Kognitivní toxicita indukovaná radioterapií v éře precizní onkologie – od patofyziologie ke strategiím omezení toxicity

Stiahnuť PDF English version

Autori: C. C. Mirestean ^1,2; R. I. Iancu ^3,4; D. T. Iancu ^3,5
Pôsobisko autorov: University of Medicine and Pharmacy of Craiova, Craiova, Romania ¹; Railways Clinical Hospital, Iasi, Romania ²; “Gr. T. Popa” University of Medicine and Pharmacy, Iasi, Romania ³; “St. Spiridon” Emergency Hospital, Iasi, Romania ⁴; Regional Institute of Oncology, Iasi, Romania ⁵
Vyšlo v časopise: Cesk Slov Neurol N 2023; 86(5): 322-329
Kategória: Přehledný referát
doi: https://doi.org/10.48095/cccsnn2023322

Súhrn

Radioterapie je jedným ze základních složek léčby pacientů s intrakraniálními metastázami. Součástí nechirurgické léčby mozkových metastáz jsou celomozkové ozáření (whole brain radiotherapy – WBRT) a také stereotaktická radiochirurgie. V éře pokroku onkologické léčby s implikacemi pro dlouhodobé přežití pacientů je diskutovaným tématem toxicita těchto léčebných postupů, u které nemůžeme přehlédnout kognitivní poruchy. Mechanizmů, na jejichž základě kognitivní poruchy vznikají, je několik a jsou stále předmětem výzkumu. Zaměřujeme se na patofyziologické elementy, které se podílí na kognitivních poruchách, a na strategie, jakými jsou hipokampus šetřící (hippocampal avoidance; HA) WBRT pro kandidáty na cílenou léčbu s různými histologickými typy nádorů, která přechází hematoencefalickou bariéru. I když je léčba HA-WBRT plus memantinem jakožto standard stále předmětem diskuzí, v případech mnohočetných mozkových metastáz nebo metastáz, u kterých není vhodná cílená radioterapie, a u pacientů s očekávaným přežitím > 4 měsíce je nutné aplikovat strategii pro prevence poruch kognitivních funkcí. V budoucnu musí být do analýz a studií zařazeny nové studie, které zhodnotí kognitivní funkce u pacientů s dlouhodobým přežitím, ale také další faktory, jako je počet a objem mozkových metastáz, jejich intrakraniální a extrakraniální lokalizace a efekt moderních onkologických terapií.

Klíčová slova:

demence – kognitivní porucha – mozkové metastazy – celomozkové ozáření – šetření hippokampu – memantin

Zdroje

1. DeAngelis LM, Seiferheld W, Schold SC et al. Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study 93-10. J Clin Oncol 2002; 20 (24): 4643–4648. doi: 10.1200/JCO.2002.11.013.

2. Wilke C, Grosshans D, Duman J et al. Radiation-induced cognitive toxicity: pathophysiology and interventions to reduce toxicity in adults. Neuro Oncol 2018; 20 (5): 597–607. doi: 10.1093/neuonc/nox195.

3. Nabors LB, Portnow J, Ammirati M et al. NCCN Guidelines Insights: Central Nervous System Cancers, Version 1.2017. J Natl Compr Canc Netw 2017; 15 (11): 1331–1345. doi: 10.6004/jnccn.2017.0166.

4. Lehrer EJ, Jones BM, Dickstein DR et al. The cognitive effects of radiotherapy for brain metastases. Front Oncol 2022; 12: 893264. doi: 10.3389/fonc.2022.893264.

5. Monje ML, Mizumatsu S, Fike JR et al. Irradiation induces neural precursor-cell dysfunction. Nat Med 2002; 8 (9): 955–962. doi: 10.1038/nm749.

6. Rola R, Raber J, Rizk A et al. Radiation-induced impairment of hippocampal neurogenesis is associated with cognitive deficits in young mice. Exp Neurol 2004; 188 (2): 316–330. doi: 10.1016/j.expneurol.2004.05.005.

7. Tökés T, Varga G, Garab D et al. Peripheral inflammatory activation after hippocampus irradiation in the rat. Int J Radiat Biol 2014; 90 (1): 1–6. doi: 10.3109/09553002. 2013.836617.

8. Ding X, Zhang HB, Qiu H et al. Cranial irradiation induces cognitive decline associated with altered dendritic spine morphology in the young rat hippocampus. Childs Nerv Syst 2022; 38 (10): 1867–1875. doi: 10.1007/s00381-022-05646-w.

