bluuebunny/crossref_metadata_2025 huggingface dataset:
Alterations in neural activation in the ventral frontoparietal network during complex magnocellular stimuli in developmental dyslexia associated with READ1 deletion
Authors: Mascheretti Sara , Arrigoni Filippo , Toraldo Alessio , Giubergia Alice , Andreola Chiara , Villa Martina , Lampis Valentina , Giorda Roberto , Villa Marco , Peruzzo Denis
Published: June 2024

Background

An intronic deletion within intron 2 of the DCDC2 gene encompassing the entire READ1 (hereafter, READ1d) has been associated in both children with developmental dyslexia (DD) and typical readers (TRs), with interindividual variation in reading performance and motion perception as well as with structural and functional brain alterations. Visual motion perception -- specifically processed by the magnocellular (M) stream -- has been reported to be a solid and reliable endophenotype of DD. Hence, we predicted that READ1d should affect neural activations in brain regions sensitive to M stream demands as reading proficiency changes.

Methods

We investigated neural activations during two M-eliciting fMRI visual tasks (full-field sinusoidal gratings controlled for spatial and temporal frequencies and luminance contrast, and sensitivity to motion coherence at 6%, 15% and 40% dot coherence levels) in four subject groups: children with DD with/without READ1d, and TRs with/without READ1d.

Results

At the Bonferroni-corrected level of significance, reading skills showed a significant effect in the right polar frontal cortex during the full-field sinusoidal gratings-M task. Regardless of the presence/absence of the READ1d, subjects with poor reading proficiency showed hyperactivation in this region of interest (ROI) compared to subjects with better reading scores. Moreover, a significant interaction was found between READ1d and reading performance in the left frontal opercular area 4 during the 15% coherent motion sensitivity task. Among subjects with poor reading performance, neural activation in this ROI during this specific task was higher for subjects without READ1d than for READ1d carriers. The difference vanished as reading skills increased.

Conclusions

Our findings showed a READ1d-moderated genetic vulnerability to alterations in neural activation in the ventral attentive and salient networks during the processing of relevant stimuli in subjects with poor reading proficiency.
Mapping implementation strategies to reach community-dwelling older adults in Northwest Switzerland
Authors: Mendieta Maria Jose , Goderis Geert , Zeller Andreas , Yip Olivia , Siqeca Flaka , Zúñiga Franziska , Zullig Leah L. , De Geest Sabina M. , Deschodt Mieke , Flamaing Johan , Dhaini Suzanne ,   the INSPIRE Consortium, Urfer Pia , Briel Matthias , Schwenkglenks Matthias , Vounatsou Penelope , Quinto Carlos , Blozik Eva , Obas Katrina
Published: June 2024

Background

In Northwestern Switzerland, recent legislation tackles the needs of community-dwelling older adults by creating Information and Advice Centers (IACs). IACs are a new service in the community that aims to assess the needs and provide information on age-related issues to community-dwelling older adults and their families. Previous studies reported difficulties in reaching community-dwelling older adults for community-based programs. We aimed to: 1) systematically identify implementation strategies to promote the IAC among community care providers, older adults and informal caregivers; 2) monitor the delivery of these strategies by the IAC management; and 3) describe the impact of those strategies on reach of community-dwelling older adults. This study was conducted as part of the TRANS-SENIOR project.

Methods

As part of the INSPIRE feasibility assessment, we conducted a pre-test post-test study between March and September 2022. The sample included 8,840 older adults aged 65 + visiting/calling or being referred to the IAC for the first time. Implementation strategies were selected using implementation mapping and organized in bundles for each group of community care providers and older adults/caregivers. Our evaluation included: estimation of fidelity to the delivery of implementation strategies and bundles by the IAC management and their coverage; referral source of older adults to the IAC; and impact of the strategies on reach of the IAC on the 65 + population living in the care region. Adaptations to the strategies were documented using the FRAME-IS. Descriptive statistics were calculated and reported.

Results

Seven implementation strategies were selected and organized in bundles for each community care provider and older adults and their caregivers. The lowest fidelity score was found in implementation strategies selected for nursing homes whereas the highest score corresponded to strategies targeting older adults and caregivers. “Informational visits” was the strategy with the lowest coverage (2.5% for nursing homes and 10.5% for hospitals and specialized clinics). The main referral sources were self-referrals and referrals by caregivers, followed by nursing homes. The IAC reach among the 65 + population was 5.4%.

Conclusion

We demonstrated the use of implementation mapping to select implementation strategies to reach community-dwelling older adults. The reach was low suggesting that higher fidelity to the delivery of the strategies, and reflection on the causal pathway of the implementation strategies might be needed.
Two cases of atrial myxoma with calcification and ossification as the main features
Authors: Yin Yafei , Deng Juan , Liu Yuan , Zheng Jingxin , Zhang Yun , Bai Qizhi , Xu Yali , Yang Guoliang
Published: June 2024

Background

Cardiac myxomas are the most common type of primary cardiac tumors in adults, but they can have variable features that make them difficult to diagnose. We report two cases of atrial myxoma with calcification or ossification, which are rare pathological subgroups of myxoma.

Case presentation

A 47-year-old woman and a 35-year-old man presented to our hospital with different symptoms. Both patients had a history of chronic diseases. Transthoracic and transesophageal echocardiography revealed a mass in the left or right atrium, respectively, with strong echogenicity and echogenic shadows. The masses were suspected to be malignant tumors with calcification or ossification. Contrast transthoracic echocardiography(cTEE) showed low blood supply within the lesions. The patients underwent surgical resection of the atrial mass, and the pathology confirmed myxoma with partial ossification or massive calcification.

