Vol 15, No 2 (2019)
Review paper
Published online: 2019-05-17
Benefits and difficulties during brain radiotherapy planning with hippocampus sparing
Oncol Clin Pract 2019;15(2):104-110.
Abstract
Radiotherapy (RT) is frequently used in the treatment of primary and secondary brain tumours, as well as in prophylactic cranial irradiation (PCI). The hippocampus plays a key function in the process of remembering, relaying information from short-term to long-term memory as consolidation, and spatial orientation. Sparing the hippocampus during brain radiotherapy aims to prevent hippocampal-dependent cognitive function deterioration. This procedure requires a good knowledge of the brain’s radiological anatomy and use of modern radiotherapy techniques.
This article presents the validity of hippocampus sparing during brain radiotherapy, the potential benefits of using this procedure, available clinical premises regarding patient qualification, and technical difficulties in the brain’s RT planning with hippocampus avoidance.
Keywords: hippocampus sparingbrain radiotherapycognitive function
References
- Chera BS, Amdur RJ, Patel P, et al. A radiation oncologist's guide to contouring the hippocampus. Am J Clin Oncol. 2009; 32(1): 20–22.
- Kazda T, Jancalek R, Pospisil P, et al. Why and how to spare the hippocampus during brain radiotherapy: the developing role of hippocampal avoidance in cranial radiotherapy. Radiat Oncol. 2014; 9: 139.
- Kier EL, Kim JH, Fulbright RK, et al. Embryology of the human fetal hippocampus: MR imaging, anatomy, and histology. AJNR Am J Neuroradiol. 1997; 18(3): 525–532.
- Barazzuol L, Rickett N, Ju L, et al. Low levels of endogenous or X-ray-induced DNA double-strand breaks activate apoptosis in adult neural stem cells. J Cell Sci. 2015; 128(19): 3597–3606.
- Lv X, He H, Yang Y, et al. Radiation-induced hippocampal atrophy in patients with nasopharyngeal carcinoma early after radiotherapy: a longitudinal MR-based hippocampal subfield analysis. Brain Imaging Behav. 2018 [Epub ahead of print].
- Monje ML, Mizumatsu S, Fike JR, et al. Irradiation induces neural precursor-cell dysfunction. Nat Med. 2002; 8(9): 955–962.
- Mizumatsu S, Monje ML, Morhardt DR, et al. Extreme sensitivity of adult neurogenesis to low doses of X-irradiation. Cancer Res. 2003; 63(14): 4021–4027.
- Tofilon PJ, Fike JR. The radioresponse of the central nervous system: a dynamic process. Radiat Res. 2000; 153(4): 357–370.
- Murray KJ, Scott C, Zachariah B, et al. Importance of the mini-mental status examination in the treatment of patients with brain metastases: a report from the Radiation Therapy Oncology Group protocol 91-04. Int J Radiat Oncol Biol Phys. 2000; 48(1): 59–64.
- Chang EL, Wefel JS, Hess KR, et al. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 2009; 10(11): 1037–1044.
- Li J, Bentzen SM, Renschler M, et al. Regression after whole-brain radiation therapy for brain metastases correlates with survival and improved neurocognitive function. J Clin Oncol. 2007; 25(10): 1260–1266.
- Welzel G, Fleckenstein K, Schaefer J, et al. Memory function before and after whole brain radiotherapy in patients with and without brain metastases. Int J Radiat Oncol Biol Phys. 2008; 72(5): 1311–1318.
- Scoccianti S, Ricardi U. Treatment of brain metastases: review of phase III randomized controlled trials. Radiother Oncol. 2012; 102(2): 168–179.
- Oğurel T, Oğurel R, Özer MA, et al. Mini-mental state exam versus Montreal Cognitive Assessment in patients with diabetic retinopathy. Niger J Clin Pract. 2015; 18(6): 786–789.
- Welzel G, Fleckenstein K, Mai SK, et al. Acute neurocognitive impairment during cranial radiation therapy in patients with intracranial tumors. Strahlenther Onkol. 2008; 184(12): 647–654.
- Kanard A, Frytak S, Jatoi A. Cognitive dysfunction in patients with small-cell lung cancer: incidence, causes, and suggestions on management. J Support Oncol. 2004; 2(2): 127–140.
- Falkowski A, Kurcz I. Procesy poznawcze. JS, Psychologia ogólna. Podręcznik akademicki, t. 2. GWP, Gdańsk 2006.
