Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2024, 168(3):206-215 | DOI: 10.5507/bp.2024.012

Challenges with hippocampal MR spectroscopy as a surrogate for pre-radiotherapy assessment of neurocognitive impairment in patients with brain metastasis

Iveta Selingerova1, Klara Holikova2, Tomas Chodur3, Ludmila Hynkova4, 5, Petr Pospisil4, 5, Martin Bulik2, Renata Belanova6, Kamila Siffelova3, Ivana Kolouskova7, Marek Slavik4, 5, Petr Burkon4, 5, Roman Hrstka1, Radim Jancalek8, 9, Jiri Sana7, 10, Pavel Slampa4, 5, Tomas Kazda1, 4, 5
1 Research Center for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic
2 Department of Medical Imaging, St. Anne's University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
3 Unit of Clinical Psychology, Masaryk Memorial Cancer Institute, Brno, Czech Republic
4 Department of Radiation Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic
5 Department of Radiation Oncology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
6 Department of Radiology, Masaryk Memorial Cancer Institute, Brno, Czech Republic
7 Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute and Faculty of Medicine, Masaryk University, Brno, Czech Republic
8 Department of Neurosurgery, St. Anne's University Hospital Brno, Brno, Czech Republic
9 Department of Neurosurgery, St. Anne's University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
10 Central European Institute of Technology, Masaryk University, Brno, Czech Republic

Aim: Patients with multiple brain metastases (BM) benefit from hippocampal-avoiding whole brain radiotherapy (HA-WBRT), the challenging and less available form of WBRT. This study explores potential of pre-radiotherapy (pre-RT) hippocampal magnetic resonance spectroscopy (MRS) measuring hippocampal neuronal density as an imaging surrogate and predictive tool for assessing neurocognitive functions (NCF).

Methods: 43 BM patients underwent pre-RT hippocampal MRS. N-acetyl aspartate (NAA) concentration, a marker for neuronal density (weighted by creatine (Cr) and choline (Cho) concentrations), and neurocognitive function (NCF) tests (HVLT and BVMT) performed by certified psychologists were evaluated. Clinical variables and NAA concentrations were correlated with pre-RT NCFs.

Results: HVLT and BVMT subtests showed pre-RT deterioration except for BVMT recognition. Significantly better NCFs were observed in women in HVLT subsets. Significantly higher NAA/Cr + Cho was measured in women (median 0.63 vs. 0.55; P=0.048) in the left hippocampus (no difference in the right hippocampus). In men, a positive correlation (0.51, P=0.018) between total brain volume and HVLT-TR, between left hippocampal NAA/Cr + Cho and HVLT-R (0.45, P=0.063), and between right hippocampal NAA/Cr + Cho and BVMT-recognition (0.49, P=0.054) was observed. In women, a borderline significant negative correlation was observed between left hippocampal NAA/Cr + Cho and BVMT-TR (-0.43, P=0.076) and between right NAA/Cr + Cho and HVLT-DR (-0.42, P=0.051).

Conclusion: Borderline statistically significant correlations were observed with speculative interpretation underlying the challenges of hippocampal MRS as a surrogate for neurocognitive impairment. Further studies need to be done to ascertain the opportunities for imaging predictors of benefit from memory sparing radiotherapy.

Keywords: hippocampus, MR spectroscopy, neurocognitive function, radiotherapy

Received: January 29, 2024; Revised: March 19, 2024; Accepted: March 22, 2024; Prepublished online: April 15, 2024; Published: September 12, 2024  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Selingerova, I., Holikova, K., Chodur, T., Hynkova, L., Pospisil, P., Bulik, M., ... Kazda, T. (2024). Challenges with hippocampal MR spectroscopy as a surrogate for pre-radiotherapy assessment of neurocognitive impairment in patients with brain metastasis. Biomedical papers, 168(3), 206-215. doi: 10.5507/bp.2024.012
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • Open full article

