A Study of the Clinical Value of Dynamic Multi-omics Integration Model to Predict Neoadjuvant Therapy Response in Locally Advanced Rectal Cancer (T3-4NxM0)
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Predictive Cancer Model
- Sponsor
- Sixth Affiliated Hospital, Sun Yat-sen University
- Enrollment
- 106
- Locations
- 1
- Primary Endpoint
- Area under curve(AUC)
- Status
- Recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
The goal of this observational study is to establish a dynamic multi-omics integration model for predicting pathological complete response (pCR) after neoadjuvant treatment in locally advanced (T3-4NxM0) rectal cancer, providing support for subsequent patient selection for the watch-and-wait strategy. The main question it aims to answer is:
What is the predictive value of this model to assess individual achievement of pathological complete response (pCR) after neoadjuvant treatment? Eligible patients will be prospectively enrolled, and the clinical features of their pre-neoadjuvant treatment, during-treatment, and post-treatment preoperative will be collected and annotated.
Detailed Description
This is a single-center, prospective, observational phase II clinical study aimed at validating a dynamic multi-omics (imaging, pathology, molecular biomarkers) integration model for predicting pathological complete response (pCR) after neoadjuvant treatment in locally advanced (T3-4NxM0) rectal cancer. Specifically, the study aims to validate the predictive accuracy of the dynamic multi-omics prediction model and determine whether it outperforms other conventional prediction models based on single-modality imaging, pathology, and molecular biomarkers. Eligible patients will be prospectively enrolled, and images of their pre-neoadjuvant treatment, during-treatment, and post-treatment preoperative magnetic resonance imaging (MRI) scans, histopathology slides stained with hematoxylin and eosin (H\&E), carcinoembryonic antigen (CEA), and circulating tumor DNA (ctDNA) will be collected and annotated. MRI, H\&E images, CEA, ctDNA, and their change features will be applied to the prediction model to assess individual achievement of pathological complete response (pCR) after neoadjuvant treatment. The predictive results will be further compared with the pathological tumor response obtained from resected specimens.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed rectal adenocarcinoma;
- •Clinical stage T3-4NxM0, with or without positive Mesorectum Fascia(MRF), and with or without positive Extra-Mural Venous Invasion(EMVI);
- •Preoperative staging method: All patients undergo preoperative staging with enhanced CT. Criteria for mesorectal lymph node metastasis: Short axis ≥ 10mm lymph nodes or lymph node morphology and CT characteristics consistent with typical lymph node metastasis. Preoperative chest, abdominal CT, and pelvic MRI exclude distant metastases;
- •Absence of signs of intestinal obstruction; or relief of obstruction after proximal colon diversion surgery;
- •No history of previous colorectal surgery;
- •No history of previous chemotherapy or radiotherapy;
- •No history of previous biological therapy (such as monoclonal antibodies), immunotherapy \[such as anti-programmed cell death protein 1(PD-1) antibodies, anti-PD-L1 antibodies, anti-PD-L2 antibodies, or anti-Cytotoxic T Lymphocyte-Associated Antigen-4(CTLA-4)\], or other investigational drug therapy;
- •No history of previous hormonal therapy: no restrictions;
- •Signed informed consent form.
Exclusion Criteria
- •Patients requiring antiarrhythmic therapy (excluding β-blockers or digoxin), symptomatic coronary artery disease, recent myocardial infarction within the past 6 months, or congestive heart failure exceeding New York Heart Association(NYHA) class II;
- •Poorly controlled severe hypertension;
- •History of HIV infection or active chronic hepatitis B or C (high viral DNA load);
- •Active pulmonary tuberculosis (TB) or receiving anti-TB treatment, or having received anti-TB treatment within the past year;
- •Other active clinically severe infections ;
- •Evidence of distant metastases outside the pelvis preoperatively;
- •Cachexia, organ decompensation;
- •History of pelvic or abdominal radiotherapy;
- •Multifocal colorectal cancer;
- •Patients requiring management for epileptic seizures (e.g., with steroids or antiepileptic therapy);
Outcomes
Primary Outcomes
Area under curve(AUC)
Time Frame: through study completion, an average of 6 months
Area under curve of prediction model
Secondary Outcomes
- Positive predictive value(PPV)(through study completion, an average of 6 months)
- Sensitivity(through study completion, an average of 6 months)
- Specificity(through study completion, an average of 6 months)
- Negative predictive value(NPV)(through study completion, an average of 6 months)