TY - JOUR
T1 - Pathological Evaluation of Resected Colorectal Liver Metastases
T2 - mFOLFOX6 Plus Bevacizumab versus mFOLFOX6 Plus Cetuximab in the Phase II ATOM Trial
AU - Takahashi, Takao
AU - Ishida, Kazuyuki
AU - Emi, Yasunori
AU - Sakamoto, Michiie
AU - Imura, Johji
AU - Aishima, Shinichi
AU - Muro, Kei
AU - Uetake, Hiroyuki
AU - Oki, Eiji
AU - Katayose, Yu
AU - Yoshida, Kazuhiro
AU - Unno, Michiaki
AU - Hyodo, Ichinosuke
AU - Tomita, Naohiro
AU - Sugihara, Kenichi
AU - Maehara, Yoshihiko
N1 - Funding Information:
T.T. has received research funding from Yakult Honsha and lecture fees from Takeda, Sanofi, Taiho, Chugai, and Merck. Y.E. has received personal fees from Chugai. M.S. has received grants from Chugai, Eisai, Olympus, Fujifilm, and CYTLIMIC. K.M. has received grants from MSD, Daiichi Sankyo, Solasia, Astellas Amgen Biopharma, Parexel International, Pfizer, and Merck Serono; personal fees from Takeda, Bayer, Bristol-Myers Squibb, and Eli Lilly; and grants and personal fees from Chugai, Taiho, Ono, and Sanofi. H.U. has received grants from Taiho, Chugai, Takeda, and Yakult. E.O. has received lecture fees from Chugai, Merck, Taiho, Eli Lilly, Bayer Japan, and Takeda. K.Y. has received grants and personal fees from Chugai, Merck Serono, Yakult Honsha, and Nippon Kayaku and grants from Kyowa Kirin, during the conduct of the study, and grants and personal fees from Johnson & Johnson K.K., Taiho, Daiichi Sankyo, Tsumura, Takeda, Asahi Kasei, Sanofi, Eli Lilly Japan K.K., Covidien Japan, Novartis, MSD, and Ono; grants from Abbott Japan, Abbvie, Otsuka, Koninklijke Philips, Toray Medical, Astellas, Biogen Japan, Celgene, Eisai, GlaxoSmithKline K.K., Kaken, KCI, and Meiji Seika; and personal fees from AstraZeneca, Bristol-Myers Squibb Japan, Olympus, Pfizer, Sanwa Kagaku Kenkyusho, SBI, Terumo, Denka, EA, and Teijin. M.U. received grants from Chugai, Yakult Honsha, and Takeda and received personal fees from Merck Serono, Chugai, Yakult Honsha, and Takeda, during the conduct of the study, and grants from Taiho, Novartis, Asahi Kasei, Asteras, Toyama Chem, Pfizer, MSD, Bayer, Sanofi, EA, and Shionogi and personal fees from Taiho, Novatis, Asahi Kasei, Pfizer, Teijin, Eisai, Daiichi Sankyo, Johnson & Johnson, Boston Scientific, Covidien/Medtronic, Nobelpharma, Ono, and Mylan. I.H. has received grants and personal fees from Taiho, Chugai, Daiichi-Sankyo, Yakult-Honsha, Eli Lilly, Takeda, and Ono. N.T. has received grants from Taiho, Chugai, and Sysmex, outside the submitted work. K.S. has received grants and personal fees from Chugai, personal fees from Merck Serono, grants and personal fees from Taiho, and personal fees from Bayer and Takeda. The remaining authors have no conflict of interest to declare.
Funding Information:
This study was supported by Chugai Pharmaceutical, Co., Ltd. The study was conducted by EPS Corporation. The sponsor had no role in the study design; in the collection, analysis, or interpretation of data; in the writing of the report; or in the decision to submit the article for publication.
Publisher Copyright:
© 2022 by the authors.
PY - 2022/9
Y1 - 2022/9
N2 - We compared the preplanned histopathological responses of resected liver metastases from patients who received modified FOLFOX6 plus bevacizumab or modified FOLFOX6 plus cetuximab for liver-limited colorectal metastases in the ATOM trial. Fibrosis and viable tumor cells in tumor regression grade (TRG), infarct-like necrosis in modified TRG (mTRG), and dangerous halo (DH) were assessed. Fifty-five patients (28 and 27 patients in the bevacizumab and cetuximab arms, respectively) were divided into the low (viable tumor cells ≤ 50%) and high (>50%) TRG or mTRG groups. DH was characterized as absent/rare or focal/diffuse. Compared to the bevacizumab arm, the cetuximab arm was more effective, with respect to low TRG (13 vs. 23 patients) and absent/rare DH (14 vs. 19 patients), respectively. Low mTRG was similarly observed in both arms. Low TRG/mTRG and absent/rare DH showed better relapse-free survival (RFS) than high TRG/mTRG and focal/diffuse DH. In the bevacizumab arm, a significant difference in RFS existed between the low and high TRG groups, while in the cetuximab arm, for TRG, mTRG, and DH, the low and absent/rare groups demonstrated significantly longer RFS than the high and focal/diffuse groups, respectively. TRG could estimate RFS in patients who underwent liver metastasectomy after bevacizumab or cetuximab chemotherapy.
AB - We compared the preplanned histopathological responses of resected liver metastases from patients who received modified FOLFOX6 plus bevacizumab or modified FOLFOX6 plus cetuximab for liver-limited colorectal metastases in the ATOM trial. Fibrosis and viable tumor cells in tumor regression grade (TRG), infarct-like necrosis in modified TRG (mTRG), and dangerous halo (DH) were assessed. Fifty-five patients (28 and 27 patients in the bevacizumab and cetuximab arms, respectively) were divided into the low (viable tumor cells ≤ 50%) and high (>50%) TRG or mTRG groups. DH was characterized as absent/rare or focal/diffuse. Compared to the bevacizumab arm, the cetuximab arm was more effective, with respect to low TRG (13 vs. 23 patients) and absent/rare DH (14 vs. 19 patients), respectively. Low mTRG was similarly observed in both arms. Low TRG/mTRG and absent/rare DH showed better relapse-free survival (RFS) than high TRG/mTRG and focal/diffuse DH. In the bevacizumab arm, a significant difference in RFS existed between the low and high TRG groups, while in the cetuximab arm, for TRG, mTRG, and DH, the low and absent/rare groups demonstrated significantly longer RFS than the high and focal/diffuse groups, respectively. TRG could estimate RFS in patients who underwent liver metastasectomy after bevacizumab or cetuximab chemotherapy.
UR - http://www.scopus.com/inward/record.url?scp=85138684213&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85138684213&partnerID=8YFLogxK
U2 - 10.3390/cancers14184392
DO - 10.3390/cancers14184392
M3 - Article
AN - SCOPUS:85138684213
SN - 2072-6694
VL - 14
JO - Cancers
JF - Cancers
IS - 18
M1 - 4392
ER -
