Skip to main content
SpringerLink
Log in

Brain Toxicity

  • Chapter
  • First Online:
Advances in Radiation Oncology in Lung Cancer

Part of the book series: Medical Radiology ((Med Radiol Radiat Oncol))

  • 343 Accesses

Abstract

Since lung cancer generally has a high, stage-, histology-, and molecular subtype-dependent propensity for brain metastases, many patients receive prophylactic or therapeutic radiotherapy to the brain and are therefore at risk of acute, subacute, or chronic side effects. Certain types of systemic treatment might also cause brain toxicity. In this chapter the different types of toxicity, the pathogenesis, and emerging prevention and treatment strategies are reviewed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Acharya MM, Christie LA, Lan ML et al (2009) Rescue of radiation-induced cognitive impairment through cranial transplantation of human embryonic stem cells. Proc Natl Acad Sci U S A 106:19150–19155

    Google Scholar 

  • Ahles TA, Saykin A (2001) Cognitive effects of standard dose chemotherapy in patients with cancer. Cancer Investig 19:812–820

    Google Scholar 

  • Andratschke N, Nieder C, Price RE, Rivera B, Ang KK (2005) Potential role of growth factors in diminishing radiation therapy neural tissue injury. Semin Oncol 32(Suppl. 3):S67–S70

    Google Scholar 

  • Ang KK, Jiang GL, Feng Y, Stephens LC, Tucker SL, Price RE (2001) Extent and kinetics of recovery of occult spinal cord injury. Int J Radiat Oncol Biol Phys 50:1013–1020

    Google Scholar 

  • Armstrong CL, Hunter JV, Ledakis GE et al (2002) Late cognitive and radiographic changes related to radiotherapy: initial prospective findings. Neurology 59:40–48

    Google Scholar 

  • Betlazar C, Middleton RJ, Banati RB, Liu GJ (2016) The impact of high and low dose ionising radiation on the central nervous system. Redox Biol 9:144–156

    Google Scholar 

  • Bodensohn R, Hadi I, Fleischmann DF et al (2020) Bevacizumab as a treatment option for radiation necrosis after cranial radiation therapy: a retrospective monocentric analysis. Strahlenther Onkol 196:70–76

    Google Scholar 

  • Boothe D, Young R, Yamada Y, Prager A, Chan T, Beal K (2013) Bevacizumab as a treatment for radiation necrosis of brain metastases post stereotactic radiosurgery. Neuro-Oncology 15:1257–1263

    Google Scholar 

  • Brown PD, Pugh S, Laack NN, Radiation Therapy Oncology Group (RTOG) et al (2013) Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial. Neuro-Oncology 15:1429–1437

    Google Scholar 

  • Brown PD, Jaeckle K, Ballman KV et al (2016) Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases: A randomized clinical trial. JAMA 316:401–409

    Google Scholar 

  • Brown PD, Ballman KV, Cerhan JH et al (2017) 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 18:1049–1060

    Google Scholar 

  • Brown PD, Gondi V, Pugh S, for NRG Oncology et al (2020) Hippocampal avoidance during whole-brain radiotherapy plus memantine for patients with brain metastases: Phase III trial NRG Oncology CC001. J Clin Oncol 38:1019–1029

    Google Scholar 

  • Calvo W, Hopewell JW, Reinhold HS, Yeung TK (1988) Time- and dose-related changes in the white matter of the rat brain after single doses of X–rays. Br J Biol 61:1043–1052

    Google Scholar 

  • Chang EL, Wefel JS, Hess KR et al (2009) Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol 10:1037–1044

    Google Scholar 

  • Chiang CS, McBride WH (1991) Radiation enhances tumor necrosis factor alpha production by murine brain cells. Brain Res 566:265–269

    Google Scholar 

  • Chiang CS, McBride WH, Withers HR (1993) Radiation-induced astrocytic and microglial responses in mouse brain. Radiother Oncol 29:60–68

    Google Scholar 

  • Cicciarello R, D’Avella D, Gagliardi ME et al (1996) Time-related ultrastructural changes in an experimental model of whole brain irradiation. Neurosurgery 38:772–779

