bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world data of cancer-associated venous thromboembolism in a tertiary-care hospital in India.
Authors: Mahapatra Manoranjan , Upadhaya Prashun , Aggarwal Mukul , Dass Jasmita , PUSHPAM DEEPAM , Dhawan Rishi , Kumar Pradeep , Viswanathan Ganesh Kumar , Seth Tulika 
Published: June 2024

e23298 Background: Cancer-associated venous thromboembolism (VTE) is a leading cause of morbidity and mortality in patients with various malignancies. Anticoagulation is crucial for preventing and treating thrombosis associated with cancer. However, its use faces challenges due to increased risks of bleeding, recurrent thrombosis and complexities in dosing, particularly in patients with concurrent comorbidities. Prophylactic anticoagulation is under-utilized and the cost of low- molecular-weight heparin (LMWH) and direct oral anticoagulants is a major barrier in developing countries. Methods: It was an ambispective observational study. All the cancer-associated thrombosis patients attending the thrombosis clinic at a tertiary-level referral hospital based in north India between 2018 and 2023 were analysed. Patient demographics, disease-related and treatment-related parameters were collected and analysed. The study was approved by the Institute Ethics Committee. Results: A total of 1312 patients attended the thrombosis clinic during study period, of which 139 (10.59%) cases were Cancer-associated VTE. The median age was 48 years and 61.2% were female. Most of VTE (54.6%) occurred within 6 months of cancer diagnosis and only 7% occurred after 3 years. Gynaecological malignancies (25.18%) and adenocarcinomas (21.58%) were the most common site and histological type of cancer respectively. Common risk factors observed for VTE development were: active cancer (80.3%), active chemotherapy (36.7%), cancer surgery (15.1%). Lower limb thrombosis was the most commonly seen type (46%), while abdominal and pulmonary thrombosis were seen in 17% and 7.9% respectively. Out of total patients, 124 (89.2%) patients received anticoagulation. Low molecular weight heparin (LMWH) was used as an initial anticoagulation in majority (52.41%) and direct oral anticoagulant (DOACs) was used as long term anticoagulation in 54% of patients. In 26 patients, anticoagulation was interrupted, the major reasons being bleeding and thrombocytopenia. There was no significant difference in frequency of bleeding with use of different anticoagulants (P = 0.48). Conclusions: Most cases of cancer associated VTE occur shortly after cancer diagnosis. Prophylactic anticoagulation is still underutilized in our patients with cancer. Early suspicion and prompt treatment can improve quality of life in such patients.
Real-world outcomes and molecular correlates of incorporating immunotherapy (IO) and bevacizumab (Bev) in treating patients with peritoneal mesothelioma (PeM): A comparative analysis with pleural mesothelioma (PM).
Authors: Huey Ryan W. , Gandhi Nishant , Helmink Beth A. , Overman Michael J. , Malpica Anais , Estrella Jeannelyn , Taggart Melissa , Allam Joelle , Scally Christopher , Mansfield Paul F. , Matamoros Aurelio , Elliott Andrew , VanderWalde Ari , Ma Patrick C. , Halmos Balazs , Liu Stephen V , Fournier Keith F. , Raghav Kanwal Pratap Singh 
Published: June 2024

e23300 Background: Nivolumab/Ipilimumab (IO) and Bev/Chemo are now considered standards of care for patients (pts) with advanced PM, based on randomized (CheckMate743 and MAPS) trials. By extrapolation, they are also endorsed by guidelines and used clinically in pts with PeM. Due to lack of any prospective data, we evaluated real-world effectiveness of these agents in PeM (vs PM) and investigated molecular correlates underlying their therapeutic impact. Methods: The study cohort was composed of mesothelioma pts (N = 723) who underwent DNA (592-gene panel or whole exome)/RNA (whole transcriptome) [PeM (221/224) and PM (493/499)] sequencing at Caris Life Sciences (Phoenix, AZ). Treatment and real-world survival (OS) were obtained from insurance claims and calculated from time of tissue collection to last contact. Hazard ratio (HR) was calculated using Cox proportional hazards model. Tumor microenvironment (TME) estimates were calculated from bulk RNA sequencing using QuanTIseq method. Significance was determined using Chi-square, Mann Whitney U and log-rank tests and corrected for multiple comparisons (q-value < 0.05) when applicable. Results: PeM (vs PM) had a higher proportion of females (46% vs 29%) and younger age (62 vs 73 years; both p < 0.001). 