Circulating Tumor DNA and T Cell Repertoire Predict Radiotherapeutic Outcomes in NSCLC Patients With Brain Metastasis

NCT ID: NCT05737589

Last Updated: 2023-02-21

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 50 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-02-13
• Study Completion Date: 2024-10-01

Brief Summary

Collection of ctDNA and TCR data to predict the efficacy and prognosis of brain radiotherapy in patients with brain metastases from non-small cell lung cancer (NSCLC) in a comprehensive manner

Detailed Description

The scarcity of biopsies or focal resections for brain metastases limits the discovery of biomarkers for diagnosing and prognosis of NSCLC patients with brain metastases. Circulating tumor DNA (ctDNA) is derived from the necrosis, apoptosis, and secretion of tumor cells and is widely distributed in various body fluids, including peripheral blood and cerebrospinal fluid (CSF). Genomic alterations in blood and CSF ctDNA are prognostic markers in NSCLC patients with brain metastases. Still, they have limited predictive power. T cell-mediated immune responses are essential to suppress carcinogenesis and metastasis in NSCLC. Targeted sequencing in the highly variable complementarity determining region 3 (CDR3) region of the T cell receptor (TCR) β-chain provides a powerful approach to quantifying the diversity of T cells. Radiotherapy causes antigen exposure through direct local destruction of cancer cells, which activates the local and systemic immune system. Radiotherapy can also cause intracellular DNA damage, and the ensuing mutations in DNA mismatch repair defects may increase neoantigen load, triggering an immune response. The TCR, closely related to immune system modifications, can also be altered by radiotherapy. However, no clinical studies have explored ctDNA and TCR to predict the efficacy and prognosis of brain radiotherapy in patients with NSCLC brain metastases. Therefore, we retrieved the visit data of 50 patients with advanced NSCLC brain metastases who received brain radiotherapy through the hospital electronic medical record system and recorded the ctDNA and TCR values of patients' blood and CSF at baseline (within 2 weeks before radiotherapy), T0 (within 24 hours after the completion of radiotherapy) and T28 (28 days after the completion of radiotherapy), disease progression recurrence and survival time by examining. The dynamic changes of ctDNA and TCR during brain radiotherapy were studied to comprehensively assess the ability of ctDNA and TCR to predict the efficacy and prognosis of brain radiotherapy in patients with NSCLC brain metastases.

Conditions

Carcinoma, Non-Small-Cell Lung; Brain Metastases

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Observation group

This is an observational study, no interventions will be applied to patients in the observation group, and only blood and cerebrospinal fluid ctDNA and TCR data of patients with brain metastases from non-small cell lung cancer treated with radiotherapy will be recorded to predict patient prognosis. Peripheral blood and CSF samples were collected at baseline, 24 h (T0), and 28 days (T28) after completion of radiotherapy and underwent deep sequencing of ctDNA and TCR. The 6-month response rates of brain metastases and systemic lesions were evaluated based on Response Evaluation Criteria in Solid Tumors version 1.1 for further study.

Whole-brain radiotherapy

Intervention Type: RADIATION

Radiotherapy is administered to the patient's brain lesions, and the subject's specific treatment plan is developed by two specialized physicians.

Interventions

Whole-brain radiotherapy

Radiotherapy is administered to the patient's brain lesions, and the subject's specific treatment plan is developed by two specialized physicians.

Intervention Type: RADIATION

Other Intervention Names

Stereotactic radiotherapy

Eligibility Criteria

Inclusion Criteria

1. Age > 18 years

2. Patients must have histologically or cytologically confirmed NSCLC and imaging-confirmed primary non-small cell lung cancer with brain metastases

3. ECOG PS score of 0-2

4. At least 1 lesion meeting RECIST 1.1 target lesion (TL) criteria at baseline. Must have baseline assessment imaging of the tumor by CT or MRI scan within 28 days prior to treatment

5. No prior radiation therapy to the tumor, including but not limited to whole brain radiotherapy, prophylactic brain irradiation, stereotactic radiation therapy, etc.

6. Major organ function indicators meet the criteria for conventional radiation therapy Adequate organ and bone marrow function is defined as follows

1. Hemoglobin ≥ 9.0 g/dL

2. absolute neutrophil count ≥ 1.5 × 109 / L

3. Platelet count ≥ 100 × 109 / L

4. Serum bilirubin ≤ 1.5 × the upper limit of normal (ULN). The above criteria were not applied to patients diagnosed with Gilbert's syndrome, but these patients were allowed to be enrolled after consultation between the study physician and their primary care physician.

5. Alanine aminotransferase ALT or aspartate aminotransferase AST ≤ 2.5 × ULN

6. Creatinine clearance (CL) > 40 mL/min calculated or actually measured according to the Cockcroft-Gault method (based on actual body weight) Men. Creatinine CL = Body weight (kg) × (140 - age) (mL/min) 72 x serum creatinine (mg/dL) Females. Creatinine CL = Body weight (kg) × (140 - age) × 0.85 (mL/min) 72 × serum creatinine (mg/dL)

7. Female subjects of childbearing age must exclude pregnancy

8. Life expectancy >12 weeks

9. Body weight >30Kg

Exclusion Criteria

1. History of allogeneic organ transplantation

2. Active or previously documented autoimmune or inflammatory disease (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis (except diverticular disease), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener's syndrome [granulomatous vasculitis, Graves' disease, rheumatoid arthritis, pituitary inflammation, uveitis, etc.])

3. History of active primary immunodeficiency

4. Other malignancies within the last 3 years.

5. Presence of uncontrolled co-morbidities including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmias, active interstitial lung disease, a severe chronic gastrointestinal disease with diarrhea or mental illness that limits compliance with study requirements, significantly increases the risk of AE or affects the patient's life/ social conditions

6. Active infection at the time of treatment, including tuberculosis (clinical assessment includes history, physical examination, imaging findings, and tuberculosis screening consistent with local clinical practice), hepatitis B (known hepatitis B surface antigen positive [HBsAg] result), hepatitis C virus (HCV) or human immunodeficiency virus (HIV 1/2 antibody positive). Patients with previous hepatitis B virus (HBV) infection or cured HBV infection (defined as the presence of positive hepatitis B core antibodies and negative HBsAg) may participate in this study. patients with positive HCV antibodies who are negative for HCV ribonucleic acid (RNA) by polymerase chain reaction only may participate in this study.

7. Stage IV NSCLC according to the 8th edition of the International Society for the Study of Lung Cancer Thoracic Oncology Staging Manual

8. Histological findings of NSCLC with mixed small cell component

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Xiaorong Dong

OTHER

Sponsor Role: lead

Responsible Party

Xiaorong Dong

Professor/Chief Physician

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Xiaorong Dong, Dr.

Role: STUDY_CHAIR

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Locations

Union hospital

Wuhan, Hubei, China

Countries

China

Central Contacts

Xiaorong Dong, Dr.

Role: CONTACT

xiaorongdong@hust.edu.cn

13986252286

Other Identifiers

DTO-20230201

Identifier Type: -

Identifier Source: org_study_id