bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preliminary results from a phase II study comparing sunitinib alone or with stereotactic body radiotherapy (SBRT) for newly diagnosed oligometastatic renal cell carcinoma.
Authors: Liu Yang , Wei Wensu , Zhang Zhiling , Liu Ruiqi , Gao Jianming , Guo Shengjie , Han Hui , Dong Pei , He Liru , Zhou Fangjian 
Published: June 2023

4533 Background: Although SBRT has become an option for oligometastatic renal cell carcinoma (oligoRCC), current trials supporting SBRT haven’t been adequately persuasive given their single-arm, non-first-line design. Our study aimed to explore if SBRT improves oncologic outcomes compared with standard first-line systemic therapy in oligoRCC. Methods: This an open-label, double-arm phase II controlled trial enrolling treatment naïve oligoRCC patients (pts), defined as ≤ 5 metastatic lesions (ChiCTR1800017136). No liver or brain metastasis was allowed. Nephrectomy was mandatory before enrollment. Pts were allocated 1:1 to receive either sunitinib alone (control arm) or sunitinib plus SBRT (SBRT arm). Sunitinib was started as 50 mg daily for 4 weeks, followed by 2 weeks off treatment. SBRT was delivered to all metastatic sites within 2 months after sunitinib initiation, with 35-50Gy in 5 fractions. Primary endpoint was objective response rate (ORR); secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. Data from pts with ≥ 1 year of follow-up were reported this time. Results: Starting in 2018, the trial has currently completed its accrual, with 48 pts enrolled. Forty-two pts had ≥ 1 year of follow-up and were evaluable for the present analysis. Pt characteristics for SBRT and control arms: median age 51 vs 59 years (p=0.094); synchronous metastasis 31.8% vs 10.0% (p=0.179); clear cell carcinoma 77.3% vs 80.0% (p=1.000); IMDC low or intermediate risk 86.4% vs 80.0% (p=1.000); solitary metastasis 45.5% vs 25.0% (p=0.167). Thirty-four sites received SBRT, most frequently to bone (61.8%) and soft tissue (17.6%) metastasis. The 1-year local control rate after SBRT was 93.8%. ORR (81.8% vs. 25.0%, p=0.000) and DCR (90.9% vs. 60.0%, p=0.047) were significantly higher in SBRT arm than those in control arm. The 1y-PFS was 72.7% for SBRT arm and 35.0% for control arm (HR 0.33, 95% CI 0.16-0.69, p= 0.003). And the 1y-OS was 95.5% for SBRT arm and 80.0% for control arm (HR 1.06, 95% CI 0.31-3.67, p=0.923). Grade 3-4 treatment-related AEs occurred in 66.7% and 62.5% pts in SBRT arm and control arm (p=0.763), respectively. SBRT-related Grade 3-4 toxicity included radiation enteritis (n=1, grade 3) and radiation pneumonitis (n=1, grade 3). Conclusions: Our results showed promising efficacy and acceptable toxicity of SBRT plus sunitinib when compared with sunitinib alone for oligoRCC. Complete results are awaited in 2023 after follow-up completion of the entire cohort. Clinical trial information: ChiCTR1800017136.
Preliminary results from a phase I/II study of IMM0306, a CD47 and CD20 bispecific monoclonal antibody-trap, in patients with relapsed or refractory CD20-positive B-cell non-Hodgkin's lymphoma.
