Multimodal Model Predicts Treatment Efficacy and CIP Risk in Advanced NSCLC With Immunotherapy and Chemotherapy

The Multimodal Model Predicts the Efficacy of Immunotherapy Checkpoint Inhibitors Combined With Chemotherapy for the Treatment of Advanced Non-small Cell Lung Cancer and the Occurrence Risk of Chemotherapy-induced Pneumonitis

Immunotherapy is a crucial first-line treatment for advanced non-small cell lung cancer (NSCLC) without gene mutations. However, chemotherapy-induced pneumonitis (CIP) is a common adverse effect of immunotherapy, with severe cases even posing a threat to life. Therefore, identifying effective biomarkers and models for predicting the efficacy of immunotherapy in NSCLC is of great significance. At present, there is still a lack of effective predictive indicators in clinical practice. This study aims to construct a multimodal model based on factors such as chest CT, pulmonary function, cellular immunity, and cytokine levels to accurately predict the efficacy of combined therapy and the occurrence of related adverse reactions in NSCLC, in order to provide a reference for individualized treatment.

Study Overview

• Status: Completed
• Conditions: NSCLC
• Intervention / Treatment: Other: This study is an observational study; the intervention is not applicable.

Detailed Description

This is an observational cross-sectional retrospective study.

• Study Type: Observational
• Enrollment (Actual): 3000

Contacts and Locations

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • 180 Fenglin Road

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with inoperable stage IIIB to IV NSCLS using immune checkpoint inhibitors in combination with chemotherapy.

Description

Inclusion Criteria:

1. Consistent with the "Chinese Medical Association Guidelines for the Diagnosis and Treatment of Lung Cancer (2018 Edition)," histologically confirmed as NSCLC;
2. According to the 8th edition of the AJCC TNM staging system, it is stage III B to IV and not suitable for surgery;
3. Age ≥18 years;
4. First-time recipients of immunotherapy combined with chemotherapy;
5. Baseline data within 1 month before the start of treatment is complete (at least including chest CT, pulmonary function, and laboratory tests);
6. At least 1 measurable lesion according to RECIST 1.1;
7. Receiving immune checkpoint inhibitor therapy for more than 2 cycles;
8. Clinical data is complete.

Exclusion Criteria:

1. Presence of other malignant tumors;
2. Previous exposure to immunotherapy or systemic chemotherapy;
3. Patients with severe dysfunction of vital organs (heart, liver, lungs, kidneys) and bone marrow at baseline;
4. Presence of severe infectious diseases, active autoimmune diseases, or immune deficiencies that significantly affect immune function;
5. Organ transplantation;
6. Pregnant or lactating women;
7. Incomplete clinical treatment or follow-up information.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Training cohort; for feature selection and model construction	Other: This study is an observational study; the intervention is not applicable.; This study is an observational study; the intervention is not applicable.
Internal validation cohort; for hyperparameter optimization and overfitting monitoring	Other: This study is an observational study; the intervention is not applicable.; This study is an observational study; the intervention is not applicable.
External validation cohort; an independent cohort for final model validation	Other: This study is an observational study; the intervention is not applicable.; This study is an observational study; the intervention is not applicable.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	Time from the first dose of immune-checkpoint inhibitor plus chemotherapy to the earliest date of radiologic progression (per RECIST 1.1) or death from any cause.	From first dose through 31 August 2025, corresponding to a maximum follow-up of approximately 5.5 years (~290 weeks).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The disease control rate (DCR)	Proportion of patients achieving complete response (CR), partial response (PR), or stable disease (SD) as best overall response per RECIST 1.1.	Tumor response assessed every 6 weeks (±1 week) for up to 24 weeks or until progression/death/cut-off (31 Aug 2025); the proportion will be calculated from the best response recorded within the first 24 weeks (4 cycles) per RECIST 1.1.
Checkpoint inhibitor pneumonitis (CIP)	an immune-related adverse event (irAE) endpoint refers to new pulmonary infiltrates on chest imaging after immune checkpoint inhibitor (ICI) treatment, accompanied by dyspnea and/or other respiratory signs/symptoms (including cough and exertional dyspnea), excluding new pulmonary infections or tumor progression.	Within 4 months after the initiation of immunotherapy combined with chemotherapy.

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital
• Investigators: Principal Investigator: Nuo Xu, Shanghai Zhongshan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Actual): February 28, 2025
• Study Completion (Actual): August 31, 2025

Study Registration Dates

• First Submitted: November 15, 2025
• First Submitted That Met QC Criteria: November 20, 2025
• First Posted (Actual): November 24, 2025

Study Record Updates

• Last Update Posted (Actual): November 24, 2025
• Last Update Submitted That Met QC Criteria: November 20, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: B2025-594R

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