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Are disseminated tumor cells in bone marrow and tumor-stroma ratio clinically applicable for patients undergoing surgical resection of primary colorectal cancer? The Leiden MRD study

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ABSTRACT

Purpose: Current TNM staging does not appropriately identify high-risk colorectal cancer (CRC) patients. The aim of this study was to evaluate whether the presence of disseminated tumor cells (DTCs) in the bone marrow (BM) and the presence of stroma in the primary tumor, i.e., the tumor-stroma ratio (TSR), in patients undergoing surgical resection of primary CRC provides information relevant for disease outcome.

Methods: Patients with primary CRC (n = 125), consecutively admitted for curative resection between 2001 and 2007, were included in the study. All patients underwent BM aspiration before surgery. Detection of tumor cells was performed using immunocytochemical staining for cytokeratin (CK-ICC). The TSR was determined on diagnostic H&E stained sections of primary tumors.

Results: DTCs were detected in the BM of 23/125 patients (18 %). No association was found between BM status and overall survival (HR 0.97 (95 % CI 0.45–2.09), p = 0.93). Also, no significant difference was found in their 5-year survival rate (resp. 72 % and 68 % for BM-positive versus BM-negative patients). The TSR was found to be associated with a worse overall survival (HR 2.16, 95 % CI 1.02–4.57, p = 0.04) with 5-year survival rates of 84 % versus 62 % for stroma-low and stroma-high patients, respectively. No relation was found between the presence of DTCs and TSR.

Conclusions: Our data indicate that the presence of DTCs in the BM of CRC patients is not associated with disease outcome. The TSR was, however, found to be associated with a worse overall survival, which indicates that for CRC the tumor microenvironment plays an important role in its behavior and prognosis.

No MeSH data available.


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Kaplan-Meier survival curves for CK-ICC negative and CK-ICC positive patients: overall survival (a) and disease-free survival (b) in lymph node-negative patients after surgery for primary colorectal cancer
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Fig2: Kaplan-Meier survival curves for CK-ICC negative and CK-ICC positive patients: overall survival (a) and disease-free survival (b) in lymph node-negative patients after surgery for primary colorectal cancer

Mentions: In the lymph node-negative (stage I-II) patients, no significant difference was observed between the BM-negative and BM-positive cases in OS or DFS (Fig. 2); HR 0.85 (95 % CI 0.24–3.04), p = 0.80 and HR 1.83 (95 % CI 0.66–5.09), p = 0.25, respectively. Also in the group of elderly patients (>70 years), no significant difference was found between the BM-negative and BM-positive cases in OS (n = 58; p = 0.25) or DFS (n = 49; p = 0.24). Adjustment for sex, age, tumor location and chemotherapy did not change the results for any of these survival analyses.Fig. 2


Are disseminated tumor cells in bone marrow and tumor-stroma ratio clinically applicable for patients undergoing surgical resection of primary colorectal cancer? The Leiden MRD study
Kaplan-Meier survival curves for CK-ICC negative and CK-ICC positive patients: overall survival (a) and disease-free survival (b) in lymph node-negative patients after surgery for primary colorectal cancer
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC5121180&req=5

Fig2: Kaplan-Meier survival curves for CK-ICC negative and CK-ICC positive patients: overall survival (a) and disease-free survival (b) in lymph node-negative patients after surgery for primary colorectal cancer
Mentions: In the lymph node-negative (stage I-II) patients, no significant difference was observed between the BM-negative and BM-positive cases in OS or DFS (Fig. 2); HR 0.85 (95 % CI 0.24–3.04), p = 0.80 and HR 1.83 (95 % CI 0.66–5.09), p = 0.25, respectively. Also in the group of elderly patients (>70 years), no significant difference was found between the BM-negative and BM-positive cases in OS (n = 58; p = 0.25) or DFS (n = 49; p = 0.24). Adjustment for sex, age, tumor location and chemotherapy did not change the results for any of these survival analyses.Fig. 2

View Article: PubMed Central - PubMed

ABSTRACT

Purpose: Current TNM staging does not appropriately identify high-risk colorectal cancer (CRC) patients. The aim of this study was to evaluate whether the presence of disseminated tumor cells (DTCs) in the bone marrow (BM) and the presence of stroma in the primary tumor, i.e., the tumor-stroma ratio (TSR), in patients undergoing surgical resection of primary CRC provides information relevant for disease outcome.

Methods: Patients with primary CRC (n = 125), consecutively admitted for curative resection between 2001 and 2007, were included in the study. All patients underwent BM aspiration before surgery. Detection of tumor cells was performed using immunocytochemical staining for cytokeratin (CK-ICC). The TSR was determined on diagnostic H&E stained sections of primary tumors.

Results: DTCs were detected in the BM of 23/125 patients (18 %). No association was found between BM status and overall survival (HR 0.97 (95 % CI 0.45–2.09), p = 0.93). Also, no significant difference was found in their 5-year survival rate (resp. 72 % and 68 % for BM-positive versus BM-negative patients). The TSR was found to be associated with a worse overall survival (HR 2.16, 95 % CI 1.02–4.57, p = 0.04) with 5-year survival rates of 84 % versus 62 % for stroma-low and stroma-high patients, respectively. No relation was found between the presence of DTCs and TSR.

Conclusions: Our data indicate that the presence of DTCs in the BM of CRC patients is not associated with disease outcome. The TSR was, however, found to be associated with a worse overall survival, which indicates that for CRC the tumor microenvironment plays an important role in its behavior and prognosis.

No MeSH data available.


Related in: MedlinePlus