Citations

12079 Background: Many troublesome symptoms experienced by men with prostate cancer are not specific to a particular disease state or treatment modality. As such, these issues' scope is neither fully appreciated nor characterized in the reporting of clinical trial data. A modern accounting of poorly controlled symptoms is needed to better inform survivorship and supportive care efforts. Methods: Data are drawn from the Enhanced, EHR-facilitated Cancer Symptom Control (E2C2) study, a cluster-randomized stepped wedge trial examining the effectiveness of routine symptom assessment and management on patient-centered outcomes and healthcare utilization (NCT03892967). This is a population-level study supporting patients with cancer, who are cared for in medical oncology clinics across the Midwest United States. The trial utilizes an automated symptom monitoring system with EHR-enabled algorithms for symptom triage and intervention. The current analysis focuses on pre-intervention surveys. The cohort includes E2C2 participants with prostate cancer (as determined by the Mayo Clinic Cancer Registry) receiving curative or palliative-intent therapies, along with prostate cancer survivors who previously completed their treatment. The prevalence of SPPADE symptoms (sleep disturbance, pain, impaired physical function, anxiety, depression, fatigue [low energy]) was assessed using 0 to 10 numerical rating scales (NRS), with scores of 4-6 indicating moderate symptoms and 7-10 indicating severe symptoms. Results: A total of 1,388 men with prostate cancer completed a pre-intervention survey between March 2019 and January 2023. The median age at completion of first survey was 74 years. The cohort includes patients living in diverse settings, including urban (n=718, 52%), micropolitan (n=250, 18%), small town (n=218, 16%), and rural (n=200, 14%) environments. The proportion of patients experiencing moderate-to-severe symptoms (NRS score ≥4) was 47% for fatigue, 40% for impaired physical function, 32% for sleep disturbance, 27% for pain, 22% for anxiety, and 20% for depression/emotional distress. The three domains with the highest prevalence of severe symptoms (NRS score ≥7) were fatigue (17%), impaired physical function (12%), and sleep disturbance (10%). Conclusions: Proactive symptom monitoring identifies a high overall burden of moderate-to-severe symptoms, particularly fatigue and impaired physical function, among prostate cancer patients and survivors. Collaborative care approaches and symptom control trials are needed to mitigate and manage these burdensome symptoms. Clinical trial information: NCT03892967 . [Table: see text]

12065 Background: Incidence of cancer, including colorectal, breast, pancreas, kidney, and uterine cancer, is increasing in younger populations. Adolescents and young adults (AYA, defined as age 15-39) with cancer face unique challenges. This study aimed to characterize how symptom burden differs between AYA and non-AYA (aged 40+) patients with cancer. Methods: We performed a subgroup analysis of the E2C2 study, a cluster-randomized, pragmatic trial examining the effectiveness of routine symptom assessment and guideline-based management on patient-centered and healthcare utilization metrics during and following cancer treatment. Six symptoms [Sleep disturbance, Pain, Physical function impairment, Anxiety, Depression, and Energy deficit/fatigue (SPPADE)] were evaluated using 11-point numerical rating scales (NRS). Symptom severity was classified as mild (0-3), moderate (4-6), or severe (7-10). We conducted a subgroup analysis of symptom burden among AYA patients (defined as age 18-39 in this study), using their first-reported NRS scores. Results: The E2C2 cohort included 2,598 AYA patients and 38,061 non-AYA patients who completed >1 SPPADE NRS on at least one survey. AYA patients were more likely than non-AYA patients to report severe anxiety ( p<0.0001) and depression ( p<0.0001) (Table). Non-AYA patients were more likely to report severe pain ( p=0.02179), fatigue ( p=0.0022), and physical function limitations ( p<0.0001). Sociodemographic differences were also noted. A higher proportion of AYA patients held a bachelor’s degree or higher (38% vs 28%), were employed (73% vs 37%), and lived in an urban setting (67% vs 56%), compared to non-AYA patients. Non-AYA patients were more likely to have government insurance (63% vs 21%) and to be married (72% vs 59%). Conclusions: AYA patients with cancer were more likely to report severe depression and anxiety compared to their counterparts age 40 and above, underscoring the need for targeted and tailored psycho-oncology care for this population. [Table: see text]

11514 Background: The role of immunotherapy remains uncertain in most sarcomas. We recently showed significant antitumor benefit for cabozantinib (C) with N in AS previously treated with a taxane. Since chemotherapy-immunotherapy combinations may synergize, and paclitaxel remains a standard of care option for advanced AS, we hypothesized that P+N would be more effective than P alone. Methods: We report Arm 1 (P+N) and Arm 2 (P) of this open label, multi-arm, phase II study. Pts all had locally advanced/metastatic AS, and no prior taxane (including adjuvant) or checkpoint inhibitor prior to entry. Pts were randomized 1:1 (stratified scalp/face vs other) to receive P 80 mg/m2 on days 1, 8, 15 every 4 weeks (wks), with (Arm 1) or without (Arm 2) N (480 mg intravenously every 4 wks). A pt could remain on study beyond disease progression (PD), after the initial 12 wk evaluation (4 wk confirmatory scan required), but responses were censored at 12 wks. Primary endpoint was progression-free survival (PFS) comparing P+N to P, with an assumed improvement from a median of 4 to 7 months with N added to P (power = 85.3%, alpha = 0.148, and one interim analysis (Wieand rule) for futility planned after 30 events). Secondary endpoints were overall response rate (ORR), adverse events (AEs), overall survival (OS), and pt reported outcomes (PRO). At PD, Arm 2 (P) pts were permitted to receive C+N. Results: 62 evaluable pts (P+N = 30, P = 32 pts) were balanced for age, race, ECOG PS 0 vs. 1, site of disease (including radiation related vs. not), while P+N had more females (60%) and P had more males (63%). Median PFS for P+N was 7.2 mo (5.3-17 mo), and 8.3 mo (4.0-18 mo) for P (hazard ratio (HR) 1.01 (95%CI: 0.55-1.9), p = 0.96). Median PFS for scalp/face was 16 mo (95%CI: 10-NR) for P+N and 8.3 mo (95%CI: 3.7-NR) for P. Median PFS for all others was 5.5 mo (95%CI 4.3-16) for P+N, and 6.0 mo (95%CI 4.1-NR) for P. Median OS was 18 mo (13-NR) in P+N, and 23 mo (15-NR) in P (HR 1.3 (95%CI: 0.63-2.7), p = 0.48). Overall confirmed ORR: P+N = 33% (10/30 pts, with 4 partial responses (PR) and 6 complete responses (CR) with scalp/face ORR = 73%, all others ORR = 11%). Overall ORR for P = 34% (11/32 pts, with 7 PR and 4 CR, with scalp/face ORR = 38%, all others ORR = 26%). Grade 3-4 AEs regardless of attribution occurred in 57% of P+N, and 44% of P, most commonly ( > 10%) fatigue, AST increase, and dyspnea for P+N (n = 3 each), and anemia (n = 4) for P. Conclusions: P alone can be an effective therapy in a subset of pts with AS. The combination of P+N failed to demonstrate improvement in median PFS over P alone, but may show benefit in scalp/face AS. OS trended better with P alone. No new safety signals were observed. The impact of weekly steroid premedication prior to P+N on these outcomes remains to be determined. PRO and exploratory analyses are ongoing. Support: U10CA180821, U10CA180882, U24 CA196171; NCT04339738. https://acknowledgments.alliancefound.org . Clinical trial information: NCT04339738 .

e17059 Background: It is unclear if patients with different HRR gene-mutated mCRPC derive consistent benefit from treatment with PARPi and API combination. Approval labels for PARPi+API are inconsistent across regulatory bodies in the US (Food and Drug Administration, FDA) and Europe (European Medical Agency, EMA), adding to confusion among practicing clinicians. Therefore, we aimed to assess the differential efficacy of PARP+API therapy by different genes using up-to-date trial evidence. Methods: We maintain a living meta-analysis on mCRPC treatments that is updated when new data becomes available. Here, we report data from phase III randomized control trials (RCTs) assessing PARPi+API in 1L mCRPC. The outcomes of interest included radiographic progression-free survival (rPFS) and overall survival (OS). Hazard ratios (HR) for rPFS and OS by different genes were summarized using random effects meta-analysis via inverse variance approach. Results: We have screened 27376 references since the inception of this living review. Here, we report data from three trials (15 references) with a total of 1618 patients. Frequently reported HRR gene mutations in the included trials were BRCA2 (35%), ATM (21%), CDK12 (12.2%), CHEK2 (12.2%), BRCA1 (4.6%), and PALB2 (3.4%). In terms of rPFS, statistical benefit was observed in BRCA (0.28; 95% CI: 0.13-0.59) and CDK12 (0.58; 95% CI: 0.35-0.95) subgroups, whereas no statistically significant benefit was seen in PALB2 (0.53; 95% CI: 0.21-1.32), ATM (0.93; 95% CI, 0.57-1.53), and CHEK2 (0.92; 95% CI: 0.53-1.61) subgroups. For OS, benefit was observed in BRCA (0.47; 95%CI: 0.31-0.71) subgroup. While not statistically significant, a signal of meaningful OS benefit was observed in PALB2 (0.33; 95%CI: 0.10-1.16) but no OS benefit was observed in ATM (0.97; 95% CI: 0.57-1.67), CDK12 (0.80; 95% CI: 0.36-1.78), and CHEK2 (0.81; 95% CI: 0.37-1.75) subgroups. Conclusions: Current results show that mCRPC patients with BRCA and CDK12 alterations had delayed disease progression with PARPi+API as 1L therapy. BRCA mutations are also associated with improved OS, while patients with CHEK2 and ATM derived no significant benefit with PARPi+API combination. [Table: see text]

Abstract Hip pain is a common concern among athletes. With gluteal tendinopathy, femoroacetabular impingement, and osteoarthritis predominating sports medicine and musculoskeletal practices, less common etiologies may be overlooked. Complex pelvic anatomy and variable pain referral patterns may make identifying an accurate diagnosis challenging. Employing a systematic approach to evaluation and having a thorough understanding of hip region anatomy are essential. A potentially overlooked cause of anterolateral hip pain is iliotibial band origin tendinopathy. Patients often present with pain around the anterolateral hip and tenderness to palpation at the anterolateral iliac crest. While patients with iliotibial band origin tendinopathy usually respond to nonsurgical intervention, there is little literature to guide evaluation and treatment, highlighting a gap in the recognition of this condition. The purpose of this narrative review is to describe the anatomy of the proximal iliotibial band origin, outline the clinical diagnosis and imaging findings of ITBOT, and summarize current treatment options.

2565 Background: Mesothelin (MSLN) is overexpressed in mesothelioma and other solid tumors making it the focus of multiple targeted therapies, including antibody drug conjugates (ADCs), T cell receptor (TCR) fusion constructs, and chimeric antigen receptor T-cell (CAR-T) products. However, the clinical efficacy of these treatments remains limited. We hypothesize that soluble MSLN (sMSLN) in the plasma binds to MSLN-targeted therapies before reaching the tumor. Our study aimed to evaluate the effects of sMSLN on a MSLN-targeting antibody, anetumab, and explore methods to reduce sMSLN. Methods: Exploratory analysis in NCT03126630: sMSLN testing was performed on blood samples from participants enrolled in NCT03126630 at the Molecular Targets Core Lab, National Cancer Institute. The median was used to categorize high and low levels of sMSLN. Survival was estimated with the Kaplan-Meier method and compared between groups with the log rank test. Anetumab immunoprecipitation: Anetumab was covalently coupled to Dynabeads at 5 µg per mg of beads to immunoprecipitate MSLN from two plasma samples. Assays were performed in duplicate. Therapeutics plasma exchange (TPE):Whole blood samples were collected before and after one plasma volume of TPE with albumin as the replacement fluid in patients undergoing routine TPE for various medical conditions, such as autoimmune diseases and hyperviscosity syndromes. Plasma levels of sMSLN were measured with an ELISA assay in matched pre- and post-TPE plasma samples. Results: We obtained sMSLN levels from 40 patients enrolled in NCT03126630. For patients treated with both anetumab ravtansine and pembrolizumab, median progression free survival (PFS) was shorter in the high sMSLN group (5 months) vs the low sMSLN group (12 months). For patients treated with pembrolizumab alone, PFS was similar for patients with high and low sMSLN (4 vs 3.4 months). Anetumab significantly reduced the concentration of sMSLN in plasma samples as detected by MSLN ELISA (p<0.05), demonstrating that sMSLN can bind to and sequester anetumab. Next, we evaluated TPE as a mechanism to reduce sMSLN. We obtained pre- and post-TPE plasma samples from 15 patients undergoing routine TPE for various medical conditions. TPE consistently reduced sMSLN (p<0.05) with an average decrease of 43.6% or 15.4 ng/mL. Conclusions: We found that high sMSLN levels are associated with shorter PFS for anetumab ravtansine, but not pembrolizumab. Additionally, anetumab binds to sMSLN in the plasma, which suggests that sMSLN can sequester anti-MSLN antibodies and may limit the efficacy of MSLN-targeted therapies. High levels of sMSLN could potentially be used as a biomarker to select which patients should not receive MSLN-targeting therapies. Furthermore, our results indicate that sMSLN reduction is feasible with TPE. Decreasing sMSLN could restore the activity of MSLN-targeted therapies.

1559 Background: Timely access to specialty Palliative Care (SPC) services provides significant benefits to hospitalized patients with cancer, including improvements in quality of life. However, many patients with cancer who could benefit from SPC suffer from lack of timely referral or do not receive SPC services. A previously published trial of an artificial intelligence/machine learning (AI/ML) model to predict need for SPC at Mayo Clinic increased timely SPC consultation of hospitalized patients overall. We sought to review the performance of this algorithm in patients with cancer across an expanded hospitalized population. Methods: The study population consisted of all patients admitted into a Mayo Clinic hospital in Minnesota, Wisconsin, Arizona and Florida between January 2020 and September 2023. Due to the size of the cohort a case-control sample of three controls for every case was created. Patients were considered to be a patient with cancer if they had at least one billing diagnosis up to 1 year prior to their index hospitalization from any of the 5 HCC categories denoting cancer: Metastatic Cancer and Acute Leukemia (HCC 8); Lung and Other Severe Cancers (HCC 9); Lymphoma and Other Cancers (HCC 10); Colorectal, Bladder, and Other Cancers (HCC 11); and Breast, Prostate, and Other Cancers and Tumors (HCC 12). The training data set consisted of 107,076 patient encounters with a total of 8,355,090 time periods of constant risk. An AI/ML model using gradient boosting methods which contained 269 variables (both static and time-varying) of various classes with SPC consultation treated as a time-to-event outcome was trained. Results: Due to the longitudinal nature of the prediction, performance was assessed using the max score AUC (using the max score a patient received during a given encounter prior to an event or discharge) to produce the AUC. The model had an overall AUC of 0.932 (0.929, 0.935 – 95% CI). We saw a decrease in performance of the AI/ML model in the Oncology population with an overall performance of 0.818 (0.806, 0.83). Some of the most influential variables were previous SPC visit, age, metastatic disease, acute leukemia diagnosis, and pain scores. Conclusions: An AI/ML model can effectively predict the need for an inpatient PC consult in a population of hospitalized patients with cancer. [Table: see text]

Abstract Aims Patients with pulmonary hypertension (PH) are grouped based upon clinical and haemodynamic characteristics. Groups 2 (G2, left heart disease [LHD]) and 3 (G3, lung disease or hypoxaemia) are most common. Many patients display overlapping characteristics of heart and lung disease (G2–3), but this group is not well-characterized. Methods and results Patients with PH enrolled in the prospective, NHLBI-sponsored PVDOMICS network underwent intensive clinical, biomarker, imaging, gas exchange and exercise phenotyping. Patients with pure G2, pure G3, or overlapping G2–3 PH were compared across multiple phenotypic domains. Of all patients with predominant G2 (n = 136), 66 (49%) were deemed to have secondary lung disease/hypoxaemia contributors (G2/3), and of all patients categorized as predominant G3 (n = 172), 41 (24%) were judged to have a component of secondary LHD (G3/2), such that 107 had G2–3 (combined G2/3 and G3/2). As compared with G3, patients with G2 and G2–3 were more obese and had greater prevalence of hypertension, atrial fibrillation, and coronary disease. Patients with G2 and G2–3 were more anaemic, with poorer kidney function, more cardiac dysfunction, and higher N-terminal pro-B-type natriuretic peptide than G3. Lung diffusion was more impaired in G3 and G2–3, but commonly abnormal even in G2. Exercise capacity was severely and similarly impaired across all groups, with no differences in 6-min walk distance or peak oxygen consumption, and pulmonary vasoreactivity to nitric oxide did not differ. In a multivariable Cox regression model, patients with G2 had lower risk of death or transplant compared with G3 (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.30–0.86), and patients with G2–3 also displayed lower risk compared with G3 (HR 0.57, 95% CI 0.38–0.86). Conclusions Overlap is common in patients with a pulmonary or cardiac basis for PH. While lung structure/function is clearly more impaired in G3 and G2–3 than G2, pulmonary abnormalities are common in G2, even when clinically judged as isolated LHD. Further study is required to identify optimal systematic evaluations to guide therapeutic innovation for PH associated with combined heart and lung disease. Clinical Trial Registration: ClinicalTrials.gov NCT02980887.

1083 Background: T-DXd and SG are both FDA-approved treatments for patients (pts) with HER2-low MBC, but little data exists on the sequential use of these ADCs. Methods: In this multicenter retrospective cohort study, we identified pts with HER2-low MBC treated sequentially with both T-DXd and SG in either order, with or without intervening therapies (IntTx), at 5 academic centers between 2020-2023. We previously reported real-world progression free survival (rwPFS) and real-world overall survival (rwOS) by HR-status and ADC sequence order. Here we provide updated rwPFS and rwOS data, as well as new subgroup analyses by age, sites of disease, and use of IntTx between ADCs for HR- and HR+ disease. Results: 84 pts with HER2-low MBC treated with both T-DXd and SG were included, including 56 pts with HR+/HER2-low MBC (66.7%) and 28 pts with HR-/HER2-low MBC (33.3%). Prior to the start of ADC1, median age was 58 yrs and 22 pts were >65 yrs (26.2%), 65 pts (77.4%) had visceral disease, and 14 pts (16.7%) had central nervous system (CNS) disease. 36 pts (42.9%) had an IntTx between ADCs. Table 1 shows updated rwPFS and rwOS data by HR-status and ADC sequence order. For pts with HR+ and HR- MBC, there was no difference in ADC1 rwPFS or ADC2 rwPFS by age ≤65 vs. >65 yr or by presence vs. absence of visceral disease. For pts with HR- MBC, ADC1 rwPFS and rwOS was shorter for pts with CNS disease vs. pts without CNS disease (rwPFS 5.4 mo (n=6) vs. 8.5 mo (n=22), p=0.03; rwOS 11.6 mo vs. 21.1 mo, p<0.01 respectively). For pts with HR+ and HR- MBC, there was no difference in ADC2 rwPFS with or without receipt of IntTx. There was no difference in time to treatment failure for first IntTx vs. ADC2 if no InTx was given. Conclusions: This is one of the largest multicenter cohorts of pts treated with sequential ADCs for HER2-low MBC. Median rwPFS was longer for ADC1 than ADC2 in all subgroups, regardless of HR-status, ADC sequence order, age ≤65 or >65 yr, presence of visceral disease, or use of IntTx. Among pts with HR-/HER2-low MBC, pts with CNS disease had shorter ADC1 rwPFS and rwOS than pts without CNS disease. [Table: see text]