scholarly journals Potential of circulating tumor DNA as a predictor of therapeutic responses to immune checkpoint blockades in metastatic renal cell carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yeon Jeong Kim ◽  
Yumi Kang ◽  
Jun Seop Kim ◽  
Hyun Hwan Sung ◽  
Hwang Gyun Jeon ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Deep Sequencing ◽  
Immune Checkpoint ◽  
Circulating Tumor Dna ◽  
First Line ◽  
Primary Tumors ◽  
Predictive Role ◽  
Targeted Deep Sequencing ◽  
Tumor Dna

AbstractWe evaluated the predictive role of circulating tumor DNA (ctDNA) detection by targeted deep sequencing in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint blockades (ICB). To determine the feasibility of ctDNA detection in our panel encompassing 40 genes, we collected 10 ml of blood from 20 patients at the time of radical nephrectomy. We analyzed somatic mutations in primary tumors and ctDNA samples from these patients. We finally collected 10 ml of blood before and after 1 month of treatment, respectively, from four patients with mRCC who received first-line ICB treatment. Variants were detected in primary tumors of 15 patients (75%) and ctDNA was detected in the plasma of 9 patients (45%). We examined the predictive role of ctDNA in four patients who received first-line ICB therapy. In two patients showing partial response, ctDNA levels decreased after 1 month of ICB treatment. However, in one patient who showed disease progression, ctDNA levels increased after 1 month of ICB treatment. Taken together, ctDNA detection in plasma by targeted deep sequencing was feasible in patients with RCC. Moreover, the levels of ctDNA could be an early predictor of treatment response in patients with mRCC who receive ICB therapy.

Prognostic and predictive role of fumarate hydratase in metastatic clear cell renal cell carcinoma.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 617-617
Author(s):  
Claudio Vernieri ◽  
Giovanni Fucà ◽  
Simona Massa ◽  
Raffaele Ratta ◽  
Elena Verzoni ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Fumarate Hydratase ◽  
First Line ◽  
Primary Tumors ◽  
Predictive Role ◽  
The Impact

617 Background: Metabolic disruption is frequent in renal cell carcinoma (RCC). Loss of the mitochondrial fumarate hydratase (FH) enzyme is associated with enhanced glycolytic metabolism, angiogenesis and clinical aggressiveness in type 2 papillary RCC. However, FH expression has never been evaluated in clear cell RCC (ccRCC). In this study, we investigated the impact of FH expression on the outcomes of patients (pts) with metastatic ccRCC (mccRCC). Methods: We included pts with mccRCC, for whom formalin-fixed, paraffin embedded (FFPE) tissue from the primary tumor had been obtained before initiation of systemic treatment. FH levels were evaluated by immunohistochemistry (IHC), and were defined as “normal” if FH expression in most cancer cells was comparable to the adjacent normal tubular cells and “low” in the opposite case. We evaluated the association between FH levels and clinico-pathological characteristics through the chi-squared or Fisher’s exact test. The log-rank test was used to compare survival between patient subgroups. Results: We evaluated 49 mccRCC pts, of whom 36 (73.5%) had synchronous metastases. FH levels were normal in 29 (59.2%) pts and low in 20 (40.8%) pts. FH expression was not associated with patient age (p = 0.5), sex (p = 0.34), tumor grade (p = 0.66), T stage (p = 0.38), N stage (p = 0.88), metastatic disease at the time of diagnosis (p = 0.4), number of metastatic sites (p = 1) or sarcomatoid morphology (p = 0.36). 44 pts received first-line therapy with tyrosine kinase inhibitors (TKIs). In pts with low as compared to normal FH levels, median progression free survival (mPFS) during any first-line treatment was 34 and 10.1 months, respectively (HR 0.39, 95% CI 0.18-0.85; p = 0.014), while mPFS during first-line TKI therapy was 34 and 8.42 months, respectively (HR 0.4, 95% CI 0.17-0.94; p = 0.03). Median overall survival (OS) was not reached in pts with FH-low tumors, while it was 22.9 months in normally expressing ones (HR 0.14, 95% CI 0.032-0.63; p = 0.028). Conclusions: In mccRCC pts, low FH expression in primary tumors is associated with longer PFS during any first-line or TKI treatment, and also with better OS. This is the first study to reveal a prognostic and predictive role of FH levels in mccRCC.

Evolution of Circulating Tumor DNA Profile from First-line to Subsequent Therapy in Metastatic Renal Cell Carcinoma

2017 ◽  
Vol 72 (4) ◽  
pp. 557-564 ◽  
Author(s):  
Sumanta K. Pal ◽  
Guru Sonpavde ◽  
Neeraj Agarwal ◽  
Nicholas J. Vogelzang ◽  
Sandy Srinivas ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Circulating Tumor Dna ◽  
First Line ◽  
Dna Profile ◽  
Tumor Dna

scholarly journals Circulating Tumor DNA Using Tagged Targeted Deep Sequencing to Assess Minimal Residual Disease in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Gabriella Cirmena ◽  
Anna Garuti ◽  
Marilena De Mariano ◽  
Simona Coco ◽  
Lorenzo Ferrando ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Practice ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Deep Sequencing ◽  
Circulating Tumor Dna ◽  
Clinical Relapse ◽  
Breast Cancer Patients ◽  
Targeted Deep Sequencing ◽  
Tumor Dna

In breast cancer patients undergoing neoadjuvant chemotherapy before surgery, there is an unmet need for noninvasive predictive biomarkers of response. The analysis of circulating tumor DNA (ctDNA) in particular has been the object of several reports, but few of them have studied the applicability of tagged targeted deep sequencing (tTDS) to clinical practice and its performance compared with droplet digital PCR (ddPCR). Here, we present the first results from an ongoing study involving a prospectively accrued, monocentric cohort of patients affected by invasive breast cancer, undergoing neoadjuvant chemotherapy followed by surgery with curative intent as per clinical practice. A pretreatment tumor biopsy and plasma samples were collected before and during treatment, after surgery, and every six months henceforth or until relapse, whichever came first. Pretreatment biopsies were sequenced with a 409-gene massive parallel sequencing (MPS) panel, allowing the identification of target mutations and their research in plasma by tTDS and ddPCR as a complementary approach. Using tTDS, we demonstrated the presence of at least one deleterious mutation in all the relapsed cases we studied (n = 4), with an average lead time of six months before clinical relapse. The association with ddPCR was suboptimal, and only one relapsed patient could be identified with such method. tTDS shows potential as an early noninvasive method for the detection of MRD in BC patients.

The Role of Circulating Tumor DNA in Renal Cell Carcinoma

2018 ◽  
Vol 19 (2) ◽  
Author(s):  
Paulo G. Bergerot ◽  
Andrew W. Hahn ◽  
Cristiane Decat Bergerot ◽  
Jeremy Jones ◽  
Sumanta Kumar Pal
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Circulating Tumor Dna ◽  
Tumor Dna
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