a Feasibility Study of iHD-SRT for BM

Isotoxic High Dose (iHD) Fractionated Stereotactic Radiation Therapy (fSRT) for Intact Brain Metastases : a Feasibility Study

Brain metastasis is the most challenging disease in the field of tumor treatment, with a median overall survival of only 1-2 months for untreated patients. Stereotactic radiotherapy (SRT) has the advantages of precise positioning, relatively concentrated dosage, shorter course, and lower toxicity. Several studies could effectively protect cognitive function and achieve better tumor control rate. Currently, it has gradually replaced WBRT as standard local treatment choice for brain metastases. SRT includes Stereotactic Radiosurgery (SRS) and Fractional Stereotactic Radiotherapy (fSRT). With the continuous updating of domestic radiation therapy equipment, the use of high-resolution multi leaf gratings enables the accuracy of fSRT based on linear accelerators to reach 0.5mm or even lower levels, and has gradually become one of the main choices for local treatment of a limited number of patients with brain metastases.

However, there is currently no prospective randomized controlled study data analyzing the clinical benefits of different segmentation and dosages of SRT. In retrospective data comparing different segmentation schemes, researchers found that higher BED was associated with better local control. However, the ASTRO guidelines recommend relatively conservative doses for SRT of brain metastases, especially as the lesion volume increases, and the recommended dose of BED10 for SRT was only 48 Gy (30 Gy/5 Fx). This is based on the consideration that higher radiation exposure will bring a higher risk of radiation-induced brain necrosis. However, with the continuous updates of SRT treatment equipment and technology, existing technologies can achieve higher dose coverage for more brain metastases while meeting the normal tissue limit. Therefore, this study conducted a prospective intervention study to explore the feasibility and safety of optimizing SRT dosage based on normal tissue tolerance for the treatment of brain metastases, in order to further improve the therapeutic effect of intracranial lesions with brain metastases.

This study is designed as a single arm open prospective study, assuming that under this treatment regimen, the proportion of patients with lesion prescription dose BED10>50 Gy is 90%, and the incidence of radiation-induced brain necrosis within 1 year is 8.5%. The planned enrollment period is 2 years and follow-up period is 1 year. A total of 35 people need to be enrolled.

Study Overview

• Status: Recruiting
• Conditions: Brain Metastases, Adult; Stereotactic Radiotherapy
• Intervention / Treatment: Radiation: iHD-SRT

• Study Type: Interventional
• Enrollment (Estimated): 35
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dan Ou, MD; Phone Number: 8618801970632; Email: od12341@rjh.com.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Recruiting
      • Ruijin Hospital
      • Contact: Dan Ou; Phone Number: +8618801970632; Email: od12341@rjh.com.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Ability to understand and willingness to participate the research and sign the consent form
• ECOG PS 0-2
• The primary or metastatic lesion was confirmed by pathological histology as a malignant tumor
• Head MRI diagnosis of brain metastasis with measurable lesions and technically feasible SRT (no more than 15 in number and 20cc in volume)
• Estimated survival time ≥ 3 months

Exclusion Criteria:

• Diffuse brain metastases, or combined with meningeal metastases, or technically difficult to perform SRT
• With severe internal medicine complications or absolute contraindications for radiotherapy
• other sufficient reasons to be unqualified, such as potential non-compliance with the clinical protocol, etc

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: iHD-SRT; isotoxic high dose SRT	Radiation: iHD-SRT; received isotoxic individualized fSRT, with BED 10>50Gy and <100Gy, and strict OAR limits

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
proportion of patients receiving BED 10 >50 Gy	proportion of patients receiving BED 10 >50 Gy	through treatment completion, an average of 1 month
the incidence of radiation-induced brain necrosis	The incidence of radiation-induced brain necrosis	1 year

Collaborators and Investigators

• Sponsor: Ruijin Hospital
• Investigators: Principal Investigator: Jiayi Chen, Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: January 19, 2024
• First Submitted That Met QC Criteria: January 28, 2024
• First Posted (Actual): January 30, 2024

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasm Metastasis; Brain Neoplasms
• Other Study ID Numbers: 2024（006）

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No