Prognosis of the course and systemic therapy of patients with brain metastases of solid tumors (literature review)
Keywords:brain metastases, blood-brain barrier, prognosis of survival, systemic antitumor therapy, radiotherapy, palliative treatment, review
AbstractThe review deals with the systemic therapy of patients with brain metastases taking into account the prognosis of the oncological disease. Considering the fact that the presence of brain metastases significantly worsens the prognosis of the course, this article presents an overview of scales for predicting the survival of patients with brain metastases, their characteristics taking into account the application both in routine clinical practice and in clinical trials. Brain metastases occur 10 times more often than primary tumors of the central nervous system and are diagnosed in 10–20 % of cancer patients. Given the prevalence and the absence of generally accepted clinical recommendations for the treatment of patients with brain metastases, this paper reviews the existing prognostic factors determining the treatment tactics, presents data on the role of the blood brain barrier in the pathogenesis and efficacy of the brain metastases therapy. Possible mechanisms of resistance to systemic antitumor therapy, ways to overcome them were considered, as well as the results of studies on the effectiveness of systemic antitumor therapy in patients with brain metastases of the solid tumors. This review of literature indicates the importance of applying a multidisciplinary approach to determining the treatment mode with the use of scales for assessing the prognosis of course, which, in turn, will lead to a more justified prescription of radiation therapy, surgical treatment, systemic antitumor and symptomatic therapy in order to preserve neurological and neurocognitive function, and the quality of life of patients.
Mehta M., Vogelbaum M.A., Chang S. et al. Neoplasms of the central nervous system. In: DeVita V.T. Jr, Lawrence T.S., Rosenberg S.A. Cancer: Principles and Practice of Oncology. 9th ed. — Philadelphia, Pa: Lippincott Williams & Wilkins, 2011. — P. 1700-49.
Villano J.L., Durbin E.B., Normandeau C., Thakkar J.P., Moirangthem V., Davis F.G. Incidence of brain metastasis at initial presentation of lung cancer // Neuro Oncol. 2015; 17(1): 122-128. — doi: 10.1093/neuonc/nou099.
Ippen F.M., Mahadevan A., Wong E.T., Uhlmann E.J., Sengupta S., Kasper E.M. Stereotactic radiosurgery for renal cancer brain metastasis: Prognostic factors and the role of whole-brain radiation and surgical resection // Journal of Oncology. 2015: 636918. — doi: 10.1155/2015/636918, 0.44.
Christensen T.D., Spindler K.L., Palshof J.A., Nielsen D.L. Systematic review: brain metastases from colorectal cancer-Incidence and patient characteristics // BMC Cancer. 2016; 16: 260. — doi: 10.1186/s12885-016-2290-5.
Wilhelm I., Molnar J., Fazakas C., Hasko J., Krizbai I.A. Role of the blood-brain barrier in the formation of brain metastases // Int. J. Mol. Sci. 2013; 14: 1383-1411. — doi: 10.3390/ijms14011383.
Vernur V.A., Ahluwalia M.S. Prognostic scores for brain metastasis patients: use in clinical practice and trial design // Chin. Clin. Oncol. 2015; 4(2): 18. — doi: 10.3978/j.issn.2304-3865.2015.06.01.
Lin X., DeAngelis L.M. Treatment of Brain Metastases // Journal of Clinical Oncology. 2015; 33 (30): 3475-3484. — doi: 10.1200/JCO.2015.60.9503.
Sperduto P.W., Yang T.J., Beal K. et al. 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 Oncology, published online Nov 17, 2016. — doi: 10.1001/jamaoncol.2016.3834.
Sperduto P.W., Jiang W., Brown P.D. et al. Estimating Survival in Melanoma Patients with Brain Metastases: An Update of the Graded Prognostic Assessment for Melanoma Using Molecular Markers (Melanoma-molGPA) // Int. J. Radiat. Onc. Biol. Phys. 2017, on-line 10/17/17, print issue 11/15/17.
Liubota R., Cheshuk V., Vereshchako R., Zotov O., Zaychuk V., Anikusko N., Liubota I. The impact of locoregional treatment on survival of patients with primary metastatic breast cancer// Exp. Oncol. 2017; 39 (1): 75-77.
Wrobel J.K., Toborek M. Blood-brain barrier remodeling during brain metastasis formation // Mol. Med. 2016; 22: 32-40. — doi: 10.2119/molmed.2015.00207.
Abbott N.J., Ronnback L., Hansson E. Astrocyte-endothelial interactions at the blood-brain barrier // Nat. Rev. Neurosci. 2006; 7(1): 41-8. — doi: 10.1038/nrn1824.
Rahmathulla G., Toms S.A., Weil R.J. The molecular biology of brain metastasis // J. Oncol. 2012; 2012723541. — doi: 10.1155/2012/723541.