20% and 22% of PeM were treated with IO or Bev/Chemo, with similar utilization rates in PM of 22% and 24%, respectively. OS estimates and comparisons are shown in Table. Prevalence of mutations in key mesothelioma associated genes ( BAP1, NF2, TP53 and SETD2) was not significantly different between PeM and PM. NF2 (10.1 vs 51.3 m for wild type; p < 0.001) and TP53 (10.4 vs 46.6 m for wild type; p < 0.006) mutations were associated with worse OS in PeM but not in PM. Prevalence of high tumor mutation burden (≥10 mut/Mb: 1.0% vs 3.4%; q = 0.37) and PD-L1+ (18.7% vs 28.8%; q = 0.07) tumors was slightly lower in PeM than PM. Macrophage fractions, M2 were higher (1.5-fold) and M1 were lower (0.8-fold) in PeM (both q < 0.05) compared to PM. Conclusions: In this large real-world analysis, use of IO appears to be associated with improved outcomes in PeM, despite a potentially immunosuppressive TME. Notably, addition of Bev did not appear to improve outcomes in PeM, in contrast to PM. These results highlight variances in clinical utility/value of these therapies. Molecular mechanisms underlying these outcome differences warrant further investigation. [Table: see text]
Trastuzumab biosimilars interchangeability: Preliminary real-world data in neoadjuvant breast cancer setting.
Authors: Nunes Joao Soares , Prestes Ana Paula , Carneiro Marcela Bechara , Marra Ana Claudia Machado , Marquezini Isabela Rovel 
Published: June 2024

e23305 Background: Interchangeability (IC) among biosimilar compounds is still an issue not completely addressed, due to concerns on adverse events, immunogenicity, and efficacy. Many regulatory agencies around the world have adopted IC aside of appropriate clinical trials evaluation. Brazil’s Public Health System (SUS) has centrally provided trastuzumab (T) for breast cancer (BC) and firstly adopted biosimilars in 2020, after their regulatory approval 2 years before. After T biossimilar adoption there was an improvement of access for its all clinical indications, however different compounds had been offered to patients (pts) along their treatment. The aim of this study is evaluating the impact of these exchanges of types of T on patient-based registry. Methods: We reviewed all pharma and clinical data between 2020 and 2022 from all pts, stage III, Her2-Positive, who received neoadjuvant treatment based on chemotherapy plus trastuzumab in a Comprehensive Cancer Center in Southern Brazil. The main objective is measuring the rates of changes among T biosimilar compounds, and its impact in pathological response (pCR), toxicity and treatment-failure rates. Chi-square, Fisher’s Exact, t-test, or Mann-Whitney testing, as appropriate, was used to compare events between groups. Results: Along the studied period, SUS had offered 3 T biosimilars: ABP 980 (Amgen), CT-P6 (Celltrion), SB3 (Samsung), plus reference trastuzumab (Roche). The standard regimen was ACq21 4cycles followed by Taxane (Docetaxel q21 or weekly Paclitaxel) plus T 4cycles. 146 pts were eligible to analysis. 83 pts received only one type of T compound (non-interchangeability group – NICG), 63 pts received at least 2 different T compounds along the treatment (Interchangeability Group – ICG). Both groups were comparable in terms of clinical features (age, ER/PR status, menopausal status, PS, tumor size, and staging of axillary lymph nodes). Rate of IC along the time was 11%, 53% and 33% in 2020, 2021 and 2022, respectively. pCR was 32,5% in NICG versus 33,3% in ICG (p:NS). In total, 3pts had their treatments interrupted due to toxicity (1pt cardiac, 2pts hematologic). Conclusions: Although IC among biosimilars compound had been globally accepted, it was not clinically fully tested. Brazilian Ministry of Health, as the only provider, has a policy based on lowest cost for trastuzumab compound, causing constant changes along pts treatments. Furthermore, it is expected that Brazil has the potential to evaluate the IC in thousands of pts prospectively next years. Hereby, we could demonstrate preliminary based on retrospective data that exchange among different biosimilar compounds did not interfere significantly on pCR, nor raised any new safety or clinical concerns.