Authors: Yang Jianliang , Song Yongping , Li Zhiming , Zhang Mingzhi , Zhou Keshu , Wang Zhen , Jing Hongmei , Yu Li , Ma Huizi , Zhao Xiwen , Li Wei , Meng Wei , Tian Wenzhi , Shi Yuankai 
Published: June 2023

7527 Background: IMM0306 is a fusion protein of CD20 monoclonal antibody with the CD47 binding domain of SIRPα on both heavy chains. It has a higher affinity for CD20 than for CD47, thus enabling its preferential and simultaneous binding to CD20 and CD47 on malignant B cells rather than to CD47-postive normal tissues. Here, we report the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy results of the dose escalation stage in a phase I/II study in patients (pts) with relapsed or refractory CD20-positive B-cell non-Hodgkin's lymphoma. Methods: This is a first-in-human, open-label, phase I/II study of IMM0306. The ongoing Phase I part (0.04, 0.1, 0.25, 0.5, 0.8, 1.2, 1.6, 2.0 mg/kg, IV) followed an accelerated titration and standard 3+3 design. IMM0306 was administered once per week after a 2-week single-dose period, until disease progression or intolerable toxicity. Dose-limiting toxicity (DLT) was evaluated in the first 28 days. Safety was evaluated per CTCAE 5.0, tumor assessments performed once every 8 weeks, PK and PD were also assessed. Results: As of the data cut-off date on Dec 15th, 2022, 42 pts were enrolled. 18 (43%) pts received 3 or more prior lines of therapy, all pts received prior anti-CD20 therapy. No DLTs were observed up to 2.0 mg/kg. The most frequent treatment related adverse events (TRAEs) were lymphocyte decreased (61.9%), white blood cell (WBC) decreased (61.9%), anemia (59.5%), neutrophil (ANC) decreased (40.5%), platelet (PLT) decreased (40.5%), infusion-related reactions (31.0%). Grade ≥ 3 TRAEs occurred in 30 (71.4%) pts, the most frequent grade ≥ 3 TRAEs were lymphocyte decreased (59.5%), WBC decreased (16.7%), ANC decreased (11.9%). Three treatment related SAEs were PLT decreased (grade 4), chest pain (grade 2) and diarrhea (grade 3). In 38 response evaluable pts, 2 follicular lymphoma (FL) pts achieved CR, 1 marginal zone lymphoma (MZL) pt and 2 FL pts achieved PR and 13 pts showed SD. 26 pts were treated at doses ≥ 0.8 mg/kg, among whom 11 were FL pts. Of these 11 FL pts, 4 (36%) responded including 2 CR both at 1.2 mg/kg and 2 PR at 1.2 and 1.6 mg/kg respectively. IMM0306 exhibited approximate dose-proportional increase in PK exposure from 0.5 to 2.0 mg/kg and no obvious accumulation was observed after repeated dosing. B-cell counts depleted rapidly at doses ≥ 0.8 mg/kg. Elevated cytokines levels were observed after first dosing of IMM0306, but multiple dosing did not stimulate further cytokine activation. Conclusions: IMM0306 was well-tolerated and with a robust preliminary anti-tumor activity especially in pts with R/R FL and MZL. The phase I/II study is ongoing. Clinical trial information: CTR20192612 .
A phase 2a study evaluating the efficacy and safety of sutetinib in patients with advanced non–small-cell lung cancer (NSCLC) harboring uncommon EGFR mutations.
Authors: Wu Fengying , Zhou Fei , Zhao Fuyou , Zhang Wei , Wang Lei , Yu Jia , Xiong Anweng , Zhao Jing , Li Wei , Gao Guanghui , He Yayi , Bo Bing , Meng Shuyan , Han Baohui , Zhou Caicun 
Published: June 2023

9131 Background: Although non-small cell lung cancer (NSCLC) patients with tumor harboring classical Epidermal Growth Factor Receptor (EGFR) mutations have numerous therapeutic choices, uncommon EGFR mutation NSCLC patients have limited treatment options. Sutetinib is a selective tyrosine kinase inhibitor (TKI) targeting uncommon EGFR mutations. Methods: In this multicenter, open-label phase 2a study, treatment-naïve adults with NSCLC harboring uncommon EGFR mutations (G719X, S768I, L861Q) received oral sutetinib monotherapy at 80 or 64 mg/day (Chinese trial register CTR20190681). The primary endpoint was objective response rate (ORR) per RECIST v1.1. Secondary endpoints included duration of response (DoR), overall survival (OS), safety and tolerability. Adverse events (AEs) were graded according to the CTCAE v5.0. Results: Sutetinib was administered to 30 NSCLC patients at 80 (n = 15) or 64 (n = 15) mg/day. Median age was 60 years old (range 47-74 years). Twenty patients (66.7%) were females, 10 patients (33.3%) had a history of smoking. Patients had an ECOG PS of 0 (10.0%) or 1 (90.0%). Tumors had a G719X (36.7%), L861Q (30.0%), or S768I (20.0%) EGFR mutation, or a combination of these uncommon EGFR mutations (13.3%). None had EGFR T790M, L858R, exon 19 deletions, or exon 20 insertions. The ORR was 71.4% (20/28), including 92.9% (13/14) and 50.0% (7/14) in the 80 and 64 mg/day cohorts, respectively. The disease control rate (DCR) was 96.4%, including 100.0% (14/14) and 92.8% (13/14) in the 80 and 64 mg/day cohorts, respectively. All responses were partial responses. The median DoR was 12.5 months (20.3 and 9.2 months in the 80 and 64 mg/day cohorts, respectively). One-year OS was 84.7% (92.9% and 75.0% in the 80 and 64 mg/day cohorts, respectively). As of 15 January 2022 (database lock), 11 (36.7%) patients were still receiving sutetinib treatment. Grade ≥3 treatment emerged AEs were similar in the 80 mg/day (80.0%, 12/15) and 64 mg/day (73.3%, 11/15) cohorts. The most frequently reported grade ≥3 Treatment-related AEs (TRAEs) were diarrhea (36.7%), abnormal liver function (13.3%), and rash (10.0%). One grade 4 TRAE was observed: hypokalemia in the 64 mg/day cohort. Conclusions: Sutetinib demonstrated a high response rate with durable antitumor activity in patients with NSCLC harboring uncommon EGFR mutations. The toxicities are expected and comparable to other EGFR TKIs. A multi-center phase 2b study is ongoing in the United States and China to further evaluate Sutetinib in uncommon EGFR mutation NSCLC. Clinical trial information: CTR20190681 .
Metformin with neoadjuvant chemotherapy in localized triple negative and HER2neu-positive breast cancer: A prospective phase 2 open label randomised controlled trial (McBETH).
Authors: B M Mouna Bidaraguppe , kumar akash , Batra Atul , Sharma Vinod , Kataria Babita , Gogia Ajay , Mathur Sandeep , Sharma Aparna 
Published: June 2023

TPS631 Background: Repurposing of drugs in cancer is an attractive strategy and metformin has long been an agent with promising yet unproven activity in breast cancer. Despite some recent studies showing inadequate efficacy in adjuvant setting, there is a lack of well powered studies in neo-adjuvant setting in localised breast cancer. Few past studies suggest that metformin may have anticancer effects in the subsets of Her2 neu positive as well as Triple negative breast cancer (TNBC). We initiated this study to investigate if metformin in combination with standard neo-adjuvant chemotherapy is effective in improving pathological complete response rates in these subsets among localised breast cancers. Methods: This is an investigator initiated randomised, open label, parallel-group superiority trial. All non diabetic localised chemo-naïve breast cancer patients aged ≥18 years planned for neo-adjuvant chemotherapy will be randomly allocated (stratified by HER 2 positive and TNBC) to receive standard neo-adjuvant chemotherapy with or without metformin (850mg twice daily) till the day of surgery. The patients will be followed up until the surgery. The primary objective of this study is to compare the pathological complete response rates(ypT0ypN0) in each arm. The secondary objectives are to compare pathological complete response rates in predefined subsets of HER2 positive and triple negative breast cancer, clinical response rates in each arm, patient reported outcomes in each arm (ESAS-r Scale), breast conservation surgery rates in each arm, incidence and severity of adverse events in both arms. Trial statistical design: Planned accrual is total 242 patients including 10% drop out rate. It is a superiority design with an absolute improvement of 11% in pathological complete response from a baseline of 33% in the standard arm. Conduct to date: study activation: May 2022. Enrolment: 116 subjects. Clinical trial information: REF/2022/05/054208.