    References

    1. Mahajan A, Ahmed S, McAleer MF, Weinberg JS, Li J, Brown P, Settle S, Prabhu SS, Lang FF, Levine N, McGovern S, Sulman E, McCutcheon IE, Azeem S, Cahill D, Tatsui C, Heimberger AB, Ferguson S, Ghia A, Demonte F, Raza S, Guha-Thakurta N, Yang J, Sawaya R, Hess KR, Rao G. Post-operative stereotactic radiosurgery versus observation for completely resected brain metastases: a single-centre, randomised, controlled, phase 3 trial. Lancet Oncol 2017;18(8):1040-8. Go to original source... Go to PubMed...
    2. Brown PD, Ballman KV, Cerhan JH, Anderson SK, Carrero XW, Whitton AC, Greenspoon J, Parney IF, Laack NN, Ashman JB, Bahary JP, Hadjipanayis CG, Urbanic JJ, Barker FG, Farace E, Khuntia D, Giannini C, Buckner JC, Galanis E, Roberge D. Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC.3): a multicentre, randomised, controlled, phase 3 trial. Lancet Oncol 2017;18(8):1049-60. Go to original source... Go to PubMed...
    3. Vogelbaum MA, Brown PD, Messersmith H, Brastianos PK, Burri S, Cahill D, Dunn IF, Gaspar LE, Gatson NT, Gondi V, Jordan JT, Lassman AB, Maues J, Mohile N, Redjal N, Stevens G, Sulman E, van den Bent M, Wallace HJ, Weinberg JS, Zadeh G, Schiff D. Treatment for Brain Metastases: ASCO-SNO-ASTRO Guideline. J Clin Oncol 2022;40(5):492-516. Go to original source... Go to PubMed...
    4. Schiff D, Messersmith H, Brastianos PK, Brown PD, Burri S, Dunn IF, Gaspar LE, Gondi V, Jordan JT, Maues J, Mohile N, Redjal N, Stevens GH, Sulman EP, van den Bent M, Wallace HJ, Zadeh G, Vogelbaum MA. Radiation Therapy for Brain Metastases: ASCO Guideline Endorsement of ASTRO Guideline. J Clin Oncol 2022;40(20):2271-6. Go to original source... Go to PubMed...
    5. Le Rhun E, Guckenberger M, Smits M, Dummer R, Bachelot T, Sahm F, Galldiks N, de Azambuja E, Berghoff AS, Metellus P, Peters S, Hong YK, Winkler F, Schadendorf D, van den Bent M, Seoane J, Stahel R, Minniti G, Wesseling P, Weller M, Preusser M; EANO Executive Board and ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. EANO-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of patients with brain metastasis from solid tumours. Ann Oncol 2021;32(11):1332-47. Go to original source... Go to PubMed...
    6. Raza GH, Capone L, Tini P, Giraffa M, Gentile P, Minniti G. Single-isocenter multiple-target stereotactic radiosurgery for multiple brain metastases: dosimetric evaluation of two automated treatment planning systems. Radiat Oncol 2022;17(1):116. Go to original source... Go to PubMed...
    7. Palmer JD, Sebastian NT, Chu J, DiCostanzo D, Bell EH, Grecula J, Arnett A, Blakaj DM, McGregor J, Elder JB, Lu L, Zoller W, Addington M, Lonser R, Chakravarti A, Brown PD, Raval R. Single-Isocenter Multitarget Stereotactic Radiosurgery Is Safe and Effective in the Treatment of Multiple Brain Metastases. Adv Radiat Oncol 2019;5(1):70-6. Go to original source... Go to PubMed...
    8. Gondi V, Deshmukh S, Brown PD, Wefel JS, Armstrong TS, Tome WA, Gilbert MR, Konski A, Robinson CG, Bovi JA, Benzinger TL, Roberge D, Kundapur V, Kaufman I, Shah S, Usuki KY, Baschnagel AM, Mehta MP, Kachnic LA. Sustained Preservation of Cognition and Prevention of Patient-Reported Symptoms With Hippocampal Avoidance During Whole-Brain Radiation Therapy for Brain Metastases: Final Results of NRG Oncology CC001. Int J Radiat Oncol Biol Phys 2023;117(3):571-80. Go to original source... Go to PubMed...