    Google Scholar 

  • Co J, De Moraes MV, Katznelson R et al (2019) Hyperbaric oxygen for radiation necrosis of the brain. Can J Neurol Sci 30:1–8

    Google Scholar 

  • De Angelis LM, Delattre JY, Posner JB (1989) Radiation induced dementia in patients cured of brain metastases. Neurology 39:789–796

    Google Scholar 

  • Dietrich J, Prust M, Kaiser J (2015) Chemotherapy, cognitive impairment and hippocampal toxicity. Neuroscience 309:224–232

    Google Scholar 

  • Eguren-Santamaria I, Sanmamed MF, Goldberg SB et al (2020) PD-1/PD-L1 blockers in NSCLC brain metastases: Challenging paradigms and clinical practice. Clin Cancer Res 26:4186–4197

    Google Scholar 

  • Fike JR, Gobbel GT, Marton LJ, Seilhan TM (1994) Radiation brain injury is reduced by the polyamine inhibitor α-difluoromethylornithine. Radiat Res 138:99–106

    Google Scholar 

  • Fike JR, Rosi S, Limoli CL (2009) Neural precursor cells and central nervous system radiation sensitivity. Semin Radiat Oncol 19:122–132

    Google Scholar 

  • Galldiks N, Abdulla DS, Scheffler M et al (2020a) Treatment monitoring of immunotherapy and targeted therapy using 18F-FET PET in patients with melanoma and lung cancer brain metastases: initial experiences. J Nucl Med 62(4):464–470. https://doi.org/10.2967/jnumed.120.248278

    Article  Google Scholar 

  • Galldiks N, Kocher M, Ceccon G et al (2020b) Imaging challenges of immunotherapy and targeted therapy in patients with brain metastases: response, progression, and pseudoprogression. Neuro-Oncology 22:17–30

    Google Scholar 

  • Glantz MJ, Burger PC, Friedman AH, Radtke RA, Massey EW, Schold SC (1994) Treatment of radiation-induced nervous system injury with heparin and warfarin. Neurology 44:2020–2027

    Google Scholar 

  • Gobbel GT, Bellinzona M, Vogt AR, Gupta N, Fike JR, Chan PH (1998) Response of postmitotic neurons to x-irradiation: Implications for the role of DNA damage in neuronal apoptosis. J Neurosci 18:147–155

    Google Scholar 

  • Gondi V, Tomé WA, Mehta MP (2010) Why avoid the hippocampus? A comprehensive review. Radiother Oncol 97:370–376

    Google Scholar 

  • Gondi V, Pugh SL, Tome WA et al (2014) 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 32:3810–3816

    Google Scholar 

  • Greene-Schloesser D, Payne V, Peiffer AM et al (2014) The peroxisomal proliferator-activated receptor (PPAR) α agonist, fenofibrate, prevents fractionated whole-brain irradiation-induced cognitive impairment. Radiat Res 181:33–44

    Google Scholar 

  • Gu C, Casaccia-Bonnefil P, Srinivasan A, Chao MV (1999) Oligodendrocyte apoptosis mediated by caspase activation. J Neurosci 19:3043–3049

    Google Scholar 

  • Hanbury DB, Robbins ME, Bourland JD et al (2015) Pathology of fractionated whole-brain irradiation in rhesus monkeys (Macaca mulatta). Radiat Res 183:367–374

    Google Scholar 

  • Hayakawa K, Borchardt PE, Sakuma S, Ijichi A, Niibe H, Tofilon PJ (1997) Microglial cytokine gene induction after irradiation is affected by morphologic differentiation. Radiat Med 15:405–410

    Google Scholar 

  • Helis CA, Hughes RT, Glenn CW et al (2020) Predictors of adverse radiation effect in brain metastasis patients treated with stereotactic radiosurgery and immune checkpoint inhibitor therapy. Int J Radiat Oncol Biol Phys 108:295–303

    Google Scholar 

  • Herskovic AM, Orton CG (1986) Elective brain irradiation for small cell anaplastic lung cancer. Int J Radiat Oncol Biol Phys 12:427–429

    Google Scholar 

  • Hisahara S, Shoji S, Okano H, Miura M (1997) ICE/CED3 family executes oligodendrocyte apoptosis by tumor necrosis factor. J Neurochem 69:10–20

    Google Scholar 

  • Hladik D, Tapio S (2016) Effects of ionizing radiation on the mammalian brain. Mutat Res 770:219–230

    Google Scholar 

  • Hong JH, Chiang CS, Campbell IL, Sun JR, Withers HR, McBride WH (1995) Induction of acute phase gene expression by brain irradiation. Int J Radiat Oncol Biol Phys 33:619–626

    Google Scholar 

  • Hong CS, Beckta JM, Kundishora AJ, Elsamadicy AA, Chiang VL (2020) Laser interstitial thermal therapy for treatment of cerebral radiation necrosis. Int J Hyperth 37:68–76

    Google Scholar 

  • Hopewell JW, van der Kogel AJ (1999) Pathophysiological mechanisms leading to the development of late radiation-induced damage to the central nervous system. Front Radiat Ther Oncol 33:265–275

    Google Scholar 

  • Hopewell JW, Calvo W, Campling D, Reinhold HS, Rezvani M, Yeung TK (1989) Effects of radiation on the microvasculature. Front Radiat Ther Oncol 23:85–95

    Google Scholar 

  • Hulshof MC, Stark NM, van der Kleij A, Sminia P, Smeding HM, Gonzalez D (2002) Hyperbaric oxygen therapy for cognitive disorders after irradiation of the brain. Strahlenther Onkol 178:192–198

    Google Scholar 

  • Jimenez RB, Alexander BM, Mahadevan A et al (2017) The impact of different stereotactic radiation therapy regimens for brain metastases on local control and toxicity. Adv Radiat Oncol 2:391–397

    Google Scholar 

  • Johnson BE, Patronas N, Hayes W et al (1990) Neurologic, computed cranial tomographic, and magnetic resonance imaging abnormalities in patients with small-cell lung cancer: further follow-up of 6- to 13-year survivors. J Clin Oncol 8:48–56

    Google Scholar 

  • Kamiryo T, Kassell NF, Thai QA, Lopes MB, Lee KS, Steiner L (1996) Histological changes in the normal rat brain after gamma irradiation. Acta Neurochir 138:451–459

    Google Scholar 

  • Keime-Guibert F, Napolitano M, Delattre JY (1998) Neurological complications of radiotherapy and chemotherapy. J Neurol 245:695–708

    Google Scholar 

  • Klein M, Drijver AJ, van den Bent MJ et al (2021) Memory in low-grade glioma patients treated with radiotherapy or Temozolomide. A correlative analysis of EORTC study 22033-26033. Neuro Oncol 23(5):803–811. https://doi.org/10.1093/neuonc/noaa252

    Article  Google Scholar 

  • Knitter JR, Erly WK, Stea BD et al (2018) Interval change in diffusion and perfusion MRI parameters for the assessment of pseudoprogression in cerebral metastases treated with stereotactic radiation. AJR Am J Roentgenol 211:168–175

    Google Scholar 

  • Kondziolka D, Mori Y, Martinez AJ, McLaughlin MR, Flickinger JC, Lunsford LD (1999) Beneficial effects of the radioprotectant 21-aminosteroid U-74389G in a radiosurgery rat malignant glioma model. Int J Radiat Oncol Biol Phys 44:179–184

    Google Scholar 

  • Larocca JN, Farooq M, Norton WT (1997) Induction of oligodendrocyte apoptosis by C2-ceramide. Neurochem Res 22:529–534

    Google Scholar 

  • Laukkanen E, Klanoff H, Allan B, Graeb D, Murray N (1988) The role of prophylactic brain irradiation in limited stage small cell lung cancer: clinical, neuropsychological, and CT sequelae. Int J Radiat Oncol Biol Phys 14:1109–1117

    Google Scholar 

  • Laurin D, Verreault R, Lindsay J, Rockwood K (2001) Physical activity and risk of cognitive impairment and dementia in elderly persons. Arch Neurol 58:498–504

