bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thyroid imaging reporting and data system with MRI morphological features for thyroid nodules: diagnostic performance and unnecessary biopsy rate
Authors: Zheng Tingting , Zhang Yuan , Wang Hao , Tang Lang , Xie Xiaoli , Fu Qingyin , Wu Pu-Yeh , Song Bin 
Published: June 2024

Abstract
Background
To assess MRI-based morphological features in improving the American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS) for categorizing thyroid nodules.

Methods
A retrospective analysis was performed on 728 thyroid nodules (453 benign and 275 malignant) that postoperative pathology confirmed. Univariate and multivariate logistic regression analyses were used to find independent predictors of MRI morphological features in benign and malignant thyroid nodules. The improved method involved increasing the ACR-TIRADS level by one when there are independent predictors of MRI-based morphological features, whether individually or in combination, and conversely decreasing it by one. The study compared the performance of conventional ACR-TIRADS and different improved versions.

Results
Among the various MRI morphological features analyzed, restricted diffusion and reversed halo sign were determined to be significant independent risk factors for malignant thyroid nodules (OR = 45.1, 95% CI = 23.2–87.5, P < 0.001; OR = 38.0, 95% CI = 20.4–70.7, P < 0.001) and were subsequently included in the final assessment of performance. The areas under the receiver operating characteristic curves (AUCs) for both the conventional and four improved ACR-TIRADSs were 0.887 (95% CI: 0.861–0.909), 0.945 (95% CI: 0.926–0.961), 0.947 (95% CI: 0.928–0.962), 0.945 (95% CI: 0.926–0.961) and 0.951 (95% CI: 0.932–0.965), respectively. The unnecessary biopsy rates for the conventional and four improved ACR-TIRADSs were 62.8%, 30.0%, 27.1%, 26.8% and 29.1%, respectively, while the malignant missed diagnosis rates were 1.1%, 2.8%, 3.7%, 5.4% and 1.2%.

Conclusions
MRI morphological features with ACR-TIRADS has improved diagnostic performance and reduce unnecessary biopsy rate while maintaining a low malignant missed diagnosis rate.
The association between dietary meal intake habits and coronary artery stenosis and cardio-metabolic risk factors
Authors: Taftian Marzieh , Sasanfar Bahareh , Sarebanhassanabadi Mohammadtaghi , Seyedhosseini Seyedmostafa , Khayyatzadeh Sayyed Saeid , Madadizadeh Farzan , Motallaei Maryam , Beigrezaei Sara , Golvardi-Yazdi Faezeh , Mirjalili Fatemeh , Salehi-Abargouei Amin 
Published: June 2024

Abstract
Background and objective
We are not aware of studies examining the association between dietary meal intake habits (DMIH) and severity of coronary artery stenosis (CAS). This study was conducted to investigate the relationship between DMIH and the severity of CAS as well as cardiometabolic risk factors in adults undergoing coronary angiography.

Methods
This cross-sectional study was done on 720 patients undergoing coronary angiography (aged 35–75 years) who were admitted to Afshar Hospital, a referral hospital for cardiovascular diseases in Yazd, Iran. Data on DMIH were gathered by interview. Blood samples were taken for biochemical analysis. Blood pressure, anthropometric indices, and body composition were also evaluated. The relationship between DMIH and the severity of CAS [examined by angiography based on Gensini Score (GS) and Syntax Score (SS)] and cardiometabolic risk factors were assessed using logistic regression and the analysis of covariance (ANCOVA), respectively, in crude and multivariable adjusted models.

Results
After adjustment for all possible confounding variables, the study revealed that people who ate 3 meals/day had a lower risk of severe CAS compared to people who ate 2 or fewer meals (OR = 0.48, 95% CI: 0.26, 0.88, P-trend = 0.02). There was an inverse association between the number of snacks /day and the severity of CAS (OR = 0.43, 95% CI: 0.22, 0.87, P-trend = 0.02). There was also an inverse relationship between breakfast frequency/week and the severity of CAS based on both GS and SS (P < 0.05). Breakfast consumption, meal frequency, lunch consumption, snack frequency, and more food consumption on holidays were also associated with different cardiometabolic markers and anthropometric measures (P < 0.05).