Dexamethasone and exercise for cancer-related fatigue: A phase III randomized controlled trial.
Authors: Noronha Vanita , Goud Supriya , Mahajan Sarika Gautam , Sharma Rangita , Yadav Akanksha , Pawar Akash , Chintala Sravan Kumar , Shah Minit Jalan , More Sucheta Bhagwan , Menon Nandini Sharrel , Patil Vijay Maruti , Singh Ajaykumar Chandrabhan , Shah Srushti , Nawale Kavita Prakash , Nakti Dipti , Daptardar Anuradha , Karuvandan Naveen , Sarkar Laboni , Suman Mannavi , Prabhash Kumar 
Published: June 2023

LBA12098 Background: Cancer-related fatigue (CRF) significantly impacts QoL of patients. Dexamethasone with physical activity may improve CRF. Methods: Phase III randomized study in patients with advanced cancer on palliative intent therapy, with ECOG PS 0-2, and fatigue score > 4/10 on numeric rating scale. Intervention included oral dexamethasone 8 mg twice daily for 7 days, and exercise (aerobic + resistance). Results: From Dec 2022 to Feb 2023, we enrolled 114 pts; 56 in intervention arm, and 58 in standard arm. Median age was 56 yrs (IQR, 47.8 to 65), with 74 (64.9%) males. Common tumors were lung (75, 65.8%), head-and-neck (12, 11%), and breast (10, 8.8%). Compliance was 87.3% (n=48) for dexa, and 70.9% (n=39) for exercise. Primary endpoint of mean improvement in FACIT-Fatigue subscale on day 8 was 3.22 (SD, 12.69) in intervention, compared to 1.73 (SD, 9.97) in standard arm; P =0.495. However, 54.5% patients in intervention had at least 3 points (minimal clinically relevant) decrease in fatigue, vs 41.8% in control; P=0.182. By day 29, mean change in FACIT-Fatigue scores compared to baseline was similar in intervention vs control; 2.61 (SD, 14.64) vs 2.68 (SD, 12.87), respectively; P=0.978. Although overall symptoms (ESAS) and general QoL were similar, there was a significant improvement in fatigue symptom on EORTC QLQ-C30 in intervention on day 29 compared to baseline; P=0.013. Sleep quality also significantly improved on Day 29 in intervention; P=0.018. On EORTC-QLQ FA12 (cancer-related fatigue QoL), physical fatigue improved significantly from baseline to Day 8 in intervention versus control; P=0.035; with no difference in emotional or cognitive fatigue, interference with daily life, or social sequelae. There was no difference in grade ≥ 3 adverse events between groups; 18 (32.7%) in intervention group versus 18 (30.5%) in control group; P=0.799. Conclusions: Dexamethasone and exercise did not lead to a statistically significant improvement in fatigue by FACT-Fatigue scale, although it resulted in greater proportion of pts with clinically relevant improvements in fatigue. The intervention significantly improved QoL fatigue symptom score and reduced physical fatigue on QoL, along with improving sleep quality. Clinical trial information: CTRI/2022/09/045678 . [Table: see text]
Pembrolizumab plus axitinib versus sunitinib as first-line therapy for advanced clear cell renal cell carcinoma: 5-year analysis of KEYNOTE-426.
Authors: Rini Brian I. , Plimack Elizabeth R. , Stus Viktor , Gafanov Rustem , Waddell Tom , Nosov Dmitry , Pouliot Frederic , Alekseev Boris , Soulieres Denis , Melichar Bohuslav , Vynnychenko Ihor O. , Azevedo Sergio Jobim , Borchiellini Delphine , McDermott Raymond S. , Bedke Jens , Tamada Satoshi , Wu Sterling , Burgents Joseph , Molife L. Rhoda , Powles Thomas 
Published: June 2023

LBA4501 Background: At the first interim analysis of the randomized, open-label, phase 3 KEYNOTE-426 (NCT02853331) study, 1L pembro + axi showed statistically significant OS, PFS, and ORR over sun for advanced ccRCC. We report results with 5-y minimum follow-up. Methods: Adults with confirmed locally advanced or metastatic ccRCC with or without sarcomatoid features, no previous systemic therapy for metastatic ccRCC, KPS ≥70%, and ≥1 lesion measurable per RECIST v1.1 were randomly assigned 1:1 to receive pembro 200 mg IV Q3W for 35 doses (~2 y) + axi 5 mg PO BID or sun 50 mg PO QD on a 4-wk-on/2-wk-off schedule. Dual primary end points were OS and PFS per RECIST v1.1 by blinded independent central review (BICR). Secondary end points included ORR and DOR per RECIST v1.1 by BICR, and safety. A post hoc analysis adjusting for the effect of subsequent therapy on OS using a 2-stage adjustment model was conducted. Results: Of 861 enrolled patients (pts), 432 were assigned to pembro + axi and 429 to sun. Median study follow-up was 67.2 mo (range, 60.0-75.0). Efficacy for the ITT population and IMDC risk subgroups are shown in table. For pembro + axi vs sun, the 60-mo OS rates were 41.9% vs 37.1%, and the 60-mo PFS rates were 18.3% vs 7.3%. Median DOR (range) was 23.6 mo (1.4+ to 68.6+) for pembro + axi and 15.3 mo (2.3-68.3) for sun. In pts who discontinued treatment, 237/381 pts (62.2%) in the pembro + axi arm and 300/406 pts (73.9%) in the sun arm received subsequent anticancer treatment. The HR for OS when adjusted for subsequent therapy was 0.67 (95% CI, 0.52-0.84). Clinical data on pts who completed 2 y of pembro will be presented. No new safety signals were observed. Conclusions: After 5 y of follow-up, pembro + axi had sustained OS, PFS, and ORR benefits over sun in advanced ccRCC. These results are the longest follow-up to date of an anti–PD-1/L1 inhibitor + VEGFR TKI in this pt population and continue to support the use of pembro + axi as a 1L standard of care for advanced ccRCC. Clinical trial information: NCT02853331 .
Art on Film at Finch College: Reproductive Labor in the Enrichment Economy
Authors: Ridlen Tim 
Published: June 2023

Abstract
Finch College was a small women's liberal arts college located on the Upper East Side of Manhattan open from 1900 to 1975. The Contemporary Wing of the Finch College Museum of Art held a number of important exhibitions for conceptual art, experimental media, and film organized by the museum's curator, Elayne Varian, from 1966 to 1975. This article addresses how ideas of process, reproduction, and documentation were being reconfigured at Finch, especially in film and media art of the 1960s. Robert Morris's film installation, Finch College Project (US, 1969), is emblematic of this larger turn toward process in the visual arts; however, Varian's Projected Art exhibitions complicate our understanding of how and why artistic process became a subject of interest. In light of what Boltanski and Esquerre have recently identified as an “enrichment economy” and what feminist thinkers of the time theorized as reproductive labor, works in the Projected Art series shift attention to the reproductive labor of caring for, curating, collecting, and consuming visual art and film. I argue that Varian's exhibitions as a whole complicate our understanding of process-oriented work during the postwar period, especially film and media that moved into gallery exhibition spaces. These works attacked the existing modes of production by turning toward process, complicating the status of photographic reproduction, and contributing their own surplus value through reproductive labor.
