Yale Urology Research [Q4: October-December 2023]

The following is a comprehensive list of Yale Urology publications for the 4th quarter of calendar year 2023. The listing is separated into primary and secondary faculty sections, then in descending published date order. Listed items include cite details and portions of each abstract/summary.

Primary Faculty

Smani S, Novosel M, Sutherland R, Jeong F, Jalfon M, Marks V, Rajwa P, Nolazco JI, Washington SL, Renzulli JF II, Sprenkle P, Kim IY, Leapman MS. Association between sociodemographic factors and diagnosis of lethal prostate cancer in early life. Urol Oncol. 2023 Dec 30:S1078-1439(23)00341-1. doi: 10.1016/j.urolonc.2023.10.005. Epub ahead of print. PMID: 38161105.

Conclusions: Sociodemographic disparities in diagnosis at advanced stages of CaP were more pronounced in younger patients, particularly with respect to insurance status. These findings may support greater attention to differential use of early CaP screening based on patient health insurance.

Cunningham SD, [Rickey LM], et al. Psychosocial factors associated with lower urinary tract symptoms one year postpartum. International journal of environmental research and public health. 01/2024;21(1):40. doi: 10.3390/ijerph21010040.

Although the risk of postpartum LUTSs has traditionally been attributed to clinical factors, the current analysis demonstrates the importance of psychosocial factors as well. In light of the high prevalence of postpartum LUTSs and the attendant impact on the lives of individuals who give birth, future postpartum research should incorporate psychosocial factors in addition to individual biologic and behavioral contributors. Delineating these mechanisms will enable improved screening across the perinatal period and inform strategies to maintain postpartum bladder health and prevent LUTSs over the life course.

Jalfon M, Gardezi M, Heckscher D, Shaheen D, Maciejewski KR, Li F, Rickey L, Foster H, Cavallo JA. Agreement and Reliability of Patient-measured Postvoid Residual Bladder Volumes. Urology. 2023 Dec 12:S0090-4295(23)01059-2. doi: 10.1016/j.urology.2023.11.026. Epub ahead of print. PMID: 38092325.

Conclusion: Patient self-measurement of PVR using smart-device integrated portable ultrasound probes is feasible, reliable, and preferred by patients. Limits of agreement between patient self-measurement and standard bladder scanner measurements exceeded our clinically acceptable difference threshold, though the inherent error of ultrasound-based bladder volume measurements should be considered. Longitudinal PVR assessments in nonhealthcare settings may facilitate remote monitoring of voiding dysfunction patients.

Thompson CB, Vousden KH, Johnson RS, Koppenol WH, Sies H, Lu Z, Finley LWS, Frezza C, Kim J, Hu Z, Bartman CR. A century of the Warburg effect. Nat Metab. 2023 Nov;5(11):1840-1843. doi: 10.1038/s42255-023-00927-3. PMID: 37990075.

In 1923, Otto Warburg published his landmark study, in which he described his seminal observations related to metabolic shifts in cancer, often referred to as the Warburg effect. His work laid the foundation for an understanding of how metabolic reconfiguration contributes to cancer onset and progression. Several researchers in the field share their thoughts on what this discovery means to them and how it has inspired their scientific journey.

Zhang J, [Onofrey J], et al. 2023 IEEE nuclear science symposium, medical imaging conference and international symposium on room-temperature semiconductor detectors (NSS MIC RTSD). Spatial Normalization to Improve Deep Learning-based Head Motion Correction in PET. 11/2023:1-1. doi: 10.1109/NSSMICRTSD49126.2023.10338387.

To improve the accuracy of motion prediction, we propose using spatial normalization (SN) in DL-HMC to mitigate the negative effects of varying reference frame positions. We tested our proposed SN-DL-HMC method on a multi-subject dataset and compared its performance with other methods.

Lieffrig EV, [Onofrey JA], et al. 2023 IEEE nuclear science symposium, medical imaging conference and international symposium on room-temperature semiconductor detectors (NSS MIC RTSD). Image Intensity Normalization Benefits Deep Learning Brain PET Motion Correction. 11/2023:1-1. doi: 10.1109/NSSMICRTSD49126.2023.10338194.

