tbuckley/cabot-search huggingface dataset:
i-Biomarker CaDx: A circulating miRNA-based multi-cancer detection tool with explainable AI for prostate cancer.
Authors: Alexandru George Floares, Adrian Vasile Zety, Carmen Floares, George Calin, Eduardo Kreutz Carvalho, Florin Manolache
Journal: Journal of Clinical Oncology (2024)

272 Background: Prostate cancer is a pressing concern, demanding early and accurate detection for effective intervention. Conventional methods, like digital rectal exams and prostate-specific antigen (PSA) tests, often lack the required specificity. Circulating microRNAs (miRNAs) have emerged as promising non-invasive biomarkers for various cancers, including prostate cancer. The i-Biomarker CaDx is a cutting-edge, technology-neutral platform designed for multi-cancer early detection, boasting an impressive accuracy rate of 99-100%. This study aims to assess the effectiveness of i-Biomarker CaDx specifically for prostate cancer using publicly endorsed datasets while leveraging explainable artificial intelligence (XAI) to gain deeper insights. Methods: The utilized dataset (GSE112264) contains 809 prostate cancer patients matched with an equal number of age-matched healthy controls from multiple datasets. Microarray technology was employed to profile circulating miRNAs. A diverse range of classification paradigms, including decision trees, neural networks, and support vector machines, were utilized for attribute identification, classification, and seamless integration of XAI. Rigorous hyperparameter optimization was conducted, and the best-performing classifiers were amalgamated into the final model, weighted by their respective efficacies. We assessed i-Biomarker CaDx's performance through rigorous cross-validation and independent test datasets. The XAI component provided detailed insights into miRNA variations associated with diagnostic outcomes. Results: Our findings reveal that i-Biomarker CaDx exhibits exceptional diagnostic accuracy, achieving a remarkable 100% accuracy rate when evaluated on the designated dataset. Diagnostic metrics, including sensitivity, specificity, and predictive values, surpass conventional prostate cancer diagnostic methods like digital rectal exams and PSA tests. The designed models, incorporating decision trees, neural networks, and support vector machines, effectively decipher intricate miRNA relationships relevant to prostate cancer using XAI. Thus, our analyses shed light on miRNA patterns and their associations with prostate cancer, enhancing the understanding of the underlying molecular complexities of the disease. Conclusions: i-Biomarker CaDx, a pioneering technology-agnostic multi-cancer early diagnostic platform, demonstrates outstanding performance in detecting prostate cancer, surpassing traditional diagnostic methods. The integration of XAI allows for in-depth exploration of miRNA alterations and their impact on prostate cancer, enriching our interpretations at both the population and individual levels. These findings underscore the substantial potential of i-Biomarker CaDx as a transformative, non-invasive diagnostic tool for prostate cancer.
Difference in high-risk prostate cancer detection between transrectal and transperineal fusion approaches.
Authors: Sofiya Semko, Axel Heidenreich, Pia Paffenholz, David A. Pfister, Maksym Pikul
Journal: Journal of Clinical Oncology (2024)

273 Background: Present study aimed to gain insight into whether patients with high-risk prostate cancer (defined as Gleason 8-10) are being more precisely diagnosed by MRI fusion technique compared to TRUS-guided biopsy. Methods: A special retrospective cohort study database analysis was planned and conducted by urological department of University clinic of Cologne. After the database cut off the group of 779 patients with prostate cancer that underwent biopsy and further surgical treatment (radical prostatectomy) was selected. it was split into 2 cohorts according to biopsy type: TRUS guided biopsy and transperineal Fusion Biopsy. Standard systemic approach included 12 cores in TRUS and 18 in MRI-guided cohorts. Additional 5-6 cores were taken from the region of interest in the Fusion group. All the patients during analysis were divided into risk groups: Gleason 6 (3+3) - low risk group, Gleason 7a (3+4) - intermediate risk group, favourable prognosis, Gleason 7b (4+3) - intermediate risk group, unfavourable prognosis, Gleason 8-10 – high group. Concordance of primary and postoperative pathology was estimated by using re-grading levels and migration from low\intermediate to high-risk group. Additionally, the presence of one or more risk factors (perineural and lymphovascular invasion, presence of cribriform pattern, etc.) in primary specimens was evaluated. Results: The groups were statistically equal by age (p = 0,16), PSA risk-groups (χ2= 1,36; p = 0,53), density division ( χ2= 0,58; p = 0,74), prostate volume (p = 0,23) and ECOG status (Me [25 %; 75 %] p = 0,17). There were no significant differences between groups in terms of final pathology – number of cases in low, intermediate and high risk groups (χ2= 1,37; p= 0,5). Difference was observed in lower rate of upgrading to high-risk group and higher detection of risk factors in favour of transperineal-targeted biopsy (Table). Exposure of targeted biopsy increased the probability of detecting high risk PCa by 39% compared to systemic cores (OR 1.39, 95% CI: 0.9 - 1.9; p = 0,06). Conclusions: Transperineal fusion biopsy can be characterised by a higher possibility of detecting high-risk prostate cancer compared to conventional transrectal methods. A higher probability of discovering risk factors after transperineal fusion biopsy might be an important tool for proper staging and risk-adapted treatment strategy.[Table: see text]
Clinical study of rezvilutamide inhibiting the flare effect of GnRH agonists in the treatment of newly diagnosed metastatic prostate cancer.
