The following is a comprehensive list of Yale Urology faculty publications for the 1st quarter of calendar year 2023. The listing is separated into primary and secondary faculty sections, then in descending published date order. Most references include cite details and portions of each abstract/summary.
PRIMARY FACULTY
Tram NK, Chou TH, Janse SA, Bobbey AJ, Audino AN, Onofrey JA, Stacy MR. Deep learning of image-derived measures of body composition in pediatric, adolescent, and young adult lymphoma: association with late treatment effects. Eur Radiol. 2023 Mar 29. doi: 10.1007/s00330-023-09587-z. Epub ahead of print. PMID: 36988714.
Key Points: Deep learning-guided CT image analysis of body composition measures achieved high agreement level with manual image analysis. • Pediatric patients with more fat and less muscle during the course of cancer treatment were more likely to experience a serious adverse event compared to their clinical counterparts. • Deep learning of body composition may add value to routine CT imaging by offering real-time monitoring of pediatric, adolescent, and young adults at high risk for late effects of cancer treatment.
Sterling J, Daneshvar M, Nikolavsky D. Transurethral ventral inlay buccal mucosa graft urethroplasty: technique and intermediate outcomes. BJU Int. 2023 Mar 14. doi: 10.1111/bju.16007. Epub ahead of print. PMID: 36919248.
Objective: To outline our step-by-step surgical technique for a transurethral ventral buccal mucosa graft inlay urethroplasty to treat fossa navicularis and distal urethral strictures.
LaCoursiere DY, Kane Low L, Putnam S, Wyman JF, Newman DK, Cunningham S, Rickey L, Berry A, Gahagan S, Vaughan CP, Brown O, Brady SS; Prevention of Lower Urinary Tract Symptoms (PLUS) Research Consortium. Development of a tool to assess bladder health knowledge, attitudes, and beliefs (BH-KAB). Neurourol Urodyn. 2023 Mar 11. doi: 10.1002/nau.25168. Epub ahead of print. PMID: 36905331.
Conclusion: The PLUS BH-KAB instrument may be used independently or in conjunction with other KAB instruments for a more comprehensive assessment of women's KAB related to bladder health. The BH-KAB instrument can inform clinical conversations, health education programming, and research examining potential determinants of bladder health, LUTS, and related behavioral habits (e.g., toileting, fluid intake, pelvic muscle exercises).
Lukacz ES, Falke C, Geynisman-Tan J, Wyman JF, Mueller ER, Markland AD, Rickey L, Lowder JL, Rudser K, Kane Low L, Newman DK; Prevention of Lower Urinary Tract Symptoms (PLUS) Research Consortium. Healthy bladder storage and emptying functions in community-dwelling women measured by a 2-day bladder health diary. Neurourol Urodyn. 2023 Apr;42(4):725-735. doi: 10.1002/nau.25169. Epub 2023 Mar 9. PMID: 36891924; PMCID: PMC10101892.
Conclusion: The prevalence of overall healthy bladder function was very low based on our strict definition of health as measured on a 2-day diary. However, most women had healthy voiding frequency and denied pain or urinary leakage. Postvoid dribbling and urgency most commonly contributed to an overall unhealthy bladder. Further investigation is needed to determine whether these diary derived measures are meaningful for patient-oriented bladder health research.
Moses KA, Sprenkle PC, Bahler C, Box G, Carlsson SV, Catalona WJ, Dahl DM, Dall'Era M, Davis JW, Drake BF, Epstein JI, Etzioni RB, Farrington TA, Garraway IP, Jarrard D, Kauffman E, Kaye D, Kibel AS, LaGrange CA, Maroni P, Ponsky L, Reys B, Salami SS, Sanchez A, Seibert TM, Shaneyfelt TM, Smaldone MC, Sonn G, Tyson MD, Vapiwala N, Wake R, Washington S, Yu A, Yuh B, Berardi RA, Freedman-Cass DA. NCCN Guidelines® Insights: Prostate Cancer Early Detection, Version 1.2023. J Natl Compr Canc Netw. 2023 Mar;21(3):236-246. doi: 10.6004/jnccn.2023.0014. PMID: 36898362.
