Survival benefit of adjuvant chemotherapy based on molecular residual disease detection in resected colorectal liver metastases: Subgroup analysis from CIRCULATE-Japan GALAXY

K Kataoka; K Mori; Y Nakamura; J Watanabe; N Akazawa; K Hirata; M Yokota; K Kato; M Kotaka; K Yamazaki; Y Kagawa; S Mishima; K Ando; M Miyo; H Yukami; G Laliotis; S Sharma; C C Palsuledesai; M Rabinowitz; A Jurdi; M C Liu; A Aleshin; D Kotani; H Bando; H Taniguchi; I Takemasa; T Kato; T Yoshino; E Oki

doi:10.1016/j.annonc.2024.08.2240

Survival benefit of adjuvant chemotherapy based on molecular residual disease detection in resected colorectal liver metastases: Subgroup analysis from CIRCULATE-Japan GALAXY

Ann Oncol. 2024 Aug 21:S0923-7534(24)03763-3. doi: 10.1016/j.annonc.2024.08.2240. Online ahead of print.

Authors

K Kataoka¹, K Mori², Y Nakamura³, J Watanabe⁴, N Akazawa⁵, K Hirata⁶, M Yokota⁷, K Kato⁸, M Kotaka⁹, K Yamazaki¹⁰, Y Kagawa¹¹, S Mishima¹², K Ando¹³, M Miyo¹⁴, H Yukami¹⁵, G Laliotis¹⁶, S Sharma¹⁶, C C Palsuledesai¹⁶, M Rabinowitz¹⁶, A Jurdi¹⁶, M C Liu¹⁶, A Aleshin¹⁶, D Kotani¹², H Bando¹², H Taniguchi¹⁷, I Takemasa¹⁴, T Kato¹⁸, T Yoshino¹⁹, E Oki²⁰

Affiliations

¹ Division of Lower GI Surgery, Department of Gastroenterological Surgery, Hyogo Medical University, Nishinomiya, Japan.
² Department of Biostatistics, Clinical Research Center, Shizuoka Cancer Center, Shunto, Japan.
³ Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan; Translational Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan; International Research Promotion Office, National Cancer Center Hospital East, Kashiwa, Japan.
⁴ Department of Colorectal Surgery, Kansai Medical University, Hirakata, Japan; Department of Surgery, Gastroenterological Center, Yokohama City University Medical Center, Yokohama.
⁵ Department of Gastroenterological Surgery, Sendai City Medical Center Sendai Open Hospital, Sendai, Japan.
⁶ Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
⁷ Department of General Surgery, Kurashiki Central Hospital, Kurashiki, Japan.
⁸ Department of Surgery, Teine-Keijinkai Hospital, Sapporo, Japan.
⁹ Gastrointestinal Cancer Center, Sano Hospital, Kobe, Japan.
¹⁰ Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Sunto-gun, Japan.
¹¹ Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan; Department of Gastroenterological Surgery, Osaka General Medical Center, Osaka, Japan.
¹² Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
¹³ Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
¹⁴ Department of Surgery, Surgical Oncology and Science, Sapporo Medical University, Sapporo, Japan.
¹⁵ Cancer Chemotherapy Center, Osaka Medical and Pharmaceutical University, Takatsuki, Japan.
¹⁶ Natera, Inc., Austin, Texas, USA.
¹⁷ Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
¹⁸ Department of Surgery, NHO Osaka National Hospital, Osaka, Japan.
¹⁹ Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan; Department of Gastroenterological surgery/Pediatric surgery, Graduate School of Medicine, Gifu University, Gifu, Japan; Kindai University Faculty of Medicine, Higashiosaka City, Japan.
²⁰ Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: oki.eiji.857@m.kyushu-u.ac.jp.

PMID: 39293512
DOI: 10.1016/j.annonc.2024.08.2240

Abstract

Background: The prognostic role of circulating-tumor DNA (ctDNA)-based molecular residual disease (MRD) detection and its utility for postsurgical risk-stratification has been reported in colorectal cancer. In this study, we explored the use of ctDNA-based MRD detection in patients with colorectal liver metastases (CLM), for whom the survival benefit of adjuvant chemotherapy (ACT) after surgical resection remains unclear.

Methods: Patients with CLM without extrahepatic disease from GALAXY study (UMIN000039205) were included. The disease-free survival (DFS) benefit of ACT was evaluated in MRD-positive and -negative groups after adjusting for age, gender, number and size of liver metastases, RAS status, and previous history of oxaliplatin for primary cancer. ctDNA was detected using a personalized, tumor-informed 16-plex mPCR-NGS assay. ctDNA-based MRD status was evaluated 2 to 10 weeks after curative surgery, before the start of ACT.

Results: Among 6,061 patients registered in GALAXY, 190 surgically resected CLM patients without any preoperative chemotherapy were included with a median follow-up of 24 (1-48) months. ctDNA positivity in the MRD window was 32.1% (61/190). ACT was administered to 25.1% (48/190) of patients. In the MRD-positive group, 24-month DFS was higher for patients treated with ACT (33.3% vs. not reached, adjusted HR: 0.07, P <0.0001); whereas no benefit of ACT was seen in the MRD-negative group (24-month DFS: 72.3% vs. 62.2%, adjusted HR: 0.68, P =0.371). Multivariate analysis showed that the size of liver metastases (HR: 3.94, P =0.031) was prognostic of DFS in the MRD-positive group. However, in the MRD-negative group, none of the clinicopathological factors were prognostic of DFS.

Conclusions: Our data suggest that ACT may offer notable clinical benefits in MRD-positive patients with CLM. MRD status-based risk-stratification could be potentially incorporated in future clinical trials for CLM.

Keywords: Colorectal liver metastases; adjuvant chemotherapy; circulating tumor DNA; disease-free survival; prognostic biomarker.