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NCT Number: NCT07638709

Impact of Radiotherapy-Immunotherapy Timing in NSCLC Brain Metastases

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.

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Key information

Conditions

Non Small Cell Lung Brain Metastasases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Brain radiotherapy

Radiation

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.

Primary outcomes

  1. Intracranial Progression-Free Survival (iPFS)

    Time frame: 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 outcomes

  1. Intracranial Objective Response Rate (iORR)

    Time frame: 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.

  2. Overall Survival (OS)

    Time frame: Up to approximately 2 years.

    Defined as the time from study enrollment to death from any cause.

  3. Duration of Response (DOR)

    Time frame: 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.

  4. Best Overall Response (BOR)

    Time frame: Up to approximately 2 years.

    The best disease response recorded from the start of the study treatment until disease progression or recurrence.

  5. Intracranial Disease Control Rate (iDCR)

    Time frame: 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).

  6. Incidence of Grade ≥3 Immune-Related Adverse Events (irAEs)

    Time frame: 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.

  7. Incidence of Radiation Necrosis and Severe Brain Edema

    Time frame: 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.

Other outcomes

  1. Parasagittal Dura (PSD) Volume

    Time frame: 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).

  2. Meningeal Lymphatic Drainage Rate

    Time frame: 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.

  3. Meningeal Lymphatic Vessel Diameter

    Time frame: 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).

  4. Deep Cervical Lymph Node (dCLN) Inflow Rate

    Time frame: 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Rongrong Zhou, MD, PHD

CONTACT

[email protected]

+8613875898127

Weihua Liao, MD, PHD

CONTACT

[email protected]

+8613973126486

Sponsors and collaborators

Lead sponsor

Xiangya Hospital of Central South University

Other

Registry information

Official study title

Immune Microenvironment-driven Radiotherapy-immunotherapy Combined With Time-series Strategy for NSCLC Brain Metastases: an Exploratory Study Based on a Clinical Cohort.

Acronym: (RT-ICI)

Important dates

Study start
2026
Primary completion
2029
Study completion
2030
First posted
Jun 10, 2026
Registry last updated
Jun 10, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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