bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unveiling the impact: Exploring thrombotic outcomes in hospitalized patients with COVID-19—Comparing those with and without a cancer diagnosis.
Authors: Bhinder Muhammad Mujtaba , Davis Elaine A. , Welch Christine A. , Kamran Amir Shahzad 
Published: June 2024

e23318 Background: There is a shared hypercoagulable association of COVID-19 and cancer, noting an increased risk of thromboembolic events (TEE)in both conditions. The current study focuses on patients with concurrent COVID-19 and underlying cancer and compares incidence of TEE and related outcomes in this complex intersection of acute viral infection and oncological challenges. Methods: In this retrospective cohort study, we examined data from the Charleston Area Medical Center’s (CAMC) COVID-19 Registry, involving 5,479 adult, symptomatic, PCR-positive COVID-19 hospitalized patients (3/1/2020 to 1/20/2024). Demographics, co-morbidities, lab values, treatments, and outcomes were assessed. Propensity score matching (3:1) non-cancer patients vs those with an active cancer diagnosis was undertaken using sex and age. SAS 9.4 was utilized for the analysis. The groups were compared using Chi-square/Fisher’s Exact tests for categorical variables and t-tests for continuous variables and a logistic regression modelling to determine differences in key variables, the incidence of thromboembolic events and other outcomes. Results: After propensity matching, 1,623 non-cancer and 427 active cancer patients were included. The incidence of venous thromboembolism (VTE) was higher in the active cancer group (9.42% vs 4.2%, P < 0.001) with no significant differences in acute stroke. Intensive care unit (ICU) admissions, mechanical or non-invasive ventilation requirement, and mortality were not different although more patients with cancer were discharged to hospice (11.8% vs 3.3%, P < 0.001). However, mean D-dimer results in both groups were > 2.5 mg/L, it was not performed consistently. The active cancer group had greater frequencies of abnormal ferritin levels (59.1% vs 49.1%, P=0.01), and elevated procalcitonin levels > 0.05 ng/mL (72.9% vs 60.6%, p < 0.001). Among key treatments, remdesivir was used more frequently in cancer patients (41.4% vs 35.7%, P < 0.01). In addition to the cancer diagnosis (OR = 1.729 95% CI [1.1-2.8] P =0.02), LOS > / = 7days was also a predictor of TEE (OR= 1.825 95% CI [1.1-2.9] P < 0.01). Conclusions: Symptomatic VTE rates in our COVID-19 and active cancer cohort align with published studies. Diligence in evaluation of D-dimer, early detection of TEE and adherence to published guidelines in prophylaxis and treatment is recommended.
Evaluating hemoglobin thresholds for blood transfusions in oncology patients admitted in the intensive care unit.
Authors: Boban Abijha Biju , Strike Andrew , Patel Dhaval , Rynarzewska Ania 
Published: June 2024

e23319 Background: Current guidelines recommend transfusing at a hemoglobin (Hb) threshold of 7g/dl. There is a lack of evidence to support a specific threshold for transfusion in patients with active malignancy admitted to the Intensive Care Unit (ICU). This study attempts to determine an evidence-based threshold for blood transfusions in cancer. Methods: A retrospective study was done to study 561 patients with an active cancer diagnosis admitted to Northeast Georgia Medical Center ICU between 2017 and 2023 that received at least one unit of blood transfusion. Chi-Square test of association with Bonferoni correction was applied to the top five common cancers seen in ICU: Leukemia, Lymphoma, Brain tumors, Lung cancers, and GI cancers. It compared three thresholds of transfusion and looked for any change in mortality risk, readmissions, need for multiple transfusions, prevalence of new onset or recurrent heart failure, development of altered mental status, or cardiac arrest. The three thresholds for transfusions that were studied were < 7g/dL, < 8 g/dL, and > 8 g/dL. The studied cancer types were further divided into either hematologic or solid tumors. Results: There was a decrease in overall cancer readmissions compared to expected over 30 days by 64%, 60 days by 44%, and 90 days by 47.5% when transfused for a Hb threshold of <8 g/dL compared to an increase of 22.8%, 18.2%, and 18.8% in 30-, 60-, and 90-day readmissions when transfused for a Hb threshold of <7 g/dL. When divided by cancer types, there was a significant decrease from expected by 30%, 47.5%, and 56% in 30-, 60-, and 90-day readmissions for patients with solid tumors for a Hb threshold of < 8 g/dL. Mortality risk decreased by 50% and the need for multiple transfusions decreased by 21% when transfused for a Hb threshold of < 8 g/dl. Of note, there was no significant association between transfusion levels and associated reactions. There was a decrease of 82% in altered mental status when transfused for threshold of Hb <8 g/dL. Finally, significant association was not found with AKI, cardiac arrest, or heart failure and any Hb transfusion thresholds. Conclusions: Based on these results, there is a significant mortality benefit and decreased length of stay for cancer patients admitted to ICU when blood transfusion is undertaken at a hemoglobin threshold of <8g/dL. These results should be further investigated in a randomized controlled trial.