    Google Scholar 

  • Lawrence YR, Li XA, El Naqa I, Hahn CA, Marks LB, Merchant TE, Dicker AP (2010) Radiation dose-volume effects in the brain. Int J Radiat Oncol Biol Phys 76:S20–S27

    Google Scholar 

  • Le Pechoux C, Laplanche A, Faivre-Finn C et al (2011) Clinical neurological outcome and quality of life among patients with limited small-cell cancer treated with two different doses of prophylactic cranial irradiation in the intergroup phase III trial (PCI 99-01, EORT 22003-08004, RTOG 0212 and IFCT 99-01). Ann Oncol 22:1154–1163

    Google Scholar 

  • Leavitt RJ, Limoli CL, Baulch JE (2019) miRNA-based therapeutic potential of stem cell-derived extracellular vesicles: a safe cell-free treatment to ameliorate radiation-induced brain injury. Int J Radiat Biol 95:427–435

    Google Scholar 

  • Levin VA, Bidaut L, Hou P et al (2011) Randomized double-blind placebo-controlled trial of bevacizumab therapy for radiation necrosis of the central nervous system. Int J Radiat Oncol Biol Phys 79:1487–1495

    Google Scholar 

  • Lichtenwalner RJ, Forbes ME, Bennett SA, Lynch CD, Riddle DR (2001) Intracerebroventricular infusion of insulin-like growth factor-1 ameliorates the age-related decline in hippocampal neurogenesis. Neuroscience 107:603–613

    Google Scholar 

  • Lin NU, Lee EQ, Aoyama H, Response Assessment in Neuro-Oncology (RANO) Group et al (2015) Response assessment criteria for brain metastases: proposal from the RANO group. Lancet Oncol 16:e270–e278

    Google Scholar 

  • Ljubimova NV, Levitman MK, Plotnikova ED, Eidus LK (1991) Endothelial cell population dynamics in rat brain after local irradiation. Br J Radiol 64:934–940

    Google Scholar 

  • Lohmann P, Galldiks N, Kocher M et al (2020) Radiomics in neuro-oncology: Basics, workflow, and applications. Methods S1046-2023(19):30317–30312

    Google Scholar 

  • Loi M, Caini S, Scoccianti S et al (2020) Stereotactic reirradiation for local failure of brain metastases following previous radiosurgery: Systematic review and meta-analysis. Crit Rev Oncol Hematol 153:103043

    Google Scholar 

  • Madsen TM, Kristjansen PE, Bolwig TG, Wortwein G (2003) Arrested neuronal proliferation and impaired hippocampal function following fractionated irradiation in the adult rat. Neuroscience 119:635–642

    Google Scholar 

  • Mayo C, Martel MK, Marks LB, Flickinger J, Nam J, Kirkpatrick J (2010) Radiation dose-volume effects of optic nerves and chiasm. Int J Radiat Oncol Biol Phys 76:S28–S35

    Google Scholar 

  • Mehta MP (2015) The controversy surrounding the use of whole-brain radiotherapy in brain metastases patients. Neuro-Oncology 17:919–923

    Google Scholar 

  • Mildenberger M, Beach TG, McGeer EG, Ludgate CM (1990) An animal model of prophylactic cranial irradiation: histologic effects at acute, early and delayed stages. Int J Radiat Oncol Biol Phys 18:1051–1060

    Google Scholar 

  • Monje ML, Mizumatsu S, Fike JR, Palmer TD (2002) Irradiation induces neural precursor-cell dysfunction. Nature Med 8:928–930

    Google Scholar 

  • Monje ML, Vogel H, Masek M et al (2007) Impaired human hippocampal neurogenesis after treatment for central nervous system malignancies. Ann Neurol 62:515–520

    Google Scholar 

  • Montay-Gruel P, Acharya MM, Petersson K et al (2019) Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species. Proc Natl Acad Sci U S A 116:10943–10951

