Skip to main content

Advertisement

SpringerLink
Log in

Neurologic Complications of Cancer Therapies

  • Neuro-Oncology (P.Y. Wen, Section Editor)
  • Published:
Current Neurology and Neuroscience Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

To review the neurologic complications of systemic anti-cancer therapies and radiation therapy.

Recent Findings

Although many of the newer systemic therapies have more favorable side effect profiles than traditional cytotoxic chemotherapy, neurotoxicity has been seen with some of newer targeted therapies, immunotherapy, and T cell engaging therapies, including CAR-T therapy. The most recent advances in radiation-induced neurotoxicity have focused on the prevention and the management of cognitive dysfunction, a known long-term complication of brain irradiation.

Summary

Cancer therapies can damage both the central and the peripheral nervous systems, and the damage may not always be reversible. Neurologists and oncologists must be aware of the neurotoxicities associated with newer treatments, particularly CAR-T therapy and immunotherapy. Early recognition and appropriate management can help minimize neurologic injury.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Lee E. Overview of neurologic complications of platinum-based chemotherapy. In: Drews R, Wen P, editors. Up to Date, Inc. 2021.

  2. Lee E. Overview of neurologic complications of conventional non-platinum cancer chemotherapy. In: Loeffler J, Wen P, editors. Up to Date, Inc. 2021.

  3. Lee E, Wen P. Neurologic complications of cancer treatment with molecularly targeted and biologic agents. In: Drews R, editor. Up to Date, Inc. 2020.

  4. Dietrich J. Neurotoxicity of cancer therapies. Continuum (Minneapolis, Minn). 2020;26(6):1646–72. https://doi.org/10.1212/con.0000000000000943. This recent article reviews the neurologic complications of cancer therapies.

    Article  Google Scholar 

  5. Santomasso BD. Anticancer drugs and the nervous system. Continuum (Minneapolis, Minn). 2020;26(3):732–64. https://doi.org/10.1212/con.0000000000000873. This recent article reviews the neurologic complications of anti-cancer drugs.

    Article  Google Scholar 

  6. Cavaletti G, Alberti P, Marmiroli P. Chemotherapy-induced peripheral neurotoxicity in cancer survivors: an underdiagnosed clinical entity? Am Soc Clin Oncol Educ Book. 2015;35:e553–60. https://doi.org/10.14694/EdBook_AM.2015.35.e553.

    Article  Google Scholar 

  7. Loprinzi CL, Lacchetti C, Bleeker J, Cavaletti G, Chauhan C, Hertz DL, et al. Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: ASCO guideline update. J Clin Oncol. 2020;38(28):3325–48. https://doi.org/10.1200/JCO.20.01399.

    Article  PubMed  Google Scholar 

  8. Jordan B, Margulies A, Cardoso F, Cavaletti G, Haugnes HS, Jahn P, et al. Systemic anticancer therapy-induced peripheral and central neurotoxicity: ESMO-EONS-EANO clinical practice guidelines for diagnosis, prevention, treatment and follow-up. Ann Oncol. 2020;31(10):1306–19. https://doi.org/10.1016/j.annonc.2020.07.003.

    Article  CAS  PubMed  Google Scholar 

  9. Burger JA, Wiestner A. Targeting B cell receptor signalling in cancer: preclinical and clinical advances. Nat Rev Cancer. 2018;18(3):148–67. https://doi.org/10.1038/nrc.2017.121.

    Article  CAS  PubMed  Google Scholar 

  10. Chamilos G, Lionakis MS, Kontoyiannis DP. Call for action: invasive fungal infections associated with ibrutinib and other small molecule kinase inhibitors targeting immune signaling pathways. Clin Infect Dis. 2018;66(1):140–8. https://doi.org/10.1093/cid/cix687.

    Article  CAS  PubMed  Google Scholar 

  11. Maschmeyer G, De Greef J, Mellinghoff SC, Nasari A, Thiebaut-Bertrand A, Bergeron A, et al. Infections associated with immunotherapeutic and molecular targeted agents in hematology and oncology. A position paper by the European Conference on Infections in Leukemia (ECIL). Leukemia. 2019;33(4):844–62. https://doi.org/10.1038/s41375-019-0388-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Lionakis MS, Dunleavy K, Roschewski M, Widemann BC, Butman JA, Schmitz R, et al. Inhibition of B cell receptor signaling by ibrutinib in primary CNS lymphoma. Cancer Cell. 2017;31(6):833-43.e5. https://doi.org/10.1016/j.ccell.2017.04.012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Frei M, Aitken SL, Jain N, Thompson P, Wierda W, Kontoyiannis DP, et al. Incidence and characterization of fungal infections in chronic lymphocytic leukemia patients receiving ibrutinib. Leuk Lymphoma. 2020;61(10):2488–91. https://doi.org/10.1080/10428194.2020.1775215.

    Article  CAS  PubMed  Google Scholar 

  14. Wilson P, Melville K. Disseminated cryptococcal infection in a patient receiving acalabrutinib for chronic lymphocytic leukemia. Infect Dis Clin Pract. 2019;27(3):160–2.

    Article  Google Scholar 

  15. Alkharabsheh O, Alsayed A, Morlote DM, Mehta A. Cerebral invasive aspergillosis in a case of chronic lymphocytic leukemia with bruton tyrosine kinase inhibitor. Curr Oncol. 2021;28(1):837–41. https://doi.org/10.3390/curroncol28010081.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Rubin DB, Vaitkevicius H. Neurological complications of cancer immunotherapy (CAR T cells). J Neurol Sci. 2021;424:117405. https://doi.org/10.1016/j.jns.2021.117405.

    Article  CAS  PubMed  Google Scholar 

  17. Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL, et al. Chimeric antigen receptor T-cell therapy—assessment and management of toxicities. Nat Rev Clin Oncol. 2018;15(1):47–62. https://doi.org/10.1038/nrclinonc.2017.148.

    Article  CAS  PubMed  Google Scholar 

  18. Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant. 2019;25(4):625–38. https://doi.org/10.1016/j.bbmt.2018.12.758 This paper summarizes the ASTCT consensus guidelines for management of ICANS associated with CAR-T therapy.

    Article  CAS  PubMed  Google Scholar 

  19. Reagan PM, Neelapu SS. How I manage: pathophysiology and management of toxicity of chimeric antigen receptor T-cell therapies. J Clin Oncol. 2021;39(5):456–66. https://doi.org/10.1200/JCO.20.01616.

    Article  PubMed  Google Scholar 

  20. Goebeler M-E, Bargou RC. T cell-engaging therapies—BiTEs and beyond. Nat Rev Clin Oncol. 2020;17(7):418–34. https://doi.org/10.1038/s41571-020-0347-5.

    Article  PubMed  Google Scholar 

  21. Danyelza® (naxitamab-gqgk) injection [package insert on the Internet]. New York (NY): Y-mAbs Therapeutics, Inc., 2020 [cited 2021 May 12]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761171lbl.pdf.

  22. Roth P, Winklhofer S, Müller AMS, Dummer R, Mair MJ, Gramatzki D, et al. Neurological complications of cancer immunotherapy. Cancer Treat Rev. 2021;97: 102189. https://doi.org/10.1016/j.ctrv.2021.102189.

    Article  CAS  PubMed  Google Scholar 

  23. Marini A, Bernardini A, Gigli GL, Valente M, Muñiz-Castrillo S, Honnorat J, et al. Neurologic adverse events of immune checkpoint inhibitors: a systematic review. Neurology. 2021;96(16):754–66. https://doi.org/10.1212/wnl.0000000000011795.

    Article  CAS  PubMed  Google Scholar 

  24. National Comprehensive Cancer Network. Management of immunotherapy‐related toxicities (Version 3.2021). https://www.nccn.org/professionals/physician_gls/pdf/immunotherapy.pdf. Accessed 15 May 2021. These NCCN guidelines discuss the work up and management of immunotherapy-related toxicities including neurologic toxicites and is updated periodically.

  25. Bendell JC, Rodon J, Burris HA, de Jonge M, Verweij J, Birle D, et al. Phase I, dose-escalation study of BKM120, an oral pan-class I PI3K inhibitor, in patients with advanced solid tumors. J Clin Oncol. 2012;30(3):282–90. https://doi.org/10.1200/jco.2011.36.1360.

    Article  CAS  PubMed  Google Scholar 

  26. Rodon J, Braña I, Siu LL, De Jonge MJ, Homji N, Mills D, et al. Phase I dose-escalation and -expansion study of buparlisib (BKM120), an oral pan-class I PI3K inhibitor, in patients with advanced solid tumors. Invest New Drugs. 2014;32(4):670–81. https://doi.org/10.1007/s10637-014-0082-9.

    Article  CAS  PubMed  Google Scholar 

  27. Ragon BK, Kantarjian H, Jabbour E, Ravandi F, Cortes J, Borthakur G, et al. Buparlisib, a PI3K inhibitor, demonstrates acceptable tolerability and preliminary activity in a phase I trial of patients with advanced leukemias. Am J Hematol. 2017;92(1):7–11. https://doi.org/10.1002/ajh.24568.

    Article  CAS  PubMed  Google Scholar 

  28. Laetsch TW, Hong DS. Tropomyosin receptor kinase inhibitors for the treatment of TRK fusion cancer. Clin Cancer Res. 2021. https://doi.org/10.1158/1078-0432.Ccr-21-0465.

  29. Liu D, Flory J, Lin A, Offin M, Falcon CJ, Murciano-Goroff YR, et al. Characterization of on-target adverse events caused by TRK inhibitor therapy. Ann Oncol. 2020;31(9):1207–15. https://doi.org/10.1016/j.annonc.2020.05.006.

    Article  CAS  PubMed  Google Scholar 

  30. Hong DS, DuBois SG, Kummar S, Farago AF, Albert CM, Rohrberg KS, et al. Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials. Lancet Oncol. 2020;21(4):531–40. https://doi.org/10.1016/S1470-2045(19)30856-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Drilon A, Siena S, Dziadziuszko R, Barlesi F, Krebs MG, Shaw AT, et al. Entrectinib in ROS1 fusion-positive non-small-cell lung cancer: integrated analysis of three phase 1–2 trials. Lancet Oncol. 2020;21(2):261–70. https://doi.org/10.1016/S1470-2045(19)30690-4.

    Article  CAS  PubMed  Google Scholar 

  32. Doebele RC, Drilon A, Paz-Ares L, Siena S, Shaw AT, Farago AF, et al. Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1–2 trials. Lancet Oncol. 2020;21(2):271–82. https://doi.org/10.1016/S1470-2045(19)30691-6.

    Article  CAS  PubMed  Google Scholar 

  33. Drilon A, Siena S, Ou S-HI, Patel M, Ahn MJ, Lee J, et al. Safety and antitumor activity of the multitargeted pan-TRK, ROS1, and ALK inhibitor entrectinib: combined results from two phase I trials (ALKA-372–001 and STARTRK-1). Cancer Discov. 2017;7(4):400–9. https://doi.org/10.1158/2159-8290.CD-16-1237.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Ayvakit® (avapritinib) tablets [package insert on the Internet]. Cambridge (MA): ABlueprint Medicines Corporatio, 2020 [cited 2021 May 16]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212608s000lbl.pdf.

  35. Joseph CP, Abaricia SN, Angelis MA, Polson K, Jones RL, Kang Y-K, et al. Optimal avapritinib treatment strategies for patients with metastatic or unresectable gastrointestinal stromal tumors. Oncologist. 2021;26(4):e622–31. https://doi.org/10.1002/onco.13632.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Lobrena® (lorlatinib) capsules [package insert on the Internet]. New York (NY): Pfizer Labs, 2021 [cited 2021 May 16]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/210868s004lbl.pdf.

