TY - JOUR
T1 - Multicenter validation study of pathologic response and tumor thickness at the tumor-normal liver interface as independent predictors of disease-free survival after preoperative chemotherapy and surgery for colorectal liver metastases
AU - Brouquet, Antoine
AU - Zimmitti, Giuseppe
AU - Kopetz, Scott
AU - Stift, Judith
AU - Julié, Catherine
AU - Lemaistre, Anne Isabelle
AU - Agarwal, Atin
AU - Patel, Viren
AU - Benoist, Stephane
AU - Nordlinger, Bernard
AU - Gandini, Alessandro
AU - Rivoire, Michel
AU - Stremitzer, Stefan
AU - Gruenberger, Thomas
AU - Vauthey, Jean Nicolas
AU - Maru, Dipen M.
PY - 2013/8/1
Y1 - 2013/8/1
N2 - BACKGROUND To validate pathologic markers of response to preoperative chemotherapy as predictors of disease-free survival (DFS) after resection of colorectal liver metastases (CLM). METHODS One hundred seventy-one patients who underwent resection of CLM after preoperative chemotherapy at 4 centers were studied. Pathologic response - defined as the proportion of tumor cells remaining (complete, 0%; major, <50%; minor, ≥50%) and tumor thickness at the tumor-normal liver interface (TNI) (<0.5 mm, 0.5 to <5 mm, ≥5 mm) - was assessed by a central pathology reviewer and local pathologists. RESULTS Pathologic response was complete in 8% of patients, major in 49% of patients, and minor in 43% of patients. Tumor thickness at the TNI was <0.5 mm in 21% of patients, 0.5 to <5 mm in 56% of patients, and ≥5 mm in 23% of patients. On multivariate analyses, using either pathologic response or tumor thickness at TNI, pathologic response (P =.002,.009), tumor thickness at TNI (P = 0.015, <.001), duration of preoperative chemotherapy (P =.028,.043), number of CLM (P =.038,. 037), and margin (P =.011,.016) were associated with DFS. In a multivariate analysis using both parameters, tumor thickness at TNI (P =.004,.015), duration of preoperative chemotherapy (P =.025), number of nodules (P =.027), and margin (P =.014) were associated with DFS. Tumor size by pathology examination was the predictor of pathologic response. Predictors of tumor thickness at the TNI were tumor size and chemotherapy regimen. There was near perfect agreement for pathologic response (κ =.82) and substantial agreement (κ =.76) for tumor thickness between the central reviewer and local pathologists. CONCLUSIONS Pathologic response and tumor thickness at the TNI are valid predictors of DFS after preoperative chemotherapy and surgery for CLM.
AB - BACKGROUND To validate pathologic markers of response to preoperative chemotherapy as predictors of disease-free survival (DFS) after resection of colorectal liver metastases (CLM). METHODS One hundred seventy-one patients who underwent resection of CLM after preoperative chemotherapy at 4 centers were studied. Pathologic response - defined as the proportion of tumor cells remaining (complete, 0%; major, <50%; minor, ≥50%) and tumor thickness at the tumor-normal liver interface (TNI) (<0.5 mm, 0.5 to <5 mm, ≥5 mm) - was assessed by a central pathology reviewer and local pathologists. RESULTS Pathologic response was complete in 8% of patients, major in 49% of patients, and minor in 43% of patients. Tumor thickness at the TNI was <0.5 mm in 21% of patients, 0.5 to <5 mm in 56% of patients, and ≥5 mm in 23% of patients. On multivariate analyses, using either pathologic response or tumor thickness at TNI, pathologic response (P =.002,.009), tumor thickness at TNI (P = 0.015, <.001), duration of preoperative chemotherapy (P =.028,.043), number of CLM (P =.038,. 037), and margin (P =.011,.016) were associated with DFS. In a multivariate analysis using both parameters, tumor thickness at TNI (P =.004,.015), duration of preoperative chemotherapy (P =.025), number of nodules (P =.027), and margin (P =.014) were associated with DFS. Tumor size by pathology examination was the predictor of pathologic response. Predictors of tumor thickness at the TNI were tumor size and chemotherapy regimen. There was near perfect agreement for pathologic response (κ =.82) and substantial agreement (κ =.76) for tumor thickness between the central reviewer and local pathologists. CONCLUSIONS Pathologic response and tumor thickness at the TNI are valid predictors of DFS after preoperative chemotherapy and surgery for CLM.
KW - colorectal liver metastases
KW - preoperative chemotherapy; Avastin; survival; pathology response; validation; multicenter study
KW - tumor regression
KW - tumor-normal liver interface
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U2 - 10.1002/cncr.28097
DO - 10.1002/cncr.28097
M3 - Article
C2 - 23868456
AN - SCOPUS:84880571481
SN - 0008-543X
VL - 119
SP - 2778
EP - 2788
JO - Cancer
JF - Cancer
IS - 15
ER -