Conclusion

We report two rare cases of atrial myxoma with calcification or ossification and analyze their ultrasonographic features. Transthoracic echocardiography and cTEE can provide valuable information for the diagnosis and management of such mass. However, distinguishing calcification and ossification in myxoma from calcification in malignant tumors is challenging. More studies are needed to understand the pathogenesis and imaging characteristics of these myxoma variants.
Non-malignant pathological results from CT-guided biopsy for pulmonary nodules: a predictive model for identifying false-negative results
Authors: Wang Xu-Zhou , Wang Jing-Ya , Meng Tao , Shi Yi-Bing , Sun Jin-Jun
Published: June 2024

Background

Computed tomography (CT)-guided biopsy (CTB) procedures are commonly used to aid in the diagnosis of pulmonary nodules (PNs). When CTB findings indicate a non-malignant lesion, it is critical to correctly determine false-negative results. Therefore, the current study was designed to construct a predictive model for predicting false-negative cases among patients receiving CTB for PNs who receive non-malignant results.

Materials and methods

From January 2016 to December 2020, consecutive patients from two centers who received CTB-based non-malignant pathology results while undergoing evaluation for PNs were examined retrospectively. A training cohort was used to discover characteristics that predicted false negative results, allowing the development of a predictive model. The remaining patients were used to establish a testing cohort that served to validate predictive model accuracy.

Results

The training cohort included 102 patients with PNs who showed non-malignant pathology results based on CTB. Each patient underwent CTB for a single nodule. Among these patients, 85 and 17 patients, respectively, showed true negative and false negative PNs. Through univariate and multivariate analyses, higher standardized maximum uptake values (SUVmax, P = 0.001) and CTB-based findings of suspected malignant cells (P = 0.043) were identified as being predictive of false negative results. Following that, these two predictors were combined to produce a predictive model. The model achieved an area under the receiver operating characteristic curve (AUC) of 0.945. Furthermore, it demonstrated sensitivity and specificity values of 88.2% and 87.1% respectively. The testing cohort included 62 patients, each of whom had a single PN. When the developed model was used to evaluate this testing cohort, this yielded an AUC value of 0.851.

Conclusions

In patients with PNs, the predictive model developed herein demonstrated good diagnostic effectiveness for identifying false-negative CTB-based non-malignant pathology data.
Clinical outcomes of aortic root repair using pericardial autograft for acute type a aortic dissection
Authors: Liu Chuang , Wang Yao , Ouyang Peigang , Sun Yangxue , Huang Lingchen , Sun Xiaogang , Qian Xiangyang , Yu Cuntao , Guo Hongwei
Published: June 2024

Background

For acute type A aortic dissection involving the aortic root with root diameter no more than 45 mm, there are various aortic root repair techniques. In this study, a novel surgical technique using a pericardial autograft for aortic root repair was introduced. We described its surgical steps in detail and compare its clinical outcomes with direct suture technique.

Methods

Between July 2017 and August 2022, 95 patients with acute type A aortic dissection who underwent aortic root repair were enrolled, including aortic root repair using pericardial autograft (group A, n = 49) or direct suture (group B, n = 46). The patient’s clinical data were retrospectively analyzed, and a 5-year follow-up was conducted.

Results

The 30-day mortality, re-exploration for bleeding, postoperative new-onset renal failure requiring continuous renal replacement therapy, stroke, and paraplegia occurred in 3%, 4%, 11%, 5%, and 2% of the overall patients, respectively. There was no significant difference in the 30-day mortality and complication rate between the two groups. The 30-day mortality and re-exploration for bleeding marked the primary endpoint events. Logistic regression analysis indicated that there was a significant correlation between the primary endpoint events and surgical technique (odds ratio, 0.002; 95% confidence interval, 0-0.159; P = 0.026). The aortic valve insufficiency of the two groups were significantly improved after operation (group A, P < 0.001; group B, P < 0.001). During follow-up, there was no significant difference in short-term survival between the two groups after surgery (log-rank P = 0.75), and all patients were free from reoperation for aortic disease.

Conclusions

Patients who underwent aortic root repair using pericardial autograft tended to have reduced 30-day mortality and a lower risk of re-exploration for bleeding. Using pericardial autograft for aortic root repair is a safe and useful approach for patients with acute type A aortic dissection involving the aortic root.
Uniportal versus multiportal video-assisted thoracoscopic surgery for spontaneous pneumothorax
Authors: Janssen Nicky , Franssen Aimée J.P.M. , Ramos González Arlette A. , Laven Iris E.W.G. , Jansen Yanina J.L. , Daemen Jean H.T. , Lozekoot Pieter W.J. , Hulsewé Karel W.E. , Vissers Yvonne L.J. , de Loos Erik R.
Published: June 2024

Background

Multiportal video-assisted thoracic surgery (mVATS) is the standard approach for the surgical treatment of spontaneous pneumothorax. However, uniportal VATS (uVATS) has emerged as an alternative aiming to minimize surgical morbidity. This study aims to strengthen the evidence on the safety and efficiency of uVATS compared to mVATS.

