Cancer UrologyCancer UrologyОнкоурология1726-97761996-1812Publishing House ABV Press127010.17650/1726-9776-2020-16-2-152-161REVIEWОБЗОРLate complications of the treatment of patients with germ cell tumorsПоздние Осложнения Лечения Больных Герминогенными ОпухолямиDanielyanD. G.ДаниелянД. Г.
Russian Federation

Danielyan Daniel Genrievich

8 Trubetskaya St., Moscow 119991

Даниел Генриевич Даниелян

119991 Москва, ул. Трубецкая, 8mementomori07@mail.ruSalimovaA. A.СалимоваА. А.
Russian Federation

Salimova Alina Abdulovna

8 Trubetskaya St., Moscow 119991

Алина Абдуловна Салимова

119991 Москва, ул. Трубецкая, 8alina.salimova@gmail.comBulanovA. A.БулановА. А.
Russian Federation

Bulanov Anatoly Anatolyevich

24 Kashirskoe Shosse, Moscow 115478

Анатолий Анатольевич Буланов

115478 Москва, Каширское шоссе, 24

a_bulanov@mail.ruhttps://orcid.org/0000-0001-5615-7806FedyaninM. Yu.ФедянинМ. Ю.
Russian Federation

Fedyanin Mikhail Yuryevich

24 Kashirskoe Shosse, Moscow 115478; 24Miklukho-Maklaya St., Moscow 117198

Михаил Юрьевич Федянин, 4381-5628.

115478 Москва, Каширское шоссе, 24; 117198 Москва, ул. Миклухо-Маклая, 21

fedianinmu@mail.ruhttps://orcid.org/0000-0003-2245-214XTryakinA. A.ТрякинА. А.
Russian Federation

Tryakin Alexey Aleksandrovich

24 Kashirskoe Shosse, Moscow 115478; 22Akademika Pavlova St., Moscow 119415; 47Zaki Validi St., Ufa 450008, Republic of Bashkortostan; 86 Entuziastov Shosse, Moscow 111123

Алексей Александрович Трякин, 7708-5775.

115478 Москва, Каширское шоссе, 24; 119415Москва, ул. Академика Павлова, 22; Республика Башкортостан, 450008 Уфа, ул. Заки Валиди, 47; 111123 Москва, шоссе Энтузиастов, 86

atryakin@mail.ruI.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of RussiaФГАОУВО Первый Московский государственный медицинский университет им. И.М. Сеченова (Сеченовский Университет) Минздрава РоссииN.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaФГБУ Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина Минздрава РоссииPeoples’ Friendship University of RussiaФГАОУВО Российский университет дружбы народовClinic “K + 31 City”АО К+31 СитиBashkir State Medical University, Ministry of Health of RussiaНИИонкологии, ФГБОУ ВО «Башкирский государственный медицинский университет» Минздрава России47Zaki Validi St., Ufa 450008, Republic of BashkortostanГБУЗ Московский клинический научный центр им. А.С. Логинова Департамента здравоохранения г. Москвы.S. Loginov Moscow Clinical Scientific Center, Moscow Healthcare Department300620201621521612203202018062020https://oncourology.abvpress.ru/oncur/article/view/1270

Germ cell tumors are one of the highly sensitive to chemotherapy, and about 80 % of patients can be cured even having metastases. Apartfrom acute toxicity, chemotherapy is characterized by late complications that occur many years later and not only negatively affect the quality of life, but in some cases are life-threatening. The review summarizes the results of studies on the late complications’ occurrence and prevention when treating patients with germ cell tumors.