9. Greene-Schloesser D, Robbins ME. Radiation-induced cognitive impairment – from bench to bedside. Neuro Oncol 2012; 14 (Suppl 4): iv37–44. doi: 10.1093/neuonc/nos196.

10. Bai H, Han B. The effectiveness of erlotinib against brain metastases in non-small cell lung cancer patients. Am J Clin Oncol 2013; 36 (2): 110–115. doi: 10.1097/COC. 0b013e3182438c91.

11. Hotta K, Kiura K, Ueoka H et al. Effect of gefitinib (“Iressa”, ZD1839) on brain metastases in patients with advanced non-small-cell lung cancer. Lung Cancer 2004; 46 (2): 255–261. doi: 10.1016/j.lungcan.2004.04.036.

12. Fabi A, Alesini D, Valle E et al. T-DM1 and brain metastases: clinical outcome in HER2-positive metastatic breast cancer. Breast 2018; 41: 137–143. doi: 10.1016/ j.breast.2018.07.004.

13. Cetin B, Benekli M, Oksuzoglu B et al. Lapatinib plus capecitabine for brain metastases in patients with human epidermal growth factor receptor 2-positive advanced breast cancer: a review of the Anatolian Society of Medical Oncology (ASMO) experience. Onkologie 2012; 35 (12): 740–745. doi: 10.1159/000345040.

14. Cihan YB. Lapatinib? or radiotherapy? in cranial metastasis of breast cancer. Eur J Breast Health 2019; 15 (3): 205–206. doi: 10.5152/ejbh.2019.4874.

15. Ippolito E, Silipigni S, Matteucci P et al. Radiotherapy for HER 2 positive brain metastases: urgent need for a paradigm shift. Cancers 2022; 14 (6): 1514. doi: 10.3390/cancers14061514.

16. Kowalczyk L, Bartsch R, Singer CF et al. Adverse events of trastuzumab emtansine (T-DM1) in the treatment of HER2-positive breast cancer patients. Breast Care 2017; 12 (6): 401–408. doi: 10.1159/000480492.

17. Davies MA, Saiag P, Robert C et al. Dabrafenib plus trametinib in patients with BRAFV600-mutant melanoma brain metastases (COMBI-MB): a multicentre, multicohort, open-label, phase 2 trial. Lancet Oncol 2017; 18 (7): 863–873. doi: 10.1016/S1470-2045 (17) 30429-1.

18. Bauer TM, Felip E, Solomon BJ et al. Clinical management of adverse events associated with lorlatinib. Oncologist 2019; 24 (8): 1103–1110. doi: 10.1634/theoncologist.2018-0380.

19. Welsh JW, Komaki R, Amini A et al. Phase II trial of erlotinib plus concurrent whole-brain radiation therapy for patients with brain metastases from non-small--cell lung cancer. J Clin Oncol 2013; 31 (7): 895–902. doi: 10.1200/JCO.2011.40.1174.

20. Chen G, Feng J, Zhou C et al. Quality of life (QoL) analyses from OPTIMAL (CTONG-0802), a phase III, randomised, open-label study of first-line erlotinib versus chemotherapy in patients with advanced EGFR mutation-positive non-small-cell lung cancer (NSCLC). Ann Oncol 2013; 24 (6): 1615–1622. doi: 10.1093/annonc/mdt012.

21. Pesce GA, Klingbiel D, Ribi K et al. Outcome, quality of life and cognitive function of patients with brain metastases from non-small cell lung cancer treated with whole brain radiotherapy combined with gefitinib or temozolomide. A randomised phase II trial of the Swiss Group for Clinical Cancer Research (SAKK 70/03). Eur J Cancer 2012; 48 (3): 377–384. doi: 10.1016/j.ejca.2011.10.016.

22. Institute for Quality and Efficiency in Health Care (IQWiG, Germany). Dacomitinib (non-small-cell lung cancer) – benefit assessment according to §35a Social Code Book V. [online]. Available from: https: //www.iqwig.de/download/a19-39_dacomitinib_extract-of-dossier-assessment_v1-0.pdf.

23. Sekine A, Satoh H, Ikeda S et al. Rapid effect of osimertinib re-challenge on brain metastases developing during salvage cytotoxic chemotherapy after osimertinib treatment failure: a case report. Mol Clin Oncol 2019; 10 (4): 451–453. doi: 10.3892/mco.2019.1818.