    Google Scholar 

  • Morris GM, Coderre JA, Bywaters A (1996) Boron neutron capture irradiation of the rat spinal cord: histopathological evidence of a vascular-mediated pathogenesis. Radiat Res 146:313–320

    Google Scholar 

  • Munley MT, Marks LB, Hardenbergh PH, Bentel GC (2001) Functional imaging of normal tissues with nuclear medicine: applications in radiotherapy. Semin Radiat Oncol 11:28–36

    Google Scholar 

  • Murphy ES, Xie H, Merchant TE, Yu JS, Chao ST, Suh JH (2015) Review of cranial radiotherapy-induced vasculopathy. J Neuro-Oncol 122:421–429

    Google Scholar 

  • Nakajima T, Kumabe T, Kanamori M et al (2009) Differential diagnosis between radiation necrosis and glioma progression using sequential proton magnetic resonance spectroscopy and methionine positron emission tomography. Neurol Med Chir (Tokyo) 49:394–401

    Google Scholar 

  • Nieder C, Leicht A, Motaref B, Nestle U, Niewald M, Schnabel K (1999) Late radiation toxicity after whole-brain radiotherapy: the influence of antiepileptic drugs. Am J Clin Oncol 22:573–579

    Google Scholar 

  • Nieder C, Andratschke N, Astner ST (2007) Experimental concepts for toxicity prevention and tissue restoration after central nervous system irradiation. Radiat Oncol 2:23

    Google Scholar 

  • Nieder C, Bremnes RM, Andratschke NH (2009) Prognostic scores in patients with brain metastases from non-small cell lung cancer. J Thorac Oncol 4:1337–1341

    Google Scholar 

  • Nieder C, Mehta MP, Geinitz H, Grosu AL (2018) Prognostic and predictive factors in patients with brain metastases from solid tumors: a review of published nomograms. Crit Rev Oncol Hematol 126:13–18

    Google Scholar 

  • Nieder C, Guckenberger M, Gaspar LE et al (2019) Management of patients with brain metastases from non-small cell lung cancer and adverse prognostic features: multi-national radiation treatment recommendations are heterogeneous. Radiat Oncol 14:33

    Google Scholar 

  • Nosaki K, Seto T, Shimokawa M, Takahashi T, Yamamoto N (2018) Is prophylactic cranial irradiation (PCI) needed in patients with extensive-stage small cell lung cancer showing complete response to first-line chemotherapy? Radiother Oncol 127:344–348

    Google Scholar 

  • Parihar VK, Pasha J, Tran KK, Craver BM, Acharya MM, Limoli CL (2015) Persistent changes in neuronal structure and synaptic plasticity caused by proton irradiation. Brain Struct Funct 220:1161–1171

    Google Scholar 

  • Pena LA, Fuks Z, Kolesnick RN (2000) Radiation-induced apoptosis of endothelial cells in the murine central nervous system: protection by fibroblast growth factor and sphingomyelinase deficiency. Cancer Res 60:321–327

    Google Scholar 

  • Perrini P, Scollato A, Cioffi F, Conti R, Di Lorenzo N (2002) Radiation leukoencephalopathy associated with moderate hydrocephalus: intracranial pressure monitoring and results of ventriculoperitoneal shunting. Neurol Sci 23:237–241

    Google Scholar 

  • Popp I, Rau S, Hintz M et al (2020) Hippocampus-avoidance whole-brain radiation therapy with a simultaneous integrated boost for multiple brain metastases. Cancer 126:2694–2703

    Google Scholar 

  • Rajeswaran A, Trojan A, Burnand B, Giannelli M (2008) Efficacy and side effects of cisplatin- and carboplatin-based doublet chemotherapeutic regimens versus non-platinum-based doublet chemotherapeutic regimens as first line treatment of metastatic non-small cell lung carcinoma: a systematic review of randomized controlled trials. Lung Cancer 59:1–11

    Google Scholar 

  • Raju U, Gumin GJ, Tofilon PJ (2000) Radiation-induced transcription factor activation in the rat cerebral cortex. Int J Radiat Biol 76:1045–1053

