Turkiye Klinikleri Journal of Internal Medicine

.: REVIEW
Kanser Tedavileri ve Alopesi: Bir Sistematik Derleme
Cancer Treatments and Alopecia: A Systematic Review
Bilgin DEMİRa, Sabri BARUTCAa
aAydın Adnan Menderes Üniversitesi Tıp Fakültesi, İç Hastalıkları ABD, Tıbbi Onkoloji BD, Aydın, TÜRKİYE
Turkiye Klinikleri J Intern Med. 2021;6(2):96-104
doi: 10.5336/intermed.2021-81828
Article Language: TR
Full Text
ÖZET
 Kanser tedavilerine ikincil alopesi, en sık ve en fark edilebilir yan etkiler arasında olup, genellikle geçici ancak seyrek olarak kalıcı da olabilen kısmi veya tam saç kaybı durumudur. Hastalar için en rahatsız edici ve istenmeyen yan etki olabilir. Kemoterapi (KT) sonrası olduğu gibi onkolojide kullanılan hedefe yönelik tedaviler, biyolojik ve immünolojik tedavileri de içeren yeni tedavi yöntemleri sonrasında da görülebilmektedir. Kanser tedavilerine ikincil alopesi, genellikle skatrisyel olmayan alopesi olarak ortaya çıkar. Alopesinin değerlendirilmesinde, 'Amerikan Ulusal Kanser Enstitüsü Yan Etkiler İçin Ortak Terminoloji Kriterleri' ve 'Dean Alopesi Ölçeği' gibi çeşitli ölçekler kullanılmaktadır. Genellikle KT uygulaması sonrasında 2-3. haftalarda başlar ve düzelmesi 3 aya kadar uzayabilir. En sık ve şiddetli alopesi oluşturan KT ajanları arasında alkilleyici ajanlar, antimikrotübül ajanlar, antitümör antibiyotikleri ve topoizomeraz inhibitörleri yer alır. Potansiyel olarak alopesi oluşturabilen bir tedavi öncesinde hasta bilgilendirilerek hazırlanmalıdır. Bu yaklaşım, saç dökülmesine bağlı psikolojik travmayı en aza indirmek açısından önemlidir. Alopesiyi önleme ve tedavi amacıyla bazı uygulamalar yapılmaktadır. Bunlar, saç köküne verilen ilaç miktarını fiziksel olarak azaltmaya yönelik stratejileri ve farmakolojik uygulamaları içerir. İki farklı otomatik hipotermi cihazı 'DigniCap ve Paxman', Amerikan Gıda ve İlaç Dairesi tarafından (neo) adjuvan KT alan hastalarda onaylanmıştır. Preklinik çalışmalar, alopesinin önlenmesine yönelik farmakolojik uygulamaların yararlı olabileceğine işaret etse de günümüzde hiçbir farmakolojik uygulama, kanser tedavilerine bağlı alopeside onaylanmamıştır. Kanser tedavilerine ikincil alopesinin önlenmesi ve tedavisi konusunda daha fazla araştırmaya ihtiyaç duyulmaktadır.

Anahtar Kelimeler: Alopesi; ilaç tedavisi; tümörler; önleme ve kontrol
ABSTRACT
 Alopecia is the partial or total loss of scalp hair and it is also among the most common and remarkable toxicities of cancer treatments, which is usually transient, though can also be permanent in that case. Treatment related alopecia in cancer can sometimes be the most unwanted and disturbing complication. As in the case of chemotherapy (CT), targeted treatments, biological and immunological therapies can also result with alopecia. Alopecia related to cancer treatments is generally seen in non-scatricial form. The most common scalas used in the classification of alopecia are 'American National Cancer Institute Common Terminology Criteria for Adverse Effects' and 'Dean's Alopecia Scala'. Alopecia generally appears in the 2nd to 3rd weeks of CT and recovers up to 3 months. Among the CT agents the most frequent and severe alopecia is usually seen with alkylating and anti-microtubuler agents, as well as anti-tumor antibiotics and topoisomerase inhibitors. The patients have to be informed before a potentially alopecia causing treatment. This policy is extremely important for the prevention and to minimize the psychological trauma. Certain procedures are used to prevent or treat the alopecia. These include the strategies to decrease the amount of drugscalp hair interactions physically and pharmacological treatments. Two different automatic hypothermia devices (DigniCap and Paxman) are approved by the American Food and Drug Agency for (neo) adjuvant CT. Although some preclinic studies indicate the benefit of certain pharmacological agents, currently, none of these have been approved in cancer treatments related alopecia. In the era of both prevention and therapy of cancer treatments related alopecia more extended studies are certainly needed.

