tbuckley/cabot-search huggingface dataset:
Identifying racial disparities in adverse dispositions following major surgery for prostate cancer using machine learning.
Authors: Atulya Aman Khosla, Nitya Batra, Mohammad Arfat Ganiyani, Karan Jatwani, Rohit Singh, Lakshmi Prajwala Chedella Venkata, Mukesh Roy, Venkataraghavan Ramamoorthy, Muni B. Rubens, Anshul Saxena, Rohan Garje, Ishmael A. Jaiyesimi
Journal: Journal of Clinical Oncology (2024)

269 Background: Machine learning has shown potential in accurately predicting outcomes after urologic surgery, allowing for improved patient selection, risk stratification, and predicting discharge dispositions. Healthcare disparities pose a major public health challenge, leading to unequal health outcomes for different patient groups. Successful measures to mitigate these disparities rely on precise recognition of the demographic groups impacted. In this study, we utilized AI and ML models to predict such adverse outcomes so that early intervention may lead to timely and optimal prostate cancer care. Methods: Using the 2016–2021 ACS National Surgical Quality Improvement Program (NSQIP) data, we identified 84,064 patients who underwent prostatectomy or surgeries related to excision of the prostate. We used Gradient Boosted Trees, Random Forests, and Deep Learning to examine the association between various variables from demographic, clinical, preoperative labs, past medical history domains, and non-home discharge disposition after cancer surgery. Accuracy rates were utilized to compare various models. Results: The median [Q1, Q3] age of the sample was 65.0 [59.0, 69.0] years. The total median [Q1, Q3] hospital length of stay and operation time of the sample was 1.0 [1.0, 2.0] days and 200.0 [153.0, 257.0] minutes, respectively. White non-Hispanic (WNH) patients constituted 62% (n = 52,444) of the sample, and Black non-Hispanic (BNH) were 11% (n = 9547). Smoking prevalence was higher among BNH cases (18.6%) as compared to WNH cases (10.9%). The proportion of cases requiring hypertension medication was 66.6% among BNH compared to 52.6% among WNH. The 30-day readmission rates for WNH, BNH, and White Hispanic (WH) cases were 6.4%, 6%, and 5.6%, respectively. The mortality rates for WNH, BNH, and WH cases were 0.3%, 0.3%, and 0.2%, respectively. The non-home discharge rates for WNH, BNH, and WH cases were 19.8%, 20.6%, and 22.4%, respectively. The machine learning model results showed that the Deep Learning model performed best in predicting discharge disposition after prostatectomy for prostate cancer, with an accuracy of 80.48%. Race was present in the list of important factors, indicating that race had a significant association with the outcome. Conclusions: Our study demonstrated that using a national registry, ML models can accurately identify patient populations affected by healthcare disparities. We found that racial disparities in adverse dispositions persisted after adjusting for covariates. Interventions aimed at reducing these disparities are warranted to improve the quality of life of this subgroup of patients. [Table: see text]
Using automated machine learning to detect kidney anomalies.
Authors: Rushil Rawal, John Heard, Peris Castaneda, Joshua Davood, Michael Ahdoot
Journal: Journal of Clinical Oncology (2024)

483 Background: Artificial Intelligence (AI) in Urology has been used for many conditions including benign prostatic hyperplasia (BPH), urological oncology, and kidney transplant. Many computer models use algorithms that may be intricate for urologists to implement, but automated machine learning (AML) can be used to create simple models. Here we expand the use of AI and AML in image detection of kidney tumors, stones, and unremarkable kidney from computed tomography (CT) using Google Vertex AI, a machine learning platform that allows for the building, training, and deployment of models. Methods: Google Vertex AI machine learning system was trained to perform image detection. CT Kidney images were taken from publicly available data from Kaggle, an online database and machine learning platform. Images are from multiple hospitals in Dhaka, Bangladesh. 300 CT Kidney Images were uploaded on Google Vertex AI: 100 tumors, 100 stone, and 100 normal. 240 images were used to train the model, 30 for validation, and a final 30 images for assessing the accuracy of predictions after the training phase. To comprehensively evaluate our model, CT kidney images from the Cedars Sinai Medical Center were employed for further testing. All training images lacked annotations and were solely classified as normal, stone, or tumor. Results: True positivity rate for image detection during model training was 100% for tumors, stones, and normal CTs. We further tested accuracy using Cedars Sinai patient images, using 10 tumors, 10 stones, and 5 normal. The accuracy of the AI prediction was 80%, 70%, and 100%, respectively. Conclusions: Artificial Intelligence can be useful in interpreting urological imaging even in a minimally trained system. A model such as ours may allow for rapid identification and labeling of renal masses, kidney stones, and normal studies with moderate fidelity. Further training of this model may increase accuracy.
