Gut Microbiomes, Neoadjuvant Chemoimmunotherapy, Non-Small Cell Carcinoma of Lung
Conditions
Keywords
NSCLC, Gut Microbiomes
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
Interventions
DRUGNeoadjuvant chemoimmunotherapy
neoadjuvant chemoimmunotherapy typically involves a PD-1 inhibitor-such as nivolumab, sintilimab, or camrelizumab-combined with platinum-based doublet chemotherapy (e.g., paclitaxel plus cisplatin for squamous cell carcinoma, or pemetrexed plus cisplatin for adenocarcinoma). The standard regimen includes three treatment cycles administered every three weeks, followed by surgical resection within 4-6 weeks. Some patients may receive up to one year of adjuvant immunotherapy postoperatively.
Sponsors
Guangdong Provincial People's Hospital
Southern Medical University, China
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age between 18 and 80 years; 2. Newly diagnosed, driver gene-negative non-small cell lung cancer (NSCLC) confirmed by histopathology (Stage IIA-IIIB); 3. At least one measurable lesion as defined by RECIST version 1.1; Eastern Cooperative Oncology Group (ECOG) performance status of 0-1; 4. No prior systemic therapy or radiotherapy; 5. Eligible for surgical resection and suitable for neoadjuvant immunotherapy or chemotherapy as determined by multidisciplinary evaluation; 6. Signed written informed consent prior to study participation; 7. Adequate pulmonary ventilation and diffusion function confirmed by pre-enrollment pulmonary function test to allow for surgical resection.
Exclusion criteria
1. Requirement for systemic glucocorticoid therapy or other immunosuppressive treatments; 2. Use of antibiotics or presence of infections requiring antibiotic therapy within the past 3 months; 3. Probiotic use within 3 months prior to enrollment; 4. Presence of obstructive pneumonia, cancerous cavitation, or active pulmonary tuberculosis; 5. Presence of bronchiectasis, concurrent pulmonary infections, pulmonary fibrosis, or uncontrolled diabetes mellitus; 6. Presence of a primary tumor in another organ; 7. Receipt of chemotherapy or any other cancer treatment prior to enrollment; 8. Confirmed brain metastases by contrast-enhanced MRI before enrollment; 9. Active or pre-existing autoimmune diseases; 10. Uncontrolled comorbidities including heart failure, uncontrolled hypertension, unstable angina, or interstitial lung disease; 11. Positive for hepatitis B surface antigen or detectable hepatitis C RNA requiring treatment; 12. Known history or positive test for human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS); 13. Pregnant or breastfeeding women; 14. Previous treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibodies.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic complete response (pCR) | 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
| Measure | Time frame | Description |
|---|---|---|
| Major pathological response (MPR) | From surgery to the end of the 1-month postoperative （periodPerioperative/Periprocedural） | Major pathological response (MPR) is defined as ≤10% residual viable tumor cells in the resected primary tumor specimen after neoadjuvant therapy, as determined by histopathological evaluation |
| Radiological response | From the time of enrollment through the completion of surgery（Perioperative/Periprocedural） | Defined as radiographic change assesed by RECIST 1.1 |
| Immune-related adverse event (irAE) | From the time of enrollment through the completion of surgery（Perioperative/Periprocedural） | defined as all levels of adverse drug reactions in antitumor immunotherapy that are judged to be related to immune mechanisms, excluding non-specific infusion reactions |
| gut microbiomes | From the time of enrollment through the completion of surgery（Perioperative/Periprocedural） | Defined as microbial composition, diversity, and functional activity measured by metagenomic sequencing |
| Disease free survival (DFS） | From the postoperative period through 1 year after surgery | Defined as the time from the date of definitive treatment (e.g., surgery) until the date of recurrence of cancer, the occurrence of a second primary cancer, or death from any cause, whichever occurs first. |
Countries
China
Contacts
CONTACTWenzhao Zhong M.D., Doctoral degree
CONTACTXi Zhang M.D.
Outcome results
None listed