Synchronous Brain Metastases as a Poor Prognosis Factor in Clear Cell Renal Carcinoma: A Strong Argument for Systematic Brain Screening

Abstract PurposeBrain metastases (BM) usually represent a poor prognostic factor in solid tumors. About 10% of patients with renal cancer (RCC) will present BM. Local therapies such as stereotactic radiotherapy (SRT), whole brain radiotherapy (WBRT), and surgery are used to achieve brain control. We compared survival between patients with synchronous BM (SynBM group) and metachronous BM (MetaBM group). MethodsIt is a retrospective study of patients with clear cell renal cell carcinoma (ccRCC) and BM treated with TKI between 2005 and 2019 at the Centre Léon Bérard in Lyon. We collected prognostic factors: The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk score, the TNM stage, the histological subtypes and the Fuhrman grade. Overall survival (OS) was defined from diagnosis of metastatic ccRCC to death. Brain progression-free survival (B-PFS) was defined from focal brain therapy to brain progression or death.Results99 patients were analyzed, 44 in the SynBM group and 55 in the MetaBM group. OS in the MetaBM group was 49.4 months versus 19.6 months in the SynBM group, p=0.0002. The median time from diagnosis of metastasic disease to apparition of BM in the MetaBM group was 22.9 months (4.3; 125.7). SRT was used for 101 lesions (66.4%), WBRT for 25 patients (16.4%), surgery for 21 lesions (13.8%), surgery followed by radiation for 5 lesions (3.3%). B-PFS for all patients was 7 months (IC95% [5.0-10.5]). ConclusionsSurvival of patients with synchronous BM is inferior to that of patients with metachronous BM. Outcome is poor in both cases after diagnosis of BM. Brain screening should be encouraged at time of diagnosis of metastatis in ccRCC.

Download Full-text

Nuclear and cytosolic pS727-STAT3 levels correlate with overall survival of patients affected by clear cell renal cell carcinoma (ccRCC)

Scientific Reports ◽

10.1038/s41598-021-86218-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jazmine Arévalo ◽

David Lorente ◽

Enrique Trilla ◽

María Teresa Salcedo ◽

Juan Morote ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Cell Renal Cell Carcinoma ◽

Independent Manner ◽

Fuhrman Grade ◽

Transcription 3 ◽

Aggressive Subtype

AbstractClear cell renal cell carcinoma (ccRCC) is the most frequent and aggressive subtype of renal carcinoma. So far, the basis of its oncogenesis remains unclear resulting in a deficiency of usable and reliable biomarkers for its clinical management. Previously, we showed that nuclear expression of the signal transducer and activator of transcription 3 (STAT3), phosphorylated at its serine 727 (pS727), was inversely proportional to the overall survival of ccRCC patients. Therefore, in the present study, we validated the value of pS727-STAT3 as a clinically relevant biomarker in ccRCC. This work is a retrospective study on 82 ccRCC patients treated with nephrectomy and followed-up for 10 years. Immunohistochemical expression of pS727-STAT3 was analyzed on a tissue microarray and nuclear and cytosolic levels were correlated with clinical outcome of patients. Our results showed that pS727-STAT3 levels, whether in the nucleus (p = 0.002; 95% CI 1.004–1.026) or the cytosol (p = 0.040; 95% CI 1.003–1.042), significantly correlate with patients’ survival in an independent-manner of clinicopathological features (Fuhrman grade, risk group, and tumor size). Moreover, we report that patients with high pS727-STAT3 levels who undergone adjuvant therapy exhibited a significant stabilization of the disease (~ 20 months), indicating that pS727-STAT3 can pinpoint a subset of patients susceptible to respond well to treatment. In summary, we demonstrated that high pS727-STAT3 levels (regardless of their cellular location) correlate with low overall survival of ccRCC patients, and we suggested the use of pS727-STAT3 as a prognostic biomarker to select patients for adjuvant treatment to increase their survival.

Download Full-text

Obstructive sleep apnea and Fuhrman grade in patients with clear cell renal cell carcinoma treated surgically

World Journal of Urology ◽

10.1007/s00345-016-1830-6 ◽

2016 ◽

Vol 35 (1) ◽

pp. 51-56 ◽

Cited By ~ 7

Author(s):

Antoni Vilaseca ◽

Daniel P. Nguyen ◽

Emily A. Vertosick ◽

Renato B. Corradi ◽

Mireia Musquera ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Cell Renal Cell Carcinoma ◽

Fuhrman Grade ◽

Obstructive Sleep

Download Full-text

NOVEL PLASMA GLYCOPROTEIN BIOMARKERS PREDICT PROGRESSION-FREE SURVIVAL IN SURGICALLY RESECTED CLEAR CELL RENAL CELL CARCINOMA

10.1101/2022.01.11.21268517 ◽

2022 ◽

Author(s):

Daniel Serie ◽

Amanda A Myers ◽

Daniela A Haehn ◽

Alexander Parker ◽

Essa Bajalia ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Differential Expression ◽