Герминогенные опухоли являются одной из высокочувствительных к химиотерапии опухолей, позволяющая излечить около 80% больных даже при наличии метастазов. Кроме хорошо известной острой токсичности лечения, для химиотерапии характерны поздние осложнения, реализующиеся спустя многие годы и способные не только негативно влиять на качество жизни, но и в ряде случаев представлять для нее угрозу. В данной обзорной статье обобщены результаты исследований, посвященных вопросам возникновения и профилактики поздних осложнений терапии больных герминогенными опухолями.

germ cell tumorseminomachemotherapyradiation therapylate complicationneurotoxicitycardiotoxicitysecondary tumorГерминогенная опухольсеминомахимиотерапиялучевая терапияпоздние осложнениянейротоксичностькардиотоксичностьвторичные опухолиMeinardi M.T., Gietema J.A., van der Graaf W.T. et al. Cardiovascular morbidity in long-term survivors of metastatic testicular cancer. J Clin Oncol 2000;18:1725-32. DOI: 10.1200/JC0.2000.18.8.1725.Nuver J., Smit A.J., Sleijfer D.T. et al. Microalbuminuria, decreased fibrinolysis and inflammation as early signs of atherosclerosis in long-term survivors of disseminated testicular cancer. Eur J Cancer 2004;40(5):701-6. DOI: 10.1016/j.ejca.2003.12.012.Thogersen A.M., Jansson J.H., Boman K. et al. High plasminogen activator inhibitor and tissue plasminogen activator levels in plasma precede a first acute myocardial infarction in both men and women: evidence for fibrinolytic system as an independent primary risk factor. Circulation 1998;98(21):2241—7. DOI: 10.1161/01.cir.98.21.2241.Juhan-Vague I., Pyke S.D., Alessi M.C. et al. Fibrinolytic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. ECAT Study Group. European Concerted Action on Thrombosis and Disabilities. Circulation Circulation 1996;94(9):2057—63. DOI: 10.1161/01.cir.94.9.2057.Gietema, J.A., Meinardi, M.T., Messerschmidt J. et al. Circulating plasma platinum more than 10 years after cisplatin treatment for testicular cancer. Lancet 2000;355(9209):1075—6. DOI: 10.1016/s0140-6736(00)02044-4.Bosl G.J., Leitner S.P., Atlas S.A. et al. Increased plasma renin and aldosterone in patients treated with cisplatin-based chemotherapy for metastatic germ-cell tumors. J Clin Oncol 1986;4(11):1684—9. DOI: 10.1200/JCO.1986.4.11.1684.Vogelzang N.J., Bosl G.J., Johnson K., Kennedy B.J. Raynaud’s phenomenon a common toxicity after combination chemotherapy for testicular cancer. Ann Intern Med 1981;95(3):288—92. DOI: 10.7326/0003-4819-95-3-288.Glendenning J.L., Barbachano Y., Norman A.R. et al. Long-term neurologic and peripheral vascular toxitiy after chemotherapy treatment of testicular cancer. Cancer 2010;116(10):2322—31. DOI: 10.1002/cncr.24981.Hanks G.E., Peters T., Owen J. Seminoma of the testis: long-term beneficial and deleterious results of radiation. Int J Ra-diat Oncol Biol Phys 1992;24(5):913—9. DOI: 10.1016/0360-3016(92)90475-w.Zagars G.K., Ballo M.T., Lee A.K., Strom S.S. Mortality after cure of testicular seminoma. J Clin Oncol 2004;22(4):640—7. DOI: 10.1200/JCO.2004.05.205.Haugnes H.S., Wethal T., Aass N. et al. Cardiovascular risk factors and morbidity in long-term survivors of testicular cancer: a 20-year follow-up study. J Clin Oncol 2010;28(30):4649—57. DOI: 10.1200/JCO.2010.29.9362.Huddart R.A., Norman A., Shahidi M. et al. Cardiovascular disease as a long-term complication of treatment for testicular cancer. J Clin Oncol 2003;21(8):1513—23. DOI: 10.1200/JCO.2003.04.173.Wethal T., Kjekshus J., Roislien