bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunohistochemical markers in the prognostic model for survival of patients with diffuse large B-cell lymphoma.
Authors: Kobilov Odiljon , Kamishov Sergey 
Published: June 2024

e19055 Background: Currently, relevant issues include the study of the role of immunohistochemical markers in patients with diffuse large B-cell lymphoma (DLBCL) with extranodal involvement to predict the outcomes of the conducted therapy. Methods: A retrospective study included 81 patients with diffuse large B-cell lymphoma (DLBCL) involving the liver and spleen with extranodal manifestations, who underwent treatment and were under outpatient monitoring in a hospital setting. The average age of the patients was 60.7±7.5 years. The expression of pan-B-cell antigens CD20, CD79A, PAX 5 (monomorphic intense nuclear expression), CD5, CD45, CD30, BCL-2, BCL-6, Ki-67, MUM1, GCET1, FOXP1 was examined in the patients. To exclude the polymorphic blastoid variant of lymphoma with CD5 expression in mantle cells, the study of cyclin D1 expression was conducted. Results: All patients began treatment with R-CHOP chemotherapy. In 37 cases, this regimen had to be replaced with DHAP in 23 (62.2%) patients due to the low effectiveness of the 1st-line chemotherapy, and in 14 (37.8%) after completing the full course (6 cycles) of treatment. Over the 6-year observation period, despite identical treatment, the 5-year survival rate was 60.5%. Among 32 (39.5%) patients, there was a fatal outcome due to the progression of the pathological process during treatment. Moderate expression was characteristic for the markers CD5, CD30, PAX-5, FOXP1, and GCET1, while high expression was observed for CD10, CD45, CD79A, Bcl-6, MUM1, and Ki-67. High expression of Bcl-2, Bcl-6, GCET1, and Ki-67 exceeding 60% is a prognostically unfavorable factor significantly impacting the survival of patients. The most unfavorable outcomes were observed with the combination of Bcl-2 and Ki-67 expression exceeding 60% along with CD-45. The combination of Ki-67 expression exceeding 60%, CD-79, and MUM1 also resulted in an unfavorable outcome in all cases. The prognostic scale, using Cox's proportional hazard, allows predicting the prognosis of diffuse large B-cell lymphoma with extranodal involvement with a probability of 87.2%. Conclusions: In our studies, it has been demonstrated that adverse immunohistochemical characteristics of diffuse large B-cell lymphoma with extranodal involvement include high expression of Bcl-2, Bcl-6, GCET1, and a Ki-67 proliferation index exceeding 60% (p<0.025).
Diagnosis disclosure patterns among patients with plasma cell disorders.
Authors: Malik Maria , Dalvi Akshay , Derkach Andriy , Sahagun Sanchez Aldana Ana M. , Hurtado Martínez Jorge Arturo , Merlo Gia , Ahlstrom Jennifer M. , Hydren Jay R. , Usmani Saad Zafar , Chimonas Susan , Ortiz Robin , Shah Urvi A. 
Published: June 2024

e19536 Background: Disclosing or withholding information relating to a precancer or cancer diagnosis – including plasma cell disorders (PCDs) like monoclonal gammopathy, smoldering myeloma, and multiple myeloma – across social networks may impact how patients cope with their diagnosis and prognosis. The purpose of this survey was to investigate diagnosis disclosure patterns among patients with PCDs and identify areas for interventions that effectively utilize social support to navigate cancer diagnoses. Methods: We invited participants with PCDs to answer a 34 question online survey about their diagnosis disclosure patterns and perceptions on the HealthTree Cure Hub between April and December 2024. De-identified aggregated responses were analyzed. Results: A total of 510 participants responded (84% with cancer and 15% with precancer). Almost all (98%) reported sharing their diagnosis (Table 1). The most frequent primary individuals to share with were a spouse, domestic partner, or significant other (60%) and friend (s) (10%). Common reasons that participants chose to share included expecting support (45%), empowering others/spreading awareness (31%), and feeling in control (29%). Most (79%) participants reported that sharing information (with the individual they shared the most with) had a positive impact in their coping, with only 4% reporting a negative effect. Study limitations include selection bias. Conclusions: Patients with PCDs have a variety of motivations for sharing their diagnosis and generally perceive disclosure among their primary social networks to be beneficial to their coping. Oncologists may promote coping by encouraging disclosure. [Table: see text]
FIT-001: A phase 1 clinical trial of the farnesyl transferase inhibitor KO-2806 alone or as part of combination therapy for advanced solid tumors.
Authors: Hanna Glenn J. , Adkins Douglas , Thomas Jacob Stephen , Yang Bruce Justine , Patel Manish R. , Sonpavde Guru P. , Henry Jason Timothy , Bendris Nawal , Zhang Zijing , Mitra Amitava , Gasco Hernandez Amaya , Saunders Andrew , Dale Stephen 
Published: June 2024

