Organ-Specific Differences in Immunotherapy Response Among Metastatic Cancer Patients

Real-world Evidence and Multi-omics Insights Into Differential Immunotherapy Responses Between Primary and Metastatic Sites

This study examines how tumors in different metastatic organs respond to immune checkpoint inhibitor (ICB) therapy in real-world clinical practice. ICB therapy helps the immune system recognize and attack cancer cells, but treatment responses may vary depending on where the cancer has spread. Common metastatic sites such as the liver, brain, lung, and bone each have unique immune environments that may influence treatment outcomes.

The investigators will review the medical records of approximately 1,000 adults with solid tumors who received ICB therapy at Sun Yat-sen Memorial Hospital, the Third Affiliated Hospital of Sun Yat-sen University, and the First Affiliated Hospital of Chongqing Medical University since 2016. The study will compare treatment response, time until disease progression, and overall survival among patients with different metastatic sites. Additional outcomes include disease control, immunotherapy-related side effects, and concordance between primary and metastatic tumor responses.

The study will also analyze available molecular and immune-profiling datasets to explore biological mechanisms that may explain organ-specific differences in ICB response. The goal is to improve understanding of how metastatic sites influence immunotherapy effectiveness and to support future treatment decision-making.

Study Overview

• Status: Completed
• Conditions: Solid Tumors; Brain Metastasis; Immune Checkpoint Inhibitors; Metastatic Cancers; Metastatic Cancer to Liver; Metastatic Cancer to the Lung; Metastatic Cancer to the Bone; Tumor Immune Microenvironment

• Study Type: Observational
• Enrollment (Actual): 938

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

This study includes adults with solid tumors who developed metastatic cancer in the brain, liver, lung, or bone. All participants received first-line or second-line immune checkpoint inhibitor (ICB) therapy and completed at least three treatment cycles with available imaging follow-up. The study population represents real-world patients treated at Sun Yat-sen Memorial Hospital, the Third Affiliated Hospital of Sun Yat-sen University, and the First Affiliated Hospital of Chongqing Medical University, with complete clinical and survival data that allow evaluation of organ-specific treatment response and progression. Individuals with unclear metastatic sites, incomplete treatment information, or major data gaps were not included.

Description

Inclusion Criteria:

• Age ≥18 years.
• Pathologically confirmed solid tumor with a documented primary tumor site.
• At least one metastatic site in the brain, liver, lung, or bone confirmed by imaging or pathology (single or multiple lesions allowed).
• Received first-line or second-line immune checkpoint inhibitor (ICB) therapy, including PD-1, PD-L1, or CTLA-4 inhibitors, either alone or in combination.
• Completed at least 3 cycles of ICB therapy.
• At least one evaluable imaging follow-up after initiation of immunotherapy.
• Available clinical and follow-up data, including treatment initiation date, response assessment, progression status, and survival status.
• Meets institutional ethics requirements for retrospective studies.

Exclusion Criteria:

• Unclear or undocumented metastatic site, or lack of imaging/pathologic evidence supporting metastasis.
• ICB treatment regimen cannot be clearly determined (e.g., unclear combination therapy components).
• Missing more than 20% of key clinical variables or incomplete follow-up data (e.g., missing PFS or OS information).
• Received fewer than 3 cycles of ICB therapy.
• Major treatment interruption or poor treatment adherence.
• Concurrent active malignancy that may interfere with outcome assessment.
• Severe immune-related disease (e.g., systemic lupus erythematosus) or organ transplantation requiring long-term immunosuppression.
• Participation in another interventional clinical trial that may affect treatment evaluation.
• Data errors or logical inconsistencies that cannot be resolved after review.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Metastatic cancers treated with immune checkpoint inhibitors

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Organ-Specific Objective Response Rate (osORR)	osORR is the percentage of patients whose tumors in a specific metastatic organ (brain, liver, lung, or bone) achieve a complete response (CR) or partial response (PR) following immunotherapy, as assessed according to RECIST v1.1. Each metastatic organ is evaluated separately.	At first radiographic assessment after immunotherapy initiation (approximately 6-12 weeks).
Organ-Specific Progression-Free Survival (osPFS)	osPFS is defined as the time from initiation of immunotherapy to disease progression within the specific metastatic organ or death from any cause, whichever occurs first. Progression is assessed according to RECIST v1.1 based on target lesions within the corresponding organ, regardless of progression occurring in other organs.	Up to 5 years.
Overall Survival (OS)	In this retrospective study, OS is defined as the time from initiation of immune checkpoint blockade (ICB) therapy to death from any cause. Survival time is determined using available longitudinal follow-up records. Patients who are alive at the last follow-up will be censored.	From start of ICB treatment until death from any cause (up to 5 years).

Collaborators and Investigators

• Sponsor: Wenlong Zhong, MD
• Collaborators: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University; Third Affiliated Hospital, Sun Yat-Sen University; First Affiliated Hospital of Chongqing Medical University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Actual): May 20, 2026
• Study Completion (Actual): May 20, 2026

Study Registration Dates

• First Submitted: May 28, 2026
• First Submitted That Met QC Criteria: June 3, 2026
• First Posted (Actual): June 8, 2026

Study Record Updates

• Last Update Posted (Actual): June 8, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Nervous System Neoplasms; Central Nervous System Neoplasms; Neoplasms; Brain Neoplasms
• Other Study ID Numbers: SYSKY-2025-902-01

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
• product manufactured in and exported from the U.S.: No