The goal of this study is to develop and refine an integrated minimally invasive care pathway for resectable lung cancer in the immunotherapy era, establishing a novel precision perioperative immunotherapy paradigm encompassing original techniques and clinical applications.
Lung cancer remains the leading cause of cancer-related mortality in China and globally, imposing a substantial disease burden on society. Although comprehensive treatment strategies centered on surgery have improved patient outcomes, and perioperative immunotherapy-particularly immune checkpoint inhibitors-has profoundly reshaped the therapeutic landscape, significant knowledge gaps and critical challenges persist in this field. These challenges include uncertain beneficiary populations, poorly understood immune mechanisms, inaccurate efficacy prediction, difficult determination of resection margins, controversial efficacy assessment, and lack of effective early warning for adverse reactions. This study will systematically identify biomarkers for early diagnosis and recurrence monitoring through multi-omic analysis of peripheral blood immune cell subsets and non-invasive liquid biopsies; investigate the tumor immune microenvironment's role in immunotherapy response mechanisms and predict treatment efficacy via multi-omic studies of tissue specimens; develop novel AI- and radiomics-assisted pathological assessment systems and prognostic prediction models; implement perioperative symptom assessment for timely identification of immune-related adverse events (irAEs) while conducting prehabilitation training for perioperative nursing care.
Study Type
OBSERVATIONAL
Enrollment
350
Pathological Complete Response (pCR)
Pathologic Complete Response (pCR) is defined as the absence of residual tumor in both the primary lung tumor site and all sampled regional lymph nodes after neoadjuvant immunotherapy, confirmed through systematic pathological examination of the surgical specimen.
Time frame: At surgery (typically 3-6 months post-treatment initiation)
Major Pathological Response (MPR)
Major Pathologic Response (MPR) is defined as the presence of ≤10% residual viable tumor cells in both the primary lung tumor site and sampled regional lymph nodes after neoadjuvant immunotherapy, confirmed through systematic pathological examination of the surgical specimen.
Time frame: At surgery (typically 3-6 months post-treatment initiation)
Objective Response Rate (ORR)
ORR is defined as the proportion of patients achieving either a complete response (CR; disappearance of all target lesions) or partial response (PR; ≥30% reduction in the sum of target lesion diameters) during or after neoadjuvant immunotherapy, as assessed by serial imaging (CT/PET-CT) using iRECIST criteria.
Time frame: After two cycles or four cycles of neoadjuvant therapy (each cycle is 21 days).
Recurrence-free Survival (RFS)
Time from randomization to disease recurrence or death from any cause.
Time frame: Through study completion, an average of 2 years
Overall Survival (OS)
Time from randomization to death from any cause.
Time frame: Through study completion, an average of 2 years
MRD (minimal residual disease) dynamics after neoadjuvant immunotherapy
Postoperative dynamics of ctDNA-based MRD and timely detection of recurrence or metastasis in lung cancer patients receiving neoadjuvant immunotherapy.
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Time frame: Periprocedural and every three to six months post-treatment (up to three years)
Symptom Severity Score
Assessment of perioperative symptom burden (e.g., pain, fatigue) using validated scales like the MDASI-C (M. D. Anderson Symptom Inventory) for lung cancer patients.
Time frame: Preoperative (T1: 2-4 weeks pre-surgery), postoperative (e.g., T3: 12-24 hours post-surgery, T5: 30 days post-surgery), and up to 90 days post-surgery.
Immune-Related Adverse Event (irAE) Incidence
Frequency and severity of adverse events (e.g., rash, colitis) related to immunotherapy, graded using standardized criteria like CTCAE (Common Terminology Criteria for Adverse Events).
Time frame: Periprocedural and up to 6 months post-treatment.
Changes in PD-L1 expression (TPS) and TIL subpopulations (CD8+/FOXP3+ ratios, et al) before and after neoadjuvant immunotherapy
PD-L1 expression (22C3 pharmDx assay; TPS ≥1% cutoff), multiplex immunofluorescence (CD8: clone C8/144B; FOXP3: clone 236A/E7) and multomoics analyses were performed on paired pre-/post-NAD biopsies.
Time frame: Periprocedural.