- 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.
- Chang EL, Wefel JS, Hess KR, et al. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 2009; 10(11): 1037–1044.
- Meyers CA, Brown PD. Role and relevance of neurocognitive assessment in clinical trials of patients with CNS tumors. J Clin Oncol. 2006; 24(8): 1305–1309.
- 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.
- Jehn CF, Becker B, Flath B, et al. Neurocognitive function, brain-derived neurotrophic factor (BDNF) and IL-6 levels in cancer patients with depression. J Neuroimmunol. 2015; 287: 88–92.
- Petty F, Noyes R. Depression secondary to cancer. Biol Psychiatry. 1981; 16(12): 1203–1220.
- 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.
- Marsh JC, Herskovic AM, Gielda BT, et al. Intracranial metastatic disease spares the limbic circuit: a review of 697 metastatic lesions in 107 patients. Int J Radiat Oncol Biol Phys. 2010; 76(2): 504–512.
- Ghia A, Tomé WA, Thomas S, et al. Distribution of brain metastases in relation to the hippocampus: implications for neurocognitive functional preservation. Int J Radiat Oncol Biol Phys. 2007; 68(4): 971–977.
- Sun A, Bae K, Gore EM, et al. Phase III trial of prophylactic cranial irradiation compared with observation in patients with locally advanced non-small-cell lung cancer: neurocognitive and quality-of-life analysis. J Clin Oncol. 2011; 29(3): 279–286.
- 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.
- www.rtog.org/CoreLab/ContouringAtlases/HippocampalSparing.aspx.
- Cacao E, Cucinotta FA. Modeling Heavy-Ion Impairment of Hippocampal Neurogenesis after Acute and Fractionated Irradiation. Radiat Res. 2016; 186(6): 624–637.
- Konopka-Filippow M, Sierko E, Hempel D, et al. Learning curve and interobserver variability in contouring hippocampus under the guidelines of Radiation Therapy Oncology Group 0933 hippocampal sparing atlas recommendations. Radiother Oncol. 2018; 127: S1238.
- Kim M, Wu G, Li W, et al. Automatic hippocampus segmentation of 7.0 Tesla MR images by combining multiple atlases and auto-context models. Neuroimage. 2013; 83: 335–345.
- Artaechevarria X, Munoz-Barrutia A, Ortiz-de-Solorzano C. Combination strategies in multi-atlas image segmentation: application to brain MR data. IEEE Trans Med Imaging. 2009; 28(8): 1266–1277.
- Heckemann RA, Hajnal JV, Aljabar P, et al. Automatic anatomical brain MRI segmentation combining label propagation and decision fusion. Neuroimage. 2006; 33(1): 115–126.
- Tu Z, Bai X. Auto-context and its application to high-level vision tasks and 3D brain image segmentation. IEEE Trans Pattern Anal Mach Intell. 2010; 32(10): 1744–1757.
- Dekeyzer S, De Kock I, Nikoubashman O, et al. "Unforgettable" — a pictorial essay on anatomy and pathology of the hippocampus. Insights Imaging. 2017; 8(2): 199–212.
- Wang S, Zheng D, Zhang C, et al. Automatic planning on hippocampal avoidance whole-brain radiotherapy. Med Dosim. 2017; 42(1): 63–68.
- Becerril-Villanueva E, Ponce-Regalado MD, Pérez-Sánchez G, et al. Chronic infection with Mycobacterium lepraemurium induces alterations in the hippocampus associated with memory loss. Sci Rep. 2018; 8(1): 9063.
- Yuede CM, Timson BF, Hettinger JC, et al. Interactions between stress and physical activity on Alzheimer's disease pathology. Neurobiol Stress. 2018; 8: 158–171.
- Peters MEM, Kockelkoren R, de Brouwer EJM, et al. Histological validation of calcifications in the human hippocampus as seen on computed tomography. PLoS One. 2018; 13(5): e0197073.
- Marsh JC, Godbole R, Diaz AZ, et al. Sparing of the hippocampus, limbic circuit and neural stem cell compartment during partial brain radiotherapy for glioma: a dosimetric feasibility study. J Med Imaging Radiat Oncol. 2011; 55(4): 442–449.
- Canyilmaz E, Uslu GD, Colak F, et al. Comparison of dose distributions hippocampus in high grade gliomas irradiation with linac-based imrt and volumetric arc therapy: a dosimetric study. Springerplus. 2015; 4: 114.