Our results demonstrate that normalizing images with the intensity of the earliest frame significantly decreases motion prediction error on testing subjects compared to data that are not normalized or normalized using other strategies. Reconstructions and Standard Uptake Value analysis further confirm this observation. We validate the proposed method on data from two tracers.

Zeng T, Zhang J, Lieffrig EV, Cai Z, Chen F, You C, Naganawa M, Lu Y, Onofrey JA. Fast Reconstruction for Deep Learning PET Head Motion Correction. Med Image Comput Comput Assist Interv. 2023 Oct;14229:710-719. doi: 10.1007/978-3-031-43999-5_67. Epub 2023 Oct 1. PMID: 38174207; PMCID: PMC10758999.

The main characteristics of the proposed method are: (i) the adoption of a high-resolution short-frame fast reconstruction workflow; (ii) the development of a novel encoder for PET data representation extraction; and (iii) the implementation of data augmentation techniques. Ablation studies are conducted to assess the individual contributions of each of these design choices … All code is publicly available on GitHub: https://github.com/OnofreyLab/dl-hmc_fast_recon_miccai2023.

Marks VA, Hsiang WR, Nie J, Umer W, Haleem A, Galal B, Pak I, Kim D, Salazar MC, Pantel H, Berger ER, Boffa DJ, Cavallo JA, Leapman MS. Telehealth Availability for Cancer Care During the COVID-19 Pandemic: Cross-Sectional Study. JMIR Cancer. 2023 Nov 2;9:e45518. doi: 10.2196/45518. PMID: 37917149; PMCID: PMC10654905.

Conclusions: Despite an increase in telehealth services for patients with cancer during the COVID-19 pandemic, we identified differences in access across cancer hospitals, which may relate to measures of clinical volume, affiliation, and infrastructure.

Khajir G, Sun T, Wang H, Sprenkle PC, Adeniran AJ, Cai G, Levi AW. Cytologic evaluation of upper urinary tract specimens: An institutional retrospective study using The Paris System for Reporting Urine Cytology second edition with histopathologic follow-up. Cytopathology. 2023 Nov 2. doi: 10.1111/cyt.13328. Epub ahead of print. PMID: 37916579.

Cytologic evaluation of the upper urinary tract (UUT) can be challenging due to instrumentation artefacts. This study retrospectively reviewed UUT specimens using The Paris System for Reporting Urinary Cytopathology, second edition (TPS 2.0), compared it with the original reporting system (ORS) and correlated it with histopathologic follow-up.

Heckscher D, Jalfon M, Buck MB, Abello A, Nguyen JV, Casilla-Lennon M, Leapman MS, Hittelman AB, Teitelbaum J, Emerson BL, Kenney PA, Cavallo JA, Lambert S. Implementation of a health system intervention to reduce time from presentation to surgical intervention for pediatric testicular torsion. J Pediatr Urol. 2023 Nov 2:S1477-5131(23)00498-9. doi: 10.1016/j.jpurol.2023.10.042. Epub ahead of print. PMID: 38030428.

Testicular salvage rates for torsion are time-dependent¹. Door to detorsion time has been identified as an independent testicular survival factor². We describe an initiative to reduce door to incision (DTI) time for pediatric testicular torsion.

Kashima S [Kenney PA, Hurwitz M, Braun D], et al. 542 TIGIT as a potential therapeutic target in renal cell carcinoma. Regular and Young Investigator Award Abstracts. 11/2023:A616-A616. doi: 10.1136/jitc-2023-SITC2023.0542.

Rahman SN, [Leapman M, Hurwitz M], et al. Total and treatment-related costs of care associated with in patients with metastatic renal cell carcinoma receiving targeted or immune therapy. JCO oncology practice. 11/2023;19(11_suppl):28-28. doi: 10.1200/OP.2023.19.11_suppl.28.

Khajir G, Press B, Lokeshwar S, Ghabili K, Rahman S, Gardezi M, Washington S, Cooperberg MR, Sprenkle P, Leapman MS. Prostate cancer risk stratification using magnetic resonance imaging-ultrasound fusion vs systematic prostate biopsy. JNCI Cancer Spectr. 2023 Oct 31;7(6):pkad099. doi: 10.1093/jncics/pkad099. PMID: 38085220; PMCID: PMC10733209.

