Prediction of Postoperative Treatment Efficacy and Recurrence Risk of High-risk GIST Based on Liquid Biopsy MRD

Официальное название

Prediction of Postoperative Treatment Efficacy and Recurrence Risk of High-risk GIST Based on Minimal Residual Disease Detected by Liquid Biopsy

Обзор

So far, MRD assessment by liquid biopsy (ctDNA) has not been used to predict postoperative treatment efficacy and recurrence risk of GIST patients because of special disease characteristics and technological limitations. Therefore, we conducted this prospective multi-center, single-arm observational study to collect 45 operable patients with locally advanced, suspected high-risk GIST. NGS genetic testing platform is used to detect tumour tissues and peripheral ctDNA will also be dectected. we try to explore the correlation between PFS/OS and MRD in high-risk GIST patients by analyzing the relationship between dynamic changes in ctDNA mutation spectrum and postoperative adjuvant therapy efficacy, and to evaluate MRD-based genomic characteristics to guide further treatment.

Подробное описание

Assessing MRD (Minimal Residual Disease) and predicting the postoperative adjuvant treatment efficacy and recurrence risk of tumor patients based on ctDNA (circulating tumor DNA) detected by liquid biopsy have been exploratorily studied and applied in many types of cancers. However, as for GISTs (gastrointestinal stromal tumors), the most common mesenchymal neoplasm of the gastrointestinal tract, they have less peripheral ctDNA fragments compared with those tumors of hematological or epithelial origins. Since there are also some limitations of previous detection technology and detection depth, prospective study for prediction of postoperative treatment efficacy and recurrence risk of high-risk GIST is lacking.

In this study, a prospective multi-center, single-arm observational study is conducted to collect operable patients with locally advanced GIST. According to results of preoperative imaging examinations or pathological biopsy, 45 high-risk GIST patients will be screened and enrolled. Next-Generation Sequencing (NGS) genetic testing platform (Burning Rock Oncoscreen Plus TM) is used to detect the baseline tumour tissues (detection depth 1000X) of these patients. And peripheral ctDNA (detection depth 30000X) of multiple pre/postoperative time points will be detected. The genetic profile and clinical information of each patient will be collected. Combining all the information, bioinformatics analysis will be carried out on the gene detection results of these patients at each time point, and the correlation between the postoperative recurrence time and the ctDNA positive rate/postoperative clearance rate of patients will be compared. The characteristics changes and dynamic changes of tumor release degree will also be analyzed. To explore the correlation between PFS/OS and MRD in high-risk GIST patients, we plan to analyze the relationship between dynamic changes in ctDNA mutation spectrum and postoperative adjuvant therapy efficacy, and to evaluate MRD-based genomic characteristics to guide further treatment.

Вмешательства

• Диагностический тест liquid biopsy
  A test that enables the diagnosis or analysis of tumors using only a blood or fluid sample rather than a solid tissue biopsy.

Первичные конечные точки

• recurrence [Срок оценки: 3 to 5 years]

Критерии участия

Критерии включения

• Patients aged between 18 and 80
• Patients suspected for high-risk GIST by preoperative imaging examinations or diagnosed with high-risk GIST by pathological biopsy, who have not received preoperative neoadjuvant treatment
• Patients must have not received any treatment including radiotherapy, chemotherapy or surgery
• The function of other organs including liver and kidneys is good enough so that the patients could tolerate targeted therapy and surgery
• Postoperative pathology conformed the diagnosis of high-risk GIST
• Patients and their families could understand the protocol of this study and voluntarily agree to participate in. Signed informed consents are required

Критерии исключения

• Previous medical history of malignant tumors or synchronous other malignancies
• Emergent surgery because of bowel obstruction, perforation or bleeding
• Pregnant or lactant women
• Medical history of severe mental illness
• Patients with contraindication for targeted therapy and surgery
• Non-R0 resection
• Postoperative pathology conformed the diagnosis of non-high-risk GIST
• Patients with distant metastasis
• Other situations in which researchers consider that the patient is unsuitable for this study

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Только случаи

Центры проведения

Китай · 1 центр

• Peking University People'S Hospital — Пекин

Публикации

• Connolly EM, Gaffney E, Reynolds JV. Gastrointestinal stromal tumours. Br J Surg. 2003 Oct;90(10):1178-86. doi: 10.1002/bjs.4352. PMID 14515284
• Tran T, Davila JA, El-Serag HB. The epidemiology of malignant gastrointestinal stromal tumors: an analysis of 1,458 cases from 1992 to 2000. Am J Gastroenterol. 2005 Jan;100(1):162-8. doi: 10.1111/j.1572-0241.2005.40709.x. PMID 15654796
• Graadt van Roggen JF, van Velthuysen ML, Hogendoorn PC. The histopathological differential diagnosis of gastrointestinal stromal tumours. J Clin Pathol. 2001 Feb;54(2):96-102. doi: 10.1136/jcp.54.2.96. PMID 11215292
• Chan JK. Mesenchymal tumors of the gastrointestinal tract: a paradise for acronyms (STUMP, GIST, GANT, and now GIPACT), implication of c-kit in genesis, and yet another of the many emerging roles of the interstitial cell of Cajal in the pathogenesis of gastrointestinal diseases? Adv Anat Pathol. 1999 Jan;6(1):19-40. doi: 10.1097/00125480-199901000-00003. PMID 10197236
• Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, Kawano K, Hanada M, Kurata A, Takeda M, Muhammad Tunio G, Matsuzawa Y, Kanakura Y, Shinomura Y, Kitamura Y. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 1998 Jan 23;279(5350):577-80. doi: 10.1126/science.279.5350.577. PMID 9438854
• Hirota S, Ohashi A, Nishida T, Isozaki K, Kinoshita K, Shinomura Y, Kitamura Y. Gain-of-function mutations of platelet-derived growth factor receptor alpha gene in gastrointestinal stromal tumors. Gastroenterology. 2003 Sep;125(3):660-7. doi: 10.1016/s0016-5085(03)01046-1. PMID 12949711
• Heinrich MC, Corless CL, Duensing A, McGreevey L, Chen CJ, Joseph N, Singer S, Griffith DJ, Haley A, Town A, Demetri GD, Fletcher CD, Fletcher JA. PDGFRA activating mutations in gastrointestinal stromal tumors. Science. 2003 Jan 31;299(5607):708-10. doi: 10.1126/science.1079666. Epub 2003 Jan 9. PMID 12522257
• Li J, Shen L. The current status of and prospects in research regarding gastrointestinal stromal tumors in China. Cancer. 2020 May 1;126 Suppl 9:2048-2053. doi: 10.1002/cncr.32684. PMID 32293728

Идентификаторы

NCT: NCT05408897 · WCJZL202103

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