Comparative Analysis of Tumor Cell Dissemination to the Sentinel Lymph Nodes and to the Bone Marrow in Patients With Nonmetastasized Colon Cancer: A Prospective Multicenter Study
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Comparative Analysis of Tumor Cell Dissemination to the Sentinel Lymph Nodes and to the Bone Marrow in Patients With Nonmetastasized Colon Cancer: A Prospective Multicenter Study. / Weixler, Benjamin; Viehl, Carsten T; Warschkow, Rene; Guller, Ulrich; Ramser, Michaela; Sauter, Guido; Zuber, Markus.
in: JAMA SURG, Jahrgang 152, Nr. 10, 01.10.2017, S. 912-920.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Comparative Analysis of Tumor Cell Dissemination to the Sentinel Lymph Nodes and to the Bone Marrow in Patients With Nonmetastasized Colon Cancer: A Prospective Multicenter Study
AU - Weixler, Benjamin
AU - Viehl, Carsten T
AU - Warschkow, Rene
AU - Guller, Ulrich
AU - Ramser, Michaela
AU - Sauter, Guido
AU - Zuber, Markus
PY - 2017/10/1
Y1 - 2017/10/1
N2 - Importance: Small nodal tumor infiltrates (SNTI; isolated tumor cells and micrometastases) in sentinel lymph nodes and bone marrow micrometastases (BMM) were independently described as prognostic factors in patients with colon cancer.Objective: To examine the association between the occurrence of SNTI and BMM as well as their prognostic relevance.Design, Setting, and Participants: This prospective study was conducted at 3 university-affiliated institutions in Switzerland between May 2000 and December 2006. Statistical analyses were performed in October 2016. A total of 122 patients with stage I to III colon cancer were included. Follow-up time exceeded 6 years, with no patients lost to follow-up.Interventions: Bone marrow aspiration from the iliac crests and in vivo sentinel lymph node mapping were performed during open standard oncological resection. Bone marrow aspirates were stained with the pancytokeratin marker A45-B/B3. All sentinel lymph nodes underwent multilevel sectioning and were stained with hematoxylin-eosin and the pancytokeratin marker AE1/AE3.Main Outcomes and Measures: Association of SNTI in sentinel lymph nodes and BMM in patients with stage I to III colon cancer and the prognostic effect on disease-free survival (DFS) and overall survival (OS).Results: Of the 122 patients, 63 (51.6%) were female, with a mean (SD) age of 71.2 (11.7) years. Small nodal tumor infiltrates and BMM were found in a total of 21 patients (17.2%) and 46 patients (37.7%), respectively. The occurrence of BMM was not associated with the presence of SNTI by standard correlation (κ, -0.07; 95% CI, -0.29 to 0.14; P = .49) nor by univariate logistic regression analysis (odds ratio, 0.64; 95% CI, 0.22-1.67; P = .37) or multivariate logistic regression analysis (odds ratio, 1.09; 95% CI, 0.34-3.28; P = .88). The presence of SNTI was an independent negative prognostic factor for DFS (hazard ratio [HR], 2.93; 95% CI, 1.24-6.93; P = .02) and OS (HR, 4.04; 95% CI, 1.56-10.45; P = .005), as was BMM (HR, 2.07; 95% CI, 1.06-4.06; P = .04; and HR, 2.68; 95% CI, 1.26-5.70; P = .01; respectively). The combined detection of BMM and SNTI demonstrated the poorest DFS (HR, 6.73; 95% CI, 2.29-19.76; P = .006) and OS (HR, 5.96; 95% CI, 1.66-21.49; P = .03).Conclusions and Relevance: This study demonstrates no association between the occurrence of SNTI and BMM in patients with stage I to III colon cancer. However, both SNTI and BMM are independent negative prognostic factors regarding DFS and OS, and the occurrence of both is associated with significantly worse prognosis compared with either one of them.Trial Registration: clinicaltrials.gov Identifier: NCT00826579.
AB - Importance: Small nodal tumor infiltrates (SNTI; isolated tumor cells and micrometastases) in sentinel lymph nodes and bone marrow micrometastases (BMM) were independently described as prognostic factors in patients with colon cancer.Objective: To examine the association between the occurrence of SNTI and BMM as well as their prognostic relevance.Design, Setting, and Participants: This prospective study was conducted at 3 university-affiliated institutions in Switzerland between May 2000 and December 2006. Statistical analyses were performed in October 2016. A total of 122 patients with stage I to III colon cancer were included. Follow-up time exceeded 6 years, with no patients lost to follow-up.Interventions: Bone marrow aspiration from the iliac crests and in vivo sentinel lymph node mapping were performed during open standard oncological resection. Bone marrow aspirates were stained with the pancytokeratin marker A45-B/B3. All sentinel lymph nodes underwent multilevel sectioning and were stained with hematoxylin-eosin and the pancytokeratin marker AE1/AE3.Main Outcomes and Measures: Association of SNTI in sentinel lymph nodes and BMM in patients with stage I to III colon cancer and the prognostic effect on disease-free survival (DFS) and overall survival (OS).Results: Of the 122 patients, 63 (51.6%) were female, with a mean (SD) age of 71.2 (11.7) years. Small nodal tumor infiltrates and BMM were found in a total of 21 patients (17.2%) and 46 patients (37.7%), respectively. The occurrence of BMM was not associated with the presence of SNTI by standard correlation (κ, -0.07; 95% CI, -0.29 to 0.14; P = .49) nor by univariate logistic regression analysis (odds ratio, 0.64; 95% CI, 0.22-1.67; P = .37) or multivariate logistic regression analysis (odds ratio, 1.09; 95% CI, 0.34-3.28; P = .88). The presence of SNTI was an independent negative prognostic factor for DFS (hazard ratio [HR], 2.93; 95% CI, 1.24-6.93; P = .02) and OS (HR, 4.04; 95% CI, 1.56-10.45; P = .005), as was BMM (HR, 2.07; 95% CI, 1.06-4.06; P = .04; and HR, 2.68; 95% CI, 1.26-5.70; P = .01; respectively). The combined detection of BMM and SNTI demonstrated the poorest DFS (HR, 6.73; 95% CI, 2.29-19.76; P = .006) and OS (HR, 5.96; 95% CI, 1.66-21.49; P = .03).Conclusions and Relevance: This study demonstrates no association between the occurrence of SNTI and BMM in patients with stage I to III colon cancer. However, both SNTI and BMM are independent negative prognostic factors regarding DFS and OS, and the occurrence of both is associated with significantly worse prognosis compared with either one of them.Trial Registration: clinicaltrials.gov Identifier: NCT00826579.
KW - Aged
KW - Bone Marrow
KW - Colonic Neoplasms
KW - Disease-Free Survival
KW - Female
KW - Follow-Up Studies
KW - Humans
KW - Male
KW - Middle Aged
KW - Neoplasm Micrometastasis
KW - Neoplasm Staging
KW - Prospective Studies
KW - Sentinel Lymph Node
KW - Survival Rate
KW - Comparative Study
KW - Journal Article
KW - Multicenter Study
U2 - 10.1001/jamasurg.2017.1514
DO - 10.1001/jamasurg.2017.1514
M3 - SCORING: Journal article
C2 - 28593306
VL - 152
SP - 912
EP - 920
JO - JAMA SURG
JF - JAMA SURG
SN - 2168-6254
IS - 10
ER -