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.
Visão geral do estudo
Status
Intervenção / Tratamento
Tipo de estudo
Inscrição (Estimado)
Contactos e Locais
Contato de estudo
- Nome: Rongrong Zhou, MD, PHD
- Número de telefone: +8613875898127
- E-mail: zhourr@csu.edu.cn
Estude backup de contato
- Nome: Weihua Liao, MD, PHD
- Número de telefone: +8613973126486
- E-mail: ouwenliao@163.com
Locais de estudo
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Hunan
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Changsha, Hunan, China
- Xiangya Hospital of Central South University
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Contato:
- Rongrong Zhou, MD, PHD
- Número de telefone: +8613875898127
- E-mail: zhourr@csu.edu.cn
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Contato:
- Weihua Liao, MD, PHD
- Número de telefone: +8613973126486
- E-mail: ouwenliao@163.com
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Subinvestigador:
- Xianjing Chu, MD
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Adulto
- Adulto mais velho
Aceita Voluntários Saudáveis
Método de amostragem
População do estudo
Descrição
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.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
Coortes e Intervenções
Grupo / Coorte |
Intervenção / Tratamento |
|---|---|
|
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. |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Intracranial Progression-Free Survival (iPFS)
Prazo: 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).
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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.
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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).
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Intracranial Objective Response Rate (iORR)
Prazo: 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.
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Up to approximately 2 years.
|
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Overall Survival (OS)
Prazo: Up to approximately 2 years.
|
Defined as the time from study enrollment to death from any cause.
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Up to approximately 2 years.
|
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Duration of Response (DOR)
Prazo: Up to approximately 2 years.
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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.
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Up to approximately 2 years.
|
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Best Overall Response (BOR)
Prazo: Up to approximately 2 years.
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The best disease response recorded from the start of the study treatment until disease progression or recurrence.
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Up to approximately 2 years.
|
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Intracranial Disease Control Rate (iDCR)
Prazo: At 24 weeks
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The proportion of patients who achieve CR, PR, or Stable Disease (SD) maintained for at least a specified time period (e.g., 24 weeks).
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At 24 weeks
|
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Incidence of Grade ≥3 Immune-Related Adverse Events (irAEs)
Prazo: From enrollment up to 1 years after the last dose of immunotherapy.
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Evaluated and tracked according to the NCI CTCAE v5.0 and specific irAE management guidelines to assess the safety of different treatment sequences.
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From enrollment up to 1 years after the last dose of immunotherapy.
|
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Incidence of Radiation Necrosis and Severe Brain Edema
Prazo: Up to approximately 2 years.
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Dynamic monitoring and evaluation of the occurrence of radiation necrosis and Grade ≥3 radiation-induced brain edema, utilizing RANO-BM and related imaging criteria.
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Up to approximately 2 years.
|
Outras medidas de resultado
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Parasagittal Dura (PSD) Volume
Prazo: 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).
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Baseline and follow-up MRI assessments up to approximately 2 years.
|
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Meningeal Lymphatic Drainage Rate
Prazo: 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.
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Baseline and follow-up MRI assessments up to approximately 2 years.
|
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Meningeal Lymphatic Vessel Diameter
Prazo: Baseline and follow-up MRI assessments up to approximately 2 years.
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Mean diameter of visualized meningeal lymphatic vessels measured on contrast-enhanced 7.0T MRI using standardized image analysis methods and reported in millimeters (mm).
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Baseline and follow-up MRI assessments up to approximately 2 years.
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Deep Cervical Lymph Node (dCLN) Inflow Rate
Prazo: 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.
|
Colaboradores e Investigadores
Patrocinador
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Estimado)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Outros números de identificação do estudo
- 2026051108
- ZXQ2026B05 (Número de outro subsídio/financiamento: Central South University)
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