aCGH Analysis of Predictive Biomarkers for Response to Bevacizumab plus Oxaliplatin- or Irinotecan-Based Chemotherapy in Patients with Metastatic Colorectal Cancer

Yoshihiko Fujita, Masataka Taguri, Kentaro Yamazaki, Junji Tsurutani, Kazuko Sakai, Takahiro Tsushima, Michitaka Nagase, Hiroshi Tamagawa, Shinya Ueda, Takao Tamura, Yasushi Tsuji, Kohei Murata, Koichi Taira, Tadamichi Denda, Toshikazu Moriwaki, Sadao Funai, Takako Eguchi Nakajima, Kei Muro, Akihito Tsuji, Motoki Yoshida & 11 others Koichi Suyama, Takuya Kurimoto, Naotoshi Sugimoto, Eishi Baba, Nobuhiko Seki, Mikio Sato, Takaya Shimura, Narikazu Boku, Ichinosuke Hyodo, Takeharu Yamanaka, Kazuto Nishio

研究成果: ジャーナルへの寄稿記事

抄録

Background: The randomized phase III study (WJOG4407G) showed equivalent efficacy between FOLFOX and FOLFIRI in combination with bevacizumab as the first-line treatment for metastatic colorectal cancer (mCRC). We studied whole genome copy number profiles using array-based comparative genomic hybridization (aCGH) analysis of tumor tissue samples obtained in this study. The aim of this study was to identify gene copy number alterations that could aid in selecting either FOLFOX or FOLFIRI in combination with bevacizumab for patients with mCRC. Materials and Methods: DNA was purified from 154 pretreatment formalin-fixed paraffin-embedded tissue samples (75 from the FOLFOX arm and 79 from the FOLFIRI arm) of 395 patients enrolled in the WJOG4407G trial and analyzed by aCGH. Genomic regions greater than 1.2-fold were regarded as copy number gain (CNG). Results: Patient characteristics between the treatment arms were well balanced except for tumor laterality (left side; 64% in FOLFOX arm and 80% in FOLFIRI arm, p =.07). FOLFIRI showed a trend toward better response rate (RR), progression-free survival (PFS) and overall survival (OS) than FOLFOX in the patients with CNG of chromosome 8q24.1 (Fisher's exact test, p =.134 for RR; interaction test, p =.102 for PFS and p =.003 for OS) and 8q24.2 (Fisher's exact test, p =.179 for RR; interaction test, p =.144 for PFS and p =.002 for OS). Conclusion: Chromosome 8q24.1–q24.2 may contain genes that could potentially serve as predictive markers for selecting either FOLFOX or FOLFIRI in combination with bevacizumab for treatment of patients with mCRC. Implications for Practice: Bevacizumab has been used as a standard first-line treatment for patients with metastatic colorectal cancer (mCRC) in combination with either oxaliplatin-based or irinotecan-based chemotherapy. Until now, there has been no predictive marker to choose between the two combination chemotherapies. This array-based comparative genomic hybridization analysis revealed that the difference in therapeutic effect between the two combination chemotherapies is prominent in patients with mCRC with gene copy number gain in chromosome 8p24.1–p24.2. Such patients showed more favorable response and survival when treated with irinotecan-based combination chemotherapy. Overlapping genes commonly found in this region may be predictive biomarkers of the efficacy of the combination chemotherapy with bevacizumab.

元の言語英語
ページ(範囲)327-337
ページ数11
ジャーナルOncologist
24
発行部数3
DOI
出版物ステータス出版済み - 3 1 2019

Fingerprint

irinotecan
oxaliplatin
Comparative Genomic Hybridization
Colorectal Neoplasms
Biomarkers
Drug Therapy
Combination Drug Therapy
Disease-Free Survival
Gene Dosage
Survival
Chromosomes
Overlapping Genes
Bevacizumab
Neoplasm Genes
Therapeutic Uses
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

aCGH Analysis of Predictive Biomarkers for Response to Bevacizumab plus Oxaliplatin- or Irinotecan-Based Chemotherapy in Patients with Metastatic Colorectal Cancer. / Fujita, Yoshihiko; Taguri, Masataka; Yamazaki, Kentaro; Tsurutani, Junji; Sakai, Kazuko; Tsushima, Takahiro; Nagase, Michitaka; Tamagawa, Hiroshi; Ueda, Shinya; Tamura, Takao; Tsuji, Yasushi; Murata, Kohei; Taira, Koichi; Denda, Tadamichi; Moriwaki, Toshikazu; Funai, Sadao; Nakajima, Takako Eguchi; Muro, Kei; Tsuji, Akihito; Yoshida, Motoki; Suyama, Koichi; Kurimoto, Takuya; Sugimoto, Naotoshi; Baba, Eishi; Seki, Nobuhiko; Sato, Mikio; Shimura, Takaya; Boku, Narikazu; Hyodo, Ichinosuke; Yamanaka, Takeharu; Nishio, Kazuto.

