tbuckley/cabot-search huggingface dataset:
A phase 1 safety and feasibility study of intratumoral placement of bicalutamide implants combined with radiotherapy for localized prostate cancer.
Authors: Deborah E. Citrin, Baris Turkbey, Krishnan Patel, Stephanie A Harmon, Peter A Pinto, Brad Wood, Sandeep Gurram, Holly Ning, Debbie-Ann Nathan, Pujan K Desai, Maithili Rairkar, Peter Choyke, Pamela N. Munster, Cassidy Mileti
Journal: Journal of Clinical Oncology (2024)

TPS5126 Background: Systemic androgen deprivation therapy (ADT) is an integral part of therapy for unfavorable intermediate or high-risk prostate cancer treated with radiation therapy (RT). However, systemic anti-androgens are associated with considerable cardiovascular, metabolic, and sexual side effects leading to omission and contraindication in many men. We tested the feasibility of replacing systemic ADT with targeted local delivery of an anti-androgen agent (bicalutamide, Biolen Implant). The Biolen implant consists of a medical grade silicone polymer mixed with 6.3mg bicalutamide into a solid rod-shaped scaffold approximately 0.95 x 15 mm in size. Pre-clinical studies have demonstrated that a silicone/bicalutamide implant is a feasible method for durable localized delivery of an anti-androgen into the prostate. Results for the preclinical studies were presented at the AACR Symposium in April 2023 (Poster # 5261). Methods: Trial Design: This study (CP-002, NCT04943536) is a prospective, single-center, single-arm feasibility study to assess the safety, feasibility and PK profile for Biolen for the localized delivery of bicalutamide into the prostate when delivered with radiotherapy. Up to 20 participants with intermediate to high risk localized prostate cancer who are planned to receive RT and are candidates for systemic ADT will be enrolled. Study participants will have placement of the drug eluting Biolen (bicalutamide) implants. Participants will receive standard of care radiation 9 weeks after implant and will be followed through 2 years post radiation. Patients will undergo plasma collection after Biolen implant at Day 1, 3, Week 1, 2, 4 and seminal fluid collection at 4-7 and 8 weeks for assessment of bicalutamide levels. An MRI will be performed at 6 and 24 months after completion of radiation. Key Eligibility: Patients must have at least 1 MRI detected, biopsy proven localized prostate cancer lesion in whom prostate radiation and ADT is appropriate therapy (such as Intermediate Risk localized prostate cancer). Patients diagnosed as one of the following: a) NCCN intermediate risk prostate cancer, b) NCCN high risk prostate cancer due to Gleason Grade 4 or 5 AND refuses to receive systemic ADT, c) NCCN high risk prostate cancer due to PSA &gt; 20 AND refuses to receive systemic ADT. Trial Status: The study is ongoing at the NCI and 9 patients have been enrolled to date. Clinical trial information: NCT04943536 .
Performance characteristics of ExoDx urinary biomarker: A single-institution analysis.
Authors: Andeulazia Murdock, Vincent Eric Xu, Ryan Michael Antar, Faozia Pio, Nicholas Bowler, Michael Joseph Whalen
Journal: Journal of Clinical Oncology (2024)

e17090 Background: Prostate cancer screening relies on prostate-specific antigen, which may lead to unnecessary prostate biopsies. The ExoDx Prostate (EPI) test, a urinary exosome assay, has been developed for the detection of clinically significant (Gleason Grade Group ≥2) prostate cancer (csPCa) to improve specificity. This study analyzes the performance characteristics of EPI compared to/in concert with a multiparametric MRI (mpMRI)-based pathway at a single academic institution. Methods: Patients who underwent EPI testing between 10/2019 to 5/2023 were reviewed for EPI score, demographics, MRI characteristics, and biopsy results. Patients were categorized by EPI score (high risk ≥ 15.6 vs. low risk &lt; 15.6). Outcome variables of biopsy and MRI were compared between EPI risk groups using Chi square and Mann Whitney-U test. Spearman correlation was used to estimate the correlation between EPI score and PI-RADS and Gleason score. Receiver operator curve (ROC) analysis assessed the performance of EPI and PI-RADS score for prediction of csPCa. An optimal cutoff value was determined for EPI using ROC, and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were assessed. Statistical comparisons were two-sided with a p-value &lt;0.05 being statistically significant. Results: Of n=173 patients with EPI scores, 28.9% were low risk and 71.1% were high risk. EPI had weak correlation with PI-RADS score on prostate MRI (r = 0.30, p &lt;0.001). An optimal EPI score cutoff for the detection of csPCa of 26.43 was determined (sensitivity 0.720, specificity 0.537, PPV 0.367, NPV 0.800). On ROC analysis, PI-RADS with score of ≥4 had better predictive performance for detecting csPCa with an Area Under the Curve (AUC) of 74.6% (sensitivity: 0.696, specificity: 0.721, PPV: 0.485, NPV: 0.862), versus an AUC of 63.1% with EPI testing. By utilizing a criteria of PI-RADS score ≥4 and EPI ≥ 26.43, we found improved PPV and specificity over either alone (PPV: 0.556 vs 0.485 vs 0.367, respectively) (specificity: 0.873 vs 0.721 vs 0.537, respectively). In addition, we found that with utilization of either PI-RADS score ≥4 or EPI ≥ 26.43, there was improved NPV and sensitivity (NPV: 0.962 vs 0.862 vs 0.800, respectively) (sensitivity: 0.957 vs 0.696 vs 0.720, respectively). Conclusions: Our study supports EPI testing as a way to assess risk for csPCa, ideally in combination with mpMRI, and also prompts reevaluation of 15.6 as an optimal cutoff EPI score.
Immunologic effects of B cell depletion on T cells in high-risk prostate cancer.
Authors: Sangwoo Shawn Kim, Jamillah Murtadha, Sayuri Miyauchi, Stephen T Ryan, Jing Zhang, Emily Pittman, Karen Messer, Michael Karin, Christopher J. Kane, Ahmed Shabaik, Stephen B. Howell, Christina Jamieson, Andrew Sharabi
Journal: Journal of Clinical Oncology (2024)

5096 Background: High-risk prostate cancer (HR-PCa) remains one of the leading causes of cancer-related death. Previous studies reported that a high density of immunosuppressive B cells in HR-PCa resection specimens was found to correlate with biochemical failure. In this context, a single arm prospective study assessing neoadjuvant rituximab, an anti-CD20 monoclonal antibody used to deplete B cells, was previously conducted on patients with HR-PCa eligible for radical prostatectomy (“PROTUX”). Here, we performed deep TCR sequencing to elucidate the impact of B cell depletion on T cells in prostate cancer patients. Methods: A single arm study enrolled patients with HR-PCa to receive neoadjuvant rituximab prior to radical prostatectomy (NCT: 01804712). Patients were treated with rituximab 375 mg/m 2 once weekly for 4 treatments followed by prostatectomy within 14 days of the final treatment of rituximab. A matched cohort of patients with HR-PCa who underwent prostatectomy without any prior therapy were used as controls. Specimens from 14 patients were retrieved and genomic DNA was isolated using a QIAamp DNA FFPE Advanced UNG kit. TCR sequencing was performed with Adaptive Biotechnologies using the Ultradeep TCRB v4b assay. Data were then analyzed using the Adaptive immunoSEQ Analyzer. Groups were compared using a Mann-Whitney U test. Statistical analysis and graphing were done in Prism 10 and R. Results: We observed that patients treated with rituximab had higher TCRb productive clonality (0.080 vs 0.026, p = 0.03). Strikingly, the calculated number of T cells present in prostatectomy samples was significantly greater in patients receiving rituximab compared to controls (1.18 cells/ng DNA input vs 0.10 cells/ng, p = 0.002). Maximum productive frequency and the cumulative frequency of the top 10 clones were not significantly different between the two cohorts. However, we found that the T cells from patients who received rituximab had longer TCRb CDR3 regions (proportion CDR3 ≥16 amino acids of 0.232 vs 0.197, p = 0.007), suggesting a less antigen-experienced phenotype. Conclusions: Using specimens from a clinical trial assessing the use of neoadjuvant rituximab in HR-PCa, we found that B cell depletion can significantly affect T cell infiltration, clonality, and phenotype. Given the increasing appreciation for crosstalk between T cells and B cells in mediating anti-tumor immune responses, these findings suggest a context dependent role of B-cells in patients with HR-PCa. Clinical trial information: NCT01804712 .
Disparity in education and disease stage in patients with testicular germ cell tumors.
Authors: Michal Chovanec, Rateb Alzeer, Nikola Hapakova, Katarina Kalavska, Peter Lesko, Jana Obertova, Zuzana Orszaghova, Patrik Palacka, Katarina Rejlekova, Daniela Svetlovska, Zuzana Sycova-Mila, Lucia Vasilkova, Michal Mego
Journal: Journal of Clinical Oncology (2024)

e17108 Background: Disparities may result in delayed staging and worse outcomes in cancer patients. Testicular germ cell tumors (GCTs) have excellent prognosis. However, disparities in education may have detrimental effect on early diagnosis and treatment. This study evaluated differences in staging and disease burden based on education in GCT patients treated at National Cancer Institute in Slovakia. Methods: Our institutional database was searched for GCT patients treated at National Cancer Institute in Slovakia between 1984 and 2023. Educational status was categorized as: basic/high-school and university. Educational status was correlated with disease stage, IGCCCG risk group, non-metastatic vs metastatic disease and size of retroperitoneal lymph nodes. Methods of descriptive statistics Chi-squared test and logistic regression were used for statistical analysis. Results: This retrospective study included 232 patients treated for stage I or metastatic GCT. Of the patients, 7 (3%), 114 (49%) and 111 (48%) had basic, high-school and university education, respectively. 46 patients (20%) had stage I disease and 186 patients (80%) were treated for metastatic disease. Patients who had basic/high-school education were diagnosed with metastatic disease more commonly compared to patients with university degree (p = 0.01). The Odds ratio for higher risk in patients without university education was 4.6 (95% CI 1.4-15.1). IGCCCG risk group, nodal stage or presence of non-pulmonary visceral metastases did not correlate with educational status (all p&gt;0.05). Conclusions: GCT patients with basic- and/or high-school education are diagnosed with metastatic disease more frequently than those with university education. Our study may suffer from referral bias. Raising awareness in schools is imperative for early diagnosis of GCTs.
Dissecting and Visualizing the Functional Diversity of Cardiac Macrophages
Authors: Megan Holt, Julia Lin, Markus Cicka, Anthony Wong, Slava Epelman, Kory J. Lavine
Journal: Circulation Research (2024)

Cardiac macrophages represent a functionally diverse population of cells involved in cardiac homeostasis, repair, and remodeling. With recent advancements in single-cell technologies, it is possible to elucidate specific macrophage subsets based on transcriptional signatures and cell surface protein expression to gain a deep understanding of macrophage diversity in the heart. The use of fate-mapping technologies and parabiosis studies have provided insight into the ontogeny and dynamics of macrophages identifying subsets derived from embryonic and adult definitive hematopoietic progenitors that include tissue-resident and bone marrow monocyte-derived macrophages, respectively. Within the heart, these subsets have distinct tissue niches and functional roles in the setting of homeostasis and disease, with cardiac resident macrophages representing a protective cell population while bone marrow monocyte-derived cardiac macrophages have a context-dependent effect, triggering both proinflammatory tissue injury, but also promoting reparative functions. With the increased understanding of the clinical relevance of cardiac macrophage subsets, there has been an increasing need to detect and measure cardiac macrophage compositions in living animals and patients. New molecular tracers compatible with positron emission tomography/computerized tomography and positron emission tomography/ magnetic resonance imaging have enabled investigators to noninvasively and serially visualize cardiac macrophage subsets within the heart to define associations with disease and measure treatment responses. Today, advancements within this thriving field are poised to fuel an era of clinical translation.
An NCDB demographic and socioeconomic analysis of mixed acinar ductal carcinoma.
Authors: Sierra Alban, Nicoline Breytenbach, Amber Chang, Jyztine Reyes, Peter T. Silberstein, Craig Heise, Beau Hsia
Journal: Journal of Clinical Oncology (2024)

e17097 Background: Mixed acinar ductal carcinoma (MADC) is a rare form of prostate carcinoma with both acinar carcinoma and ductal adenocarcinoma components, originating in the prostate. Despite their infrequent occurrence, mixed carcinomas have demonstrated increasing prevalence in recent years and are associated with poor prognosis. This is especially concerning since prostate malignancies are one of the most common in men across the world. Thus, understanding the demographic patterns related to this malignancy can offer insight into its epidemiology, diagnosis, and relevant risk factors. The National Cancer Database (NCDB) was used to analyze these patterns in mixed acinar ductal carcinoma. Methods: A retrospective cohort analysis using data from the NCDB was performed for patients diagnosed with mixed acinar ductal carcinoma, ICD-O-3 Code 8552, between 2018 and 2020 (N = 206). Demographic factors were analyzed using descriptive statistics, including age, sex, race, Hispanic heritage, type of facility, distance from facility, and Charles/Deyo score. Statistical regression analysis was used to evaluate incidence patterns. Results: Between 2018 and 2020, 206 patients with a MADC diagnosis were identified with a gradually increasing incidence of diagnosis (R² = 0.2276). Of this cohort, an overwhelming majority identified as male (98.5%) and of White (83%) and non-Hispanic (95.6%) origin. The majority of patients (54.4%) received coverage from Medicare and another 39.5% were under private insurance/managed care. The most common primary site was the prostate (95.1%). NCDB Analytic Staging was not applicable in most cases (82%) and most individuals had a total Charlson-Deyo comorbidity score of 0 (77.2%). The average age at diagnosis was 67.2 years (SD = 8.6, range = 43 – 90 years). Most patients (84.0%) received surgery; following resection of the primary tumor, over half of these patients (53.4%) had no residual tumor. Many of the patients (97.4%) survived at least thirty days after primary surgery, with a similar survival rate (94.9%) after ninety days. The estimated two-year survival rate was 93.9% and the mean survival after diagnosis was 43.2 months (3.6 years). Conclusions: Based on our literature searches, this is the first analysis using NCDB data for mixed acinar ductal carcinoma addressing the lack of understanding of the demographic aspects of the disease. MADC patients were mostly White and non-Hispanic males. Most of these patients held Medicare as a primary insurance, likely due to the overall older population impacted by this cancer. MADC primarily affected the prostate and the patients typically had a favorable prognosis following surgery of the primary site. Additional investigations are necessary to determine the effects of these socioeconomic and demographic factors on individuals with mixed acinar ductal carcinoma.
Experience with de-intensification of intensified treatment in metastatic castration-sensitive prostate cancer in Venezuela: A pilot study.
Authors: Carlos Eduardo Sucre, Oscar Sucre, Rudy Cavaniel, Santiago Sucre, Guillermo Borga
Journal: Journal of Clinical Oncology (2024)

e17080 Background: Novel therapeutic approaches in recent years have changed the management of metastatic castration-sensitive prostate cancer (mCSPC). Traditionally, an antiandrogenic agent was used for androgen deprivation (AD); currently, the approach is to do treatment intensification with AD plus an additional medication (such as abiraterone, enzalutamide, docetaxel, among others). Historically, intermittent versus sustained AD have been considered as equally effective therapeutic measures. In developing countries, treatment adherence has been limited by access to some of these medications, as well as financial toxicity. Recently a new therapeutic approach has been proposed, one which entails treatment de-intensification in patients with a negative PSA after 1 year of treatment, aiming to decrease adverse events and improve treatment adherence. Methods: We included patients with mCSPC that received treatment intensification with AD plus either abiraterone or enzalutamide. Concurrent use of docetaxel was allowed. After at least twelve months of treatment and with a PSA level under 0.2 ng/mL, we proceeded to suspend intensified therapy, maintaining AD alone (de-intensification). These patients were followed up every 12 weeks, with a clinical evaluation plus PSA measurement. Patients that were deemed to have biochemical progression were excluded from the study, and underwent full imaging evaluation as well as a change in their current therapy on a case-by-case basis. Results: A total of 28 patients with mCSPC are included, with a mean age of 71.71 years. Thirteen patients have synchronic disease (46.42%), and fifteen patients have metachronic disease (53.58%). Of the original 28 patients, 16 patients have low volume disease (57.14%) and 12 have high volume (42.85%). Concurrently, 26 out of the 28 included patients had a negative PSA after six months of follow up (92.85%). To this date, 18 patients have completed twelve months of follow up, out of which 15 patients have maintained a negative PSA (83.3% of total sample). Out of the other 3 that developed biochemical progression, 2 of them had high volume disease and all 3 had a Gleason 8 score. Conclusions: Treatment de-intensification appears to be an acceptable therapeutic approach. This strategy could prove most beneficial in developing countries, where access to some medications is limited, and could improve treatment adherence in the long run. Adverse events associated to medications is also minimized with this approach. It’s also possible that this new therapeutic approach is most beneficial in lower risk patients (Gleason score &lt; 8, low volume metastatic disease). In order to make these results more robust, a larger population sample and longer follow up is required.
Autoimmune Myocarditis, Old Dogs and New Tricks
Authors: Taejoon Won, Evelyn J. Song, Hannah M. Kalinoski, Javid J. Moslehi, Daniela Čiháková
Journal: Circulation Research (2024)

Autoimmunity significantly contributes to the pathogenesis of myocarditis, underscored by its increased frequency in autoimmune diseases such as systemic lupus erythematosus and polymyositis. Even in cases of myocarditis caused by viral infections, dysregulated immune responses contribute to pathogenesis. However, whether triggered by existing autoimmune conditions or viral infections, the precise antigens and immunologic pathways driving myocarditis remain incompletely understood. The emergence of myocarditis associated with immune checkpoint inhibitor therapy, commonly used for treating cancer, has afforded an opportunity to understand autoimmune mechanisms in myocarditis, with autoreactive T cells specific for cardiac myosin playing a pivotal role. Despite their self-antigen recognition, cardiac myosin-specific T cells can be present in healthy individuals due to bypassing the thymic selection stage. In recent studies, novel modalities in suppressing the activity of pathogenic T cells including cardiac myosin-specific T cells have proven effective in treating autoimmune myocarditis. This review offers an overview of the current understanding of heart antigens, autoantibodies, and immune cells as the autoimmune mechanisms underlying various forms of myocarditis, along with the latest updates on clinical management and prospects for future research.
Germline gene-specific associations in a large prostate cancer cohort.
Authors: Hiba M Khan, Sarah M. Nielsen Young, Emily M. Russell, Ed Esplin, W. Michael Korn, Heather H. Cheng
Journal: Journal of Clinical Oncology (2024)

5102 Background: Identification of pathogenic germline variants (PGV) in patients (pts) with prostate cancer (PC) enables precision therapy and cascade testing. Equitable advances in precision PC management require more detailed understanding of gene-level associations. Herein we describe PC gene-specific demography in a large cohort of PC pts. Methods: Germline genetic testing (GGT) (Invitae Corp.) and insurance claims (Komodo Healthcare Map) data were linked for PC pts from 2015-2023. ICD/CPT codes were used to define PC personal and family history and disease stage (early-stage = codes for active surveillance or definitive local treatment; advanced = remaining pts). PC genes analyzed were those in NCCN PC guidelines with &gt;100 PGV+ pts: ATM, BRCA1, BRCA2, CHEK2, HOXB13 and mismatch repair (MMR) genes ( EPCAM, MLH1, MSH2, MSH6, PMS2). Two sample t-tests were used for age and chi-square tests were used for other variables, with a Bonferroni correction for post hoc analysis. Results: 14,979 pts had GGT: 68% with advanced disease (enriched for BRCA2) and 32% with early-stage. Mean diagnosis age was 64, and significantly younger for ATM/ BRCA2/ HOXB13+ pts (p&lt;0.04) (Table). BRCA2was the most common PGV but was not enriched in any clinician-reported race/ethnicity. CHEK2/MMR+ pts were more likely to be White ( post hoc p&lt;0.001). The Midwest had the highest frequency of PGV (12%). A lower proportion of CHEK2+ pts resided in the South ( post hoc p&lt;0.001). 26% of PGV+ pts had documented PC family history, which was significantly associated with BRCA2/HOXB13, and negatively correlated with MMR (p&lt;0.02 for both). Conclusions: In this cohort of ~15,000 PC pts, gene-specific associations were detected that warrant further study. Three-quarters of pts with PGV had no claims for family PC history, highlighting the importance of GGT in all pts meeting criteria, independent of family history. Further analysis of linked data will assess real-world treatment decisions and outcomes by GGT result. [Table: see text]