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Utility of circulating tumour DNA for prognosis and prediction of therapeutic effect in locally recurrent rectal cancer: study protocol for a multi-institutional, prospective observational study (JCOG1801A1, CAP-LR study)

INTRODUCTION: In locally recurrent rectal cancer (LRRC), surgery is a standard treatment for resectable disease. However, short-term and long-term outcomes are unsatisfactory due to the invasive nature of surgical procedures and the high proportion of local recurrence. Consequently, the identificati...

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Autores principales: Hashimoto, Tadayoshi, Tsukada, Yuichiro, Ito, Masaaki, Kanato, Keisuke, Mizusawa, Junki, Fukuda, Haruhiko, Tsukamoto, Shunsuke, Takashima, Atsuo, Kanemitsu, Yukihide
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10432635/
https://www.ncbi.nlm.nih.gov/pubmed/37586869
http://dx.doi.org/10.1136/bmjopen-2023-073217
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author Hashimoto, Tadayoshi
Tsukada, Yuichiro
Ito, Masaaki
Kanato, Keisuke
Mizusawa, Junki
Fukuda, Haruhiko
Tsukamoto, Shunsuke
Takashima, Atsuo
Kanemitsu, Yukihide
author_facet Hashimoto, Tadayoshi
Tsukada, Yuichiro
Ito, Masaaki
Kanato, Keisuke
Mizusawa, Junki
Fukuda, Haruhiko
Tsukamoto, Shunsuke
Takashima, Atsuo
Kanemitsu, Yukihide
author_sort Hashimoto, Tadayoshi
collection PubMed
description INTRODUCTION: In locally recurrent rectal cancer (LRRC), surgery is a standard treatment for resectable disease. However, short-term and long-term outcomes are unsatisfactory due to the invasive nature of surgical procedures and the high proportion of local recurrence. Consequently, the identification of reliable prognostic and predictive biomarkers to guide treatment decisions may improve outcomes. The presence of circulating tumour DNA (ctDNA) in plasma after surgery may signify the presence of minimal residual disease (MRD) in various cancers. Therefore, we have launched a multi-institutional prospective observational study of ctDNA for MRD detection in conjunction with JCOG1801, a randomised, controlled phase III trial evaluating the efficacy of preoperative chemoradiotherapy (pre-CRT) compared with up-front surgery for LRRC (jRCTs031190076, NCT04288999). METHODS AND ANALYSIS: JCOG1801A1 is the first correlative study that assesses ctDNA in LRRC patients enrolled in JCOG1801. Patients randomised to up-front surgery will provide whole blood samples at three time points (prior to surgery, after surgery and after postoperative chemotherapy); those to pre-CRT will provide at five time points (prior to pre-CRT, after pre-CRT, prior to surgery, after surgery and after postoperative chemotherapy). Cell-free DNA will be extracted from plasma and analysed by Guardant Reveal, a tumour tissue–agnostic assay that assesses both genomic alterations and methylation patterns to determine the presence or absence of ctDNA. We will compare the prognosis and treatment response of patients according to their ctDNA status after surgery and at other time points. ETHICS AND DISSEMINATION: The study protocol received approval from the Institutional Review Board of National Cancer Center Hospital East on behalf of the participating institutions in February 2023. The study is conducted in accordance with the precepts established in the Declaration of Helsinki and Ethical Guidelines for Medical and Biological Research Involving Human Subjects. Written informed consent will be obtained from all eligible patients prior to registration.
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spelling pubmed-104326352023-08-18 Utility of circulating tumour DNA for prognosis and prediction of therapeutic effect in locally recurrent rectal cancer: study protocol for a multi-institutional, prospective observational study (JCOG1801A1, CAP-LR study) Hashimoto, Tadayoshi Tsukada, Yuichiro Ito, Masaaki Kanato, Keisuke Mizusawa, Junki Fukuda, Haruhiko Tsukamoto, Shunsuke Takashima, Atsuo Kanemitsu, Yukihide BMJ Open Oncology INTRODUCTION: In locally recurrent rectal cancer (LRRC), surgery is a standard treatment for resectable disease. However, short-term and long-term outcomes are unsatisfactory due to the invasive nature of surgical procedures and the high proportion of local recurrence. Consequently, the identification of reliable prognostic and predictive biomarkers to guide treatment decisions may improve outcomes. The presence of circulating tumour DNA (ctDNA) in plasma after surgery may signify the presence of minimal residual disease (MRD) in various cancers. Therefore, we have launched a multi-institutional prospective observational study of ctDNA for MRD detection in conjunction with JCOG1801, a randomised, controlled phase III trial evaluating the efficacy of preoperative chemoradiotherapy (pre-CRT) compared with up-front surgery for LRRC (jRCTs031190076, NCT04288999). METHODS AND ANALYSIS: JCOG1801A1 is the first correlative study that assesses ctDNA in LRRC patients enrolled in JCOG1801. Patients randomised to up-front surgery will provide whole blood samples at three time points (prior to surgery, after surgery and after postoperative chemotherapy); those to pre-CRT will provide at five time points (prior to pre-CRT, after pre-CRT, prior to surgery, after surgery and after postoperative chemotherapy). Cell-free DNA will be extracted from plasma and analysed by Guardant Reveal, a tumour tissue–agnostic assay that assesses both genomic alterations and methylation patterns to determine the presence or absence of ctDNA. We will compare the prognosis and treatment response of patients according to their ctDNA status after surgery and at other time points. ETHICS AND DISSEMINATION: The study protocol received approval from the Institutional Review Board of National Cancer Center Hospital East on behalf of the participating institutions in February 2023. The study is conducted in accordance with the precepts established in the Declaration of Helsinki and Ethical Guidelines for Medical and Biological Research Involving Human Subjects. Written informed consent will be obtained from all eligible patients prior to registration. BMJ Publishing Group 2023-08-16 /pmc/articles/PMC10432635/ /pubmed/37586869 http://dx.doi.org/10.1136/bmjopen-2023-073217 Text en © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Oncology
Hashimoto, Tadayoshi
Tsukada, Yuichiro
Ito, Masaaki
Kanato, Keisuke
Mizusawa, Junki
Fukuda, Haruhiko
Tsukamoto, Shunsuke
Takashima, Atsuo
Kanemitsu, Yukihide
Utility of circulating tumour DNA for prognosis and prediction of therapeutic effect in locally recurrent rectal cancer: study protocol for a multi-institutional, prospective observational study (JCOG1801A1, CAP-LR study)
title Utility of circulating tumour DNA for prognosis and prediction of therapeutic effect in locally recurrent rectal cancer: study protocol for a multi-institutional, prospective observational study (JCOG1801A1, CAP-LR study)
title_full Utility of circulating tumour DNA for prognosis and prediction of therapeutic effect in locally recurrent rectal cancer: study protocol for a multi-institutional, prospective observational study (JCOG1801A1, CAP-LR study)
title_fullStr Utility of circulating tumour DNA for prognosis and prediction of therapeutic effect in locally recurrent rectal cancer: study protocol for a multi-institutional, prospective observational study (JCOG1801A1, CAP-LR study)
title_full_unstemmed Utility of circulating tumour DNA for prognosis and prediction of therapeutic effect in locally recurrent rectal cancer: study protocol for a multi-institutional, prospective observational study (JCOG1801A1, CAP-LR study)
title_short Utility of circulating tumour DNA for prognosis and prediction of therapeutic effect in locally recurrent rectal cancer: study protocol for a multi-institutional, prospective observational study (JCOG1801A1, CAP-LR study)
title_sort utility of circulating tumour dna for prognosis and prediction of therapeutic effect in locally recurrent rectal cancer: study protocol for a multi-institutional, prospective observational study (jcog1801a1, cap-lr study)
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10432635/
https://www.ncbi.nlm.nih.gov/pubmed/37586869
http://dx.doi.org/10.1136/bmjopen-2023-073217
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