bluuebunny/crossref_metadata_2025_split huggingface dataset:
Portal vein thrombosis in gastrointestinal cancers: Insights into prevalence and prognosis—A nationwide inpatient analysis 2018-2020.
Authors: Ginjupalli Manasa , Hotwani Priya , Jayakumar Jayalekshmi , Gaddam Mrunanjali , Iqbal Rabia , Vachhani Bhavyakumar , Sanghvi Ankushi , Sharma Anuj , Nanavaty Dhairya , Kumar Vikash , Clement Jincy 
Published: July 2024

e16382 Background: The relation between cancer and thrombotic events has been well established over the past decade. Cancer is a prothrombotic state and thrombosis is the second most common cause of death in cancer. While portal vein thrombosis (PVT) has been extensively studied in individuals with Hepatocellular Carcinoma (HCC), its significance in other Gastrointestinal (GI) cancers is often overlooked. This study aims to investigate the prevalence and prognostic impact of PVT across various GI cancers. Methods: A retrospective analysis was performed on the National Inpatient Sample database (2018-2020) and the ICD-10 codes to identify the patients > 18 years old with primary diagnosis of GI cancers (pancreatic, HCC, gastric, small intestinal[SI], colorectal). Prevalence of PVT in individual GI cancers and effect of PVT on mortality, length of stay and Hospital cost utilization was studied. Multivariable regression analyses were performed adjusting for demographics, hospital-level characteristics, and relevant comorbidities. These included Age, Sex, Race, obesity, Smoking, Hypertension, Diabetes, CKD, liver disease, CHF, CAD, Hypothyroidism. Results: Our study analyzed data from 2,313,888 individuals with GI cancers, Including HCC, Gastric cancer, SI cancer, colorectal and pancreatic cancer, The incidence of PVT varied across cancer types, with 12.9% in pancreatic cancer, 0.74% in HCC, 0.99% in gastric cancer, 0.47% in colorectal cancer, and 3.6% in pancreatic cancer. Multivariate regression analysis, adjusting for confounders, revealed a significant association between PVT and increased mortality in various GI cancers. Specifically, the odds ratio (OR) for mortality in pancreatic cancer was 1.31 (p < 0.001), in HCC was 1.39 (p < 0.001), in gastric cancer was 1.88 (p < 0.001), and in colorectal cancer was 2.10 (p < 0.001). However, the incidence of mortality in SI cancer did not yield a significant result OR 1.42 [p- value 0.369] [Table 1]. Additionally, Our findings revealed an increase in length of stay and total healthcare resource utilization across all GI cancers for individuals with PVT compared to without PVT. Conclusions: There is a statistically significant effect of symptomatic and asymptomatic PVT on mortality in various other GI cancers in addition to HCC, which has been established and studied widely. Further prospective studies are needed to study the effect of diagnosing PVT earlier in the disease to predict mortality and other major complications in GI cancers.[Table: see text]
Real world data of leuprorelin castration efficacy in patients with prostate cancer: A comprehensive assessment of 1,744 tests.
Authors: Lages Dr. Paulo Sergio , Zulli Guilherme Augusto , Bergerot Paulo Gustavo , Barbosa Michelle , Carcano Flavio Mavignier , Lages Luciana , Azevedo Anita Chavez , Vargas Pivato de Almeida Daniel 
Published: July 2024

e17000 Background: Androgen deprivation therapy (ADT) has been standing the cornerstone of systemic prostate cancer (PCa) treatment, since Huggins’ findings.Gonadotropin-releasing hormone (GnRH) agonists or antagonists has been used broadly as ADT. However, the majority of studies has focused on Gosserelin, leading to a lack of dedicated investigations into the efficacy of leuprorelin, despite its large use on practice. In this real-world study, we thoroughly analyzed data of testosterone tests in order to comprehensively assess the leuprorelin castration efficacy on the PCa management. Methods: We gathered data from patients diagnosed with PCa who were undergoing treatment with leuprorelin alone or in combination with a novel hormonal agent (NHA) in a single cancer center. The tests spanned a nine-year period from 2014 to 2023 and we assessed the testosterone levels in baseline and after leuprorelin administration, as well as their distribution according to clinicopathologic variables. Results: A total of 1,754 test reports were retrieved from 240 individual pts. The median baseline testosterone level was 317 ng/mL (range: 37-1,136) prior to leuprorelin initiation and the distribution across Gleason grades was: 20 pts had grade 1, 30 pts had grade 2, 61 pts had grade 3, 51 pts had grade 4, and 40 pts had grade 5. Testosterone levels < 50 ng/mL were achieved in 1,730 tests (98.7%) and testosterone levels < 20 ng/mL were found in 1,485 tests (84.7%). A total of 80 pts received combined treatment with leuprorelin + NHA, of which the majority received abiraterone/prednisone (n=52; 65%) or apalutamide (n=11; 13.8%). Following ADT discontinuation, 91 pts presented testosterone levels ≥ 50 ng/mL after a median interval of 258.5 days (range:82-710). Conclusions: In this comprehensive real world database analysis, leuprorelin is able to achieve suitable testosterone suppression levels in nearly the whole study population, such as are seen in others GnRH agonists pivotal trials. Deeper and maintained testosterone suppression levels is predictive of longer time to castration-resistant PCa and real life use of leuprorelin seems to meet this need.
