bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations Between Radiation Oncologist Demographic Factors and Segmentation Similarity Benchmarks: Insights From a Crowd-Sourced Challenge Using Bayesian Estimation
Authors: Wahid Kareem A. , Sahin Onur , Kundu Suprateek , Lin Diana , Alanis Anthony , Tehami Salik , Kamel Serageldin , Duke Simon , Sherer Michael V. , Rasmussen Mathis , Korreman Stine , Fuentes David , Cislo Michael , Nelms Benjamin E. , Christodouleas John P. , Murphy James D. , Mohamed Abdallah S.R. , He Renjie , Naser Mohammed A. , Gillespie Erin F. , Fuller Clifton D. 
Published: June 2024

PURPOSE The quality of radiotherapy auto-segmentation training data, primarily derived from clinician observers, is of utmost importance. However, the factors influencing the quality of clinician-derived segmentations are poorly understood; our study aims to quantify these factors. METHODS Organ at risk (OAR) and tumor-related segmentations provided by radiation oncologists from the Contouring Collaborative for Consensus in Radiation Oncology data set were used. Segmentations were derived from five disease sites: breast, sarcoma, head and neck (H&N), gynecologic (GYN), and GI. Segmentation quality was determined on a structure-by-structure basis by comparing the observer segmentations with an expert-derived consensus, which served as a reference standard benchmark. The Dice similarity coefficient (DSC) was primarily used as a metric for the comparisons. DSC was stratified into binary groups on the basis of structure-specific expert-derived interobserver variability (IOV) cutoffs. Generalized linear mixed-effects models using Bayesian estimation were used to investigate the association between demographic variables and the binarized DSC for each disease site. Variables with a highest density interval excluding zero were considered to substantially affect the outcome measure. RESULTS Five hundred seventy-four, 110, 452, 112, and 48 segmentations were used for the breast, sarcoma, H&N, GYN, and GI cases, respectively. The median percentage of segmentations that crossed the expert DSC IOV cutoff when stratified by structure type was 55% and 31% for OARs and tumors, respectively. Regression analysis revealed that the structure being tumor-related had a substantial negative impact on binarized DSC for the breast, sarcoma, H&N, and GI cases. There were no recurring relationships between segmentation quality and demographic variables across the cases, with most variables demonstrating large standard deviations. CONCLUSION Our study highlights substantial uncertainty surrounding conventionally presumed factors influencing segmentation quality relative to benchmarks.
Sintilimab, doxorubicin and ifosfamide (AI) as first-line treatment in patients with advanced undifferentiated pleomorphic sarcoma (UPS), synovial sarcoma (SS), myxoid liposarcoma (MLPS) and de-differentiated liposarcoma (DDLPS): A single-arm phase 2 trial.
Authors: Liu Xin , Guo Yanjing , Yan Wangjun , Chen Yong , Xu Yu , Wang Chun-Meng , Yao Weiqiang , Wang Jian , Yu Lin , Jiang Shiyu , Zhang Xiaowei , Luo Zhiguo 
Published: June 2024

11505 Background: Anti-PD-1 antibody had showed encouraging activity as salvage treatment in patients with certain subtypes of advanced soft tissue sarcoma. However, its role in first-line setting is uncertain. We assessed the safety and activity of sintilimab, an anti-PD-1 antibody, combined with doxorubicin (ADM) and ifosfamide (IFO) in patients with advanced undifferentiated pleomorphic sarcoma (UPS), synovial sarcoma (SS), myxoid liposarcoma (MLPS) and de-differentiated liposarcoma (DDLPS). Methods: This is a single-arm, phase 2 study. Systemic treatment naïve patients with metastatic or unresectable locally advanced UPS, SS, MLPS and DDLPS were treated with sintilimab (200mg, d1), ADM (60mg/m2, d1) and IFO (1.8 g/m2/d, d1-5) every 3 weeks for up to 6 cycles, followed by sintilimab maintenance until disease progression, unacceptable toxicities or up to 2 years. The primary endpoint was objective response rate (ORR, per RECIST 1.1), and secondary endpoints included progression free survival (PFS), overall survival (OS) and safety. Results: Between June 2020 and June 2023, 46 eligible patients were enrolled. 31 were male, and the median age was 47 years old. Of the 41 evaluable pts, ORR was 68.3% (28/41), including 7/8 (87.5%) UPS, 13/20 (65.0%) SS, 3/3 (100%) MLPS and 5/10 (50%) DDLPS patients. At a median follow-up time of 28.0 months (95% CI: 9.4-46.7 months), the median PFS and OS were 9.0 months (95% CI: 6.5-11.5 months) and 19.9 months (95% CI: 14.9-24.9 months), respectively. 1 DLT was observed in the first six patients during the DLT observation window. The most frequent ≥ grade 3 adverse events were leucopenia (50.0%), neutropenia (45.7%), thrombocytopenia (21.7%), anemia (21.7%), and febrile neutropenia (21.7%). Conclusions: The primary endpoint of ORR was met. This study indicated promising efficacy and safety of sintilimab combined with AI in the first-line treatment of UPS, SS, MLPS and DDLPS. Clinical trial information: NCT04356872 .
