Differential histopathologic parameters in colorectal cancer liver metastases resected after triplets plus bevacizumab or cetuximab: a pooled analysis of five ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-04

AUTHORS

Chiara Cremolini, Massimo Milione, Federica Marmorino, Federica Morano, Gemma Zucchelli, Alessia Mennitto, Michele Prisciandaro, Sara Lonardi, Alessio Pellegrinelli, Daniele Rossini, Francesca Bergamo, Giuseppe Aprile, Lucio Urbani, Luca Morelli, Marta Schirripa, Giovanni Gerardo Cardellino, Matteo Fassan, Gabriella Fontanini, Filippo de Braud, Vincenzo Mazzaferro, Alfredo Falcone, Filippo Pietrantonio

ABSTRACT

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 < 0.001) and an unsignificant advantage from cetuximab vs bevacizumab was evident in RFS (p = 0.116). In the pushing HGP (N = 66), a significant benefit from bevacizumab vs cetuximab (p = 0.017) was observed. No difference was described in the replacement HGP (N = 65, p = 0.615). CONCLUSIONS: The histopathologic response is the only independent determinant of survival in patients resected after triplets plus a biologic. When associated with triplet chemotherapy, bevacizumab induces a higher histopathologic response rate than cetuximab. The assessment of HGPs should be further explored as a predictor of benefit from available targeted agents. More... »

PAGES

955-965

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41416-018-0015-z

DOI

http://dx.doi.org/10.1038/s41416-018-0015-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1101488401

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29531324


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