Conclusion
According to the results of the present study, meal frequency and breakfast consumption might be inversely associated with CAS and cardiometabolic risk factors.
Reproducibility and repeatability of quantitative T2 and T2* mapping of osteosarcomas in a mouse model
Authors: Roudi Raheleh , Pisani Laura J. , Pisani Fabrizio , Liang Tie , Daldrup-Link Heike E. 
Published: June 2024

Abstract
Background
New immunotherapies activate tumor-associated macrophages (TAMs) in the osteosarcoma microenvironment. Iron oxide nanoparticles (IONPs) are phagocytosed by TAMs and, therefore, enable TAM detection on T2*- and T2-weighted magnetic resonance images. We assessed the repeatability and reproducibility of T2*- and T2-mapping of osteosarcomas in a mouse model.

Methods
Fifteen BALB/c mice bearing-murine osteosarcomas underwent magnetic resonance imaging (MRI) on 3-T and 7-T scanners before and after intravenous IONP infusion, using T2*-weighted multi-gradient-echo, T2-weighted fast spin-echo, and T2-weighted multi-echo sequences. Each sequence was repeated twice. Tumor T2 and T2* relaxation times were measured twice by two independent investigators. Repeatability and reproducibility of measurements were assessed.

Results
We found excellent agreement between duplicate acquisitions for both T2* and T2 measurements at either magnetic field strength, by the same individual (repeatability), and between individuals (reproducibility). The repeatability concordance correlation coefficient (CCC) for T2* values were 0.99 (coefficients of variation (CoV) 4.43%) for reader 1 and 0.98 (CoV 5.82%) for reader 2. The reproducibility of T2* values between the two readers was 0.99 (CoV 3.32%) for the first acquisitions and 0.99 (CoV 6.30%) for the second acquisitions. Regarding T2 values, the repeatability of CCC was similar for both readers, 0.98 (CoV 3.64% for reader 1 and 4.45% for reader 2). The CCC of the reproducibility of T2 was 0.99 (CoV 3.1%) for the first acquisition and 0.98 (CoV 4.38%) for the second acquisition.

Conclusions
Our results demonstrated high repeatability and reproducibility of quantitative T2* and T2 mapping for monitoring the presence of TAMs in osteosarcomas.

Relevance statement
T2* and T2 measurements of osteosarcomas on IONP-enhanced MRI could allow identifying patients who may benefit from TAM-modulating immunotherapies and for monitoring treatment response. The technique described here could be also applied across a wide range of other solid tumors.

Key points
• Optimal integration of TAM-modulating immunotherapies with conventional chemotherapy remains poorly elucidated.
• We found high repeatability of T2* and T2 measurements of osteosarcomas in a mouse model, both with and without IONPs contrast, at 3-T and 7-T MRI field strengths.
• T2 and T2* mapping may be used to determine response to macrophage-modulating cancer immunotherapies.

Graphical Abstract
Unraveling Alzheimer’s: the promise of aducanumab, lecanemab, and donanemab
Authors: Ameen Taha Basit , Kashif Syeda Naveera , Abbas Syed Muhammad Iraj , Babar Kulsoom , Ali Syed Muhammad Sinaan , Raheem Abdul 
Published: June 2024