Extracorporeal irradiation and reimplantation for bone sarcomas: Medium- and long-term oncologic and functional outcomes.
Authors: Mishra Biplab , Shah Mandip C , Jani Kinjal 
Published: June 2024

11524 Background: Extracorporeal irradiation is an effective and established method for limb salvage in the management of malignant bone tumours.We analyzed the oncological and functional outcomes of extracorporeal radiotherapy (ECRT) and reimplantation done for bone sarcomas. Methods: 67 patients (29 osteosarcoma, 27 Ewing’s sarcoma, 11 others; mean age 16 years) were treated with ECRT between 2010 and 2022. Femur was commonest bone (33) followed by tibia (11) and humerus (11). 48 had a metadiaphyseal while 19 had osteoarticular resections. A single dose of 50 Gy was delivered to the resected bone segments. The irradiated bones were reimplanted immediately as a biological graft. Construct was stabilized with long locking plates. Osteoarticular ECRT was coupled with joint replacement. Patients were treated with chemotherapy as per standard protocol. Functional outcome was assessed by Musculoskeletal Tumor Society (MSTS) scoring system. Results: The mean resected length of bone was 17 cm (9 to 26). All 67 patients were available at a mean follow-up of 66 months (22 to 166). The mean time to union for all osteotomy sites was 6 months (2 to 17): metaphyseal osteotomy sites united quicker than diaphyseal osteotomy sites (3.8 months (3 to 6) versus 9.5 months (4 to 17)). 2 deep infections necessitated removal of the ECRT segment. There were 2 local recurrences in soft-tissue needing amputation. 6 of the remaining 113 (5.3%) junctions remained ununited which needed additional bone grafting. 5/6 junctions united after bone grafting. 1 remained ununited needing cementation across the segment. At the time of final follow-up, 47 patients were free of disease, one was alive with disease and 19 had died of disease. The mean Musculoskeletal Tumor Society Score at the last follow-up was 26 (18 to 30). Conclusions: The radiated bone acts as a size-matched allograft and has very good union rates. The complication rates are very low. Extracorporeal irradiation is an oncologically safe and biological reconstruction technique for limb salvage in sarcomas and has good functional results. It should be recommended to all suitable patients.
Apatinib combined with ifosfamide and etoposide versus ifosfamide and etoposide in relapsed or refractory osteosarcoma (OAIE/PKUPH-sarcoma 11): A multicenter, randomized controlled trial.