Linear muscle segmentation for metastatic renal cell carcinoma.
Authors: Edouard Nicaise, Benjamin Schmeusser, Adil Ali, Eric Midenberg, Arnold Raul Palacios, Ethan Kearns, Sriram Ambadi, Dattatraya H. Patil, Shreyas S. Joshi, Vikram M Narayan, Sarah P. Psutka, Bassel Nazha, Jacqueline T Brown, Kenneth Ogan, Mehmet Asim Bilen, Viraj A. Master
Journal: Journal of Clinical Oncology (2024)

380 Background: Baseline sarcopenia and postoperative changes in muscle mass are independently associated with overall survival in patients with metastatic renal cell carcinoma (mRCC) undergoing cytoreductive nephrectomy (CN). Here we examine the relationship between preoperative (baseline) and postoperative changes in muscle quantity with survival outcomes following CN as determined by linear segmentation, a fast and clinic-friendly tool. Methods: Our nephrectomy database was reviewed for patients with clear cell, papillary, or chromophobe mRCC who underwent CN. Linear segmentation of bilateral psoas/paraspinal muscles was completed for baseline imaging within 60 days of surgery and imaging up to 1 year postoperatively. ANOVA for numerical and chi-square for categorical variables were used to test for differences according to change in linear muscle index (LMI, cm2/m2). Multivariable models estimated COX hazard ratios for cancer-specific survival (CSS) and overall survival (OS). Kaplan Meier curves estimated CSS and OS. Results: From 2004-2020, 190 patients were identified 48 stable LMI (25.3%; &lt;5% change [0Δ]), 54 increase LMI (28.4%; +5% change [+Δ]), and 88 decrease LMI (46.3%; -5% change [-Δ]). Median time from baseline imaging to surgery was 18 days, while time from surgery to postoperative imaging was 119 days. Patients with +Δ had lower baseline LMI than -Δ or 0Δ (28.5 vs. 32.4 vs.32.5 cm2/m2; p=0.003). 0Δ LMI had lower rates of pN1 disease than other groups (27.1% [0Δ] vs. 42.6% [+Δ] vs. 45.5% [-Δ]; p=0.019). No other differences in pathology were noted. Median CSS and OS were highest among patients with 0Δ LMI (CSS: not reached [0Δ] vs. 61.9 [+Δ] vs. 37.4 [-Δ] months; p=0.0018 || OS: 67.2 [0Δ] vs. 48.5 [+Δ] vs. 26.4 [-Δ] months; p=0.0007). Median follow-up was 56 months for survivors. The table lists factors associated with increased risk of cancer-specific mortality. Conclusions: Change in muscle mass after CN, as measured by the linear muscle segmentation technique, is independently associated with OS and CSS in patients following CN. Of note, lack of change demonstrated greatest survival, potentially secondary to high baseline muscle mass. [Table: see text]
Pre-orchiectomy serum miRNA-371a-3p and 372-3p levels in men with clinically localized testicular masses.
Authors: Fady Baky, Richard Matulewicz, Andrea Knezevic, Fei Ye, Brandon Williams, Maria Bromberg, Nicole Benfante, Alisa Valentino, Rachel Kantor, Rachel So, Jahwa Hossain, Joel Sheinfeld, Samuel A Funt, Darren R. Feldman
Journal: Journal of Clinical Oncology (2024)

519 Background: MicroRNA (miRNA) are short noncoding RNAs involved in regulation of gene expression and have shown promise as novel biomarkers in the diagnosis and management of testicular germ cell tumors (GCT). We report the accuracy of our combined miRNA assay in men with Clinical Stage I (CSI) GCTs. We also sought to explore the relationship between miRNA levels and patient and oncologic variables to better understand how these factors may influence miRNA results. Methods: We retrospectively identified patients at Memorial Sloan Kettering (MSK) with a newly identified testicular mass concerning for GCT who were planned for radical or partial orchiectomy and had pre-orchiectomy MSK miRNA Assay (miRNA-371a-3p and miRNA-372-3p, collectively MMA) drawn. All patients had clinically localized disease based on initial staging imaging and normalized traditional serum tumor markers (STM) post-orchiectomy. Specific miRNA levels were determined using stem-loop RT-qPCR (quantitative reverse transcription PCR), as described previously. Patient and disease factors were abstracted from the medical record. Outcomes of interest were sensitivity, specificity, PPV and NPV of MMA, and area under the receiver operating characteristic curve (AUC) of miRNA-371a-3p and 372-3p levels, calculated relative to detection of viable GCT at orchiectomy. We explored the