J. et al. Treatment-related differences in cardiovascular risk factors in long-term survivors of testicular cancer. J Cancer Surviv 2007; 1(1):8—16. DOI: 10.1007/s11764-007-0012-3.Sagstuen H., Aass N., Fossa S.D. et al. Blood pressure and body mass index in long-term survivors of testicular cancer. J Clin Oncol 2005;23(22):4980—90. DOI: 10.1200/JCO.2005.06.882.De Haas E.C., Altena R., Boezen H.M. et al. Early development of the metabolic syndrome after chemotherapy for testicular cancer. Ann Oncol 2013;24(3):749—55. DOI: 10.1093/annonc/mds527.Altena R., de Haas E.C., Nuver J. et al. Evaluation of sub-acute changes in cardiac function after cisplatin-based combination chemotherapy for testicular cancer. Br J Cancer 2009;100(12):1861—6. DOI: 10.1038/sj.bjc.6605095.Altena R., Hummel Y.M., Nuver J. et al. Longitudinal changes in cardiac function after cisplatinbased chemotherapy for testicular cancer. Ann Oncol 2011;22(10):2286—93. DOI: 10.1093/annonc/mdr408.Timp J.F., Braekkan S.K., Versteeg H.H., Cannegieter S.C. Epidemiology of cancer-associated venous thrombosis. Blood 2013;122(10):1712—23. DOI: 10.1182/blood-2013-04-460121.Weijl N.I., Rutten M.F., Zwinderman A.H. et al. Thromboembolic events during chemotherapy for germ cell cancer: a cohort study and review of the literature. J Clin Oncol 2000;18(10):2169—78. DOI: 10.1200/JCO.2000.18.10.2169.Moore R.A., Adel N., Riedel E. et al. High incidence of thromboembolic events in patients treated with cisplatin-based chemotherapy: a large retrospective analysis. J Clin Oncol 2011;29(25):3466—73. DOI: 10.1200/JCO.2011.35.5669.Tran B., Ruiz-Morales J.M., Gonzalez-Billalabeitia E. et al. Large retroperitoneal lymphadenopathy and increased risk of venous thromboembolism in patients receiving first-line chemotherapy for metastatic germ cell tumors: a study by the global germ cell cancer group (G3). Cancer Med 2020;9(1):116-24. DOI: 10.1002/cam4.2674.Lauritsen J., Hansen M.K., Bandak M. et al. Cardiovascular risk factors and disease after male germ cell cancer. J Clin Oncol 2020;38(6):584-92. DOI: 10.1200/JCO.19.01180.Alekperov R. Raynaud’s phenomenon in the rheumatologist’s practice. Sovremennaya revmatologiya = Modern Rheumatology Journal 2014;8(2):48—57. (In Russ.).Алекперов Р.Т. Синдром Рейно в практике ревматолога. Современная ревматология 2014;8(2):48—57.Anderson M. Other secondary causes. In: Raynaud’s phenomenon. A guide to pathogenesis and treatment. Eds.: F. Wigley, A. Herrick, N. Flavahan. New York: Springer, 2014. Pp. 141-162.Toumbis-Ioannou E., Cohen P.R. Chemotherapy-induced Raynaud’s phenomenon. Cleve Clin J Med 1994,61(3):195—9. DOI:10.3949/ccjm.61.3.195.Schildmann E., Davies A. Paraneoplastic Raynaud’s phenomenon — good palliation after a multidisciplinary approach. J Pain Symptom Manage 2010;39(4):779—83. DOI: 10.1016/j.jpainsymman.2009.09.006.Bessis D., Legouffe E., Guilhou J.J. Gemcitabine-associated scleroderma-like changes of the lower extremities. J Am Acad Dermatol 2004;51(2):S73—6. DOI: 10.1016/j.jaad.2001.07.001.Clowse M.E., Wigley F.M. Digital necrosis related to carboplatin and gemcitabine therapy in systemic sclerosis. J Rheumatol 2003;30(6):1341—3.De Angelis R., Bugatti L., Cerioni A. et al. Diffuse scleroderma occurring after the use of paclitaxel for ovarian cancer. Clin Rheumatol 2003;22(1):49—52. DOI: 10.1007/s10067-002-0635-8.Finch W.R., Rodnan G.P., Buckingham R.B. et al. Bleomycin-induced scleroderma. J Rheumatol 1980;7(5):651—9.Hansen S., Olsen N., Rossing N., Rorth