% (95% CI 9.9%, 81.6%) and all three responders were PWH. Absolute lymphocyte counts, CD4 ⁺ and CD8 ⁺ T-cell counts increased among all participants following administration of NT-I7. Participants who experienced a response had HIV and lower CD4/CD8 ratio at baseline and throughout the study as compared with those who did not have KS response to NT-I7. Conclusions Preliminary data demonstrate safety and activity of IL-7 in patients with KS and activity specifically among individuals HIV-associated KS. Trial registration number NCT04893018 .

BCMA-targeted CAR T-cells transformed the treatment of relapsed and refractory multiple myeloma (RRMM), yet improvements are needed in manufacturing, toxicity and efficacy. We conducted a phase 1 clinical trial of BMS-986354, an autologous BCMA CAR T manufactured using an optimized NEX-T® process, in participants with triple-class exposed, RRMM. The 65 participants had a median of 5 (range 3–13) prior regimens, 39% had cytogenetic high-risk, 91% triple-class refractory, and 43% extra-medullar disease. Part A (dose-escalation) of the study enrolled participants in cohorts receiving 20 (N = 7), 40 (N = 24), or 80 (N = 11)x 10⁶ CAR + T-cells. In part B (expansion), an additional 23 participants were treated at the recommended phase 2 dose, 40 ×10⁶ CAR + T cells. Across dose levels, cytokine release syndrome (CRS) occurred in 82% (2% grade ≥3), neurotoxicity in 8% (2% grade ≥3), and infections in 32% of participants (5% grade ≥ 3). The response rate was 95%, with 46% achieving complete responses. Median progression-free survival was 12.3 months (95% CI 11.3–16). Compared to orvacabtagene autoleucel (same CAR construct, conventional manufacturing), BMS-986354 had higher proportion of T central memory cells, were less differentiated and had enhanced potency and proliferative capacity, supporting the use of NEX-T® in future CAR T development.

Purpose: Results from prior studies show contradictory evidence in determining if utilization of renal ischemia during partial nephrectomies (PN) results in worse renal functional outcomes. Data assessing a large cohort of patients with no ischemia PN is lacking. The purpose of this study is to evaluate if the use and type of renal ischemia during partial nephrectomy (PN) affects renal functional outcomes. Materials and methods: A retrospective review of 742 patients undergoing PN were assessed and split into four cohorts: no ischemia (n = 455), cold ischemia (n = 63), warm ischemia time (WIT) <30 minutes (n = 164), WIT ≥30 min (n = 60). Twelve-month relative glomerular filtration rate (GFR) changes and split function were assessed amongst the cohorts. Univariate and multivariable regression analysis were utilized to determine predictors of post-operative acute kidney injury (AKI) and long-term renal functional outcomes. Results: No difference in the mean relative decrease in GFR was noted amongst the four cohorts at either the 3-month (8.7% ± 25.5, p = 0.1) or 12-month (7.5% ± 19.0, p = 0.2) period. On multivariable analysis, age (coef: 0.3, p <0.001), EBL (coef: 0.2 per 100ml, p = 0.02), baseline GFR (coef: 2 per 10 units, p <0.001), number of tumors resected (coef: 0.4, p = 0.02) and post-operative AKI (coef: 8.3, p < 0.001) were predictive of a higher percentage decrease in 12-month GFR while male sex (coef: -6.3, p = 0.001) was inversely related. The type of ischemia or length of WIT was not associated with 12-month GFR change. Conclusions: In patients undergoing PN, the use of and type of ischemia affects short-term but not long-term renal functional outcomes. Facility will multiple ischemia techniques may be useful in the management of patients requiring complex PN.

Molecular subtypes, such as defined by The Cancer Genome Atlas (TCGA), delineate a cancer’s underlying biology, bringing hope to inform a patient’s prognosis and treatment plan. However, most approaches used in the discovery of subtypes are not suitable for assigning subtype labels to new cancer specimens from other studies or clinical trials. Here, we address this barrier by applying five different machine learning approaches to multi-omic data from 8,791 TCGA tumor samples comprising 106 subtypes from 26 different cancer cohorts to build models based upon small numbers of features that can classify new samples into previously defined TCGA molecular subtypes—a step toward molecular subtype application in the clinic. We validate select classifiers using external datasets. Predictive performance and classifier-selected features yield insight into the different machine-learning approaches and genomic data platforms. For each cancer and data type we provide containerized versions of the top-performing models as a public resource.

TPS511 Background: Treatment options for patients with gastroesophageal adenocarcinoma (GEA) are limited and prognosis is poor. KEYMAKER-U06 is a multicenter, open-label, phase 1/2, umbrella platform study designed to evaluate investigational agents with or without pembrolizumab and/or chemotherapy for GEA. Substudy 06C (NCT06469944) will be conducted to evaluate sacituzumab tirumotecan(TROP2 antibody-drug conjugate; formerly MK-2870/SKB264) plus pembrolizumab plus investigator’s choice of chemotherapy as first-line therapy for patients with advanced or metastatic GEA. Substudy 06D (NCT06445972) will be conducted to evaluate sacituzumab tirumotecan plus paclitaxel as second-line therapy for patients with advanced or metastatic GEA. Methods: In both substudies, patients aged ≥18 years with confirmed advanced or metastatic HER2-negative GEA (gastric, gastroesophageal junction, or esophageal adenocarcinoma), measurable disease per RECIST v1.1 by investigator review and verified by blinded independent central review (BICR), and an Eastern Cooperative Oncology Group performance status score of 0 or 1 are eligible; patients in substudy 06C should be treatment naive and patients in substudy 06D should have disease progression on or after 1 prior therapy. Both substudies will have a safety lead-in phase of ≤10 patients to determine the recommended phase 2 dose of sacituzumab tirumotecan when used in combination with pembrolizumab plus chemotherapy (substudy 06C) or paclitaxel (substudy 06D). In the safety lead-in phase, patients will receive sacituzumab tirumotecan 3 mg/kg or 4 mg/kg IV per a Bayesian optimal interval design. In the efficacy phase of substudy 06C, ≅120 patients (including 10 patients in safety lead-in) will be allocated or randomly assigned to receive pembrolizumab 400 mg IV every 6 weeks plus investigator’s choice of chemotherapy (arm 1) or sacituzumab tirumotecan IV on days 1, 15, and 29 of each 6-week cycle plus pembrolizumab plus investigator’s choice of chemotherapy (arm 2). In the efficacy phase of substudy 06D, ≅80 patients (including 10 patients in safety lead-in) will be allocated or randomly assigned to receive ramucirumab 8 mg/kg IV on days 1 and 15 of each 4-week cycle plus paclitaxel 80 mg/m ² IV on days 1, 8, and 15 of each 4-week cycle (arm 1) or sacituzumab tirumotecan IV on days 1, 15, and 29 of each 6-week cycle plus paclitaxel (arm 2). Primary outcomes for both substudies are safety and tolerability for the safety lead-in and ORR per RECIST v1.1. by BICR for the efficacy phase (calculated based on pooled data from safety lead-in and efficacy phase); secondary outcomes include DOR and PFS per RECIST v1.1 by BICR, OS, safety, and tolerability. Enrollment is ongoing in both substudies. Clinical trial information: NCT06469944 ; NCT06445972 .

TPS672 Background: Neuroendocrine neoplasms (NENs) consist of neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs), which are rare malignancies found in various anatomical sites, including the gastrointestinal tract, pancreatic islets, lungs, and adrenal glands. Poorly differentiated NECs are classified as high-grade carcinomas that bear resemblance to small-cell lung cancer (SCLC). Treatment for poorly differentiated NECs typically follows small-cell carcinoma guidelines, utilizing platinum-based regimens; however, these patients experience a high risk of relapse and demonstrate a limited response to additional systemic therapies. Adrenocortical carcinoma (ACC) is another rare malignancy associated with a median survival of approximately 14.5 months post-diagnosis, and advanced disease management options show limited efficacy. Currently, no targeted therapies have demonstrated significant effectiveness for this condition. Preclinical investigations have indicated that Delta-like non-canonical notch ligand 1 (DLK1) is expressed in various neuroendocrine neoplasms, including ACC, SCLC, neuroblastoma, pheochromocytoma, and paraganglioma. ADCT-701, a humanized antibody targeting DLK1, has shown potential in suppressing tumor growth and enhancing survival across multiple cancer models expressing this marker. Methods: This Phase I dose escalation study (NCT06041516) aims to enroll adult patients with histologically or cytologically confirmed neuroendocrine neoplasms or malignant ACC with evaluable disease, as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Participants will be part of a dose-finding trial. A 3+3 design is utilized to assess up to ten different dose levels of ADCT-701. Dose escalation continues unless dose-limiting toxicities occur, the maximum tolerated dose (MTD) is reached, or an optimal dose is established. The primary endpoint of the study is to ascertain the recommended phase 2 dose of ADCT-701 in patients with neuroendocrine neoplasms or malignant adrenocortical carcinoma. Secondary endpoints will assess safety, preliminary tumor activity, response rate, overall survival, pharmacokinetics, and the immunogenicity profile of ADCT-701. The trial aims to enroll up to 70 evaluable patients across a maximum of 10 dose levels. For further details, please refer to clinical trial information NCT06041516. Clinical trial information: NCT06041516 .