AbstractAlzheimer’s disease (AD) is a neurodegenerative condition that causes cognitive decline, memory loss, and reduced personal autonomy. The pathology of AD involves the aggregation of abnormal brain proteins, specifically beta-amyloid plaques and tau tangles, disrupting neuronal communication and leading to the loss of brain cells. Aducanumab, a monoclonal antibody, demonstrates promise in clinical trials by selectively binding to aggregated amyloid-beta, leading to a notable decrease in plaque burden and potential cognitive benefits. However, regulatory approval for aducanumab remains controversial. Lecanemab and donanemab are recent additions to the AD’s treatment landscape, both targeting aggregated amyloid-beta. Lecanemab shares similarities with aducanumab in its mechanism of action, while donanemab employs a distinct approach by binding to a specific truncated form of amyloid-beta. Positive outcomes have been observed in early-stage clinical trials for both drugs, demonstrating a reduction in amyloid-beta plaques. While aducanumab’s approval offers hope for AD’s treatment, ongoing studies on lecanemab and donanemab are imperative for a comprehensive understanding of their potential in disease modification. Here, we show in this review the potential AD treatments, with a focus on their primary action targeting the reduction of amyloid-beta plaques ultimately giving a broader insight on the topic. The review emphasizes the necessity for long-term efficacy and safety data to assess the overall impact of these drugs on cognitive decline and functional outcomes for future researchers to endeavor. In conclusion, the development of amyloid-beta targeting monoclonal antibodies represents a significant stride in AD’s treatment, demanding further investigation to ascertain their true potential and role in the therapeutic arsenal for this challenging condition.
PD-L1, tumor mutational burden (TMB) and long-term survival in patients with non-small cell lung cancer (NSCLC) and brain metastases.
Authors: Adib Elio , Nassar Amin , Kwiatkowski David J. , Aizer Ayal 
Published: June 2024

2034 Background: Brain metastases (BM) affect up to 50% of patients with NSCLC and are associated with poor prognosis in patients with non-targetable genomic alterations. Radiation forms the typical mainstay of intracranial management in such patients given the historically guarded intracranial efficacy of most systemic options. Immunotherapy-based approaches have shown promise but the extent that patients with BM may display extended survival with combination radiation- and immunotherapy-based approaches remains unclear. Methods: We identified 160 patients harboring non-squamous NSCLC with 486 newly-diagnosed BM between 2015-2023 managed with brain-directed radiation (either stereotactic-based, SRT or whole brain radiation therapy, WBRT) and immune checkpoint inhibition within 3 months of radiation at Dana-Farber Cancer Institute/Brigham and Women’s Hospital (Boston, MA). PD-L1 tumor expression was categorized as <1%, 1-49%, 50-89%, and ≥90% based on immunohistochemistry. TMB was assessed via targeted next-generation sequencing. Cox-proportional hazards regression was used to assess all-cause mortality while Fine-Gray competing risks regression was used to assess other time-to-event based outcomes. Results: The median number of BM was 3 (IQR 1-7). Neurosurgical resection in advance of radiation was performed in 51/160 (32%) pts. SRT was used in 130/160 (81%) versus 30/160 (19%) patients treated with WBRT, respectively. Median follow-up time was 30.1 months (mo). Higher PD-L1 expression was associated with significantly longer overall survival (OS) with a median survival in patients with PD-L1<1%, 1-49%, 50-89% and ≥90% being 11.8, 14.4, 29.5 and 33.1 months, respectively (Table). Similarly, time to systemic death (TTSD) was longer in patients with higher PD-L1 expression, while time to neurologic death (TTND) was not different across categories. Higher TMB (≥10 vs. <10 mutations/megabase) was not associated with significantly longer OS, TTSD or TTND. Conclusions: Higher PD-L1 tumor expression was associated improved all-cause mortality, largely driven by reduction in systemic death. A significant percentage of patients with a very high PD-L1 displayed long-term survival, highlighting the potential importance of multimodality therapy in such patients, and demonstrating that clinicians should be cognizant of treatment-associated long-term toxicities in this population. [Table: see text]
Phase 1 LITESPARK-001 study of belzutifan in advanced solid tumors: Results of the glioblastoma cohort.
Authors: Strowd Roy E. , De La Fuente Macarena Ines , Bauer Todd Michael , Papadopoulos Kyriakos P. , Chen Ke , Perini Rodolfo F. , Liu Yanfang , McDermott David F. 
Published: June 2024

