TY - JOUR
T1 - Differential histopathologic parameters in colorectal cancer liver metastases resected after triplets plus bevacizumab or cetuximab: a pooled analysis of five prospective trials
AU - Cremolini, Chiara
AU - Milione, Massimo
AU - Marmorino, Federica
AU - Morano, Federica
AU - Zucchelli, Gemma
AU - Mennitto, Alessia
AU - Prisciandaro, Michele
AU - Lonardi, Sara
AU - Pellegrinelli, Alessio
AU - Rossini, Daniele
AU - Bergamo, Francesca
AU - Aprile, Giuseppe
AU - Urbani, Lucio
AU - Morelli, Luca
AU - Schirripa, Marta
AU - Cardellino, Giovanni Gerardo
AU - Fassan, Matteo
AU - Fontanini, Gabriella
AU - de Braud, Filippo
AU - Mazzaferro, Vincenzo
AU - Falcone, Alfredo
AU - Pietrantonio, Filippo
PY - 2018/4/1
Y1 - 2018/4/1
N2 - BACKGROUND: Many factors, including histopathologic parameters, seem to influence the prognosis of patients undergoing resection of colorectal cancer liver metastases (CRCLM), although their relative weight is unclear. Histopathologic growth patterns (HGPs) of CRCLM may affect sensitivity to antiangiogenics. We aimed at evaluating differences in histopathologic parameters of response according to the use of bevacizumab or cetuximab as first-line targeted agents, and at exploring the prognostic and predictive role of HGPs.METHODS: We performed a comprehensive histopathologic characterisation of CRCLM from 159 patients who underwent secondary resection, after receiving triplets FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan) or COI (capecitabine, oxaliplatin, and irinotecan) plus bevacizumab (N = 103) vs cetuximab (N = 56) in five first-line no-profit clinical trials.RESULTS: Both major histopathologic response (tumour regression grade TRG1-2, 32 vs 14%, p = 0.013) and infarct-like necrosis (80 vs 64%, p = 0.035) were significantly higher in the bevacizumab than in the cetuximab group. Achieving major response positively affected relapse-free survival (RFS) (p = 0.012) and overall survival (OS) (p = 0.045), also in multivariable models (RFS, p = 0.008; OS, p = 0.033). In the desmoplastic HGP (N = 28), a higher percentage of major response was reported (57 vs 17% in pushing and 22% in replacement HGP, p
AB - BACKGROUND: Many factors, including histopathologic parameters, seem to influence the prognosis of patients undergoing resection of colorectal cancer liver metastases (CRCLM), although their relative weight is unclear. Histopathologic growth patterns (HGPs) of CRCLM may affect sensitivity to antiangiogenics. We aimed at evaluating differences in histopathologic parameters of response according to the use of bevacizumab or cetuximab as first-line targeted agents, and at exploring the prognostic and predictive role of HGPs.METHODS: We performed a comprehensive histopathologic characterisation of CRCLM from 159 patients who underwent secondary resection, after receiving triplets FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan) or COI (capecitabine, oxaliplatin, and irinotecan) plus bevacizumab (N = 103) vs cetuximab (N = 56) in five first-line no-profit clinical trials.RESULTS: Both major histopathologic response (tumour regression grade TRG1-2, 32 vs 14%, p = 0.013) and infarct-like necrosis (80 vs 64%, p = 0.035) were significantly higher in the bevacizumab than in the cetuximab group. Achieving major response positively affected relapse-free survival (RFS) (p = 0.012) and overall survival (OS) (p = 0.045), also in multivariable models (RFS, p = 0.008; OS, p = 0.033). In the desmoplastic HGP (N = 28), a higher percentage of major response was reported (57 vs 17% in pushing and 22% in replacement HGP, p
U2 - 10.1038/s41416-018-0015-z
DO - 10.1038/s41416-018-0015-z
M3 - Article
SN - 0007-0920
VL - 118
SP - 955
EP - 965
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 7
ER -