bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular characterization and biomarker identification in pediatric B-cell acute lymphoblastic leukemia.
Authors: Du Yu , Zhang Xiankai , Sun Ming , Yang Li , Long Fei , Qi Shanshan , Luo Linlin , Wang Chenxuan , Lv Xiaoyan , Wu Xiaoying , Zhu Liuqing , Ou Qiuxiang , Xiong Hao 
Published: June 2024

6524 Background: B-cell acute lymphoblastic leukemia (B-ALL) is the most prevalent hematologic malignancy in children and a leading cause of mortality. Despite high cure rates, the management of B-ALL remains challenging due to its high heterogeneity and propensity for relapse. This study aimed to delineate molecular features of pediatric B-ALL and explore the clinical utility of circulating tumor DNA (ctDNA) as a biomarker in B-ALL. Methods: The study analyzed 146 primary pediatric B-ALL patients who were diagnosed from August 2020 to April 2023 and received systemic chemotherapy in Wuhan Children's Hospital. Baseline bone marrow (BM) and plasma samples were collected for next-generation sequencing (NGS) to profile the mutational landscape. BM samples collected on day 19 of the treatment were utilized for minimal residual disease (MRD) testing to assess treatment efficacy. Transcriptomic profiling of baseline BM samples was performed via bulk RNA sequencing. Fisher's exact test and the Wilcoxon rank sum test were utilized to compare categorical and continuous variables between groups, respectively. A two‐tailed P-value<0.05 was considered statistically significant unless indicated otherwise. Results: Transcriptomic analysis revealed that 86.3% of patients (126 out of 146) could be categorized into 13 distinct molecular subtypes, with hyperdiploidy emerging as the predominant subtype. Baseline BM NGS identified gene fusions in 61% of patients, including 37 novel fusions previously unreported in B-ALL. Specifically, the KMT2A-TRIM29 novel fusion was detected and validated in a male child diagnosed with the KMT2A-rearranged subtype. Despite initially responding well to therapy, the patient experienced disease progression after a year, indicating a poor prognosis. We also found that elevated mutant counts and maximum-variant-allele-frequency (maxVAF) in baseline BM were associated with significantly poorer response to chemotherapy ( P=0.0012 and 0.028, respectively). Additionally, MRD-negative patients exhibited upregulated expression of immune-related pathways ( P<0.01) and increased CD8+ T cell infiltration ( P=0.047), indicating a more active immune microenvironment in better responding tumors. Baseline plasma ctDNA, which exhibited high mutational concordance with paired baseline BM samples, also demonstrated significant associations with chemotherapy efficacy, highlighting its potential as a non-invasive tool for disease monitoring and treatment outcome prediction. Conclusions: This study elucidated novel gene fusions and potential biomarkers for treatment response in pediatric B-ALL. Importantly, both baseline plasma ctDNA and BM samples offer promising prognostic insights into chemotherapy responses, paving the way for non-invasive monitoring strategies in the management of pediatric B-ALL.
In-depth analysis of responders in the phase 3 PhALLCON trial of ponatinib vs imatinib in newly diagnosed Ph+ ALL.
Authors: Jabbour Elias , Kantarjian Hagop M. , Aldoss Ibrahim , Montesinos Pau , Leonard Jessica Taft , Gomez-Almaguer David , Baer Maria R. , Gambacorti-Passerini Carlo , McCloskey James K. , Minami Yosuke , Papayannidis Cristina , Rousselot Philippe , Vachhani Pankit , Wang Eunice S. , Yang Lin , Hennessy Meliessa , Vorog Alexander , Patel Niti , Ribera-Santasusana Jose-Maria 
Published: June 2024

6533 Background: Ponatinib, a third-generation BCR::ABL TKI, has potent activity against all clinically relevant BCR::ABL1 variants, including T315I. PhALLCON (NCT03589326), a phase 3 trial comparing frontline TKIs in adults with Ph+ ALL, met its primary endpoint with a higher rate of minimum residual disease–negative (MRD-neg) complete remission (CR) at end of induction (EOI) with ponatinib vs imatinib (34.4%/16.7%; P=0.002). Here, we report response rates of MRD-neg at any time and PFS by age and BCR::ABL1 variant subgroups. Methods: Adults with newly diagnosed Ph+ ALL were randomized 2:1 to ponatinib (30 mg QD reduced to 15 mg QD upon MRD-neg CR at or after EOI) or imatinib (600 mg QD) plus 