Authors: Xie Lu , Xu Jie , Sun Xin , Liang Xin , Liu Kuisheng , Sun Kunkun , Li Yuan , Liu Rong , Wang Du , Shao Shurong , Li Peiyu , Pang Zheng , Zhou Guangxin , Wu Sujia , Hua Yingqi , Hu Haiyan , Yang Yi , Ji Tao , Guo Wei , Tang Xiaodong 
Published: June 2024

11527 Background: Retrospective studies have suggested the potential of apatinib, an anti-angiogenesis tyrosine kinase inhibitor, plus ifosfamide and etoposide (IE) over IE in advanced osteosarcoma. This trial aimed to further compared apatinib plus IE versus IE alone in patients with advanced osteosarcomas post first-line chemotherapy failure. Methods: In this multicenter, randomized controlled trial, patients with histologically confirmed osteosarcoma, progressing after at least one prior line of chemotherapy, were randomized (2:1) to either apatinib plus IE or IE alone. The apatinib plus IE group received oral apatinib 500mg daily plus ifosfamide (1.8 g/m2/d) and etoposide (100 mg/m2/d) on days 1-3, every 3 weeks. The IE group received IE on days 1-5, every 3 weeks. Apatinib was continued until disease progression or for a maximum of one year, and IE was administered for up to 10 cycles. The primary endpoint was progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1. Results: A total of 81 patients were enrolled, with 53 receiving apatinib and IE, while 28 using IE alone. The median follow-up period was 9.5 (interquartile range, 7.1 to 13.0) months. The apatinib plus IE group showed a median PFS of 5.5 months (95% confidence interval [CI], 3.9 to 6.7), compared to 3.4 months (95% CI, 1.4 to 4.6) in the IE group, yielding a hazard ratio of 0.41 (95% CI, 0.24 to 0.71), P=0.0010. Objective response rates were 32.1% (95% CI, 19.9 to 46.3) for the apatinib plus IE group and 25.0% (95% CI, 10.7 to 44.9) for the IE group. Disease control rates were numerically higher in the apatinib plus IE group at 90.6% (95% CI, 79.3 to 96.9), compared to 60.7% (95% CI, 40.6 to 78.5) in the IE group. The median time to response was 1.4 months (95% CI, 1.2 to 2.6) for the apatinib plus IE group and 1.5 months (95% CI, 1.3 to 2.0) for the IE group. Duration of response also favored the apatinib plus IE group, with a median of 6.1 months (95% CI, 1.9 to 8.0) compared to 4.1 months (95% CI, 1.7 to not estimated [NE]) in the IE group. The median overall survival has not yet been reached in either group. Grade 3-4 treatment-related adverse events occurred in 69.8% of patients in the apatinib plus IE group and 64.3% in the IE group, with the most common events being white blood cell count decreased and neutrophil count decreased. Conclusions: Apatinib plus IE demonstrated a significant improvement in PFS in patients with advanced osteosarcomas, with an acceptable safety. Clinical trial information: NCT05277480 . [Table: see text]
Efficacy and safety of IBI110 (anti-LAG-3 antibody) plus sintilimab (anti-PD-1 antibody) in patients with advanced alveolar soft part sarcoma: Results from a phase II study.
Authors: Liu Jiayong , Tan Zhichao , Fan Zhengfu , Bai Chujie , Xue Ruifeng , Li Shu , Gao Tian , Zhang Lu , Wang Xinyu 
Published: June 2024

11559 Background: Lymphocyte-activation gene 3 (LAG-3) has emerged as a novel target for immunotherapy (IO). Co-inhibition of LAG-3 and PD-1 may enhance immune checkpoint inhibition with synergistic effects. Herein, we report a phase II study evaluating the safety and efficacy of an anti-LAG-3 antibody (IBI110) plus sintilimab in patients (pts) with advanced alveolar soft part sarcoma (ASPS). Methods: Eligible pts with metastatic or unresectable ASPS were enrolled in two cohorts: cohort A (IO-naïve, defined as no history of previous immune checkpoint inhibitors, including but not limited to anti-PD-1/PD-L1/CTLA-4 antibodies) and cohort B (IO-failed, defined as imaging-confirmed disease progression after treatment with anti-PD-1/PD-L1 antibodies). All pts received IBI110 200 mg plus sintilimab 200 mg intravenously once every three weeks (Q3W). The primary endpoints were objective response rate (ORR) and progression-free survival (PFS), assessed by the investigator per RECIST v1.1, and safety. Secondary endpoints included overall survival (OS) and 6-month PFS rate. Results: As of January 20, 2024, the study enrolled 28 pts (males: 57.1%, median age: 30.5 years, ECOG PS 0: 100%; TNM stage IV: 100%; lung metastasis: 100%), including 20 pts in cohort A and 8 pts in cohort B. The median treatment duration was 11 cycles. There were 15 pts in cohort A and 4 pts in cohort B remaining on treatment as of the cutoff date. Response was evaluable in 27 pts. The best responses were 3 complete responses (CR), 8 partial responses (PR), and 9 stable diseases (SD) in cohort A; 2 PR and 5 SD in cohort B. ORR was 55.0% in cohort A and 28.6% in cohort B. The 6-month PFS rate was 94.7% in cohorts A and 66.7% in cohort B. At a median follow-up of 8.0 months, median PFS was not reached in cohort A and was 14.7 months in cohort B. Median OS was not reached in both cohorts. Treatment-related adverse events (TRAEs) occurred in 27 (96.4%) pts, including grade ≥3 TRAEs in 9 (32.1%) pts. The most frequent TRAEs were hyperuricemia (57.1%), increased blood lactate dehydrogenase (42.9%), and hypertriglyceridemia (42.9%), all of which were grade 1-2. Immune-related adverse events (irAEs) occurred in 27 (96.4%) pts, including grade ≥3 irAEs in 9 (32.1%) pts. Serious TRAE occurred in 2 (7.1%) pts with type 1 diabetes mellitus. TRAE leading to treatment interruption occurred in 1 (3.6%) pt due to type 1 diabetes mellitus. No TRAE led to treatment discontinuation or death. Conclusions: Co-inhibition of LAG-3 and PD-1 showed encouraging efficacy in pts with advanced ASPS. Compared to anti-PD-1 monotherapy, the combination treatment improved ORR in IO-naïve pts and restored IO effectiveness in previously IO-failed pts. The safety profiles were acceptable and manageable in all pts. Clinical trial information: MR-11-22-004975.
Proactive, automated monitoring of uncontrolled symptoms in prostate cancer survivors across the cancer control continuum.
Authors: Muniz Miguel , Childs Daniel S , Ruddy Kathryn Jean , Grzegorczyk Veronica , Pachman Deirdre R. , Morgans Alicia K. , Cobran Ewan Kemar , Griffin Joan M. , Smith Ashley Wilder , Kroenke Kurt , Loprinzi Charles L. , Costello Brian Addis , Orme Jacob , Riaz Irbaz Bin , Sartor A. Oliver , Mitchell Sandra A. , Cheville Andrea L. 
Published: June 2024

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]
A decision support intervention for patients with advanced lung cancer amid growing therapeutic complexity: Results of a randomized controlled trial.
Authors: Villalobos Matthias , Unsoeld Laura , Deis Nicole , Siegle Anja , Thomas Michael 
Published: June 2024

12103 Background: In the last decade the therapeutic algorithms in lung cancer have changed dramatically because of the continuous approval of new drugs, leading to steadily improving survival. However, recent studies show that the growing complexity has also led to a negative impact on prognostic awareness and patient-physician communication. In a setting of mostly frail patients, this uncertainty jeopardizes goal-concordant care. Consequently, the guideline recommendations of patient-empowerment and shared decision-making are more important than ever, but evidence-based, comprehensively implemented tools are still lacking. Methods: Randomized controlled, open, mono-center trial (n=138) with two arms: A) use of a decision aid incl. clarification of personal values accompanied by a decision-coaching session vs. B) usual care; stratified block randomization according to the characteristic of preferred decision-making at baseline; primary endpoint: clarity of personal values (Value Clarity Subscale of the Decisional Conflict Scale). Secondary outcomes: patients' self-efficacy (DSES), decisional conflict (DCS), perceived preparation for and involvement in decision-making (PDMS and PICS), general health and emotional state (EQ-5D-5L and HADS). In addition to the descriptive evaluation, group comparisons between the two arms were performed (non-parametric comparison: van Elteren test). Results: The evaluation showed high values for decisional conflict in both groups (total mean score arm A 41,25 and arm B 38,65), exposing relevant conflict in 57,6% of patients, highest in the subscale for information (64,4%) and uncertainty (58,9%). PDMS showed that most patients considered the intervention helpful (“prepare for the next visit with your doctor”: 83,8%, “prepare to talk to your doctor about what matters most to you”: 81,6%, “help to know that decision depends on what matters most to you”: 81,6%). The PICS-subscale “patient information” (active information-seeking behavior) showed a statistically significant difference between the two groups (arm A: 2,86 vs arm B: 3,12; p=0,048). All other outcomes showed no significant differences with equally high DCS scores in both arms’ follow-up. Conclusions: Patients with advanced lung cancer show a strikingly high decisional conflict. Despite successfully empowering perceived preparation for decision-making and decreasing information needs in the encounter with the physician, the intervention was not strong enough to improve significantly the decisional conflict. In a setting of constantly changing oncological information and increasing prognostic uncertainty, tailored support that flexibly adapts to individual needs in decision-making is urgently needed. Clinical trial information: DRKS00028023 .