The NCCN Guidelines for Prostate Cancer Early Detection provide recommendations for individuals with a prostate who opt to participate in an early detection program after receiving the appropriate counseling on the pros and cons. These NCCN Guidelines Insights provide a summary of recent updates to the NCCN Guidelines with regard to the testing protocol, use of multiparametric MRI, and management of negative biopsy results to optimize the detection of clinically significant prostate cancer and minimize the detection of indolent disease.
Lee J, [Sprenkle P]. Abstract no. 160 MR susceptibility-weighted imaging during transurethral prostate sono-ablation procedures for guidance of device placement to counter effect of intra-prostatic calcifications. Journal of vascular and interventional radiology. 03/2023;34(3):S74-S75. doi: 10.1016/j.jvir.2022.12.214.
Conclusion: Intraprocedural SWI detected all CT-identified calcifications, tending to overestimate the diameter but guiding effective device positioning. CT remains the gold standard for pre-TULSA calcification screening, and further studies are warranted to optimize SWI protocols, correlate the size of calcifications on CT and SWI, and predict their impact on ablation coverage.
Chow RD, [Leapman MS, Hurwitz ME]. Evolution of systemic therapy from 2015 to 2019 for older patients in the united states with metastatic renal cell carcinoma. Journal of clinical oncology. 02/2023;41(6_suppl):610-610. doi: 10.1200/JCO.2023.41.6_suppl.610.
Background: Immune checkpoint inhibitors (IOs) and oral anti-cancer agents (OAAs) have demonstrated survival improvements in randomized trials of patients with metastatic renal cell carcinoma (mRCC). IOs were approved as second-line mRCC therapy in 2015 (nivolumab), followed by first-line approval in 2018 (ipilimumab/nivolumab). Real-world changes in overall treatment rates and IO usage have not been examined in patients over 65, who are often underrepresented in trials. Disparities in mRCC outcomes have persisted in the era of these novel therapies, raising the question of whether receipt of IOs and OAAs varies by race and ethnicity.
Leapman M. Patient experiences with tissue-based genomic testing during active surveillance for prostate cancer. Journal of clinical oncology. 02/2023;41(6_suppl):333-333. doi: 10.1200/JCO.2023.41.6_suppl.333.
Background: Tissue-based gene expression (genomic) tests improve estimates of prostate cancer aggressiveness and are increasingly used for patients considering or engaged in active surveillance; however, little is known about patient experiences with genomic testing and its role in decision-making for active surveillance.
Novosel M, [Leapman MS]. Associations between patient sociodemographic factors and non-treatment for localized prostate cancer. Journal of clinical oncology. 02/2023;41(6_suppl):307-307. doi: 10.1200/JCO.2023.41.6_suppl.307.
Conclusions: Patient race and insurance are significantly associated with non-treatment for aggressive prostate cancer.
Smani S, [Sprenkle P, Leapman M]. Association between sociodemographic factors and diagnosis of advanced prostate cancer in early life. Journal of clinical oncology. 02/2023;41(6_suppl):32-32. doi: 10.1200/JCO.2023.41.6_suppl.32.
Conclusions: Sociodemographic disparities in advanced stages of prostate cancer diagnosis were more pronounced in younger patients, particularly with respect to insurance status. These findings may support greater attention to differential use of early prostate cancer screening by health insurance.
Sutherland R, [Leapman M]. “It just makes sense to me”: Patient experiences with prostate MRI during prostate cancer active surveillance. Journal of clinical oncology. 02/2023;41(6_suppl):334-334. doi: 10.1200/JCO.2023.41.6_suppl.334.