TPS4607 Background: Farnesyl transferase inhibitors (FTIs) block post-translational modification of RAS and other farnesylated proteins. HRAS-driven tumors are highly sensitive to FTI treatment. Recent clinical trials (NCT03719690, NCT02383927) of the FTI, tipifarnib, in patients with HRAS-mutant ( HRAS-m) head and neck squamous cell carcinoma harboring high variant allele frequency mutations (VAF ≥20%), showed objective response rates of up to 50% and favorable long-term outcomes. KO-2806 is a next-generation FTI that has increased potency and improved pharmacokinetic properties. In preclinical studies, KO-2806 has been shown to: (1) enhance tumor growth inhibition of tyrosine kinase inhibitors, including cabozantinib, in multiple clear cell renal cell carcinoma (ccRCC) cell line- and patient-derived xenograft models; and (2) enhance activity of KRAS inhibitors, including adagrasib, in KRAS mutant non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic ductal adenocarcinoma (PDAC) mouse models. These preclinical data support clinical investigation of KO-2806 alone and in combination therapy. Methods: FIT-001 is a first-in-human, multicenter, open-label clinical trial that will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics (Pd), and preliminary antitumor activity of KO-2806 as monotherapy or in combination therapy in advanced solid tumors (KO-2806-001; NCT06026410). Up to 270 patients will be enrolled in phase 1a and phase 1b combined across 50 sites. Phase 1a will have separate monotherapy and combination dose-escalation arms. As monotherapy, the study will enroll patients with N/K/HRAS alterations in specific solid tumor types, such as NSCLC, CRC, and PDAC, who are refractory to standard-of-care therapies. KO-2806 and cabozantinib will be combined in patients with advanced or metastatic ccRCC who progressed on ≥1 prior line of immunotherapy-based systemic therapy; KO-2806 and adagrasib will be combined in patients with KRAS-G12C mutant locally advanced or metastatic NSCLC who received ≥1 prior systemic therapy. On the basis of emerging data from phase 1a, two Pd cohorts (n≤12) with mandatory pre- and on-treatment tumor biopsies may be enrolled. In each Phase 1b dose expansion, patients will receive the recommended phase 2 dose [RP2D] of KO-2806 with cabozantinib (in ccRCC) or adagrasib (in NSCLC), or will be randomized by dose if 2 potential KO-2806 RP2Ds are identified for a combination. Other combination arms may also be considered. The study began accrual in October 2023. Clinical trial information: NCT06026410 .
SECuRE: A dose escalation/expansion study to assess the anti-tumor efficacy of 67Cu-SAR-bisPSMA in patients with metastatic castrate resistant prostate cancer.
Authors: Johnson Geoffrey , Lengyelova Eva , Nordquist Luke , Prasad Vikas , Anderson Monique , Gervasio Othon , Parker Michelle , Miller Robert M. , Sartor A. Oliver , Tagawa Scott T. 
Published: June 2024

