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adiotherapy-induced cognitive dysfunction is a severe complication following radiotherapy for nasopharyngeal carcinoma (NPC). Our previous studies have demonstrated that abnormalities in brain function and structural connectivity after radiotherapy play a significant role in the occurrence of radiation-induced cognitive dysfunction. However, the key risk factors and underlying neural mechanisms remain unclear. Research has shown that increased blood-brain barrier (BBB) permeability after radiotherapy is an important mechanism leading to cognitive dysfunction, and different APOE gene subtypes can regulate BBB permeability. Therefore, APOE gene polymorphisms are likely to influence post-radiotherapy vascular barrier permeability in NPC patients, thereby affecting their brain function and structural connectivity changes, and ultimately impacting their cognitive function.
This project aims to establish a longitudinal brain imaging database for NPC patients with different APOE genotypes before and after radiotherapy, based on previous research findings. The project will integrate dynamic contrast-enhanced MRI (DCE-MR), resting-state functional MRI (fMRI), and diffusion spectrum imaging (DSI) techniques. By comparing DCE-derived metrics across different genotype groups, the study seeks to identify brain regions with BBB damage differences between APOE genotype groups before and after radiotherapy. Furthermore, it will investigate how BBB damage in these brain regions mediates functional and structural connectivity abnormalities, and their relationship with radiation-induced cognitive dysfunction. The goal is to clarify the neural regulation mechanism of APOE gene polymorphisms in radiation-induced cognitive dysfunction and to identify risk factors for radiation-induced cognitive dysfunction. This research will provide a theoretical basis and valuable reference for the individualized prevention and treatment of radiation-induced cognitive dysfunction.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Using DCE-MRI, fMRI, and DSI, establish a longitudinal brain functional and structural imaging database for three groups of nasopharyngeal carcinoma patients before and 18 months after radiotherapy. | Other |
Sagittal data acquisition is performed with the following parameters: TR = 8.16 ms, TE = 3.18 ms, inversion time (TI) = 800 ms, flip angle (FA) = 8°, matrix = 256 × 256, FOV = 256 mm × 256 mm, voxel size = 1 mm × 1 mm × 1 mm, and 176 slices scanned. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Blood-Brain Barrier Permeability as Measured by Ktrans Values from DCE-MRI | The change in blood-brain barrier permeability will be quantified using the volume transfer constant (Ktrans) derived from Dynamic Contrast-Enhanced MRI (DCE-MRI). Ktrans values will be measured at baseline (pre-radiotherapy) and at 18 months post-radiotherapy. The difference in Ktrans values between these time points will be calculated to assess the change in permeability. | From enrollment to 18 months after the completion of radiotherapy |
| Change in Functional Connectivity as Measured by Resting-State fMRI | Functional connectivity will be assessed using resting-state functional MRI (fMRI). The strength of functional connections between specific brain regions, particularly those identified as having significant blood-brain barrier damage, will be measured at baseline and at 18 months post-radiotherapy. The change in functional connectivity strength will be calculated and reported. | From enrollment to 18 months after the completion of radiotherapy |
| Change in Structural Connectivity as Measured by Diffusion Spectrum Imaging (DSI) | Structural connectivity will be evaluated using Diffusion Spectrum Imaging (DSI). The integrity of white matter tracts, particularly those connecting regions with significant blood-brain barrier damage, will be measured at baseline and at 18 months post-radiotherapy. The change in structural connectivity, as indicated by metrics such as fractional anisotropy (FA) and mean diffusivity (MD), will be calculated and reported. | From enrollment to 18 months after the completion of radiotherapy |
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Inclusion Criteria:
Patients newly diagnosed with nasopharyngeal carcinoma, pathologically confirmed, and who have not received anti - tumor treatments such as surgery, induction chemotherapy, or radiotherapy.
All patients are of Han ethnicity and right - handed. Patients are aged between 20 and 60 years old, with an educational level of junior high school or above.
The clinical stage of the included patients is AJCC 8th edition stage I - IVa, without distant metastasis, and patients are scheduled to receive intensity - modulated radiotherapy (IMRT) according to the clinical plan.
Patients have no other serious systemic diseases except nasopharyngeal carcinoma.
There is no intracranial invasion of nasopharyngeal carcinoma. Routine MRI examinations (including T1WI, T2WI, and FLAIR) are negative. The baseline basic cognitive assessment scales (MoCA and MMSE) before radiotherapy are normal.
Patients have no family history of mental illness. Patients have no history of neurological diseases or head trauma. After fully understanding the experimental content, the subjects agree to participate in this project and sign the informed consent form
Exclusion Criteria:
Patients diagnosed with Alzheimer's disease (AD) before being included. AD is diagnosed by psychiatrists according to the 9th Revision of the International Classification of Diseases, Clinical Modification (ICD - 9 - CM).
Patients with intracranial lesions detected by routine MRI examinations. Patients with contraindications to magnetic resonance examinations. Patients with concurrent other diseases. Patients with tumor recurrence who need re - radiotherapy, or those who cannot adhere to and complete IMRT treatment.
