Hippocampal protection during preventive cranial irradiation and neurocognitive functions in patients with small cell lung cancer
Abstract
Background: In small cell lung cancer (SCLC), limiting the radiation dose in the hippocampus area during preventive cranial irradiation (PCI) can reduce nerve injury and cognitive decline. This study was done to compare changes in cognitive functions between hippocampal-protected (3D-H) and non-hippocampal-protected (3D) patients during PCI.
Materials and methods: the study group included 113 patients with SCLC qualified to PCI divided in two subgroups: 3D-H (n = 74) and 3D (n = 39). Two diagnostic and screening tests, Mini-Mental State Examination (MMSE) Short Scale and Montreal Cognitive Assessment (MoCA) Scale, have been applied before the start of irradiation, immediately after and 3 months after PCI.
Results: The doses delivered to the volume of the left and right hippocampus were similar and amounted to 12.00 Gy and 12.05 Gy, respectively. There were no differences between 3D-H and 3D groups in the MoCA and MMSE tests at any time point. In both groups the values in MoCA and MMSE scales differed between time points I, II and III. The patients in the 3D-H group were less likely than patients in 3D group to experience significant cognitive decline on the MoCA scale (p = 0.003), but not on the MMSE scale (p = 0.103).
Conclusions: Following PCI, SCLC patients experience significant cognitive decline, even when the radiation dose in the hippocampal area is reduced. This trend continues for at least 3 months following the PCI. In hippocampal-protected patients significant cognitive decline assessed on the MoCA scale is less common than in non-hippocampal-protected patients.
Keywords: preventive cranial irradiationhippocampal sparingsmall cell lung cancerneurocognitive dysfunction
References
- Saltos A, Shafique M, Chiappori A. Update on the Biology, Management, and Treatment of Small Cell Lung Cancer (SCLC). Front Oncol. 2020; 10: 1074.
- Gazdar AF, Bunn PA, Minna JD. Small-cell lung cancer: what we know, what we need to know and the path forward. Nat Rev Cancer. 2017; 17(12): 725–737.
- Siegel RL, Miller KD, Fuchs HE, et al. Cancer Statistics, 2021. CA Cancer J Clin. 2021; 71(1): 7–33.
- Rudin CM, Brambilla E, Faivre-Finn C, et al. Small Cell Lung Cancer: Can Recent Advances in Biology and Molecular Biology Be Translated into Improved Outcomes? J Thorac Oncol. 2016; 11(4): 453–474.
- Zhu Y, Cui Y, Zheng X, et al. Small-cell lung cancer brain metastasis: From molecular mechanisms to diagnosis and treatment. Biochim Biophys Acta Mol Basis Dis. 2022; 1868(12): 166557.
- Lukas RV, Gondi V, Kamson DO, et al. State-of-the-art considerations in small cell lung cancer brain metastases. Oncotarget. 2017; 8(41): 71223–71233.
- Cho SeJ, Sunwoo L, Baik SH, et al. Brain metastasis detection using machine learning: a systematic review and meta-analysis. Neuro Oncol. 2021; 23(2): 214–225.
- Blanchard P, Le Péchoux C. Prophylactic cranial irradiation in lung cancer. Curr Opin Oncol. 2010; 22(2): 94–101.
- Zhang W, Jiang W, Luan L, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer: a systematic review of the literature with meta-analysis. BMC Cancer. 2014; 14: 793.
- Davies AM, Lara PN, Lau DH, et al. Treatment of extensive small cell lung cancer. Hematol Oncol Clin North Am. 2004; 18(2): 373–385.
- Bogart JA, Waqar SN, Mix MD. Radiation and Systemic Therapy for Limited-Stage Small-Cell Lung Cancer. J Clin Oncol. 2022; 40(6): 661–670.
- Maeng CH, Song JU, Shim SR, et al. The Role of Prophylactic Cranial Irradiation in Patients With Extensive Stage Small Cell Lung Cancer: A Systematic Review and Meta-Analysis. J Thorac Oncol. 2018; 13(6): 840–848.