20 cycles of reduced-intensity chemotherapy (induction: 3 cycles; consolidation: 6 cycles; maintenance: 11 cycles), followed by single-agent ponatinib or imatinib until disease progression or unacceptable toxicity. Hematopoietic stem cell transplant (HSCT) was per investigator’s discretion. Post hoc analyses compared MRD-neg ( BCR:: ABL1IS ≤0.01%; MR4) at any time and PFS (any-cause death, failure to achieve CR by EOI, relapse from CR, or failure to achieve/loss of MRD-neg) by age (</≥65 y) and BCR:: ABL1 variant (p190/p210). Data cutoff: Aug 12, 2022. Results: In the population of randomized patients (pts) with p190/p210 confirmed by central lab (n=232; 154/78 ponatinib/imatinib; median follow-up 20.1 mo), 68% vs 50% in the ponatinib vs imatinib arms were MRD-neg at any time, with similar benefit of ponatinib across age and variant subgroups (Table). Median PFS was more than twice as long with ponatinib vs imatinib across subgroups (Table). Pts achieving MRD-neg at any time were less likely to have HSCT with ponatinib vs imatinib (32%/56%). Among 107/42 pts without HSCT, exposure was >2-fold longer in the ponatinib vs imatinib arms (median 12.8/5.1 mo) with comparable rates of arterial occlusive (3%/2%) and venous thromboembolic events (11%/12%), and discontinuations due to TEAEs (13%/14%). Conclusions: Ponatinib was superior to imatinib in combination with reduced-intensity chemotherapy for frontline treatment of Ph+ ALL, with higher rates of MRD-neg at any time, substantially longer PFS across age and BCR::ABL1 variant subgroups, and a safety profile comparable to imatinib. Clinical trial information: NCT03589326 . [Table: see text]
Evaluation of treatment outcomes with CPX-351 in adults with AML: A meta-analysis.
Authors: Sandhu Michael , Ashok Kumar Prashanth , Shi Charles W , Sidhu Jasleen , Ombada Mulham , Parekh Deevyashali , Ghimire Krishna Bilas , Gentile Teresa 
Published: June 2024

6540 Background: CPX-351 is a liposomal formulation of cytarabine and daunorubicin which has shown survival benefit when compared to 7+3 in older adults with myelodysplasia-related (AML-MRC) and therapy-related AML (t-AML). Aiming to investigate the clinical efficacy of CPX-351 against 7+3 in adults with AML, we performed a meta-analysis. Methods: A systematic search with controlled vocabulary encompassing AML, CPX-351 and 7+3 was conducted in PubMed, Embase, Scopus, and Cochrane on November 1, 2023 with no search restrictions. 3461 were found; 2581 were left after duplicates were removed using Mendeley 1.19.8. Remaining records were imported into Rayyan and independently screened by 2 reviewers. 8 studies were included in the analysis as they provided data for both CPX-351 and 7+3. 17 studies only including CPX-351 were identified. RevMan was used to analyze the Odds Ratio (OR) with 95% Confidence Interval (CI), derived from random effects (RE) model with Mantel-Haenszel (MH) method. Results: We identified 8 studies comparing CPX-351 to 7+3, encompassing a total of 1368 total patients: 44% (604/1368) received CPX-351, 56% (764/1368) received 7+3. Most patients had AML-MRC or t-AML. The median age in the CPX-351 group was 66 (range 58-67) and in the 7+3 group was 67 (range 58-67). The median overall survival grossly favored CPX-351 with 10.3 months (range 8.8-22 months) compared to 6.2 months (range 4.6-12 months) in 7+3. The OR of complete remission (CR) for CPX-351 versus 7+3 using the RE model was 1.66 (CI=1.15-2.39, p=0.006, I2=55%). Similarly, the OR of patients undergoing hematopoietic stem cell transplantation (HSCT) for CPX-351 versus 7+3 was 1.52 (CI=1.01-2.30, p=0.05, I2=47%). Including the additional 17 studies with CPX-351, the overall CR rate for all patients was 49%. Average 30-day mortality with CPX-351 was 4.9%. Conclusions: From our analysis, the OR of attaining CR and HSCT were shown to be significantly improved with CPX-351 when compared to conventional 7+3 chemotherapy in adult patients with AML. Both groups had similar median age, and patients in the CPX-351 arm had longer median overall survival. Our meta-analysis highlights that while CPX-351 achieves CR/HSCT at a higher rate than 7+3, data in younger populations (<60 years old) and patients with de novo AML are sparse. Heterogeneity between studies and lack of mutational analysis are limitations of our study. [Table: see text]
Treatment of acute myeloid leukemia with Orca-T.