    9. Kazda T, Pospíšil P, Doleželová H, Jančálek R, Slampa P. Whole brain radiotherapy: Consequences for personalized medicine. Rep Pract Oncol Radiother 2013;18(3):133-8. Go to original source... Go to PubMed...
    10. Gondi V, Bauman G, Bradfield L, Burri SH, Cabrera AR, Cunningham DA, Eaton BR, Hattangadi-Gluth JA, Kim MM, Kotecha R, Kraemer L, Li J, Nagpal S, Rusthoven CG, Suh JH, Tomé WA, Wang TJ, Zimmer AS, Ziu M, Brown PD. Radiation Therapy for Brain Metastases: An ASTRO Clinical Practice Guideline. Pract Radiat Oncol 2022;12(4):265-82. Go to original source... Go to PubMed...
    11. Brown PD, Ahluwalia MS, Khan OH, Asher AL, Wefel JS, Gondi V. Whole-Brain Radiotherapy for Brain Metastases: Evolution or Revolution? J Clin Oncol 2018;36(5):483-91. Go to original source... Go to PubMed...
    12. Pospisil P, Kazda T, Bulik M, Dobiaskova M, Burkon P, Hynkova L, Slampa P, Jancalek R. Hippocampal proton MR spectroscopy as a novel approach in the assessment of radiation injury and the correlation to neurocognitive function impairment: initial experiences. Radiat Oncol 2015;10:211. Go to original source... Go to PubMed...
    13. Pospisil P, Kazda T, Hynkova L, Bulik M, Dobiaskova M, Burkon P, Laack NN, Slampa P, Jancalek R. Post-WBRT cognitive impairment and hippocampal neuronal depletion measured by in vivo metabolic MR spectroscopy: Results of prospective investigational study. Radiother Oncol 2017;122(3):373-9. Go to original source... Go to PubMed...
    14. Sperduto PW, Berkey B, Gaspar LE, Mehta M, Curran W. A new prognostic index and comparison to three other indices for patients with brain metastases: an analysis of 1,960 patients in the RTOG database. Int J Radiat Oncol Biol Phys 2008;70(2):510-4. Go to original source... Go to PubMed...
    15. Provencher SW. Automatic quantitation of localized in vivo 1H spectra with LCModel. NMR Biomed 2001;14(4):260-4. Go to original source... Go to PubMed...
    16. Hsu YY, Chen MC, Lim KE, Chang C. Reproducibility of hippocampal single-Voxel proton MR spectroscopy and chemical shift imaging. AJR Am J Roentgenol 2001;176(2):529-36. Go to original source... Go to PubMed...
    17. Gondi V, Tome WA, Rowley HA, Mehta MP. Hippocampal contouring: A Contouring Atlas for RTOG 0933. Available from: https://www.nrgoncology.org/ciro-brain [accessed 2024 Jan 15]
    18. Abraham CD, Pugh SL, Bovi JA, Gondi V, Mehta MP, Benzinger T, Owen CJ, Lo SS, Kundapur V, Brown PD, Sun AY, Howard SP, DeNittis AS, Robinson CG, Kachnic LA. Association of Pretreatment Hippocampal Volume With Neurocognitive Function in Patients Treated With Hippocampal Avoidance Whole Brain Radiation Therapy for Brain Metastases: Secondary Analysis of NRG Oncology/RTOG 0933. Adv Radiat Oncol 2021;7(6):100859. Go to original source... Go to PubMed...
    19. Benedict RH, Groninger L, Schretlen D, Dobraski M. Shpritz B. Revision of the Brief Visuospatial Memory Test: Studies of normal performance, reliability, and validity. Psychol Assess 1996;8(2):145-53. Go to original source...
