编者按：在2024年欧洲肿瘤内科学会亚洲年会（ESMO ASIA 2024）上中国结直肠癌领域TIP摘要研究共有9个，此前我们已经整理了其中4个（ESMO ASIA 2024丨从徐瑞华教授等中国研究者入选的TiP摘要看结直肠癌最新研发动向），本文将整理剩余的由中山大学附属第六医院黄俊教授团队领衔的5项研究，以飨读者。

摘要号：117TiP

标题：减孔腹腔镜手术治疗结肠和上段直肠癌患者的安全性和有效性：一项多中心、前瞻性、随机、Ⅲ期研究

背景

根治性切除术仍是非转移性结直肠癌（CRC）治疗的基石。传统腹腔镜手术往往需要助手参与，而助手技能和经验的不足可能导致意外损伤和干扰手术进程。减孔腹腔镜手术通过简化设置，即外科医生使用两个操作孔，助手使用一个观察孔，使得外科医生能够独立完成手术。这种方法有望减少因助手经验不足而导致的手术时间延长和损伤。此外，减孔腹腔镜手术的切口更少，意味着术后疼痛减轻、恢复更快，同时减少了资源使用和医疗费用。

试验设计

临床试验识别号

NCT05953662

摘要号：121TiP 

标题：低位直肠癌Parks术与Bacon吻合术后肛门功能比较：一项多中心、前瞻性、随机对照研究

背景

试验设计

临床试验识别号

NCT05943444

摘要号：122TiP

标题：DNA错配修复缺陷或微卫星高度不稳定远端直肠癌患者接受PD-1单抗治疗后达到病理完全缓解的“观察等待”策略（BASKET）

背景

试验设计

临床试验识别号

摘要号：123TiP

标题：预测局部晚期直肠癌新辅助治疗反应的动态多组学整合模型

背景

试验设计

临床试验识别号

摘要号：124TiP

标题：局部晚期dMMR/MSI-H型同时多原发性结直肠癌患者接受PD-1单抗联合或不联合 mFOLFOX6 新辅助治疗的安全性和有效性

背景

试验设计

临床试验识别号

摘要原文

117TiP - Safety and efficacy of reduced-port laparoscopic surgery for patients with colon and upper rectal cancer: A multicenter, prospective, randomized phase III study

Background

Radical resection remains the cornerstone treatment for non-metastatic colorectal cancer (CRC). Conventional laparoscopic surgeries often involve assistants whose limited skills and experience may lead to inadvertent injuries and surgeon interference. Reduced-port laparoscopic surgery, with its simplified setup of two operation ports for the surgeon and one observation port for the assistant, allows for independent surgeon completion of the procedure. This approach potentially mitigates prolonged operation times and injuries due to inexperienced assistants. Additionally, reduced-port laparoscopy entails fewer incisions, translating to reduced postoperative pain, quicker recovery, and decreased resource utilization and medical expenses.

Trial design

This multicenter, open-label, randomized phase III trial with a parallel design is conducted in China. Patients are randomized (1:1) to either the reduced-port laparoscopic surgery group or the conventional laparoscopic surgery group using a computerized randomization management system. The reduced-port laparoscopic surgery group undergoes surgery with three ports, while the conventional laparoscopic surgery group undergoes surgery with five ports. This study represents the first prospective randomized controlled trial assessing the safety and efficacy of reduced-port laparoscopic surgery for resectable CRC. The study aims to evaluate perioperative complications, R0 resection rates, and 3-year disease-free and overall survival rates. Key inclusion criteria include preoperative clinical tumor stage I-III (cTxNxM0) CRC, histologically confirmed colorectal adenocarcinoma, and patient capacity to provide informed consent. Main exclusion criteria comprise a history of other malignant tumors, complications necessitating emergency surgery, non-resectable lymph node metastasis, high ASA grading, and/or elevated ECOG scores. A total of 500 patients are planned for enrollment, with 128 patients enrolled as of May 5th, 2024. The trial is registered with ClinicalTrials.gov (NCT05953662) and ongoing.