Methods

From January 2004 to December 2020, records of patients who had undergone surgical treatment for primary or secondary spontaneous pneumothorax were evaluated for eligibility. Patients who had undergone pleurectomy combined with bullectomy or apical wedge resection via uVATS or mVATS were included. Surgical characteristics and postoperative data were compared between patients who had undergone surgery via uVATS or mVATS. Univariable and multivariable analyses were performed to determine whether the surgical approach was associated with any complication (primary outcome), major complications (i.e., Clavien-Dindo ≥ 3), recurrence, prolonged hospitalization or prolonged chest drainage duration (secondary outcomes).

Results

A total of 212 patients were enrolled. Patients treated via uVATS (n = 71) and mVATS (n = 141) were significantly different in pneumothorax type (secondary spontaneous; uVATS: 54 [76%], mVATS: 79 [56%]; p = 0.004). No significant differences were observed in (major) complications and recurrence rates between both groups. Multivariable analyses revealed that the surgical approach was no significant predictor for the primary or secondary outcomes.

Conclusions

This study indicates that uVATS is non-inferior to mVATS in the surgical treatment of spontaneous pneumothorax regarding safety and efficiency, and thus the uVATS approach has the potential for further improvements in the perioperative surgical care for spontaneous pneumothorax.
Fluffy-like amphiphilic graphene oxide and its effects on improving the antibacterial activity and thermal outstanding of ethyl cellulose /polyvinyl alcohol hydrogel film
Authors: Tohamy Hebat-Allah S. , El-Masry Hossam M.
Published: June 2024

The antibacterial characteristics of graphene oxide (GO-SB) nano-sheets generated by charring sugarcane bagasse (SB) are described in this study. The antibacterial capability of GO-SB was improved when it was grafted with ethyl cellulose (EC) and polyvinyl alcohol (PVA) to form GO-SB/EC/PVA hydrogels. Characterization of GO-SB nanosheets and GO-SB/EC/PVA hydrogels was accomplished by using FTIR, SEM, XRD, and thermal studies. The antimicrobial activity was carried out against Gram positive bacteria [Micrococcus leutus & Staphylococcus aureus], Gram negative bacteria [Escherichia coli, Pseudomonas aeruginosa] and pathogenic fungal yeast [Candida albicans] applying the disc diffusion method. The disc diffusion method results showed that the improved GO-SB/EC/PVA exhibited a reasonable level of antimicrobial capability against Micrococcus leutus, demonstrating that the antimicrobial improvement of GO-SB was more effective in the GO-SB/EC/PVA hydrogels by increasing the inhibition zone of Gram-positive bacteria, Micrococcus leutus from (13.0 to 16.0 mm).

Graphical abstract
A case study to investigate the effects of Chlorhexidine mouthwash on serum cytokines levels in children with Asthma
Authors: Sadr Saeed , Eslaminezhad Sahar , Mehrabi Nasab Entezar , Arora Poonam , Yavari Bahram , Khodabandehloo Hadi , Jafari Davood , Borji Mohammad , Athari Seyyed Shamsadin
Published: June 2024

Asthma is an airways inflammatory disease and the most common chronic disease of childhood, which causes most hospital visits and placing a heavy financial burden on families and communities. Interleukins 4, 5 and 13, play a central role in the pathogenesis of asthma. Given the importance of oral hygiene in asthmatic patients and IL-4 and 5 are involved in the inflammatory process of periodontitis, the effect of chlorhexidine as mouthwash on asthma attacks in children on serum cytokines is necessary. In this study, 375 children with asthma were divided into two groups using or non-using chlorhexidine. Blood samples were taken and cytokines were measured by ELISA. From 375 patients, 17 patients were excluded. In this study, 171 males and 187 females participated and there were 180 patients in asthma group and 178 patients in asthma/Chlorhexidine group. The levels of IL-4, IL-5 and IL-13 had no significant difference (p > 0.05) between Asthma and Asthma/Chlorhexidine groups. Using chlorhexidine as mouthwash in children with asthma had no effect on the type 2 cytokines and may not trigger an asthma attack via allergo-inflammatory mechanism.
Leaching of liquation-feeding furnace dross as a first step for germanium recovery
Authors: Drzazga Michał , Ciszewski Mateusz , Kozłowicz Sylwia , Maj Izabela , Ochmański Michał , Radoń Adrian
Published: June 2024

Objective

Germanium, an important component of electronics, is considered by many global economies as a critical raw material. Therefore, investigating its potential new sources is crucial for prospective technology development. This paper presents the investigation results on the leaching of liquation-feeding furnace dross using sulfuric and oxalic acid solutions.

Results

The dross contained mostly zinc (68.0% wt.) but also elevated germanium concentration (0.68% wt.). The influence of temperature, time, initial acid concentration, and liquid-to-solid phase ratio (L:S) was examined. It was found that germanium availability via leaching is limited—maximum leaching yields using aqueous solutions of sulfuric and oxalic acids were 60% (80 °C, 2 h, 15% wt. H2SO4, L:S 25:1) and 57% (80 °C, 3 h, 12.5% wt. H2C2O4, L:S 10:1), respectively.
Diagnostic performance of plasma pTau217, pTau181, Aβ1-42 and Aβ1-40 in the LUMIPULSE automated platform for the detection of Alzheimer disease
Authors: Arranz Javier , Zhu Nuole , Rubio-Guerra Sara , Rodríguez-Baz Íñigo , Ferrer Rosa , Carmona-Iragui María , Barroeta Isabel , Illán-Gala Ignacio , Santos-Santos Miguel , Fortea Juan , Lleó Alberto , Tondo Mireia , Alcolea Daniel
Published: June 2024

Background

Recently developed blood markers for Alzheimer's disease (AD) detection have high accuracy but usually require ultra-sensitive analytic tools not commonly available in clinical laboratories, and their performance in clinical practice is unknown.