Image-guided approaches improve the diagnostic yield of prostate biopsy and frequently modify estimates of clinical risk. To better understand the impact of magnetic resonance imaging-ultrasound fusion targeted biopsy (MRF-TB) on risk assessment, we compared the distribution of National Comprehensive Cancer Network (NCCN) risk groupings, as calculated from MRF-TB vs systematic biopsy alone.

Zeevi T, Leapman MS, Sprenkle PC, Venkataraman R, Staib LH, Onofrey JA. Reliable Prostate Cancer Risk Mapping from MRI Using Targeted and Systematic Core Needle Biopsy Histopathology. IEEE Trans Biomed Eng. 2023 Oct 24;PP. doi: 10.1109/TBME.2023.3326799. Epub ahead of print. PMID: 37874731.

Objective: To compute a dense prostate cancer risk map for the individual patient post-biopsy from magnetic resonance imaging (MRI) and to provide a more reliable evaluation of its fitness in prostate regions that were not identified as suspicious for cancer by a human-reader in pre- and intra-biopsy imaging analysis.

Smani S, Reddy S, Kong V, Kellner D. Osteitis pubis following holmium laser enucleation of the prostate. BMJ Case Rep. 2023 Oct 13;16(10):e257637. doi: 10.1136/bcr-2023-257637. PMID: 37832974; PMCID: PMC10583065.

Osteitis pubis is a rare, inflammatory condition involving the pubic symphysis. While osteitis pubis has been reported following many urological procedures, including those addressing bladder outlet obstruction such as transurethral resection of the prostate, it has never been reported after holmium laser enucleation of the prostate (HoLEP). Here, we detail the clinical course of a patient found to have osteitis pubis following HoLEP.

Gross M, Arora S, Huber S, Kücükkaya AS, Onofrey JA. LiverHccSeg: A publicly available multiphasic MRI dataset with liver and HCC tumor segmentations and inter-rater agreement analysis. Data Brief. 2023 Oct 10;51:109662. doi: 10.1016/j.dib.2023.109662. PMID: 37869619; PMCID: PMC10587725.

The applications of LiverHccSeg can be manifold, ranging from testing machine learning algorithms on public external data to radiomic feature analyses. Leveraging the inter-rater agreement analysis within the dataset, researchers can investigate the impact of variability on segmentation performance and explore methods to enhance the accuracy and robustness of liver and tumor segmentation algorithms in HCC patients. By making this dataset publicly available, LiverHccSeg aims to foster collaborations, facilitate innovative solutions, and ultimately improve patient outcomes in the diagnosis and treatment of HCC.

Van Metre Baum L, K C M, Soulos PR, Jeffery MM, Ruddy KJ, Lerro CC, Lee H, Graham DJ, Rivera DR, Leapman MS, Jairam V, Dinan MA, Gross CP, Park HS. Trends in New and Persistent Opioid Use in Older Adults with and without Cancer. J Natl Cancer Inst. 2023 Oct 6:djad206. doi: 10.1093/jnci/djad206. Epub ahead of print. PMID: 37802882.

Background: The impact of ongoing efforts to decrease opioid use on patients with cancer remains undefined. Our objective was to determine trends in new and additional opioid use in patients with and without cancer.

Zeng T, Zhang J, Lieffrig EV, Cai Z, Chen F, You C, Naganawa M, Lu Y, Onofrey JA. Fast Reconstruction for Deep Learning PET Head Motion Correction. Med Image Comput Comput Assist Interv. 2023 Oct;14229:710-719. doi: 10.1007/978-3-031-43999-5_67. Epub 2023 Oct 1. PMID: 38174207; PMCID: PMC10758999.

Our results demonstrate that the proposed method outperforms other methods on all subjects, and can accurately estimate motion for subjects out of the training set. All code is publicly available on GitHub: https://github.com/OnofreyLab/dl-hmc_fast_recon_miccai2023.

Cai Z, Zeng T, Lieffrig EV, Zhang J, Chen F, Toyonaga T, You C, Xin J, Zheng N, Lu Y, Duncan JS, Onofrey JA. Cross-Attention for Improved Motion Correction in Brain PET. Mach Learn Clin Neuroimaging (2023). 2023 Oct;14312:34-45. doi: 10.1007/978-3-031-44858-4_4. Epub 2023 Oct 1. PMID: 38174216; PMCID: PMC10758996.

