Multicenter fresh frozen tissue sampling in colorectal cancer: does the quality meet the standards for state of the art biomarker research?

The growing interest in the molecular subclassification of colorectal cancers is increasingly facilitated by large multicenter biobanking initiatives. The quality of tissue sampling is pivotal for successful translational research. This study shows the quality of fresh frozen tissue sampling within a multicenter cohort study for colorectal cancer (CRC) patients. Each of the seven participating hospitals randomly contributed ten tissue samples, which were collected following Standard Operating Procedures (SOP) using established techniques. To indicate if the amount of intact RNA is sufficient for molecular discovery research and prove SOP compliance, the RNA integrity number (RIN) was determined. Samples with a RIN < 6 were measured a second time and when consistently low a third time. The highest RIN was used for further analysis. 91% of the tissue samples had a RIN ≥ 6 (91%). The remaining six samples had a RIN between 5 and 6 (4.5%) or lower than 5 (4.5%). The median overall RIN was 7.3 (range 2.9-9.0). The median RIN of samples in the university hospital homing the biobank was 7.7 and the median RIN for the teaching hospitals was 7.3, ranging from 6.5 to 7.8. No differences were found in the outcome of different hospitals (p = 0.39). This study shows that the collection of high quality fresh frozen samples of colorectal cancers is feasible in a multicenter design with complete SOP adherence. Thus, using basic sampling techniques large patient cohorts can be organized for predictive and prognostic (bio)marker research for CRC.

Prognostic value of circulating tumour cells for early recurrence after resection of colorectal liver metastases.

BACKGROUND: Despite good outcomes for many, a substantial group of patients undergoing metastasectomy for isolated liver metastases from colorectal cancer (CRC) experience early recurrence. We have investigated whether circulating tumour cell (CTC) detection can identify patients developing disease recurrence within 1 year after liver metastasectomy. METHODS: In CRC patients undergoing liver metastasectomy, 30 ml peripheral blood was withdrawn preoperatively. CTCs were detected by the CellSearch system after a density-gradient-based enrichment step. RESULTS: One hundred and seventy-three samples from 151 individual patients were analysed. In 75 samples (43%), CTCs were detected, 16% had ⩾3 CTCs/7.5 ml of blood. Eighty-two patients (47%) experienced early disease recurrence (<1 year). The 1-year recurrence rate between patients with or without detectable CTCs were similar (47% vs 48%) or with a low or high CTC count (<3 or ⩾3 CTCs/7.5 ml of blood) (50% vs 47%). Also disease-free and overall survival were similar between patients with or without CTCs. CONCLUSIONS: The presence of CTCs in preoperative peripheral blood samples does not identify patients at risk for early disease recurrence after curative resection of colorectal liver metastases. Other parameters are needed to better identify patients at high risk to relapse after liver metastasectomy for CRC.

Optimizing the outcome of surgery in patients with rectal cancer and synchronous liver metastases.

BACKGROUND: This study evaluated the outcome of patients treated for rectal cancer and synchronous hepatic metastases in the era of effective induction radiotherapy and chemotherapy. METHODS: All patients undergoing surgical treatment of rectal cancer and synchronous liver metastases between 2000 and 2007 were identified retrospectively from a prospectively collected database. Three approaches were followed: the classical staged, the simultaneous and the liver-first approach. RESULTS: Of 57 patients identified, the primary tumour was resected first in 29 patients (group 1), simultaneous resection was performed in eight patients (group 2), and 20 patients underwent a liver-first approach (group 3). The overall morbidity rate was 24.6 per cent; there was no in-hospital mortality. Median in-hospital stay was significantly shorter for the simultaneous approach (9 days versus 18 and 15 days for groups 1 and 3 respectively; P < 0.001). The overall 5-year survival rate was 38 per cent, with an estimated median survival of 47 months. CONCLUSION: Long-term survival can be achieved using an individualized approach, with curative intent, in patients with rectal cancer and synchronous liver metastases. Simultaneous resections as well as the liver-first approach are attractive alternatives to traditional staged resections.

'Staged' liver resection in synchronous and metachronous colorectal hepatic metastases: differences in clinicopathological features and outcome.

AIM: Approximately 25% of the patients with colorectal cancer already have liver metastases at diagnosis and another 30% will develop them subsequently. The features and prognosis of patients with synchronous and metachronus colorectal liver metastases, treated with primary resection first followed by partial liver resection were analysed. METHOD: Curative staged resection of liver metastases was performed in 272 consecutive patients. Demographics, characteristics of the primary tumour and metastatic tumours, surgery-related data and outcome were analysed. RESULTS: Synchronous metastases were present in 105 (39%) patients and metachronous metastases in 167 (61%). More patients in the synchronous group had an advanced primary tumour (T3/T4 and/or node positivity), more than three liver metastases and bilobar distribution. A significantly higher percentage of patients in the synchronous group received neoadjuvant chemotherapy. The 5-year survival rate in the group of 272 patients was 38%. Patients with more than three metastases had a significantly worse survival rate. There were no differences in disease-free and overall survival rates between the synchronous and metachronous group. CONCLUSION: Although patients with synchronous colorectal liver metastases may have poorer biological features, there was no difference in 5-year disease-free and overall survival compared with patients with metachronous metastases. This may be explained by the observation that patients in the synchronous group received significantly more neoadjuvant chemotherapy.

Local treatment for recurrent colorectal hepatic metastases after partial hepatectomy.

OBJECTIVE: The objective of the study was to identify patients who may benefit from local treatment in recurrent colorectal liver metastases. MATERIALS AND METHODS: A total of 51 consecutive patients were treated for hepatic recurrence(s) after an initial partial hepatic resection. Surgery was considered as the primary treatment option for eligible patients. Patients with a small liver remnant after major hepatectomy were treated with radiofrequency ablation (RFA) or stereotactic body radiation therapy (SRx). SRx was given as an outpatient, emerging local treatment option for patients with intra-hepatic recurrences not eligible for surgery or RFA. Partial liver resection was performed in 36 patients (70%), RFA in ten patients (20%), and SRx in five patients (10%). RESULTS: Median hospital stay was 7 (range, 3-62) days with a morbidity of 16% without in-hospital death. None of the patients received adjuvant chemotherapy. There was no difference in recurrence or survival between the three treatment modalities. Overall 5-year survival was 35% with an estimated median survival of 37 months. Patients with a disease-free interval between first hepatectomy and hepatic recurrence less than 6 months did not survive 3 years. CONCLUSIONS: Resection, RFA, and SRx can be performed safely in patients with recurrent colorectal liver metastases and offer a survival that seems comparable to primary liver resections of colorectal liver metastases.