relationship between pre-orchiectomy miRNA-371a-3p and 372-3p levels and various patient and pathologic factors using Spearman correlation and Wilcoxon rank-sum test. Results: Forty-eight patients were included in this study, 39 of whom had viable GCT at orchiectomy and 9 with no cancer or non-GCTs. Thirty-seven patients with GCT had positive pre-orchiectomy MMA results (sensitivity 94.9%, 95% CI: 88-100), while 1 of 9 patients (Leydig cell tumor) without viable GCT had a positive MMA result (specificity 88.9%, 95% CI: 68.4-100). MMA PPV was 97.4% (95% CI: 92.3-100) and NPV was 80% (95% CI: 55.2-100). AUC of miRNA-371a-3p and miRNA-372-3p was 96% (95% CI: 91.0-100) and 92% (95% CI: 84.2-99.9), respectively. Pre-orchiectomy miRNA-371a-3p and miRNA-372-3p levels were positively correlated with tumor size (Spearman coefficient ρ=0.64, 0.63, respectively; p&lt;0.001), and with serum HCG (ρ=0.55, 0.56; p&lt;0.001) and LDH (ρ=0.46, 0.46; p&lt;0.001), but not AFP (ρ=0.19, 0.17; p=0.20, 0.24). Pre-orchiectomy MMA was not associated with other tested pathologic or patient characteristics including age, BMI, renal function, liver function and andrology labs. Conclusions: miRNA 371a-3p and 372-3p are highly sensitive and specific for presence of viable GCT in patients with clinically localized disease. Tumor size was the only studied pathologic factor or patient characteristic correlated with MMA levels.
Differential treatment effect on overall survival (OS) based on early prostate-specific antigen (PSA) response in metastatic hormone-sensitive prostate cancer (mHSPC): A secondary analysis of TITAN trial.
Authors: Soumyajit Roy, Shawn Malone, Yilun Sun, Christopher J.D. Wallis, Amar Upadhyaya Kishan, Scott C. Morgan, Georges Gebrael, Umang Swami, Angela Jia, Jason R Brown, Fred Saad, Neeraj Agarwal, Daniel Eidelberg Spratt
Journal: Journal of Clinical Oncology (2024)

126 Background: Early PSA response has been found to be associated with improved outcome in mHSPC patients treated with androgen deprivation therapy (ADT) plus androgen receptor pathway inhibitors (ARPI). However, it is unknown if the treatment effect on OS varies based on early PSA response in these patients. Methods: We performed a secondary analysis of TITAN study in which men with mHSPC were randomly assigned to ADT plus placebo vs. ADT plus apalutamide (ADT+APA). To compare the association of OS with early PSA response, defined as achieving a PSA nadir of ≤0.2 ng/mL at ≤6 months of randomization, between two arms, we applied multivariable Cox regression model on a landmark population with an interaction term between the treatment arm and PSA response. Adjusted OS were calculated. Confounders were chosen based on their association with PSA response and OS. Results: Overall, 1049 patients were eligible with 526 in the ADT arm and 523 in the ADT+APA arm. Approximately 24% (125/526) patients in the ADT arm and 62% (323/523) patients in the ADT+APA arm achieved early PSA nadir. On landmark analysis, ADT+APA was associated with improved OS among those with an early PSA nadir (HR: 0.66; 95% CI: 0.44-1.00) but no improvement in OS among those without an early PSA nadir (HR: 1.15 [0.87-1.46]) with differential treatment effect between groups stratified by early PSA nadir by 6 months (p=0.03). Adjusted 4-year OS for patients who reached PSA nadir was 66% (95% CI: 56-75) in the ADT alone arm and 78% [74-83] in the ADT+APA arm while for patients who did not reach PSA nadir, adjusted 4-year OS was 46% [41-52] and 47% [40-54] in the ADT alone and ADT+APA arm, respectively. Numbers needed to treat (NNT) was 7.8 (95% CI: 6 to 15) for the overall landmark population, 7.7 [5 to 36] for patients with PSA nadir by 6 months, and 55 [10 to -4] for those without PSA nadir, respectively. Conclusions: In this exploratory analysis of TITAN study, early PSA nadir at or before 6 months was associated with superior OS in both treatment arms. However, there was evidence of differential treatment effect on OS based on early PSA nadir with no beneficial effect from ADT+APA in those who did not reach early PSA nadir. Patients with lack of early PSA nadir had inferior and similar OS in both treatment groups. Further investigation is needed to determine how to best manage patients treated with doublet therapy without an early PSA response.
