ctDNA Monitoring to Predict the Efficacy of TNT for Rectal Cancer

Официальное название

ctDNA Monitoring to Predict the Efficacy of Total Neoadjuvant Therapy for Rectal Cancer

Обзор

This is a prospective observational study with three primary objectives: Objective 1: Evaluate the detection rate and changes in circulating tumor DNA (ctDNA) levels in blood samples from colorectal cancer patients before, during, and after total neoadjuvant therapy (TNT). Determine the detection rate and change of CtDNA in blood samples of cancer patients before, during, and after TNT then assess changes in ctDNA expression within the study population during treatment. * Determine the ctDNA positivity rate before treatment. * Determine the ctDNA positivity rate during TNT. * Determine the ctDNA positivity rate after TNT and assess ctDNA level changes during treatment. Objective 2: Investigate the relationship between ctDNA expression and MRI/CT scan imaging with the pathological complete response (pCR) to neoadjuvant therapy : * Correlation between ctDNA detection and pCR/TRG/NAR score. Calculate the Positive Prediction Value - PPV, Negative Prediction Value - NPV of ctDNA, * Correlation between MRI/CT scan imaging and pCR. Calculate the PPV and NPV of MRI/CT scan * Combination of ctDNA detection and MRI/CT scan imaging to predict pCR. Calculate the PPV and NPV of the combined markers. Objective 3: Evaluate the relationship between post-TNT ctDNA expression and disease-free survival in colorectal cancer patients.

Подробное описание

This is a prospective observational study conducted at the Medical Genetics Institute (MGI), in collaboration with 3 hospitals (175 Military Hospital, Nguyen Tri Phuong Hospital, and 108 Military Central Hospital). Participants must meet all inclusion criteria and no exclusion criteria (detailed in the eligibility section).

Sample Collection

* 10 mL of peripheral blood (Streck tubes) is collected for ctDNA analysis at 3 time points: pre-TNT (at diagnosis), middle of treatment (after chemoradiotherapy or after chemotherapy), and post-TNT (before surgery). * 6-8 slides (6um thickness/slide) of FFPE biopsy tumor samples before treatment * 6-8 slides (6um thickness/slide) of FFPE tumor samples collected after surgery. This sample is used to compare the mutational profiles with the corresponding biopsy samples.

Clinical results for collection

* Age, sex, medical history * Number, size, and stage (TNM) of tumor * MRI and/or CT scan images and reports at pre-treatment, mid-treatment, and end-treatment (before surgery) * Histopathological evaluation of biopsy and surgery tissues, and conclusion of pathological response

* TNM classification, pCR conclusion * TRG conclusion * Disease-free survival follow-up for 2 years

Первичные конечные точки

• To investigate the detection rate and change of ctDNA in blood samples of rectal cancer patients during total neoadjuvant therapy [Срок оценки: 12 months]
• To investigate the relationship between ctDNA expression and MRI/CT scan imaging with pCR response in total neoadjuvant therapy (TNT) [Срок оценки: 6 months]
• Evaluate the relationship between post-TNT ctDNA expression and disease-free survival in colorectal cancer patients in 2 years [Срок оценки: 24 months]

Критерии участия

Критерии включения

• 18 years and older, both genders
• Patients are diagnosed with stage II-III rectal cancer and indicated for total neoadjuvant therapy
• Biopsy FFPE sample is available at the time of diagnosis
• Patients consented to participate in the study

Критерии исключения

• Stage I rectal cancer, recurrent or metastatic cancer
• Other cancer metastasis to the rectum
• Patients are indicated for chemoradiation therapy only
• Have been or are being treated for cancer
• Patients do not agree to participate in the studies.

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

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Вьетнам · 1 центр

• Medical Genetics Institute — Ho Chi Minh City

Публикации

• Kim MJ, Lee DW, Kang HC, Park JW, Ryoo SB, Han SW, Kim KS, Chie EK, Oh JH, Jeong WK, Kim BH, Nam EM, Jeong SY. Total neoadjuvant therapy with short-course radiotherapy Versus long-course neoadjuvant chemoradiotherapy in Locally Advanced Rectal cancer, Korean trial (TV-LARK trial): study protocol of a multicentre randomized controlled trial. BMC Cancer. 2023 Aug 8;23(1):734. doi: 10.1186/s12885-023 PMID 37553666
• Johnson GGRJ, Park J, Helewa RM, Goldenberg BA, Nashed M, Hyun E. Total neoadjuvant therapy for rectal cancer: a guide for surgeons. Can J Surg. 2023 Apr 21;66(2):E196-E201. doi: 10.1503/cjs.005822. Print 2023 Mar-Apr. PMID 37085291
• Lopez-Campos F, Martin-Martin M, Fornell-Perez R, Garcia-Perez JC, Die-Trill J, Fuentes-Mateos R, Lopez-Duran S, Dominguez-Rullan J, Ferreiro R, Riquelme-Oliveira A, Hervas-Moron A, Counago F. Watch and wait approach in rectal cancer: Current controversies and future directions. World J Gastroenterol. 2020 Aug 7;26(29):4218-4239. doi: 10.3748/wjg.v26.i29.4218. PMID 32848330
• Li LH, Chen ZF, Wang XF, Liu X, Jiang WZ, Zhuo SM, Jiang LW, Guan GX, Chen JX. Monitoring neoadjuvant therapy responses in rectal cancer using multimodal nonlinear optical microscopy. Oncotarget. 2017 Nov 3;8(63):107323-107333. doi: 10.18632/oncotarget.22366. eCollection 2017 Dec 5. PMID 29291032
• Feeney G, Sehgal R, Sheehan M, Hogan A, Regan M, Joyce M, Kerin M. Neoadjuvant radiotherapy for rectal cancer management. World J Gastroenterol. 2019 Sep 7;25(33):4850-4869. doi: 10.3748/wjg.v25.i33.4850. PMID 31543678
• Glynne-Jones R, Wyrwicz L, Tiret E, Brown G, Rodel C, Cervantes A, Arnold D; ESMO Guidelines Committee. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017 Jul 1;28(suppl_4):iv22-iv40. doi: 10.1093/annonc/mdx224. No abstract available. PMID 28881920
• Hu H, Huang J, Lan P, Wang L, Huang M, Wang J, Deng Y. CEA clearance pattern as a predictor of tumor response to neoadjuvant treatment in rectal cancer: a post-hoc analysis of FOWARC trial. BMC Cancer. 2018 Nov 20;18(1):1145. doi: 10.1186/s12885-018-4997-y. PMID 30458734
• Yan YY, Guo QR, Wang FH, Adhikari R, Zhu ZY, Zhang HY, Zhou WM, Yu H, Li JQ, Zhang JY. Cell-Free DNA: Hope and Potential Application in Cancer. Front Cell Dev Biol. 2021 Feb 22;9:639233. doi: 10.3389/fcell.2021.639233. eCollection 2021. PMID 33693004

Идентификаторы

NCT: NCT06589388 · GS_ZTR

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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