Clinical trial identification

NCT05953662.

121TiP - Comparison of postoperative anal function between parks and bacon techniques in lower rectal cancer: A multicenter, prospective, randomized control study

Background

Lower rectal cancer (LRC), defined as tumors located ≤ 3cm from the dentate line, poses challenges in selecting optimal surgical approaches for anal preservation while ensuring oncological outcomes. Previous studies have shown comparable disease-free and overall survival rates between Parks' and Bacon's operations. However, evidence from large-scale randomized controlled trials directly comparing their effects on postoperative anal function, quality of life, complications, and overall survival in LRC patients is lacking.

Trial design

This prospective, multicentric, randomized controlled trial conducted in China aims to address this gap in knowledge. LRC patients meeting inclusion criteria are randomly assigned in a 1:1 ratio to either the Parks’ operation group or the Bacon’s operation group using a computerized randomization management system. Parks’ operation involves colon anal anastomosis, while Bacon’s operation involves colon anal pull-out anastomosis. Postoperative anal function is assessed using rectoanal manometry and the Low Anterior Resection Syndrome (LARS) score at 3 months, 6 months, and 1year post-surgery. Quality of life scores and the incidence of postoperative anastomotic complications are also evaluated. Key inclusion criteria include pathological confirmation of LRC with ≤ 3cm distance from the tumor to the dentate line by MRI, suitability for anal preservation surgery discussed by a multidisciplinary team, and patient ability to provide informed consent. Main exclusion criteria encompass history of other malignancies, emergent complications requiring immediate surgery, unresectable tumor extension, high ASA grading, and/or elevated ECOG scores. The study plans to enroll 265 patients, with 8 patients enrolled as of May 5th, 2024. Registration with ClinicalTrials.gov (NCT05943444) has been completed.

Clinical trial identification

NCT05943444.

122TiP - Watch and wait in patients with DNA mismatch repair-deficient or microsatellite instability-high distal rectal cancer accessed pathological complete response after PD-1 monoclonal antibody therapy (BASKET)

Background

PD-1 monoclonal antibody therapy has demonstrated significant efficacy in DNA mismatch repair-deficient or microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC). Notably, neoadjuvant immunotherapy has shown promising pathological complete response (pCR) rates in these patients. However, radical resection in distal rectal cancer (RC) may lead to functional impairments and psychological distress. The feasibility and safety of a watch and wait approach in patients with early stage and locally advanced (stage I-III) dMMR/MSI-H distal RC achieving clinical complete response (cCR) after PD-1 monoclonal antibody therapy remain uncertain.

Trial design

The BASKET study is an open-label, multicenter, prospective phase II trial conducted in China. Patients with stage I-III dMMR/MSI-H distal RC received neoadjuvant immunotherapy with 200 mg sintilimab (PD-1 monoclonal antibody) intravenously on day 1 of each 3-week cycle for 6 cycles. Patients achieving cCR after PD-1 monoclonal antibody therapy were enrolled and initiated a watch and wait approach. This study is the first prospective evaluation of the efficacy and safety of watch and wait in these patients. Precise clinical evidence from this study will inform individualized precision treatment for distal RC patients, aiming to preserve organ function and improve quality of life. Key inclusion criteria comprised tumor biopsy confirmed dMMR by immunohistochemical (IHC) staining or MSI-H by next-generation sequencing, MRI-identified tumor located below the peritoneal reflection, and clinical staging TxNxM0. cCR was assessed by enhanced CT/MRI and confirmed by biopsy. Stage IV distal RC, multiple CRC, active autoimmune diseases, and long-term corticosteroid use were among the main exclusion criteria. A total of 47 patients are planned for enrollment. As of May 1, 2024, 10 patients have been enrolled. The study is registered with ClinicalTrials.gov (NCT04643041) and ongoing.

123TiP - Dynamic multi-omics integration modelto predict neoadjuvant therapy response in locally advanced rectal cancer

Background

Neoadjuvant therapies have significantly enhanced the pathological complete response (pCR) rates and prognosis in colorectal cancer (CRC) patients. The increased pCR rates may correlate with reductions in carcinoembryonic antigen (CEA) levels, tumor size, circulating tumor DNA (ctDNA) levels, neutrophil-to-lymphocyte ratio (NLR), and enhanced signal on magnetic resonance imaging (MRI). Accurately predicting pCR after neoadjuvant therapy could inform the adoption of a watch and wait strategy for patients with locally advanced rectal cancer (LACR).

Trial design

This multicenter, prospective, observational phase II clinical study aims to develop and validate a dynamic multi-omics integration model for predicting pCR after neoadjuvant treatment in LACR (T3-4NxM0) patients. Specifically, it is the first prospective study to assess the predictive accuracy of this dynamic multi-omics model and determine its superiority over conventional prediction models based on single-modality imaging, pathology, or molecular biomarkers. Eligible patients will be prospectivelyenrolled, and pre-neoadjuvant treatment, during-treatment, and preoperative MRI scans, histopathology slides stained with hematoxylin and eosin (H&E), CEA, NLR, and ctDNA will be collected and annotated. Changes in these features along with preoperative multistage biopsy results will be incorporated into the prediction model to forecast individual achievement of pCR after neoadjuvant treatment. Predictive results will be validated with pathological tumor response evaluated from resected specimens. Key inclusion criteria include histologically confirmed rectal adenocarcinoma, clinical stage T3-4NxM0 and no history of previous chemoradiotherapy or colorectal surgery. Main exclusion criteria encompass complications requiring long-term use of immunosuppressive drugs, substance abuse, or social conditions interfering with study participation or assessment, and history of other malignant tumors within 5 years or evidence of distant metastases outside the pelvis preoperatively. The study aims to enroll 106 patients. The study is registered with ClinicalTrials.gov (NCT06364371) and is ongoing.

Clinical trial identification

NCT06364371.

124TiP - Safety and efficacy of PD-1 monoclonal antibody with or without mFOLFOX6 neoadjuvant therapy in patients with local advanced deficient mismatch repair/microsatellite instability-high synchronous multiple primary colorectal cancer

Background

Synchronous multiple primary colorectal cancer (sMPCC) is a clinically rare entity, but its incidence has been on the rise in recent years. Our previous research revealed a significantly higher incidence of deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) in patients with sMPCC compared to those with single primary colorectal cancer (SPCRC). PD-1 monoclonal antibody therapy has demonstrated remarkable efficacy in dMMR/MSI-H SPCRC patients. However, the safety and efficacy of neoadjuvant immunotherapy in patients with locally advanced dMMR/MSI-H sMPCC remain uncertain.

Trial design

This open-label, multicenter, single-arm, prospective phase II study conducted in China aims to assess the safety and efficacy of neoadjuvant immunotherapy in patients with locally advanced dMMR/MSI-H sMPCC. Patients are categorized into three sub-types: type 1, with both dMMR/MSI-H and proficient mismatch repair/microsatellite stable (pMMR/MSS) lesions; type 2, with all lesions exhibiting dMMR/MSI-H; and type 3, with all lesions showing pMMR/MSS. Enrolled patients include those with type 1 and type 2. Patients with mixed MMR status receive neoadjuvant combination therapy comprising mFOLFOX6 and PD-1 monoclonal antibody every 2 weeks for 6 cycles, while patients with dMMR/MSI-H receive neoadjuvant immunotherapy with PD-1 monoclonal antibody in the same cycles. This study represents the first prospective investigation into the safety and efficacy of neoadjuvant immunotherapy in patients with locally advanced dMMR/MSI-H sMPCC. The findings of this study are anticipated to inform personalized treatment strategies for sMPCC patients. Key inclusion criteria encompass histological confirmation of sMPCC, immunohistochemical or next-generation sequencing identification of dMMR/MSI-H, and clinical staging (cT3-4NxM0). Main exclusion criteria include stage IV, other malignant tumors within 5 years, long-term exposure to immunosuppressive agents, and refusal to provide informed consent. A total of 17 patients are planned for enrollment.

Clinical trial identification

NCT06002789.