M. Vascular toxicity and the mechanism underlying Raynaud’s phenomenon in patients treated with cisplatin, vinblastine and bleomycin. Ann Oncol 1990;1(4):289—92. DOI: 10.1093/oxfordjournals.annonc. a057750.Kannarkat G., Lasher E.E., Schiff D. Neurologic complications of chemotherapy agenys. Curr Opin Neurol 2007;20:719—25. DOI: 10.1097/WCO.0b013e3282f1a06e.Paice J.A. Periferal neuropathy: experimental findings, clinical approaches. J Support Oncol 2005:5:61—3.Paice J.A. Chemotherapy-indused periferal neuropathy: the dangerous but understudied syndrome. Pain management SIG Newsletter 2007;17:1. Available at: http:/onsopcontent.ons.org/Publications/ Sig Newsletters/pm/pm17.1.htlm.Fung C., Dinh P. Jr, Ardeshir-Rouhani-Fard S. et al. Toxicities associated with cisplatin-based chemotherapy and radiotherapy in long-term testicular cancer survivors. Adv Urol 2018;2018:8671832. DOI: 10.1155/2018/8671832.Cerny T., Khpfer A. The enigma of ifo-sfamide encephalopathy. Ann Oncol 1992;3:679—81. DOI: 10.1093/ oxfordjournals.annonc.a058317.Yin H., Yang Q., Cao Z. et al. Activation of NLRX1-mediated autophagy accelerates the ototoxic potential of cisplatin in auditory cells. Toxicol Appl Pharmacol 2018;343:16—28. DOI: 10.1016/j.taap.2018.02.007.Reddel R.R., Kefford R.F., Grant J.M. et al. Ototoxicity in patients receiving cisplatin: importance of dose and method of drug administration. Cancer Treat Rep 1982;66(1):19—23.Bokemeyer C., Berger C.C., Hartmann J.T. et al. Analysis of risk factors for cisplatin-induced ototoxicity in patients with testicular cancer. Br J Cancer 1998;77:1355—62. DOI: 10.1038/bjc.1998.226.Brydoy M., Oldenburg J., Klepp O. et al. Observational study of prevalence of longterm Raynaud-like phenomena and neurological side effects intesticular cancer survivors. J Natl Cancer Inst 2009;101:1682—95. DOI: 10.1093/jnci/djp413.Fossa S.D., de Wit R., Roberts J.T. et al. Quality of life in good prognosis patients with metastatic germ cell cancer: a prospective study of the European Organization for Research and Treatment of Cancer Genitourinary Group/Medical Research Council Testicular Cancer Study Group (30941/TE20). J Clin Oncol 2003;21:1107—18. DOI: 10.1200/JCO.2003.02.075.Wheeler H.E., Gamazon E.R., Frisina R.D. et al. Variants in WFS1 and other mendelian deafness genes are associated with cisplatin-associated ototoxicity. Clin Cancer Res 2017;23(13):3325—33. DOI: 10.1158/1078-0432.CCR-16-2809.Travis L.B., Curtis R.E., Storm H. et al. Risk of second malignant neoplasms among long-term survivors of testicular cancer. J Natl Cancer Inst 1997;89(19):1429—39. DOI: 10.1093/jnci/89.19.1429.Travis L.B., Andersson M., Gospodarowicz M. et al. Treatment-associated leukemia following testicular cancer. J Natl Cancer Inst 2000;92(14):1165—71. DOI: 10.1093/jnci/92.14.1165.Necchi A., Lo Vullo S., Secondino S. et al. Secondary malignancies after high-dose chemotherapy in germ cell tumor patients: a 34-year retrospective study of the European Society for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant 2018;53(6):722—8. DOI: 10.1038/s41409-017-0079-z.Fung C., Fossa S.D., Milano M.T. et al. Solid tumors after chemotherapy or surgery for testicular nonseminoma: a population-based study. J Clin Oncol 2013;31(30):3807—14. DOI: 10.1200/JCO.2013.50.3409.Van den Belt A., de Wit R., Gietema J.A. et al. Treatment-specific risks of second malignancies and cardiovascular disease in 5-year survivors of testicular cancer. J Clin Oncol 2007;25(28):4370—8. DOI: 