Correlation between circulating tumor biomarkers and positron-emission tomography in advanced non-small cell lung cancer

Abstract

Background: Circulating tumor cells (CTCs) and plasma circulating-free DNA (cfDNA) are promising candidates as non-invasive prognostic markers in malignant diseases. 18-fluorodeoxyglucose positron emission tomography integrated with computed tomography (18FDG-PET/TC) has a well-recognized diagnostic and prognostic value in non-small cell lung cancer (NSCLC). Very little is known about the mutual relationship between circulating biomarkers (CTCs and cfDNA) and 18FDG-PET/CT indicators in NSCLC. Methods: Peripheral blood samples from 28 patients affected by advanced/ metastatic NSCLC were collected before starting first-line chemotherapy. CTCs were isolated by size using a filtration-based device (ScreenCell) and then identified and enumerated; cfDNA was isolated from plasma (QIAamp DNA Blood Mini Kit, Qiagen) and quantified by qPCR method using human telomerase reverse transcriptase (hTERT). All patients underwent 18FDG-PET/TC (Biograph 16 Siemens) at baseline. Maximum diameter (dmax) of the primary lesion (T), dmax of the greater lymph nodal (N), and metastatic (M) lesions were measured. Similarly, maximum and mean standardized uptake value (SUVmax, SUVmean) and size-incorporated SUVmax (SIMaxSUV) were computed for T, N and M, respectively; SIMaxSUV was calculated with the following formula for T, N, and M: SIMaxSUV= SUVMax∗dmax. Presence (B+) and absence (B-) of metabolically active bone lesions (bone mets) were recorded. The association among CTCs, cfDNA and 18FDG-PET/CT-derived parameters was evaluated through multivariate analysis. T-test was performed to evaluate the difference in CTCs and cfDNA in B+ and Bgroups, respectively. Results: Twenty-eight patients were evaluated; median age was 66 years (range: 51-80); male/female ratio was 18/10; 15 patients were current smokers, while 11 were former-smokers and 2 were never-smokers. Histo-types were grouped as it follows: adenocarcinoma= 22; squamous cell carcinoma= 5; not otherwise specified NSCLC= 1. Nine patients out of 28 had metabolically active bone lesions. Median CTC count was 7 CTCs/3ml (range: 0-47 CTCs/3ml), while median HTERT copy number was 109.0 (range: 16.7-1405-5). At multivariate analysis, SUVmax of T was the only variable independently associat ed with cfDNA (p=0.036). No correlations were highlighted between CTCs and all PETderived parameters. A trend towards significance between high HTERT and the presence of metabolically active bone lesions was observed (p=0.058). Conclusion: Our data demonstrate that the expression of cfDNA is correlated with the metabolic activity of the primary tumor lesion. Since SIMaxSUV was not correlated with HTERT, it appears that the expression of cfDNA depends from tumor metabolism rather than its burden. Further analyses on 18FDG-PET/TC-derived metabolic tumor volume are ongoing. (Table Presented).