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Clear-cell Renal Cell Carcinoma: Molecular Characterization of IMDC Risk Groups and Sarcomatoid Tumors
- Source :
- Clinical Genitourinary Cancer, Clinical Genitourinary Cancer, Elsevier, 2019, 17 (5), pp.e981-e994. ⟨10.1016/j.clgc.2019.05.009⟩, Clinical Genitourinary Cancer, 2019, 17 (5), pp.e981-e994. ⟨10.1016/j.clgc.2019.05.009⟩
- Publication Year :
- 2019
- Publisher :
- HAL CCSD, 2019.
-
Abstract
- INTRODUCTION: Recent trials have suggested predictive biomarkers in advanced clear-cell renal cell carcinoma (accRCC): International Metastatic RCC Database Consortium (IMDC) good risk or angiogenic gene signature for sunitinib and IMDC intermediate/poor risk for ipilimumab-nivolumab and T-effector cell signature or sarcomatoid dedifferentiation for atezolizumab-bevacizumab. We hypothesized that earlier described molecular subtypes, ccrcc1 to ccrcc4, could provide similar information as a single generic biomarker and molecularly characterize the heterogeneous intermediate-risk group. PATIENTS AND METHODS: Patients with accRCC treated with systemic therapies were included. We assessed associations between the 5 biomarkers and their impact on progression-free survival (PFS) and response rate (RR) on first-line sunitinib or pazopanib. The cutoff percentage of sarcomatoid dedifferentiation with optimal discriminative value was determined. RESULTS: In total, 430 patients were included (163 with molecular data). The molecular ccrcc2 subtype identified tumors with higher angiogenic gene expression across IMDC risk groups: prevalence was high in IMDC good risk and low in IMDC poor risk (P < .001). Molecular subtype, IMDC, and angiogenic gene expression had comparable C-indices to predict PFS and RR (range, 60%-66%). The ccrcc2 subtype and angiogenic gene expression were positive predictors of PFS in IMDC intermediate-risk patients (P = .006; P = .04). Immune signature did not differ between IMDC groups, but was strongly correlated with molecular subtype (P = .8 and P = .0007). A cutoff value of 25% sarcomatoid differentiation discriminated tumors with distinct molecular characteristics and therapeutic sensitivity. CONCLUSION: In accRCC, molecular subtypes can explain differences in IMDC risk group, expression of angiogenesis and immune response genes, and sarcomatoid dedifferentiation. They can identify molecularly different patient populations within the heterogeneous IMDC intermediate group and select patients for systemic therapies. ispartof: CLINICAL GENITOURINARY CANCER vol:17 issue:5 pages:E981-E994 ispartof: location:United States status: published
- Subjects :
- Male
Oncology
medicine.medical_specialty
Indazoles
Angiogenesis
Urology
Cell
030232 urology & nephrology
Angiogenesis Inhibitors
[SDV.CAN]Life Sciences [q-bio]/Cancer
Immune checkpoint inhibitor
Antibodies, Monoclonal, Humanized
Pazopanib
Molecular subtype
03 medical and health sciences
0302 clinical medicine
Renal cell carcinoma
Internal medicine
Biomarkers, Tumor
medicine
Sunitinib
Humans
Molecular Targeted Therapy
Precision Medicine
Carcinoma, Renal Cell
ComputingMilieux_MISCELLANEOUS
Sulfonamides
business.industry
Biomarker
Gene signature
medicine.disease
Survival Analysis
Kidney Neoplasms
3. Good health
Bevacizumab
Clear cell renal cell carcinoma
Pyrimidines
Treatment Outcome
medicine.anatomical_structure
030220 oncology & carcinogenesis
Biomarker (medicine)
Female
business
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 15587673
- Database :
- OpenAIRE
- Journal :
- Clinical Genitourinary Cancer, Clinical Genitourinary Cancer, Elsevier, 2019, 17 (5), pp.e981-e994. ⟨10.1016/j.clgc.2019.05.009⟩, Clinical Genitourinary Cancer, 2019, 17 (5), pp.e981-e994. ⟨10.1016/j.clgc.2019.05.009⟩
- Accession number :
- edsair.doi.dedup.....ab6dac2d13ea1013fedbdc6b96d2acfc