Hippocampus-Avoidance Whole-Brain Radiation Therapy With Simultaneous Integrated Boost for BMs of NSCLC

April 15, 2025 updated by: Yatian Liu

Hippocampus-Avoidance Whole-Brain Radiation Therapy With Simultaneous Integrated Boost for Multiple Brain Metastases in Non-small Cell Lung Cancer

WBRT (whole-brain radiation therapy) exhibits poor tumor control and decreased NCF (neurocognitive function). Herein, we investigated the safety and efficacy of HA-WBRT+SIB (hippocampus-avoidance whole-brain radiation therapy with simultaneous integrated boost) in NSCLC (non-small cell lung cancer) with multiple brain metastases.We conducted a prospective, single-arm phase II trial administering 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) for multiple brain metastases (≥4) of NSCLC. Cognitive performance was assessed by the HVLT-R DR (Hopkins Verbal LearningTest-Revised delayed Recall).A-WBRT+SIB emerges as a promising and safe therapeutic, improving intracranial tumor control and protecting cognitive function in NSCLC with multiple brain metastases.

Study Overview

Status

Active, not recruiting

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

Interventional

Enrollment (Estimated)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Nanjing, China
        • Yatian Liu

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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
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)
Radiation: ippocampus-Avoidance Whole-Brain Radiation Therapy With Simultaneous Integrated Boost
hippocampus-Avoidance Whole-Brain Radiation Therapy With Simultaneous Integrated Boost

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.
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
measured from HA-WBRT+SIB initiation to existing or new metastases intracranial progression, death, or last follow-up.
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.
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
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
measured as the progression of existing intracranial metastases
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
described as the progression of existing or new intracerebral metastases.
From date of enrollment until the date of the progression of existing or new intracerebral metastases assessed up to 20 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Yatian Liu

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2021

Primary Completion (Estimated)

January 1, 2026

Study Completion (Estimated)

January 1, 2026

Study Registration Dates

First Submitted

August 13, 2024

First Submitted That Met QC Criteria

August 15, 2024

First Posted (Actual)

August 16, 2024

Study Record Updates

Last Update Posted (Actual)

April 18, 2025

Last Update Submitted That Met QC Criteria

April 15, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

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)?

NO

IPD Plan Description

The results of the study have not been published

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Non-small Cell Lung Cancer

Clinical Trials on ippocampus-Avoidance Whole-Brain Radiation Therapy With Simultaneous Integrated Boost

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Macedonia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe