Clinical trial: NCT06376292
Section: Alternatives
Subsections: 9 Alternative Solutions

If the subjects do not participate in this study or withdraw from the study, they can continue to receive treatment according to the standard diagnosis and treatment plan, or participate in other studies, etc.
Clinical trial: NCT06376292
Section: Confidentiality
Subsections: 10 Confidentiality Of Your Personal Information

Your medical records (including research medical records and physical and chemical examination reports, etc.) will be kept in the hospital according to regulations. Except for researchers, ethics committees, monitoring, auditing, pharmaceutical management departments, and other relevant personnel who will be allowed to access your medical records, other personnel unrelated to the study have no right to access your medical records without permission. The public report of the results of this study will not disclose your personal identity. We will be within the allowed range Internally, make every effort to protect the privacy of your personal medical information.  
11 Termination of research **participation** Whether to participate in this study depends entirely on your voluntary choice. You may refuse to participate in this study, or withdraw from the study without reason at any time during the study process, which will not affect your relationship with the doctor, nor will it affect the loss of your medical or other benefits. In addition, your participation may be terminated due to the following reasons Related to this study: 1. You did not follow the instructions of the research doctor.  
2. You have encountered a serious situation that may require treatment. 3. The research doctor believes that terminating the study is most beneficial for your health and wellbeing.
Clinical trial: NCT06376292
Section: Participant Responsibilities
Subsections: 4 What Do You Need To Do If You Participate In The Research

You will conduct screening and evaluation according to the inclusion criteria of this plan. If you agree to participate, you will sign an informed consent form(ICF). After completing all screening activities, if eligible for enrollment, intrathecal injection will be performed. The subjects received a comprehensive treatment plan consisting mainly of whole brain radiation therapy combined with intrathecal injection of Thiotepa, with 2 cycles of injection per week. The efficacy and safety were evaluated every 2 cycles.  
You can voluntarily withdraw from the study at any time, or the participant or sponsor may withdraw due to safety or behavior reasons Request for withdrawal due to reasons such as failure to comply with the research visit time or steps required by the protocol
Clinical trial: NCT06376292
Section: Procedures
Subsections: 3 Specific Procedures And Processes

This study is a prospective, one arm clinical exploratory study evaluating the combination of whole brain radiation therapy and intrathecal injection of Thiotepa for systemic treatment of primary diseases in patients with meningeal metastases of different solid tumors in our hospital. This study plans to include 20 subjects in the intention to analyze (ITT) population for a duration of 2 years. Observe patient safety indicators and survival data during the research process. This study is divided into three stages: screening period, intrathecal injection, and follow-up period.  
The screening period is 28 days before the first administration. Intrathecal injection: Subjects who meet the inclusion criteria but do not meet the exclusion criteria will receive intrathecal injection after signing an informed consent form. The subjects received a comprehensive treatment plan consisting mainly of whole brain 30Gy/10F radiotherapy combined with intrathecal injection of Thiotepa. The injection was administered by qualified individuals (certified personnel in the radiotherapy department of our hospital) twice a week for a total of 4 weeks. Thiotepa was injected 10mg each time, mixed with cerebrospinal fluid, and then injected slowly for 5-10 minutes. Evaluate the efficacy and safety every 2 cycles. If there is disease progression or serious adverse events, immediately withdraw from this study. Follow up period: After stopping the study treatment, the subjects enter the follow-up period. CT or MRI enhanced scans should be performed every month during the follow-up period to observe PFS until the end of the follow-up period. For subjects who did not withdraw their informed consent form, survival information (i.e. date and cause of death, subsequent tumor treatment, etc.) will be collected every month through telephone and/or clinical visits.
Clinical trial: NCT06376292
Section: Purpose of Research
Subsections: 1. Research Background|2. Research Objectives 2.1 Research Purpose:

Tumor meningeal metastasis (LM) refers to the metastasis that occurs when tumor cells spread to the subarachnoid space and spread to the meninges with the flow of cerebrospinal fluid (CSF). The occurrence of LM is less common than brain parenchymal metastasis, but more deadly. LM can occur in non small cell lung cancer (NSCLC), breast cancer (BC), melanoma and other malignant solid tumors. Compared to the 20% to 65% incidence of brain metastasis in NSCLC patients, the proportion of LM occurring in NSCLC patients is only 3% to 5%. However, the prognosis of LM patients is worse, and for untreated patients, the median overall survival (mOS) is only 6-8 weeks.  
With tumor treatment, survival can be extended to several months The mOS of LM BC is approximately 3.5 to 4.4 months, LM NSCLC is 3 to 6 months, and LM melanoma is 1.7 to 2.5 months. The diagnosis and treatment of LM are extremely important and challenging. According to the EANO-ESMO guidelines, imaging is one of the diagnostic criteria, but the positivity rate is low and the patient's condition becomes severe when imaging features are present.  
The treatment of LM includes comprehensive treatment methods such as intrathecal drug therapy, systemic drug therapy, and local radiotherapy. Due to the presence of the blood-brain barrier (BBB), systemic drugs cannot exert their effects at the meninges. Therefore, intrathecal injection of drugs has become the best choice for LM due to its advantage of directly acting on the lesion site. There is limited research on drugs used for intrathecal injection of LM, so the main intrathecal chemotherapy drugs in clinical practice are methotrexate, liposome cytarabine, and thiotepa. Shandong Cancer Hospital shared a case of HER2 (+) LM BC patients who achieved a 16 month survival benefit through a regimen of pyrrolitinib+vinorelbine rhythm chemotherapy+intrathecal injection of methotrexate. For LM patients whose condition worsens after treatment with methotrexate, Thiotepa can be used as a salvage treatment. A retrospective study included 30 LM patients who failed methotrexate treatment and received 10mg of intrathecal injection twice a week. Among them, 14 cases (47%) had cytological reactions to intrathecal injection of cetepete. The EANO-ESMO
guidelines recommend intrathecal drug therapy if tumor cells are found in CSF, regardless of MRI findings. Radiation therapy is also one of the treatment methods, but the bone marrow suppression caused by whole brain and spinal cord radiation therapy is significant, with limited dosage, which leads to interruption of systemic treatment and poor prognosis. The combination regimen in this study can quickly control symptoms by intrathecal injection of chemotherapy drugs, while opening the blood-brain barrier through whole brain radiotherapy, combined with systemic treatment for the primary disease, to achieve better therapeutic effects.  
2 / 6 Therefore, studying the effectiveness and safety of comprehensive treatment mainly consisting of whole brain radiotherapy combined with intrathecal injection of chemotherapy drugs for LM of different tumors can help guide clinical treatment decisions. This is a scientific problem that urgently needs to be solved in the field of cancer. Here, we conduct a single arm prospective exploratory study to provide treatment opportunities for more patients.

The aim of this prospective study is to evaluate the effectiveness and safety of whole brain radiation therapy, intrathecal injection of Thiotepa, combined with systemic treatment for primary diseases in patients with different solid tumor meningeal metastases in our hospital.