Non-Small-Cell Lung Cancer
Conditions
Keywords
lung cancer, radiotherapy, immunotherapy, single-cell sequencing, SBRT, peripheral blood mononuclear cell, minimalResidual disease
Brief summary
This study aims to evaluate the efficacy and safety of SBRT combined with Puterizumab immunotherapy for non-small cell lung cancer with pulmonary metastases, and to determine the correlation between MRD and treatment efficacy. Through single-cell sequencing and spatial transcriptome information analysis, the underlying mechanisms will be analyzed to provide a basis for improving the new precision treatment methods for tumor immunotherapy resistance.
Interventions
RADIATIONStereotactic Body Radiation Therapy，SBRT
The enrolled subjects will receive SBRT treatment for lung metastases.The dose segmentation is 10Gy/f, with a total dose of 50Gy/5f, once every other day.
DRUGPuterizumab
Within 7-14 days after SBRT, Puterizumab should be used (dosage: recommended dosage of 200mg, intravenous infusion, infusion time of 60 minutes (± 15 minutes), once every 3 weeks (Q3W), for 6-8 months or intolerable toxicity).
Sponsors
Sir Run Run Shaw Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. age≥18 2. Non small cell lung cancer patients who have experienced pulmonary metastasis after PD-1 immunotherapy in the past 3. Voluntarily participate in this study and sign an informed consent form 4. The presence of evaluable size and number of pulmonary metastases on chest CT 5. There are indications for lung puncture biopsy 6. General physical condition (ECOG) 0-1 7. The laboratory test meets the following standards: white blood cell count\>3.5 × 109/L, absolute value of neutrophils\>1.8 × 109/L, platelet count ≥ 75 × 109/L, hemoglobin ≥ 100g/L; NR ≤ 1.5, and APTT ≤ 1.5 times the upper limit of normal value or partial prothrombin time (PT) ≤ 1.5 times the upper limit of normal value; Total bilirubin ≤ 1.25 times the upper limit of normal value; ALT and AST\<5 times the upper limit of normal values; 24-hour creatinine clearance rate\>50mL/min or blood creatinine\<1.5 times the upper limit of normal value.
Exclusion criteria
1. Unable to tolerate or refuse further immunotherapy 2. Vulnerable groups, including individuals with mental illness, cognitive impairment, critically ill patients, minors, pregnant women, illiteracy, etc
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| tumor response rate | From the date of enrollment until the first record of tumor progression or any cause of death (whichever comes first), evaluations will be conducted 3 weeks and every 3 months after SBRT for up to 48 months. | The tumor response rate will evaluate the local control of lung metastases，referring to the evaluation criteria for solid tumor efficacy RECIST 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Minor Residual Lesions | From the date of enrollment until the first record of tumor progression or any cause of death (whichever comes first), evaluations will be conducted 3 weeks and every 3 months after SBRT for up to 48 months. | Using the minimal residual disease (MRD) panel for ctDNA molecular residual detection, and through ctDNA multi-node assessment, we can dynamically monitor the therapeutic efficacy and disease recurrence. |
| progression-free survival | From the date of enrollment until the first record of tumor progression or any cause of death (whichever comes first), evaluations will be conducted 3 weeks and every 3 months after SBRT for up to 48 months. | PFS is the time from enrollment to tumor progression or death. |
| overall survival | From the date of enrollment until the first record of tumor progression or any cause of death (whichever comes first), evaluations will be conducted 3 weeks and every 3 months after SBRT for up to 48 months. | OS is the time from enrollment to death due to any reason. |
| RTOG acute radiation injury grading | From the date of enrollment until the first record of tumor progression or any cause of death (whichever comes first), evaluations will be conducted during the entire SBRT process and monthly after SBRT for up to 12 months. | Refer to the acute radiation injury grading standards of the United States Collaborative Group on Tumor Radiotherapy (RTOG) |
| QLQ-30 score | From the date of enrollment until the first record of tumor progression or any cause of death (whichever comes first), evaluations will be conducted 3 weeks and every 3 months after SBRT for up to 48 months. | The quality of life will be evaluated using the QLQ-30 score. |
| Lymphocyte subpopulation analysis | From the date of enrollment until the first record of tumor progression or any cause of death (whichever comes first), evaluations will be conducted 3 weeks and every 3 months after SBRT for up to 48 months. | Using flow cytometry to detect the count and percentage of lymphocytes, including CD3+, CD3+, CD4+, CD3+, CD8+, CD4+/CD8+, and CD3-CD56+. |
Contacts
Primary ContactXiaonan Sun, Ph D
Backup ContactXuyun Xie, MD
Outcome results
None listed