    20. Brown PD, Gondi V, Pugh S, Tome WA, Wefel JS, Armstrong TS, Bovi JA, Robinson C, Konski A, Khuntia D, Grosshans D, Benzinger TLS, Bruner D, Gilbert MR, Roberge D, Kundapur V, Devisetty K, Shah S, Usuki K, Anderson BM, Stea B, Yoon H, Li J, Laack NN, Kruser TJ, Chmura SJ, Shi W, Deshmukh S, Mehta MP, Kachnic LA; for NRG Oncology. Hippocampal Avoidance During Whole-Brain Radiotherapy Plus Memantine for Patients With Brain Metastases: Phase III Trial NRG Oncology CC001. J Clin Oncol 2020;38(10):1019-29. Go to original source... Go to PubMed...
    21. Woods K, Shen ZL, Xu Z, Zhang H, Natsuaki Y, Cheng K, Li V, Kim N, Ma L, Chang E. Hippocampal sparing radiation therapy for brain metastases: treatment techniques and clinical implementation. Chin Clin Oncol 2023;12(5):56. Go to original source... Go to PubMed...
    22. Barbour AB, Jacobs CD, Williamson H, Floyd SR, Suneja G, Torok JA, Kirkpatrick JP. Radiation Therapy Practice Patterns for Brain Metastases in the United States in the Stereotactic Radiosurgery Era. Adv Radiat Oncol 2019;5(1):43-52. Go to original source... Go to PubMed...
    23. Slade AN, Stanic S. The impact of RTOG 0614 and RTOG 0933 trials in routine clinical practice: The US Survey of Utilization of Memantine and IMRT planning for hippocampus sparing in patients receiving whole brain radiotherapy for brain metastases. Contemp Clin Trials 2016;47:74-7. Go to original source... Go to PubMed...
    24. Barry P, Amsbaugh M, Ziegler C, Dragun A. Patterns of care with regard to whole-brain radiotherapy technique and delivery among academic centers in the United States. Journal of Community and Supportive Oncology 2017;15(2):89-94. Go to original source...
    25. Sammaddar D, Basu A, Roy P, Chowdhury H. Incidence and clinical profile of brain metastasis treated with whole brain radiotherapy in a tertiary hospital in eastern India: A retrospective audit. Indian J Cancer 2023;60(3):337-44. Go to original source... Go to PubMed...
    26. Jairam V, Park HS, Yu JB, Bindra RS, Contessa JN, Jethwa KR. Practice Patterns Related to Mitigation of Neurocognitive Decline in Patients Receiving Whole Brain Radiation Therapy. Adv Radiat Oncol 2022;7(4):100949. Go to original source... Go to PubMed...
    27. Bovi JA, Pugh SL, Sabsevitz D, Robinson CG, Paulson E, Mehta MP, Gondi V, Kundapur V, Shahin MS, Chao ST, Machtay M, DeNittis AS, Laack NN, Greenspoon JN, Moore KN, Huang J, Dominello MM, Kachnic LA. Pretreatment Volume of MRI-Determined White Matter Injury Predicts Neurocognitive Decline After Hippocampal Avoidant Whole-Brain Radiation Therapy for Brain Metastases: Secondary Analysis of NRG Oncology Radiation Therapy Oncology Group 0933. Adv Radiat Oncol 2019;4(4):579-86. Go to original source... Go to PubMed...
    28. Leskinen S, Shah HA, Yaffe B, Schneider SJ, Ben-Shalom N, Boockvar JA, D'Amico RS, Wernicke AG. Hippocampal avoidance in whole brain radiotherapy and prophylactic cranial irradiation: a systematic review and meta-analysis. J Neurooncol 2023;163(3):515-27. Go to original source... Go to PubMed...
    29. Sozinova EV, Kozlovskiy SA, Vartanov AV, Skvortsova VB, Pirogov YA, Anisimov NV, Kupriyanov DA. The role of hippocampal parts in verbal memory and activation processes. International Journal of Psychophysiology 2008;69(3):312. Go to original source...

    This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0), which permits use, distribution, and reproduction in any medium, provided the original publication is properly cited. No use, distribution or reproduction is permitted which does not comply with these terms.


    Return to the content