Ultrasound-Guided High-Intensity Focused Ultrasound Combined With PD-1 Blockade in Patients With Liver Metastases From Lung Cancer: Protocol for a Single-Arm Phase 2 Trial
Bibliographic record
Abstract
BACKGROUND: While immunotherapy has revolutionized oncological management, its efficacy in lung cancer patients with liver metastases remains limited, potentially due to the unique immunosuppressive microenvironment of the liver. Local liver treatment has been shown to enhance the immunotherapy response, and high-intensity focused ultrasound (HIFU), a minimally invasive local treatment, has demonstrated promising results in combination with immunotherapy. However, clinical data regarding HIFU in lung cancer with liver metastases are limited. OBJECTIVE: We designed the HILL (Ultrasound-Guided High-Intensity Focused Ultrasound Combined With PD-1 Blockade in Patients With Liver Metastases From Lung Cancer) study to investigate the effectiveness and safety of HIFU in combination with immunotherapy for lung cancer with liver metastases. METHODS: The HILL study is a single-armed, single-center, phase 2 clinical trial that will enroll 30 patients with lung cancer and liver metastases. The treatment regimen involves administering HIFU to liver metastases 1 week before the first dose of a programmed cell death protein (PD)-1 blockade, which is then administered every 3 weeks. The primary aim is to determine the overall response rate based on immune-related response criteria. Secondary aims include safety, progression-free survival, overall response, overall survival, and quality of life. Exploratory studies will also be conducted using whole blood, plasma, archival cancer tissue, and tumor biopsies during progression or relapse to identify potential biomarkers. RESULTS: The study was funded on March 14, 2022, and received ethical approval on April 27, 2022. Clinical trial registration was completed by June 10, 2022, with participant recruitment beginning on July 10, 2022. Data collection commenced on July 14, 2022, with the enrollment of the first patient. By April 2024, 6 participants had been recruited. The results are expected to be published in December 2026. CONCLUSIONS: This study seeks to improve treatment outcomes for lung cancer patients with liver metastases by combining HIFU and PD-1 inhibition. The study also aims to identify potential biomarkers through exploratory research that can aid in selecting patients for optimized outcomes in the future. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200061076; https://www.chictr.org.cn/showproj.html?proj=170967. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/59152.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.014 | 0.010 |
| Meta-epidemiology (narrow) | 0.005 | 0.002 |
| Meta-epidemiology (broad) | 0.006 | 0.003 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.003 | 0.002 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.006 | 0.007 |
| Insufficient payload (model declined to judge) | 0.025 | 0.007 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".