2054 Background: Patients with progressive/recurrent glioblastoma (GBM) have very poor prognosis, and novel treatments are urgently needed. Hypoxia is a prominent feature of the tumor microenvironment in GBM and has been implicated as a potential mechanism of resistance to radiation therapy, which is a key part of standard-of-care treatment for GBM. HIF-2α has been suggested as a key therapeutic target because it plays a role in stabilizing the hypoxic environment in GBM tumors. Belzutifan, a first-in-class HIF-2α, has shown efficacy in advanced renal cell carcinoma and in von Hippel-Lindau disease–related renal cell carcinoma, pancreatic neuroendocrine tumors, and central nervous system hemangioblastomas. The phase 1 LITESPARK-001 trial (NCT02974738) was designed to evaluate belzutifan across solid tumors. Here, we report results from the GBM expansion cohort of LITESPARK-001. Methods: Patients enrolled in the GBM cohort had histologically confirmed, IDH wild type GBM that is first recurrent following radiation therapy and temozolomide according to the Response Assessment in Neuro-Oncology (RANO) criteria and had a measurable contrast-enhancing lesion by MRI imaging and a Karnofsky performance scale score ≥60%. Patients received belzutifan 120 mg by mouth twice daily. End points for this cohort included objective response rate (ORR), clinical benefit rate (CBR, CR + PR + SD of any duration), and progression-free survival (PFS) per RANO criteria by investigator assessment and safety. Results: Overall, 25 patients were enrolled in the GBM cohort. Median age was 63 years (range, 35-75), and most patients were male (n = 15; 60%). Median follow-up was of 1.9 months (range, 0.7-5.1). ORR was 0% (95% CI, 0.0-13.7) and CBR was 8% (95% CI, 1.0-26.0). Median PFS was 1.4 months (95% CI, 1.1-1.8). All patients (100%) experienced ≥1 adverse event and 15 (60%) experienced a grade 3-5 adverse event. The most common adverse events were anemia (n = 16 [64%]), fatigue (n = 13 [52%]), headache (n = 8 [32%]), muscular weakness (n = 8 [32%]). Two patients (8%) died from adverse events (both disease progression). No deaths were considered related to treatment. Conclusions: Antitumor activity was not observed with belzutifan for patients with GBM who received prior radiation therapy and temozolomide. The safety profile was similar to previous studies with belzutifan. Further efforts are warranted to identify therapies for patients with glioblastoma to improve outcomes. Clinical trial information: NCT02974738 .
Phase 1/2 study of the TGF-β-trap-enhanced oncolytic adenovirus, AdAPT-001, plus an immune checkpoint inhibitor for patients with immune refractory cancers.
Authors: Conley Anthony Paul , Ravi Vinod , Roland Christina Lynn , Reid Tony R. , Larson Chris , Caroen Scott , Williams Jeannie Ann , Oronsky Bryan , Stirn Meaghan , Abrouk Nacer , Burbano Erica , Kennedy Lucy Boyce 
Published: June 2024