Comparison of drug treatment intent in stage IV solid tumors in EU4+UK.
Authors: Gallo Federico , Ng Elsa 
Published: June 2024

e23323 Background: The goal of cancer treatment may vary based on multiple factors. This study uses real-world data to compare treatment intent, and its evolution over time among patients with solid tumors; whilst we focus on stage IV cohorts, a comparison vs. stage I-III patients is also made, for context. Methods: Ipsos’ Global Oncology Monitor is a multi-stakeholder, physician-reported syndicated patient record database. 3,308 solid tumor-treating physicians (France = 834, Germany = 709, Italy = 578, Spain = 626, UK = 561) were screened for seniority and caseload and submitted data on 329,154 patients (France = 64,985, Germany = 77,709, Italy = 64,507, Spain = 65,427, UK = 56,526). Data were collected online from January 2020 to September 2023. Sample data were projected to the wider clinical population using market sizing extrapolations. Results: Of all solid tumor patients reported, regardless of stage, control cancer spread and/or growth (extend life) is the most common cited goal by sampled physicians when choosing drug therapy for the patient in question (average ~50% reported patients). This is followed by intent of eliminating cancer cells to undetectable levels (curative), while the intent to ease cancer symptoms (palliative) is typically less likely to be selected. Treatment intent at stage I-III showed similar trends, with curative being the most common goal (average ~70% of reported patients). When focusing on Stage IV solid tumors we observe life extension generally emerging as the main intention; a more nuanced analysis reveals similarity between Germany and Spain, where palliative intent is cited more often by sampled physicians compare to other regional counterparts. These differences are shown in Table 1. Little change seen in curative intent from 2020 to 2023 across all regions, except UK, where a downward trend is reflected from Q3 2022 onwards with a concurrent increase in extend life. Conclusions: This study indicates that treating to cure is a common aim for EU4+UK sampled physicians when giving drug therapy to stage I-III solid tumor patients, whilst extending life is the notable goal when considering stage IV patients. Additional analysis of tumor- and region-specific changes over time may help establish any potential influences on drug treatment choice due to factors such as reimbursement and treatment type availability. Further investigation using comparator cohort is warranted. [Table: see text]
Chalazion associated with proteasome inhibitors approved for multiple myeloma: Analysis of FAERS database.
Authors: Singh Harkarandeep , Kaur Uttamjot , Neupane Niraj , Saeed Hassan , Kharel Himal , Gill Prabhsimrat , Shrestha Asis 
Published: June 2024

e23325 Background: Proteasome inhibitors (PI) are a class of drugs used in the treatment of Multiple Myeloma. The FDA has approved three PIs for this indication (Bortezomib, Carfilzomib, and Ixazomib). Various studies, and case reports have described the occurrence of chalazion with Bortezomib use and subsequent discontinuation of therapy but it’s association with other PIs from the class remains poorly understood. Methods: We conducted a retrospective pharmacovigilance study using the FDA Adverse Event Reporting System database to analyze the strength of association of chalazion with Bortezomib, and with other Proteasome Inhibitors in patients above 18 years of age. We employed disproportionality signal analysis and calculated the reporting odds ratio with a 95% confidence interval. Results: Within the FAERS database, a total of 78,596 adverse events were reported with the use of the three FDA approved PIs in adults, out of which chalazion accounted for 56 cases. Most of the cases were reported with Bortezomib use (54 cases), followed by Carfilzomib (2 cases), and Ixazomib (1 case). In cases with mention of sex, and age, 64.7% were in females, and 35.3% in male patients, whereas 47% patients were within the age group of 18-64, and 53% being above 64 years of age. While most of the cases had non-serious outcomes, death was reported in 2 cases, and hospitalization was needed for 5 cases. Only Bortezomib was associated with a significantly positive signal strength (ROR 32.9, 95% CI 25.1-43.1, Chi-squared Yates 1596.27). Conclusions: The study offers the largest retrospective review of association of chalazion with proteasome inhibitors. It is most strongly associated with Bortezomib use, and females are twice as likely to develop it as compared to males. Elderly patients also seem to be at a slightly higher risk. Overall, chalazion seems to account for only a small number of side effects reported with proteasome inhibitors, and a majority of cases have non-serious outcomes.