Nationwide real-world usage of blood-based (liquid) biomarker testing in Japan.
Authors: Yatabe Yasushi , Ennishi Daisuke , Kotera Yuko , Watanabe Ryosuke 
Published: June 2024

e23311 Background: Despite the advances in precision oncology with biomarker testing including CGP (comprehensive genomic profiling), not all patients are able to benefit from tissue-guided treatment decisions, underscoring a significant demand for advancements in liquid-based biomarker testing for such patients. However, the treatment landscape based on the application and integration of liquid biopsy in clinical practice has yet to be fully characterized in Japan. Methods: Center for Cancer Genomics and Advanced Therapeutics (C-CAT), the national datacenter in Japan, was established by the Ministry of Health, Labour and Welfare (MHLW) with the start of cancer genome medicine since June 2019. The database collects the clinical and genomic data from 68,242 patients who underwent CGP by the end of 2023. This study included all patient records who underwent liquid CGP testing using FoundationOne Liquid test from the C-CAT database up to June 2023. Results: We analyzed data from 7,461 records, where the patients had an average age of 65.1 (±12.0) years; 58.8% were male. A majority (51.3%) exhibited an ECOG performance status of 0, and 66.5% reported a family history of carcinoma. Predominant cancer types included pancreatic (1,825; 24.5%), prostate (1,182; 15.8%) and biliary tract cancers (838; 11.2%). Following review by an MTB (molecular tumor board), new treatments were initiated in 5.8% (434) of cases, with targeted therapy (181; 41.7%) and chemotherapy (174; 40.9%) being the primary interventions. Separately, 9 (2.1%) of new treatments post-MTB occurred as part of clinical trials. Median (IQR) durations from specimen collection to MTB, MTB to treatment initiation, and specimen collection to post-MTB treatment were 28 (24-34), 35 (13-64), and 63 (42-94) days, respectively. The largest proportion of biomarker testing occurred after the start of second line of therapy (1,720; 23.1%) Pancreatic and biliary tract cancer patients tend to have biomarker testing at the earlier line, whereas prostate and ovarian cancer patients tend to have at the later line. Conclusions: Although the positioning of liquid CGP testing may differ among cancer types, it is important for patients to select appropriate tissue- and liquid-based biomarker testing at the right timing. Understanding this descriptive landscape of biomarker tests utilized in real-world settings will aid decision-making for addressing unmet needs (e.g., low accessibility to treatment) in cancer genome medicine and its positioning in improving the standard of cancer care.
Incidence and outcomes of atrial fibrillation in different cancer subtypes: A propensity-matched analysis of Nationwide Readmissions Database.
Authors: Farooq Faryal , Kumar Manoj , Sultan Muhammad , Afzal Muhammad Sohaib , Nasir Bilal , Byreddi Laxman Yashwant , Devarkonda Vishal , Atluri Sundeep , Ali Shafaqat 
Published: June 2024

e23324 Background: Significant concern exists over the cardiotoxic effects of chemo & radiation therapy used in the management of cancer patients. With different cancers requiring different chemo-radiotherapy regimens, cardiotoxicity risk is quite variable. We aim to evaluate the rates of atrial fibrillation (AF) in various cancers. Methods: The national readmission database (2016-2020) was queried to identify all-cause admissions for patients with active malignancy of any origin. The study population was divided into six subgroups based on the type of cancer (colorectal, renal, lung, breast, prostate, and hematological). Multivariate regression analysis was utilized for adjusted odds of mortality. A propensity score matching (PSM) model matched malignancy of interest with other malignancies to obtain incidence rates. Results: Among 10.6 million all-cause cancer-related hospitalizations, about 1.5 million (14%) developed atrial fibrillation (AF). On propensity-matched cohorts, AF had its highest incidence in hospitalizations associated with hematological malignancies (17%), followed by prostate (16.5%), lung (15.9%), renal (12.5%), colorectal (11.5%) & breast (10.5%) malignancies [p < 0.05]. Moreover, cancer hospitalizations complicated by AF were associated with higher mortality. AF was associated with the highest odds of mortality in breast cancer (aOR:1.60), followed by colorectal (aOR:1.59), hematological (aOR:1.55), prostrate (aOR:1.52), renal (aOR:1.51) & lung (aOR:1.51) malignancies [p < 0.001]. The rates of 30-day AF-related readmission were highest in hematological malignancies (21%), followed by lung (18.8%), colorectal (17.1%), breast (16.1%), prostate (15.7%) & renal (12.5%) malignancies [p < 0.05]. Conclusions: The rate of AF in nationwide hospitalizations among cancer patients was ~ 14%. AF was found to have the highest incidence & readmission in hematological malignancies, while AF-related mortality was highest among breast cancer.