Conclusions: These findings reveal that patients highly value prostate MRI as a tool that enhances the confidence in the initial diagnosis and monitoring of prostate cancer. This work can inform future studies to optimize the patient experience, education and counseling during active surveillance for prostate cancer.
Leapman MS, Wang R, Loeb S, Seibert TM, Gaylis FD, Lowentritt B, Brown GA, Chen R, Lin D, Witte J, Cooperberg MR, Catalona WJ, Gross CP, Ma X. Use of Monitoring Tests Among Patients With Localized Prostate Cancer Managed With Observation. J Urol. 2023 Apr;209(4):710-718. doi: 10.1097/JU.0000000000003159. Epub 2023 Feb 8. PMID: 36753746.
Conclusions: Use of recommended monitoring tests including repeat prostate biopsy remains low among Medicare beneficiaries undergoing observation for low- and intermediate-risk prostate cancer.
Laditi F, Nie J, Hsiang W, Umer W, Haleem A, Marks V, Buck M, Leapman MS. Access to urologic cancer care for Medicaid-insured patients. Urol Oncol. 2023 Apr;41(4):206.e21-206.e27. doi: 10.1016/j.urolonc.2023.01.014. Epub 2023 Feb 4. PMID: 36740488.
Background: The expansion of state Medicaid programs associated with the Affordable Care Act has led to significant increases in insurance coverage for economically vulnerable patients, however barriers to accessing cancer care still exist. To develop strategies to improve healthcare access, we characterized access to new urologic cancer care for patients with Medicaid insurance in the United States.
Shi L, Zhang J, Toyonaga T, Shao D, Onofrey JA, Lu Y. Deep learning-based attenuation map generation with simultaneously reconstructed PET activity and attenuation and low-dose application. Phys Med Biol. 2023 Jan 24;68(3). doi: 10.1088/1361-6560/acaf49. PMID: 36584395.
Main results: Clinical evaluation of tumor quantification as well as physics-based figure-of-merit metric evaluation validated the promising performance of our proposed method. For both full-dose and low-dose studies, the proposed framework achieved <1% error in tumor standardized uptake value measures.
Franco I, Hoebeke PB, Dobremez E, Titanji W, Geib T, Jenkins B, Yushmanova I, Austin PF. Long-term Safety and Tolerability of Repeated Treatments With OnabotulinumtoxinA in Children With Neurogenic Detrusor Overactivity. J Urol. 2023 Apr;209(4):774-784. doi: 10.1097/JU.0000000000003157. Epub 2023 Jan 19. PMID: 36655470.
Conclusions: OnabotulinumtoxinA continued to be well tolerated after repeated treatments in pediatric neurogenic detrusor overactivity patients with similar safety profiles across dose groups. Treatment-emergent adverse events were primarily urological with no new safety concerns.
Press B, Gardezi M, Kim DD, Lokeshwar S, Rahman S, Siev M, Ghiraldi E, Lerner L, Kellner D. Ejaculatory Preserving Holmium Laser Enucleation of the Median Lobe: Preserving Sexual Function While Improving Urinary Outcomes. Urology. 2023 Mar;173:175-179. doi: 10.1016/j.urology.2022.12.035. Epub 2023 Jan 14. PMID: 36646177.
Objective: To evaluate perioperative outcomes related to sexual and urinary function in patients who underwent a holmium laser enucleation of the prostate (HoLEP) with selective laser enucleation of the median lobe.
Leapman MS, Thiel CL, Gordon IO, Nolte AC, Perecman A, Loeb S, Overcash M, Sherman JD. Environmental Impact of Prostate Magnetic Resonance Imaging and Transrectal Ultrasound Guided Prostate Biopsy. Eur Urol. 2023 May;83(5):463-471. doi: 10.1016/j.eururo.2022.12.008. Epub 2023 Jan 11. PMID: 36635108.
Conclusions: A prostate biopsy contributes a calculable environmental footprint. Modifying or reducing the number of biopsies performed through existing evidence-based approaches would decrease health care pollution from the procedure.
