A Prospective Observational Study of Changes in Cortisol Levels After Neoadjuvant Immunotherapy and Their Prognostic Value in Patients With NSCLC

This study is an open, prospective and observational clinical trial. Adopting a prospective cohort study design, it selects patients with non-small cell lung cancer who receive neoadjuvant immunotherapy as the research subjects. Through systematic follow-up, it monitors the dynamic changes of cortisol levels of patients at different treatment stages and after surgery, and analyzes the associations between these changes and disease progression, treatment effect and adverse reactions.

Study Overview

• Status: Active, not recruiting
• Conditions: NSCLC

Detailed Description

This is a single-center prospective observational cohort study. No experimental intervention will be performed on the participants, all clinical treatments and examinations are fully in accordance with the routine clinical diagnosis and treatment specifications for resectable non-small cell lung cancer. We only prospectively collect the clinical data and laboratory test results of the participants to analyze the correlation between perioperative dynamic changes of cortisol and the outcomes of neoadjuvant immunochemotherapy.

• Study Type: Observational
• Enrollment (Estimated): 330

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Guangdong Provincial People's Hospital, Guangzhou, Guangdong 510000

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This is a single-center prospective observational cohort study. The study population includes adult patients aged 18-75 years with histologically confirmed resectable stage ⅡA-ⅢB non-small cell lung cancer (NSCLC), who receive standard neoadjuvant PD-1/PD-L1 inhibitor combined with platinum-based chemotherapy followed by radical surgery in our center.

Description

Inclusion Criteria:

1. Histologically confirmed primary non-small cell lung cancer (NSCLC), with clinical stage ⅡA-ⅢB resectable/potentially resectable disease, assessed according to the 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system.
2. Aged 18 to 75 years old, with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
3. Planned to receive standard neoadjuvant PD-1/PD-L1 immune checkpoint inhibitor combined with platinum-based doublet chemotherapy, followed by radical surgical resection.
4. Have complete clinical data, and can complete the scheduled perioperative blood tests (including serum cortisol and ACTH level detection) and follow-up visits according to the study protocol.
5. Voluntarily participate in this study, sign the written informed consent form, and are willing to cooperate with the research team to complete the study-related examinations and follow-up.

Exclusion Criteria:

1. Patients with confirmed pituitary or adrenal diseases, or abnormal baseline serum cortisol/ACTH levels outside the normal reference range before enrollment.
2. Patients with a history of long-term systemic glucocorticoid use within 3 months before enrollment, or perioperative glucocorticoid use before the postoperative cortisol test.
3. Patients with a history of other primary malignant tumors within 5 years before enrollment (except for cured basal cell carcinoma of the skin or cervical carcinoma in situ).
4. Patients with severe autoimmune diseases, severe liver and kidney dysfunction, severe cardiovascular and cerebrovascular diseases, or other comorbidities that cannot tolerate neoadjuvant therapy and radical surgery.
5. Patients who did not receive radical surgical resection after neoadjuvant therapy.
6. Patients with incomplete clinical data, who cannot complete the scheduled blood tests or follow-up visits.
7. Pregnant or lactating women.
8. Patients with mental illness or other conditions that cannot comply with the study protocol.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Prospective Observational Cohort of Resectable NSCLC Patients; This cohort includes patients with pathologically confirmed resectable stage ⅡA-ⅢB non-small cell lung cancer (NSCLC) who receive standard neoadjuvant PD-1/PD-L1 inhibitor combined with platinum-based doublet chemotherapy followed by radical surgery. This is a purely observational cohort: no study-specific intervention will be applied, all treatments and examinations are performed in full accordance with routine clinical practice. We will prospectively collect patients' clinical data, laboratory test results (including serum cortisol and ACTH levels) and pathological outcomes, to analyze the correlation between perioperative dynamic changes of cortisol and neoadjuvant treatment efficacy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Pathological Response (MPR) Rate	Proportion of patients who achieved major pathological response, defined as viable residual tumor cells ≤10% in the resected primary tumor specimen after neoadjuvant immunochemotherapy, assessed according to IASLC standardized criteria.	Within 30 days after radical surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation Between Perioperative Cortisol Dynamic Changes and Pathological Response	The correlation between the relative change rate of serum cortisol (from baseline before neoadjuvant therapy to 1 day after surgery) and the proportion of residual viable tumor cells, as well as the achievement of MPR/pCR.	From baseline (within 7 days before neoadjuvant treatment initiation) to 7 days after radical surgery
Incidence of Immune Checkpoint Inhibitor (ICIs)-Related Adrenocortical Dysfunction	The cumulative incidence of ICIs-related secondary adrenocortical dysfunction, including clinical and subclinical adrenocortical insufficiency, confirmed by serum cortisol and adrenocorticotropic hormone (ACTH) test results, assessed according to the Endocrine Society Clinical Practice Guidelines.	From neoadjuvant treatment initiation to 12 months after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Immune-Related Adverse Events (irAEs)	The cumulative incidence of all-grade and grade ≥3 irAEs during neoadjuvant treatment and 12 months after surgery, including endocrine toxicity, pulmonary toxicity, cutaneous toxicity, etc., graded according to CTCAE version 5.0.	From neoadjuvant treatment initiation to 12 months after surgery
Disease-Free Survival (DFS)	The time from radical surgery to the first occurrence of tumor recurrence, distant metastasis, or all-cause death, whichever comes first.	From radical surgery to 36 months after surgery
Overall Survival (OS)	The time from the initiation of neoadjuvant treatment to all-cause death.	From neoadjuvant treatment initiation to 36 months after treatment initiation

Collaborators and Investigators

• Sponsor: Guangdong Provincial People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: April 8, 2026
• First Submitted That Met QC Criteria: April 8, 2026
• First Posted (Actual): April 15, 2026

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 8, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: KY2025-935

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No