Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
Yoshinori Kagawa , Jun Watanabe , Mamoru Uemura , Koji Ando , Akira Inoue , Yujiro Nishizawa , Yusuke Suwa , Keigo Chida , Tsuyoshi Hata , Yuki Sekido , Ryota Nakanishi , Koichi Okuya , Masaaki Miyo , Koji Oba , George Laliotis , Yoshiaki Nakamura , Hideaki Bando , Takayuki Yoshino , Ichiro Takemasa , Eiji Oki
Background: Total neoadjuvant therapy (TNT) has dramatically shifted the treatment paradigm for locally advanced rectal cancer (LARC), prolonging survival with high rates of pathologic complete response (pCR) and introducing opportunities for nonoperative management (NOM). However, there is a need for robust predictive biomarkers of TNT efficacy, local cancer regrowth in NOM, and overall prognosis. Circulating tumor DNA (ctDNA) is a minimally invasive biomarker used to detect molecular residual disease (MRD) and predict recurrence in colorectal cancer after curative resection. The effectiveness of ctDNA MRD status specifically as a predictive biomarker for TNT was evaluated in the Phase II TNT study, ENSEMBLE-1 (jRCTs051200113), conducted in Japan. Methods: Patients with LARC undergoing TNT were enrolled in ENSEMBLE-1. Protocol treatment was defined as short-course radiotherapy (SCRT: 25Gy) followed by six cycles of CAPOX and total mesorectal excision (TME). NOM was allowed if a clinical complete response (cCR) was achieved after TNT. ctDNA was measured by SignateraTM (Natera, Inc.) at the following time points: baseline (pre-treatment), after SCRT, after 4 cycles of CAPOX, before TME, and post operatively at 4w, 12w, 24, 36 and 48w in the GALAXY trial (UMIN000039205). Results: A total of 30 patients were enrolled in the study. After completing TNT, TME and NOM were performed in 20 and 7 patients, respectively. ctDNA was measured in 26 patients (TME: 19 patients, NOM: 7 patients). ctDNA was detected in 100% (25/25) at baseline, 81% (21/26) after SCRT, 31% (8/26) after 4 cycles of CAPOX, and 45% (9/20) after TNT. The attached table shows the results of statistical analyses of the correlation between ctDNA status, clinical response, TME or NOM, and pathologic complete response (pCR). It was found that ctDNA status after SCRT and after 4 cycles of CAPOX was associated with cCR or non cCR (p=0.007 and p=0.007, respectively). Additionally, ctDNA status after TNT was associated with pCR or non pCR (p=0.029). Conclusions: Our study demonstrates that ctDNA-based MRD may predict TNT response in LARC patients. Negative ctDNA during treatment correlates with favorable responses and may be an aid in NOM decision making. Clinical trial information: jRCTs051200113.
After SCRT (N = 26) | After 4 cycles of CAPOX (N = 26) | After TNT (N = 20) | |
---|---|---|---|
Clinical Response cCR or non cCR | P = 0.007 | P = 0.007 | P = 0.157 |
Treatment after TNT NOM or TME | P = 0.101 | P = 0.062 | P = 0.479 |
Pathological response after TME pCR or non pCR | P = 0.095 | P = 0.102 | P = 0.029 |
Fisher's exact test was used to statistically examine the correlation between ctDNA MRD status and the factors at each timing.
cCR: clinical complete response, pCR: pathological complete response, SCRT: short-course radiation therapy, TNT: total neoadjuvant therapy, TME: total mesorectal excision.
Disclaimer
This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org
Abstract Disclosures
2023 ASCO Annual Meeting
First Author: Arash Velayati
2024 ASCO Gastrointestinal Cancers Symposium
First Author: Meng Wang
2023 ASCO Gastrointestinal Cancers Symposium
First Author: Akihisa Matsuda
2024 ASCO Gastrointestinal Cancers Symposium
First Author: Alessandro Audisio