Choksi AU, [Kim IY]. The disparities in clinical trials addressing urologic conditions among lower-income countries. Frontiers in Urology. 01/2023;2. doi: 10.3389/fruro.2022.1069265.
Discussion: A majority of urologic clinical trials are being conducted in high-income countries which does not coincide with the global burden of disease of urologic conditions.
Rajwa P, Quhal F, Pradere B, Gandaglia G, Ploussard G, Leapman MS, Gore JL, Paradysz A, Tilki D, Merseburger AS, Morgan TM, Briganti A, Palapattu GS, Shariat SF. Prostate cancer risk, screening and management in patients with germline BRCA1/2 mutations. Nat Rev Urol. 2023 Apr;20(4):205-216. doi: 10.1038/s41585-022-00680-4. Epub 2023 Jan 4. PMID: 36600087.
Prostate-specific antigen (PSA) measurement or prostate magnetic resonance imaging (MRI) alone is an imperfect indicator of clinically significant prostate cancer; therefore, BRCA1/2 mutation carriers might benefit from refined risk stratification strategies.
Sterling J, Policastro C, Elyaguov J, Simhan J, Nikolavsky D. How and why tobacco use affects reconstructive surgical practice: a contemporary narrative review. Transl Androl Urol. 2023 Jan 30;12(1):112-127. doi: 10.21037/tau-22-427. Epub 2023 Jan 3. PMID: 36760864; PMCID: PMC9906109.
Background and Objective: The overall negative impact of tobacco use on an individual's health has been well documented but the literature on tobacco's impact on post-surgical outcomes, specifically the outcomes after urologic surgery, is not as clear cut. The aim of this narrative review is to provide urologists with the information needed to have a nuanced pre-operative counseling conversation with patients about tobacco use. Here we combine publications on the histologic and physiologic changes induced by nicotine and tobacco use with publications from the wider surgical literature on post-operative outcomes in tobacco users.
Sterling J. Advances in reconstructive urology: A review of the 2022 literature. International Journal of Reconstructive Urology. 2023;1(1):4. doi: 10.4103/IJRU.IJRU_3_23.
The purpose of this article was to identify and highlight the high-impact recent literature published within reconstructive urology during the past year. Original research, systematic reviews, and videos from the Gold Journal, BJUI, World Journal of Urology International, SIU Journal, Neurourology Urodynamics, Journal of Urology, and European Urology were included.
SECONDARY FACULTY
Atkins MB, Jegede OA, Haas NB, McDermott DF, Bilen MA, Stein M, Sosman JA, Alter R, Plimack ER, Ornstein MC, Hurwitz M, Peace DJ, Signoretti S, Denize T, Cimadamore A, Wu CJ, Braun D, Einstein D, Catalano PJ, Hammers H. Phase II study of nivolumab and salvage nivolumab/ipilimumab in treatment-naïve patients with advanced non-clear cell renal cell carcinoma (HCRN GU16-260-Cohort B). J Immunother Cancer. 2023 Mar;11(3):e004780. doi: 10.1136/jitc-2022-004780. PMID: 36948504; PMCID: PMC10040058.
Conclusions: Nivolumab monotherapy has limited activity in treatment-naïve nccRCC with most responses (4 of 5) seen in patients with sarcomatoid and/or unclassified tumors. Toxicity is consistent with prior nivolumab studies. Salvage treatment with nivolumab/ipilimumab was provided in half of these patients with minimal activity.
Autio KA, Higano CS, Nordquist L, Appleman LJ, Zhang T, Zhu XH, Babiker H, Vogelzang NJ, Prasad SM, Schweizer MT, Madan RA, Billotte S, Cavazos N, Bogg O, Li R, Chan K, Cho H, Kaneda M, Wang IM, Zheng J, Tang SY, Hollingsworth R, Kern KA, Petrylak DP. First-in-human, phase 1 study of PF-06753512, a vaccine-based immunotherapy regimen (VBIR), in non-metastatic hormone-sensitive biochemical recurrence and metastatic castration-resistant prostate cancer (mCRPC). J Immunother Cancer. 2023 Mar;11(3):e005702. doi: 10.1136/jitc-2022-005702. PMID: 36948505; PMCID: PMC10040068.