Understanding clonal heterogeneity and mechanisms of methotrexate resistance in two osteosarcoma PDX models.
Authors: Jusu Sylvester , Longo-Sorbello Giuseppe S. A. , Zhongting Zhang , Zhaohui Xu , Roth Michael , Harrison Douglas James , Gill Jonathan Benjamin , Gorlick Richard Greg 
Published: June 2024

e23512 Background: Osteosarcoma is a primary malignant bone tumor that is known to have significant intratumoral heterogeneity with branched cancer evolution. The lung is the most frequent site of metastatic disease and relapse occurs in more than 30 % children and young adults. It has been revealed that the metastatic ability and resistance of cancers including osteosarcoma might be due to the presence of a subset of cells within the intra-tumorally heterogeneous population. We investigated the emergence of resistant clonal subpopulations following targeted methotrexate treatment in two patient derived xenograft (PDX) models in vitro and in vivo. Our aim was to not only track the subclonal population of cells that establish in the lungs but also to identify clonal drivers and the mutational signature of the genes and pathways involved in MTX resistance. Methods: We previously established 20 barcoded osteosarcoma PDX models and demonstrated that the application of methotrexate (MTX-IC95) treatment as a selective pressure in seven models produces clonal subpopulations that were more resistant to MTX. In the current work we used barcoded next generation and RNA sequencing techniques to map the clonal and transcriptomic architecture of MTX resistant single clones in M36 and OS252 PDX models. We next injected the barcoded PDX cells intratibially in twenty severe combined immunodeficiency disease (SCID) mice to track the clonal population/subpopulation of cells that metastasize to the lungs. Following primary tumor growth, limb amputation was carried out and mice were treated with methotrexate or vehicle for two weeks. Primary tumor, blood and lung samples were collected after death from metastasis or euthanasia. All samples collected were snap frozen in liquid nitrogen and stored at -800C. DNA and RNA was extracted and analyzed by PCR, NGS or WES to map clonality, mutational and evolutionary profiles. Results: MTX treated single clones showed diversity and barcode abundance when compared to vehicle; barcode abundance reduced in the resistant clonal subpopulations when compared to the vehicles. Ten unique subclones were shared in both vehicle and MTX resistant clones in M36 while OS252 had only one shared subclone respectively. More than 50% of the injected mice developed primary tumors and matched lung micrometastases. We are currently analyzing both targeted and RNA sequencing results to further understand clonality, the mutational signature of the genes (DHFR, MTR, FPGS, GGH) and pathways involved in MTX resistance. Conclusions: We investigated mechanism of methotrexate resistance in two barcoded PDX models in vitro and in vivo using cytotoxicity, next generation and RNA sequencing techniques. Targeted amplicon sequencing of key genes involved in antifolate pathway will yield new information on clonal evolution and mechanisms of resistance.
Correlation between imatinib trough concentration and efficacy in patients with advanced GIST with different genotypes.