- Nakahara Y, Sasaki J, Fukui T, et al. The role of prophylactic cranial irradiation for patients with small-cell lung cancer. Jpn J Clin Oncol. 2018; 48(1): 26–30.
- Aupérin A, Arriagada R, Pignon JP, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med. 1999; 341(7): 476–484.
- Owonikoko TK, Ramalingam S. Small cell lung cancer in elderly patients: a review. J Natl Compr Canc Netw. 2008; 6(3): 333–344.
- Chalubinska-Fendler J, Kepka L. Prophylactic cranial irradiation in non-small cell lung cancer: evidence and future development. J Thorac Dis. 2021; 13(5): 3279–3288.
- Belderbos JSA, De Ruysscher DKM, De Jaeger K, et al. Why Did the Randomized Trial of Prophylactic Cranial Irradiation With or Without Hippocampus Avoidance in SCLC Not Reveal a Difference? J Thorac Oncol. 2021; 16(6): e42–e45.
- Nasreddine ZS, Phillips NA, Bédirian V, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005; 53(4): 695–699.
- Sokołowska N, Sokołowski R, Oleksy E, et al. Usefulness of the Polish versions of the Montreal Cognitive Assessment 7.2 and the Mini-Mental State Examination as screening instruments for the detection of mild neurocognitive disorder. Neurol Neurochir Pol. 2020; 54(5): 440–448.
- Tan HH, Xu J, Teoh HL, et al. Decline in changing Montreal Cognitive Assessment (MoCA) scores is associated with post-stroke cognitive decline determined by a formal neuropsychological evaluation. PLoS One. 2017; 12(3): e0173291.
- Gondi V, Pugh SL, Tome WA, et al. Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): a phase II multi-institutional trial. J Clin Oncol. 2014; 32(34): 3810–3816.
- Gondi V, Deshmukh S, Brown PD, et al. 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): 571–580.
- Meyers CA, Smith JA, Bezjak A, et al. Neurocognitive function and progression in patients with brain metastases treated with whole-brain radiation and motexafin gadolinium: results of a randomized phase III trial. J Clin Oncol. 2004; 22(1): 157–165.
- Regine WF, Schmitt FA, Scott CB, et al. Feasibility of neurocognitive outcome evaluations in patients with brain metastases in a multi-institutional cooperative group setting: results of Radiation Therapy Oncology Group trial BR-0018. Int J Radiat Oncol Biol Phys. 2004; 58(5): 1346–1352.
- Slotman BJ, Mauer ME, Bottomley A, et al. Prophylactic cranial irradiation in extensive disease small-cell lung cancer: short-term health-related quality of life and patient reported symptoms: results of an international Phase III randomized controlled trial by the EORTC Radiation Oncology and Lung Cancer Groups. J Clin Oncol. 2009; 27(1): 78–84.
- Wang B, Fu S, Huang Y, et al. The Effect of Hippocampal Avoidance Whole Brain Radiotherapy on the Preservation of Long-Term Neurocognitive Function in Non-Small Cell Lung Cancer Patients With Brain Metastasis. Technol Cancer Res Treat. 2021; 20: 15330338211034269.
- Wu Y, Zhang Yi, Yuan X, et al. Influence of education level on MMSE and MoCA scores of elderly inpatients. Appl Neuropsychol Adult. 2023; 30(4): 414–418.
- Jia X, Wang Z, Huang F, et al. A comparison of the Mini-Mental State Examination (MMSE) with the Montreal Cognitive Assessment (MoCA) for mild cognitive impairment screening in Chinese middle-aged and older population: a cross-sectional study. BMC Psychiatry. 2021; 21(1): 485.
- Borland E, Nägga K, Nilsson PM, et al. The Montreal Cognitive Assessment: Normative Data from a Large Swedish Population-Based Cohort. J Alzheimers Dis. 2017; 59(3): 893–901.
- Rambe AS, Fitri FI. Correlation between the Montreal Cognitive Assessment-Indonesian Version (Moca-INA) and the Mini-Mental State Examination (MMSE) in Elderly. Open Access Maced J Med Sci. 2017; 5(7): 915–919.