Safety and Efficacy of NOM and OPFS Versus RO for dMMR/MSI-H or POLE-Mutated Gastrointestinal Cancers

Официальное название

Safety and Efficacy of Nonoperative Management (NOM) and Organ Preservation First Strategy (OPFS) Versus Radical Operation (RO) for dMMR/MSI-H or POLE-Mutated Gastrointestinal Cancers: A Single-Center, Bidirectional Registry Study

Обзор

Purpose: The purpose of this study is to evaluate the safety and efficacy of Non-Operative Management (NOM) and Organ Preservation First Strategy (OPFS) compared with Radical Operation (RO) in patients with deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) or POLE-mutated gastrointestinal cancers. Background \& Design: With the remarkable efficacy of neoadjuvant immunotherapy in dMMR/MSI-H or POLE-mutated gastrointestinal tumors, organ preservation has become a promising alternative to highly invasive surgeries. The NOR-MP trial is a single-center, bidirectional registry study consisting of two parts: a retrospective cohort study and a prospective observational registry. Intervention Group (NOM/OPFS): Patients who achieve a clinical complete response (cCR) or near-cCR after neoadjuvant immunotherapy will undergo a "Watch \& Wait" (W\&W) strategy. Patients with near-cCR or non-cCR who are eligible for organ preservation will undergo local excision (LE) or endoscopic resection (including ESD or EMR). Comparison Group (Radical Operation): Patients who undergo standard radical surgical resection after neoadjuvant immunotherapy. The study aims to determine whether an organ-preserving approach can achieve comparable oncological outcomes and safety profiles while significantly improving patients' quality of life compared to radical surgery.

Подробное описание

The NOR-MP trial is a single-center, bidirectional registry study designed to compare the clinical outcomes of Organ Preservation First Strategy (OPFS) / Non-Operative Management (NOM) against standard Radical Operation (RO) for patients diagnosed with dMMR/MSI-H or POLE-mutated gastrointestinal cancers. The study is divided into two sequential parts based on the nature of data collection:

Part 1: Retrospective Cohort Study

This part retrospectively reviews the medical records of eligible patients with dMMR/MSI-H or POLE-mutated gastrointestinal cancers who previously completed neoadjuvant immunotherapy. Patients are allocated into two historical cohorts:

Experimental Cohort (NOM/OPFS): Patients who achieved cCR/near-cCR after neoadjuvant immunotherapy and entered the "Watch \& Wait" (W\&W) program, as well as those with near-cCR or non-cCR who underwent local excision (LE) or endoscopic resection (including Endoscopic Submucosal Dissection \[ESD\] or Endoscopic Mucosal Resection \[EMR\]).

Control Cohort (RO): Patients who underwent radical surgical operation after neoadjuvant immunotherapy. Pathological outcomes (including the proportions of ypCR, ypTisN0, and ypT1-2N0) and surgical safety data will be collected and analyzed.

Part 2: Prospective Registry Study

This part prospectively enrolls newly diagnosed patients with dMMR/MSI-H or POLE-mutated gastrointestinal cancers receiving neoadjuvant immunotherapy. Following treatment evaluation by the multi-disciplinary NOR-MP research team, patients are enrolled into two parallel observational tracks:

Experimental Cohort (NOM/OPFS): Patients eligible for and consenting to NOM or OPFS. This includes the W\&W strategy for those achieving cCR/near-cCR, and LE or endoscopic resection (ESD/EMR) for those with near-cCR or non-cCR.

Control Cohort (RO): Patients who proceed to standard radical operation. Pathological response distribution (proportions of ypCR, ypTisN0, ypT1-2N0, and ypT3+ diseases) and short-to-long-term surgical safety endpoints will be prospectively documented.

By comparing the retrospective and prospective cohorts, this study evaluates whether the omission of radical surgery is oncologically safe and preserves organ function without compromising long-term survival.

Вмешательства

• Другое NOM/OPFS
  Patients eligible for and consenting to NOM or OPFS. This includes the W\&W strategy for those achieving cCR/near-cCR, and LE or endoscopic resection (ESD/EMR) for those with near-cCR or non-cCR.

Первичные конечные точки

• Organ Preservation Rate (for OPFS/NOM group) [Срок оценки: Up to 3 years after the completion of neoadjuvant immunotherapy.]

Вторичные конечные точки (5)

• Surgical Safety and Postoperative Complications [Срок оценки: Within 30 days and 90 days post-surgery.]
• Pathological Response Distribution (for RO group) [Срок оценки: At the time of radical surgery (typically within 4-12 weeks post-immunotherapy).]
• Local Regrowth / Recurrence Rate [Срок оценки: Followed up at regular intervals (every 3-6 months) up to 3 years.]
• Overall Survival (OS) [Срок оценки: Up to 5 years.]
• Disease-Free Survival (DFS) / Disease-Specific Survival (DSS) [Срок оценки: From enrollment/treatment initiation up to 5 years.]

Критерии участия

Критерии включения

• Histologically confirmed primary gastrointestinal adenocarcinoma or squamous cell carcinoma (e.g., colorectal cancer, gastric cancer, gastroesophageal junction cancer).
• Confirmed as deficient mismatch repair (dMMR) by immunohistochemistry (IHC), high microsatellite instability (MSI-H) by polymerase chain reaction (PCR) or next-generation sequencing (NGS), or harboring POLE exonuclease domain mutations.
• Received neoadjuvant/conversion immunotherapy (immune checkpoint inhibitors, either monotherapy or combination therapy) prior to treatment response evaluation.
• For the Retrospective Cohort (Part 1): Patients treated between \[Start Month/Year\] and \[End Month/Year\] who completed evaluation and subsequent strategy (NOM/OPFS or RO).
• For the Prospective Cohort (Part 2): Newly diagnosed patients who consent to long-term follow-up and multi-disciplinary team (MDT) assessment for organ preservation or radical surgery.
• Age ≥ 18 years at the time of diagnosis.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Критерии исключения

• Concurrently diagnosed with other active malignant tumors within the past 5 years.
• Patients with proficient mismatch repair (pMMR) / microsatellite stable (MSS) tumors, or wild-type POLE status.
• Evidence of untreatable distant metastasis or systemic disease that precludes local tumor management (NOM/OPFS or radical operation).
• Inability to undergo regular endoscopic, radiological (MRI/CT), or clinical follow-up due to compliance or geographic reasons.
• Refusal to sign the informed consent form (applicable to the prospective cohort).

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

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07642323 · PKUCH-NORMP trial

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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