Authors: Pantin Jeremy Mark , Patel Sagar S. , Faramand Rawan , Gandhi Arpita , Salhotra Amandeep , Oliai Caspian , Srour Samer Ali , Dholaria Bhagirathbhai R. , Pavlova Anna , McClellan J. Scott , Agodoa Irene , Li Ai , Fernhoff Nathaniel , Abedi Mehrdad , Meyer Everett 
Published: June 2024

6552 Background: Allogeneic hematopoietic stem cell transplants (alloHSCT) offer a potential curative treatment for many hematological cancers, however, traditional alloHSCT is associated with high mortality from complications including infection, graft versus host disease (GvHD) and relapse. Orca-T is an investigational allogeneic T-cell immunotherapy that includes stem and immune cells, derived from allogeneic donors, that leverages highly purified, polyclonal donor regulatory T cells to control alloreactive immune responses. In this sub-group analysis, we evaluated the safety and efficacy of patients with acute myeloid leukemia who were treated with Orca-T. Methods: Data from 37 patients with the diagnosis of acute myeloid leukemia (AML) in CR/CRi who received myeloablative conditioning with busulfan, fludarabine, and thiotepa (BFT) followed by Orca-T by 6/30/22 as part of a multicenter phase 1b single-arm trial (NCT04013685) are reported here. Patients enrolled in the phase 1b trial who did not meet these criteria were not included in this analysis. Patients received BFT prior to Orca-T, followed by single-agent GvHD prophylaxis with tacrolimus, and had an 8/8 related or unrelated matched donor. Donors were matched via DNA-based high-resolution typing of HLA-A, -B, -C, and -DRB1. Results: Orca-T was successfully manufactured at a centralized GMP facility, distributed, and infused at study sites throughout the U.S. Vein-to-vein time (i.e. time between end of donor apheresis to start of recipient’s Orca-T infusion) was < 72 hours for all patients, with the majority < 60 hours. Median age was 51 years, 49% were female and 16% were of Hispanic or Latino ethnicity. Twenty-three (62%) had matched related donors and 14 (38%) had matched unrelated donors. Baseline HCT-CI score was 3 and 4 in 27% and 8% of the patients, respectively. The majority had intermediate DRI scores (89%) and 41% were MRD positive at baseline. The median duration of follow-up was 14 months. Relapse-free survival at 12 months was 81.4% (95% CI: 62.9, 91.2). Non-relapse mortality and overall survival were 0% and 100% at 12 months, respectively. Conclusions: These encouraging results suggest that investigational Orca-T could represent a reduced toxicity alternative to conventional alloHSCT. This combination of Orca-T with myeloablative BFT led to > 80% RFS without treatment related mortality, and 100% overall survival in this AML patient population. These outcomes were accomplished with consistent and reliable cell manufacturing and distribution of Orca-T at a national scale. A multi-center randomized controlled phase 3 trial comparing Orca-T to SOC, utilizing BFT or TBI-based conditioning, will complete enrollment during the first half of 2024. (NCT05316701). Clinical trial information: NCT04013685 .
Impact of pneumocystis pneumonia on clinical outcomes in patients with lung malignancy compared to other malignancies.
