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Non-muscle-invasive bladder cancer (NMIBC) prognosis varies significantly due to the biological and clinical heterogeneity. High-risk stage T1-G3, comprising 15–20% of NMIBCs, involves the lamina propria and is associated with higher rates of recurrence, progression, and cancer-specific mortality. In the present study, we have evaluated the enumeration of tumour-derived extracellular vesicles (tdEVs) and circulating tumour cells (CTCs) in high-risk NMIBC patients and their correlation with survival outcomes such as time to progression (TTP), and cancer-specific survival (CSS). Eighty-three high-risk T1-G3 NMIBC patients treated between September 2010 and January 2013 were included. Blood samples were collected before a transurethral resection of the bladder (TURB) and analysed using the CellSearch® system. The presence of at least one CTC was associated with a shorter TTP and CSS. Extending follow-up to 120 months and incorporating automated tdEV evaluation using ACCEPT software demonstrated that tdEV count may additionally stratify patient risk. Combining tdEVs and CTCs improves risk stratification for NMIBC progression, suggesting that tdEVs could be valuable biomarkers for prognosis and disease monitoring. Further research is needed to confirm these findings and establish the clinical significance of tdEVs in early-stage cancers. [ABSTRACT FROM AUTHOR]

Background: A large amount of evidence from clinical studies has demonstrated that circulating tumor cells are strong predictors of outcomes in many cancers. However, the clinical significance of CTC enumeration in metastatic colorectal cancer is still questioned. The aim of this study was to evaluate the clinical value of CTC dynamics in mCRC patients receiving first-line treatments. Materials and methods: Serial CTC data from 218 patients were used to identify CTC trajectory patterns during the course of treatment. CTCs were evaluated at baseline, at a first-time point check and at the radiological progression of the disease. CTC dynamics were correlated with clinical endpoints. Results: Using a cut-off of ≥1 CTC/7.5 mL, four prognostic trajectories were outlined. The best prognosis was obtained for patients with no evidence of CTCs at any timepoints, with a significant difference compared to all other groups. Lower PFS and OS were recognized in group 4 (CTCs always positive) at 7 and 16 months, respectively. Conclusions: We confirmed the clinical value of CTC positivity, even with only one cell detected. CTC trajectories are better prognostic indicators than CTC enumeration at baseline. The reported prognostic groups might help to improve risk stratification, providing potential biomarkers to monitor first-line treatments. [ABSTRACT FROM AUTHOR]

Background: Circulating tumor cells (CTCs) are responsible for the metastatic dissemination of colorectal cancer (CRC) to the liver, lungs and lymph nodes. CTCs rarity and heterogeneity strongly limit the elucidation of their biological features, as well as preclinical drug sensitivity studies aimed at metastasis prevention. Methods: We generated organoids from CTCs isolated from an orthotopic CRC xenograft model. CTCs-derived organoids (CTCDOs) were characterized through proteome profiling, immunohistochemistry, immunofluorescence, flow cytometry, tumor-forming capacity and drug screening assays. The expression of intra- and extracellular markers found in CTCDOs was validated on CTCs isolated from the peripheral blood of CRC patients. Results: CTCDOs exhibited a hybrid epithelial-mesenchymal transition (EMT) state and an increased expression of stemness-associated markers including the two homeobox transcription factors Goosecoid and Pancreatic Duodenal Homeobox Gene-1 (PDX1), which were also detected in CTCs from CRC patients. Functionally, CTCDOs showed a higher migratory/invasive ability and a different response to pathway-targeted drugs as compared to xenograft-derived organoids (XDOs). Specifically, CTCDOs were more sensitive than XDOs to drugs affecting the Survivin pathway, which decreased the levels of Survivin and X-Linked Inhibitor of Apoptosis Protein (XIAP) inducing CTCDOs death. Conclusions: These results indicate that CTCDOs recapitulate several features of colorectal CTCs and may be used to investigate the features of metastatic CRC cells, to identify new prognostic biomarkers and to devise new potential strategies for metastasis prevention. [ABSTRACT FROM AUTHOR]

The presence of circulating tumor cells (CTCs) in the blood of patients with metastatic breast, colorectal and prostate cancer have been widely investigated; however, few studies have examined CTCs in patients with laryngeal cancer. The present pilot study aimed to detect pre- and postoperative CTCs in the blood of patients with laryngeal cancer and evaluate the association with prognosis. Eight patients with laryngeal squamous cell carcinoma (LSCC) at stage III were included in the present study and underwent total or subtotal laryngectomy and radical bilateral neck lymph node dissection. Blood samples were collected from all patients before and after surgery at different time-points. The following processing steps were followed; preoperative blood sampling, surgery, postoperative blood sampling at 3, 6 and 12 month follow-ups, and prognostic association analysis. CTCs were retained on ScreenCell filters for cytological characterization. The presence of CTCs was associated with a less favorable prognosis, whereas a decrease of CTCs in the postoperative sampling was observed in patients who exhibited an improved therapeutic response. The results of the present pilot study revealed a possible association between the presence of CTCs and a less favorable prognosis in patients with LSCC; therefore, these preliminary findings may encourage further research into the incorporation of a liquid biopsy in the management of LSCC, as this may help identify patients with occult metastatic disease earlier and in a non-invasive manner. In addition, this approach may represent novel independent prognostic factor for use in the clinical evaluation of patients with LSCC. [ABSTRACT FROM AUTHOR]

OBJECTIVE To evaluate the prognostic significance of survivin in tumour tissues and that of survivin-expressing circulating tumour cells (CTCs) in T1G3 bladder tumours, as the prognosis of T1G3 bladder cancer is highly variable and unpredictable from clinical and pathological prognostic factors. PATIENTS AND METHODS The study included 54 patients with T1G3 non-muscle-invasive bladder cancer. Additional inclusion criteria were: tumour size <3 cm, absence of carcinoma in situ and multifocality. The planned follow-up was 24 months. Survivin was evaluated by reverse transcription-polymerase chain reaction in tumour tissues. CTCs were isolated from blood by CELLectionTM Dynabeads (Invitrogen, Carlsbad, CA, USA) coated with the monoclonal antibody towards the human epithelial cell adhesion molecule. Cells were lysed and Dynabeads Oligo(dT) was used to capture poly A + mRNA. cDNA was synthesized and analysed for the expression of CD45, CK8 and survivin. The primary endpoint was disease-free survival (DFS); the favourable group at 24 months was defined as that with no clinical evidence of disease; the unfavourable group was that with evidence of recurrent disease or progressive disease. Tumour survivin expression and presence of CTC were correlated with DFS. Multivariate analysis was used to investigate whether the presence of CTC was an independent indicator of DFS. RESULTS Survivin was found in half of the tumours; patients with survivin-negative tumours had a longer DFS than those with survivin-positive tumours (chi-square, P = 0.029). CTCs were found in 24/54 patients (44%); 92% of CTC expressed survivin. The difference in DFS between CTC–ve and CTC+ve patients was statistically significant (chi-square, P < 0.001). The presence of CTC was an independent prognostic factor for DFS ( P < 0.001). CONCLUSION The presence of CTC is an independent prognostic factor in patients with T1G3 bladder cancer. [ABSTRACT FROM AUTHOR]

Molecular alterations are not randomly distributed in colorectal cancer (CRC), but rather clustered on the basis of primary tumor location underlying the importance of colorectal cancer sidedness. We aimed to investigate whether circulating tumor cells (CTC) characterization might help clarify how different the patterns of dissemination might be relative to the behavior of left- (LCC) compared to right-sided (RCC) cancers. We retrospectively analyzed patients with metastatic CRC who had undergone standard baseline CTC evaluation before starting any first-line systemic treatment. Enumeration of CTC in left- and right-sided tumors were compared. The highest prognostic impact was exerted by CTC in left-sided primary cancer patients, even though the lowest median number of cells was detected in this subgroup of patients. CTC exhibit phenotypic heterogeneity, with a predominant mesenchymal phenotype found in CTC from distal compared to proximal primary tumors. Most CTC in RCC patients exhibited an apoptotic pattern. CTC in left-sided colon cancer patients exhibit a predominant mesenchymal phenotype. This might imply a substantial difference in the biology of proximal and distal cancers, associated with different patterns of tumor cells dissemination. The poor prognosis of right-sided CRC is not determined by the hematogenous dissemination of tumor cells, which appears to be predominantly a passive shedding of non-viable cells. Conversely, the subgroup of poor-prognosis left-sided CRC is reliably identified by the presence of mesenchymal CTC. [ABSTRACT FROM AUTHOR]