682 Background: Participation in pancreatic ductal adenocarcinoma (PDAC) clinical trials remains dismal among patients from minoritized groups. This study aimed to investigate if clinical trial design, including eligibility criteria, affects representation of minoritized populations. Methods: United States Phase I-IV PDAC clinical trials between 2000-2020 were extracted from the ClinicalTrials.gov database. The Surveillance, Epidemiology, and End Results (SEER) database was used to determine cancer incidence linked with years of trial enrollment. Enrollment fraction (EF) was defined as the number of trial participants divided by the incidence of PDAC in each racial and ethnic group. Representation Quotient (RQ) was defined as the proportion of trial participants divided by proportion of PDAC incidence for each subgroup, where underrepresentation was RQ <1.0. Results: 8451 patients from 228 unique PDAC clinical trials were analyzed. 55.7% (n=128) and 44.3% (n=102) trials reported racial and ethnic demographic data, respectively. Non-Hispanic Black (NHB), Non-Hispanic Asian/Pacific Islander (NHAPI), Non-Hispanic American Indian/Alaskan Native (NHAIAN), and Hispanic patients were underrepresented (Table). NHB patients were more likely to be underrepresented in trials for metastatic PDAC disease (89.4% vs. 73.8% of trials, p=0.035). NHB patients demonstrated an increase in median RQ (0.28 vs. 0.48) in trials from 2000-2010 vs. 2011-2020, while Hispanic patients had a decreased median RQ (0.36 vs. 0.25). Trials with renal insufficiency exclusion criteria without cutoffs or explicit methodology were more likely to accrue NHB patients (RQ 0.88 vs. 0.46, p=0.02), whereas trials that used a creatinine cutoff or the modified Cockcroft-Gault (CG) formula did not significantly affect RQ. Other eligibility criteria including cardiac history, HIV, Hepatitis B/C, and receipt of neoadjuvant therapy did not significantly affect RQ for any racial or ethnic group. Trial location and funding source did not affect RQ for any group. Conclusions: Systemic barriers persist in minority enrollment in PDAC clinical trials. Clinical trial design optimizing inclusive eligibility requirements is a first feasible step in increasing minority clinical trial enrollment. Racial and ethnic representation in pancreatic ductal adenocarcinoma clinical trials. Enrollment Fraction (Median, IQR) Representation Quotient (Median, IQR) NHW 0.28 (0.12-0.62) 1.17 (1.09-1.24) NHB 0.15 (0-0.33) 0.47 (0-0.87) NHAPI 0 (0-0.23) 0 (0-0.45) NHAIAN 0 (0-0) 0 (0-0) Hispanic 0.07 (0-0.21) 0.26 (0-0.68) *Abbreviations: Interquartile Range (IQR), Non-Hispanic Black (NHB), Non-Hispanic Asian/Pacific Islander (NHAPI), Non-Hispanic American Indian/Alaskan Native (NHAIAN).

764 Background: Pancreatic acinar cell carcinoma (PACC) is a rare exocrine tumor of the pancreas that comprises 0.2-2% of all pancreatic malignancies. There are no prospective randomized studies in this disease and most data about PACC comes from retrospective database analyses and case reports. Methods: The Cancer Moonshot-funded My Pediatric and Adult Rare Tumor (MyPART) network’s Rare Solid Tumor Natural History study (NCT03739827) is a prospective, single-institution observational study that enrolls patients of all ages with rare solid tumors (<15 cases per 100,000 people per year), including PACC. Patients can participate remotely (field cohort) or visit the NIH for annual evaluations (in-person cohort). All participants complete medical and family histories, patient reported outcomes (PROs) measures, and provide saliva for DNA analysis. Relevant data such as clinical and family histories, surgical and molecular pathology, and imaging results are extracted from patient medical records and entered in the central study database. Archival tumor samples (when available) are analyzed using a 500+ gene panel (TruSight500, Illumina) and discussed in a molecular tumor board. Patients participating in the in-person cohort undergo additional evaluations including clinical examination, imaging studies, genetic counseling, and blood sample collection for clinical and research purposes (standard clinical labs, germline DNA/RNA, immune phenotypes, cytokines) as indicated. Results: From 09/2021 until 09/2024, 17 PACC patients (n=13 for the field cohort, n=4 for the in-person cohort) were accrued. The mean age of diagnosis is 64.7 (48-78) years, and the male to female ratio is 14:3. At the time of diagnosis, 6 patients had Stage I or II, 1 had Stage III, and 10 had Stage IV disease. The median follow-up time since accrual is 7.6 months, and 4 patients have died. No patients have been lost to follow-up. Of the 6 patients diagnosed with early-stage disease, 5 had surgery and all received adjuvant chemotherapy, while 1 patient is receiving neoadjuvant chemotherapy. Among the 9 patients diagnosed with advanced disease, 8 received platinum-based regimens as a first-line therapy. Tumor molecular profiling was available for 16 patients. The most common tumor mutations observed were in CDKN2A (29.4%), BRCA2 (29.4%), and SMAD4 (23.5%). Six patients received targeted therapies matched to their tumor molecular profile. Conclusions: The demographic profile of our cohort aligns with previous studies, with a mean age of diagnosis in the early-to-mid 60s and a high male to female ratio. Our cohort highlights a shift in first-line treatment to platinum-based therapies over the past decade. Many PACC tumors have targetable mutations found in molecular profiling, and the efficacy of matched therapy warrants further exploration. Clinical trial information: NCT03739827 .