10.1200/JCO.2006.10.5296.Travis L.B., Fossa S.D., Schonfeld S.J. et al. Second cancers among 40,576 testicular cancer patients: focus on longterm survivors. J Natl Cancer Inst 2005;97(18):1354—65. DOI: 10.1093/jnci/dji278.Hauptmann M., Fossa S.D., Stovall M. et al. Increased stomach cancer risk following radiotherapy for testicular cancer. Br J Cancer 2015;112(1):44— 51. DOI: 10.1038/bjc.2014.552.Hauptmann M., Borge Johannesen T., Gilbert E.S. et al. Increased pancreatic cancer risk following radiotherapy for testicular cancer. Br J Cancer 2016;115(7):901 —8. DOI: 10.1038/bjc.2016.272.Travis L.B., Beard C., Allan J.M. et al. Testicular cancer survivorship: research strategies and recommendations. J Natl Cancer Inst 2010;102(15):1114—30. DOI: 10.1093/jnci/djq216.Kollmannsber C., Hartmann J.T., Kanz L., Bokemeyer C. Therapy-related malignancies following treatment of germ cell cancer. Int J Cancer 1999;83(6):860—3. DOI: 10.1002/(sici)1097-0215(19991210)83:6<860::aid-ijc32>3.0.co;2-l.Haugnes H.S., Oldenburg J., Bremnes R.M. Pulmonary and cardio vascular toxicity in long-term testicular cancer survivors 2015;33(9):399—406. DOI: 10.1016/j.urolonc.2014.11.012.Maroto P., Anguera G., Martin C. Long-term toxicity of the treatment for germ cell-cancer: a review. Critical Rev Oncol/Hematol 2018;121:62-7. DOI: 10.1016/j.critrevonc.2017.11.015Boyer M., Raghavan D., Harris P.J. et al. Lack of late toxicity in patients treated with cisplatin-containing combination chemotherapy for metastatic testicular cancer. J Clin Oncol 1990;8:21-6. DOI: 10.1200/JCO.1990.8.1.21.Haugnes H.S., Aass N., Fossa S.D. et al. Bremnes pulmonary function in long-term survivors of testicular cancer. J Clin Oncol 2009;27(17):2779-86 DOI: 10.1200/JCO.2008.18.5181.O’Sullivan J.M., Huddart R.A., Norman A.R., et al. Predicting the risk of bleomycin lung toxicity in patients with germ-cell tumours. Ann Oncol 2003;14:91-6. DOI: 10.1093/annonc/mdg020.Necchi A., Miceli R., Oualla K. et al: Effect of bleomycin administration on the development of pulmonary toxicity in patients with metastatic germ cell tumors receiving first-line chemotherapy: a meta-analysis of randomized studies. Clin Genitourin Cancer 2017;15:213-20. DOI: 10.1016/j.clgc.2016.08.021.Hendry W.F., Stedronska J., Jones C.R. et al. Semen analysis in testicular cancer and Hodgkin’s disease: pre- and posttreatment findings and implications for cryopreservation. Br J Urol 1983;55(6):769—73. DOI: 10.1111/j.1464-410x.1983.tb03423.x.Gurgan T., Salman C., Demirol A. Pregnancy and assisted reproduction techniques in men and women after cancer treatment. Placenta 2008;29 Suppl B:152—9. DOI: 10.1016/j.placenta.2008.07.007.Nurmio M., Keros V., Lahteenmaki P. Effect of childhood acute lymphoblastic leukemia therapy on spermatogonia populations and future fertility. J Clin Endocrinol Metab 2009;94(6):2119—22. DOI: 10.1210/jc.2009-0060.Lampe H., Horwich A., Norman A. et al. Fertility after chemotherapy for testicular germ cell cancers. J Clin Onco. 1997;15(1):239—45. DOI: 10.1200/JCO.1997.15.1.239.Rowley M.J., Leach D.R., Warner G.A., Heller C.G. Effect of graded doses of ionizing radiation on the human testis. Radiat Res 1974;59(3):665-78.Centola G.M., Keller J.W., Henzler M., Rubin P. Effect of low-dose testicular irradiation on sperm count and fertility in patients with testicular seminoma. J Androl 1994;15(6):608—13.Sklar C.A., Robison L.L., Nesbit M.E. et al. Effects of radiation on testicular function in long-term survivors of childhood