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Purpose: Several immune checkpoint inhibitors (ICIs) are FDA approved for treatment of genitourinary (GU) malignancies. We aim to determine demographic and clinicopathologic characteristics that significantly affect clinical outcomes in patients with advanced stage GU malignancies treated with ICIs., Materials and Methods: We performed a single-center, consecutive, retrospective cohort analysis on patients with metastatic or unresectable GU malignancies who were treated with ICIs at the University of Michigan. Immune-related adverse events (irAEs), putative immune-mediated allergies, and overall response rates (ORR) were assessed. Comorbidity index scores were calculated. Survival analysis was performed to evaluate progression-free survival (PFS) and overall survival (OS), stratifying and controlling for a variety of clinicopathologic baseline factors including site of metastases., Results: A total of 160 patients were identified with advanced renal cell carcinoma (RCC) or urothelial carcinoma. Median PFS and OS were 5.0 and 23.6 months for RCC, and 2.8 and 9.6 months for urothelial carcinoma, respectively. Patients who experienced increased frequency and higher grade irAEs had better ICI treatment response (P < 0.0001). Presence of liver metastases was associated with poor response to ICI therapy (P = 0.001). Multivariable modeling demonstrates that patients with urothelial carcinoma and liver metastases had statistically worse PFS and OS compared to patients with RCC or other sites of metastases, respectively., Conclusion: Greater frequency and higher grades of irAEs are associated with better treatment response in patients with RCC and urothelial malignancy receiving ICI therapy. The presence of liver metastases denotes a negative predictive marker for immunotherapy efficacy., Summary: Immune checkpoint inhibitors (ICI) are increasingly used to treat genitourinary (GU) malignancies. However, clinical data regarding patients with advanced-stage GU malignancies treated with ICI is lacking. Thus, we performed a single-center, retrospective cohort study on patients with metastatic and unresectable renal cell carcinoma (RCC) and urothelial carcinoma who were treated with ICIs at the University of Michigan to provide demographic and clinicopathologic data regarding this population. We specifically focused on immune-related adverse events (irAEs), immune-mediated allergies, and the associated overall response rates (ORR). To better assess performance status, we calculated comorbidity scores for all patients. Finally, survival analyses for progression-free survival (PFS) and overall survival (OS) were performed using Kaplan-Meier analysis and Cox proportional hazards modeling, stratifying and controlling for clinicopathologic baseline factors, including sites of metastases, in our multivariable analysis. A total of 160 patients were identified with advanced RCC or urothelial carcinoma. We found decreased PFS (2.8 vs. 5.0 months) and decreased OS (9.8 vs. 23.6 months) for urothelial carcinoma compared to RCC patients. We noted that patients who experienced increased frequency and higher grades of irAEs had better treatment ORR with ICI therapy (P ≤ 0.0001). The presence of liver metastases was associated with worse ORR (P = 0.001), PFS (P = 0.0014), and OS (P = 0.0028) compared to other sites of metastases including lymph node, lung, and CNS/bone. The poor PFS and OS associated with urothelial carcinoma and liver metastases were preserved in our multivariable modeling after controlling for pertinent clinical factors. We conclude that greater frequency and higher grades of irAEs are associated with better treatment response in GU malignancy patients receiving ICI, a finding that is consistent with published studies in other cancers. The presence of liver metastases represents a significantly poor predictive marker in GU malignancy treated with ICI. Our findings contribute to the growing body of literature that seeks to understand the clinicopathologic variables and outcomes associated with ICI therapy., Competing Interests: Declaration of competing interest Dr. Ajjai Alva serves as a consultant for Merck, AstraZeneca, Bristol-Myers Squibb, and Pfizer/EMD Serono. Dr. Ajjai Alva receives research funding through the University of Michigan from Merck, Genentech, Prometheus Laboratories, Mirati Therapeutics, Roche, Bayer, Progenics, Astellas Pharma, Arcus Biosciences, AstraZeneca, Bristol-Myers Squibb, and Clovis Oncology. Dr. Jeremy Taylor serves as a consultant for Sarepta. Dr. Vincent Ma, Dr. Christopher Su, Miriam Hu, Stephanie Daignault-Newton, Olesia Kellezi, Megan Dal, Miloni Sha, Stephanie Erickson, Jessica Lora, Reema Hamasha, Alicia Ali, Sabrina Yancey, Leah Kiros, Hannah Balicki, Daniel Winfield, and Dr. Michael Green have no conflict of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Abstract: This study evaluated the technical feasibility of 2-dimensional transvaginal shear wave elastography to quantify cervical stiffness in nonpregnant and pregnant women and established normal values in each group. With institutional review board approval, we performed a prospective study with an age-matched historical control design. Sixteen premenopausal nonpregnant women without cervical pathology and 17 low-risk pregnant women (gestational age 17-33 weeks) were enrolled. Cervical shear wave speeds were measured on a SuperSonic Aixplorer machine. The mean shear wave speeds of anterior cervix were 4.96 ± 1.96 m/s in nonpregnant women and 1.92 ± 0.31 m/s in pregnant women. No significant stiffness difference was found between the anterior and posterior cervix (P = 0.15). The upper cervix was stiffer than the lower cervix in the pregnant women (P = 0.00012). Transvaginal shear wave elastography reveals that cervix at a midterm gestation is significantly softer than nonpregnant cervix (P < 0.0001) and suggests a spatial stiffness gradient along the length of the cervix, consistent with histopathology and limited elastography literature. Our results indicate the potential of transvaginal shear wave elastography to provide objective and quantitative estimates of cervical stiffness, especially during pregnancy., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)