    Google Scholar 

  • Robbins ME, Payne V, Tommasi E et al (2009) The AT1 receptor antagonist, L-158,809, prevents or ameliorates fractionated whole-brain irradiation-induced cognitive impairment. Int J Radiat Oncol Biol Phys 73:499–505

    Google Scholar 

  • Romagna A, Unterrainer M, Schmid-Tannwald C et al (2016) Suspected recurrence of brain metastases after focused high dose radiotherapy: can [18F]FET- PET overcome diagnostic uncertainties? Radiat Oncol 11:139

    Google Scholar 

  • Roth NM, Sontag MR, Kiani MF (1999) Early effects of ionizing radiation on the microvascular networks in normal tissue. Radiat Res 151:270–277

    Google Scholar 

  • Rubin P, Gash DM, Hansen JT, Nelson DF, Williams JP (1994) Disruption of the blood-brain barrier as the primary effect of CNS irradiation. Radiother Oncol 31:51–60

    Google Scholar 

  • Rusthoven CG, Kavanagh BD (2017) Prophylactic cranial irradiation (PCI) versus active MRI surveillance for small cell lung cancer: The case for equipoise. J Thorac Oncol 12:1746–1754

    Google Scholar 

  • Satoh J, Kastrukoff LF, Kim SU (1991) Cytokine-induced expression of intercellular adhesion molecule-1 (ICAM1) in cultured human oligodendrocytes and astrocytes. J Neuropathol Exp Neurol 50:215–226

    Google Scholar 

  • Schaue D, Kachikwu EL, McBride WH (2012) Cytokines in radiobiological responses: a review. Radiat Res 178:505–523

    Google Scholar 

  • Schultheiss TE, Kun LE, Ang KK, Stephens LC (1995) Radiation response of the central nervous system. Int J Radiat Oncol Biol Phys 31:1093–1112

    Google Scholar 

  • Sims EC, Plowman PN (2001) Stereotactic radiosurgery XII. Large AVM and the failure of the radiation response modifier gamma linolenic acid to improve the therapeutic ratio. Br J Neurosurg 15:28–34

    Google Scholar 

  • Sloan AE, Arnold SM, St. Clair WH, Regine WF (2003) Brain injury: current management and investigations. Semin Radiat Oncol 13:309–321

    Google Scholar 

  • Smith SM, Limoli CL (2017) Stem cell therapies for the resolution of radiation injury to the brain. Curr Stem Cell Rep 3:342–347

    Google Scholar 

  • Sperduto PW, Yang TJ, Beal K et al (2017) Estimating survival in patients with lung cancer and brain metastases: An update of the Graded Prognostic Assessment for lung cancer using molecular markers (Lung-molGPA). JAMA Oncol 3:827–831

    Google Scholar 

  • Sun A, Bae K, Gore EM et al (2011) 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 29:279–286

    Google Scholar 

  • Takahashi T, Yamanaka T, Seto T et al (2017) Prophylactic cranial irradiation versus observation in patients with extensive-disease small-cell lung cancer: a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol 18:663–671

    Google Scholar 

  • Tanaka J, Fujita H, Matsuda S, Toku K, Sakanaka M, Maeda N (1997) Glucocorticoid- and mineralocorticoid receptors in microglial cells: the two receptors mediate differential effects of corticosteroids. Glia 20:23–37

    Google Scholar 

  • Tofilon PJ, Fike JR (2000) The radioresponse of the central nervous system: a dynamic process. Radiat Res 153:357–370

    Google Scholar 

  • Tomé WA, Gökhan Ş, Gulinello ME et al (2016) Hippocampal-dependent neurocognitive impairment following cranial irradiation observed in pre-clinical models: current knowledge and possible future directions. Br J Radiol 89:20150762

    Google Scholar 

  • Torres IJ, Mundt AJ, Sweeney PJ, Castillo M, Macdonald RL (2003) A longitudinal neuropsychological study of partial brain radiation in adults with brain tumors. Neurology 60:1113–1118

    Google Scholar 

  • Twijnstra A, Boon PJ, Lormans ACM, Ten Velde GPM (1987) Neurotoxicity of prophylactic cranial irradiation in patients with small cell carcinoma of the lung. Eur J Cancer Clin Oncol 23:983–986