Left - handed or ambidextrous patients. Patients with a history of head trauma or mental/neurological diseases. Patients aged less than 20 or more than 60 years old. Patients with serious systemic diseases such as heart, lung, or kidney diseases.
Patients with diabetes or hypertension. Patients who cannot cooperate to complete the neurocognitive scale tests.
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Collect nasopharyngeal carcinoma patients who seek medical treatment at Sun Yat - sen University Cancer Center
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Medical Imaging, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy | Guangzhou | Guangdong | 523000 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35900209 | Background | Lozupone M, Imbimbo BP, Balducci C, Lo Vecchio F, Bisceglia P, Latino RR, Leone M, Dibello V, Solfrizzi V, Greco A, Daniele A, Watling M, Seripa D, Panza F. Does the imbalance in the apolipoprotein E isoforms underlie the pathophysiological process of sporadic Alzheimer's disease? Alzheimers Dement. 2023 Jan;19(1):353-368. doi: 10.1002/alz.12728. Epub 2022 Jul 28. | |
| 29618365 |
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| China |
| Main BS, Villapol S, Sloley SS, Barton DJ, Parsadanian M, Agbaegbu C, Stefos K, McCann MS, Washington PM, Rodriguez OC, Burns MP. Apolipoprotein E4 impairs spontaneous blood brain barrier repair following traumatic brain injury. Mol Neurodegener. 2018 Apr 4;13(1):17. doi: 10.1186/s13024-018-0249-5. |
| 34957486 | Background | Jackson RJ, Meltzer JC, Nguyen H, Commins C, Bennett RE, Hudry E, Hyman BT. APOE4 derived from astrocytes leads to blood-brain barrier impairment. Brain. 2022 Oct 21;145(10):3582-3593. doi: 10.1093/brain/awab478. |
| 22622580 | Background | Bell RD, Winkler EA, Singh I, Sagare AP, Deane R, Wu Z, Holtzman DM, Betsholtz C, Armulik A, Sallstrom J, Berk BC, Zlokovic BV. Apolipoprotein E controls cerebrovascular integrity via cyclophilin A. Nature. 2012 May 16;485(7399):512-6. doi: 10.1038/nature11087. |
| 22701557 | Background | Tang Y, Luo D, Rong X, Shi X, Peng Y. Psychological disorders, cognitive dysfunction and quality of life in nasopharyngeal carcinoma patients with radiation-induced brain injury. PLoS One. 2012;7(6):e36529. doi: 10.1371/journal.pone.0036529. Epub 2012 Jun 11. |
| 33302001 | Background | Penn IW, Chung CH, Huang YC, Chen MC, Sun CA, Yip PK, Chien WC. Increased risk of dementia in patients with nasopharyngeal cancer treated with radiation therapy: A nationwide population-based cohort study. Arch Gerontol Geriatr. 2021 Mar-Apr;93:104303. doi: 10.1016/j.archger.2020.104303. Epub 2020 Nov 22. |
| 34327577 | Background | Zheng Z, Wang B, Zhao Q, Zhang Y, Wei J, Meng L, Xin Y, Jiang X. Research progress on mechanism and imaging of temporal lobe injury induced by radiotherapy for head and neck cancer. Eur Radiol. 2022 Jan;32(1):319-330. doi: 10.1007/s00330-021-08164-6. Epub 2021 Jul 29. |
| 20044217 | Background | Hsiao KY, Yeh SA, Chang CC, Tsai PC, Wu JM, Gau JS. Cognitive function before and after intensity-modulated radiation therapy in patients with nasopharyngeal carcinoma: a prospective study. Int J Radiat Oncol Biol Phys. 2010 Jul 1;77(3):722-6. doi: 10.1016/j.ijrobp.2009.06.080. Epub 2010 Jan 13. |
| 10798963 | Background | Tofilon PJ, Fike JR. The radioresponse of the central nervous system: a dynamic process. Radiat Res. 2000 Apr;153(4):357-70. doi: 10.1667/0033-7587(2000)153[0357:trotcn]2.0.co;2. |
| 30279047 | Result | McDowell LJ, Ringash J, Xu W, Chan B, Lu L, Waldron J, Rock K, So N, Huang SH, Giuliani M, Hope A, O'Sullivan B, Bratman SV, Cho J, Kim J, Jang R, Bayley A, Bernstein LJ. A cross sectional study in cognitive and neurobehavioral impairment in long-term nasopharyngeal cancer survivors treated with intensity-modulated radiotherapy. Radiother Oncol. 2019 Feb;131:179-185. doi: 10.1016/j.radonc.2018.09.012. Epub 2018 Sep 29. |
| ID | Term |
|---|---|
| D000077274 | Nasopharyngeal Carcinoma |
| ID | Term |
|---|---|
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009303 | Nasopharyngeal Neoplasms |
| D010610 | Pharyngeal Neoplasms |
| D010039 | Otorhinolaryngologic Neoplasms |
| D006258 | Head and Neck Neoplasms |
| D009371 | Neoplasms by Site |
| D009302 | Nasopharyngeal Diseases |
| D010608 | Pharyngeal Diseases |
| D009057 | Stomatognathic Diseases |
| D010038 | Otorhinolaryngologic Diseases |
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