- Chan JL, Lee SW, Fraass BA, et al. Survival and failure patterns of high-grade gliomas after three-dimensional conformal radiotherapy. J Clin Oncol. 2002; 20(6): 1635–1642.
- Marsh J, Godbole R, Diaz A, et al. Feasibility of cognitive sparing approaches in children with intracranial tumors requiring partial brain radiotherapy: A dosimetric study using tomotherapy. journal of Cancer Therapeutics and Research. 2012; 1(1): 1.
- Brodin NP, Munck af Rosenschöld P, Blomstrand M, et al. Hippocampal sparing radiotherapy for pediatric medulloblastoma: impact of treatment margins and treatment technique. Neuro Oncol. 2014; 16(4): 594–602.
- Lester JF, MacBeth FR, Coles B. Prophylactic cranial irradiation for preventing brain metastases in patients undergoing radical treatment for non-small-cell lung cancer: a Cochrane Review. Int J Radiat Oncol Biol Phys. 2005; 63(3): 690–694.
- Stuschke M, Pöttgen C. Prophylactic cranial irradiation as a component of intensified initial treatment of locally advanced non-small cell lung cancer. Lung Cancer. 2003; 42 Suppl 1: S53–S56.
- Le Péchoux C, Dunant A, Senan S, et al. Prophylactic Cranial Irradiation (PCI) Collaborative Group. Standard-dose versus higher-dose prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer in complete remission after chemotherapy and thoracic radiotherapy (PCI 99-01, EORTC 22003-08004, RTOG 0212, and IFCT 99-01): a randomised clinical trial. Lancet Oncol. 2009; 10(5): 467–474.
- Redmond KJ, Hales RK, Anderson-Keightly H, et al. Prospective Study of Hippocampal-Sparing Prophylactic Cranial Irradiation in Limited-Stage Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2017; 98(3): 603–611.
- Tarnawski R, Michalecki L, Blamek S, et al. Feasibility of reducing the irradiation dose in regions of active neurogenesis for prophylactic cranial irradiation in patients with small-cell lung cancer. Neoplasma. 2011; 58(6): 507–515.
- Marsh JC, Gielda BT, Herskovic AM, et al. Cognitive Sparing during the Administration of Whole Brain Radiotherapy and Prophylactic Cranial Irradiation: Current Concepts and Approaches. J Oncol. 2010; 2010: 198208.
- Tallet AV, Azria D, Barlesi F, et al. Neurocognitive function impairment after whole brain radiotherapy for brain metastases: actual assessment. Radiat Oncol. 2012; 7: 77.
- Nevelsky A, Ieumwananonthachai N, Kaidar-Person O, et al. Hippocampal-sparing whole-brain radiotherapy using Elekta equipment. J Appl Clin Med Phys. 2013; 14(3): 4205.
- 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, Tolakanahalli R, Mehta MP, et al. Hippocampal-sparing whole-brain radiotherapy: a "how-to" technique using helical tomotherapy and linear accelerator-based intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys. 2010; 78(4): 1244–1252.
- Krayenbuehl J, Di Martino M, Guckenberger M, et al. Improved plan quality with automated radiotherapy planning for whole brain with hippocampus sparing: a comparison to the RTOG 0933 trial. Radiat Oncol. 2017; 12(1): 161.
- Zhao L, Shen Y, Guo JD, et al. Analyses of distribution and dosimetry of brain metastases in small cell lung cancer with relation to the neural stem cell regions: feasibility of sparing the hippocampus in prophylactic cranial irradiation. Radiat Oncol. 2017; 12(1): 118.
- Gondi V, Mehta MP, Pugh S, et al. Memory Preservation With Conformal Avoidance of the Hippocampus During Whole-Brain Radiation Therapy for Patients With Brain Metastases: Primary Endpoint Results of RTOG 0933. Int J Radiat Oncol Biol Phys. 2013; 87(5): 1186.
- Daniela Falco M, Giancaterino S, D'Andrea M, et al. Hippocampal sparing approach in fractionated stereotactic brain VMAT radio therapy: A retrospective feasibility analysis. J Appl Clin Med Phys. 2018; 19(1): 86–93.
- Di Carlo C, Trignani M, Caravatta L, et al. Hippocampal sparing in stereotactic radiotherapy for brain metastases: To contour or not contour the hippocampus? Cancer Radiother. 2018; 22(2): 120–125.