Systemic Biomarkers to Predict Radiation-Induced Neurocognitive Decline

NCT06779487 | Recruiting DMC

• 1 other identifier: 4580
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Radiation constitutes an integral component in the management of primary brain tumors in pediatric and young adults like medulloblastoma, ependymoma, low-grade glioma, pituitary tumors, etc. A decline in neurocognitive outcomes is a multifactorial effect occurring from the primary disease as well as associated with treatments, including radiation. Since many of these tumors are highly curable, it is crucial to reduce long-term side effects, including memory loss, to improve the quality of life in these patients, leading to better rehabilitation. Radiation-induced neurocognitive deterioration is postulated to occur from multiple factors like neuroinflammation, vascular damage, and depletion of neural stem cells. The proposed study will prospectively evaluate 200 pediatric and young adults with brain tumors treated with radiotherapy. Biological samples (peripheral blood and cerebrospinal fluid) will be procured during routine investigations (an additional amount will be collected for study purposes without the need for additional investigations). Serial blood markers (whenever available pre-operative and before, during, and after completion of radiation) of neuroinflammation and neural markers will be tested in patients undergoing radiation as part of their standard treatment, and correlate with the neurocognitive outcomes measured by age-appropriate Wechsler intelligence scales. Also, the impact of clinical (e.g. age) and radiotherapy parameters like volume, dose of radiation, and technique (photon versus proton therapy) on acute (during radiotherapy) and late systemic inflammatory markers will be analyzed. The study will even provide the opportunity to know the influence of radiation on systemic neuroinflammatory markers in the human population, providing better biological insights into the neurocognitive decline. If proven successful, these biomarkers can be used in routine clinical practice for early intervention to improve neurocognitive function in patients receiving radiation (even for other histology or other patients receiving radiation like brain metastasis).

Conditions

Brain Tumors; Medulloblastoma; Glioma; Ependymoma

Keywords

Brain Tumor; Radiotherapy; Proton Beam Therapy; Neuro-cognition; Bio-markers

Outcome Measures

Primary Outcomes (1)

• Biomarkers associated with radiation-induced neurocognitive decline

  Differential values of individual biomarkers will be compared for patient groups with or without neurocognitive decline using Mann Whitney U test and independent t-test.

  84 months

Eligibility Criteria

• Age: 5 Years - 39 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

1. Age 5-39 years 2. Histological diagnosis of primary brain tumor 3. Decision for treatment with radical intent radiotherapy 4. Signed assent and parental consent form for pediatric age group and signed consent form for adults.

You may qualify if:

• Age 5-39 years
• Histological diagnosis of primary brain tumor
• Decision for treatment with radical intent radiotherapy
• Signed assent and parental consent form for pediatric age group and signed consent form for adults.

You may not qualify if:

• Inability to undergo neurocognitive evaluation
• Palliative radiotherapy.
• Expected life expectancy \< 1 year

Sponsors & Collaborators

• Tata Memorial Centre: lead

Study Sites (1)

Tata Memorial Hospital (TMH) Parel, and Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Kharghar

Mumbai, Maharashtra, 400012,, India

RECRUITING

Related Publications (5)

• Ayoub R, Ruddy RM, Cox E, Oyefiade A, Derkach D, Laughlin S, Ades-Aron B, Shirzadi Z, Fieremans E, MacIntosh BJ, de Medeiros CB, Skocic J, Bouffet E, Miller FD, Morshead CM, Mabbott DJ. Assessment of cognitive and neural recovery in survivors of pediatric brain tumors in a pilot clinical trial using metformin. Nat Med. 2020 Aug;26(8):1285-1294. doi: 10.1038/s41591-020-0985-2. Epub 2020 Jul 27.

  PMID: 32719487 RESULT

• Brown PD, Pugh S, Laack NN, Wefel JS, Khuntia D, Meyers C, Choucair A, Fox S, Suh JH, Roberge D, Kavadi V, Bentzen SM, Mehta MP, Watkins-Bruner D; Radiation Therapy Oncology Group (RTOG). Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial. Neuro Oncol. 2013 Oct;15(10):1429-37. doi: 10.1093/neuonc/not114. Epub 2013 Aug 16.

  PMID: 23956241 RESULT

• Kahalley LS, Peterson R, Ris MD, Janzen L, Okcu MF, Grosshans DR, Ramaswamy V, Paulino AC, Hodgson D, Mahajan A, Tsang DS, Laperriere N, Whitehead WE, Dauser RC, Taylor MD, Conklin HM, Chintagumpala M, Bouffet E, Mabbott D. Superior Intellectual Outcomes After Proton Radiotherapy Compared With Photon Radiotherapy for Pediatric Medulloblastoma. J Clin Oncol. 2020 Feb 10;38(5):454-461. doi: 10.1200/JCO.19.01706. Epub 2019 Nov 27.

  PMID: 31774710 RESULT

• Salloum R, Chen Y, Yasui Y, Packer R, Leisenring W, Wells E, King A, Howell R, Gibson TM, Krull KR, Robison LL, Oeffinger KC, Fouladi M, Armstrong GT. Late Morbidity and Mortality Among Medulloblastoma Survivors Diagnosed Across Three Decades: A Report From the Childhood Cancer Survivor Study. J Clin Oncol. 2019 Mar 20;37(9):731-740. doi: 10.1200/JCO.18.00969. Epub 2019 Feb 7.

  PMID: 30730781 RESULT

• Ostrom QT, Price M, Neff C, Cioffi G, Waite KA, Kruchko C, Barnholtz-Sloan JS. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2016-2020. Neuro Oncol. 2023 Oct 4;25(12 Suppl 2):iv1-iv99. doi: 10.1093/neuonc/noad149.

  PMID: 37793125 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral blood

MeSH Terms

Conditions

Brain Neoplasms; Medulloblastoma; Glioma; Ependymoma

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neuroectodermal Tumors, Primitive; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Radiation Oncology

Study Record Dates

• First Submitted: January 11, 2025
• First Posted: January 16, 2025
• Study Start: February 11, 2025
• Primary Completion (Estimated): February 1, 2032
• Study Completion (Estimated): February 1, 2032
• Last Updated: April 11, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)