Authors: Shaogang Wang, Zhihua Wang, Zhiquan Hu, Chunguang Yang
Journal: Journal of Clinical Oncology (2024)

TPS233 Background: To prevent ‘flare-up’ phenomenon, mainstream guidelines recommend offering a first-generation antiandrogen for ≥7 days to metastatic prostate cancer starting GnRH agonist. Our previous study found that in the 3-day regimen of a new AR antagonist apalutamide (that is, GnRH agonist was given 3 days after application of apalutamide), PSA decreased by 5-10% on day 1, and PSA decreased by about 1/3 after 3 days of oral administration, which was equivalent to the inhibition of PSA synthesis by bicalutamide for 4 weeks, and no clinical symptoms were worsened. Since the blood concentration of the new AR antagonists could reach nearly 80% of the peak concentration after 1 hour of oral administration, our research group further tried the 1-hour regimen (that is, GnRH agonist was given after 1 hour of application of apalutamide), and 8 patients showed an increase in serum testosterone, but no increase in PSA and aggravation of clinical symptoms, which initially indicated the feasibility of the 1-hour regimen. The objective of this study is to explore the efficacy and mechanism of the combined application of rezvilutamide and GnRH agonist (Goserelin Microspheres for Injection) on mHSPC to prevent flare-up. Methods: This is a multicenter, prospective, randomized controlled study (ChiCTR2300076106). Key inclusion criteria: Age ≥ 18 years, first diagnosis of prostate adenocarcinoma by histologically confirmed within 1 month; at least one distant metastasis (extrinsic pelvic lymph node metastasis, bone metastasis, or visceral metastasis); PSA ≥ 2ng/ml and serum testosterone ≥ 150ng/dl. Sixty mHSPC patients are expected to be enrolled and treated with rezvilutamide combined with GnRH agonist. The patients will be randomized 1:1 into the 1-day regimen (oral rezvilutamide 1 day in advance) and the 1-hour regimen (oral rezvilutamide 1 hour in advance) with 30 patients each. The GnRH agonist treatment is 3.6 mg Goserelin Microspheres for Injection i.m. every 4 weeks. Collect patient baseline data: Age, tumor size, pathological classification, TNM stage, Gleason score, clinical symptoms, PSA level, testosterone level. Periodic review of laboratory tests (PSA, LH, testosterone, etc.), imaging changes (magnetic resonance, CT, PET/CT, etc.), changes in clinical symptoms, changes in survival status, etc. The occurrence of flare-up effects and hormone levels on day 1, day 3, day 7, day 14, and day 28 after medication will be described. Kaplan-Meier survival analysis and Cox proportional-hazards model were used to evaluate the above indicators. Clinical trial information: ChiCTR2300076106 .
Real world evidence from a retrospective multi-center analysis on first-line therapy for metastatic renal cell carcinoma with non-clear cell and/or sarcomatoid histologies.