Deeken J.F., Löscher W. The blood-brain barrier and cancer: Transporters, treatment, and Trojan horses // Clin. Cancer Res. 2007; 13: 1663-1674. — doi: 10.1158/1078-0432.CCR-06-2854.
Zhang Y., Schuetz J.D., Elmquist W.F., Miller D.W. Plasma membrane localization of multidrug resistance-associated protein homologs in brain capillary endothelial cells // J. Pharmacol. Exp. Ther. 2004; 311: 449-55.
Horsey A.J., Cox M.H., Sarwat S., Kerr I.D. The multidrug transporter ABCG2: still more questions than answers // Biochem. Soc. Trans. 2016; 44: 824-830. — doi: 10.1042/BST20160014.
Agarwal S., Uchida Y., Mittapalli R.K., Sane R., Terasaki T., Elmquist W.F. Quantitative proteomics of transporter expression in brain capillary endothelial cells isolated from P-glycoprotein (P-gp), breast cancer resistance protein (Bcrp), and P-gp/Bcrp knockout mice // Drug. metabolism and disposition: the biological fate of chemicals. 2012; 40: 1164-1169.
Murrell D.H., Zarghami N., Jensen M.D., Chambers A.F., Wong E. & Foster P.J. Evaluating changes to blood-brain barrier integrity in brain metastasis over time and after radiation treatment // Translational Oncology. 2016; 9(3): 219-227.
Sandipan R. Strategic Drug Delivery Targeted to the brain // A Review. Der. Pharmacia Sinica. 2012; 3 (1): 76-92.
Cerna T., Stiborova M., Adam V., Kizek R., Eckschlager T. Nanocarrier drugs in the treatment of brain tumors // J. Cancer Metastasis Treat. 2016; 2: 407-16.
Kostaras X., Cusano F., Kline G.A., Roa W., Easaw J. Use of dexamethasone in patients with high-grade glioma: a clinical practice guideline // Curr. Oncol. 2014; 21(3): e493-503.
Ahluwalia M.S., Vogelbaum M.V., Chao S.T., Mehta M.M. Brain metastasis and treatment // F1000Prime Rep. 2014; 6: 114.10.12703/P6-114.
Lombardi G., Di Stefano A.L., Farina P., Zagonel V., Tabouret E. Systemic treatments for brain metastases from breast cancer, non-small cell lung cancer, melanoma and renal cell carcinoma: an overview of the literature // Cancer Treat. Rev. 2014; 40: 951-9.
Harry C. Brastianos, Daniel P. Cahill, Priscilla K. Brastianos, Systemic Therapy of Brain Metastases // Current. Neurology and Neuroscience Reports, 2015, 15, 2.
Cortés J., Rugo H.S., Awada A., Twelves C., Perez E.A., Im S.-A. et al. Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial // Breast. Cancer Res. Treat. 2017; 165(2): 329-41. — doi: 10.1007/s10549-017-4304-7.
Chamberlain M.C., Baik C.S., Gadi V.K., Bhatia S., Chow L. Systemic therapy of brain metastases: non-small cell lung cancer, breast cancer, and melanoma // Neuro-Oncology. 2017; 19 (1): i1-i24. — doi: 10.1093/neuonc/now197.
Metro G., Chiari R., Ricciuti B. et al. Pharmacotherapeutic options for treating brain metastases in non-small cell lung cancer // Expert. Opin. Pharmacother. 2015; 16: 2601-13. — doi: 10.1517/14656566.2015.1094056.
Naskhletashvili D.R., Gorbunova V.A., Bychkov M.B., Chmutin G.E., Karahan V.B., Aloshin V.A., Moskvina E.A. Gemcitabine plus cisplatin in patients with heavily pretreated breast cancer with brain metastases // Journal of Clinical Oncology. 2010 (suppl; abstr 1125); 28: 7s.
Erten C., Demir L., Somali I., Alacacioglu A., Kucukzeybek Y., Akyol M., Can A., Dirican A., Bayoglu V., Tarhan M.O. Cisplatin plus gemcitabine for treatment of breast cancer patients with brain metastases; a preferential option for triple negative patients? // Asian Pac. J. Cancer Prev. 2013; 14(6): 3711-3717. — doi: 10.7314/APJCP.2013.14.6.3711.
Jacot W., Gerlotto-Borne M.C., Thezenas S., Pouderoux S., Poujol S., About M., Romieu G. Carmustine and methotrexate in combination after whole brain radiation therapy in breast cancer patients presenting with brain metastases: a retrospective study // BMC Cancer. 2010; 10: 257. — doi: 10.1186/1471-2407-10-257.
Inno A., Di Noia V., D’Argento E., Modena A., Gori S. State of the art of chemotherapy for the treatment of central nervous system metastases from non-small cell lung cancer // Transl. Lung. Cancer Res. 2016; 5: 599-609.