Conclusions: PrCa VBIR overall demonstrated safety signals similar to other ICI combination trials; significant side effects were seen in some patients with BCR. It stimulated antigen-specific immunity across all cohorts and resulted in modest antitumor activity in patients with BCR without using ADT.
Petrylak DP. Pembrolizumab plus docetaxel for patients with metastatic castration-resistant prostate cancer (mCRPC): Randomized, double-blind, phase 3 KEYNOTE-921 study. Journal of clinical oncology. 02/2023;41(6_suppl):19-19. doi: 10.1200/JCO.2023.41.6_suppl.19.
Conclusions: The addition of pembrolizumab to docetaxel did not significantly improve rPFS or OS for pts with mCRPC and did not result in a notable increase in treatment-related AEs.
Petrylak DP. Patient-reported outcomes (PROs) in KEYNOTE-921: Pembrolizumab (pembro) plus docetaxel for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). Journal of clinical oncology. 02/2023;41(6_suppl):129-129. doi: 10.1200/JCO.2023.41.6_suppl.129.
Conclusions: HRQoL and disease-related symptom scores at all analyzed time points, as well as TTD and TTPP, were similar between the 2 trial arms. These data suggest that pembro + docetaxel did not negatively impact QoL in pts with mCRPC treated with prior NHA.
O'Donnell PH, [Petrylak DP]. Enfortumab vedotin (EV) alone or in combination with pembrolizumab (P) in previously untreated cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer (la/mUC): Subgroup analyses of confirmed objective response rate (cORR) from EV-103 cohort K. Journal of clinical oncology. 02/2023;41(6_suppl):499-499. doi: 10.1200/JCO.2023.41.6_suppl.499.’
Conclusions: EV+P showed promising cORR in 1L cisplatin-ineligible pts w/ la/mUC; activity was consistently observed across a range of pre-specified subgroups including those with poor prognosis. EV+P TRAEs were manageable w/ close monitoring and appropriate dose modifications w/ a meaningful duration of treatment. EV+P has the potential to address high unmet needs in 1L la/mUC and MIBC and is being further evaluated in 3 Phase 3 trials (NCT04223856, NCT04700124, NCT03924895).
Choueiri TK, [Braun DA]. Biomarker analysis from the phase 3 CheckMate 9ER trial of nivolumab cabozantinib v sunitinib for advanced renal cell carcinoma (aRCC). Journal of clinical oncology. 02/2023;41(6_suppl):608-608. doi: 10.1200/JCO.2023.41.6_suppl.608.
Conclusions: In this exploratory post hoc analysis, biomarkers previously found to be predictive of anti-PD-L1 ± anti-VEGF outcomes, including established GES, were not predictive of efficacy with anti-PD-1 + anti-VEGF (N+C) using Cox PH models. This suggests that key determinants of response to anti–PD-1 v anti–PD-L1 therapies may differ.
Milowsky MI, [Petrylak DP]. Patient-reported outcomes (PROs) in cisplatin-ineligible patients (pts) with locally advanced or metastatic urothelial cancer (la/mUC) treated with enfortumab vedotin (EV) alone or in combination with pembrolizumab (P) in the phase 1b/2 EV-103 cohort K study. Journal of clinical oncology. 02/2023;41(6_suppl):439-439. doi: 10.1200/JCO.2023.41.6_suppl.439.
Conclusions: PRO data showed that EV+P in cisplatin-ineligible pts with la/mUC was associated with preservation or improvement of QOL, functioning, and symptoms. Improvement in pain was demonstrated consistently in both PRO instruments and treatment arms. These PRO data complement the clinical outcomes of EV+P in 1L cisplatin-ineligible pts with la/mUC.
