Circulating tumor cells as a predictor and prognostic tool for metastatic clear cell renal carcinoma: An immunocytochemistry and genomic analysis.

BACKGROUND: Treatment of metastatic clear cell renal carcinoma (mccRCC) has changed dramatically over the past 20 years, without improvement in the development of biomarkers. Recently, circulating tumor cells (CTCs) have been validated as a prognostic and predictive tool for many solid tumors. OBJECTIVE: We evaluated CTCs in blood samples obtained from patients diagnosed with mccRCC. Comparisons of CTC counts, protein expression profiling, and DNA mutants were made in relation to overall survival and progression-free survival. METHODS: CTCs were isolated from 10 mL blood samples using the ISET® system (Isolation by SizE of Tumor Cells; Rarecells, France) and counted. Protein expression was evaluated in immunocytochemistry assays. DNA mutations were identified with next generation sequencing (NGS). RESULTS: Blood samples (10 mL) were collected from 12 patients with mccRCC before the start of first-line systemic therapy, and again 30 and 60 days after the start of treatment. All 12 patients had CTCs detected at baseline (median, 1.5 CTCs/mL; range: 0.25-7.75). Patients with CTC counts greater than the median had two or more metastatic sites and exhibited worse progression-free survival (19.7 months) compared to those with CTC counts less than the median (31.1 months). Disease progression was observed in 7/12 patients during the study. Five of these patients had baseline CTC counts greater than the median, one had higher CTC levels at the second blood collection, and one patient had CTCs present at 1 CTC/mL which positively stained for PD-L1, N-cadherin, VEGF, and SETD2. CTC DNA from six patients with worse outcomes was subjected to NGS. However, no conclusions could be made due to the low variant allele frequencies. CONCLUSION: Detection of CTCs in patients with mccRCC receiving first-line treatment is a feasible tool with prognostic potential since increased numbers of CTCs were found to be associated with metastasis and disease progression.

Prognostic impact and potential predictive role of baseline circulating tumor cells in locally advanced head and neck squamous cell carcinoma.

OBJECTIVES: The prognostic impact of circulating tumor cells (CTCs) or circulating tumor microemboli (CTM) in locally advanced head and neck squamous cell carcinoma (LA-HNSCC) is yet to be determined, with conflicting results in previous trials. The role of induction chemotherapy (ICT) in the management of LA-HNSCC is controversial with no predictive biomarkers to guide treatment strategy in this scenario. The aim of this trial is to determine the prognostic impact of CTCs and CTM, their biomarkers expression by immunocytochemistry (ICC), and its potential role as predictors of ICT benefit in LA-HNSCC. MATERIALS AND METHODS: Prospective study, with newly diagnosed stage III/IV non-metastatic LA-HNSCC patients treated with curative intent. Blood samples analyzed for CTCs and CTM before treatment using the ISET method. RESULTS: A total of 83 patients were included. CTCs counts were an independent prognostic factor for overall survival (OS; HR: 1.17; 95 %CI: 1.05-1.31; p = 0.005) and progression free survival (PFS; HR:1.14; 95 %CI: 1.03-1.26; p = 0.007). Using the Lausen and Schumacher technique, 2.8 CTCs/mL for OS and 3.8 CTCs/mL for PFS were defined as the best cut-offs. CTM were detected in 27.7% of patients, correlating with worse PFS (HR = 2.70; IC95%: 1.30-5.58; p = 0.007). MRP-7 expression in CTM correlated with worse OS (HR = 3.49; 95 %CI: 1.01-12.04; p = 0.047) and PFS (HR = 3.62; 95 %CI: 1.08-12.13; p = 0.037). CTCs counts were predictive of complete response to treatment (OR = 0.74; 95 %CI: 0.58-0.95; p = 0.022) and high counts (cut-off 3.8/mL) and CTM were potential predictors of ICT benefit. CONCLUSION: CTCs/CTM had significant prognostic impact and potential role as predictors of ICT benefit in LA-HNSCC.