Plasma DNA and deoxyribonuclease in testicular germ cell tumors.
Authors: Michal Mego, Barbora Vlkova, Katarina Kalavska, Zuzana Cierna, Katarina Rejlekova, Natalia Udvorkova, Kristina Majtanova, Peter Lesko, Jana Obertova, Zuzana Orszaghova, Patrik Palacka, Zuzana Sycova-Mila, Jozef Mardiak, Michal Chovanec, Lucia Kucerova, Peter Celec
Journal: Journal of Clinical Oncology (2024)

518 Background: Despite high cure rate, small proportion of patients with germ cell tumors (GCTs) experience relapse and eventually die as a consequence of their disease. Tumor-derived DNA, but also total extracellular DNA (ecDNA) in plasma were found to be associated with the prognosis in different types of cancer. Deoxyribonuclease (DNase) catalyzes the cleavage of ecDNA and is likely the main metabolic pathway of ecDNA degradation. We hypothesized that DNase activity might modulate the association between ecDNA and prognosis. This study aimed to determine the prognostic value of ecDNA of different subcellular origin and plasma DNase activity in GCTs. Methods: This study included 117 patients with testicular GCTs starting a new line of therapy and 19 healthy controls. Plasma ecDNA was quantified using fluorometry (total ecDNA) and using PCR (nuclear – ncDNA and mitochondrial DNA – mtDNA). DNase activity was assessed using the single radial enzyme diffusion method in a DNA-containing gel. An in vivo experiment in mice was conducted to evaluate the effect of DNase I treatment alone and in combination with cisplatin on the xenografts derived from the human embryonal carcinoma cell line variant NTERA-2 CisR. Results: Plasma ecDNA was higher in patients with GCTs compared to healthy controls (mean ng/ml ± SEM: 6.2 ± 0.6 vs.1.2 ± 2.2). Patients with high total ecDNA, ncDNA but not mtDNA had inferior PFS and OS compared to patients with low ecDNA (all p &lt; 0.05). There was an inverse relationship between plasma DNase and ecDNA as well as between plasma DNase and clinical outcome (HR=2.96, 95%CI 1.39-6.32, P = 0.01 for PFS and HR=4.88, 95%CI 2.06-11.53, p = 0.005 for OS, respectively). Our experiments on selected model human GCT cell lines confirmed the lack of cytotoxic or inhibitory effects of DNase I in vitro. The animal experiment showed that the combination treatment with DNase I and cisplatin substantially reduced the growth of the NTERA-2 cisplatin-resistant xenografts (by 30%). Conclusions: We confirmed the prognostic value of ecDNA and proved it for the first time for DNase in patients with GCTs. We suggest that based on the animal experiment there is strong rationale to add DNase to cisplatin in refractory GCTs. Although the mechanisms are unclear and could involve reduced inflammatory response to ecDNA, we hypothesize that degradation of ecDNA by DNase might contribute to a better control of the tumor progression by cisplatin in patients with progressing or relapsing GCTs.
A phase Ib trial of enzalutamide with oral decitabine/cedazuridine in metastatic castration-resistant prostate cancer (CRPC).
Authors: Arya Mariam Roy, Dharmesh Gopalakrishnan, Karan Jatwani, Kelly Green, Bailey Farmer, Neha Jaiswal, Kristopher Attwood, Ellis Glenn Levine, Himisha Beltran, David Goodrich, Gurkamal S. Chatta
Journal: Journal of Clinical Oncology (2024)

TPS252 Background: Exposure to androgen receptor (AR)-pathway inhibitors like enzalutamide (Enza) is associated with the emergence of AR low subclones that coexist with AR high subclones in CRPC. These AR low cells, including those in neuroendocrine prostate cancer (NEPC), are not critically dependent on AR signaling for survival and proliferation. Alterations in RB1, TP53, and PTEN tend to co-occur in human AR low CRPC and NEPC. These as well as tumors from triple knockout mouse models demonstrate altered expression of epigenetic reprogramming factors, including consistent upregulation of DNA methyltransferase 1 (DNMT1). 1 DNA methylation in CpG islands is increased in human CRPC/NEPC as well as CRPC xenograft models indicating that elevated DNMT activity may correlate with resistance to AR-targeted therapies. 2 Treatment with decitabine (Dec), a DNMT inhibitor, delays the development of AR low NEPC and increases Enza sensitivity in murine models of prostate cancer. 