Rectal Cancer CTC Trial

Официальное название

Impact of Neoadjuvant Chemoradiotherapy Versus Surgery Alone on Circulating Tumor Cells in Patients With Stage II-III Rectal Cancer and Negative Circumferential Resection Margin: a Multicenter Randomized Clinical Trial

Обзор

This prospective, multi-centre, randomised clinical trial aims to compare the effect of neoadjuvant chemoradiotherapy versus primary surgery on circulating tumor cells (CTCs) in patients with stage II-III rectal cancer without circumferential resection mar-gin involvement. CTCs are considered a promising biomarker for disease dissemination and treatment response. Patients will be randomized to either primary surgical resection with total mesorectal excision or long-course neoadjuvant chemoradiotherapy followed by surgery. Serial blood samples will be collected at predefined time points to assess the presence and dynamics of CTCs. Secondary endpoints include perioperative morbidity and mortality, local recurrence rate, disease-free survival, and overall survival. The results of this study may provide new insights into the prognostic role of CTCs and contribute to optimising treatment strategies for rectal cancer.

Подробное описание

Colorectal cancer remains one of the most common malignancies worldwide, and rectal cancer requires a multidisciplinary treatment approach. For patients with locally advanced rectal cancer, neoadjuvant chemoradiotherapy (nCRT) followed by surgical resection has been widely used to reduce the risk of local recurrence. However, the indication for nCRT in patients without circumferential resection margin (CRM) involvement remains controversial. While some studies have suggested benefits of nCRT, others have shown comparable oncological outcomes with primary surgery when high-quality total mesorectal excision (TME) is performed.

Circulating tumor cells (CTCs) are malignant cells detectable in peripheral blood that have been associated with metastatic potential and poor prognosis in various cancers, including colorectal cancer. Monitoring the presence and dynamics of CTCs offers a minimally invasive "liquid biopsy" approach that may provide prognostic information and reflect treatment efficacy. Existing evidence suggests that changes in CTC levels after surgery or systemic therapy may correlate with recurrence risk and survival, but relevant data in rectal cancer patients undergoing multimodal treatment are limited.

This prospective, multi-centre, randomised clinical trial will enrol patients with stage II-III rectal cancer without evidence of CRM involvement on staging magnetic resonance imaging (MRI). Eligible patients will be randomized into two study arms:

1. Primary surgery arm: radical surgical resection with total mesorectal excision (TME). 2. Neoadjuvant therapy arm: long-course neoadjuvant chemoradiotherapy fol-lowed by delayed surgical resection.

Peripheral blood samples will be collected at predefined time points in both groups to determine the presence and quantity of CTCs. The primary objective is to compare the effect of neoadjuvant chemoradiotherapy versus surgery alone on CTC dynamics.

Secondary objectives include:

* Evaluation of short-term surgical outcomes (perioperative complications, 30-day morbidity and mortality). * Assessment of long-term oncological outcomes (local recurrence, disease-free survival, and overall survival at 3 and 5 years).

By integrating CTC monitoring into a modern randomized clinical trial design, this study aims to clarify the prognostic value of CTCs in rectal cancer and determine whether specific treatment strategies are associated with more favourable biological and clinical outcomes. The findings may contribute to more individualised treatment planning and potentially reduce the risk of recurrence and mortality in rectal cancer patients.

Вмешательства

• Процедура Primary Surgery
  Patients undergo radical surgical resection with TME without preceding neoadjuvant therapy
• Процедура Neoadjuvant radiochemotherapy and surgery
  Neoadjuvant treatment: long-course pelvic radiotherapy (conventional fractionation) with concurrent chemotherapy (standard fluoropyrimidine-based regimen)

Первичные конечные точки

• Circulating Tumor Cells (CTC) Dynamics - neoadjuvant treatment - shape [Срок оценки: (1) before the initiation of CRT, (2) 1 week and (3) 1 month after the initiation of CRT, (4) preoperatively (1-2 weeks before surgery), (5) 1 week postoperatively, and (6) 1 month postoperatively]
• Circulating Tumor Cells (CTC) Dynamics - neoadjuvant treatment - size [Срок оценки: (1) before the initiation of CRT, (2) 1 week and (3) 1 month after the initiation of CRT, (4) preoperatively (1-2 weeks before surgery), (5) 1 week postoperatively, and (6) 1 month postoperatively]
• Circulating Tumor Cells (CTC) Dynamics - neoadjuvant treatment - DAPI positivity [Срок оценки: (1) before the initiation of CRT, (2) 1 week and (3) 1 month after the initiation of CRT, (4) preoperatively (1-2 weeks before surgery), (5) 1 week postoperatively, and (6) 1 month postoperatively]
• Circulating Tumor Cells (CTC) Dynamics - neoadjuvant treatment - pancytokeratin and/or EpCAM positivity [Срок оценки: (1) before the initiation of CRT, (2) 1 week and (3) 1 month after the initiation of CRT, (4) preoperatively (1-2 weeks before surgery), (5) 1 week postoperatively, and (6) 1 month postoperatively]
• Circulating Tumor Cells (CTC) Dynamics - neoadjuvant treatment - CD45 negativity [Срок оценки: (1) before the initiation of CRT, (2) 1 week and (3) 1 month after the initiation of CRT, (4) preoperatively (1-2 weeks before surgery), (5) 1 week postoperatively, and (6) 1 month postoperatively]
• Circulating Tumor Cells (CTC) Dynamics - primary surgery - shape [Срок оценки: (1) preoperatively (1-2 weeks before surgery), (2) 1 week postoperatively, and (3) 1 month postoperatively]
• Circulating Tumor Cells (CTC) Dynamics - primary surgery - size [Срок оценки: (1) preoperatively (1-2 weeks before surgery), (2) 1 week postoperatively, and (3) 1 month postoperatively]
• Circulating Tumor Cells (CTC) Dynamics - primary surgery - DAPI positivity [Срок оценки: (1) preoperatively (1-2 weeks before surgery), (2) 1 week postoperatively, and (3) 1 month postoperatively]
• Circulating Tumor Cells (CTC) Dynamics - primary surgery - pancytokeratin and/or EpCAM positivity [Срок оценки: (1) preoperatively (1-2 weeks before surgery), (2) 1 week postoperatively, and (3) 1 month postoperatively]
• Circulating Tumor Cells (CTC) Dynamics - primary surgery - CD45 negativity [Срок оценки: (1) preoperatively (1-2 weeks before surgery), (2) 1 week postoperatively, and (3) 1 month postoperatively]

Вторичные конечные точки (6)

• Short-term postoperative outcomes - preoperative complications [Срок оценки: Within 30 days after surgery]
• Short-term postoperative outcomes - 30-day morbidity [Срок оценки: Within 30 days after surgery]
• Short-term postoperative outcomes - 30-day mortality [Срок оценки: Within 30 days after surgery]
• Local recurrence rate [Срок оценки: Up to 5 years]
• Disease-free survival (DFS) [Срок оценки: 3 and 5 years after surgery]
• Overall survival (OS) [Срок оценки: 3 and 5 years after surgery]

Критерии участия

Критерии включения

• Age ≥ 18 years
• Histologically confirmed rectal adenocarcinoma within 12 cm from anal verge
• Stage II (cT3-4 N0 M0) or stage III (cT1-4 N1-2, M0)
• Negative circumferential resection margin on staging MRI
• ASA physical status I-III
• Signed informed consent

Критерии исключения

• Tumor infiltration beyond fascia recti propria on MRI
• Metastatic disease (stage IV)
• Recurrent rectal cancer
• Other concurrent malignancies
• Emergency surgery required
• Contraindication to surgery under general anesthesia

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Чехия · 4 центра

• University Hospital Olomouc — Olomouc
• Palacky University Olomouc, Faculty of Medicine — Olomouc
• University Hospital Ostrava — Ostrava
• Municipal Hospital Ostrava - Fifejdy — Ostrava

Публикации

• Lu CY, Uen YH, Tsai HL, Chuang SC, Hou MF, Wu DC, Juo SH, Lin SR, Wang JY. Molecular detection of persistent postoperative circulating tumour cells in stages II and III colon cancer patients via multiple blood sampling: prognostic significance of detection for early relapse. Br J Cancer. 2011 Mar 29;104(7):1178-84. doi: 10.1038/bjc.2011.40. Epub 2011 Feb 22. PMID 21343933
• Hinz S, Roder C, Tepel J, Hendricks A, Schafmayer C, Becker T, Kalthoff H. Cytokeratin 20 positive circulating tumor cells are a marker for response after neoadjuvant chemoradiation but not for prognosis in patients with rectal cancer. BMC Cancer. 2015 Dec 16;15:953. doi: 10.1186/s12885-015-1989-z. PMID 26674974
• Yadav A, Kumar A, Siddiqui MH. Detection of circulating tumour cells in colorectal cancer: Emerging techniques and clinical implications. World J Clin Oncol. 2021 Dec 24;12(12):1169-1181. doi: 10.5306/wjco.v12.i12.1169. PMID 35070736
• Burz C, Pop VV, Buiga R, Daniel S, Samasca G, Aldea C, Lupan I. Circulating tumor cells in clinical research and monitoring patients with colorectal cancer. Oncotarget. 2018 May 11;9(36):24561-24571. doi: 10.18632/oncotarget.25337. eCollection 2018 May 11. PMID 29849961
• Wu J, Li Z, Zou J, Li L, Cui N, Hao T, Yi K, Yang J, Wu Y. A meta-analysis of the value of circulating tumor cells in monitoring postoperative recurrence and metastasis of colorectal cancer. PLoS One. 2022 Sep 19;17(9):e0274282. doi: 10.1371/journal.pone.0274282. eCollection 2022. PMID 36121855
• Sun W, Li G, Wan J, Zhu J, Shen W, Zhang Z. Circulating tumor cells: A promising marker of predicting tumor response in rectal cancer patients receiving neoadjuvant chemo-radiation therapy. Oncotarget. 2016 Oct 25;7(43):69507-69517. doi: 10.18632/oncotarget.10875. PMID 27486758
• Pan RJ, Hong HJ, Sun J, Yu CR, Liu HS, Li PY, Zheng MH. Detection and Clinical Value of Circulating Tumor Cells as an Assisted Prognostic Marker in Colorectal Cancer Patients. Cancer Manag Res. 2021 Jun 8;13:4567-4578. doi: 10.2147/CMAR.S300554. eCollection 2021. PMID 34135633
• Tseng M, Soon YY, Vellayappan B, Ho F, Tey J. Radiation therapy for rectal cancer. J Gastrointest Oncol. 2019 Dec;10(6):1238-1250. doi: 10.21037/jgo.2018.12.04. PMID 31949945

Идентификаторы

NCT: NCT07194616 · RECTA-CTC

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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