Impact of Radiotherapy-Immunotherapy Timing in NSCLC Brain Metastases ((RT-ICI))
Immune Microenvironment-driven Radiotherapy-immunotherapy Combined With Time-series Strategy for NSCLC Brain Metastases: an Exploratory Study Based on a Clinical Cohort.
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:
- Does the timing of the two treatments change how long the brain tumor stays stable and how long participants live?
- What medical problems do participants have when receiving these treatments at different times?
- 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:
- Allow researchers to collect information about their treatment, health, and medical imaging during regular checkups.
- Give a small blood sample during their routine blood draws.
- Have standard magnetic resonance imaging (MRI) scans of their brain.
調査の概要
研究の種類
入学 (推定)
連絡先と場所
研究連絡先
- 名前：Rongrong Zhou, MD, PHD
- 電話番号：+8613875898127
- メール：zhourr@csu.edu.cn
研究連絡先のバックアップ
- 名前：Weihua Liao, MD, PHD
- 電話番号：+8613973126486
- メール：ouwenliao@163.com
研究場所
-
-
Hunan
-
Changsha、Hunan、中国
- Xiangya Hospital of Central South University
-
コンタクト：
- Rongrong Zhou, MD, PHD
- 電話番号：+8613875898127
- メール：zhourr@csu.edu.cn
-
コンタクト：
- Weihua Liao, MD, PHD
- 電話番号：+8613973126486
- メール：ouwenliao@163.com
-
副調査官：
- Xianjing Chu, MD
-
-
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
サンプリング方法
調査対象母集団
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
コホートと介入
グループ/コホート |
介入・治療 |
|---|---|
|
Non-small cell lung cancer brain metastases
This cohort comprises adult patients (aged 18 years and older) with histologically or cytologically confirmed (NSCLC who have brain metastases confirmed by contrast-enhanced head MRI. Participants in this cohort are scheduled to receive standard-of-care radiotherapy combined with PD-1/PD-L1 immune checkpoint inhibitors based on real-world clinical treatment plans. Eligible participants must have an ECOG performance status of 0 to 2, an expected survival of at least 3 months, and be either driver-gene negative or have experienced disease progression following prior targeted therapies. The cohort strictly excludes patients who have a history of WBRT, SRS for brain metastases, or brain surgery. Additionally, individuals with contraindications to MRI (or intolerance to gadolinium contrast agents), active autoimmune diseases requiring systemic treatment or long-term high-dose immunosuppressants, and pregnant or lactating women are excluded. |
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. |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Intracranial Progression-Free Survival (iPFS)
時間枠：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.
|
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).
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Intracranial Objective Response Rate (iORR)
時間枠：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.
|
Up to approximately 2 years.
|
|
Overall Survival (OS)
時間枠：Up to approximately 2 years.
|
Defined as the time from study enrollment to death from any cause.
|
Up to approximately 2 years.
|
|
Duration of Response (DOR)
時間枠：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.
|
Up to approximately 2 years.
|
|
Best Overall Response (BOR)
時間枠：Up to approximately 2 years.
|
The best disease response recorded from the start of the study treatment until disease progression or recurrence.
|
Up to approximately 2 years.
|
|
Intracranial Disease Control Rate (iDCR)
時間枠：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).
|
At 24 weeks
|
|
Incidence of Grade ≥3 Immune-Related Adverse Events (irAEs)
時間枠：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.
|
From enrollment up to 1 years after the last dose of immunotherapy.
|
|
Incidence of Radiation Necrosis and Severe Brain Edema
時間枠：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.
|
Up to approximately 2 years.
|
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Parasagittal Dura (PSD) Volume
時間枠：Baseline and follow-up MRI assessments up to approximately 2 years.
|
Quantitative measurement of the parasagittal dura (PSD) volume derived from contrast-enhanced 7.0T MRI.
PSD volume will be calculated using standardized image segmentation and volumetric analysis procedures and reported in cubic millimeters (mm³).
|
Baseline and follow-up MRI assessments up to approximately 2 years.
|
|
Meningeal Lymphatic Drainage Rate
時間枠：Baseline and follow-up MRI assessments up to approximately 2 years.
|
Quantitative assessment of meningeal lymphatic drainage efficiency measured using contrast-enhanced 7.0T MRI.
Drainage rate will be calculated according to predefined imaging analysis protocols and expressed as a percentage or kinetic parameter reflecting lymphatic drainage function.
|
Baseline and follow-up MRI assessments up to approximately 2 years.
|
|
Meningeal Lymphatic Vessel Diameter
時間枠：Baseline and follow-up MRI assessments up to approximately 2 years.
|
Mean diameter of visualized meningeal lymphatic vessels measured on contrast-enhanced 7.0T MRI using standardized image analysis methods and reported in millimeters (mm).
|
Baseline and follow-up MRI assessments up to approximately 2 years.
|
|
Deep Cervical Lymph Node (dCLN) Inflow Rate
時間枠：Baseline and follow-up MRI assessments up to approximately 2 years.
|
Quantitative assessment of contrast agent inflow into deep cervical lymph nodes measured using contrast-enhanced 7.0T MRI.
The inflow rate will be used as an indicator of meningeal lymphatic drainage function.
|
Baseline and follow-up MRI assessments up to approximately 2 years.
|
協力者と研究者
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
その他の研究ID番号
- 2026051108
- ZXQ2026B05 (その他の助成金/資金番号：Central South University)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。