Petrelli F., Ghidini M., Lonati V., Tomasello G., Borgonovo K., Ghilardi M. et al. The efficacy of lapatinib and capecitabine in HER-2 positive breast cancer with brain metastases: a systematic review and pooled analysis // Eur. J. Cancer. 2017; 84: 141-8.10.1016/j.ejca.2017.07.024.
Iuchi T., Shingyoji M., Sakaida T. et al. Phase II trial of gefitinib alone without radiation therapy for Japanese patients with brain metastases from EGFR-mutant lung adenocarcinoma // Lung. Cancer. 2013; 82(2): 282-287.
Gerber N.K., Yamada Y., Rimner A., Shi W., Riely G.J., Beal K., Yu H.A., Chan T.A., Zhang Z., Wu A.J. Erlotinib versus radiation therapy for brain metastases in patients with EGFR-mutant lung adenocarcinoma // Int. J. Radiat. Oncol. Biol. Phys. 2014; 89: 322-329. — doi: 10.1016/j.ijrobp.2014.02.022.
McArthur G.A., Maio M., Arance A., Nathan P., Blank C., Avril M.F., Garbe C., Hauschild A., Schadendorf D., Hamid O., Fluck M., Thebeau M., Schachter J., Kefford R., Chamberlain M., Makrutzki M., Robson S., Gonzalez R., Margolin K. Vemurafenib in metastatic melanoma patients with brain metastases: an open-label, single-arm, phase 2, multicentre study // Ann. Oncol. 2017; 28: 634-41. — doi: 0.1093/annonc/mdw641.
Azer M.W., Menzies A.M., Haydu L.E., Kefford R.F., Long G.V. Patterns of response and progression in patients with BRAF-mutant melanoma metastatic to the brain who were treated with dabrafenib // Cancer. 2014; 120: 530-6.
Xing P., Wang S., Hao X. et al. Clinical data from the real world: efficacy of Crizotinib in Chinese patients with advanced ALK-rearranged non-small cell lung cancer and brain metastases // Oncotarget. 2016; 7: 84666-84674.
Shaw A., Mehra R., Tan D.S.W. et al. Ceritinib (LDK378) for the treatment of patients with ALK-rearranged (ALK+) non-small cell lung cancer (nsclc) and brain metastasis (bm) in the ascend-1 trial // Neuro. Oncol. 2014; 16(suppl 5): 39.
Crino L., Ahn M.J., De Marinis F. et al. Multicenter Phase II Study of Whole-Body and Intracranial Activity With Ceritinib in Patients With ALK-Rearranged Non-Small-Cell Lung Cancer Previously Treated With Chemotherapy and Crizotinib: Results From ASCEND-2 // J. Clin. Oncol. 2016; 34: 2866-73. 10.1200/JCO.2015.65.5936.
Felip E., Orlov S., Park K. et al. Ascend-3: a single-arm, open-label, multicenter phase II study of ceritinib in alki-naive adult patients (pts) with ALK-rearranged (ALK+) non-small cell lung cancer (nsclc) [abstract 8060] // J. Clin. Oncol. 2015; 33.
Gadgeel S.M., Shaw A.T., Govindan R. et al. Pooled Analysis of CNS Response to Alectinib in Two Studies of Pretreated Patients With ALK-Positive Non-Small-Cell Lung Cancer // J. Clin. Oncol. 2016; 34: 4079-85.
Besse B., Le Moulec S., Mazières J., Senellart H., Barlesi F., Chouaid C. et al. Bevacizumab in patients with nonsquamous non-small cell lung cancer and asymptomatic, untreated brain metastases (BRAIN): a nonrandomized, phase II study // Clin. Cancer. Res. 2015; 21: 1896-903.
Yap Y.S., Cornelio G.H., Devi B.C. Brain metastases in Asian HER2-positive breast cancer patients: anti-HER2 treatments and their impact on survival // Br. J. Cancer. 2012; 107: 1075-1082.
Margolin K., Ernstoff M.S., Hamid O., Lawrence D., McDermott D., Puzanov I. et al. Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial // Lancet Oncol. 2012; 13: 459-65.
Di Giacomo A.M., Ascierto P.A., Queirolo P., Pilla L., Ridolfi R., Santinami M., Testori A., Simeone E., Guidoboni M., Maurichi A., Orgiano L., Spadola G., Del Vecchio M. et al. Three-year follow-up of advanced melanoma patients who received ipilimumab plus fotemustine in the Italian Network for Tumor Biotherapy (NIBIT)-M1 phase II study // Ann. Oncol. 2015; 26: 798-803.
Goldberg S.B., Gettinger S.N., Mahajan A., Chiang A.C., Herbst R.S., Sznol M. et al. Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial // Lancet Oncol. 2016; 17: 976-83.
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