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A Prospective Study of the Impact of Hippocampal Avoidance During Whole Brain Radiotherapy on Neurocognitive Function Decline

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2017 by Chang Gung Memorial Hospital
Sponsor:
Information provided by (Responsible Party):
Chang Gung Memorial Hospital
ClinicalTrials.gov Identifier:
NCT02504788
First received: July 16, 2015
Last updated: April 17, 2017
Last verified: April 2017
  Purpose

Whole brain radiotherapy (WBRT) has long been a practical and effective therapeutic modality for various settings of management in radiation oncology. For example, the indications for WBRT should include brain metastasis or metastases, the setting of prophylactic cranial irradiation (PCI) used mainly for patients with limited-stage small cell lung cancer, and even some patients with extensive-stage small cell lung cancer. The rationales for WBRT are essentially based on that it can target both microscopic and gross intracranial disease.

In addition to providing rapid alleviation of neurologic symptoms and enhanced intracranial disease control, WBRT might also prolong the time to develop neurocognitive function (NCF) decline. However, paradoxically NCF decline can also occur due to a sequel of WBRT. In terms of the time course of WBRT-induced NCF decline, it might vary considerably according to the specific domains which are selected to be measured. Early neurocognitive decline occurs within the first 1 - 4 months after WBRT for brain metastases. The domains of early neurocognitive decline principally involve verbal and short-term memory recall.

Since several decades ago, it has been understood that hippocampus plays an essential role in memory function. Not little evidence supports that radiation-induced damage to hippocampus should be strongly associated with NCF impairment. Furthermore, several studies have shown that isodose distribution in hippocampus is closely related to neurocognitive function in patients with benign or low-grade brain tumors. As a consequence, it is hypothesized that conformal hippocampal sparing during the course of WBRT (HS-WBRT) might provide significant preservation in terms of cognitive function.

This prospective cohort study aims to explore and evaluate the impact of the delivery of HS-WBRT on the pattern of NCF change and the extent of NCF decline in patients receiving prophylactic or therapeutic WBRT. As compared with previous related and relevant studies, it will also be investigated whether neurocognitive functional preservation can be achieved via the integration of hippocampal sparing with the course of WBRT.


Condition Intervention Phase
Brain Metastasis
Brain Metastases
Radiation: hippocampal-sparing WBRT
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment

Further study details as provided by Chang Gung Memorial Hospital:

Primary Outcome Measures:
  • The primary endpoint is delayed recall, as determined by the change/decline in verbal memory (WMS III- Word List score) from the baseline assessment to 4 months after the start of HS-WBRT. [ Time Frame: 4 months after the start of HS-WBRT ]
    Neurocognitive assessment: including memory, executive functions, and psychomotor speed. This neurocognitive outcome was delayed recall, as determined by the change/decline in either verbal memory [Wechsler Memory Scale - 3rd edition (WMS III) - Word List score] or non-verbal memory (WMS III- Visual Reproduction score) from the baseline assessment to 4 months after the start of the course of WBRT with hippocampus sparing (HS-WBRT). Additionally, the follow-up of neurocognitive assessment will also be administered at 12 months and up to 18 months after the start of HS-WBRT.

  • The primary endpoint is delayed recall, as determined by the change/decline in non-verbal memory (WMS III- Visual Reproduction score) from the baseline assessment to 4 months after the start of HS-WBRT. [ Time Frame: 4 months after the start of HS-WBRT ]
    Neurocognitive assessment: including memory, executive functions, and psychomotor speed. This neurocognitive outcome was delayed recall, as determined by the change/decline in either verbal memory [Wechsler Memory Scale - 3rd edition (WMS III) - Word List score] or non-verbal memory (WMS III- Visual Reproduction score) from the baseline assessment to 4 months after the start of the course of WBRT with hippocampus sparing (HS-WBRT). Additionally, the follow-up of neurocognitive assessment will also be administered at 12 months and up to 18 months after the start of HS-WBRT.


Secondary Outcome Measures:
  • Overall survival time, indicated by the time from the date of recruitment to the date of expiring [ Time Frame: up to 18 months ]
  • The time from the date of recruitment to that of intracranial progression/failure noted on brain MRI or CT [ Time Frame: up to 18 months ]

Estimated Enrollment: 100
Study Start Date: March 2014
Estimated Study Completion Date: December 31, 2019
Estimated Primary Completion Date: December 31, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hippocampal-sparing WBRT
All studied patients should undergo a computed tomography (CT) simulation scan encompassing the entire head region with 1.25‐mm slice thickness using a thermoplastic mask for immobilization. To achieve conformal hippocampal sparing during the delivery of whole brain radiation (WBRT), the technique of volumetric modulated arc therapy (VMAT) via Linac‐based RapidArc®.In terms of dose prescription, a dose of 30 Gy in 12 fractions was prescribed to whole-brain planning target volume (PTV) if the role of RT was considered either adjuvant following craniotomy with tumor removal or therapeutic for treating oligometastatic brain disease.
Radiation: hippocampal-sparing WBRT

  Eligibility

Ages Eligible for Study:   18 Years to 84 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with pathologically-confirmed non-hematopoietic malignancy who are referred for therapeutic or prophylactic WBRT
  • Good performance status no worse than Eastern Cooperative Group (ECOG) of 2 or a general status of Karnofsky Score (KPS) at least 70 %
  • The number and extent of brain metastatic lesions should be no more than three metastatic foci with a greatest diameter no more than 4 cm

Exclusion Criteria:

  • Patients with MRI-identified metastasis within 5 mm perihippocampally
  • Clinical suspicion of leptomeningeal spreading
  • History of prior radiotherapy including stereotactic radiosurgery delivered to brain/head region for any reasons
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02504788

Contacts
Contact: Chi-Cheng Chuang, M.D. +886-33281200 ext 2412 ccc2915@cgmh.org.tw
Contact: Shinn-Yn Lin, M.D. +886-33281200 ext 7172 rt3126@gmail.com

Locations
Taiwan
Chang Gung Memorial Hospital Recruiting
Taoyuan, Taiwan, 333
Contact: Shinn-Yn Lin, M.D.    +886-33281200 ext 7172    rt3126@gmail.com   
Sponsors and Collaborators
Chang Gung Memorial Hospital
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Chang Gung Memorial Hospital
ClinicalTrials.gov Identifier: NCT02504788     History of Changes
Other Study ID Numbers: 101-4151B
Study First Received: July 16, 2015
Last Updated: April 17, 2017
Individual Participant Data  
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Chang Gung Memorial Hospital:
Whole Brain Radiotherapy (WBRT)
Neurocognitive Functions (NCFs)
Hippocampus
Hippocampus Sparing during Whole Brain Radiotherapy (HS-WBRT)

Additional relevant MeSH terms:
Neoplasm Metastasis
Brain Neoplasms
Neoplastic Processes
Neoplasms
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on April 27, 2017