2506 Background: The benefit of immune checkpoint inhibition is limited to 20-40% of patients. Moreover, acquired resistance often arises. Also, certain tumor types like breast are more CI-refractory. Therefore, the focus is on new combination strategies to increase clinical benefit. This multicenter phase 2 trial evaluated AdAPT-001, an oncolytic adenovirus armed with a “TGF-β trap” that neutralizes the immunosuppressive cytokine, TGF-β, +/- a checkpoint inhibitor (CI) in resistant patients some of whom previously failed a CI. Methods: Eligible patients with refractory tumors, many of them sarcomas, received 1 or more intratumoral injections of AdAPT-001 at dose level 1 x 1012 viral particles every 2 weeks +/- a CI at Investigator discretion. The CI was administered every 2nd-3rd week. Adverse events were recorded and managed. The primary endpoints of this combination therapy were objective response rate (ORR) and progression free survival (PFS). Results: 36 patients (22 males and 14 females) enrolled with a median age of 60.8 years (range 23-86) from Feb 2023-Dec 2023. 24/36 enrolled patients received AdAPT-001 with a CI and 12 patients received AdAPT-001 single agent. The most common treatment related adverse events (TRAE) were transient flu-like symptoms (fever, chills, vomiting, fatigue) 10/36 (27.7%), and injection related events 10/36 (27.7%). Notably, only 1 patient, 1/24 (4.0%), developed an immune-related AE, hypophysitis. All other related AEs were Grade 1/2. 33/36 patients were evaluable for response analysis; monotherapy produced 2/9 (22.2%) favorable responses (complete response (CR): eccrine carcinoma; confirmed partial response (cPR): acral melanoma); and produced a 4/9 (44.4%) clinical benefit rate defined as CR/PR/SD greater than 12 weeks. The combination of AdAPT-001 plus a CI produced 7/24 (29.1%) favorable responses (1 clinical CR: angiosarcoma; 6 cPRs: 3 sarcoma, 1 triple negative breast cancer, 1 head and neck cancer, 1 squamous cell carcinoma; and a 15/24 (62.5%) clinical benefit rate defined as CR/PR/SD greater than 12 weeks. 21/33 failed a CI before enrollment (16/24 before AdAPT-001 + CI). The PFS was 3.5 months (95% CI: 1.8-NA months). Conclusions: Combination therapy of AdAPT-001 with a CI is well tolerated and demonstrates a high ORR including 1 patient with a CR per RECIST 1.1, 1 patient with a clinical CR and 6 PRs. In several cutaneous sarcomas treated with AdAPT-001 plus a CI, radiologic SD belied how much better they looked visually--not only smaller, but less irregular and more circumscribed. Clinical trial information: NCT04673942 . [Table: see text]
Phase 1 study of BA3071, an anti–CTLA-4 conditionally active biologic, in combination with nivolumab in advanced solid tumors.
Authors: Thomas Jacob Stephen , Selfridge Jennifer Eva , Albany Costantine , Taylor Matthew H. , Mehmi Inderjit , Kwatra Vineet , Hu-Lieskovan Siwen , de Souza Paul L. , Llorin-Sangalang Judith Dubal , Aysola Kartik , Hamid Omid 
Published: June 2024

