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.

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.