Critical Hope
Authors: Kesrouany Maya Issam 
Published: June 2023

Abstract
This article explores the theory and practice of critique in the works of the Lebanese Communist intellectual Husayn Muruwwa (1910–1987) and his grandson Rabih Mroué (b. 1967). Husayn Muruwwa, one of the most important Arab intellectuals of the second half of the twentieth century, reinvented literary criticism and cultural critique in the 1950s and '60s. His grandson, one of the most prominent Arab visual artists, has been redefining the critical approach to visual representation since the Lebanese civil war. The article pits Husayn Muruwwa's critique based on collective hope and emancipation against his grandson's vision of an individualistic critique based on desire. It considers the critical and political writings of Husayn Muruwwa and Rabih Mroué's performances, video lectures, and interviews to explore specifically how they represent hope in relation to critique, and it ultimately suggests a participatory aesthetics that is common to both and that transcends their autobiographical statements and establishes resonances between their thought. Their approaches to critique, the article illustrates, play out as revised inheritances of both the Arab renaissance (nahda) and the national liberation movements in the 1970s. These revisions create a continuity that is critical to understanding the relationship between critique and hope in the Arab intellectual tradition.
Tetracycline-mediated fluorescence correlates with passage number and β-galactosidase activity in HeLa and HEK293T cells
Authors: Redwood-Sawyerr Chileab , Nesbeth Darren N. 
Published: June 2023

ABSTRACT
We report data consistent with tetracycline-mediated fluorescence having the potential to be an effective marker of senescence in immortalised cells. HeLa cells that had previously undergone more than 20 passages were transiently transfected with a plasmid encoding a novel tetracycline-inducible transgene featuring an open reading frame for green fluorescent protein. While characterising the performance of this plasmid and transfection procedure, HeLa cell fluorescence was observed to result from incubating cells with media containing 2 μg/ml tetracycline alone, without plasmid or transfection reagent. To investigate this phenomenon further, HeLa and HEK293T cells were purchased from a tissue culture collection and after cultivation over 4-23 passages, incubated with media containing 2 μg/ml tetracycline. For both cell lines, tetracycline-mediated fluorescence increase correlated with passage number increase. This effect in HeLa and HEK293T cells was also borne out by expression of β-galactosidase activity, an imperfect but widely used marker of cellular senescence. These data suggest tetracycline may have utility as a marker of cellular senescence in immortal cells and can inform future investigation and validation of this previously unreported application for this reagent.
Exploring potential strategies to enhance memory and cognition in aging mice
Authors: Bhat M Shreevatsa , M G Ramesh Babu , Dhanushkodi Anandh , Rai Prof Kiranmai S 
Published: June 2023

Background: Aging population is rapidly expanding worldwide, and age-related cognitive impairments prove detrimental for achieving a better productive and quality of life. Lack of effective therapies for age-related cognitive impairment focuses attention on developing preventive strategies, such as nutritional interventions, cell therapies and environmental manipulations. The objective of the present study was to explore the comparative benefits of potential memory-enhancing strategies like supplementation of choline (Ch) and docosahexaenoic acid (DHA) or administration of human embryonic kidney stem cell conditioned media (HEK-CM) or exposure to environmental enrichment (EE), that attenuates cognitive impairments in aging mice. Methods: 12-month-old CF1 male mice were subdivided [n=6/group] into normal aging control (NAC), saline vehicle control (SVC), Ch-DHA, EE, heat-inactivated HEK-CM (HIHEK-CM) and HEK-CM mice. Spatial working and reference memory were assessed using an eight-arm radial maze test and cognition using a novel object recognition test (NORT). Results: Spatial memory and cognition were decreased in normal aging mice. Aged mice exposed to dietary Ch-DHA or HEK-CM showed significant enhancement in spatial learning tasks, memory and cognition compared to the same in age-matched NAC mice. Ch-DHA and HEK-CM treated mice committed significantly lesser reference memory errors and attained a higher percentage of correct choices in spatial learning and memory tasks. Moreover, on testing for cognition in NORT, significantly higher number of visits to the novel object was observed in Ch-DHA supplemented and HEK-CM administered aging mice whereas HEK-CM and EE mice groups showed significantly greater number of visits to familiar object, when compared to same in age-matched NAC and HIHEK-CM groups, respectively. Conclusion: Supplementation of Ch-DHA and HEK-CM treatment strategies have a higher potential [~ 20—30%] for enhancing spatial learning, memory and cognition in normal aged mice, whereas exposure to EE seems to enhance only their short-term memory.