24. Chun YS, Kim MY, Lee SY et al. MEK1/2 inhibition rescues neurodegeneration by TFEB-mediated activation of autophagic lysosomal function in a model of Alzheimer’s disease. Mol Psychiatry 2022; 27 (11): 4770–4780. doi: 10.1038/s41380-022-01713-5.

25. Schadendorf D, Amonkar MM, Stroyakovskiy D et al. Health-related quality of life impact in a randomised phase III study of the combination of dabrafenib and trametinib versus dabrafenib monotherapy in patients with BRAF V600 metastatic melanoma. Eur J Cancer 2015; 51 (7): 833–840. doi: 10.1016/j.ejca.2015.03.004.

26. Huang Y, Li Q, Tian H et al. MEK inhibitor trametinib attenuates neuroinflammation and cognitive deficits following traumatic brain injury in mice. Am J Transl Res 2020; 12 (10): 6351–6365.

27. Bartsch R, Berghoff AS, Furtner J et al. Trastuzumab deruxtecan in HER2-positive breast cancer with brain metastases: a single-arm, phase 2 trial. Nat Med 2022; 28 (9): 1840–1847. doi: 10.1038/s41591-022-01935-8.

28. Gupta T, Basu A, Master Z et al. Planning and delivery of whole brain radiation therapy with simultaneous integrated boost to brain metastases and synchronous limited-field thoracic radiotherapy using helical tomotherapy: a preliminary experience. Technol Cancer Res Treat 2009; 8 (1): 15–22. doi: 10.1177/153303460900800103.

29. Gondi V, Hermann BP, Mehta MP et al. Hippocampal dosimetry predicts neurocognitive function impairment after fractionated stereotactic radiotherapy for benign or low-grade adult brain tumors. Int J Radiat Oncol Biol Phys 2012; 83 (4): e487–493. doi: 10.1016/j.ijrobp.2011.10.021.

30. Brown PD, Pugh S, Laack NN 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): 1429–1437. doi: 10.1093/neuonc/not114.

31. Dye NB, Gondi V, Mehta MP. Strategies for preservation of memory function in patients with brain metastases. Chin Clin Oncol 2015; 4 (2): 24. doi: 10.3978/j.issn.2304-3865.2015.05.05.

32. 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. doi: 10.1016/j.ijrobp.2010.01.039.

33. Goda JS, Dutta D, Krishna U et al. Hippocampal radiotherapy dose constraints for predicting long-term neurocognitive outcomes: mature data from a prospective trial in young patients with brain tumors. Neuro Oncol 2020; 22 (11): 1677–1685. doi: 10.1093/neuonc/noaa076.

34. Grosu AL, Frings L, Bentsalo I et al. Whole-brain irradiation with hippocampal sparing and dose escalation on metastases: neurocognitive testing and biological imaging (HIPPORAD) – a phase II prospective randomized multicenter trial (NOA-14, ARO 2015-3, DKTK-ROG). BMC Cancer 2020; 20 (1): 532. doi: 10.1186/s12885-020-07011-z.

35. Levy A, Dhermain F, Botticella A et al. Hippocampal avoidance whole-brain radiotherapy (WBRT) versus WBRT in patients with brain metastases: were hippocampi the only difference? J Clin Oncol 2020; 38 (29): 3453–3454. doi: 10.1200/JCO.20.00548.

36. Brown PD, Gondi V, Pugh S 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): 1019–1029. doi: 10.1200/JCO.19.02767.

37. Andratschke N, Belderbos J, Mayinger M et al. Hippocampal avoidance and memantine for whole-brain radiotherapy: long-term follow-up warranted. J Clin Oncol 2020; 38 (29): 3454–3455. doi: 10.1200/JCO.20.00747.

38. Brown PD, Jaeckle K, Ballman KV 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): 401–409. doi: 10.1001/jama.2016.9839.

39. Kuntz L, Noel G. Repeated irradiation of brain metastases under stereotactic conditions: a review of the literature. Cancer Radiother 2021; 25 (4): 390–399. doi: 10.1016/j.canrad.2020.08.050.

40. Bunevicius A, Lavezzo K, Shabo L et al. Quality-of-life trajectories after stereotactic radiosurgery for brain metastases. J Neurosurg 2020; 134 (6): 1791–1799. doi: 10.3171/2020.4.JNS20788.

41. Kuntz L, Le Fèvre C, Jarnet D et al. Changes in the characteristics of patients treated for brain metastases with repeat stereotactic radiotherapy (SRT): a retrospective study of 184 patients. Radiat Oncol 2023; 18 (1): 21. doi: 10.1186/s13014-023-02200-z.