In this paper, we integrate a cross-attention mechanism into the supervised deep learning network to improve motion correction across test subjects. Specifically, cross-attention learns the spatial correspondence between the reference images and moving images to explicitly focus the model on the most correlative inherent information …

Reddy S, [Rotker KL, Honig SC], et al. HIGH CAPABILITY OF CHATGPT TO ANSWER COMMON PATIENT QUESTIONS ENCOUNTERED BY REPRODUCTIVE UROLOGISTS. Fertility and sterility. 10/2023;120(4):e254. doi: 10.1016/j.fertnstert.2023.08.714.

Reproductive and Sexual Medicine remains a subspecialty with a significant lack of high-quality online sources of information. Given the limited access to male infertility specialists, ChatGPT could possibly improve patient satisfaction and reduce provider burden. Urologists should be aware of the strengths and limitations of emerging AI-based technologies as a medium for providing accurate health information to patients.

Secondary Faculty

Denize T, Jegede OA, Matar S, El Ahmar N, West DJ, Walton E, Bagheri AS, Savla V, Nabil Laimon Y, Gupta S, Vemula SV, Braun DA, Burke KP, Catalano PJ, Freeman GJ, Motzer RJ, Atkins MB, McDermott DF, Sharpe AH, Choueiri TK, Signoretti S. PD-1 Expression on Intratumoral Regulatory T Cells is Associated with Lack of Benefit from Anti-PD-1 Therapy in Metastatic Clear Cell Renal Cell Carcinoma Patients. Clin Cancer Res. 2023 Dec 7. doi: 10.1158/1078-0432.CCR-23-2274. Epub ahead of print. PMID: 38060202.

PD-1 expression on CD8+TIM-3-LAG3- tumor-infiltrating cells predicts positive response to PD-1 blockade in metastatic clear cell renal cell carcinoma (mccRCC). Since PD-1 signaling inhibition in regulatory T cells (Tregs) augments their immunosuppressive function, we hypothesized that PD-1 expression on tumor-infiltrating Tregs would predict resistance to PD-1 inhibitors.

Hoimes CJ, Flaig TW, Milowsky MI, Friedlander TW, Bilen MA, Gupta S, Srinivas S, Merchan JR, McKay RR, Petrylak DP, Sasse C, Moreno BH, Yu Y, Carret AS, Rosenberg JE. A plain language summary exploring a new treatment combination for untreated locally advanced or metastatic urothelial cancer: enfortumab vedotin plus pembrolizumab. Future Oncol. 2023 Nov 23. doi: 10.2217/fon-2023-0112. Epub ahead of print. PMID: 37994649.

In the 45 patients studied, around 16% did have serious side effects, but most side effects were manageable. Twenty-four percent of patients, however, stopped the study treatment because of their side effects. Within about 2 months of starting treatment, most patients' (73%) tumors were smaller and stayed smaller, on average, for more than 2 years.

Djureinovic D, Weiss SA, Krykbaeva I, Qu R, Vathiotis I, Moutafi M, Zhang L, Perdigoto AL, Wei W, Anderson G, Damsky W, Hurwitz M, Johnson B, Schoenfeld D, Mahajan A, Hsu F, Miller-Jensen K, Kluger Y, Sznol M, Kaech SM, Bosenberg M, Jilaveanu LB, Kluger HM. A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better. Mol Cancer. 2023 Nov 14;22(1):182. doi: 10.1186/s12943-023-01884-x. PMID: 37964379; PMCID: PMC10644655.

Stimulating inflammatory tumor associated macrophages can overcome resistance to PD-(L)1 blockade. We previously conducted a phase I trial of cabiralizumab (anti-CSF1R), sotigalimab (CD40-agonist) and nivolumab. Our current purpose was to study the activity and cellular effects of this three-drug regimen in anti-PD-1-resistant melanoma.

McKay RR, Leucht K, Xie W, Jegede O, Braun DA, Atkins MB, Grimm MO, Choueiri TK. A Pooled Analysis of 3 Phase II Trials of Salvage Nivolumab/Ipilimumab After Nivolumab in Renal Cell Carcinoma. Oncologist. 2023 Nov 10:oyad298. doi: 10.1093/oncolo/oyad298. Epub ahead of print. PMID: 37950901.