    Google Scholar 

  • Van de Pol M, Ten Velde GP, Wilmink JT, Volovics A, Twijnstra A (1997) Efficacy and safety of prophylactic cranial irradiation in patients with small cell lung cancer. J Neuro-Oncol 35:153–160

    Google Scholar 

  • Van der Kogel AJ (1986) Radiation-induced damage in the central nervous system: an interpretation of target cell responses. Br J Cancer 53(Suppl. 7):207–217

    Google Scholar 

  • Varlotto JM, Flickinger JC, Niranjan A, Bhatnagar AK, Kondziolka D, Lunsford LD (2003) Analysis of tumor control and toxicity in patients who have survived at least one year after radiosurgery for brain metastases. Int J Radiat Oncol Biol Phys 57:452–464

    Google Scholar 

  • Vogrig A, Muñiz-Castrillo S, Joubert B et al (2020) Central nervous system complications associated with immune checkpoint inhibitors. J Neurol Neurosurg Psychiatry 91:772–778

    Google Scholar 

  • Whitney KA, Lysaker PH, Steiner AR, Hook JN, Estes DD, Hanna NH (2008) Is “chemobrain” a transient state? A prospective pilot study among persons with non-small cell lung cancer. J Support Oncol 6:313–321

    Google Scholar 

  • Wilke C, Grosshans D, Duman J, Brown P, Li J (2018) Radiation-induced cognitive toxicity: pathophysiology and interventions to reduce toxicity in adults. Neuro-Oncology 20:597–607

    Google Scholar 

  • Winer A, Bodor JN, Borghaei H (2018) Identifying and managing the adverse effects of immune checkpoint blockade. J Thorac Dis 10(Suppl 3):S480–S489

    Google Scholar 

  • Witlox WJA, Ramaekers BLT, Joore MA et al (2020) Health-related quality of life after prophylactic cranial irradiation for stage III non-small cell lung cancer patients: results from the NVALT-11/DLCRG-02 phase III study. Radiother Oncol 144:65–71

    Google Scholar 

  • Wong D, Dorovini ZK (1992) Up-regulation of intercellular adhesion molecule-1 (ICAM-1) expression in primary cultures of human brain microvessel endothelial cells by cytokines and lipopolysaccharide. J Neuroimmunol 39:11–21

    Google Scholar 

  • Yuan H, Gaber MW, McColgan T, Naimark MD, Kiani MF, Merchant TE (2003) Radiation-induced permeability and leukocyte adhesion in the rat blood–brain barrier: modulation with anti-ICAM-1 antibodies. Brain Res 969:59–69

    Google Scholar 

  • Zeng H, Hendriks LEL, van Geffen WH, Witlox WJA, Eekers DBP, De Ruysscher DKM (2020) Risk factors for neurocognitive decline in lung cancer patients treated with prophylactic cranial irradiation: a systematic review. Cancer Treat Rev 88:102025

    Google Scholar 

  • Zhao W, Payne V, Tommasi E et al (2007) Administration of the peroxisomal proliferator-activated receptor (PPAR)γ agonist pioglitazone during fractionated brain irradiation prevents radiation-induced cognitive impairment. Int J Radiat Oncol Biol Phys 67:6–9

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Oncology and Palliative Medicine, Nordland Hospital, Bodø, Norway

    C. Nieder

Authors
  1. C. Nieder
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C. Nieder .

Editor information

Editors and Affiliations

  1. School of Medicine, University of Kragujevac, Kragujevac, Serbia

    Branislav Jeremić

Rights and permissions

Reprints and permissions

Copyright information

© 2021 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Nieder, C. (2021). Brain Toxicity. In: Jeremić, B. (eds) Advances in Radiation Oncology in Lung Cancer. Medical Radiology(). Springer, Cham. https://doi.org/10.1007/174_2021_281

Download citation

  • DOI: https://doi.org/10.1007/174_2021_281

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-34846-4

  • Online ISBN: 978-3-031-34847-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation