bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of the integration of remote clinical oncology pharmacists into routine precision medicine workflows on biomarker testing rates within The US Oncology Network community-based practices.
Authors: Greisl Natalie , Hale Brittney , Carroll Melissa , Cho Judy , Conkling Hilary , Farag Caroline , Jovani Juna , Keisler Meredith , Kendzierski Daniel , Roman Andrea , Howell Josh , Hough Shannon , Koselke Beth 
Published: July 2024

e13813 Background: The US Oncology Network implemented a centralized, remote clinical oncology pharmacist review program (ClinReview) into select community-based practices. Initially, pharmacists were integrated into a precision medicine workflow process to increase biomarker testing rates among patients receiving adjuvant treatment for non-small cell lung cancer, with recommendations achieving a 100% acceptance rate. Following this success, metastatic prostate cancer patients were incorporated into the established workflow, following updated guideline recommendations for both germline and somatic testing and the 2023 approvals of PARP inhibitors in the first-line treatment setting. With previously reported testing rates only reaching 60%, we sought to evaluate the impact of the pharmacist integration into the precision medicine workflow on biomarker testing in metastatic prostate patients. Methods: Over a 4-month period, ClinReview remotely identified patients with metastatic prostate cancer during normal order review. The EMR was reviewed to assess germline and somatic testing status. If testing was not ordered, the pharmacist sent a recommendation to the treating provider. Initial testing rates for germline and somatic testing, BRCA+ status and provider acceptance rates for testing recommendations were collected. Additional data was collected utilizing a de-identified database. While additional data collection is ongoing, descriptive statistics were utilized to analyze data and the impact of the pharmacists’ interventions. Results: Across 9 practices, 142 patients were initiated on treatment for metastatic prostate cancer. At the time of initial assessment, germline and somatic testing was not ordered in 50% and 37% of patients, respectively. Pharmacists recommended additional testing in 61 patients (43%) with a 73% provider acceptance rate. Findings showed equitable testing rates across racial demographics. Pharmacist workflow integration enhanced combined germline and somatic testing rates, demonstrating an improvement from a baseline of 57% up to 77% currently. Conclusions: Community oncology practices seek to provide high-value care, including offering the most current evidence-based precision medicine testing. These findings highlight the continued need for improved somatic and germline testing in metastatic prostate cancer. However, the implemented precision medicine pharmacist workflow demonstrates the positive impact a clinical pharmacist can have on both testing rates and the potential to improve therapeutic offerings within this growing treatment space. [Table: see text]
Breaking barriers: Real-world data on immunotherapy in non-small cell lung cancer with large brain metastases.
Authors: Sadagopan Narayanan , Komlodi-Pasztor Edina , Veytsman Irina 
Published: July 2024

e14002 Background: Non-small cell lung cancer (NSCLC) patients with large brain metastases (BrM) defined as > 2 cm historically face grim prognoses. Immunotherapy, emerging as a state-of-the-art treatment in NSCLC treatment, has not been extensively studied in the context of large BrM. The use of immunotherapy in these patients is complicated by factors such as steroids use and local interventions like surgery and/or radiation treatment. Methods: We conducted a retrospective study across three MedStar Georgetown Cancer Network sites to evaluate outcomes in NSCLC patients with large BrM. Inclusion criteria comprised of patients aged 18 years or older with NSCLC diagnosed between 01/01/17 to 12/31/2022 who started immunotherapy after the diagnosis of at least one BrM 2 cm or more in diameter. Intracranial progression free survival (PFS), overall survival (OS), and relevant clinical factors were analyzed. Steroid use was not included due to documentation limitations. Cox penalized regression was used to assess PFS and OS while power analysis was not done due to the sample size. Results: The study included 36 patients all of whom underwent neurosurgery and/or radiation before starting immunotherapy. Median follow up duration was 17.6 months. The population was 58.3% female, median age 64.4 years, 77.8% lung adenocarcinoma, 91.7% received pembrolizumab for immunotherapy, and median duration of immunotherapy was 178 days. Median intracranial PFS was 9.2 months and median OS reached 31 months. The hazard ratio (HR) was 0.07 (95% confidence interval (CI) 0.02-0.26) for intracranial PFS in patients who received at least 90 days of immunotherapy compared to those who received less than 90 days of immunotherapy. Each additional 30 days of immunotherapy was associated with an OS HR 0.77 (95% CI 0.67-0.90). Higher PD-L1 status was not associated with improved outcomes. Conclusions: The study highlights the potential of immunotherapy as a valuable treatment for NSCLC patients with large BrM, a population often excluded from clinical trials. In our retrospective analysis, extended immunotherapy demonstrated positive impacts on both intracranial PFS and OS. Future directions should focus on prospective evaluation of the optimal timing of immunotherapy relative to upfront large BrM treatment, with a specific emphasis on understanding the role of steroids dosing in this context.
A meta-analysis analyzing the efficacy of trastuzumab-deruxtecan (T-DXd) on central nervous system (CNS) disease in patients with metastatic breast cancer (mBC).
Authors: Ashok Kumar Prashanth , Sandhu Michael , Sravanthi Metlapalli Venkata , Desai Devashish , Suresh Kumar Vishnu Charan , Benjamin Sam 
Published: July 2024

e14012 Background: CNS metastasis from mBC portends a poor prognosis. We sought to analyze CNS activity of T-DXd through a meta-analysis. Methods: A systematic search with terms encompassing BC and T-DXd was conducted in PubMed, Embase, Scopus, and Cochrane on November 23 2023. There were no search restrictions. A total of 2318 records were identified, and duplicates were removed using Mendeley. 1189 records that remained were imported into Rayyan, and the titles were screened independently by 2 reviewers. 47/75 full texts were relevant, of which 12 [7 clinical trials and 5 retrospective study] were included for analysis. Only studies that provided stratified CNS response data for mBC were included. RevMan was used to analyze the Risk Ratio (RR) and Odds Ratio (OR) with 95% Confidence Interval (CI), derived from Random Effects (RE) model with Mantel-Haenszel (MH) method. Binary RE Pooled Proportions (PP) using DerSimonian-Laird method were determined using OpenMeta. Visual inspection of our funnel plots revealed no bias. Results: The T-DXd cohort had a total of 377 patients with a median age of 54.2 years (42.5-69). Control group (T-DM1-1, Chemotherapy-2 studies) had 86 patients with a median age of 54.5 years (54.2-54.7). All studies had previously treated patients and most of the patients received local therapy. PP with T-DXd for CNS Complete Response (CR) was 4.8% (2-7.6%). Partial Response (PR) was 50.1% (32.4-67.7%) and Stable Disease (SD) was 28.9 (20.5-37.3%). PP of Objective Response Rate (ORR) (CR+PR) was 60.9% (48.3-73.5%). Drug discontinuation rate was 18% (12.2-23.9%) and pneumonitis rate was 14.5% (9.4-19.6%). RR for Event/Progressive Disease (PD) comparing T-DXd and control group was not significant [0.96 (0.77,1.2) p=0.74, I²=0%], nor was OR for Disease Control Rate (DCR) (CR+PR+SD) [1.11 (0.63,1.96) p=0.64, I²=0%] (Table). The median Progression Free Survival (PFS) was 14.1 (8.5-18.1) months for the T-DXd and 4.3 (3-5.6) months for the control group. Conclusions: Although direct comparison between the pooled T-DXd and control group failed to reveal a difference, the pooled ORR from 10/12 studies was clinically significant at 60.9%. The median PFS for T-DXd was also longer. T-DXd could be a viable treatment option for pretreated HER2+ and low mBC with CNS metastasis. Limitation of our study is the heterogeneity between the studies, entailing the need for future clinical trials in this setting. [Table: see text]
Diagnosis and genetic characterization of CNS metastases in lung cancer via shallow whole-genome sequencing of CSF cell-free DNA.
Authors: Li Yubin , Shi Zongkun , Cao Beihe , An Juan , Ding Xiaosheng , Xu Weiran , Cao Dandan , Li Xiaoyan 
Published: July 2024

e14013 Background: The genetic characterization of CNS metastases in lung cancer is hindered by the limited sampling opportunities and genetic heterogeneity between intracranial and extracranial lesions. To address these challenges, this study uses cerebrospinal fluid (CSF) and blood samples, to detect and characterize CNS metastasis variants through shallow whole-genome sequencing (sWGS). Methods: From Dec. 2021 to Aug. 2023, 57 lung cancer patients were recruited, comprising 29 with leptomeningeal metastases (LMs) and 28 with only parenchymal brain metastases (PMs). A total of 66 blood and 112 CSF samples were collected for cfDNA sWGS to analyze chromosomal arm CNVs, focal amplifications (CN > 5) and SNV/InDels. Cytology was also conducted on 95 of these CSF samples. Variant differences between PMs and extracranial metastases (EMs) were analyzed using the MSK-MET database. Results: CSF cfDNA concentration was significantly lower than that in plasma (p < 0.0001), with 41.7% of samples unquantifiable, yet all samples successfully completed sWGS. The cfDNA tumor fraction in CSF was significantly higher than in paired plasma (p < 0.0001), and most arm CNVs and gene amplifications exclusively detected in CSF. Cytology, as the gold standard for LM diagnosis, had a sensitivity of 0.76. The sensitivity for LM diagnosis based on aneuploidy and genomic amplification fraction (GAF) were 0.51 and 0.80, respectively, without compromising specificity. Gains in 1p, 7p, 11q, 16p, and 17q, as well as losses in 9p and 9q, were significantly more frequent in PMs compared to EMs and further increased in the LMs (p < 0.05). Notably, losses in 1p, 4p, 5q, and 11p, significantly more frequent in PMs than in extracranial metastases, but showed a significant increase in gain frequency in LMs (p < 0.05). In the LM group, the frequency of EGFR L858R and amplification of nearly the entire 7p where the EGFR located, were significantly increased, whereas KRAS G12D frequency significantly decreased (p < 0.05). Conclusions: The characteristics of extremely low concentration but high tumor fraction of CSF cfDNA make it suitable for sWGS, enhancing LM diagnostic sensitivity without compromising specificity, and identifying molecular characteristics of CNS metastasis. These molecular features require further validation in larger prospective clinical cohorts, offering potential for personalized diagnosis and treatment of CNS metastases.
Prognostic factors of grade 4 IDH-mutant astrocytoma.
Authors: Maqbool Muhammad Asad , Jenkins Robert B. , Ida Cristiane M. , Burns Terry C. , Kizilbash Sani Haider 
Published: July 2024

e14019 Background: The data on the prognostic factors of grade 4 IDH-mutant astrocytoma remains limited since the 2021 update of the WHO classification of Central Nervous System tumors. This update recognizes the importance of molecular characteristics and confers a grade 4 diagnosis based on the presence of at least one of either necrosis, microvascular proliferation, or CDKN2A/B homozygous deletion. This study sought to determine the factors that impact prognosis of patients with grade 4 IDH-mutant astrocytoma. Methods: A retrospective review was performed on all patients diagnosed with grade 4 IDH-mutant astrocytoma on initial diagnosis (as defined by the 2021 WHO classification) across the three Mayo clinic campuses (Minnesota, Florida, Arizona) between 2002 and 2023. Datapoints collected included demographic, clinical, imaging, histological and molecular variables. Factors impacting survival outcomes (overall survival [OS] and progression free survival [PFS]) were evaluated using Cox regression models. Results: Sixty-two patients with grade 4 IDH-mutant astrocytoma were identified (43 based on histological criteria alone, 10 based on molecular criteria alone, and 9 based on both). The median age of the patients was 36 years, with 64.5% of the patients identified as male and 93.3% as white. 100% (n=58) of these patients received standard treatment after surgery (radiation/temozolomide). The median follow up was 3.3 years. The median PFS and OS were 3.2 and 6.9 years, respectively. The OS was impacted by an unfavorable tumor location (either tumor involving the midline or at least 3 brain lobes; 2.4 years vs. 12.8 years, HR 10.8 [95% CI 3.29-35.6], p<0.001) and CDKN2A/B homozygous deletion (2.5 years vs. NR, HR=4.3 [95% CI 1.5-12.3], p=0.0065). The PFS was impacted by an unfavorable tumor location (1.4 years vs. 4.6 years, HR=5.3 [95% CI 2.21-12.7], p=0.002), CDKN2A/B homozygous deletion (1.4 years vs. 4.6 years, HR=6.2 [95% CI 2.71-14.2], p<0.001) and MGMT promoter hypermethylation (4.6 years vs. 1.4 years, HR=0.369 [95% CI 0.154-0.883], p=0.025). Age, sex, tumor size and the use of tumor-treating fields did not significantly affect survival outcomes. Using multivariable analyses, PFS remained significantly impacted by CDKN2A/B homozygous deletion (HR=11.3 [95% CI 3.23-39.0], p=0.0001) and MGMT promoter hypermethylation (HR=0.243 [95% CI 0.082-0.717], p=0.0104), but not by an unfavorable tumor location (p=0.819). Conclusions: Both CDKN2A/B homozygous deletion and MGMT status may independently influence the progression-free survival of patients with grade 4 IDH-mutant astrocytoma.
Convolutional neural network and glioma genotyping: A systematic review.
Authors: Ashayeri Hamidreza , Abdollahi Mirsaeed , Jafarizadeh Ali , Morsali Soroush , Pedrammehr Siamak , Alizadehsani Roohallah , Gorriz Saez Juan Manuel 
Published: July 2024

e14038 Background: Gliomas are the most common primary intracranial tumors. Overall, there are 23 different glioma types, and the grading and prognosis of each type are determined by their specific mutations. Several identified mutations are IDH gene status, CDKN2A/B homozygote delegation, PTEN mutation, p53 mutation, TERT promotor mutation, H3K27M mutation, MGMT promotor methylation, trisomy 7/monozomy10, EGFR amplification, ATRX mutation, 1p/19q codeletion, and BRAF mutation. These specific mutations and genomic features can have their distinctive radiologic features seen in different magnetic resonance imaging (MRI) sequences. By using a Convolutional Neural Network (CNN) for feature extraction, the genotyping power of MRI for glioma could be increased. To address this, we systematically reviewed the use of different CNN-based models to detect the genetic context of glioma based on the MRI images. Methods: We conducted a systematic search in PubMed, Embase, Scopus, Web of Science, and Google Scholar. We included original peer-reviewed human studies (retrospective or prospective), focusing on the use of CNN in individuals with glioma. We excluded animal studies, studies with no CNN-based models, reviews, book chapters, conference abstracts, and case reports. JBI checklists were utilized for quality assessment. Results: The initial search resulted in 973 articles. after removing duplicates, 563 studies entered the screening process by title and abstract. 59 studies met our inclusion criteria (56 retrospective and 3 prospective cohort studies) with a total of 26434 glioma patients included (studies ranged from 21 – 2648 individuals). 31 studies used CNN methods only in different stages of image processing (tumor segmentation, feature extraction, image encoder) and 28 studies used CNN as a classifier and mutation predictor. ResNet was the most commonly used CNN-based model (n = 14). U-net (n = 7) and DenseNet models (n = 4) were other commonly used CNN-based models. Included studies targeted IDH status (n=44), 1p/19q codeletion (n=18), MGMT promotor methylation (n=11), ATRX mutation (n=5), TERT promotor mutation (n=5), CDKN2A/B homozygote deletion (n=3), PTEN mutation (n=3), p53 mutation (n=3), H3K27M mutation (n=2), trisomy 7/monozomy10 (n=2), EGFR amplification (n=2), and BRAF mutation (n=1). Highly severe methodological heterogeneity among these studies excluded the possibility of meta-analysis. Conclusions: Current studies have shown that, as a non-invasive method, using CNN-based models on multiple MRI sequences increases the power of early detection and prediction of glioma genetic types before pathological confirmation and has promising results. However, DL performance varies among mutations. Combining multiple DL models with clinical and radiomic features in different and larger databases can further increase the final results.
Incidence of venous thromboembolism in newly diagnosed glioblastoma multiforme and associated risk factors: A retrospective chart review.
Authors: Al Majarafi Nasser , Binjabal Duaa Omar , Pond Gregory Russell , Hirte Hal W. 
Published: July 2024

e14040 Background: Patients diagnosed with glioblastoma multiforme (GBM) are recognized as a population at high risk of developing venous thromboembolism (VTE) (1,2). A retrospective chart review of patients diagnosed with GBM at the Juravinski Cancer Centre (JCC) was performed with the primary objective to assess the incidence of the development of VTE in newly diagnosed GBM. The secondary objective was to identify patients who were at higher risk and who could benefit from prophylactic anticoagulation. Methods: This was a single-centre, retrospective cohort study. We reviewed the charts of 528 patients diagnosed with GBM at the JCC from an 8-year period from January 1, 2013 to December 31, 2020. Information on the following factors was collected: Body-mass index (BMI), comorbidities (hypertension, diabetes, dyslipidemia, smoking history), performance status, location and size of tumour, degree of resection, presence of and location of weakness, baseline blood counts, treatments administered, date of diagnosis and time to death or last follow-up. Results: Over the period of review, a total of 528 patients were identified. 111 patients (21%) were diagnosed with VTE. The location of VTE was as follows: 39 patients (35%) unilateral lower extremity deep venous thrombosis (DVT), 8 (7%) unilateral upper extremity DVT, 8 (7%) bilateral lower extremity DVT, 30 (27%) pulmonary embolism (PE), and 25 (23%) DVT and PE. Most VTE (87%) occurred within 12 months of diagnosis of GBM. On univariate and multivariate analysis, no factors were identified that contributed to an increased risk of VTE. Conclusions: Newly diagnosed patients with GBM have been shown to have a significant risk of developing VTE. The AVERT study (3) demonstrated the preventive benefit of administering a direct oral anticoagulant (DOAC) to cancer patients, including those with GBM, at high risk of developing VTE (3). Thus consideration should be given to treating patients with GBM with a DOAC at the time of diagnosis. The benefit of preventive treatment will need to be balanced against the risk of bleeding in these patients. References: 1. Marras LC et al. Cancer 2000; 89(3):640–6; 2. Lim G et al. Cureus 2018;10(5): e2678; 3. Carrier M et al. N Engl J Med 2019; 380:711-9.
Pineal gland: Sleep, malignancy and statistics.
Authors: Pereira Kristal , Ali Hassan , Thirumaran Rajesh , Desai Krishna 
Published: July 2024

e14042 Background: The pineal gland is a neuroendocrine gland located deep in the middle brain that regulates the circadian rhythm through Melatonin. Pineal parenchymal tumors arise from pineocytes, have no sexual predominance, occur most frequently in the pediatric population and result in melatonin level disruptions.Pineal region tumors can spread via CSF to other areas in the CNS. The first treatment for pineal region tumors is surgery. Treatments after surgery may include radiation, chemotherapy or clinical trials. Methods: Data was collected from Surveillance, Epidemiology and End Result database Research Plus Data, 17 Registries, Nov 2022 Sub (2000-2020). Pineal gland tumor cases that were labeled as the primary site were extracted from the data base. Further selection was made using the ICD Code D75.3 for neoplasm of pineal gland-primary site labelled. The data was stratified based on age, sex, race and survival curves were compared using the Log-Rank test (GraphPad Prism). Results: A total of 416 pineal gland tumor cases were found, of which ~ 50.48% were males. These tumors were most commonly seen in White (51.68%) patients followed by Hispanic (23.32%), Black (16.10%), Asians/Pacific Islander (6.97%) and Alaskans/Native American (0.96%) patients. The median age of diagnosis was 24.5 years. The incidence rate (per 1,000,000 population) for the general population has increased from 0.69 in 2000 to 0.73 in 2020. As of 2020, the incidence was noted to be higher in males, although overall the incidence among females has been ion the rise. Incidence rate was highest among the Native Americans/Alaskans population followed by Hispanics, Asians/Pacific Islanders, Blacks and Whites. Within the races, incidence was noted to be increasing in the Native Americans/Alaskans & Hispanic populations, stable in the Asians/Pacific Islanders & Black populations and decreasing amongst the White population over the period of 20 years. When the survival curves were compared on the basis of gender and race, the data was clinically significant only for gender. The median of survival (mOS) for males was 146 months but was undefined for females (CI:5.344-12.55, HR: 8.191, p <0.0001) mostly likely due to zero death events being recorded for females. Conclusions: Pineal gland tumors are rarely encountered malignancy with only 416 case reported in the last two decades. It has an almost equal predilection for males and females, more common in the younger population. The incidence is higher among males, although being relatively constant since 2000, and is trending up in females. Overall survival was superior in females with no reported death events. Native Americans/Alaskans are more affected overall survival is independent of the race.