TPS5116 Background: Prostate cancer (PC) is common and despite recent advances in treatment options, patients with metastatic disease still have poor outcomes, warranting the development of new effective therapies in this setting. Prostate-specific membrane antigen (PSMA) is expressed in benign and malignant prostate tissues and luminal surface of salivary/lacrimal glands, small intestine and renal tubules. The double PSMA binding moiety of SAR-bisPSMA in 64Cu-SAR-bisPSMA (imaging) and 67Cu-SAR-bisPSMA (therapy) may offer advantages compared to currently used single-target PSMA agents. Clinical evidence demonstrated 2-3 times higher uptake of 64Cu-SAR-bisPSMA compared to the single-target PSMA agent, 68Ga-PSMA-11. Pre-clinical efficacy data of 67Cu-SAR-bisPSMA in mice showed statistically significant tumor growth inhibition compared to the control group as well as a dose-dependent delay in eventual tumor regression in a PC xenograft study. These results led to the development of this clinical study, which aims to assess safety and anti-tumor efficacy of 67Cu-SAR-bisPSMA in patients with metastatic castrate resistant PC (mCRPC). Methods: SECuRE is a phase I/IIa multi-center, open-label, non-randomized, dose-escalation and cohort expansion study of 64Cu-SAR-bisPSMA and 67Cu-SAR-bisPSMA (NCT04868604). mCRPC patients with progression, prior exposure to at least one androgen receptor pathway inhibitor, and positive 64Cu-SAR-bisPSMA PET may be treated with 67Cu-SAR-bisPSMA. This study is being conducted in 3 phases: a 64Cu-SAR-bisPSMA Dosimetry Phase (n=6), a 67Cu-SAR-bisPSMA Dose Escalation Phase (n=up to 24), and a 67Cu-SAR-bisPSMA Cohort Expansion Phase (n=14). The primary and key secondary objectives include assessment of 64Cu- and 67Cu-SAR-bisPSMA safety and dosimetry, determining the maximum tolerated dose (MTD) or maximum feasible dose (MFD) and anti-tumor efficacy of 67Cu-SAR-bisPSMA. The 67Cu-SAR-bisPSMA dose levels investigated in the escalation phase include: 4 GBq (cohort 1, single dose), 8 GBq (cohort 2, single dose), 12 GBq (cohort 3, single dose) and up to 24 GBq across two doses (cohort 4, two doses at MTD or MFD). The Dose Expansion Phase of the study will allow the administration of up to 4 doses of 67Cu-SAR-bisPSMA at the MTD/MFD. Response measurements include reduction in PSA levels, radiological progression-free survival, duration of response and overall survival. Radiological response will be assessed by RECIST V1.1 and PCWG3. At the time of submission of this abstract, no dose limiting toxicities have been observed to date in the first 3 cohorts. In the United States, 4 sites are active with additional sites in planning. Additional sites in the US and Australia are currently in start-up. Clinical trial information: NCT04868604 .
Debunking the frailty-sarcopenia-ADT axis in metastatic prostate cancer with multicomponent exercise: The FIERCE trial.
Authors: Dieli-Conwright Christina Marie , Morgans Alicia K. , Gonzalo-Encabo Paola , Kang Dong-Woo , Rosenthal Michael Hayden , Vander Heiden Matthew , Uno Hajime , Wilson Rebekah L 
Published: June 2024

TPS5124 Background: Metastatic prostate cancer (mPCa) incidence is growing despite a decrease in the prevalence of prostate cancer (PCa). Androgen deprivation therapy (ADT), the mainstay treatment for mPCa, is accompanied by a number of side effects, such as decline in muscle mass and physical function, leading to the exacerbation of age-related conditions including frailty and sarcopenia. Frailty is characterized by a loss of functional reserve, where frail men with mPCa have a worse prognosis. Sarcopenia refers to a decrease in muscle mass, strength, and function, and is associated with increased mortality in men with mPCa. Notably, PCa patients who received ADT are 3 times more likely to develop frailty compared to patients who never received ADT and 2 times more likely to develop sarcopenia compared to men without cancer. Exercise plays a key role in ameliorating or preventing further deterioration of ADT-related side effects and improving muscle mass, fitness, and strength. However, while there is a number of exercise studies in men with PCa, those with mPCa have been vastly understudied, with a lack of studies focusing on frailty and sarcopenia and the mechanisms of how exercise could address such outcomes. Thus, we have designed the FIERCE Trial to assess the effects of a 16-week multicomponent exercise intervention, encompassing resistance, aerobic, and functional training on frailty and sarcopenic status and their potential mechanistic biomarkers, and disease progression. Methods: The FIERCE trial is a prospective study aiming to recruit eighty pre-frail/frail men with mPCa receiving ADT who will be randomized to an exercise or attention control group. The 16-week exercise intervention will include thrice weekly clinic supervised, resistance and functional exercise circuit training, and self-directed home-based aerobic exercise. The attention control group will receive a stretching program and will be offered the exercise program following the study period. The primary outcome will be frailty, measured by the Fried Frailty phenotype (i.e., muscle loss, exhaustion, physical activity, gait speed, and strength) and frailty associated biomarkers (IL-6, TNF-α, CRP). Secondary outcomes include sarcopenia, measured using computerized tomography scans and sarcopenia associated muscle biopsy-driven biomarkers (myokines and insulin pathway markers). An exploratory outcome will assess the effect of exercise on cancer cell line growth (LNCaP cell line). To date, eight out of planned 80 patients have been enrolled. This trial is registered in clinicaltrials.gov (NCT06040125). Clinical trial information: NCT06040125 .
ALADDIN: Evaluation of darolutamide addition to androgen deprivation therapy and radiation therapy in newly diagnosed prostate cancer with pelvic lymph nodes metastases.
Authors: Oudard Stephane , Combe Pierre , Boisserie Thomas , Hasbini Ali , Leroy Thomas , Supiot Stephane , Schick Ulrike , Mesgouez-Nebout Nathalie , Pasquier David , Fumagalli Ingrid , Khalifa Jonathan , Iriart Carole , Adrien Laville , Sargos Paul , Ruffier Amandine , Riet François-Georges , Martin Etienne , Cartier Lysian , Graff-Cailleaud Pierre , Bibault Jean-Emmanuel 
Published: June 2024

TPS5127 Background: Standard of care for patients with prostate cancer (PC) with pelvic lymph node metastases is radiotherapy (RT) with long-term androgen deprivation therapy (ADT). In the STAMPEDE trial, James et al. assessed the role of abiraterone acetate with prednisolone (AAP) earlier in the disease for N+M0 PC patients. They showed that the addition of AAP to ADT and RT significantly improved failure-free survival (FFS) from 61% to 92.5% (ESMO 2017). Darolutamide improves survival in men with castration-refractory non-metastatic prostate cancer and in mHSPC patients with the addition of ADT plus docetaxel. We hypothesize that adding Darolutamide to ADT and RT could improve FFS for these high-risk patients. Methods: The ALADDIN study (NCT05116475) is a French, prospective, phase 3 trial that will enroll an estimated 152 patients with hormone-naive prostate cancer and pelvic lymph node metastases. Eligible patients are treatment-naive for hormonal therapy, with positive lymph node disease (upper limit defined as L4/L5 interspace) determined by conventional imaging or TEP choline or PSMA, ECOG performance status of 0 to 2, and adequate major organ function. Patients will be randomized by minimization 1:1 to receive ADT + Intensity-Modulated Image-Guided Radiation Therapy (IMRT) with darolutamide or placebo (of darolutamide). IMRT will deliver 78 Gy to the prostate, 70 Gy to the metastatic lymph nodes, and 46 Gy to the pelvic lymph node areas (2 Gy per fraction, 5 days a week) with daily CBCT imaging. ADT will be achieved with LHRH agonists or antagonists for 24 months. The darolutamide regimen will be two tablets of 300 mg orally twice daily for 24 months. The primary endpoint is failure-free survival. Secondary endpoints will be: MFS, progression-free survival, safety, overall survival, and health-related quality of life. Stratification factors are D'Amico risk group and sites. The planned sample size provides 80% power to detect a difference of 20% in FFS (60 vs 80%) at a two-sided 0.05 significance level. The study is expected to last for 7 years, of which accrual will last for 2 years. The first participant was enrolled in the study in August 2022. In total, 23 centers are participating in the ALADDIN study. The DSMB occurred on November 13th 2023 and allowed the study to continue as planned. Clinical trial information: NCT05116475 .
A phase I, first-in-human study of ONO-7018 in patients with relapsed/refractory non-Hodgkin lymphoma or chronic lymphocytic leukemia.
Authors: Byrd John C. , Porcu Pierluigi , Sundermeier Thomas , Nakada Takashi , Iwata Takeyuki , Prados Sergio , Gordon Leo I. 
Published: June 2024

TPS7083 Background: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a key component of the caspase recruitment domain-containing protein 11 (CARD 11)-B-cell lymphoma/leukemia 10 (BCL 10)-MALT1 signalosome complex, which activates nuclear factor-kappaB (NF-κB) signaling in response to B-cell–receptor or T-cell–receptor stimulation. Activation of NF-κB signaling promotes survival and proliferation of B-cell lymphoma and T-cell lymphoma. ONO-7018 is an oral, potent, and selective MALT1 inhibitor that has demonstrated preclinical efficacy in several lymphoma models (Morishita D, et al. Blood. 2020). Therefore, ONO-7018 has therapeutic potential for non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). This study aims to determine the maximum tolerated dose (MTD) and to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of ONO-7018 as monotherapy in patients with relapsed or refractory NHL or CLL. Methods: This Phase I, first-in-human, open-label, multicenter study will be done in two parts, a dose-escalation phase (part 1) and a dose-expansion phase (part 2). An estimated 54 eligible patients will be enrolled. Patients must be adults with relapsed/refractory NHL or CLL with measurable disease; all acute toxic effects of prior antitumor therapy should be grade ≤1; have Eastern Cooperative Oncology Group performance status 0 to 2; and have adequate bone marrow, renal, and hepatic function. Exclusion criteria include history of other lymphoid malignancy, central nervous system involvement, active autoimmune disease, systemic and active infection, serious or uncontrolled medical disorder, and patient inability to swallow tablets. ONO-7018 will be administered orally. In part 1, patients will be assigned to a dose level cohort (≤4 dose levels: DL1-DL4) using a 3+3 dose-escalation design. In part 2, patients will be given the recommended dose level from part 1, following safety review. The primary endpoints include dose-limiting toxicity, MTD, and treatment-emergent adverse events. Secondary endpoints include pharmacokinetics, objective response rate, duration of response, progression-free survival, and overall survival. The study began February 13, 2023, and is currently recruiting; part 1 is ongoing. Clinical trial information: NCT05515406 .
Bone Health in Patients With Type 2 Diabetes
Authors: Forner Patrice , Sheu Angela 
Published: June 2024

Abstract
The association between type 2 diabetes mellitus (T2DM) and skeletal fragility is complex, with effects on bone at the cellular, molecular, and biomechanical levels. As a result, people with T2DM, compared to those without, are at increased risk of fracture, despite often having preserved bone mineral density (BMD) on dual-energy x-ray absorptiometry (DXA). Maladaptive skeletal loading and changes in bone architecture (particularly cortical porosity and low cortical volumes, the hallmark of diabetic osteopathy) are not apparent on routine DXA. Alternative imaging modalities, including quantitative computed tomography and trabecular bone score, allow for noninvasive visualization of cortical and trabecular compartments and may be useful in identifying those at risk for fractures.
Current fracture risk calculators underestimate fracture risk in T2DM, partly due to their reliance on BMD. As a result, individuals with T2DM, who are at high risk of fracture, may be overlooked for commencement of osteoporosis therapy. Rather, management of skeletal health in T2DM should include consideration of treatment initiation at lower BMD thresholds, the use of adjusted fracture risk calculators, and consideration of metabolic and nonskeletal risk factors. Antidiabetic medications have differing effects on the skeleton and treatment choice should consider the bone impacts in those at risk for fracture.
T2DM poses a unique challenge when it comes to assessing bone health and fracture risk. This article discusses the clinical burden and presentation of skeletal disease in T2DM. Two clinical cases are presented to illustrate a clinical approach in assessing and managing fracture risk in these patients.
The Digital Classicism of the Cantonese Opera Film White Snake
Authors: Luo Liang 
Published: June 2024

Abstract
This article examines the 2019 Cantonese opera film White Snake as an important case of an evolving “digital classicism,” making use of audience-based digitally produced and transmitted Chinese-language materials, among other sources. The article contextualizes the Cantonese opera film as continuing the tradition of experimenting with the White Snake theme, using the genres of local opera and opera film, and special and visual effects enabled by the newest technology. It then moves to a close reading of a series of danmu, anonymous live comments on the Cantonese opera film trailer posted on Bilibili, as important entry points for the study of audience participation in digital times. The digitally produced “ink painting–style Chinese aesthetics” of the film, its digital breakthrough as a “musical with Chinese characteristics,” as well as various forms of fan and anti-fan digital labor triggered by the film, provide further evidence on the importance of “the digital” as “processes of sense making.” The article concludes with thoughts on what difference “the digital” might be able to make in this long history of representing what has become a “classical” Chinese legend.
Surface Classicism
Authors: Chun Tarryn Li-Min 
Published: June 2024

Abstract
This article examines digital classicism in contemporary Chinese performance through the case study of an excerpt of the dance-drama Zhici qinglü 只此青綠 (Journey of a Legendary Landscape Painting) performed at the 2022 CCTV Spring Festival Gala. It argues that the mobilization of digital performance technologies in Zhici qinglü and other contemporary large-scale performance in the PRC generates what might be termed “surface classicism”—an engagement with the past that sublimates elements of classical art and literature into the realm of digitally enhanced visuality. Surface classicism lends itself to critiques of superficiality and inauthenticity, but this article demonstrates that its ubiquity in contemporary culture also creates new networks of relationality among remediations of classical poetics and imagery. Ultimately, the mediation of both liveness and spectacular technologies in contemporary, digitally enhanced performance establishes classicist poetics and imagery as a core component of shared contemporary Chinese culture and may even engender new, more accessible modes of classical erudition.