Methods

We analyzed plasma samples from 290 consecutive participants that underwent lumbar puncture in routine clinical practice in a specialized memory clinic (66 cognitively unimpaired, 130 participants with mild cognitive impairment, and 94 with dementia). Participants were classified as amyloid positive (A +) or negative (A-) according to CSF Aβ1–42/Aβ1–40 ratio. Plasma pTau217, pTau181, Aβ1–42 and Aβ1–40 were measured in the fully-automated LUMIPULSE platform. We used linear regression to compare plasma biomarkers concentrations between A + and A- groups, evaluated Spearman’s correlation between plasma and CSF and performed ROC analyses to assess their diagnostic accuracy to detect brain amyloidosis as determined by CSF Aβ1–42/Aβ1–40 ratio. We analyzed the concordance of pTau217 with CSF amyloidosis.

Results

Plasma pTau217 and pTau181 concentration were higher in A + than A- while the plasma Aβ1–42/Aβ1–40 ratio was lower in A + compared to A-. pTau181 and the Aβ1–42/Aβ1–40 ratio showed moderate correlation between plasma and CSF (Rho = 0.66 and 0.69, respectively). The areas under the ROC curve to discriminate A + from A- participants were 0.94 (95% CI 0.92–0.97) for pTau217, and 0.88 (95% CI 0.84–0.92) for both pTau181 and Aβ1–42/Aβ1–40. Chronic kidney disease (CKD) was related to increased plasma biomarker concentrations, but ratios were less affected. Plasma pTau217 had the highest fold change (× 3.2) and showed high predictive capability in discriminating A + from A-, having 4–7% misclassification rate. The global accuracy of plasma pTau217 using a two-threshold approach was robust in symptomatic groups, exceeding 90%.

Conclusion

The evaluation of blood biomarkers on an automated platform exhibited high diagnostic accuracy for AD pathophysiology, and pTau217 showed excellent diagnostic accuracy to identify participants with AD in a consecutive sample representing the routine clinical practice in a specialized memory unit.
Generalized kinetic theory of coarse-grained systems. I. Partial equilibrium and Markov approximations
Authors: Gaveau Bernard , Moreau Michel
Published: June 2024

The general kinetic theory of coarse-grained systems is presented in the abstract formalism of communication theory developed by Shannon and Weaver, Khinchin and Kolmogorov. The martingale theory shows that, under reasonable, general hypotheses, coarse-grained systems can be approximated by generalized Markov systems. For mixing systems, the Kolmogorov entropy production can be defined for nonstationary processes as Kolmogorov defined it for stationary processes.
Improving Clinical Registry Data Quality via Linkage With Survival Data From State-Based Population Registries
Authors: Smith Samuel , Drummond Kate , Dowling Anthony , Bennett Iwan , Campbell David , Freilich Ronnie , Phillips Claire , Ahern Elizabeth , Reeves Simone , Campbell Robert , Collins Ian M. , Johns Julie , Dumas Megan , Hong Wei , Gibbs Peter , Gately Lucy
Published: June 2024

PURPOSE

Real-world data (RWD) collected on patients treated as part of routine clinical care form the basis of cancer clinical registries. Capturing accurate death data can be challenging, with inaccurate survival data potentially compromising the integrity of registry-based research. Here, we explore the utility of data linkage (DL) to state-based registries to enhance the capture of survival outcomes.

METHODS

We identified consecutive adult patients with brain tumors treated in the state of Victoria from the Brain Tumour Registry Australia: Innovation and Translation (BRAIN) database, who had no recorded date of death and no follow-up within the last 6 months. Full name and date of birth were used to match patients in the BRAIN registry with those in the Victorian Births, Deaths and Marriages (BDM) registry. Overall survival (OS) outcomes were compared pre- and post-DL.

RESULTS

Of the 7,346 clinical registry patients, 5,462 (74%) had no date of death and no follow-up recorded within the last 6 months. Of the 5,462 patients, 1,588 (29%) were matched with a date of death in BDM. Factors associated with an increased number of matches were poor prognosis tumors, older age, and social disadvantage. OS was significantly overestimated pre-DL compared with post-DL for the entire cohort (pre- v post-DL: hazard ratio, 1.43; P < .001; median, 29.9 months v 16.7 months) and for most individual tumor types. This finding was present independent of the tumor prognosis.

CONCLUSION

As revealed by linkage with BDM, a high proportion of patients in a brain cancer clinical registry had missing death data, contributed to by informative censoring, inflating OS calculations. DL to pertinent registries on an ongoing basis should be considered to ensure accurate reporting of survival data and interpretation of RWD outcomes.
Cardiovascular complications associated with asciminib use: A retrospective analysis.
Authors: Savani Saloni , Pawa Arpita , Mahadevia Himil , Master Samip R.
Published: June 2024