Authors: Xia Yanzhe , Zhang Xinhua , Jiang Aiting , Guo Xiaodan , Lin Jiahui , Huang Shaoqing , Cai Shirong , He Yulong , Tang Ke-Jing 
Published: June 2024

e23515 Background: Imatinib (IM) has significantly enhanced the prognosis of patients (pts) with advanced gastrointestinal stromal tumors (GISTs). The clinical outcomes may correlate with IM exposure. However, the efficacy threshold, particularly based on different primary KIT mutant, remains undefined. This study aimed to establish the efficacy threshold of IM plasma trough concentration (Cmin) at steady-state in Chinese pts with advanced GIST, additionally to define subgroup thresholds based on various primary KIT mutations. Methods: This was a single-center, prospective, observational cohort study. Pts with histologically confirmed recurrent/metastatic GIST who received regular IM treatment and had undergone at least two measurements of steady-state IM Cmin were enrolled from Jul 2017 to Jun 2022. Clinical outcomes including objective response rate (ORR), survival, and IM Cmin were assessed. Results: A total of 168 pts with a median age of 52y were enrolled. The primary lesion locations comprised stomach, small intestine, rectum and others. Metastatic lesions were found in the liver, peritoneum, both liver and peritoneum and others. Median sum of longest diameter of target lesions was 10.7cm. Of 168 pts, 117 (69.6%) harbored KIT 11, 27 (16.1%) harbored KIT 9, 5 (3.0%) harbored PDGFRA, and 9 (5.4%) were KIT/PDGFRA wild type. During IM response period, 104 pts combined with surgical treatment (surgery or interventional therapy). After a median follow-up duration was 50.6m (range, 16.3–189.8), 72 pts had disease progression and 20 died. Estimated median progression-free survival (mPFS) for all patients was 79.4m (95%CI 55.7–103.1). The median overall survival was not reached. A Cmin threshold of ≥738ng/ml defined by log-rank test was associated with longer PFS for the whole population (P = 0.002) irrespective of other clinical characteristics. Pts with an IM Cmin below 738ng/ml exhibited a shorter mPFS (25.3m, 95%CI 41.9–97.1) compared to those surpassing this threshold (96.7m, 95%CI 65.8–127.6). The ORR for the whole population was 73.0% (CR 2.2%, PR 70.8%), with no significant difference observed between pts with IM Cmin below and above 738ng/ml. For pts with KIT 11 and KIT 9 mutations, the efficacy thresholds for IM Cmin were ≥680ng/ml and ≥1877ng/ml, respectively. Multivariate Cox regression analysis revealed that IM Cmin ≥738ng/ml, primary gastric origin, liver-only metastasis, sum of target lesions diameter ≤5cm, KIT 11 mutation, and combined with surgical treatment were favorable prognostic factors. Conclusions: IM exposure significantly correlates with clinical benefits in advanced GISTs, with an IM Cmin above 738ng/ml associated with a longer PFS in Chinese population. Considering different primary KIT mutant, a threshold of 680 ng/ml could be considered for efficacy in KIT 11 mutations, while a higher Cmin of 1877 ng/ml was necessary for KIT 9 mutation.
The prevalence of fibroadenoma-like areas in malignant phyllodes tumors of the breast: A retrospective analysis from a referral center.