acute lymphoblastic leukemia: a report from the Children Cancer Study Group. J Clin Oncol 1990;8(12):1981-7. DOI: 10.1200/JCO.1990.8.12.1981.Ghezzi M., De Toni L., Palego P. et al. Increased risk of testis failure in testicular germ cell tumor survivors undergoing radiotherapy. Oncotarget 2017;9(3):3060—8. DOI: 10.18632/oncotarget.23081.Willemse P.M., Burggraaf J., Hamdy N.A. et al. Prevalence of the metabolic syndrome and cardiovascular disease risk in chemotherapytreated testicular germ cell tumour survivors. Br J Cancer 2013;109(1):60—7. DOI: 10.1038/bjc.2013.226.Haugnes H.S., Aass N., Fossa S.D. et al. Components of the metabolic syndrome in long-term survivors of testicular cancer. Ann Oncol 2007;18(2):241—8. DOI: 10.1093/annonc/mdl372.Nuver J., Smit A.J., Wolffenbuttel B.H. et al. The metabolic syndrome and disturbances in hormone levels in longterm survivors of disseminated testicular cancer. J Clin Oncol 2005;23(16):3718—25. DOI: 10.1200/JCO.2005.02.176.Dahl A.A., Bremmes R., Dahl O. Is the sexual function compromised in long-term testicular cancer survivors? Eur Urol 2007;52(5):1438—47. DOI: 10.1016/j.eururo.2007.02.046.Sprauten M., Brydoy M., Haugnes H.S. et al. Longitudinal serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels in a population-based sample of long-term testicular cancer survivors. J Clin Oncol 2014;32(6):571—8. DOI: 10.1200/JCO.2013.51.2715.Brydoy M., Fossa S.D., Klepp O. et al. Paternity following treatment for testicular cancer. J Natl Cancer Inst. 2005 Nov 2;97(21):1580—8. DOI: 10.1093/jnci/dji339.Nijman J.M., Schraffordt Koops H., Oldhoff J. et al. Sexual function after bilateral retroperitoneal lymph node dissection for nonseminomatous testicular cancer. Arch Androl 1987;18(3):255—67. DOI: 10.3109/01485018708988491.Donohue J.P., Thornhill J.A., Foster R.S. et al. Retroperitoneal lymphadenectomy for clinical stage A testis cancer (1965 to 1989): modifications of technique and impact on ejaculation. J Urol 1993 Feb;149(2):237—43. DOI: 10.1016/s0022-5347(17)36046-9.Servaes P., Verhagen C., Bleijenberg G. Fatigue in cancer patients during and after treatment: prevalence, correlates and interventions. Eur J Cancer 2002;38(1):27—43. DOI: 10.1016/s0959-8049(01)00332-x.Mock V., Atkinson A., Barsevick A. et al. NCCN practice guidelines for cancer-related fatigue. Oncology (Williston Park) 2000;14(11A):151—61.Fossa S.D., Dahl A.A., Loge J.H. Fatigue, anxiety and depression in long-term survivors of testicular cancer. J Clin Oncol 2003;21(7):1249—54. DOI: 10.1200/JCO.2003.08.163.Orre I.J., Fossa S.D., Murison R. et al. Chronic cancer-related fatigue in longterm survivors of testicular cancer. J Psychosom Res 2008;64(4):363—71. DOI: 10.1016/j.jpsychores.2008.01.002.Doble G.R., Arver S., Bettochi C. et al. Guidelines on male hypogonadism. EAU guidelines 2015.Tsimafeyeu I., Borisov P., Zukov R. et al. Exploratory endpoints in a FARETES study of the efficacy of testosterone in metastatic renal cell carcinoma (mRCC) patients. J Clin Oncol 2019;37(7_suppl):574. DOI: 10.1200/JCO.2019.37.7_suppl.574.Sprauten M., Haugnes H.S., Brydoy M. et al. Chronic fatigue in 812 testicular cancer survivors during long-term followup: increasing prevalence and risk factors. Ann Oncol 2015;26(10):2133—40. DOI: 10.1093/annonc/mdv328.Jahnukainen K., Ehmcke J., Hou M., Schlatt S. Testicular function and fertility preservation in male cancer patients. Best Pract Res Clin Endocrinol Metab 2011;25(2):287—302. DOI: 10.1016/j.beem.2010.09.007.