Keywords: Alopecia; medication; tumors; prevention and control
REFERENCES:
  1. McGarvey EL, Baum LD, Pinkerton RC, Rogers LM. Psychological sequelae and alopecia among women with cancer. Cancer Pract. 2001;9(6):283-9. [PubMed] 
  2. Williamson H, Harcourt D, Halliwell E, Frith H, Wallace M. Adolescents' and parents' experiences of managing the psychosocial impact of appearance change during cancer treatment. J Pediatr Oncol Nurs. 2010;27(3):168-75. [Crossref]  [PubMed] 
  3. Frith H, Harcourt D, Fussell A. Anticipating an altered appearance: women undergoing chemotherapy treatment for breast cancer. Eur J Oncol Nurs. 2007;11(5):385-91. Epub 2007 May 18. [Crossref]  [PubMed] 
  4. Hansen HP. Hair loss induced by chemotherapy: an anthropological study of women, cancer and rehabilitation. Anthropol Med. 2007;14(1):15-26. [Crossref]  [PubMed] 
  5. Kim IR, Cho J, Choi EK, Kwon IG, Sung YH, Lee JE, et al. Perception, attitudes, preparedness and experience of chemotherapy-induced alopecia among breast cancer patients: a qualitative study. Asian Pac J Cancer Prev. 2012;13(4):1383-8. [Crossref]  [PubMed] 
  6. Dean JC, Salmon SE, Griffith KS. Prevention of doxorubicin-induced hair loss with scalp hypothermia. N Engl J Med. 1979;301(26):1427-9. [Crossref]  [PubMed] 
  7. Fuchs E. Skin stem cells: rising to the surface. J Cell Biol. 2008;180(2):273-84. [Crossref]  [PubMed]  [PMC] 
  8. Cotsarelis G, Millar SE. Towards a molecular understanding of hair loss and its treatment. Trends Mol Med. 2001;7(7):293-301. [Crossref]  [PubMed] 
  9. Sato N, Leopold PL, Crystal RG. Effect of adenovirus-mediated expression of Sonic hedgehog gene on hair regrowth in mice with chemotherapy-induced alopecia. J Natl Cancer Inst. 2001;93(24):1858-64. [Crossref]  [PubMed] 
  10. Sperling LC, Cowper SE. The histopathology of primary cicatricial alopecia. Semin Cutan Med Surg. 2006;25(1):41-50. [Crossref]  [PubMed] 
  11. Paus R, Haslam IS, Sharov AA, Botchkarev VA. Pathobiology of chemotherapy-induced hair loss. Lancet Oncol. 2013;14(2):e50-9. [Crossref]  [PubMed] 
  12. Trotti A, Colevas AD, Setser A, Rusch V, Jaques D, Budach V, et al. CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol. 2003;13(3): 176- Z81. [Crossref]  [PubMed] 
  13. Kanti V, Nuwayhid R, Lindner J, Hillmann K, Stroux A, Bangemann N, et al. Analysis of quantitative changes in hair growth during treatment with chemotherapy or tamoxifen in patients with breast cancer: a cohort study. Br J Dermatol. 2014;170(3):643-50. [Crossref]  [PubMed] 
  14. Chon SY, Champion RW, Geddes ER, Rashid RM. Chemotherapy-induced alopecia. J Am Acad Dermatol. 2012;67(1):e37-47. [Crossref]  [PubMed] 
  15. Yun SJ, Kim SJ. Hair loss pattern due to chemotherapy-induced anagen effluvium: a cross-sectional observation. Dermatology. 2007;215(1):36-40. [Crossref]  [PubMed] 
  16. Chung S, Low SK, Zembutsu H, Takahashi A, Kubo M, Sasa M, et al. A genome-wide association study of chemotherapy-induced alopecia in breast cancer patients. Breast Cancer Res. 2013;15(5):R81. [Crossref]  [PubMed]  [PMC] 
  17. Zarbo A, Belum VR, Sibaud V, Oudard S, Postow MA, Hsieh JJ, et al. Immune-related alopecia (areata and universalis) in cancer patients receiving immune checkpoint inhibitors. Br J Dermatol. 2017;176(6):1649-52. [Crossref]  [PubMed]  [PMC] 