2 Cedazuridine (Ced), an inhibitor of cytidine deaminase which degrades Dec, increases its oral bioavailability. We hypothesize that the combination of Enza with oral Dec/Ced will reverse acquired therapeutic resistance in AR low CRPC/NEPC tumors where DNMT activity is aberrantly elevated by RB1 and/or TP53 loss. Methods: This is a single-center, open-label, non-randomized, dose escalation/de-escalation phase Ib study of fixed drug combination (FDC) oral Dec/Ced [ASTX727, FDC 35mg/100mg] with Enza (160mg/day) in patients with Enza-refractory mCRPC. Three dose levels of ASTX727 will be evaluated using a 3+3 study design - FDC of ASTX727 will be administered on either 4 (cohort 1), 3 (cohort -1) or 5 (cohort 2) consecutive days of a 28-day cycle. The primary endpoint will be safety with determination of the maximum tolerated dose (MTD) and recommended phase II dosing (RP2D). We plan to include an expansion cohort of 10 patients at the MTD, eligibility for which will be restricted to patients with genomic alterations in RB1 and/or TP53. Correlative studies will be aimed at 1) Evaluation of DNMT1 levels and DNA methylation patterns, 2) Analysis of circulating tumor DNA to monitor changes in DNA methylation and emergence of AR low CRPC/NEPC, 3) Evaluation for tissue markers of neuroendocrine lineage, RB1 loss and/or TP53 mutations to examine for treatment emergent AR low CRPC/NEPC and its correlation with RB1 and/or TP53 loss. The study is currently open with 6 patients enrolled. 1) McCabe MT et al. Cancer Res. 2005;65(9):3624-32. 2) Ku SY et al. Science. 2017;355(6320):78-83. 3) Zorn CS et al. Clin Cancer Res. 2007;13(7):2136-43. Clinical trial information: NCT05037500 .
Cohort expansion from the phase 1 JEWEL-101 study investigating the tissue factor–targeting antibody-drug conjugate XB002 in patients with advanced solid tumors: Metastatic castration-resistant prostate cancer cohort.
Authors: Susanna Varkey Ulahannan, Melissa Lynne Johnson, Mia C. Weiss, Andrae L. Vandross, Sofia Luz Vidal-Cardenas, Mustafa Syed, Anthony W. Tolcher
Journal: Journal of Clinical Oncology (2024)

TPS237 Background: There is a high unmet need for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) that has progressed on novel hormonal therapies (NHTs) due to acquired resistance to treatment. Tissue factor (TF) is a transmembrane protein that functions as a factor VIIa receptor and initiates the extrinsic coagulation cascade. Its overexpression has been associated with disease progression and poor prognosis in multiple solid tumor types, including mCRPC. XB002 is a novel antibody-drug conjugate (ADC) composed of a high-affinity TF-directed human monoclonal antibody conjugated to zovodotin, an auristatin-based payload with a protease-cleavable linker. The zovodotin payload of XB002 is designed to have lower off-target payload deconjugation and improved tolerability compared with other auristatin-based ADCs. In preclinical studies, XB002 demonstrated antitumor activity and encouraging safety without affecting coagulation. JEWEL-101 (NCT04925284) is a phase 1, open-label, multicenter, first-in-human study evaluating XB002 alone and in combination regimens. The study consists of a dose-escalation stage to determine the recommended dose and/or maximum tolerated dose of XB002, and a tumor-specific cohort expansion stage to evaluate the safety and preliminary antitumor activity in pts with advanced solid tumors. Preliminary results from the dose-escalation stage showed XB002 was well tolerated at multiple dose levels, with low-grade ocular toxicity and no bleeding events or treatment-related peripheral neuropathy (PN). 1 Presented here is the design of the expansion cohort in pts with mCRPC. Methods: Pts with mCRPC and primary histology of adenocarcinoma are eligible; neuroendocrine differentiation and other histological features are also permitted. Pts must have documented progressive disease after 1–3 prior systemic therapies, including at least 1 prior NHT for metastatic castration-sensitive or castration-resistant disease. Prior taxane-based chemotherapy is optional, and bone-only disease without soft-tissue tumor components is allowed. No prior treatment with TF-targeting or auristatin-based ADCs is allowed, and pts with significant ocular disorders are excluded. PN not impacting activities of daily living is acceptable, and concomitant use of anticoagulants is permitted. Pts in the mCRPC cohort will be treated with XB002 single agent. The primary outcome is objective response rate per investigator assessment. Secondary outcomes include safety, pharmacokinetics, immunogenicity, progression-free survival, duration of response, and overall survival. Enrollment is ongoing in the United States, Europe, and the Asia-Pacific region. 1. Ulahannan et al. ENA 2022. Clinical trial information: NCT04925284 .