Authors: Valenza Carmine , Olmeda Edoardo , Porta Francesca Maria , De Pas Tommaso Martino , Gaeta Aurora , Castellano Grazia , Santoro Celeste , Battaiotto Elena , Chiappini Giulia , Trapani Dario , Coppola Sara , Conforti Fabio , Mattar Denise , Gandini Sara , Veronesi Paolo , Guerini Rocco Elena , Pennacchioli Elisabetta , Curigliano Giuseppe 
Published: June 2024

e23522 Background: Malignant phyllodes tumors of the breast (B-MPT) are supposed to arise de novo or to derive from a fibroadenoma/benign phyllodes tumor ("secondary"), through a MED12-dependent pathway. Secondary B-MPTs may be associated to better outcomes: both the history of previous fibroadenomas and the presence of MED12 mutations were demonstrated to be associated to improved recurrence-free survival, in small case series. We assessed the prevalence and the prognostic value of fibroadenoma-like areas (FLA) in the context of B-MPTs, which were described as potentially associated with MED12 mutations (Pareja, 2017). Methods: Single-center, retrospective, translational study conducted at European Institute of Oncology. Consecutive patients aged 18 years old or more, with non-metastatic B-MPT, who underwent surgery from Jan 2000 to Dec 2021, were included. FLA were defined as intracanalicular, pericanalicular or myxoid areas of low stromal cellularity, lacking cytologic atypia and mitotic activity. All specimens were reviewed by three pathologists. The endpoints were the cumulative incidences of distant and local recurrences. Results: 89 patients were included (Table). After a median follow-up of 6.4 years, 18 and 14 local and distant recurrences were registered, respectively. The cumulative incidences at 5-years of local and distant recurrences were 19% (95% Confidence Interval [CI], 11–28%) and 11% (95%CI, 5–18%). 47% of tumors had FLA, which were associated with lower ( < 15/10HPF) mitoses (p = 0.05). No pathologic feature was associated with distant or local relapse. The presence of FLA areas was associated with fewer local recurrences, without reaching the statistical significance (p = 0.14); no difference in terms of distant recurrences emerged (p = 0.61). Conclusions: 47% of B-MPTs are characterized by FLAs, which are associated with a lower mitotic count. The association between FLAs and fewer local recurrences did not reach the threshold for statistical significance, probably due to the small number of events. The prognostic role of FLAs needs to be assessed in a larger cohort and may potentially enhance the selection of patients deserving postoperative treatment intensification. [Table: see text]
Epithelioid hemangioendothelioma: Real-world data about a rare entity in a Portuguese tertiary cancer center.
Authors: Cabral Sara , Freitas Rita , Dunões Inês , Santos Miguel , Pereira Carolina , Pereira Patricia M. , Gouveia Emanuel Jose , Ferreira Margarida , Vaz Fatima H 
Published: June 2024

e23525 Background: Epithelioid hemangioendothelioma (EHE) is a rare entity of vascular origin, whose malignant potential is uncertain. It can develop in different locations, most commonly bone, liver and lungs. Since there are no specific associated symptoms, the diagnosis is often incidental. Due to its rarity there is no standard treatment. Our aim was to evaluate the demographic characteristics, course of disease and treatment effectivity in EHE patients in our institution in the last 25 years. Methods: We performed a retrospective study of all patients with EHE treated at our institution between January/1997 and September/2023. Statistical analysis was performed using SPSS. Normal distribution was checked using Shapiro-Wilk test. Results: From the 23 patients diagnosed with hemangioendothelioma, 20 were epithelioid (EHE) and 3 were other type. Of note, all the biopsies were centrally reviewed and since 2022 the diagnosis were confirmed with WWTR1 rearrange (3 out of 5 patients were positive). From the total number of EHE, the majority were women (n = 13, 65%). The mean age at diagnosis was 46 ± 22 years-old. Seven (35%) were asymptomatic and 13 (65%) had metastatic disease at diagnosis, all of them with lung metastasis, 2 (10%) with hepatic metastasis and 2 (10%) with bone metastasis. The most frequent primary locations were lungs (n = 5, 25%); soft tissue (n = 5, 25%), and liver (n = 4, 20%), followed by bone (n = 2,10%), stomach (n = 1, 5%), parotid gland (n = 1, 5%), superior vena cava (n = 1, 5%) and one case of unknown primary EHE. The majority of tumors were multifocal (12, 60%). Eight (40%) patients were under active surveillance, 4 (20%) underwent surgery with or without adjuvant radiotherapy, 2 (10%) underwent systemic treatment with tyrosine kinase inhibitor (pazopanib) and 2 (10%) chemotherapy (paclitaxel, doxorubicin). Two (10%) patients received a liver transplant and 2 (10%) patients underwent multiple treatment modalities. With a median follow-up of 30.89 months (3-253), 6 (30%) patients were dead at the time of analysis and mean overall survival was 142.3 months. Patients with an angiosarcoma differentiation had significantly worse mean survival outcomes (p < 0.001), 7.9 ± 4.5 months vs. 158.9 ± 37.2 months. Conclusions: The biological behavior of these tumors remains uncertain. In our cohort, the majority of patients presented with distant metastasis, but the course of the disease was very heterogeneous, regardless of the primary or metastatic site or the treatment modality. Our data emphasizes that this disease should be managed on a case-by-case basis, with a multidisciplinary approach and tailored treatment and surveillance.