Authors: Pia Paffenholz, Stefanie Zschaebitz, Jozefina Casuscelli, Emily Rinderknecht, Angelika Mattigk, Melis Gür, Philipp Ivanyi, Thomas Hilser, Christopher Darr, Subhajit Mandal, Katrin Schlack, Daniel Seidl, Analena Handke, Melanie Klee, Tim Nestler, Marc Rehlinghaus, Sameh Hijazi, Axel Heidenreich, Viktor Grünwald, Martin Schostak
Journal: Journal of Clinical Oncology (2024)

392 Background: Papillary (pRCC), chromophob (chRCC) and predominantly sarcomatoid renal cell carcinoma (sRCC) as well as RCC with sarcomatoid features are rare cancers. We evaluated real-world treatment outcomes of 1 st line treatment in these cohorts in Germany. Methods: We retrospectively analyzed patients with non-clear cell RCC treated at 17 German tertiary cancer centres. Adverse events (AE) were reported according to CTCAE 5.0, objective response rate (ORR) according to RECIST 1.1. Progression free survival (PFS) and overall survival (OS) were calculated from start of treatment to progression or death, respectively and determined by KM plots. Results: We included 189 patients with a median age of 63 years (IQR 54-72). Of these, 49% were pRCC, 12% chRCC, 12% sRCC. 17% of all RCC had a sarcomatoid features. 87% had an ECOG PS of 0/1. IMDC risk was favorable/intermediate/poor in 15/54/31%. 74% received prior nephrectomy. Lymphatic (63%) and pulmonary (51%) metastases were the most common metastatic sites. 72% patients received first-line IO-combinations (IO-IO: 36%, TKI-IO: 64%) and 28% patients TKI-monotherapy, predominantly sunitinib. AE of all grades occurred in 86% and 72% during IO-based therapy or TKI monotherapy, and CTCAE grade ≥ 3 in 46% or 36%, of which led to discontinuation of treatment in 42% or 29% of patients, respectively. ORR and survival outcomes with median follow-up of 17 months (IQR 9-30) are described in the table. Conclusions: IO-combinations are frequently applied in pRCC, chRCC and sRCC. Our data suggests that first-line IO-combinations yields higher ORR compared to single agent TKI in sRCC, but not in chRCC. However, the retrospective nature and small sample size are major limitations of our analysis. Additional analyses to tailor treatment strategies in patients with metastatic nccRCC or sRCC is warranted. [Table: see text]
Evolving treatment landscape in metastatic urothelial carcinoma (mUC) post-avelumab maintenance approval: Real-world insights from The US Oncology Network.
Authors: Haojie Li, Sneha Sura, Aram Babcock, Lisa Herms, Jinhong Guo, Paul Conkling, Sonia Franco, Puneet K. Singhal, Ronac Mamtani, Manojkumar Bupathi
Journal: Journal of Clinical Oncology (2024)

560 Background: Locally advanced/metastatic urothelial carcinoma (mUC) has poor prognosis and disproportionately affects the elderly, who often have coexisting illness and limited treatment options. According to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer (v3.2023), platinum-based chemotherapy (PBC) followed by avelumab maintenance therapy (maintA, only if there is no progression on first-line [1L] PBC), pembrolizumab (P, for platinum-ineligible), and P in combination with enfortumab vedotin (P+EV, for cisplatin-ineligible) are the preferred regimens. We evaluated real-world treatment patterns and overall survival (OS) among mUC patients during the period between maintA and P-EV approvals in the US. Methods: This retrospective cohort study was conducted using structured and chart review data from iKnowMed (iKM), The US Oncology Network electronic health record database. The cohort included adult mUC patients diagnosed between 30 April 2020 and 30 June 2021. Patients were followed from index date (date of 1L anticancer treatment) through 31 March 2023, last patient record or death, whichever occurred first. MaintA was defined as receiving avelumab after 1L PBC, with no documented progressive disease prior to avelumab start or as maintenance therapy indicated by physician notes. Descriptive statistics were used to report patient characteristics and treatment patterns. Kaplan-Meier analysis was implemented to assess OS. Results: A total of 207 patients initiated 1L treatments. The median age was 74 (range: 46 - 90+) years and 166 (80.2%) were male. Of 207 1L-treated patients, 107 (51.7%) received immune checkpoint inhibitor (ICI) monotherapy, 80 (38.6%) received PBC, and 20 (9.7%) received other treatments. The use of 1L ICI monotherapy increased with age, ranging from 15 (14.0%) among those younger than 65 to 57 (53.3%) among those aged 75 or older. Of patients who received 1L PBC, 28 (35.0%) received ICI maintenance therapy; majority of these (n = 26, 92.9%) received maintA (32.5% of patients received 1L PBC). During the follow-up, 71 (34.3%) patients received 2L treatment and 25 (12.1%) patients received 3L treatment. Majority of patients in 2L settings received antibody drug conjugates (n = 30, 42.2%) or ICI monotherapy (n = 27, 38.0%). Median (95% confidence interval) OS was 12.6 (8.5, 15.1) months for 1L-treated patients overall. Conclusions: Despite many recent advances in the therapy for mUC, these patients had poor prognosis. Notably, many 1L patients did not have the opportunities to receive 2L+ treatment, which demonstrated continuing unmet need for mUC patients. ICI monotherapy continues to be a prevalent option, especially for older patients.
Peripheral biomarker analysis in patients with advanced urothelial carcinoma (UC) after platinum chemotherapy treated with cabozantinib (CABO) plus durvalumab (DURVA): Preliminary analysis from the phase 2 ARCADIA trial.
Authors: Patrizia Giannatempo, Francesco Sgambelluri, Marco Stellato, Valentina Guadalupi, Daniele Raggi, Alessandro Rametta, Achille Bottiglieri, Melanie Claps, Ferrari Bravo Walter, Simone Oldani, Matteo Zimatore, Giuseppina Calareso, Alessandra Alessi, Laura Cattaneo, Elena Verzoni, Filippo G. De Braud, Giuseppe Procopio, Andrea Necchi, Andrea Anichini, Roberta Mortarini
Journal: Journal of Clinical Oncology (2024)

684 Background: Preliminary results of the interim analysis of the ARCADIA trial have shown that combining multitargeted receptor tyrosine kinase inhibitor CABO with the checkpoint inhibitor DURVA has promising activity and a manageable safety profile in patients (pts) affected by UC recurred or progressed after failure of at least one line of platinum-based chemotherapy for metastatic disease in a phase II study (NCT03824691). To identify peripheral blood biomarkers potentially associated with clinical response, we carried out a quantitative profiling of innate and adaptive immune subsets from a subset of treated pts. Methods: From 09/2019 and 08/2023 blood samples from 65 pts were collected at baseline and before the third treatment cycle. Absolute cell counts for 29 innate and adaptive immune subsets were determined by multiparametric flow cytometry. Results: In pre-therapy samples a significant higher counts for all CD45+ leukocytes were found in non-responders compared to responders (p=0.0053, Mann Whitney test, n= 27 patients). This was, explained by higher counts for CD16+CD15+ neutrophils (p=0.0005), classical CD14+CD16- (p=0.0119) and CD14++CD16+ intermediate (p=0.0186) monocytes, CD56dim CD16+ NK cells (p=0.0365) and Lin-HLA-DR-/LoCD33+CD14+CD15- M-MDSCs (p=0.0281). At baseline, higher neutrophils counts were associated with worse PFS (p=0.0117, log rank test), while higher eosinophils counts were associated with improved PFS (p=0.0158). Compared to responders, non-responders underwent a significant reduction in post-treatment counts for all CD45+ leukocytes (p=0,0024, Wilcoxon matched pair test), due to reduction of neutrophils (p=0.0068), CD15+CD16- eosinophils (p=0.0068), CD3+ T cells (p=0.0425) CD19+ B cells (p=0.0068), classical monocytes (p=0.0034), activated (HLA-DR+) CD56dim CD16- NK cells (p=0.0068), M-MDSCs (p=0.0161), Lin- HLA-DR-/Lo CD33+ CD14- CD15+ PMN-MDSCs (p=0.001), Lin- HLA-DR+ CD33- pDCs (p=0.0269) and Lin- HLA-DR+ CD33+ mDCs (p=0.0005). Conclusions: These preliminary findings suggest that high baseline counts for granulocytes, monocytes and MDSCs may negatively impact on response in pts treated with CABO+DURVA. Moreover, baseline neutrophils and eosinophils counts show opposite impact on PFS. Grant support: NET-2016-02361632 from Italian Health Ministry to A. Anichini. Clinical trial information: NCT03824691 .
Subcutaneous nivolumab (NIVO SC) vs intravenous nivolumab (NIVO IV) in patients with previously treated advanced or metastatic clear cell renal cell carcinoma (ccRCC): Pharmacokinetics (PK), efficacy, and safety results from CheckMate 67T.
Authors: Saby George, Maria Teresa Bourlon, Matias Rodrigo Chacon, Hernan Cutuli, Yamil Alonso Lopez Chuken, Bogdan Zurawski, Jose Mauricio Mota, Ignacio Magri, Mauricio Burotto, Murilo Luz, Juliana De Menezes, Eduardo Patricio Yanez Ruiz, Marco Maruzzo, Sergio Bracarda, Subhransu Prusty, Dhanrajsinh Rathod, Heather Vezina, Zhuoxin Yu, Yue Zhao, Laurence Albiges
Journal: Journal of Clinical Oncology (2024)

LBA360 Background: NIVO IV has improved outcomes in multiple tumor types. Evolving treatment paradigms have created a need for administration options that address treatment burden and improve efficiencies of healthcare systems. SC delivery of antibodies for various cancer indications has proved safe and effective. CheckMate 67T (NCT04810078) is a multicenter, randomized, open-label, phase 3 study that evaluated PK and objective response rate (ORR) noninferiority of NIVO SC vs IV in patients (pts) with locally advanced or metastatic ccRCC. Methods: Enrolled pts had measurable disease that progressed during or after 1–2 prior systemic regimens, no prior immuno-oncology treatment, and a Karnofsky performance score ≥ 70. Pts were randomized 1:1 to receive NIVO SC 1200 mg + recombinant human hyaluronidase PH20 Q4W or NIVO IV 3 mg/kg Q2W until disease progression, unacceptable toxicity, withdrawal of consent, completion of 2 years’ treatment, or death. The co-primary PK endpoints for noninferiority testing were time-averaged serum concentration over the first 28 days (C avgd28 ) and minimum serum concentration at steady state (C minss ) determined by a population PK analysis. ORR by blinded independent central review (BICR) was a key powered secondary endpoint for noninferiority testing. Other secondary objectives included additional PK exposure measures, safety, efficacy, and immunogenicity. Results: A total of 495 pts were randomized to NIVO SC (n = 248) or NIVO IV (n = 247). The median age was 64/66 years in the SC/IV arms. Most pts were male. Average injection time with NIVO SC was &lt; 5 minutes. Noninferiority for the co-primary PK and key powered secondary ORR endpoints was met (see table). Incidence of NIVO SC local injection-site reactions was 8.1%; reactions were low grade and transient. Most deaths were due to disease progression; study drug toxicity led to 3/1 deaths with NIVO SC/IV. Conclusions: The co-primary PK and key powered secondary ORR endpoints were met, supporting the use of NIVO SC as a new option to improve healthcare efficiency. The safety profile for NIVO SC was consistent with NIVO IV. Clinical trial information: NCT04810078 .[Table: see text]
Contemporary diagnosis of very low risk prostate cancer in a multi-centered hospital system.
Authors: Richard Bennett, Eric Li, Austin Y. Ho, Jonathan Aguiar, Ashorne Krithiesh Mahenthiran, Sai Kumar, Chalairat Suk-ouichai, Clayton Neill, Hiten Dilip Patel, Edward M. Schaeffer, Anugayathri Jawahar, Ashley Ross
Journal: Journal of Clinical Oncology (2024)

274 Background: NCCN very low risk (VLR) prostate cancer is frequently clinically insignificant and thus over-diagnosed. Use of MRI prior to patient selection for prostate biopsy and to inform biopsy targeting can reduce the diagnosis of VLR disease. Indeed, a recent publication has reported no VLR diagnoses since 2018. We sought to better understand the incidence of VLR disease in our multi-hospital institutional cohort. Methods: We retrospectively identified 3197 patients who were newly diagnosed with prostate cancer at our eleven-hospital system from January 2018 – June 2023. Within this cohort, we identified patients who met VLR criteria. Patient clinical, pathological, and imaging characteristics were collected for analysis. Biopsies were considered MRI-informed if MRI was performed within two years prior to prostate biopsy. Biopsies were considered targeted if at least one region of interest was designated on pathology. Patients who had incomplete clinical records (n=2) were excluded from analysis. Active surveillance as initial disease management was defined as no treatment within one year of diagnosis. Welch’s two-sample t-test, Pearson’s chi-squared test, and Fisher’s exact tests were performed to compare clinical characteristics. PSA was log transformed for analysis. Results: In the study period, 11% (351/3195) of men diagnosed with prostate cancer were classified as NCCN very low risk. The incidence of VLR diagnoses was steady from 2018-2023 (p=0.8) despite increased usage of MRI-informed biopsies (p&lt;0.001). Use of MRI-informed biopsy was similar for detection of VLR and higher risk disease (68% vs 72%, p=0.07). Of VLR patients who received a targeted biopsy, 69% (127/184) of disease was found in systematic regions only, 21% (39/184) was found in targeted regions only, and 10% (18/184) was found both systematically and in targeted regions. On multivariable analysis, black race, logPSA, and PIRADS 4 and 5 regions were negatively associated with VLR disease (Table). 86% (304/351) of VLR patients chose active surveillance as their initial disease management. Conclusions: VLR disease comprises a significant minority of prostate cancer diagnoses. The incidence of VLR has remained unchanged despite increased utilization of MRI-informed biopsies in our hospital system. In the majority of cases the diagnosis of VLR is made from the template biopsy (whether MRI-informed or not). Patients should, and frequently do, choose active surveillance to manage their disease. Use of nomograms and limiting biopsy of PI-RADS 3 lesions may decrease the incidence of VLR prostate cancer.[Table: see text]