2602 Background: Immune checkpoint inhibition of cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) in combination with programmed cell death protein 1 (PD-1) has demonstrated durable clinical benefit in patients with advanced solid tumors. However, dose density is limited due to toxicity. BA3071 is a conditionally active biologic (CAB) anti–CTLA-4 monoclonal antibody that blocks the interaction of CTLA-4 with its ligands CD80 and CD86 [1]. CABs are activated within the acidic tumor microenvironment. Conditional and reversible binding of BA3071 may reduce on- and off-tumor immune-related adverse events (AEs) and autoimmunity, avoid tissue-mediated drug deposition, and improve pharmacokinetics. We evaluated the safety and antitumor activity of BA3071 in patients with advanced solid tumors. Methods: Patients naïve to anti–CTLA-4 therapy with advanced solid tumors received escalating doses of single-agent BA3071 every 3 weeks (Q3W) at cycle 1, followed by combination BA3071 + nivolumab from cycle 2 onward. Treatment continued until disease progression or unacceptable toxicity. Response assessment was performed Q6W with RECIST v1.1. Results: Eighteen patients were treated with BA3071 (7–700 mg) and nivolumab (240 mg); 61% had received ≥3 lines of prior systemic therapy, and all patients had experienced failure of anti–PD-1 therapy. Four patients experienced grade 3 related treatment-emergent AEs (TEAEs; hypertension, increased lipase, atrial fibrillation, gastritis, and diabetic ketoacidosis); no grade 4 related TEAEs were observed. Two patients experienced grade 3 immune-related TEAEs (diarrhea [BA3071 350 mg] and diabetic ketoacidosis [BA3071 700 mg]). Among 16 efficacy-evaluable patients, 9 experienced stable disease, and 2 out of 5 patients receiving BA3071 in the 350-mg cohort achieved confirmed RECIST v1.1 responses (complete response in cervical carcinoma and partial response in gastroesophageal carcinoma). One patient with metastatic small cell lung cancer who received 7 mg BA3071 remained without progression for >1 year (69 weeks). Conclusions: Treatment with the novel, conditionally active anti–CTLA-4 agent BA3071, in combination with anti–PD-1 therapy (at doses higher than those currently approved for anti–CTLA-4/PD-1 therapy), yielded confirmed responses with a promising tolerability profile. Phase 1 dose escalation of BA3071 continues at 700 mg up to 1000 mg, and phase 2 monotherapy and combination therapy expansion cohorts are currently enrolling at a starting dose level of 350 mg. 1. Chang HW et al. Proc Natl Acad Sci USA.2021;118(9):e2020606118. Clinical trial information: NCT05180799 .
Tislelizumab first-line (1L) gastric/gastroesophageal junction cancer (G/GEJ) treatment efficacy on patient-reported outcome (PRO)-based symptom endpoints adjusting for informative missing data bias: Results from RATIONALE 305.
Authors: Serrano Daniel , Xu Hui , Sheng Tao , Li Liyun , Barnes Gisoo , Oh Do-Youn 
Published: June 2024

2605 Background: PRO-based symptom endpoints are rarely associated with treatment efficacy in oncology trials. PRO analyses emphasize early treatment cycles to avoid bias arising from study dropout (SDO; eg, due to death or other intercurrent events). SDO is thought to induce data missing not at random (MNAR), thereby biasing estimates and inference. However, separation between arms on other efficacy endpoints (eg, overall survival [OS]) typically occurs at cycles subsequent to the analysis period cutoff for PRO-based endpoints. This research examined treatment efficacy in PRO-based symptom endpoints in treatment cycles occurring later than typically analyzed. To protect against MNAR bias associated with later cycles, joint models (JMs) were employed. Methods: RATIONALE 305 was a randomized, double-blind, placebo-controlled, phase 3 trial comparing efficacy and safety of tislelizumab + chemotherapy (tislelizumab) with placebo + chemotherapy (chemo) as 1L treatment for patients with locally advanced, unresectable, or metastatic G/GEJ adenocarcinoma. EORTC-STO22 symptom domain scores were analyzed. Change from baseline (CFBL) in each domain was analyzed for up to 21 cycles between baseline and Cycle 38 (cycle with no less than 10% of baseline surviving). Treatment efficacy for STO22 endpoints was analyzed using JMs. The JM linked a linear mixed model (LMM) for STO22-domain CFBL to a Cox proportional hazards model for OS, adjusting LMM estimates for the potential MNAR bias arising from OS-based SDO. The LMM and Cox model were adjusted for study randomization factors of region (East Asia vs Rest of World), PD-L1 status (positive vs. negative), and peritoneal metastases (present vs. absent). All analyses were conducted using JMBayes2 package in R version 4.3.2. Results: STO22 pain results are reported; all domains will be presented. For tislelizumab (n=465) vs. chemo (n=467), subjects remaining at Cycle 38 were 46 (10%) and 28 (6%), respectively. Tislelizumab was associated with a constant lower level of pain compared with chemo (-2.08; P=0.0109). Tislelizumab was associated with a 21% reduction in risk of death ( P=0.0269). Conclusions: In this analysis, compared with chemo, tislelizumab + chemo was associated with lower pain and longer survival. Joint models for PRO-based symptom endpoints may illuminate patient-centric therapeutic benefits. [Table: see text]