A Prospective Cohort Study Investigating Gut Microbiota as an Immunomodulatory Predictor of Response to Neoadjuvant Chemoimmunotherapy in Resectable Non-small-cell Lung Cancer
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Enrollment
- 100
- Locations
- 1
- Primary Endpoint
- Pathologic complete response (pCR)
Study Overview
Brief Summary
Locally advanced lung cancer (LALC) has poor prognosis despite multimodal therapies. Neoadjuvant chemoimmunotherapy is now standard for resectable stage II-IIIB NSCLC, but patient responses vary. The gut microbiota, a key immune regulator, has been linked to immunotherapy efficacy, with microbial diversity predicting ICI response and fecal microbiota transplantation improving outcomes. While most studies focus on advanced disease, the microbiota's role in LALC during neoadjuvant therapy remains unclear. Exploring its dynamics may uncover novel biomarkers and strategies to optimize treatment
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Age between 18 and 80 years;
- •Newly diagnosed, driver gene-negative non-small cell lung cancer (NSCLC) confirmed by histopathology (Stage IIA-IIIB);
- •At least one measurable lesion as defined by RECIST version 1.1; Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
- •No prior systemic therapy or radiotherapy;
- •Eligible for surgical resection and suitable for neoadjuvant immunotherapy or chemotherapy as determined by multidisciplinary evaluation;
- •Signed written informed consent prior to study participation;
- •Adequate pulmonary ventilation and diffusion function confirmed by pre-enrollment pulmonary function test to allow for surgical resection.
Exclusion Criteria
- •Requirement for systemic glucocorticoid therapy or other immunosuppressive treatments;
- •Use of antibiotics or presence of infections requiring antibiotic therapy within the past 3 months;
- •Probiotic use within 3 months prior to enrollment;
- •Presence of obstructive pneumonia, cancerous cavitation, or active pulmonary tuberculosis;
- •Presence of bronchiectasis, concurrent pulmonary infections, pulmonary fibrosis, or uncontrolled diabetes mellitus;
- •Presence of a primary tumor in another organ;
- •Receipt of chemotherapy or any other cancer treatment prior to enrollment;
- •Confirmed brain metastases by contrast-enhanced MRI before enrollment;
- •Active or pre-existing autoimmune diseases;
- •Uncontrolled comorbidities including heart failure, uncontrolled hypertension, unstable angina, or interstitial lung disease;
- •Positive for hepatitis B surface antigen or detectable hepatitis C RNA requiring treatment;
- •Known history or positive test for human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS);
- •Pregnant or breastfeeding women;
- •Previous treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibodies.
Arms & Interventions
Response Group
a complete or partial response or stable disease lasting >6 months were classified as responders
Intervention: Neoadjuvant chemoimmunotherapy (Drug)
Non-Response Group
patients who progressed on therapy or had stable disease <6 months were classified as non-responders
Intervention: Neoadjuvant chemoimmunotherapy (Drug)
Outcomes
Primary Outcomes
Pathologic complete response (pCR)
Time Frame: From surgery to the end of the 1-month postoperative （periodPerioperative/Periprocedural）
Pathological complete response (pCR) is defined as the absence of any residual invasive cancer in the resected primary tumor and lymph nodes following neoadjuvant therapy, as assessed by histopathological examination
Secondary Outcomes
- Major pathological response (MPR)(From surgery to the end of the 1-month postoperative （periodPerioperative/Periprocedural）)
- Radiological response(From the time of enrollment through the completion of surgery（Perioperative/Periprocedural）)
- Immune-related adverse event (irAE)(From the time of enrollment through the completion of surgery（Perioperative/Periprocedural）)
- gut microbiomes(From the time of enrollment through the completion of surgery（Perioperative/Periprocedural）)
- Disease free survival (DFS）(From the postoperative period through 1 year after surgery)
Investigators
Wen-zhao ZHONG
Chief Physician
Guangdong Provincial People's Hospital