The demographics of Sertoli cell carcinoma: A National Cancer Database analysis.
Authors: Tade Yanick , Silberstein Peter T. , Heise Craig , Hsia Beau 
Published: July 2024

e17012 Background: Sertoli cell tumors (SCTs) are an extremely rare and lethal diagnosis responsible for roughly 1% of all testicular and ovarian carcinomas. No uniform treatment regimen with sufficient results has been established. Current combination of retroperitoneal lymph node dissection, chemotherapy, and radiation therapy provides the best known outcome. Analyzing trends in diagnosis may provide valuable information about its epidemiology. The National Cancer Database (NCDB) was analyzed to establish the demographic factors in diagnosed patients. Methods: A retrospective cohort study from 2004 to 2020 was conducted using the NCDB. 159 patients were found with a histologically confirmed diagnosis of SCTs (ICD-8640-3). Race, gender, Hispanic origin, type of treatment facility, insurance coverage, and distance from patient residence to treatment facility were analyzed via descriptive statistics, and trends in incidence were interpreted using regression analysis. Results: The number of patients diagnosed with SCTs has remained relatively consistent since 2004 (R^2 = 0.07), with approximately 9 diagnoses per year. Of the 159 patients found, the average age of diagnosis was 44.6 years (SD = 19.1, range = 2 – 89 years). A majority of patients were male (67%), while the remaining third were female (33%). Most of the patients were White (73%). Patient Hispanic status could not be reliably determined due to limited data. More patients were in the top income quartile (31%) than the second (24%), third (18%), or fourth (14%) quartiles, with 13% having unknown income status. Most patients were privately insured (59%), followed by coverage under Medicare/Medicaid (28%). More patients lived in metropolitan counties with a population of 250,000 or more (76%) compared to less-populated urban or rural regions (24%). The majority received treatment at comprehensive community cancer programs or academic/research programs (43%). Patients traveled an average of 30.2 miles (SD = 64.0, range = 0.5 – 474.9) to reach the treatment facility. Conclusions: SCTs remains a rare diagnosis. This study pursues a significant gap in existing knowledge on patient characteristics that may present with SCTs. Most patients were White, privately insured, in the top income quartile, and lived in metropolitan areas. This novel study may contribute data towards understanding the relationship between patient socioeconomic status and access to diagnosis. Further research is required to uncover the role of socioeconomic status in SCTs.
Real-world clinical outcomes and economic burden of early discontinuation of taxane therapy among patients with metastatic castration-resistant prostate cancer.
Authors: Patel Jeetvan , Nguyen Jennifer , Bollu Vamsi , Kang Barinder , Sawhney Amrita , Byrne Clare , Tang Jackson , Gorritz Magdaliz , Chen Chi-Chang , Shore Neal D. 
Published: July 2024

e17043 Background: Despite comprising an important part of the treatment paradigm for metastatic castration-resistant prostate cancer (mCRPC) for over a decade, real-world use of taxanes is hindered by adverse events (AEs). AEs may lead to early treatment discontinuation, which may adversely affect outcomes. The two goals of this study were to determine the proportion of mCRPC patients who discontinue taxanes early (defining the early discontinuation threshold relative to efficacy results associated with androgen receptor pathway inhibitors [ARPIs]) and to evaluate the impact of early discontinuation on clinical outcomes, AEs, and healthcare costs. Methods: This was a retrospective, observational study of adult men with mCRPC treated with an ARPI as their first-line (1L) therapy and who initiated second-line (2L) therapy with another ARPI or a taxane. The Flatiron Health electronic health record database (07/01/2012–06/30/2020) was used to estimate Kaplan-Meier overall survival (OS) curves for the taxane cohort by the number of cycles received; these were compared with patients who received ARPI at 2L. Cox regression modeling and median PFS and OS values were used to identify the number of taxane cycles needed to achieve comparable OS to ARPI. The number of taxane cycles with similar OS outcomes to ARPI was then considered the threshold for early discontinuation. In addition, the IQVIA PharMetrics Plus claims database (01/01/2013–08/31/2021) was used to estimate taxane-related AEs (based on product information) and associated healthcare costs among patients who did and did not discontinue taxanes early. Results: From Flatiron, 473 2L ARPI patients and 214 2L taxane patients were included. Similar clinical characteristics – e.g., prostate-specific antigen level, ECOG performance status, and Gleason score – were observed between the two cohorts. Overall, 2L ARPI was associated with longer median OS (15.4 vs. 13.6 months) than 2L taxane. The number of taxane cycles needed to reach comparable OS to ARPI was determined to be 8. Patients receiving >8 cycles (n=48; 22%) compared to those receiving ≤8 cycles (n=166; 78%) had longer median OS (18.4 vs. 11.9 months, respectively) and PFS (9.0 vs. 4.3 months, respectively). From PharMetrics, 158 2L taxane patients were included. Patients receiving >8 cycles (n=20; 13%) were more likely to experience an AE (95% vs. 88%) than those receiving ≤8 cycles (n=138; 87%) but had lower mean AE-related total healthcare costs per patient per month ($3,429 vs. $6,334). Conclusions: These results suggest that mCRPC patients need to receive >8 cycles of taxane at 2L to receive more clinical benefit than 2L ARPI. However, the vast majority of patients in the study discontinued taxane early, resulting in shorter survival outcomes compared to ARPI.
Charlson’s comorbidity and remission outcomes in women diagnosed with epithelial ovarian cancer.
Authors: Cannavale Kimberly L. , Mukherjee Amrita , Xu Lanfang , Gilfillan Alec , Szamreta Elizabeth A. , Monberg Matthew , Hodeib Melissa , Chao Chun 
Published: July 2024

e17562 Background: Several prior studies have examined the role of comorbidity on overall survival in ovarian cancer (OC) patients and reported an association between comorbidity and inferior overall survival. However, it is unclear if the inferior survival was solely due to the excess mortality from the comorbidities, or that the comorbidities can impact OC treatment outcomes. Our objective was to determine whether pre-existing Charlson comorbidity index (CCI) was associated with lower likelihood of achieving complete remission. Methods: This retrospective cohort study included patients diagnosed with OC of epithelial subtype between 01/01/2017-06/30/2021 at a large integrated healthcare delivery system in the United States. OC patients were identified from the healthcare system’s cancer registry or via chart review of those with the ICD-10 diagnosis code. Patient’s CCI was determined based on data from the 12-month window prior to OC diagnosis. Patients’ remission outcomes, including complete remission and clinical remission (complete + partial remission) were ascertained via chart review, considering physician’s assessment, CA125 value and imaging evidence. Data on potential confounders (pandemic period, age, race/ethnicity, FIGO stage, prior length of membership, and time to treatment) were obtained from the healthcare system’s electronic medical records. Bivariate and multivariable modified Poisson regressions adjusting for potential confounders were used to evaluate the associations between CCI and achieving complete remission or clinical remission by end of therapy. Results: A total of 799 patients diagnosed with OC were included in our study. Overall, the cohort was racially/ethnically diverse with 46.2% White, 33.8% Hispanic, 12.4% Asian, and 7.6% Black patients. In the crude analysis, those with CCI score=1 and CCI≥2 had lower likelihood of achieving complete remission, compared with those with CCI=0 (no Charlson comorbidity) [RR= 0.84 (0.76-0.93) and RR=0.72 (0.64-0.81), respectively]. In the multivariable analysis, those with CCI=1 and CCI≥2 continued to have lower likelihood of achieving complete remission, compared with those with CCI= 0 [RR= 0.84 (0.77-0.92) and RR=0.81 (0.72-0.91), respectively]. Similar findings were observed for clinical remission, although the associations were attenuated: RR= 0.95 (0.89-1.01) for CCI=1 and RR=0.92 (0.86-1.00) for CCI≥2 vs. CCI=0. Conclusions: Having Charlson comorbidity was associated with lower likelihood of achieving complete remission in OC patients. This finding suggest that pre-existing comorbidities may contribute to inferior survival via, at least in part, adversely affecting the likelihood of achieving complete remission. The potential mechanisms underlying this association should be further studied to inform patient management.