Renal Cell ◽

Clear Cell ◽

Progression Free Survival ◽

P Value ◽

Cell Renal Cell Carcinoma ◽

Free Survival ◽

Kaplan Meier

Introduction: Limited data exists on utilization of protein post-translational modifications as biomarkers for clear cell renal cell carcinoma (ccRCC). We employed high-throughput glycoproteomics to evaluate differential expression of glycoprotein-isoforms as novel markers for ccRCC progression-free survival (PFS). Methods: Plasma samples were obtained from 77 patients treated surgically for ccRCC. Glycoproteomic analyses were carried out after liquid chromatography tandem mass spectrometry. Age-adjusted Cox proportional hazard models were constructed to evaluate PFS. Optimized Harrells c-index was employed to dichotomize the collective for the construction of Kaplan-Meier curves. Results: The average length of follow-up was 3.4 (range: 0.04-9.83) years. Glycoproteomic analysis identified 39 glycopeptides and 14 non-glycosylated peptides that showed statistically significant (false discovery rate p ≤0.05) differential expression associated with PFS. Five of the glycosylated peptides conferred continuous hazard ratio of > 6 (range 6.3-11.6). These included prothrombin A2G2S glycan motif (HR=6.47, P=9.53E-05), immunoglobulin J chain FA2G2S2 motif (HR=10.69, P=0.001), clusterin A2G2 motif (HR=7.38, P=0.002), complement component C8A A2G2S2 motif (HR=11.59, P=0.002), and apolipoprotein M glycopeptide with non-fucosylated and non-sialylated hybrid-type glycan (HR=6.30, P=0.003). Kaplan-Meier curves based on dichotomous expression of these five glycopeptides resulted in hazard ratios of 3.9-10.7, all with p-value < 0.03. Kaplan-Meyer plot using the multivariable model comprising 3 of the markers yielded HR of 11.96 (p <0.0001). Conclusion: Differential glyco-isoform abundance of plasma proteins may be a useful source of biomarkers for the clinical course and prognosis of ccRCC.

Download Full-text

CT prediction of the Fuhrman grade of clear cell renal cell carcinoma (RCC): towards the development of computer-assisted diagnostic method

Abdominal Imaging ◽

10.1007/s00261-015-0531-8 ◽

2015 ◽

Vol 40 (8) ◽

pp. 3168-3174 ◽

Cited By ~ 21

Author(s):

Hannu Huhdanpaa ◽

Darryl Hwang ◽

Steven Cen ◽

Brian Quinn ◽

Megha Nayyar ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Diagnostic Method ◽

Clear Cell ◽

Computer Assisted ◽

Cell Renal Cell Carcinoma ◽

Fuhrman Grade

Download Full-text

The association between renal sinus fat area and the progression-free survival in Chinese non-metastatic clear-cell renal cell carcinoma patients

Oncotarget ◽

10.18632/oncotarget.19012 ◽

2017 ◽

Vol 8 (39) ◽

pp. 65481-65491

Author(s):

Haichao Huang ◽

Shi Chen ◽

Wei Yu ◽

Zirong Ye ◽

Wei Li ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Progression Free Survival ◽

Cell Renal Cell Carcinoma ◽

Renal Sinus ◽

Free Survival ◽

Renal Sinus Fat

Download Full-text

ASPEN: A randomized phase II trial of everolimus versus sunitinib in patients with metastatic non-clear cell renal cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.tps4590 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. TPS4590-TPS4590

Author(s):

Andrew J. Armstrong ◽

Susan Halabi ◽

Tim Eisen ◽

Walter Michael Stadler ◽

Robert R Jones ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Case Series ◽

Progression Free Survival ◽

Clinical Activity ◽

Cell Renal Cell Carcinoma ◽

Therapeutic Decisions ◽

Undifferentiated Histology

TPS4590 Background: Currently no level 1 evidence exists to guide therapeutic decisions in patients with metastatic non-clear cell renal cell carcinoma. Case series and retrospective analyses suggest that strategies targeting either the VEGF or mTOR/TORC1 pathways have clinical activity in papillary, chromophobe, or poorly differentiated histologic subtypes. Methods: We are conducting an international, randomized phase 2 trial of patients with metastatic non-clear cell RCC; either papillary, chromophobe, or undifferentiated histology; any Motzer risk group; and who have had no prior systemic therapy. All patients contribute tissue to an international biorepository for correlative genomic, genetic, and protein biomarker studies, along with companion longitudinal plasma and urine angiome studies. Patients are randomized to either everolimus or sunitinib (1:1) at FDA approved dosing until progression. The primary endpoint is progression free survival. Trial status: Seventy-three out of a planned 108 subjects have been enrolled at the time of abstract submission: median age 64, 59 white, 10 black, 4 unknown race, and includes 42 papillary and 31 chromophobe/undifferentiated histologies, 49 men and 22 women. Accrual is anticipated to be completed by December 2013. Accrual distribution by country is currently 43 (USA), 27 (UK), and 3 (Canada). The first DSMB meeting was conducted after 40 subjects completed at least 6 months of therapy and concluded that there were no unexpected safety signals and that the study should proceed. Tissue (primary, some metastatic, urine, plasma, whole blood) has been collected on all patients to date through the Duke Center for Human Genetics Biorepository. Clinical trial information: NCT01108445.

Download Full-text