:: Oncologist, 巻 24, 番号 3, 01.03.2019, p. 327-337.

研究成果: ジャーナルへの寄稿記事

Fujita, Y, Taguri, M, Yamazaki, K, Tsurutani, J, Sakai, K, Tsushima, T, Nagase, M, Tamagawa, H, Ueda, S, Tamura, T, Tsuji, Y, Murata, K, Taira, K, Denda, T, Moriwaki, T, Funai, S, Nakajima, TE, Muro, K, Tsuji, A, Yoshida, M, Suyama, K, Kurimoto, T, Sugimoto, N, Baba, E, Seki, N, Sato, M, Shimura, T, Boku, N, Hyodo, I, Yamanaka, T & Nishio, K 2019, 'aCGH Analysis of Predictive Biomarkers for Response to Bevacizumab plus Oxaliplatin- or Irinotecan-Based Chemotherapy in Patients with Metastatic Colorectal Cancer' Oncologist, 巻. 24, 番号 3, pp. 327-337. https://doi.org/10.1634/theoncologist.2018-0119
Fujita, Yoshihiko ; Taguri, Masataka ; Yamazaki, Kentaro ; Tsurutani, Junji ; Sakai, Kazuko ; Tsushima, Takahiro ; Nagase, Michitaka ; Tamagawa, Hiroshi ; Ueda, Shinya ; Tamura, Takao ; Tsuji, Yasushi ; Murata, Kohei ; Taira, Koichi ; Denda, Tadamichi ; Moriwaki, Toshikazu ; Funai, Sadao ; Nakajima, Takako Eguchi ; Muro, Kei ; Tsuji, Akihito ; Yoshida, Motoki ; Suyama, Koichi ; Kurimoto, Takuya ; Sugimoto, Naotoshi ; Baba, Eishi ; Seki, Nobuhiko ; Sato, Mikio ; Shimura, Takaya ; Boku, Narikazu ; Hyodo, Ichinosuke ; Yamanaka, Takeharu ; Nishio, Kazuto. / aCGH Analysis of Predictive Biomarkers for Response to Bevacizumab plus Oxaliplatin- or Irinotecan-Based Chemotherapy in Patients with Metastatic Colorectal Cancer. :: Oncologist. 2019 ; 巻 24, 番号 3. pp. 327-337.
@article{2276d9f5fece4fee9be3cc2f3c8ad96c,
title = "aCGH Analysis of Predictive Biomarkers for Response to Bevacizumab plus Oxaliplatin- or Irinotecan-Based Chemotherapy in Patients with Metastatic Colorectal Cancer",
abstract = "Background: The randomized phase III study (WJOG4407G) showed equivalent efficacy between FOLFOX and FOLFIRI in combination with bevacizumab as the first-line treatment for metastatic colorectal cancer (mCRC). We studied whole genome copy number profiles using array-based comparative genomic hybridization (aCGH) analysis of tumor tissue samples obtained in this study. The aim of this study was to identify gene copy number alterations that could aid in selecting either FOLFOX or FOLFIRI in combination with bevacizumab for patients with mCRC. Materials and Methods: DNA was purified from 154 pretreatment formalin-fixed paraffin-embedded tissue samples (75 from the FOLFOX arm and 79 from the FOLFIRI arm) of 395 patients enrolled in the WJOG4407G trial and analyzed by aCGH. Genomic regions greater than 1.2-fold were regarded as copy number gain (CNG). Results: Patient characteristics between the treatment arms were well balanced except for tumor laterality (left side; 64{\%} in FOLFOX arm and 80{\%} in FOLFIRI arm, p =.07). FOLFIRI showed a trend toward better response rate (RR), progression-free survival (PFS) and overall survival (OS) than FOLFOX in the patients with CNG of chromosome 8q24.1 (Fisher's exact test, p =.134 for RR; interaction test, p =.102 for PFS and p =.003 for OS) and 8q24.2 (Fisher's exact test, p =.179 for RR; interaction test, p =.144 for PFS and p =.002 for OS). Conclusion: Chromosome 8q24.1–q24.2 may contain genes that could potentially serve as predictive markers for selecting either FOLFOX or FOLFIRI in combination with bevacizumab for treatment of patients with mCRC. Implications for Practice: Bevacizumab has been used as a standard first-line treatment for patients with metastatic colorectal cancer (mCRC) in combination with either oxaliplatin-based or irinotecan-based chemotherapy. Until now, there has been no predictive marker to choose between the two combination chemotherapies. This array-based comparative genomic hybridization analysis revealed that the difference in therapeutic effect between the two combination chemotherapies is prominent in patients with mCRC with gene copy number gain in chromosome 8p24.1–p24.2. Such patients showed more favorable response and survival when treated with irinotecan-based combination chemotherapy. Overlapping genes commonly found in this region may be predictive biomarkers of the efficacy of the combination chemotherapy with bevacizumab.",
author = "Yoshihiko Fujita and Masataka Taguri and Kentaro Yamazaki and Junji Tsurutani and Kazuko Sakai and Takahiro Tsushima and Michitaka Nagase and Hiroshi Tamagawa and Shinya Ueda and Takao Tamura and Yasushi Tsuji and Kohei Murata and Koichi Taira and Tadamichi Denda and Toshikazu Moriwaki and Sadao Funai and Nakajima, {Takako Eguchi} and Kei Muro and Akihito Tsuji and Motoki Yoshida and Koichi Suyama and Takuya Kurimoto and Naotoshi Sugimoto and Eishi Baba and Nobuhiko Seki and Mikio Sato and Takaya Shimura and Narikazu Boku and Ichinosuke Hyodo and Takeharu Yamanaka and Kazuto Nishio",
year = "2019",
month = "3",
day = "1",
doi = "10.1634/theoncologist.2018-0119",
language = "English",
volume = "24",
pages = "327--337",
journal = "Oncologist",
issn = "1083-7159",
publisher = "AlphaMed Press",
number = "3",

}

TY - JOUR

T1 - aCGH Analysis of Predictive Biomarkers for Response to Bevacizumab plus Oxaliplatin- or Irinotecan-Based Chemotherapy in Patients with Metastatic Colorectal Cancer

AU - Fujita, Yoshihiko

AU - Taguri, Masataka

AU - Yamazaki, Kentaro

AU - Tsurutani, Junji

AU - Sakai, Kazuko

AU - Tsushima, Takahiro

AU - Nagase, Michitaka

AU - Tamagawa, Hiroshi

AU - Ueda, Shinya

AU - Tamura, Takao

AU - Tsuji, Yasushi

AU - Murata, Kohei

AU - Taira, Koichi

AU - Denda, Tadamichi

AU - Moriwaki, Toshikazu

AU - Funai, Sadao

AU - Nakajima, Takako Eguchi

AU - Muro, Kei

AU - Tsuji, Akihito

AU - Yoshida, Motoki

AU - Suyama, Koichi

AU - Kurimoto, Takuya

AU - Sugimoto, Naotoshi

AU - Baba, Eishi

AU - Seki, Nobuhiko

AU - Sato, Mikio

AU - Shimura, Takaya

AU - Boku, Narikazu

AU - Hyodo, Ichinosuke

AU - Yamanaka, Takeharu

AU - Nishio, Kazuto

PY - 2019/3/1

Y1 - 2019/3/1

N2 - Background: The randomized phase III study (WJOG4407G) showed equivalent efficacy between FOLFOX and FOLFIRI in combination with bevacizumab as the first-line treatment for metastatic colorectal cancer (mCRC). We studied whole genome copy number profiles using array-based comparative genomic hybridization (aCGH) analysis of tumor tissue samples obtained in this study. The aim of this study was to identify gene copy number alterations that could aid in selecting either FOLFOX or FOLFIRI in combination with bevacizumab for patients with mCRC. Materials and Methods: DNA was purified from 154 pretreatment formalin-fixed paraffin-embedded tissue samples (75 from the FOLFOX arm and 79 from the FOLFIRI arm) of 395 patients enrolled in the WJOG4407G trial and analyzed by aCGH. Genomic regions greater than 1.2-fold were regarded as copy number gain (CNG). Results: Patient characteristics between the treatment arms were well balanced except for tumor laterality (left side; 64% in FOLFOX arm and 80% in FOLFIRI arm, p =.07). FOLFIRI showed a trend toward better response rate (RR), progression-free survival (PFS) and overall survival (OS) than FOLFOX in the patients with CNG of chromosome 8q24.1 (Fisher's exact test, p =.134 for RR; interaction test, p =.102 for PFS and p =.003 for OS) and 8q24.2 (Fisher's exact test, p =.179 for RR; interaction test, p =.144 for PFS and p =.002 for OS). Conclusion: Chromosome 8q24.1–q24.2 may contain genes that could potentially serve as predictive markers for selecting either FOLFOX or FOLFIRI in combination with bevacizumab for treatment of patients with mCRC. Implications for Practice: Bevacizumab has been used as a standard first-line treatment for patients with metastatic colorectal cancer (mCRC) in combination with either oxaliplatin-based or irinotecan-based chemotherapy. Until now, there has been no predictive marker to choose between the two combination chemotherapies. This array-based comparative genomic hybridization analysis revealed that the difference in therapeutic effect between the two combination chemotherapies is prominent in patients with mCRC with gene copy number gain in chromosome 8p24.1–p24.2. Such patients showed more favorable response and survival when treated with irinotecan-based combination chemotherapy. Overlapping genes commonly found in this region may be predictive biomarkers of the efficacy of the combination chemotherapy with bevacizumab.

