Non Small Cell Lung, Brain Metastasases
Conditions
Brief summary
The goal of this observational study is to learn about the effects of the timing of radiation therapy and immunotherapy in adults with non-small cell lung cancer (NSCLC) that has spread to the brain. The main questions it aims to answer are: 1. Does the timing of the two treatments change how long the brain tumor stays stable and how long participants live? 2. What medical problems do participants have when receiving these treatments at different times? 3. How does the timing of treatments affect the body's immune system? Researchers will compare participants who receive radiation and immunotherapy 30 days or less apart to those who receive them more than 30 days apart to see if the timing affects the treatment's success and safety. Participants already receiving radiation and immunotherapy as part of their regular medical care will: 1. Allow researchers to collect information about their treatment, health, and medical imaging during regular checkups. 2. Give a small blood sample during their routine blood draws. 3. Have standard magnetic resonance imaging (MRI) scans of their brain.
Interventions
RADIATIONBrain radiotherapy
Participants in this observational study receive standard-of-care radiotherapy for brain metastases combined with PD-1/PD-L1 immune checkpoint inhibitors. The specific radiotherapy parameters (e.g., technique, target volume, and dose) and immunotherapy details (e.g., specific drug type, dosage, and administration schedule) are entirely determined by the treating physicians or multidisciplinary team (MDT) based on current clinical guidelines and real-world practice. This study does not assign, alter, or proactively intervene in any treatment plans. What distinguishes the exposure in this study is the specific tracking and categorization of the real-world timing interval and administration sequence between radiotherapy and immunotherapy (e.g., synchronous vs. asynchronous, radiation-first vs. immunotherapy-first), aiming to evaluate how these naturally occurring temporal variations impact clinical outcomes and immune status.
Sponsors
Xiangya Hospital of Central South University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years; no gender restriction; * Histologically or cytologically confirmed NSCLC, with brain metastases confirmed by contrast-enhanced cranial MRI; * Scheduled to receive radiotherapy combined with a PD-1/PD-L1 inhibitor, in accordance with real-world clinical treatment plans; * Negative for driver gene mutations, or positive for mutations but with documented failure of prior targeted therapy; * ECOG Performance Status score of 0-2, with an estimated life expectancy of ≥ 3 months; * Voluntarily signs the informed consent form and agrees to cooperate with blood/imaging data collection and follow-up procedures.
Exclusion criteria
* History of whole-brain radiotherapy, stereotactic radiotherapy for brain metastases, or brain surgery; * Presence of contraindications to MRI or inability to tolerate gadolinium-based contrast agents (e.g., severe hepatic or renal insufficiency); * Presence of active autoimmune disease requiring systemic treatment, or requirement for long-term use of high-dose immunosuppressive agents; * Pregnant or lactating women; * Other circumstances deemed by the investigator to involve severe complications or render the patient unsuitable for enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intracranial Progression-Free Survival (iPFS) | Up to approximately 2 years (Assessed every 2-3 months in the first year, and every 3-6 months thereafter until disease progression or death). | Defined as the time from study enrollment (or completion of baseline assessment) to the first documented intracranial disease progression according to the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria via blinded independent central review, or death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intracranial Objective Response Rate (iORR) | Up to approximately 2 years. | The proportion of patients achieving an intracranial Complete Response (CR) or Partial Response (PR) per RANO-BM criteria. Responses must be confirmed by consecutive imaging assessments at least 4 weeks apart. |
| Overall Survival (OS) | Up to approximately 2 years. | Defined as the time from study enrollment to death from any cause. |
| Duration of Response (DOR) | Up to approximately 2 years. | For patients achieving confirmed CR or PR, defined as the time from the first documented objective response to the first documented disease progression or death from any cause. |
| Best Overall Response (BOR) | Up to approximately 2 years. | The best disease response recorded from the start of the study treatment until disease progression or recurrence. |
| Intracranial Disease Control Rate (iDCR) | At 24 weeks | The proportion of patients who achieve CR, PR, or Stable Disease (SD) maintained for at least a specified time period (e.g., 24 weeks). |
| Incidence of Grade ≥3 Immune-Related Adverse Events (irAEs) | From enrollment up to 1 years after the last dose of immunotherapy. | Evaluated and tracked according to the NCI CTCAE v5.0 and specific irAE management guidelines to assess the safety of different treatment sequences. |
| Incidence of Radiation Necrosis and Severe Brain Edema | Up to approximately 2 years. | Dynamic monitoring and evaluation of the occurrence of radiation necrosis and Grade ≥3 radiation-induced brain edema, utilizing RANO-BM and related imaging criteria. |
Countries
China
Contacts
CONTACTRongrong Zhou, MD, PHD
CONTACTWeihua Liao, MD, PHD
Outcome results
None listed