Clinical Outcomes and Immunotherapy in Lung Cancer With Pulmonary Fibrosis (IPF-LC-IO)

Clinical Characteristics, Prognosis, and Immunotherapy Outcomes in Patients With Lung Cancer and Concomitant Pulmonary Fibrosis: An Observational Study Integrated With Single-Cell and Spatial Transcriptomics

This retrospective observational study evaluates immune checkpoint inhibitor (ICI)-related outcomes in lung cancer patients with concomitant pulmonary fibrosis/interstitial lung disease (ILD) and determines how fibrosis/ILD modifies immunotherapy effectiveness and safety. The study characterizes the clinical, radiographic, pathological, and molecular features of lung cancer with ILD and examines their associations with ICI response and survival. A comparator cohort of lung cancer patients without radiographic ILD from the same institution and time period is included to compare ICI effectiveness (e.g., response and survival outcomes) and pulmonary toxicity signals, including pneumonitis and acute ILD exacerbation.

In a translational sub-study, archived lung tumor specimens undergo single-cell and spatial transcriptomic profiling to identify fibrosis-associated tumor-microenvironment programs that may underlie differential immunotherapy outcomes.

Study Overview

• Status: Active, not recruiting
• Conditions: Pulmonary Fibrosis; Lung Cancer (Diagnosis); Interstitial Lung Diseases
• Intervention / Treatment: Other: there is no intervention

Detailed Description

Lung cancer with concomitant pulmonary fibrosis/interstitial lung disease (ILD) represents a clinically challenging population in which immune checkpoint inhibitor (ICI) treatment may be influenced by baseline lung vulnerability and a distinct tumor immune microenvironment. This single-center retrospective observational cohort study evaluates how fibrosis/ILD status and related clinical features are associated with immunotherapy use, effectiveness, and safety.

Patients with pathologically confirmed lung cancer and radiographic evidence of pulmonary fibrosis/ILD diagnosed and treated at Jiangsu Province Hospital (The First Affiliated Hospital of Nanjing Medical University) are identified. A comparator cohort of lung cancer patients without radiographic ILD from the same institution and time period is assembled to enable direct comparisons of immunotherapy outcomes. Baseline demographics, smoking history, comorbidities, pulmonary function and imaging features (when available), tumor histology and stage, relevant laboratory indices, and molecular testing results are collected and analyzed. Associations between these variables and ICI exposure or clinical outcomes are evaluated.

Primary analyses focus on immunotherapy-related endpoints, including real-world measures of ICI effectiveness such as objective response and survival outcomes captured in routine clinical care. Safety analyses include ILD-relevant outcomes such as immune-related pneumonitis, acute exacerbation of underlying ILD, treatment interruption or discontinuation, and other clinically significant pulmonary adverse events. Comparative analyses evaluate whether patients with lung cancer and fibrosis/ILD experience different ICI effectiveness or higher pulmonary toxicity risk compared with patients without ILD. Additional analyses explore which clinical, radiographic, pathological, or molecular features within the ILD cohort are associated with favorable or unfavorable immunotherapy outcomes.

To investigate potential mechanisms underlying differential immunotherapy responses in fibrosis-associated lung cancer, a translational sub-study analyzes available archived lung tumor specimens (e.g., bronchoscopic biopsy, computed tomography-guided biopsy, or surgical samples). Single-cell transcriptomics and spatial transcriptomics are performed to compare tumors arising in a fibrotic lung environment with tumors from patients without ILD. These analyses identify fibrosis-associated cellular states, immune microenvironment composition, and signaling programs that may contribute to altered immunotherapy sensitivity or toxicity. Findings from the multi-omics analyses are integrated with clinical outcome data to generate mechanistic hypotheses and potential biomarkers relevant to immunotherapy decision-making in lung cancer patients with pulmonary fibrosis/ILD.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • The First Affiliated Hospital of Nanjing Medical University

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Retrospective, single-center observational cohort study of patients with pathologically confirmed lung cancer and imaging-confirmed interstitial lung disease (ILD) diagnosed at Jiangsu Provincial People's Hospital between January 2019 and September 2025. Eligible cases will be identified from hospital information systems and clinical records. Clinical characteristics, laboratory results, imaging, pathology and molecular reports will be extracted from Hospital Information System (HIS), Laboratory Information System (LIS), and Picture Archiving and Communication System (PACS) databases. Available tumor tissue specimens (bronchoscopic biopsy, CT-guided lung biopsy, or surgically resected lung tissue) will be collected for spatial transcriptomics analysis. Patients whose tumor location does not overlap with ILD-involved areas will be excluded.

Description

Inclusion Criteria:

• Pathologically confirmed lung cancer.

Interstitial lung disease identified on chest imaging (e.g., high-resolution computed tomography).

Diagnosed and treated at Jiangsu Provincial People's Hospital between January 2019 and September 2025.

Exclusion Criteria:

• The anatomical location of the lung cancer lesion does not overlap with the ILD-involved area.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Lung cancer without pulmonary fibrosis; patients with lung cancer without lung fibrosis	Other: there is no intervention; there is no intervention
Lung cancer with pulmonary fibrosis	Other: there is no intervention; there is no intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS)	up to 36 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival (PFS)	up to 36 months
Objective response rate (ORR)	up to 36 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events (AEs)	adverse event	up to 36 months

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: February 1, 2026
• First Submitted That Met QC Criteria: February 1, 2026
• First Posted (Actual): February 9, 2026

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 15, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Lung cancer; Interstitial lung disease; Tumor microenvironment; Immune checkpoint inhibitor; Pulmonary fibrosis; Single-cell RNA sequencing
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Fibrosis; Pathological Conditions, Signs and Symptoms; Lung Neoplasms; Disease; Pulmonary Fibrosis; Lung Diseases, Interstitial
• Other Study ID Numbers: IPF-LC-001

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