  37. Bauer TM, Felip E, Solomon BJ, Thurm H, Peltz G, Chioda MD, et al. Clinical management of adverse events associated with lorlatinib. Oncologist. 2019;24(8):1103–10. https://doi.org/10.1634/theoncologist.2018-0380.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Bardia A, Hurvitz SA, Tolaney SM, Loirat D, Punie K, Oliveira M, et al. Sacituzumab govitecan in metastatic triple-negative breast cancer. N Engl J Med. 2021;384(16):1529–41. https://doi.org/10.1056/NEJMoa2028485.

    Article  CAS  PubMed  Google Scholar 

  39. Tanguturi SK, Alexander BM. Neurologic complications of radiation therapy. Neurol Clin. 2018;36(3):599–625. https://doi.org/10.1016/j.ncl.2018.04.012.

    Article  PubMed  Google Scholar 

  40. Rahman R, Alexander BM, Wen PY. Neurologic complications of cranial radiation therapy and strategies to prevent or reduce radiation toxicity. Curr Neurol Neurosci Rep. 2020;20(8):34. https://doi.org/10.1007/s11910-020-01051-5. This recent article reviews the neurologic complications of cranial radiation.

    Article  PubMed  Google Scholar 

  41. Mendel JT, Jaster AW, Yu FF, Morris LC, 3rd, Lynch PT, Shah BR et al. Fundamentals of radiation oncology for neurologic imaging. Radiographics: a review publication of the Radiological Society of North America, Inc. 2020;40(3):827–58. https://doi.org/10.1148/rg.2020190138.

  42. Brown PD, Jaeckle K, Ballman KV, Farace E, Cerhan JH, Anderson SK, et al. 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. 2016;316(4):401–9. https://doi.org/10.1001/jama.2016.9839.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Turnquist C, Harris BT, Harris CC. Radiation-induced brain injury: current concepts and therapeutic strategies targeting neuroinflammation. Neuro-oncol Adv. 2020;2(1):vdaa057. https://doi.org/10.1093/noajnl/vdaa057. This recent review article discusses the latest information known about radiation-induced brain injury.

    Article  Google Scholar 

  44. Brown PD, Pugh S, Laack NN, Wefel JS, Khuntia D, Meyers C, et al. Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial. Neuro Oncol. 2013;15(10):1429–37. https://doi.org/10.1093/neuonc/not114.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Brown PD, Gondi V, Pugh S, Tome WA, Wefel JS, Armstrong TS, et al. 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. https://doi.org/10.1200/jco.19.02767. This seminal phase 3 clinical trial of hippocampal avoidance during WBRT establishes a new standard of care for patients with brain metastases requiring WBRT.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Li J, Ludmir EB, Wang Y, Guha-Thakurta N, McAleer MF, Settle SH Jr, et al. Stereotactic radiosurgery versus whole-brain radiation therapy for patients with 4–15 brain metastases: a phase III randomized controlled trial. Int J Radiat Oncol Biol Phys. 2020;108(3):S21–2. https://doi.org/10.1016/j.ijrobp.2020.07.2108.

    Article  Google Scholar 

  47. Kahalley LS, Peterson R, Ris MD, Janzen L, Okcu MF, Grosshans DR, et al. Superior intellectual outcomes after proton radiotherapy compared with photon radiotherapy for pediatric medulloblastoma. J Clin Oncol. 2020;38(5):454–61. https://doi.org/10.1200/JCO.19.01706.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA

    Eudocia Q. Lee

Authors
  1. Eudocia Q. Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eudocia Q. Lee.

Ethics declarations

Conflict of Interest

Dr. Lee reports personal fees from Wolters Kluwer (Up to Date, Inc.), personal fees from Medlink, Inc., personal fees from American Academy of Neurology (Continuum), and personal fees from Prime Oncology, outside the submitted work.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Neuro-Oncology

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, E.Q. Neurologic Complications of Cancer Therapies. Curr Neurol Neurosci Rep 21, 66 (2021). https://doi.org/10.1007/s11910-021-01151-w

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11910-021-01151-w

Keywords

Search

Navigation