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Background: The diagnosis of active neoplastic disease was traditionally judged an absolute contraindication for extracorporeal membrane oxygenator (ECMO) because of the fear of tumor cells being scattered or seeded. The aim of this study is to compare the number of circulating tumor cells (CTCs) before and after surgery in patients receiving lung cancer resection with and without intraoperative ECMO support. Methods: This is a prospective, non-randomized, two-arms observational study comparing the number of CTCs before and after surgery in patients receiving lung cancer resection with and without intraoperative ECMO support. The ECMO arm includes patients suffering from lung cancer undergoing pulmonary resection with planned intraoperative ECMO support. The non-ECMO arm includes patients suffering from non-early-stage lung cancer undergoing pulmonary resection without planned intraoperative ECMO support. Results: Twenty patients entered the study, eight in the ECMO arm and twelve in the non-ECMO arm. We did not observe any significant difference between the ECMO and non-ECMO groups in terms of postoperative complications (p = 1.00), ICU stay (p = 0.30), hospital stay (p = 0.23), circulating tumor cells’ increase or decrease after surgery (p = 0.24), and postoperative C-reactive protein and C-reactive protein increase (p = 0.80). The procedures in the non-ECMO arm were significantly longer than those in the ECMO arm (p = 0.043). Conclusions: Intraoperative ECMO for lung cancer resections did not impact CTC increase or decrease after the procedure.

Since squamous cell carcinoma antigen (SCC-Ag) testing became commercially available on the Architect platform, the previously established method on the Abbott IMx platform has been progressively replaced. Aim of this work was to compare SCC-Ag values obtained with the 2 methods. Clinical and laboratory data of 188 patients for whom SCC-Ag determination was requested, were reviewed. IMx was used to determine the levels of SCC-Ag from June 2007 to May 2009, while the Architect system was used from June 2009 to April 2011. Only patients consistently diagnosed with no evidence of disease, for whom at least 2 determinations with each analyzer were available were used. Comparison of the results obtained with the 2 systems was then performed. Mean values for SCC-Ag were 0.56 ng/mL (Standard Error (SE): 0.08) with the IMx method, and 1.08 ng/mL (SE 0.10) with Architect (p<0.0001). False positive results were found in 4.8% of patients with the IMx method and in 9.5% of patients with Architect (p=0.049). The values of SCC-Ag determined on the Architect platform are higher than those obtained on the IMx, with a higher percentage of false positive results. © 2013 Wichtig Editore.

Pancreatic cancer patients underwent surgical resection often present distant metastases early after surgery. Detection of circulating tumor cells (CTCs) has been correlated to a worse oncological outcome in patients with advanced pancreatic cancer. The objective of this pilot study is to investigate the possible prognostic role of CTCs in patients undergoing surgery for pancreatic cancer. In 20 patients undergoing pancreatic resection, 10 mL blood sample was collected intraoperatively from both systemic circulation (SC) and portal vein (PV). Blood sample was analyzed for CTCs with CellSearch® system. All patients underwent an oncologic follow-up for at least 3 years, quarterly. CTCs were detected in nine (45 %) patients: five patients had CTCs in PV only, three patients in both SC and PV, and one patient in SC only. CTC-positive and CTC-negative patients were similar for demographics and cancer stage pattern. No significant differences were found in both overall and disease-free survival between CTC-positive and CTC-negative patients. At 3-year follow-up, portal vein CTC-positive patients presented a higher rate of liver metastases than CTC-negative patients (53 vs. 8 %, p = 0.038). CTCs were found in 45 % of the patients. No correlation between CTCs and survival was found. The presence of CTCs in portal vein has been associated to higher rate of liver metastases after surgery.

Introduction: Circulating tumor cells (CTCs) have been studied in breast cancer with the CellSearch (R) system. Given the low CTC counts in non-metastatic breast cancer, it is important to evaluate the inter-reader agreement. Methods: CellSearch (R) images (N = 272) of either CTCs or white blood cells or artifacts from 109 non-metastatic (M0) and 22 metastatic (M1) breast cancer patients from reported studies were sent to 22 readers from 15 academic laboratories and 8 readers from two Veridex laboratories. Each image was scored as No CTC vs CTC HER2-vs CTC HER2+. The 8 Veridex readers were summarized to a Veridex Consensus (VC) to compare each academic reader using % agreement and kappa (.) statistics. Agreement was compared according to disease stage and CTC counts using the Wilcoxon signed rank test. Results: For CTC definition (No CTC vs CTC), the median agreement between academic readers and VC was 92% (range 69 to 97%) with a median. of 0.83 (range 0.37 to 0.93). Lower agreement was observed in images from M0 (median 91%, range 70 to 96%) compared to M1 (median 98%, range 64 to 100%) patients (P < 0.001) and from M0 and < 3CTCs (median 87%, range 66 to 95%) compared to M0 and >= 3CTCs samples (median 95%, range 77 to 99%), (P < 0.001). For CTC HER2 expression (HER2-vs HER2+), the median agreement was 87% (range 51 to 95%) with a median. of 0.74 (range 0.25 to 0.90). Conclusions: The inter-reader agreement for CTC definition was high. Reduced agreement was observed in M0 patients with low CTC counts. Continuous training and independent image review are required.

The serial monitoring of cardiac troponin represents an effective approach for the early identification, assessment, and monitoring of chemotherapy-induced cardiac injury. Over the last few years new generations of troponin assays, referred to as sensitive and high sensitivity assays, able to detect very low concentrations of troponin, have been progressively released on different platforms. Some studies have assessed the comparability of the cTnI measurements with the new assays versus the conventional ones, but none of these in the oncological population. We compared the cTnI results determined on Stratus CS and ADVIA Centaur CP System in 70 breast cancer patients, for a total of 327 samples collected during different cycles of treatment. Correlation (Spearman = 0.732) and agreement (91.4%) between the assays were good (244 concordant negatives and 55 concordant positives), with a frequency of 8.6% discordant results among the cTnI measurements. Despite the well-known lack in the harmonization and standardization of the currently commercially available cTnI methods, we found a good clinical concordance of cTnI determination on both systems. © 2014 Informa Healthcare.

To assess the prognostic value of presurgical CA15.3 in a large cohort of patients with early breast cancer. A total of 7.942 consecutive patients with breast cancer operated at the European Institute of Oncology between 1998 and 2005 and with presurgical values of CA 15.3 available were included. We explored patterns of recurrence by baseline CA 15.3 values. Mean CA15.3 was 17.0 U/ml. CA15.3 was associated with age, tumor size, nodal involvement, Ki-67 labeling index, grade, HER2 expression, molecular subtype, and perivascular invasion. CA15.3 was independently associated with distant metastases [HR > 20 U/ml vs. ≤ 20 U/ml: 1.34 (95% CI 1.15-1.56)] and death [HR > 20 U/ml vs. ≤ 20 U/ml: 1.30 (95% CI 1.11-1.53)]. When considering CA15.3 as continuous variable, we observed a constant risk of metastasis and death from the lowest values to about 15-20 U/ml, and then a significantly increasing risk with increasing values of CA15.3. Finally, CA15.3 provided significant additional information to the common prognostic factors to predict the occurrence of metastases (C-index P value 0.04). In patients with operable breast cancer, presurgical CA15.3 value is an independent prognostic factor for metastases and deaths. CA15.3 provides additional information to the common prognostic factors and should be considered in the adjuvant therapeutic algorithm. © 2011 Springer Science+Business Media, LLC.

Circulating tumor cell (CTC) count has been shown to be an independent predictor of progression in metastatic breast, prostate, and colorectal cancer. A cutpoint is generally used to identify favorable and unfavorable response groups. In this study, we propose an approach in which the number of CTCs is analyzed as a continuous predictor, to detect the shape of the relationship between CTCs and prognosis of metastatic breast cancer. We evaluated the association of baseline CTC with progression-free survival (PFS) and overall survival (OS) in a series of 80 patients treated for advanced breast cancer at the European Institute of Oncology, Milan. The association between CTCs and prognosis was analyzed with standard categorical survival analysis and spline regression models. At baseline, median age was 55 years; 33 patients were newly diagnosed with metastatic breast cancer (41%), while 28 (35%) and 19 (24%) were pretreated with one and two previous chemotherapy lines, respectively. After a median follow-up of 28 months, 76 disease progressions and 44 deaths were observed. Kaplan-Meier curves showed a clear association between CTCs and PFS (P-value 0.03) and OS (P-value < 0.01). Patients with no CTC at baseline had a significantly better prognosis. When analyzing the CTCs as a continuous variable, we found an increase in risk with increasing number of CTCs, for both PFS and OS. The increase rate lessened after approximately 5 CTCs. CTCs represent a robust prognostic factor in the metastatic breast cancer setting. A nonlinear increase in risk of both progression and death with increasing number of CTCs was observed, with a lessening increase after approximately 5 CTCs. If distinct prognostic groups are to be identified, women with no CTC could plausibly represent a distinct favorable one.

BACKGROUND: The prognostic role of serum levels of molecular biomarkers during the perioperative period in patients with early breast cancer is not clear. PATIENTS AND METHODS: Serum VEGF and extracellular domains (ECD) of EGFR and HER2 were prospectively determined in 119 consecutive patients with early breast cancer on the day before and after surgery. RESULTS: After a median follow-up of 93 months, the preoperative value and the absolute change from pre- to postoperative serum levels of VEGF and HER2 ECD did not predict disease-free survival (DFS). A decrease after surgery of EGFR ECD correlated with a statistically significant lower DFS; each 1 ng/ml decrease in EGFR ECD serum level was associated with an increase of event risk of 15% on multivariable analysis (hazard ratio 1.15 95% confidence interval 1.04.-1.28, p=0.006). CONCLUSION: The perioperative absolute change of EGFR ECD significantly correlated with disease outcome of patients with early breast cancer. No correlation was found between preoperative and perioperative absolute change of serum VEGF and HER2 ECD.