Hippocampus-Avoidance Whole-Brain Radiation Therapy With Simultaneous Integrated Boost for BMs of NSCLC
Hippocampus-Avoidance Whole-Brain Radiation Therapy With Simultaneous Integrated Boost for Multiple Brain Metastases in Non-small Cell Lung Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Lung cancer has high incidence and mortality rates. NSCLC is the most prevalent form accounting for 85% of all lung cancer cases with approximately 40% of individuals developing brain metastases during the illness. With advancements in therapies like targeted therapy and immunotherapy, the incidence of brain metastases have raised paralleled by a rise in survival rates of NSCLC. And NSCLC patients with brain metastases only 2 to 3 months of natural survival[6]. Therefore, it is urgent to improve the prognosis and intracranial control of NSCLC patients with brain metastases.
Brain metastases patients of NSCLC should be treated with local treatment on the basis of systemic treatment. For patients of NSCLC with brain metastases who are not suitable for targeted therapy or with progressing intracranial post targeted therapy, radiotherapy emerges as a significant therapeutic.Stereotactic radiosurgery (SRS) alone should be offered to patients with one to three unresected brain metastases for patients with asymptomatic brain metastases and no systemic therapy options.While the standard treatment for multiple brain metastases (≥4) remains controversial.
WBRT is used to be a common therapy in multiple brain metastases prolonging survival of patients to 6 months. But WBRT comes with neurotoxic effects, notably cognitive impairment affecting memory and learning. This cognitive decline is mainly attributed to hippocampal damage, a crucial region for learning and memory. The RTOG0933 and NRG Oncology CC001 trials have demonstrated that HA-WBRT effectively safeguards cognitive function and enhances the quality of life in patients with brain metastases. Furthermore, considering the tolerated dose of normal brain tissue, the dose of WBRT was low (30Gy/10F) with only 60% intracranial local control rate. The landmark RTOG9508 trial has demonstrated that WBRT in combination with boosted metastases can improve local intracranial control.
Prokic et al. reported that the simultaneous integrated boost during WBRT (WBRT+SIB) demonstrated superior hippocampal sparing and biological benefits of fractionation over sequential integrated boost. Advancements in radiotherapy techniqueshave led to the innovative HA-WBRT+SIB strategy, delivering higher dosages to existing metastases while minimizing radiation exposure to the hippocampus. However, evidence for the application of HA-WBRT+SIB in multiple (≥4) brain metastases of NSCLC remains insufficient. Therefore, this study aims to investigate the efficacy and safety of HA-WBRT+SIB in patients with multiple brain metastases of NSCLC.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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-
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Nanjing, China
- Yatian Liu
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- adults (aged 18-75 years) diagnosed with NSCLC, with a KPS (Karnofsky performance status) ≥70, at least four brain metastases visible on MRI (magnetic resonance imaging) outside a 5-mm margin around the bilateral hippocampi, not suitable for targeted therapy or progressing intracranial post targeted therapy.
Exclusion Criteria:
- Ineligible participants had a history of conditions affecting cognitive function (including mental illness, brain trauma, and Alzheimer's disease), other primary malignant tumors, uncontrolled systemic disease, uncontrolled extracranial sites of gross disease, and suitable for targeted therapy.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Experimental: Hippocampus-Avoidance Whole-Brain Radiation Therapy With Simultaneous Integrated Boost
HA-WBRT (30 Gy in 12 fractions, Dmax of the hippocampal volume ≤ 17 Gy, Dmean of the hippocampal volume ≤12 Gy) +SIB (48 Gy in 12 fractions)
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hippocampus-Avoidance Whole-Brain Radiation Therapy With Simultaneous Integrated Boost
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Intracranial local progression-free survival time (iLPFS)
Time Frame: From date of enrollment until the date of progression of existing intracranial metastases or date of death from any cause, whichever came first, assessed up to 20 months
|
determined as the time from HA-WBRT+SIB initiation to death, existing intracranial metastases progression, or last follow-up.
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From date of enrollment until the date of progression of existing intracranial metastases or date of death from any cause, whichever came first, assessed up to 20 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Intracranial progression-free survival time (iPFS)
Time Frame: From date of enrollment until the date of progression of existing or new metastases intracranial or date of death from any cause, whichever came first, assessed up to 20 months
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measured from HA-WBRT+SIB initiation to existing or new metastases intracranial progression, death, or last follow-up.
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From date of enrollment until the date of progression of existing or new metastases intracranial or date of death from any cause, whichever came first, assessed up to 20 months
|
|
Cognitive function
Time Frame: From enrollment to the end of treatment at 4 weeks
|
was measured by the relative change in HVLT-R DR score from the start of HA-WBRT+SIB to 4 months after the start of HA-WBRT+SIB.
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From enrollment to the end of treatment at 4 weeks
|
|
OS (Overall survival)
Time Frame: From date of enrollment until the date of death from any cause, whichever came first, assessed up to 20 months
|
described as the time from initiation of radiation to the last follow-up or death
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From date of enrollment until the date of death from any cause, whichever came first, assessed up to 20 months
|
|
The cumulative incidence of local intracranial failure
Time Frame: From date of enrollment until the date of progression of existing intracranial metastases， assessed up to 20 months
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measured as the progression of existing intracranial metastases
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From date of enrollment until the date of progression of existing intracranial metastases， assessed up to 20 months
|
|
Cumulative incidence of intracranial failure
Time Frame: From date of enrollment until the date of the progression of existing or new intracerebral metastases assessed up to 20 months
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described as the progression of existing or new intracerebral metastases.
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From date of enrollment until the date of the progression of existing or new intracerebral metastases assessed up to 20 months
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Pathologic Processes
- Neoplasms by Site
- Neoplasms
- Respiratory Tract Diseases
- Lung Diseases
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Neoplastic Processes
- Nervous System Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Central Nervous System Neoplasms
- Lung Neoplasms
- Neoplasm Metastasis
- Carcinoma, Non-Small-Cell Lung
- Brain Neoplasms
Other Study ID Numbers
- JZ233490202001088
- 100000RMB (Other Grant/Funding Number: Nanjing Medical University of Collaborative Center)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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