Authors: Olafimihan Ayobami Gbenga , Jackson Inimfon , Ozogbo Stanley , Olatunji Gbolahan , Kokori Emmanuel , Aderinto Nicholas , Fawehinmi Praise , Mullane Michael Russell , Sueldo Alexandra , Vallejo Alejandro 
Published: June 2024

e20001 Background: Pneumocystis pneumonia (PCP) is an opportunistic infection that causes significant morbidity and mortality in cancer patients. Although infrequent in solid malignancies, limited studies suggest that PCP portends a worse outcome in patients with lung cancer. We examined hospitalization outcomes for PCP among patients with lung cancer relative to other malignancies. Methods: A retrospective cohort analysis using the Nationwide Inpatient Sample (NIS) database (2010-2019) was conducted. Using ICD-9 and ICD-10 codes, cancer patients admitted for PCP were identified and stratified based on their diagnosis of lung cancer versus other cancer types. Primary outcomes were inpatient mortality, length of stay (LOS), and total hospital charges (THC). Secondary outcomes included odds of mechanical ventilation, ICU care, bronchoscopy, and palliative care. Statistical analyses were performed using t-tests, univariate and multivariate logistic regression. Results: Among 5,408 hospitalizations for PCP in cancer patients, 10.6% had a diagnosis of lung cancer and 89.4% had other cancer types. Lung cancer patients were older (mean age: 66 vs 62 years; p = 0.001) and had a higher Charlson comorbidity burden (>2) compared to those with other cancers (69.8 vs 34.2%; p<0.001). 31% of lung cancer patients admitted for PCP died compared to 16% of patients with other cancer types ( p<0.001). Multivariate regression analysis showed that hospitalized PCP patients with lung cancer had two-fold higher odds of hospital-associated mortality relative to those with other cancer types (adjusted odds ratio (aOR): 2.2; 95% confidence interval (CI): 1.39-3.37; p = 0.001). Both cohorts had similar LOS (aOR: 0.86; P=0.61; 95% CI: 0.5-1.5) and THC (β -15,377; p=0.113; 95% CI= -34,407-3,653). Among secondary outcomes, lung cancer patients admitted for PCP had higher odds of mechanical ventilation (25.3 vs 17.7%; aOR: 1.61; p = 0.046) and palliative care utilization (24 vs 13%; p=0.002). Conclusions: Pneumocystis pneumonia is associated with significantly higher inpatient mortality among patients with lung cancer compared to other cancers. These patients also had higher rates of mechanical ventilation and palliative care utilization. Health care providers need to maintain a high index of suspicion to facilitate early diagnosis and intervention in order to mitigate adverse outcomes.[Table: see text]
Anticoagulation and lung cancer mortality: A National Inpatient Sample analysis 2020.
Authors: Kasire Sripada Preetham , Mylavarapu Maneeth , Neupane Karun 
Published: June 2024

e20003 Background: Cancer can induce a hypercoagulable state, which can lead to clinically apparent venous thromboembolism. Studies have established a relationship between hypercoagulable state and lung cancer. However, the prognosis of lung cancer patients on anticoagulation is not well studied. Furthermore, the effect of anticoagulation has remained ambiguous due to the risk of bleeding, and the decision is made clinically. In this study, we aim to determine the impact of long-term anticoagulation on mortality in patients with lung cancer hospitalizations. Methods: This is a retrospective analysis with data extracted from National Inpatient Sample (NIS) data from 2020. All the hospitalizations with lung cancer using the ICD 10 (International Classification of Diseases tenth revision) codes were included. The study cohort was grouped into those who were on long-term anticoagulants and those who were not. Demographics (age, race, sex, region, and hospital size), co-morbidities, and hospitalization costs were compared between the two groups of patients. As the primary outcome, the odds of mortality were analyzed. A p < 0.05 was considered statistically significant. Results: Out of 378470 patients who were hospitalized with lung cancer in 2020, 51,100 (13.5%) were on long-term anticoagulation therapy. The anticoagulation group was relatively older (median age, 71.64 years vs. 69.15 years), male predominant (54.69% vs 50.69%), and predominantly white (81.39% vs 76.49%). The anticoagulant group had a higher prevalence of prior history of DVT/PE (31.78% vs. 4.31%) and a higher Charleston co-morbidity index score (6.08 vs 5.85). The adjusted odds ratio of mortality in the anticoagulation group was 0.77, 95% CI (0.71-0.84, p < 0.0001). Furthermore, the average length of stay was approximately half a day shorter, and the total cost of hospitalization was $12,539 less in the anticoagulation group. Conclusions: This NIS study showed statistically significant findings, indicating that lung cancer patients who are on anticoagulation experienced lower odds of mortality, shorter length of stay, and lesser costs of hospitalization. However, the anticoagulation group was found to have a higher prevalence of co-morbidities and a higher co-morbidity index. Hence, further research with prospective studies needs to be done to understand the reasons behind these associations.
Reducing the risk of grade 3 or greater radiation pneumonitis after radical radiotherapy to the lung.