A phase I study to evaluate the safety and tolerability of JCXH-211 (a self-replicating mRNA encoding IL-12) intratumoral injection in patients with malignant solid tumors: Results from the phase Ia dose escalation.
Authors: Le Ngocdiep T. 
Published: June 2024

2539 Background: Although interleukin (IL)-12 demonstrated strong preclinical antitumor activity and potent immune-stimulating potentials clinically, systemic administration of IL-12 protein was associated with poor clinical safety profiles. IL-12 functions locally through paracrine and autocrine mechanisms, thus maximizing local concentration of IL-12 in the tumors is important. JCXH-211 is a self-replicating ribonucleic acid (srRNA) encoding human IL-12 encapsulated in lipid nanoparticles. Intratumoral (IT) administration of JCXH-211 is expected to produce the desired spatiotemporal distribution of IL-12 in the cancer lesions. srRNA features enhanced translatability in immunosuppressed tumor microenvironment (TME) than in normal tissues further limiting off-target toxicity. Additionally, the self-replicating nature of JCXH-211 engages multiple immune effector mechanisms and helps inflame TME. We present interim results of the dose escalation part of JCXH-211 IT injection as monotherapy in patients (pts) with malignant solid tumors. Enrollment for the 100 μg cohort is ongoing and updated data will be presented at the meeting. Methods: Pts with advanced solid tumors suitable for IT injection are enrolled. JCXH-211 at 5, 25, 50, and 100 μg are given every 4 weeks (Q4W). Dose Limiting Toxicities (DLT) are monitored for 28 days after 1st dose. Dose escalation follows “3+3” principle. Tumor assessment is performed Q6W using RECIST v1.1. Results: Ten pts with advanced cancers have been enrolled in 5 μg, 25 μg, and 50 μg cohorts: 3 melanoma (MEL), 3 breast cancer (BC), 2 head and neck cancer (HNSC), 1 nasopharyngeal cancer and 1 sarcoma. Nine pts completed DLT observation without DLT; 1 pt withdrew early. No drug-related SAE was reported. Most drug-related AEs were Grade 1/2 and recovered quickly. Only 1 pt in the 25 μg cohort reported 3 Grade 3 AEs possibly related to drug: lymphocytopenia (2 events) and anemia. Seven pts completed at least one post-dose tumor assessment. Three pts experienced shrinkages of the treated lesions by 13.0%, 33.3% and 43.0%, corresponding to BC, HNSC and MEL in the 5 μg, 25 μg, and 50 μg cohorts, respectively. Tumor shrinkage of 31% was also observed in a non-injected lesion of an HNSC pt receiving 25μg JCXH-211 suggesting abscopal effects. Histopathological analysis of the treated lesions demonstrated increased T and NK cell infiltration (as high as 138 folds) post study drug administration. Conclusions: JCXH-211 IT administration with doses of 5μg, 25μg, 50μg Q4W demonstrated good safety profile. Antitumor activities were observed in the heavily pretreated late-stage pts. Significant increases of T and NK cell infiltration were observed. These data support continued evaluation of JCXH-211 IT. Clinical trial information: NCT05727839 .