Petrylak DP. Primary analysis of TROPHY-U-01 cohort 2, a phase 2 study of sacituzumab govitecan (SG) in platinum (PT)-ineligible patients (pts) with metastatic urothelial cancer (mUC) that progressed after prior checkpoint inhibitor (CPI) therapy. Journal of clinical oncology. 02/2023;41(6_suppl):520-520. doi: 10.1200/JCO.2023.41.6_suppl.520.
Conclusions: SG monotherapy demonstrated a high response rate with an overall manageable safety profile in PT-ineligible pts with mUC who progressed after CPI therapy. No new safety signals were observed. These data support further evaluation of SG in pts with mUC post CPI therapy.
Sadeghi S, [Petrylak DP]. A phase III randomized trial of eribulin (E) with or without gemcitabine vs standard of care (SOC) for metastatic urothelial carcinoma (UC) refractory to or ineligible for PD/PDL1 antibody (ab): SWOG S1937. Journal of clinical oncology. 02/2023;41(6_suppl):TPS581-TPS581. doi: 10.1200/JCO.2023.41.6_suppl.TPS581.
Background: UC is 2nd most common genitourinary cancer. Current SOC offers platinum-based (PB) first line chemotherapy (chemo) with ddMVAC or gemcitabine-cisplatin (GC) regimens. For cisplatin ineligible patients (pts), SOC includes gemcitabine-carboplatin (GCa), and in select pts pembrolizumab. Erdafitinib is approved for pts with FGFR alterations and Enfortumab vedotin (EV) is approved for previously treated pts. A phase I/II CTEP study of eribulin (E) for metastatic UC (mUC) established the activity of E in UC with objective response rate (ORR) of 37.5% and a median progression free survival (PFS) of 4.1 months (mo) and median overall survival (OS) of 9.5 mo (N=150). A phase II CTEP study of gemcitabine-eribulin (GE) in cisplatin ineligible mUC showed an ORR of 50%, median OS of 11.9 mo and median PFS of 5.3 mo (N=24). The most common Grade 3-4 toxicities included: neutropenia 63%, anemia and fatigue 29%. Pts with liver metastases benefited from therapy with 5 responders in 7 pts for GE vs 12 out 49 E.
Aggarwal, R. R., [Petrylak, D. P.] (2023). First-in-class oral innate immune activator BXCL701 combined with pembrolizumab in patients with metastatic, castration-resistant prostate cancer (mCRPC) of small cell neuroendocrine (SCNC) phenotype: Phase 2a final results. American Society of Clinical Oncology. doi:10.1200/JCO.2023.41.6_suppl.176
Conclusions: Oral BXCL701 in combination with pembrolizumab demonstrates encouraging anti-tumor activity with durability of response in late-line, refractory mCRPC SCNC for which there is currently no standard of care. BXCL701 BID dosing continues to demonstrate an acceptable safety profile.
Tagawa ST, [Petrylak DP]. Updated outcomes in TROPHY-U-01 cohort 1, a phase 2 study of sacituzumab govitecan (SG) in patients (pts) with metastatic urothelial cancer (mUC) that progressed after platinum (PT)-based chemotherapy and a checkpoint inhibitor (CPI). Journal of clinical oncology. 02/2023;41(6_suppl):526-526. doi: 10.1200/JCO.2023.41.6_suppl.526.
Conclusions: At 10.5-mo med follow-up, the response rate remains high in pts with heavily pretreated mUC, including pts with visceral metastases, prior EV therapy and prior (neo)adjuvant PT therapy. No new safety signals were observed. These data support the use of SG in pts with mUC who received PT and a CPI and further evaluation of SG in earlier lines of therapy.
Atkins MB, [Hurwitz, M]. Treatment-free survival (TFS) outcomes from the phase II study of nivolumab and salvage nivolumab ipilimumab in advanced clear cell renal cell carcinoma (aRCC) (HCRN GU16-260-cohort A). Journal of clinical oncology. 02/2023;41(6_suppl):604-604. doi: 10.1200/JCO.2023.41.6_suppl.604.
Conclusions: NIVO monotherapy with salvage NIVO/IPI in non-responders is an active treatment approach in treatment-naïve pts with aRCC and results in substantial TFS and toxicity-free TFS. TFS was particularly noted in pts with FAV disease, further supporting the use of an immunotherapy-only regimen in this population.
Labaki C, [Braun DA]. Characterization of clinical outcomes among patients with advanced chromophobe renal cell carcinoma (ChRCC) treated with first-line immunotherapy (IO)-based regimens. Journal of clinical oncology. 02/2023;41(6_suppl):654-654. doi: 10.1200/JCO.2023.41.6_suppl.654.
Conclusions: In this real-world study, patients with metastatic ChRCC appear to display poor clinical outcomes even with IO-based regimens, as compared to ccRCC. The molecular determinants of poor response require further investigations.
Braun DA, [Hurwitz ME]. Examination of resistance to nivolumab monotherapy through single-cell analysis of tumors from patients enrolled in the HCRN GU16-260 study of nivolumab monotherapy. Journal of clinical oncology. 02/2023;41(6_suppl):698-698. doi: 10.1200/JCO.2023.41.6_suppl.698.
Conclusions: Single-cell transcriptomic analysis uncovered a SLAMF7+ CD8 + T cell population with markers of cytotoxicity and tissue residency that was associated with resistance to nivo monotherapy in RCC. Further, the study highlights that scRNA-seq is a viable scientific strategy for deep correlative analysis in multicenter clinical trials.
Grivas P, [Petrylak DP]. Primary analysis of TROPHY-U-01 cohort 3, a phase 2 study of sacituzumab govitecan (SG) in combination with pembrolizumab (pembro) in patients (pts) with metastatic urothelial cancer (mUC) that progressed after platinum (PT)-based therapy. Journal of clinical oncology. 02/2023;41(6_suppl):518-518. doi: 10.1200/JCO.2023.41.6_suppl.518.
Conclusions: SG plus Pembro demonstrated a high ORR and CBR with a manageable safety profile in 2L mUC in CPI-naive pts who progressed after PT-based therapy. No new safety signals were observed with the combination. These data support further evaluation of SG plus CPI in mUC.
Cieri N, [Braun DA]. Systematic identification of autosomal and Y-encoded minor histocompatibility antigens reveals predictors of chronic GvHD and candidate gvl targets. Transplantation and cellular therapy. 02/2023;29(2):S30. doi: 10.1016/S2666-6367(23)00104-5.
To systematically identify autosomal and Y chromosome-encoded mHAgs, we devised a computational pipeline based on: i) comparison of whole exomes (WES) from donor-recipient pairs to define recipient-restricted exonic non-synonymous SNPs; ii) expression filters built by incorporating the analysis of single-cell RNA expression profiles from normal and malignant hematopoietic cells, and GvHD target organs (skin, liver, GI, lung, oral mucosa and lacrimal gland). Identified recipient-restricted SNPs, expressed in GvL or GvHD tissues, then underwent HLA-I binding prediction with HLAthena.
Nassar AH, Abou Alaiwi S, Baca SC, Adib E, Corona RI, Seo JH, Fonseca MAS, Spisak S, El Zarif T, Tisza V, Braun DA, Du H, He M, Flaifel A, Alchoueiry M, Denize T, Matar SG, Acosta A, Shukla S, Hou Y, Steinharter J, Bouchard G, Berchuck JE, O'Connor E, Bell C, Nuzzo PV, Mary Lee GS, Signoretti S, Hirsch MS, Pomerantz M, Henske E, Gusev A, Lawrenson K, Choueiri TK, Kwiatkowski DJ, Freedman ML. Epigenomic charting and functional annotation of risk loci in renal cell carcinoma. Nat Commun. 2023 Jan 21;14(1):346. doi: 10.1038/s41467-023-35833-5. PMID: 36681680; PMCID: PMC9867739.
