Innovative analytic methods in the imaging of upper tract urothelial carcinoma: Radiomics, Radiogenomics and creation of a new prognostic tool for systemic therapies of UTUC
Final Report Abstract
Upper tract urothelial carcinoma (UTUC) is a rare malignancy, comprising up to 10% of all renal neoplasms. Despite radical resection via nephroureterectomy (RNU), disease relapse occurs in 47% of cases. The iatrogenic loss of functional kidney tissue limits postoperative chemotherapy options, necessitating the use of neoadjuvant chemotherapy (NAC) to optimize oncologic care. However, response rates to NAC remain around 50%, and there are currently no established preoperative biomarkers. Radiomics, an emerging imaging analysis technique, offers the potential to extract imaging data beyond standard clinical evaluation, reflecting tumor biology and molecular characteristics. However, to date few studies have been conducted on radiomic in UTUC and its predictive value on NAC has not yet been investigated. A query of the institutional data base of the Memorial Sloan Kettering Cancer Center (MSKCC) identified 92 patients who received chemotherapy prior to RNU and underwent computed tomography scans. Pathologic response to NAC was observed in 58% of patients. Tumor segmentation was performed by two independent annotators and 1,690 radiomic features (RF) were extracted, with 67% showing high inter-reader concordance. Three different machine-learning models incorporating RF and clinical parameters were built and achieved AUCs of 0.65, 0.61 and 0.74, suggesting a predictive value. This underscores the potential clinical significance of RFs in the absence of established genetic and molecular biomarkers. In addition, our research group investigated the optimal integration of surgery in the context of modern systemic therapies for renal cell carcinoma (RCC). We found that cytoreductive nephrectomy is safe following modern treatment agents and that active surveillance after consolidative nephrectomy can improve quality of life without compromising oncological outcomes in selected patients. Patients exhibiting exceptional responses to systemic therapy displayed distinct immune cell populations such as high fraction of CD8+ cytotoxic T cells, large proportion of CD4+ naive cells with unique sub-clones and CD8+ tissue resident cells. Furthermore, we investigated transcriptomics from three prospective trials used to tailor systemic therapy in RCC. A post-hoc analyses revealed differing gene expression profiles between primary and metastatic tumors, highlighting the impact of tissue site on biomarker-outcome associations. In a translational project, we focused on non-clear cell RCC with nodal disease and reported that 25% of patients remained disease-free after initial surgical treatment. Similar, salvage lymph node dissection for recurrent/metachronous lymph node metastases showed favorable outcomes, particularly in patients with lateonset disease. Exploratory genetic analyses identified frequent alterations in genes such as SETD2, TP53, B2M, and NF2 in patients with synchronous nodal disease, and higher tumor mutational burden.
Publications
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Advances in Imaging-Based Biomarkers in Renal Cell Carcinoma: A Critical Analysis of the Current Literature. Cancers, 15(2), 354.
Posada, Calderon Lina Posada; Eismann, Lennert; Reese, Stephen W.; Reznik, Ed & Hakimi, Abraham Ari
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Prognostic Factors for Survival in Patients Undergoing Surveillance After Cytoreductive Nephrectomy. Journal of Urology, 210(2), 273-279.
Reese, Stephen W.; Khaleel, Sari; Silagy, Andrew; Xie, Amy; Eismann, Lennert; Vazquez-Rivera, Katiana; Oparanozie, Arnold; Patil, Sujata; Coleman, Jonathan; Motzer, Robert; Kotecha, Ritesh R.; Russo, Paul; Voss, Martin H. & Hakimi, A. Ari
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COMPREHENSIVE IMMUNOGENOMIC EVALUATION OF PATIENTS UNDERGOING CONSOLIDATIVE CYTOREDUCTIVE NEPHRECTOMY IN METASTATIC RENAL CELL CARCINOMA PATIENTS TREATED WITH IMMUNE CHECKPOINT BLOCKADE. Urologic Oncology: Seminars and Original Investigations, 42, S44.
Reese, Stephen; Yarlagadda, Vijay; Wu, Chih-Ying; Kuo, Fengshen; Tang, Cerise; Jiang, Hui; Vuong, Lynda H.; Eismann, Lennert; Motzer, Robert; Voss, Martin H.; Reznik, Ed; Reuter, Victor; Coleman, Johnathan; Russo, Paul; Kotecha, Ritesh R.; Leslie, Christina; Chen, Yingbei & Hakimi, A. Ari
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Surgical outcomes of cytoreductive nephrectomy in patients receiving systemic immunotherapy for advanced renal cell carcinoma. Urologic Oncology: Seminars and Original Investigations, 42(2), 32.e9-32.e16.
Reese, Stephen W.; Eismann, Lennert; White, Charlie; Villada, Juan Arroyave; Khaleel, Sari; Ostrovnaya, Irina; Vazquez-Rivera, Katiana; Carlo, Maria I.; Feldman, Darren; Lee, Chung-Han; Motzer, Robert; Voss, Martin H.; Kotecha, Ritesh R.; Matulewicz, Richard S.; Goh, Alvin; Coleman, Jonathan; Russo, Paul & Hakimi, A. Ari
