Objective: The aim of the study is to assess the prognostic and predictive value of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) in bone marrow (BM) in patients with colorectal liver metastasis referred to surgery. Background: A total of 194 patients were included. Treatment of the patients was decided in a multidisciplinary team. Methods: BM aspirates and blood samples were collected at surgery, or in local anesthesia in nonresectable patients. CTCs were disclosed with CellSearch System, DTC with immunocytology. Results: Liver resection was completed in 153 patients. Forty-one patients were nonresectable, 22 preoperatively and 19 intraoperatively. The median follow-up was 22 (range 1–61) months. Relapse was diagnosed in 103 of the resected patients. Totally, 67 patients died of cancer. CTCs were detected in 19.6% of the patients. CTC positivity was significantly higher in nonresectable (46%) than in resectable patients (11.7%), P < 0.001. 13.8% of the patients had 2 or more CTCs, 31% of the nonresectable and 9.1% of the resectable patients (P = 0.001). Patients with 2 or more CTCs experienced reduced time to relapse/progression, both analyzing all patients (P = 0.002) and analyzing resectable patients (P < 0.001). Two or more CTCs was a strong predictor of progression and mortality in all subgroups of patients, together with more than 3 liver metastases, R1 resection, and extrahepatic disease. DTCs were detected in 9.9% of the patients, but not associated with clinical outcome in resectable patients. Conclusions: CTCs predict nonresectability and impaired survival. CTC analysis should be considered as a tool for decision-making before liver resection in these patients.

In patients with presumed pancreatic ductal adenocarcinoma (PDAC), biomarkers that may open for personalised, risk-adapted treatment are lacking. The study analysed the impact of CTCs-presence on the patterns of recurrence and survival in 98 patients resected for PDAC with 5–10 years of follow-up. Preoperative samples were analysed by the CellSearch^® system for EpCAM+/DAPI+/CK+/CD45-CTCs. CTCs were detected in 7 of the 98 patients. CTCs predicted a significantly shorter median disease-free survival (DFS) of 3.3 vs. 9.2 months and a median cancer specific survival (CSS)of 6.3 vs. 18.5 months. Relapse status was confirmed by imaging for 87 patients. Of these, 58 patients developed distant metastases (DM) and 29 developed isolated local recurrence (ILR) as the first sign of cancer relapse. All patients with CTCs experienced DM. pN-status and histological grade >2 were other independent risk factors for DM, but only CTCs predicted significantly shorter cancer-specific, disease-free and post-recurrence survival. Preoperative parameters did not affect clinical outcome. We conclude that CTC presence in resected PDAC patients predicted early distant metastasis and impaired survival. Preoperative CTCs alone or in combination with histopathological factors may guide initial treatment decisions in patients with resectable PDAC in the future.

Background: Presence of disseminated tumor cells (DTCs) in bone marrow (BM) after completion of systemic adjuvant treatment predicts reduced survival in breast cancer. The present study explores the use of DTCs to identify adjuvant insufficiently treated patients to be offered secondary adjuvant treatment intervention, and as a surrogate marker for therapy response. Methods: A total of 1121 patients with pN1-3 or pT1c/T2G2-3pN0-status were enrolled. All had completed primary surgery and received 6 cycles of anthracycline-containing chemotherapy. BM-aspiration was performed 8-12 weeks after chemotherapy (BM1), followed by a second BM-aspiration 6 months later (BM2). DTC-status was determined by morphological evaluation of immunocytochemically detected cytokeratin-positive cells. If DTCs were present at BM2, docetaxel (100 mg/m², 3qw, 6 courses) was administered, followed by DTC-analysis 1 month (BM3) and 13 months (BM4) after the last docetaxel infusion. Results: Clinical follow-up (FU) is still ongoing. Here, the descriptive data from the study are presented. Of 1085 patients with a reported DTC result at both BM1 and BM2, 94 patients (8.7%) were BM1 positive and 83 (7.6%) were BM2 positive. The concordance between BM1 and BM2 was 86.5%. Both at BM1 and BM2 DTC-status was significantly associated with lobular carcinomas (p = 0.02 and p = 0.03, respectively; chi-square). In addition, DTC-status at BM2 was also associated with pN-status (p = 0.009) and pT-status (p = 0.03). At BM1 28.8% and 12.8% of the DTC-positive patients had ≥2 DTCs and ≥3 DTCs, respectively. At BM2, the corresponding frequencies were 47.0% and 25.3%. Of 72 docetaxel-treated patients analyzed at BM3 and/or BM4, only 15 (20.8%) had persistent DTCs. Of 17 patients with ≥3 DTCs before docetaxel treatment, 12 patients turned negative after treatment (70.6%). The change to DTC-negativity was associated with the presence of ductal carcinoma (p = 0.009). Conclusions: After docetaxel treatment, the majority of patients experienced disappearance of DTCs. As this is not a randomized trial, the results can be due to effects of adjuvant (docetaxel/endocrine/trastuzumab) treatment and/or limitations of the methodology. The clinical significance of these results awaits mature FU data, but indicates a possibility for clinical use of DTC-status as a residual disease-monitoring tool and as a surrogate marker of treatment response. Trial registration: Clin Trials Gov NCT00248703