ctDNA-MRD Monitoring After Resection in Gastric Cancer

Official title

Personalized ctDNA-MRD in Recurrence Monitoring for Gastric Cancer Patients Undergoing Perioperative Treatment Combined With Curative Surgical Resection

Overview

Numerous studies have demonstrated that circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) detection has significant clinical value in postoperative recurrence monitoring, adjuvant treatment decision-making, and early intervention. Our previous retrospective study, using fixed ctDNA-MRD, confirmed that postoperative ctDNA-MRD can predict recurrence risk. Therefore, we plan to conduct a further prospective, multicenter, observational study, utilizing a combination of personalized ctDNA-MRD and fixed MRD panels, to dynamically monitor gastric cancer patients who have received neoadjuvant therapy followed by curative resection. The study will systematically analyze the correlation between ctDNA-MRD status and tumor recurrence and metastasis, assess its sensitivity and specificity in recurrence prediction, and compare its early warning advantage over traditional imaging techniques in predicting recurrence.

Detailed description

China has the highest incidence and mortality rates of gastric cancer in the world, with approximately 70% of patients diagnosed at an advanced stage. Perioperative treatment combined with surgery is the recommended treatment approach for advanced gastric cancer. However, a considerable proportion of patients still experience recurrence and metastasis after surgery. Imaging studies are the standard method for monitoring postoperative recurrence and metastasis, but they can only detect recurrence once the metastatic lesions have grown to a certain size. In contrast, ctDNA-MRD testing can detect residual tumor molecular signals in the blood, providing early signs of recurrence and allowing for timely intervention while the tumor is still in its "incipient stage." Previous clinical data have shown that MRD testing can identify recurrent and metastatic patients months earlier than traditional imaging methods, with the median lead time varying by cancer type: 9.5 months for breast cancer, 8.7 months for colon cancer, 5.2 months for lung cancer, and 2.8 months for bladder cancer.

Therefore, we plan to conduct a further prospective, multicenter, observational study, utilizing a combination of personalized ctDNA-MRD and fixed MRD panels, to dynamically monitor gastric cancer patients who have received neoadjuvant therapy followed by curative resection. The study will systematically analyze the correlation between ctDNA-MRD status and tumor recurrence and metastasis, assess its sensitivity and specificity in recurrence prediction, and compare its early warning advantage over traditional imaging techniques in predicting recurrence. In addition, this project will focus on establishing and improving a dynamic MRD monitoring system, laying the foundation for future interventional clinical research.

Primary outcome measures

• Predictive Accuracy of Personalized ctDNA-MRD for Postoperative Recurrence [Time frame: From the time of surgical resection to the point of resurrence within 2 years]

Secondary outcome measures (1)

• Lead time of personalized ctDNA-MRD compared to radiologic surveillance in postoperative recurrence prediction [Time frame: From ctDNA-MRD positive to the point of CT imaging showing recurrence]

Eligibility criteria

Inclusion criteria

• Patients have received neoadjuvant therapy and radical resection (R0).
• Pathologically confirmed ypTNM stage II-III gastric or gastroesophageal junction adenocarcinoma.
• Patients must be able to provide sufficient fresh tissue/biopsies or minimum 5-10 FFPE sections for NGS-WES analysis.
• Patients must be able to follow the study visit schedule and be willing to cooperate with the study by providing blood samples at the indicated time point.

Exclusion criteria

• Patients who could not receive enhanced CT, gastroscopy and other routine review after surgery.
• Patients who could not perform WES or ctDNA-MRD detection for various reasons after surgery.
• Other cases considered unsuitable for inclusion by researchers.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Cohort

Study locations

China · 1 center

• Peking University Cancer Hospital & Institute — Beijing

Publications

• Xia C, Dong X, Li H, Cao M, Sun D, He S, Yang F, Yan X, Zhang S, Li N, Chen W. Cancer statistics in China and United States, 2022: profiles, trends, and determinants. Chin Med J (Engl). 2022 Feb 9;135(5):584-590. doi: 10.1097/CM9.0000000000002108. PMID 35143424
• Tarazona N, Gimeno-Valiente F, Gambardella V, Zuniga S, Rentero-Garrido P, Huerta M, Rosello S, Martinez-Ciarpaglini C, Carbonell-Asins JA, Carrasco F, Ferrer-Martinez A, Bruixola G, Fleitas T, Martin J, Tebar-Martinez R, Moro D, Castillo J, Espi A, Roda D, Cervantes A. Targeted next-generation sequencing of circulating-tumor DNA for tracking minimal residual disease in localized colon cancer. Ann PMID 31562764
• Christensen E, Birkenkamp-Demtroder K, Sethi H, Shchegrova S, Salari R, Nordentoft I, Wu HT, Knudsen M, Lamy P, Lindskrog SV, Taber A, Balcioglu M, Vang S, Assaf Z, Sharma S, Tin AS, Srinivasan R, Hafez D, Reinert T, Navarro S, Olson A, Ram R, Dashner S, Rabinowitz M, Billings P, Sigurjonsson S, Andersen CL, Swenerton R, Aleshin A, Zimmermann B, Agerbaek M, Lin CJ, Jensen JB, Dyrskjot L. Early Det PMID 31059311
• Chaudhuri AA, Chabon JJ, Lovejoy AF, Newman AM, Stehr H, Azad TD, Khodadoust MS, Esfahani MS, Liu CL, Zhou L, Scherer F, Kurtz DM, Say C, Carter JN, Merriott DJ, Dudley JC, Binkley MS, Modlin L, Padda SK, Gensheimer MF, West RB, Shrager JB, Neal JW, Wakelee HA, Loo BW Jr, Alizadeh AA, Diehn M. Early Detection of Molecular Residual Disease in Localized Lung Cancer by Circulating Tumor DNA Profiling PMID 28899864
• Reinert T, Henriksen TV, Christensen E, Sharma S, Salari R, Sethi H, Knudsen M, Nordentoft I, Wu HT, Tin AS, Heilskov Rasmussen M, Vang S, Shchegrova S, Frydendahl Boll Johansen A, Srinivasan R, Assaf Z, Balcioglu M, Olson A, Dashner S, Hafez D, Navarro S, Goel S, Rabinowitz M, Billings P, Sigurjonsson S, Dyrskjot L, Swenerton R, Aleshin A, Laurberg S, Husted Madsen A, Kannerup AS, Stribolt K, Pal PMID 31070691
• Coombes RC, Page K, Salari R, Hastings RK, Armstrong A, Ahmed S, Ali S, Cleator S, Kenny L, Stebbing J, Rutherford M, Sethi H, Boydell A, Swenerton R, Fernandez-Garcia D, Gleason KLT, Goddard K, Guttery DS, Assaf ZJ, Wu HT, Natarajan P, Moore DA, Primrose L, Dashner S, Tin AS, Balcioglu M, Srinivasan R, Shchegrova SV, Olson A, Hafez D, Billings P, Aleshin A, Rehman F, Toghill BJ, Hills A, Louie MC PMID 30992300

Identifiers

NCT: NCT06893133 · 2025KT40

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