Nivolumab plus ipilimumab has demonstrated improved survival for treatment-naïve advanced clear cell renal cell carcinoma (RCC). A series of clinical trials evaluated the effect of salvage nivolumab plus ipilimumab in patients without an objective response to nivolumab. Given the size and heterogeneity of these studies, we performed a pooled analysis to better inform the activity of nivolumab plus ipilimumab after nivolumab.

Hugaboom M, [Hurwitz M, Braun D], et al. 1017 SLAMF7 CD8 exhausted T cell-specific gene signature is associated with resistance to PD1 blockade in renal cell carcinoma. Regular and Young Investigator Award Abstracts. 11/2023:A1125-A1125. doi: 10.1136/jitc-2023-SITC2023.1017.

Petrylak DP, Eigl BJ, George S, Heath EI, Hotte SJ, Chism DD, Nabell LM, Picus J, Cheng SY, Appleman LJ, Sonpavde GP, Morgans AK, Pourhosseini P, Wu R, Standley L, Croitoru R, Yu EY. Phase I Dose-Escalation Study of the Safety and Pharmacokinetics of AGS15E Monotherapy in Patients with Metastatic Urothelial Carcinoma. Clin Cancer Res. 2024 Jan 5;30(1):63-73. doi: 10.1158/1078-0432.CCR-22-3627. PMID: 37861407; PMCID: PMC10767306.

Purpose: Effective treatment of locally advanced or metastatic urothelial carcinoma (mUC) remains an unmet need. Antibody-drug conjugates (ADC) providing targeted drug delivery have shown antitumor activity in this setting. AGS15E is an investigational ADC that delivers the cytotoxic drug monomethyl auristatin E to cells expressing SLITRK6, a UC-associated antigen.

Sridhar S, [Petrylak DP], et al. 2365MO study EV-103 cohort L: Perioperative treatment w/ enfortumab vedotin (EV) monotherapy in cisplatin (cis)-ineligible patients (pts) w/ muscle invasive bladder cancer (MIBC). Annals of oncology. 10/2023;34:S1203. doi: 10.1016/j.annonc.2023.09.1014.

EV continues to show promising activity and was tolerable in cis-ineligible pts w/ MIBC in this ongoing trial. Both the efficacy and safety profiles were consistent with previously reported data from Cohort H. These data support the ongoing phase 3 trials evaluating EV + pembrolizumab in MIBC.

Petrylak DP. 1803P phase I/II study of bavdegalutamide, a PROTAC androgen receptor (AR) degrader in metastatic castration-resistant prostate cancer (mCRPC): Radiographic progression-free survival (rPFS) in patients (pts) with AR ligand-binding domain (LBD) mutations. Annals of oncology. 10/2023;34:S973-S974. doi: 10.1016/j.annonc.2023.09.2751.

Pts with mCRPC and mutations in AR LBD (amino acids 671-920) have poor prognosis. The oral PROteolysis TArgeting Chimera (PROTAC) AR degrader bavdegalutamide (bavdeg; ARV-110) showed clinical activity in previously treated pts with mCRPC in a phase 1/2 study (NCT03888612), with enhanced activity seen in pts with the AR LBD mutations T878 and/or H875.

Saliby RM, [Braun DA], et al. 1891P determinants of exceptional response to immune checkpoint inhibition in metastatic clear cell renal cell carcinoma. Annals of oncology. 10/2023;34:S1017. doi: 10.1016/j.annonc.2023.09.1121.

In a subset of patients (pts), immune checkpoint inhibitors (ICIs) hold the potential to achieve lasting and sustainable responses, or even complete recoveries in pts with clear cell renal cell carcinoma (ccRCC). We sought to understand the immunogenomic determinants of these exceptional responses to ICIs.

McKay RR, [Braun DA], et al. 1892P A pooled meta-analysis of salvage nivolumab/ipilimumab (N I) after nivolumab (N) in patients with advanced renal cell carcinoma (RCC). Annals of oncology. 10/2023;34:S1017-S1018. doi: 10.1016/j.annonc.2023.09.1122.

N+I has demonstrated improved survival for patients with treatment-naïve advanced clear cell RCC. A series of phase 2 trials (OMNIVORE NCT03203473; HCRN GU16-260 NCT03117309; TITAN-RCC NCT02917772) evaluated N+I in patients lacking an objective response to N. We performed a pooled meta-analysis of these studies to better inform the activity of N+I after N.

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