Bony reconstruction after internal hemipelvectomy: A retrospective analysis of 44 patients undergoing femoro-pelvic pseudoarthrosis.
Authors: Mishra Biplab , Shah Mandip C. , Anchan Chetan 
Published: June 2024

e23509 Background: After acetabular resection for sarcomas, achieving a bony femoro-pelvic fusion is very difficult, and prosthetic reconstructions have very high complication rates. We reconstructed the defects with a simple polypropylene mesh between the femoral head and the remaining part of the pelvis thereby aiming at a pseudo-arthrosis and analyzed its functional outcome. Methods: Between 2013 and 2022, 44 patients having bone tumors of the pelvis underwent acetabular resections and femoro-pelvic pseudoarthrosis. Commonest Histology was chondrosarcoma (23). According to Enneking’s classification, type II (3), type I+II (9) , type II+III (24), type I+II+IV (5), and type I+II+III (3) resections were carried out. A 30 x 30 cm polypropylene mesh was tied to the remains of the capsule around the head and was then turned on itself to make a strong braided rope-like structure. It was passed through the remaining ilium/ ischium/ sacrum and was tied to itself in proper rotation with heavy ethibond suture. In 4 cases, a proximal femur megaprosthesis and in 2, a nail cement spacer was implanted in femur to reduce shortening. Functional limb results were reported according to MSTS functional scores. Results: 37/44 patients attained independent ambulation. The mean time to full weight bearing was 4.7 months (3-9 months). There were 6 flap necrosis, 3 infections, 1 nerve injury, and 1 vascular injury. Local recurrence occurred in 6 (13%) and Systemic metastasis developed in 20 patients (47% of malignant tumors). At an average follow-up of 56 months ( 24 – 127 months), 26 are alive without any signs of disease. The average MSTS score was 22 (range 13–27). The best MSTS scores were with type II or II+III IH where ilium was left to support the femur while the worst was with type I+II+III resection patients. Patients with higher BMI have poorer functional outcomes with meshplasty. Conclusions: Mesh-pseudoarthrosis is a very simple reconstruction option that has an excellent functional outcome. It reduces surgical time and eliminates uncertainties about fusion/joint replacement. This should be strongly recommended as a method of reconstruction for patients undergoing acetabular resections.
Characterizing TP53 mutations in bone and soft tissue sarcoma.
Authors: Babatunde Olayode , Notti Ryan Quin , Tap William D. 
Published: June 2024

e23521 Background: Tumor protein P53 (TP53) is the most frequently mutated gene in cancer and most mutations inactivate wild type TP53 activity through heterogenous mechanisms. Whether different variants of mutant TP53 have different biologic potencies or clinical outcomes remain unclear. This ongoing study aims to characterize the spectrum of TP53 mutations in patients with bone and soft tissue sarcoma. Methods: We retrospectively identified and analyzed patients with bone and soft tissue sarcoma who underwent MSK-IMPACT (Memorial Sloan Kettering Cancer Center - Integrated Mutation Profiling of Actionable Cancer Targets) next-generation sequencing panel and had at least one mutation in the TP53 gene at Memorial Sloan Kettering Cancer Center. Mutations in the TP53 gene were categorized into the following sub-types: fusion, missense, splice site, or protein-truncating. Hotspots were defined as variants with frequency of 10 or greater. We queried the missense variants for the 800 most frequent variants recorded in the International Agency for Research on Cancer R20 (IARC), which were structurally characterized based on their impact on TP53 protein and rescue potencies with arsenic trioxide (ATO) in vitro (Song et al. Sci Transl Med. 2023). Results: We identified a total of 1257 patients with bone and soft tissue sarcoma who had at least one mutation in TP53. 92.5% of patients had only 1 mutation in TP53. In total, 1363 mutations were detected with 541 variants identified across all sarcoma subtypes. Most TP53 mutations were identified in soft tissue leiomyosarcoma (18.05%), uterine leiomyosarcoma (12.84%), sarcoma not otherwise specified (15.62%), undifferentiated pleomorphic sarcoma (12.11%), and osteosarcoma (7.78%). Of the 541 variants identified, the most frequent alterations were intragenic fusion (6.23%), R175H missense (2.93%), R248Q missense (2.27%), R273H missense (2.13%), and R213* protein-truncating (2.05%) mutations. Of the 800 most frequent missense variants in IARC R20 database, 233 missense variants were detected representing 52% of all mutations detected. Structural or likely structural mutations represented most of the identified missense mutations (77.46%). These mutations were clustered in the following hotspots: R175H, Y220C, R282W, H179Y, and C135Y. DNA-contact mutations were clustered in the following hotspots: R248Q, R273H, R273C, and R248W. Conclusions: This analysis highlights the heterogenous landscape of TP53 mutations in bone and soft tissue sarcomas. Structural variants are prevalent in sarcoma and occur at hotspots that may represent novel drug targets in the future.
Differences in baseline ctDNA value between Hispanic and non-Hispanic White patients with soft tissue sarcoma (STS): A single-center retrospective analysis.
Authors: Ikram Waleed , Zamora DIana , Braat Jonathan , Dinh Han , Azevedo Chelsea , Patel Shyamal , Wiseman Jason T. , Gonzalez Velez Miguel 
Published: June 2024

e23533 Background: Circulating tumor DNA (ctDNA) has shown promise as a biomarker for cancer detection and tracking in multiple malignancies like melanoma, colon and lung. Due to the heterogeneity of sarcoma, there has been limited research on ctDNA as a tool for measuring minimal residual disease (MRD). Differences in baseline in ctDNA for STS in racial minorities have been poorly studied. To identify potential racial differences in the efficacy of this tool, this study compares the quantitative values of baseline ctDNA between non-Hispanic white (NHW) and Hispanic (H) patients with soft tissue sarcoma (STS). Methods: The medical records of 33 STS patients who had ctDNA analysis from Natera™ were examined retrospectively at Dignity Health Cancer Institute.There were 19 H patients and 14 NHW patients in the group. All Black (B), Asian (A), and Other (O) racial groups were excluded due to lower numbers. GraphPad Prism software was used to examine the baseline ctDNA levels. Using continuous measures for statistical analysis, we conducted descriptive statistics and determined the mean, standard deviation, and median ctDNA levels for each group. The ctDNA levels were compared between groups using a two-tailed t-test with a significance level of p < 0.05. Results: The average ctDNA levels were 416.675 (standard deviation = 1349.394) in NHW and 300.305 (standard deviation = 1000.543) in H. The median levels were 0 for both groups. The statistical analysis showed that there was no significant differences in the baseline ctDNA levels between the two groups (p = 0.73). Furthermore, the gender distribution among NHW and Hs in the cohort was comparable, with a p-value of 1.00. Conclusions: This study establishes that there is no substantial differences in baseline levels of ctDNA between H and NHW patients with STS. These findings indicate that ctDNA levels in these populations can be equally utilized for diagnostic and monitoring reasons in clinical settings. Nevertheless, to gain a comprehensive understanding of the racial disparities in ctDNA utility and its implications in customized treatment for STS, it is necessary to conduct more extensive research with larger sample sizes and incorporate additional variables.