AB - Background: The randomized phase III study (WJOG4407G) showed equivalent efficacy between FOLFOX and FOLFIRI in combination with bevacizumab as the first-line treatment for metastatic colorectal cancer (mCRC). We studied whole genome copy number profiles using array-based comparative genomic hybridization (aCGH) analysis of tumor tissue samples obtained in this study. The aim of this study was to identify gene copy number alterations that could aid in selecting either FOLFOX or FOLFIRI in combination with bevacizumab for patients with mCRC. Materials and Methods: DNA was purified from 154 pretreatment formalin-fixed paraffin-embedded tissue samples (75 from the FOLFOX arm and 79 from the FOLFIRI arm) of 395 patients enrolled in the WJOG4407G trial and analyzed by aCGH. Genomic regions greater than 1.2-fold were regarded as copy number gain (CNG). Results: Patient characteristics between the treatment arms were well balanced except for tumor laterality (left side; 64% in FOLFOX arm and 80% in FOLFIRI arm, p =.07). FOLFIRI showed a trend toward better response rate (RR), progression-free survival (PFS) and overall survival (OS) than FOLFOX in the patients with CNG of chromosome 8q24.1 (Fisher's exact test, p =.134 for RR; interaction test, p =.102 for PFS and p =.003 for OS) and 8q24.2 (Fisher's exact test, p =.179 for RR; interaction test, p =.144 for PFS and p =.002 for OS). Conclusion: Chromosome 8q24.1–q24.2 may contain genes that could potentially serve as predictive markers for selecting either FOLFOX or FOLFIRI in combination with bevacizumab for treatment of patients with mCRC. Implications for Practice: Bevacizumab has been used as a standard first-line treatment for patients with metastatic colorectal cancer (mCRC) in combination with either oxaliplatin-based or irinotecan-based chemotherapy. Until now, there has been no predictive marker to choose between the two combination chemotherapies. This array-based comparative genomic hybridization analysis revealed that the difference in therapeutic effect between the two combination chemotherapies is prominent in patients with mCRC with gene copy number gain in chromosome 8p24.1–p24.2. Such patients showed more favorable response and survival when treated with irinotecan-based combination chemotherapy. Overlapping genes commonly found in this region may be predictive biomarkers of the efficacy of the combination chemotherapy with bevacizumab.

UR - http://www.scopus.com/inward/record.url?scp=85056622565&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056622565&partnerID=8YFLogxK

U2 - 10.1634/theoncologist.2018-0119

DO - 10.1634/theoncologist.2018-0119

M3 - Article

VL - 24

SP - 327

EP - 337

JO - Oncologist

JF - Oncologist

SN - 1083-7159

IS - 3

ER -