  18. Belum VR, Marulanda K, Ensslin C, Gorcey L, Parikh T, Wu S, et al. Alopecia in patients treated with molecularly targeted anticancer therapies. Ann Oncol. 2015;26(12):2496-502. [Crossref]  [PubMed]  [PMC] 
  19. Rugo HS, Klein P, Melin SA, Hurvitz SA, Melisko ME, Moore A, et al. Association between use of a scalp cooling device and alopecia after chemotherapy for breast cancer. JAMA. 2017;317(6):606-14. [Crossref]  [PubMed]  [PMC] 
  20. Nangia J, Wang T, Osborne C, Niravath P, Otte K, Papish S, et al. Effect of a scalp cooling device on alopecia in women undergoing chemotherapy for breast cancer: The SCALP randomized clinical trial. JAMA. 2017;317(6): 596-605. [Crossref]  [PubMed] 
  21. Alley E, Green R, Schuchter L. Cutaneous toxicities of cancer therapy. Curr Opin Oncol. 2002;14(2):212-6. [Crossref]  [PubMed] 
  22. Vowels M, Chan LL, Giri N, Russell S, Lam-Po-Tang R. Factors affecting hair regrowth after bone marrow transplantation. Bone Marrow Transplant. 1993;12(4):347-50. [PubMed] 
  23. Fonia A, Cota C, Setterfield JF, Goldberg LJ, Fenton DA, Stefanato CM. Permanent alopecia in patients with breast cancer after taxane chemotherapy and adjuvant hormonal therapy: Clinicopathologic findings in a cohort of 10 patients. J Am Acad Dermatol. 2017; 76(5):948-57. [Crossref]  [PubMed] 
  24. Kang D, Kim IR, Choi EK, Im YH, Park YH, Ahn JS, et al. Permanent chemotherapy-induced alopecia in patients with breast cancer: a 3-year prospective cohort study. Oncologist. 2019;24(3):414-20. [Crossref]  [PubMed]  [PMC] 
  25. Gallicchio L, Calhoun C, Helzlsouer KJ. Aromatase inhibitor therapy and hair loss among breast cancer survivors. Breast Cancer Res Treat. 2013;142(2):435-43. [Crossref]  [PubMed] 
  26. Saggar V, Wu S, Dickler MN, Lacouture ME. Alopecia with endocrine therapies in patients with cancer. Oncologist. 2013;18(10):1126-34. [Crossref]  [PubMed]  [PMC] 
  27. Freites-Martinez A, Shapiro J, Chan D, Fornier M, Modi S, Gajria D, et al. Endocrine therapy-induced alopecia in patients with breast cancer. JAMA Dermatol. 2018;154(6):670-5. [Crossref]  [PubMed]  [PMC] 
  28. Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, et al. Ribociclib as first-line therapy for hr-positive, advanced breast cancer. N Engl J Med. 2016;375(18):1738-48. Erratum in: N Engl J Med. 2018;379(26):2582. [Crossref]  [PubMed] 
  29. Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J, et al. MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 2017;35(32): 3638-46. [Crossref]  [PubMed] 
  30. Buzdar A, Douma J, Davidson N, Elledge R, Morgan M, Smith R, et al. Phase III, multicenter, double-blind, randomized study of letrozole, an aromatase inhibitor, for advanced breast cancer versus megestrol acetate. J Clin Oncol. 2001;19(14):3357-66. [Crossref]  [PubMed] 
  31. Alonso L, Fuchs E. The hair cycle. J Cell Sci. 2006;119(Pt 3):391-3. [Crossref]  [PubMed] 
  32. Niiyama S, Happle R, Hoffmann R. Influence of estrogens on the androgen metabolism in different subunits of human hair follicles. Eur J Dermatol. 2001;11(3):195-8. [PubMed] 