Authors: Yan Yujie , Kang Jingjing , Yang Shuangyan , Qian Cheng , Zhang Ying , Yuan Xiaoshuai , Hu Min , Zhu Yaoyao , Jiang Chenxue , Hu Minren , Zhao Ruifeng , Zhao Lan , Yaping Xu 
Published: June 2024

e20008 Background: Radiation pneumonitis (RP) is the most common adverse response in patients with lung cancer receiving thoracic radiotherapy. Higher grade RP is more likely to lead to mortality and poor quality of life, which could be abated by rigorous treatment standards formulated with individualized clinical characteristics. In this study, we aimed to identify the best clinical prognostic model for evaluating patients with lung cancer after radical radiotherapy. Methods: We collected information of RP patients in recent years and established the new consensus on the diagnosis and treatment of radiation-related pneumonitis. In a nutshell, clinical data of patients treated with radical radiotherapy were collected from August 2020 to August 2022, and part of patients from August 2021 to August 2022 was been intervented by treatment methods. The interventions included limited irradiation of the planning target volume (PTV), individualized lung dose limitation, and standardized steroid therapy. Clinical characteristics including baseline and treatment data were obtained from 693 patients, including 623 patients in the training cohort and 70 patients in the test cohort. Three models were built using different screening methods, including multivariate logistics regression (MLR), backward stepwise regression (BSR), and random forest regression (RFR), to evaluate their prognostic power. Overoptimism in the training cohorts was evaluated by four validation methods including hold-out, 10-fold, leave-one-out, and bootstrap methods, and extra data were used to evaluate the predictive performance of the model. Model calibration, Decision curve analysis (DCA), and evaluation of the nomograms for the three models were completed. Results: The incidence of RP was significantly decreased after the interventions compared to before (68.80% vs. 59.56%, P < 0.05), and the probability of grade 3 or higher RP also decreased from 11.97% to 6.67% (P < 0.05). A model of intervention, interstitial lung disease (ILD), concurrent chemoradiotherapy, standardized steroids, carbon monoxide diffusing capacity (DLCO) > 86.9%, and total lung volume exceeding 5 Gy (V5) > 35.2% for the radiological parameter had the best discriminative ability with an area under the curve of 0.963 (95% CI: 0.938–0.989) in the training chort . The calibration curve showed good agreement between the predicted and actual values, and the DCA showed a positive net benefit for the final model based on the nomogram. Conclusions: The implementation of standardized interventions for the prevention and treatment of RP accompanied with standardized use of steroids resulted in a significant decrease in the incidence of grade 3 or higher RP. Early intervention and methods for reducing the complications of high-dose steroids will be explored in future work.
Constructing a machine learning-based non-invasive liquid biopsy model for lung cancer detection via miRNA sequencing.
Authors: Hsieh Jason Chia-Hsun , Hsieh Tsung-Ting , Lee Ko-Han , Tu Yu-Hsuen , Chang Po-Ya , Wu Eva Yi-Hsuan , Chang Yu-Chuan , Lu Yen-Jung 
Published: June 2024

e20014 Background: Lung cancer is a prevalent and fatal disease, ranking second among common cancers globally. Early detection and prompt treatment significantly improve survival rates for most cancers, including lung cancer. Presently, low-dose computed tomography (LDCT) is a widely accepted tool for early lung cancer screening. However, it exhibits a high false-positive rate of up to 95%, resulting in overdiagnosis and causing anxiety among patients awaiting diagnosis results. Therefore, investigating alternative effective interventions would provide physicians with additional tools for evaluating lung cancer and making informed decisions. This study employs the concept of liquid biopsy, utilizing next-generation sequencing (NGS) to gather miRNA profiles, aiming to construct a machine learning-driven model for the detection of lung cancer. Methods: We assembled case-control cohorts, comprising 74 lung cancer cases (stage 0-II: 66; III-IV: 8) and 74 age- and gender-matched healthy control subjects, recruited from Chang Gung Memorial Hospital in Linkuo, Taiwan. Plasma derived from whole blood was collected from each subject before any cancer surgery or treatment. Subsequently, we extracted miRNA from the plasma and constructed libraries using the QIAseq miRNA Library kit for miRNA sequencing conducted on the Illumina NextSeq550 platform. RNA-seq data analysis was performed on miRNA sequencing data using the QIAGEN RNA-seq Analysis Portal 5.0. The count per million base (CPM) derived from the quantification results was utilized for differential analysis and constructing the machine learning model. To assess the model's performance, we reserved 10% of the subjects for isolated testing, while the remaining 90% underwent 10-fold cross-validation (CV). Results: The final model, built using logistic regression with six significant differentially expressed miRNAs (fold change > = 2 and P-value < = 0.01), achieved optimal performance. The 10-fold CV demonstrated accuracy: 97.73%; sensitivity: 98.48%; specificity: 96.97%; positive predictive value: 97.01%; negative predictive value: 98.46%. In isolated testing, all 16 subjects, including 8 cases and 8 controls, were correctly identified. Conclusions: This study with 148 subjects showcases the potential of NGS and machine learning for early-stage lung cancer detection via liquid biopsy. However, the sample size is relatively small, lacking cross-site subjects. Therefore, an additional multi-center clinical trial is underway to gather more subjects, aiming for a deeper investigation and more concrete conclusions in the near future.