6563

Background: Asciminib, a newly developed drug, has shown promising results in the treatment of several diseases. It is a cellular tyrosine kinase inhibitor (TKI) that specifically targets ABL myristoyl pocket (STAMP) inhibitor, responsible for the malignant growth and proliferation of leukemia cells in chronic myeloid leukemia (CML) patients, assuring a positive treatment of CML. However, as with all medications, there are possible side effects that must be carefully monitored. In comparison to Ponatinib (tyrosine kinase inhibitor) which is extensively used to treat CML and exhibits a cardiovascular risk profile, cardiovascular side effects with the use of Asciminib are rarely reported in literature, prompting its use in patients at a higher risk of these events. Through this study, we aim to highlight the cardiovascular complications associated with the use of Asciminib by integrating patient experience and clinical research. Methods: A publicly available FDA Adverse Events Reporting System (FAERS) database was utilized to review cardiovascular events associated with the use of Asciminib in patients with Chronic Myeloid leukemia (CML) between 2018-2023. Cardiovascular events such as coronary artery disease (CAD), peripheral arterial disease (PAD), and cerebrovascular accidents (CVA) were reviewed. The study focused only on adverse events reported by healthcare providers and observed in adults (above 18 years old). Results: We identified a total of 563 adverse events pertaining to the use of Asciminib in patients with CML. Of which, 63 were cardiovascular events, contributing to 11.2% of the total adverse events. Out of the reported cardiovascular side effects, 29 (46%) were due to CAD, 6 (9.5%) were due to PAD, and 28 (44.45%) were due to CVA. The mortality rate amongst patients who experienced cardiovascular side effects was 11%. Moreover, cardiovascular events contributed to 7% of all mortality associated with the use of Asciminib, with CAD contributing to most of the deaths. Conclusions: It is imperative to consider the potential of cardiovascular events in patients initiated on Asciminib. This study emphasizes the importance of using patient records and medical research to obtain complete information. Patients with underlying risk factors for the development of cardiovascular diseases should be thoroughly evaluated before drug initiation. The minimum threshold for drug discontinuation should be considered in patients with suspected heart disease.
DeLLphi-301: Tarlatamab phase 2 trial in small cell lung cancer (SCLC)—Efficacy and safety analyzed by presence of brain metastasis.
Authors: Dingemans Anne-Marie C. , Ahn Myung-Ju , Blackhall Fiona Helen , Reck Martin , Hummel Horst-Dieter , Ramalingam Suresh S. , Johnson Melissa L. , Akamatsu Hiroaki , Wolf Juergen , Sands Jacob , Owonikoko Taofeek K. , Borghaei Hossein , Mukherjee Sujoy , Huang Shuang , Martinez Pablo , Paz-Ares Luis G.
Published: June 2024

8015

Background: Brain metastases affect 40%–70% of patients with SCLC. Tarlatamab, a BiTE (bispecific T-cell engager) immunotherapy targeting delta-like ligand 3, demonstrated durable responses and promising survival outcomes in patients with previously treated SCLC (10 mg Q2W) (DeLLphi-301; NCT05060016; Ahn M-J, N Engl J Med 2023). Here, tarlatamab efficacy and safety in patients with baseline brain metastases from DeLLphi-301 are reported. Methods: The DeLLphi-301 study design has been published. Patients with treated, stable, asymptomatic brain metastases were included. Subgroup analyses for efficacy (blinded independent central review [BICR] assessments) and safety by presence or absence of baseline brain metastases were performed. Intracranial activity was assessed. Post enrollment, brain imaging was performed if clinically indicated. Results: As of 27 June 2023, 186 patients had received tarlatamab (ECOG PS: 0–1; median prior lines of therapy: 2; median follow-up: 13.6 months). 29% of patients (54/186) had treated and stable brain metastases at baseline. Most patients (91%) with brain metastases had received prior local radiotherapy; 6% each had received surgery only or both radiotherapy and surgery. Overall systemic objective response rate (ORR; RECIST 1.1) was 45.3% in patients with brain metastases and 32.6% in patients without brain metastases (Table). Any grade immune effector cell associated neurotoxicity syndrome and associated neurological events occurred in 24.1% of patients with brain metastases and in 13.6% of patients without brain metastases; grade ≥ 3 events occurred in the 100 mg group only: 9.4% and 1.8%, respectively, and did not lead to tarlatamab discontinuation in any patient with brain metastases. Analysis of intracranial activity will be presented. Conclusions: Tarlatamab showed promising efficacy and a favorable benefit-risk profile in patients with previously treated SCLC and stable brain metastases. Clinical trial information: NCT05060016 . [Table: see text]
A randomized phase II study of toripalimab consolidation or observation after concurrent chemoradiotherapy in limited-stage small cell lung cancer.
Authors: Zhang PengXin , Liu FangJie , Wang DaQuan , Zheng ShiYang , Guo JinYu , Zou YingYi , Liang Ying , Zhao Yuanyuan , Qiu Bo , Liu Hui
Published: June 2024

8098

Background: In recent years, the use of immune checkpoint inhibitors has led to significant progress in the treatment of extensive-stage small cell lung cancer. However, there is limited data on the efficacy of immunotherapy in patients with limited-stage disease (LS-SCLC). Therefore, we conducted a phase II randomized study to verify the efficacy and safety of Toripalimab consolidation following definitive concurrent chemoradiotherapy (CCRT) in patients with LS-SCLC (ClinicalTrials.gov ID: NCT04418648). Methods: Patients with LS-SCLC who had achieved complete or partial response after definitive CCRT (including four to six cycles of etoposide and cisplatin , and curative-intent thoracic radiotherapy) were randomly assigned (1:1) to receive Toripalimab consolidation (240mg intravenously, every 3 weeks for 6 months) or observation. Prophylactic cranial irradiation (PCI) was recommended but not mandatory. The primary endpoint was progression-free survival (PFS) calculated from randomization, and secondary endpoints included overall survival (OS) and toxicity. Results: As of data cutoff (November 30, 2023), a total of 64 eligible patients (intent-to-treat population) were randomly assigned to the Toripalimab group (n = 31) or the observation group (n = 33), respectively. With the median follow-up of 25 months, PFS was significantly improved with Toripalimab (hazard ratio [95% CI]: 0.47 [0.22-1.02]; P = 0.04). The median PFS in observation group was 12.3 months (95% CI, 0.04-24.50), while the median PFS in the Toripalimab group has not been reached. The 24-month PFS rate was 61.6% (95% CI, 43.0%-88.3%) in the Toripalimab group and 34.8% (95% CI, 21.5%-56.3%) in the observation group. The 24-month OS was 82.7% (95% CI, 65.2%-100%; P = 0.23) in the Toripalimab group and 59.1%(95% CI, 44.2%-79.1%) in the observation group. There were 5(16.1%) and 3 (9.1%) patients in the Toripalimab group and observation group experiencing G2+ pneumonitis respectively. No G4+ toxic events occurred in either group. Conclusions: Our preliminary results suggested Toripalimab consolidation following definitive CCRT was effective and tolerable in LS-SCLC. Clinical trial information: NCT04418648 . [Table: see text]
Exploring gut microbiome markers in predicting efficacy of immunotherapy against lung cancer.
Authors: Han Wenjie , Xu Junnan , Sun Tao , Zhou Yuhang , Feng Yun , Han Li , Liu Xiaolin
Published: June 2024

8525

Background: Immunotherapy has profoundly changed the treatment landscape for lung cancer (LC) due to its tolerable safety profile and longer sustained therapeutic response. However, only about 20% of patients with locally advanced and metastatic disease can derive long-term clinical benefit from ICIs. Previous studies have suggested that the microbiome is involved in the development of LC in some way. We aimed to use the gut microbiome (GM) to model the benefit of immunotherapy and to mine the biomarkers with a global impact on immune response. Methods: We performed human gut metagenomic analysis on the responder patients and non-responder patients with immunotherapy. A total of 296 fecal samples, including baseline samples (71 responders, 98 non-responders and 72 healthy controls), and 55 samples during treatment were enrolled in our study, the taxonomic and functional features of these samples also were excavated. A machine-learning model was developed to identify responders and non-responders. At the same time, we also explored the influence of antibiotic use on the above results. Results: Specific species, Bacteroides caccae and Bacteroides uniformis, were positively correlated with responders. In non-responders, Prevotella copri was the main enrichment species. The α diversity of microbiota in responding patients was significantly higher than that in non-responding groups, and antibiotic use increased this trend. There was no significant difference in β diversity between the two groups, but LEFSE analysis also could obtain biomarkers of biological significance between the two groups. We used the biomarkers from the above analysis to construct a random forest model, and the area under the receiver operating characteristic curve (AUC) (species level: 82.10%; genus level: 79.4%). In addition, our studies suggested that metabolism such as amino acid metabolism, valine, leucine might be important in regulating the immunotherapy response that warrants further investigation. Conclusions: Overall, our study explored the relationship between microbial composition and immunotherapy efficacy in LC patients and mined relevant markers, and further research is needed to investigate the mechanisms of action of these key strains in influencing immunotherapy in the future.
Germline NQO1c.559C>T as a biomarker of genetic susceptibility to immune checkpoint blockade resistance.
Authors: Benitez Jose Carlos , Oliver Javier , Onieva Juan Luis , Cobo Manuel , Mesas Andres , Rios-Muñoz Alberto , Perez Ruiz Elisabeth , Garrido-Barros Maria , Vazquez Rojas Paula , Martinez Beatriz , Cantero-Gonzalez Alexandra , Gonzalez Andrea , Zafra Martín Juan , Barragán Isabel , Rueda Dominguez Antonio
Published: June 2024

8537

Background: Tobacco is the main risk factor for developing lung cancer. Yet, some heavy smokers do not develop cancer while others do at young ages. The study of cancer immunology has led to the surge of immune checkpoint blockade (ICB), which transformed the treatment landscape of cancer pts. NQO1 has been associated with extreme phenotypes of high risk for the development of tobacco-induced NSCLC and with poor survival outcomes for xerographs. Development of biomarkers for ICB has been mainly focused on tumor-related factors while genetic susceptibility of the host has been poorly explored to date and some evidence suggests that genetic dysregulation may enables immune escape. Methods: From June 2016 to January 2023, 326 NSCLC pts from two main University Hospitals of Malaga (Spain) receiving ICB were prospectively enrolled, blood samples were gathered. We selected a representative set of 60 consecutive pts for exome sequencing to characterize the germline contribution to resistance (progression within the first 6 months of treatment). PBMC DNA was extracted and prepared for exome sequencing. Raw sequencing data was processed and aligned to a reference genome using BWA. Base recalibration, germline variant calling and variant filtering was performed through GATK. Survival probabilities were estimated with the Kaplan-Meier method and compared using the log-rank test. We explored the lung cancer related genes among our results. Results: Median age at diagnosis of 64 (54-85). 76,6% were men. 44/60 (73,3%) were adenocarcinoma (ADC), PD-L1≥1% in 55% of patients, 22% shown PD-L≥50%. 78% had advanced disease at diagnosis. 65% received ICB in combination with chemotherapy. We found NQO1c.559C>T in 46,6% of pts (28/60). The variation was not associated with survival outcomes in the multivariant analysis (p>0.05) but with poor OS for non-ADC histology (19.7m vs 6m for mutated and WT, respectively; p<0.01). In addition, we found 26 germline variants associated with OS and PFS, and 52 variants with response to ICB. The variants were missense or involved a stop gain/loss. Conclusions: Exome sequencing analysis of germline variants could be a suitable methodology to identify subrogated biomarkers of immune resistance in NSCLC patients. NQO1c.559C>T might help to identify poor prognosis non-ADC pts in the ICB setting.
Five-year outcomes with first-line (1L) nivolumab + ipilimumab + chemotherapy (N + I + C) vs C in patients (pts) with metastatic NSCLC (mNSCLC) in CheckMate 9LA.
Authors: Reck Martin , Ciuleanu Tudor-Eliade , Schenker Michael , Bordenave Stephanie , Cobo Manuel , Juan-Vidal Oscar , Reinmuth Niels , Richardet Eduardo , Felip Enriqueta , Menezes Juliana , Cheng Ying , Mizutani Hideaki , Carbone David Paul , Lu Shun , John Tom , Aoyama Takekazu , Mahmood Javed , Hu Nan , Eccles Laura , Paz-Ares Luis G.
Published: June 2024

8560

Background: InCheckMate 9LA (NCT03215706), 1L N + I + C demonstrated long-term, durable survival benefit vs C alone in pts with mNSCLC, regardless of tumor PD-L1 expression or histology. Here, we report updated efficacy and safety data with a 5-y follow up (f/u) and outcomes in 5-y survivors. Methods: Adults with stage IV or recurrent NSCLC, ECOG PS ≤ 1, and EGFR/ALK wild-type were randomized 1:1 to N 360 mg Q3W + I 1 mg/kg Q6W + C Q3W (2 cycles; n = 361) or C alone Q3W (4 cycles; n = 358). Maintenance pemetrexed was allowed for pts with non-squamous (NSQ) NSCLC (C arm only). Assessments were OS, PFS, ORR, DOR, treatment (tx)-free interval (TFI; time from last study tx dose to start of subsequent systemic tx or death), and safety. Exploratory analyses included quantifying the number of ipilimumab doses received by 5-y survivors, as well as PFS and TFI in these pts. Results: With a median f/u of 64.5 mo (database lock, 15 Dec 2023), clinical benefit continued to be seen with N + I + C vs C in all randomized pts (Table); 5-y OS rates were 18% vs 11%, respectively. Of pts treated with N + I + C, 11% were tx-free at 5 y. Clinical outcomes favored N + I + C vs C across tumor PD-L1 expression and histology subgroups (Table). In pts with tumor PD-L1 < 1%, 5-y OS and PFS rates with N + I + C were both ~3-fold higher than with C, and 5-y DOR rates were 25% vs 0% in the respective tx arms. Among pts who discontinued N + I + C due to tx-related adverse events (TRAEs; n = 61), 37% were alive at 5 y, and the TFI rate was 22%. In analyses of 5-y survivors, PFS favored N + I + C (n = 48) vs C (n = 30; HR, 0.52 [95% CI, 0.26–1.02]), and 5-y TFI rates were 72% vs 35%, respectively. Of 5-y survivors in the N + I + C arm, 21/48 (44%) received ≥ 17 doses of ipilimumab; of those who received < 17 doses, most had discontinued ipilimumab due to TRAEs. The extended f/u revealed no new safety signals. Conclusions: 1L N + I + C maintained long-term, durable survival benefit vs C in pts with mNSCLC at this 5-y f/u, particularly in pts with tumor PD-L1 expression < 1% or squamous (SQ) histology. N + I + C increased 5-y survivorship, with improved PFS and TFI in 5-y survivors over C. These data further underscore 1L N + I + C as an efficacious tx option for pts with mNSCLC. Clinical trial information: NCT03215706 . [Table: see text]
Efficacy and safety of bronchial arterial chemoembolization (BACE) in combination with tislelizumab for non-small cell lung cancer (NSCLC): A phase II study.
Authors: Duan Xuhua , Li Hao , Kuang Donglin , Zhang Mengfan , Xu Wenze , Liang Chao , Wang Jiacheng , Han Daqian , Ren Jianzhuang
Published: June 2024

8609

Background: Bronchial artery chemoembolization (BACE) and immune checkpoint inhibitors (ICIs) are important therapy for NSCLC. The short-term benefit from BACE is considerable while the long-term survival benefits from ICIs is remarkable. This trial is designed to determine the efficacy and safety of immunotherapy with tislelizumab in addition to BACE in stage III-Ⅳ NSCLC patients (pts) who failed, refused or ineligible to receive standard treatments. Methods: In a single-arm, phase II study (NCT05058560), stage III-IV NSCLC patients who refused or were ineligible to receive standard treatments were enrolled. Patients received BACE followed by 200 mg tislelizumab every 3 weeks until disease progression, intolerable toxicities, or discontinuation determined by the investigators. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), safety, and quality of life (QoL). Results: Thirty patients were enrolled in this study between December 2021 and August 2022. The median follow-up was 12 (range, 1.5-12) months. At the data cutoff (August 31, 2023), the median PFS was 10.5 (95% confidence interval [CI], 7.8-13.2) months and the median OS was not reached. The 3 -, 6 -, and 12-month ORR were 63.3% (95%CI, 43.9%-80.1%), 56.7% (95%CI, 37.4%-74.5%), and 30.4% (95%CI, 13.2%-52.9%), respectively. The DCR at 3 months was 80% (95%CI, 61.4%-92.3%), at 6 months was 76.7% (95%CI, 57.7%-90.1%), and at 12 months was 47.8% (95%CI, 26.8%-69.4%). The expression rate of PD-L1, tumor feeding arteries, and the application times of tislelizumab were prognostic factors for PFS. No grade 3 or higher treatment-related adverse events (TRAEs) occurred. Common grade 2 TRAEs were nausea, fever, and cough. QoL improved significantly after 1 cycle of treatment compared with baseline, including global quality of life, physical functioning, and emotional functioning. Conclusions: The study demonstrated promising efficacy and manageable safety profiles of BACE plus tislelizumab for advanced NSCLC patients, indicating a potential and effective treatment option for this population. Clinical trial information: NCT05058560 .
Factors influencing career choices and post-fellowship perspectives in adult hematology/oncology physicians: A nationwide cross-sectional study.
Authors: Gonzalez Mosquera Luis , Balanchivadze Nino , Ali Faria , Meranda Matthew , Hinojosa Castro Oscar , Kuriakose Philip
Published: June 2024

9015

Background: We aimed to investigate the timing and influence of factors behind career choices in hematology and medical oncology, assess levels of job satisfaction, and identify factors contributing to professional retention and the prevention of attrition. Methods: An anonymous survey with 13 questions was distributed to practicing hematologists and oncologists who were members of the American Society of Clinical Oncology and/or American Society of Hematology. The respondents encompassed diverse areas of primary focus within the field, varied practice settings, and all geographical regions. Results: Out of 423 respondents, 66% were male and 32% female. The majority identified as White (69%), followed by Asian (19%), Middle Eastern (4%), Hispanic (3%), and Black (1%). Most were practicing either Medical Oncology (43%) or combined Hematology/Oncology (36%), with 46% working in an academic/university setting and 57% located in an urban region. In terms of timing, about a third had decided on their career choice in medical school, with the majority of the remaining having decided by residency. While most of those surveyed were practicing in the area they had hoped to, about one-sixth (17.5%) appeared to be working in an area they hadn't planned on. Most said they would choose their current profession again (67% definitely yes, 24% likely yes). Science and academic interest (81%) ranked the highest when combining the top two responses for factors influencing choice, followed by mentor influence (47%), with work/life balance (19%) and financial considerations (6%) being less frequently cited. Satisfaction levels were generally high across key dimensions (Table), with intellectual fulfillment receiving the highest satisfaction (63.1% very satisfied, 26% satisfied). Importantly, better work/life balance (37% respondents), fewer non-medical tasks (35%), and a higher salary (20%) were key considerations to deter professional attrition. Conclusions: This study offers valuable insights into the career perspectives of Hematologists and Medical Oncologists, providing a foundation for developing strategies for career development and retention initiatives within the specialty. Efforts should be undertaken to enhance participation from different minorities within Hematology/Oncology and physicians practicing Classical Hematology to identify specific support and retention needs for these areas. [Table: see text]
Formation and evaluation of the ASCO medical education community of practice (Med Ed CoP).
Authors: Brondfield Sam , Manochakian Rami , Walsh Katherine Jean , Baggstrom Maria Quintos , Henry Elizabeth , Parikh Aparna Raj , Rangachari Deepa , Barry Maura Meredith , Gao Jennifer , Giuliani Meredith Elana , Im Annie P. , Marrone Kristen A. , McNamara Mairead Geraldine , Murphy Martina Cathryn , Rosenstein Lori J , Russell Brian , Tseng Jennifer , Schwartz Jennifer E.
Published: June 2024

9022

Background: High quality education is crucial for hematology/oncology (H/O) training and lifelong learning. However, H/O has historically prioritized clinical and research careers over medical education careers. Consequently, few programs support H/O educators. A CoP is a group that shares “a concern or passion for something they do and learn how to do it better as they interact regularly.” We formed the ASCO Med Ed CoP in 2021 to provide a collaborative network and professional development venue for H/O educators. Methods: Following a published framework for developing a global health professions educator community (Establish-Grow-Sustain), we (ASCO Education Scholars Program graduates) developed CoP mission and vision statements and a leadership structure (Establish), formed committees and projects (Grow), and gathered at the ASCO Annual Meeting and via virtual Town Halls (Sustain). In 2023, we collected demographics and evaluated the CoP using a logic model focused on inputs, activities, outputs, and impact. Results: As of December 2023, the CoP includes 238 members from 143 institutions (38 [27%] non-U.S.): 207 (87%) ASCO members; 127 (53%) women, 106 (45%) men, 5 (2%) no response (NR); 111 (47%) White, 88 (37%) Asian/Pacific Islander, 27 (11%) Latinx/Hispanic, 12 (5%) Black/African-American, 8 (3%) Middle Eastern, 1 (0.4%) African, 16 (7%) NR; 146 (61%) hematologist/oncologists, 68 (29%) trainees, 6 (3%) radiation oncologists, 3 (1%) surgical oncologists, and 15 (6%) other professionals. The logic model is displayed (Table). Conclusions: The CoP has had an impact on its members, ASCO, and beyond and continues to grow and sustain itself by recruiting broadly, driving projects forward, and making structural adjustments for long-term sustainability. Upcoming projects include providing more educational resources and measuring outcomes such as changes in members’ knowledge, skills, and attitudes. Membership diversity continues to be a challenge and a priority. [Table: see text]