  33. Dunn C, Keam SJ. Letrozole: a pharmacoeconomic review of its use in postmenopausal women with breast cancer. Phar macoeconomics. 2006;24(5):495-517. [Crossref]  [PubMed] 
  34. Hepper DM, Wu P, Anadkat MJ. Scarring alopecia associated with the epidermal growth factor receptor inhibitor erlotinib. J Am Acad Dermatol. 2011;64(5):996-8. [Crossref]  [PubMed] 
  35. Hoekzema R, Drillenburg P. Folliculitis decalvans associated with erlotinib. Clin Exp Dermatol. 2010;35(8):916-8. [Crossref]  [PubMed] 
  36. Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, et al; TARGET Study Group. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007;356(2): 125-34. Erratum in: N Engl J Med. 2007; 357(2):203. [Crossref]  [PubMed] 
  37. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al; SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008; 359(4):378-90. [Crossref]  [PubMed] 
  38. Ratain MJ, Eisen T, Stadler WM, Flaherty KT, Kaye SB, Rosner GL, et al. Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2006;24(16):2505-12. [Crossref]  [PubMed] 
  39. Autier J, Escudier B, Wechsler J, Spatz A, Robert C. Prospective study of the cutaneous adverse effects of sorafenib, a novel multikinase inhibitor. Arch Dermatol. 2008;144(7): 886-92. [Crossref]  [PubMed] 
  40. Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a rando mised phase 3 trial. Lancet. 2011;378(9807): 1931-9. Erratum in: Lancet. 2012;380(9856): 1818. [Crossref]  [PubMed] 
  41. Zhang L, Zhou Q, Ma L, Wu Z, Wang Y. Meta-analysis of dermatological toxicities associated with sorafenib. Clin Exp Dermatol. 2011;36(4):344-50. [Crossref]  [PubMed] 
  42. Chang AL, Solomon JA, Hainsworth JD, Goldberg L, McKenna E, Day BM, et al. Expanded access study of patients with advanced basal cell carcinoma treated with the Hedgehog pathway inhibitor, vismodegib. J Am Acad Dermatol. 2014;70(1):60-9. [Crossref]  [PubMed] 
  43. Lear JT, Migden MR, Lewis KD, Chang ALS, Guminski A, Gutzmer R, et al. Long-term efficacy and safety of sonidegib in patients with locally advanced and metastatic basal cell carcinoma: 30-month analysis of the randomized phase 2 BOLT study. J Eur Acad Dermatol Venereol. 2018;32(3):372-81. [Crossref]  [PubMed]  [PMC] 
  44. Minami Y, Minami H, Miyamoto T, Yoshimoto G, Kobayashi Y, Munakata W, et al. Phase I study of glasdegib (PF-04449913), an oral smoothened inhibitor, in Japanese patients with select hematologic malignancies. Cancer Sci. 2017 Aug;108(8):1628-1633. [Crossref]  [PubMed]  [PMC] 
  45. Naidoo J, Page DB, Li BT, Connell LC, Schindler K, Lacouture ME, et al. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol. 2015;26(12): 2375-91. Erratum in: Ann Oncol. 2016;27(7): 1362. [Crossref]  [PubMed]  [PMC] 
  46. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012; 366(26):2443-54. [PubMed]  [PMC] 
  47. Assi H, Wilson KS. Immune toxicities and long remission duration after ipilimumab therapy for metastatic melanoma: two illustrative cases. Curr Oncol. 2013;20(2):e165-9. [Crossref]  [PubMed]  [PMC] 
  48. Jaber SH, Cowen EW, Haworth LR, Booher SL, Berman DM, Rosenberg SA, et al. Skin reactions in a subset of patients with stage IV melanoma treated with anti-cytotoxic T-lymphocyte antigen 4 monoclonal antibody as a single agent. