bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase 1 results of the WEE1 inhibitor, azenosertib, in combination with gemcitabine (gem) in adult and pediatric patients (pts) with relapsed or refractory (R/R) osteosarcoma.
Authors: Avutu Viswatej , Livingston J. Andrew , Federman Noah , Cranmer Lee D. , Gaspar Nathalie , Toulmonde Maud , Pressey Joseph Gerald , Brahmi Mehdi , Poklepovic Andrew Stewart , Shi Qing , Jameson Nathan , Jubb Adrian Michael , Louis Chrystal Ursula , Chawla Sant P. , Tap William D. 
Published: June 2024

11525 Background: Patients with R/R osteosarcoma have poor outcomes with a historical 16-week event-free survival (EFS) of ~12% after treatment with salvage therapy (Lagmay et al, 2016). Azenosertib is a highly selective WEE1 inhibitor that induces cancer cells to accelerate through the G1/S and G2/M checkpoints without repairing damaged DNA, causing mitotic catastrophe and cell death. Azenosertib has demonstrated significant synergy with gem in non-clinical models. The purpose of this study was to evaluate the safety and tolerability, determine the maximum tolerated dose (MTD), and assess for anti-tumor activity in pts with R/R osteosarcoma receiving C and gem. Methods: This dose-finding study (NCT04833582) assessed azenosertib + gem in pts ≥12 years of age using a standard 3+3 design. The MTD was defined as the dose level with prespecified adverse events (dose-limiting toxicities [DLTs]) occurring at a rate <33%. The primary endpoint was the incidence and severity of DLTs in cycle 1. Secondary endpoints included the incidence and severity of adverse events and EFS at 18-weeks per RECIST v1.1 (time from treatment initiation until disease progression or death due to any cause). Pts were treated across 5 dose-finding cohorts, receiving azenosertib (starting dose 200 mg QD PO on a continuous schedule) and gem (starting dose 1000 mg/m2 IV on D1 and D8 of a 21D cycle) until disease progression or unacceptable toxicity. Results: As of Nov 30, 2023, 31 pts had been treated. The median age was 27y (range 12-76); 21 (68%) pts were ≤39y. Pts received a median of 3 (1-9) prior therapies. At tolerated doses, the most frequent grade ≥3 adverse events (≥20%) included thrombocytopenia and lymphopenia (33% each); there were no grade 4 thrombocytopenia events or instances of febrile neutropenia. DLTs included thrombocytopenia and gastrointestinal toxicity. The MTD was determined to be azenosertib 150 mg daily on a 5:2 schedule (5 days on, 2 days off) + gem 800 mg/m2. None of the pts treated at the MTD (n=6) required dose reductions of azenosertib due to AEs and only 1 required a dose interruption. The 18-week EFS was 39% (11/28) across all dose levels. Conclusions: Azenosertib + gem was well tolerated at the MTD and provided a greater EFS than historical control cohorts of salvage therapy in pts with R/R osteosarcoma. The MTD of the combination was well tolerated and these data support further investigation of azenosertib with gem in pts with R/R osteosarcoma in an upcoming Investigator-Initiated Phase 2 trial. Clinical trial information: NCT04833582 .
Combination targeted therapy of avapritinib and sunitinib for patients with refractory advanced gastrointestinal stromal tumors after failure of standard treatments: Early results from a multi-institutional pilot study.
Authors: Zhang Xinhua , Xia Yanzhe , Wang Ming , Chen Tao , Li Wei , Li Jian , Zhou Ye , Qian Haoran , Cai Shirong , Tang Ke-Jing , He Yulong 
Published: June 2024

11535 Background: The objective of this study was to explore the efficacy and safety of the combination of avapritinib and sunitinib in refractory GISTs. Methods: This was a multi-institutional prospective cohort study in part of a real-world trial (NCT05461664) exploring avapritinib in GIST patients (pts) after failure of standard treatments. From Jan 2022 to Sep 2023, participants were administered avapritinib at 100–200mg QD combined with sunitinib at 25–37.5mg QD continuously in 28-day cycles until PD or discontinuation. Clinical outcomes including ORR, survival and safety were assessed. Results: Twenty pts, generally heavily pretreated (65% with ≥4 prior TKIs, and 70% had progressed on ripretinib) were enrolled across seven participating centers. Median sum of target lesions was 27.0cm (range, 6.6–80.8). Among them, nine pts had primary KIT 11 mutation, 10 harbored KIT 9and one harbored KIT 17. Nine pts had KIT activation-loop (AL) mutations without KITATP-binding pocket (ABP) mutations ( KITALpos ABPneg), 2 had KIT ABP mutations without KIT AL mutations ( KITALneg ABPpos). ORR was 20% (4 PR), 15 pts (75%) had SD, one (5%) had PD with a CBR (PR+SD≥16w) of 75%, assessed via mRECIST v1.1. Tumor shrinkage was observed in 18 pts (90%), with a median best percent change in target lesions of -20.2% (range, -54.5% to 16.1%). With a median follow-up duration of 11.3 months (range, 2.3–20.9), 12 pts progressed, 3 were withdrawal, 7 were dead and 5 continued to receive combination therapy. Median PFS (mPFS) was 6.6 months (95% CI 5.8-7.4). Median OS was not reached. mPFS in pts with primary KIT 11 was similar compared to those with KIT 9. Regarding secondary KIT mutations, mPFS was numerically longer in KIT ALpos ABPneg pts compare to without (6.9 months VS 2.3 months, p=0.251). mPFS was significantly shorter in pts with KITALneg ABPpos than without (1.1 months VS 6.9 months, p<0.001). Three pts carrying KIT 16 L783V exhibited significantly longer mPFS than others (18.2 months VS 6.4 months, p=0.041). The dose of avapritinib (100–150 mg/d) and sunitinib (25–37.5 mg/d) could be tolerated. Common adverse events (AEs) were anemia, leukopenia, diarrhea, fatigue, periorbital and face oedema, and memory impairment. Common grade ≥3 AEs included leukopenia (30.0%), neutropenia (25.0%), anemia (20.0%), diarrhea (20.0%), and gastrointestinal hemorrhage (15.0%). Conclusions: The combination of avapritinib and sunitinib provided meaningful clinical benefit with an acceptable safety profile in pts with refractory GISTs, except for those harbored KITALneg ABPpos mutations. Clinical trial information: NCT05461664 .
Comparison of machine learning algorithms for the radiomic classification of gastric subepithelial tumors.
Authors: Jeong Woo Kyoung , Lee Jeong Hyun 
Published: June 2024

11536 Background: Diagnostic challenges arise in classifying gastric subepithelial tumors (SETs) due to the absence of specific imaging findings and limitations in endoscopic biopsy, particularly for deep-seated tumors. Differentiating SETs that require surgical intervention from those suitable for diagnostic imaging follow-up is crucial. Gastrointestinal stromal tumors (GIST), with malignant potential, necessitate prompt resection, while leiomyoma and schwannoma are benign and can be followed up if asymptomatic. Many radiomic approaches using machine learning (ML) were tried to classify gastric SET. Nevertheless, a comprehensive exploration of current ML algorithms still needs to be explored. Methods: The patients who underwent the surgery for gastric SET in our hospital were considered eligible subjects. All cases were confirmed by pathologic evaluation, and the cases of GIST and leiomyoma were chosen for this study. Manual segmentation and radiologist validation were performed, followed by image resampling to 1 x 1 x 1 mm resolution. Radiomics features were extracted using PyRadiomics 3.0.1, focusing on 32 first-order and shape features for interpretability and robustness. Various models, including K-nearest neighbors (KNN), support vector machines (SVM), logistic regression (LR), lightGBM, random forest (RF), and TabPFN (by Hollman N et al.), underwent evaluation. Nested cross-validation with 10 folds and 10 repetitions ensured fair comparison, and Bayesian hyperparameter optimization was conducted in a 5-fold inner CV, excluding TabPFN. Comparative evaluation included area under the receiver operating characteristics (AUROC), accuracy, balanced accuracy, and Matthew Correlation Coefficient (MCC). Results: Among the 359 eligible patients, resulting in 241 GISTs and 27 leiomyomas post-exclusion. We used 26 pre-isolated cases as a test set of the model. The model test results for various ML models in classifying gastric SETs are presented (Table). Notably, LR exhibited the highest accuracy (0.899), F1 score (0.950), and AUROC (0.653) compared to other models without statistical significance. Conclusions: Our study highlights that LR improves the accuracy of diagnosing gastric SETs. These findings contribute to refining diagnostic approaches and may optimize patient management strategies for gastric SETs.[Table: see text]
Proteomic analysis in patients with dedifferentiated liposarcoma (DDLPS) in a phase Ia/Ib study of the MDM2–p53 antagonist brigimadlin.
Authors: Jaimes Yarúa , LoRusso Patricia , Sturm Gregor , Gounder Mrinal M. , Yamamoto Noboru , Somaiah Neeta , Lugowska Iwona A. , Moreno Victor , Peltzer Alexander , Teufel Michael , Jayadeva Girish , Schöffski Patrick 
Published: June 2024

11541 Background: The tumor suppressor p53 primarily exerts its suppressive function via the transcriptional regulation of target genes. Both preclinical and clinical studies have demonstrated that restoring p53 activity elevates GDF-15, a p53 target, in plasma; however, the effects of other circulating proteins are not well understood. Brigimadlin (BI 907828), a highly potent, oral MDM2–p53 antagonist, is being investigated in an ongoing Phase Ia/Ib study (NCT03449381) in patients with advanced solid tumors, including DDLPS. To understand the effects of brigimadlin on the circulating proteome, we present data from a longitudinal proteomic analysis of plasma samples from patients with DDLPS who received brigimadlin every 3 weeks in Phase Ib. Methods: The Human DiscoveryMAP assay (Rules-Based Medicine) was used for protein analysis, measuring levels of 204 proteins with the Luminex platform. Plasma samples, collected at baseline and Cycle 3 Day 1 (C3 D1), were used for differential protein expression using a linear model. Proteins that showed a significant differential expression between cycles were further explored by incorporating additional covariates (time on treatment, best overall response, overall survival) into a Cox hazards ratio model. Results: Baseline and C3 D1 plasma samples were available from 37 patients with DDLPS. At baseline, angiopoietin-1, C-C motif chemokine 16, PAI-1, and C-C motif chemokine 5 were higher in DDLPS samples than in other tumor samples (samples from 24 patients in the same study), whereas levels of gamma enolase were lower in DDLPS samples. After patients with DDLPS were treated with brigimadlin (C3 D1), there were significant changes vs baseline in the expression of several proteins (i.e., up- or downregulation), including angiopoietin-1 (down, p = 0.02), LAP_TGF-beta (down, p = 0.02), PAI-1 (down, p = 0.085), thrombomodulin (down, p = 0.062), and serpinA7 (up, p = 0.031). Levels of AXL receptor tyrosine kinase (UFO) were downregulated in patients who achieved a CR or PR (n = 11; p = 0.0092) or SD (n = 23; p = 0.03), according to RECIST. However, in patients with PD (n = 3), baseline UFO levels were higher vs patients achieving CR/PR (mean baseline log2 expression: 3.6 µg/L vs 3.0 µg/L, respectively) and were not downregulated during treatment. Correlation of changes in thrombomodulin and neutrophil gelatinase-associated lipocalin levels with myelosuppressive events will be shown. Conclusions: These findings provide insight into the proteomic changes associated with brigimadlin treatment in patients with DDLPS and highlight potential biomarkers for treatment response and adverse events. Further investigation is needed to determine their significance and impact on patient outcomes. Clinical trial information: NCT03449381 .
An anti-EpCAM x anti-CD3 bispecific antibody, M701, for the treatment of malignant ascites due to epithelial cancer: Interim results of a prospective randomized controlled phase II trial.
Authors: Lin Rongbo , Xu Jianming , Liu Rongrui , Li Ning , Li Guiling , Zhang Tao , Zhao Jun , Li Jiayi , Sun Meili , Wang Ke , An Hanxiang , Zhang Weijie , Xu Huiting , Zeng Shan , Zhang Mingjun , Zhou Pengfei , Huang Shaoyi , Wang Xiong 
Published: June 2024

12060 Background: Malignant ascites (MA) is a significant complication in patients with late-stage epithelial cancer, associated with poor prognosis, reduced quality of life, and severe symptoms. It is usually caused by tumor cells seeding into the peritoneum, which obstructs lymphatic drainage and increases capillary permeability. Currently, there is no approved drug therapy specifically for the treatment of MA worldwide. Methods: Patients with MA due to epithelial cancer, who had received at least two prior systemic chemotherapy regimens, were enrolled and randomly assigned to the experimental arm (Arm E) and control arm (Arm C). Arm E received paracentesis and intraperitoneal (IP) infusions of 50, 400, 400, and 400μg of M701 on days 1, 4, 11, and 18. Additional M701 infusions could be given every 2 weeks without requiring punctures. Arm C received paracentesis alone as needed from day 1 to day 18. Both arms received systemic tumor treatment as determined by investigators. The primary endpoint was puncture-free survival (PuFS), defined as the time from random assignment to the next puncture or death, whichever occurred first. Secondary endpoints included overall survival (OS) and incidence of adverse events (AEs). Results: As of December 15, 2023, a total of 84 pts were enrolled, with 43 in Arm E and 41 in Arm C. The characteristics of Pts are outlined in the table. PuFS was significantly longer in Arm E compared to Arm C (median 54 vs 24 days, hazard ratios (HR) = 0.39, 95% CI 0.21-0.72, p=0.001). Subgroup analysis of PuFS indicated that patients with different types of cancer (gastric, colorectal and ovarian) all benefited from M701 infusion. OS analysis demonstrated a trend towards prolonged survival in Arm E compared to Arm C (median 113 vs 76 days, HR=0.56, 95% CI 0.31-1.03, p=0.0575). The 6-month survival rates were 35.2% and 15.8%, respectively. Subgroup analysis showed that patients with gastric cancer had significantly longer OS than the controls (median 128 vs 64 days, HR= 0.45, 95%CI 0.20-1.00, p=0.0438). Grade 3 or higher treatment-emergent AEs occurred in 52% of patients in Arm E and 57.5% of patients in Arm C. Serious AEs occurred in 38% and 50% of patients in the two arms, respectively. Only 2 cases of cytokine release syndrome (both grade 2) were reported in patients treated with M701. Conclusions: IP infusions of M701, based on systemic tumor therapy, were well tolerated and did not pose a higher risk compared to the control arm. Epithelial cancer patients with MA who received M701 treatment had longer PuFS and OS. These results are promising and support the pivotal trial of M701 as a novel treatment for MA. [Table: see text]
Characterizing disparities in receipt of palliative care for Asian Americans, Native Hawaiians, and Pacific Islanders with metastatic cancer in the United States.
Authors: Kohli Khushi , Kohli Mahi , Jain Bhav , Swami Nishwant , Ranganathan Sruthi , Chino Fumiko , Iyengar Puneeth , Yerramilli Divya , Dee Edward Christopher Christopher 
Published: June 2024

12069 Background: Despite the benefits of early palliative care (PC), inequities exist in receipt of PC for patients diagnosed with metastatic cancer. We sought to characterize disparities in receipt of PC for disaggregated Asian American, Native Hawaiian, and Pacific Islander (AA&NHPI) patients with metastatic prostate, breast, or lung cancer. Methods: The National Cancer Database (NCDB) allows for evaluation of receipt of palliative care as part of first line of treatment. Therefore, we analyzed patients with metastatic breast, lung, or prostate cancer between 2004-2018 who were White (largest reference group) or of self-identified Asian Indian/Pakistani, Chinese, Filipino, Native Hawaiian, Hmong, Japanese, Kampuchean, Korean, Laotian, Pacific Islander, Thai, or Vietnamese descent. Multivariable logistic regressions defined adjusted odds ratios and 95% confidence intervals of receiving palliative care when comparing i) White vs. AA&NHPI patients as a single cohort and ii) White vs. disaggregated AA&NHPI patients, adjusting for clinical, socioeconomic, and demographic covariates. Results: Among 775,289 individuals diagnosed with metastatic cancer, no significant differences in PC receipt were observed between White patients and aggregated AA&NHPI patients among patients with prostate cancer, breast cancer, or lung cancer. However, disaggregated analyses revealed reduced palliative care receipt for patients with breast cancer of Asian Indian/Pakistani descent (AOR=0.75, P=0.011) and for patients with lung cancer of Chinese, Vietnamese, Thai, and Asian Indian/Pakistani descent compared to White patients (Chinese AOR=0.88, P=0.001; Vietnamese AOR=0.89, P=0.032; Thai AOR=0.64, P=0.016; Asian Indian/Pakistani AOR=0.83, P=0.001). Receipt of PC was greater for patients of Japanese and Hawaiian descent with prostate cancer (Japanese AOR=1.92, P=0.001; Hawaiian AOR=2.09, P=0.009), breast cancer (Japanese AOR=1.72, P=0.001; Hawaiian AOR=1.70, P=0.021), and lung cancer (Japanese AOR=1.92, P <0.001; Hawaiian AOR=2.95, P<0.001), as well as patients of Pacific Islander descent with lung cancer (AOR=1.62, P<0.001). Conclusions: Although in aggregate AA&NHPI patients were no less likely to receive PC than White patients, we found significant within-group disparities among AA&NHPI patients with metastatic cancer. Patients of Asian Indian/Pakistani, Chinese, Vietnamese, and Thai descent were less likely to receive PC, underscoring the need for i) disaggregated research on PC access and ii) targeted interventions to address cultural, socioeconomic, and healthcare system barriers that contribute to the disparities in PC among patients with cancer.
Prevalence of cannabis related potential medication interactions (PMI) among patients with cancer during treatment.
Authors: Kim Elyssa , Cullen Jennifer , Mendiratta Prateek , Farrell Megan , Finklea Shalena , Huang Lauren , Trapl Erika , Chan Alexandre , Gerson Stanton L. , Lee Richard T. 
Published: June 2024

12073 Background: The utilization of cannabis is increasing among patients with cancer; however, limited information exists about PMI with cannabis during treatment for cancer. Methods: An NCI-funded cross-sectional survey study was conducted at a comprehensive cancer center among patients undergoing anticancer therapy. Subjects completed a survey about utilization of medications including supplements and cannabis – specifically reasons for use and type of cannabis. All patients actively taking any cannabis were identified and included for analysis. Lexicomp and Natural Medicines Comprehensive Database interaction software were used to determine PMIs. Results: A total of 61 patients (19.5%) were identified from 313 participants as actively using a form of cannabis. Subjects had a mean age of 58 (SD±13.3) and mostly self-identified as being White (70%) with one-fifth being Black (21%). The most common types of cancer were lung (18%), breast (15%), lymphoma (12%) and colorectal (12%). The most prevalent modes of cannabis intake were smoking (36%), gummies (33%), and oil/tincture/liquid (16%). The most common reasons for cannabis use included insomnia (46%), pain (41%), and mood (39%). The median number of medications used were 6 (range, 1-16) and supplements (including cannabis) were 3 (range, 1-14). A total of 1157 PMIs and 569 unique PMIs were identified among active cannabis users. The most common PMIs were prescription-supplement interactions (31.7%) and prescription-cannabis interactions (27%). Nearly two-thirds of the PMIs (61%) were labelled as moderate, followed by major interactions (18%). Among these patients, there were 412 cannabis interactions (36% of PMIs) with 124 being unique. Of these cannabis PMIs, 71% were interactions with non-anticancer prescription medications, 17% with over-the-counter medications, and 10% with anticancer agents. Most of the cannabis PMIs were categorized as moderate (87%) and major (12%) severity, and the level of evidence of these PMIs were rated as poor (60%). The most common cannabis-related PMIs were with acetaminophen (9.5%), dexamethasone (8%), and ondansetron (6.3%). The most common chemotherapy PMIs were with paclitaxel (4%) and doxorubicin (2%). Conclusions: This is one of the first studies to assess cannabis-related drug interactions in patients receiving cancer treatment, and results indicates a significant proportion of cannabis users are at risk for moderate to major PMIs including with chemotherapy.[Table: see text]
Electronic capture of cancer patients' health related social needs in a community oncology network.
Authors: Indurlal Puneeth , Neeb Jessica , Weber Dana , Mills Lydia , Payne-De Bock Judi , Osborne Evan , Crum Erin , Wilfong Lalan S. 
Published: June 2024

12105 Background: Health related social needs (HRSN) are known to have an impact on cancer patient outcomes and experience. Practices in The US Oncology Network (The Network) use the National Comprehensive Cancer Network (NCCN) Distress Thermometer (DT) as the screening tool for HRSNs. With the deployment of the NCCN DT in the electronic health record (EHR), we seek to evaluate the distress and HRSNs reported by cancer patients. Methods: Data collected using the EHR-based NCCN DT for seven practices in The Network between July and December 2023 was used to evaluate the positive finding rate, types of distress reported, and plan of action for reported problems. Screenings were conducted at different points in the care continuum depending on practice standards and preferences. Results: Between July and December 2023, a total of 269,666 screenings for 219,720 unique patients were recorded using the EHR-based NCCN DT, of which 3.1% (8,332) were recorded as patient declined. 117,363 (43.5%) screenings had a positive finding (≥1 problem, or score ≥1). Nearly 2 in 5 screenings (103,767, 38.5%) had a problem reported, with 58.2% (60,373) of those screenings reporting a problem in more than 1 problem area. A numeric distress value was recorded in 94.6% (255,046) of the screenings, with 27.2% (73,338) having a distress score of ≥ 1 and 11.6% (31,264) with a score of ≥ 4. Problem list responses are reported in the table. A distress action plan was recorded for 55.7% (65,333) of the positive findings, of which a majority (79.6%) of patients declined any assistance. Most of the action plans for referrals to appropriate assistance services were recorded for screenings with ≥3 problems reported (58.0% vs 24.6%), or with distress scores of ≥4 (65.6% vs 9.9%). Conclusions: HRSN’s are commonplace among cancer patients, and screening aids with identifying and addressing distress. Electronic capture of DT in the EHR helps oncology practices use data to facilitate holistic patient care, design and optimize support services (social work, navigation, symptom management programs), as well as gather and organize community resources to address HRSNs and ultimately identify disparities and work toward advancing health equity. [Table: see text]