While the mutational and transcriptional landscapes of renal cell carcinoma (RCC) are well-known, the epigenome is poorly understood. We characterize the epigenome of clear cell (ccRCC), papillary (pRCC), and chromophobe RCC (chRCC) by using ChIP-seq, ATAC-Seq, RNA-seq, and SNP arrays.
Nyman J, Denize T, Bakouny Z, Labaki C, Titchen BM, Bi K, Hari SN, Rosenthal J, Mehta N, Jiang B, Sharma B, Felt K, Umeton R, Braun DA, Rodig S, Choueiri TK, Signoretti S, Van Allen EM. Spatially aware deep learning reveals tumor heterogeneity patterns that encode distinct kidney cancer states. bioRxiv [Preprint]. 2023 Feb 20:2023.01.18.524545. doi: 10.1101/2023.01.18.524545. PMID: 36712053; PMCID: PMC9882334.
Here, we developed spatially aware deep learning models of tumor- and immune-related features to learn representations of ccRCC tumors using diagnostic whole-slide images (WSI) in untreated and treated contexts (n = 1102 patients).
Han S, Camp SY, Chu H, Collins R, Gillani R, Park J, Bakouny Z, Ricker CA, Reardon B, Moore N, Kofman E, Labaki C, Braun D, Choueiri TK, AlDubayan SH, Van Allen EM. Integrative Analysis of Germline Rare Variants in Clear and Non-Clear Cell Renal Cell Carcinoma. medRxiv [Preprint]. 2023 Jan 19:2023.01.18.23284664. doi: 10.1101/2023.01.18.23284664. PMID: 36712083; PMCID: PMC9882438.
Objective: To evaluate the enrichment of germline PVs in established cancer-predisposing genes (CPGs) in clear cell and non-clear cell RCC patients compared to cancer-free controls using approaches that account for population stratification and to identify unconventional types of germline RCC risk variants that confer an increased risk of developing RCC.
Dizman N, Austin M, Considine B, Jessel S, Schoenfeld D, Merl MY, Hurwitz M, Sznol M, Kluger H. Outcomes With Combination Pembrolizumab and Axitinib in Second and Further Line Treatment of Metastatic Renal Cell Carcinoma. Clin Genitourin Cancer. 2023 Apr;21(2):221-229. doi: 10.1016/j.clgc.2023.01.002. Epub 2023 Jan 12. PMID: 36681606.
Introduction: Combination immune checkpoint inhibitors (ICI) and vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGF-R-TKI), including pembrolizumab/axitinib, are approved for first-line treatment of metastatic renal cell carcinoma (mRCC). Pembrolizumab/axitinib is associated with superior progression free survival (PFS), objective response rate (ORR), and overall survival over sunitinib. However, to date, the activity and safety of pembrolizumab/axitinib in later lines of therapy has not been reported.
Bayram A, [Harmanli O]. Selecting a winning team: Management of surgical team composition in robotic surgery. Computers & industrial engineering. 01/2023;175:108819. doi: 10.1016/j.cie.2022.108819.
In this study, we address a team composition problem in robotic surgery in which we evaluate the efficiency of an operating room by assessing individual and dependent performances of surgical team members.
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Featured in this article
- David A. Braun, MD, PhD
- Jaime A. Cavallo, MD, MPHS
- Israel Franco, MD, FAAP, FACS
- Oz Harmanli, MD
- Michael Hurwitz, MD, PhD
- Daniel S. Kellner, MD
- Isaac Y. Kim, MD, PhD, MBA
- Michael S. Leapman, MD, MHS
- John Onofrey, PhD
- Daniel P. Petrylak, MD
- Leslie M. Rickey, MD, MPH
- Preston C. Sprenkle, MD
- Joshua Sterling, MD, MSc