Development and validation of an efficacy assessment platform utilizing patient-derived xenograft (PDX) models in ovarian cancer research.
Authors: Kim Min Kyu , Shin Hayeon , Kim Jae Hoon , Jun Anna , Kim Jue Young , Ryu Ji-Won , Chung Dawn 
Published: July 2024

e17564 Background: Ovarian cancer predominantly undergoes treatment through surgical and chemotherapeutic interventions. However, with an increasing rate of recurrence, there's a need for systemic chemotherapy. A paradigm shift towards personalized treatment is crucial with concerns escalating about chemotherapy resistance post PARP inhibitor treatment. This paper emphasizes the significance of preclinical drug evaluation platforms using Patient-Derived Xenograft (PDX) models, which resonate with the genuine characteristics of ovarian cancer tissues. Methods: The 112 epithelial ovarian patients' tumors sectioned to approximately 3 mm2 were subcutaneously transplanted into at least two female 5-week-old BALB/c nude mice. The xenograft tumors engrafted into mice from patient-derived tumors were defined as P1. After that, xenograft tumors serially engrafted into the following mice were termed P2 to P3. We collected and banked small pieces of tumor tissue from each passage of PDX tissue for performing Whole Exome Sequencing (WES) sequencing and RNA Sequencing. Results: We established 54 epithelial ovarian cancer PDX models that are stably growing. They show a ratio of 70.37% Serous, 11.11% clear cell, and 3.7% endometriod. The stage is 14.81% I/II, 61.11% III/IV, and 24.07% Recurrent. BRCA status consists of 59.26% wild type, 9.26% BRCA 1 mutation, 5.56% BRCA 2 mutation, and 11.11% BRAC VUS. We have obtained a variety of ovarian cancer PDX models and confirmed retained the histological characteristics of patients by H&E staining. We validated the similarity of genomic information in patients and PDX models via WES and RNA sequencing. Conclusions: We have a stable and growing PDX model that accurately reflects the actual tissue characteristics of ovarian cancer. In the future, we plan to characterize drug response further and build new models resistant to existing anti-cancer drugs. Based on these, we will validate the efficacy of new drugs and suggest strategies to overcome cancer resistance.
Effect of plasma-based molecular testing in patients with newly diagnosed advanced NSCLC on initiation of targeted agents in patients with targetable genomic alterations: A real world experience from the Middle East.
Authors: Joel Anjana , Al-Hashami Zamzam , Khan Shafquat Ali , Deshpande Prashant Ajit , Telugu Ramesh Babu , Khreis Abdallah Bilal , Nair Jayakrishnan , Bennji Sami M. 
Published: July 2024

e20514 Background: The treatment of metastatic non-small cell lung cancer ( m-NSCLC) is personalized and driven by mutational profiling of the tumour tissue at diagnosis. This study evaluates the additional clinical utility of plasma based molecular testing towards shortening time to initiation of treatment and detection of targetable mutations in a cohort of patients with newly diagnosed m-NSCLC. Methods: This is a retrospective analysis of patients with newly diagnosed advanced NSCLC referred to the Thoracic Oncology Program between September 2021 to December 2023, who underwent “paired” plasma based circulating tumour ( ct-DNA ) and tissue based next generation sequencing (NGS) testing (done less than 4 weeks apart). ct-DNA testing was performed using the Oncomine Pancancer NGS Assay (Thermo Scientific) that screens for single nucleotide variants (SNV) in hotspot regions of 52 and common fusions involving 12 genes respectively. Tissue NGS testing was performed using Oncomine Comprehensive Assay Plus (Thermo Scientific); a panel covering ~500 genes capable of identifying all single nucleotide variants, indels, fusions and copy number variants (CNV). Patient demographics and clinicopathological characteristics were collected by retrospective review of electronic medical records (EMR). Results: Among 36 patients, the median age was 66.0 years (range: 32-66), 25 (69.4%) were males, and 16 (44.4%) were never smokers. Thirty (83.3%) had adenocarcinoma and 33 (91.67%) had stage IV NSCLC. The mutation detection rate of ct-DNA was 66.7% with a concordance of 58.3% between ct-DNA and tissue NGS testing. The median turnaround time (TAT) from sample collection to reporting were12 days (IQR:8-15) and 14 days (IQR:9-24.50) for ct-DNA and tissue NGS testing respectively. Among 31 patients who started treatment, the median time to initiation of 1st line treatment was 26 days from date of first visit (IQR:18-42). Fifteen(41.7%), 6(16.7%) and 10(27.8%) started first line targeted therapy, chemotherapy and chemoimmunotherapy respectively. Twenty-three(63.89%) had targetable mutations (EGFR Exon 19 or 21, EGFR Exon 20 insertion, ALK, ROS1, MET Exon1 4 skipping, ROS1 or KRAS12C detected either in ct-DNA or tissue). Fifteen (65.21%) out of these 23 started targeted therapy as their 1st line treatment and of these 8 (53.3%) were initiated on targeted agents prior to availability of tissue NGS reports. Conclusions: Though our TAT for ct-DNA and tissue based NGS testing was similar, ct-DNA based NGS testing enables earlier initiation of targeted treatment for newly diagnosed advanced NSCLC patients with targetable mutations. In the real world, this increases access to targeted agents and may translate to a subsequent improvement in survival outcomes.
Correlation of gut dysbiosis biomarkers and peripheral thyroid hormones conversion in patients with (pts) advanced lung cancer.
Authors: Bonato Adele , Belluomini Lorenzo , Silva Carolina Alves Costa , Fidelle Marine , Birebent Roxanne , Gattazzo Federica , Parisi Claudia , Remon Masip Jordi , Lavaud Pernelle , Planchard David , Aldea Mihaela , Besse Benjamin , Barlesi Fabrice , Loupakis Fotios , Zitvogel Laurence , Derosa Lisa 
Published: July 2024

e20517 Background: Changes in gut microbiota may affect benefit from immunotherapy (IO). Gut dysbiosis can be identified by a fecal metagenomic signature (TOPOSCORE SIG1+ vs SIG2+), and/or by low levels of sMAdCAM-1. Recent studies showed that peripheral thyroid hormones conversion (fT3/fT4 ratio) has a strong prognostic role in various cancers, with low fT3/fT4 ratio predicting worse outcomes. Correlation between gut dysbiosis and metabolic stress, such as altered fT3/fT4 conversion, has not been investigated yet. Methods: A total of 77 lung cancer pts treated at Gustave Roussy Cancer Center with IO-based treatment with available measurement of baseline fT3/fT4 ratio, metagenomic data defined by TOPOSCORE category SIG1+ vs SIG2+, and/or level of sMAdCAM1 (low vs high according to the median) from the ongoing ONCOBIOTICS multicentric prospective study (NCT04567446) were selected. fT3/fT4 low vs high groups were defined adopting the median value as cut-off. Correlation between the fT3/fT4 ratio categories with TOPOSCORE and sMAdCAM1 were tested by means of a 2-sided chi-square test. Results: Baseline fT3/fT4 ratio and TOPOSCORE and/or sMAdCAM-1 data were available for 62 and 57 patients, respectively. A significant correlation was observed between fT3/fT4 ratio and TOPOSCORE category, with a higher proportion of SIG1+ pts (64.5%) vs SIG2+ (35.5%) in fT3/fT4 low group, and higher rate of SIG2+ (61.3%) vs SIG1+ (38.7%) pts in fT3/fT4 high group (p = .042). Similarly, a significant association was observed between low levels of sMAdCAM-1 and the fT3/fT4 low group (p = .047). In a independent dataset of 42 NSCLC treated with 2nd line IO, pts with low fT3/fT4 ratio had a mPFS of 1.7 mos and a mOS of 2.4 mos compared to 6.8 and 18.7 mos respectively for fT3/fT4 high pts (PFS HR = 0.56, 95%CI 0.30-1.05, p = .040; OS HR = 0.50, 95%CI 0.26-0.99, p = .030). Conclusions: Our data confirm the prognostic value of fT3/fT4 in progressing metastatic NSCLC and its correlation with gut dysbiosis markers. These findings open the way to further research for exploring specific therapeutic applications, such as tailored nutritional support and microbiota-driven interventions. Clinical trial information: NCT04567446 .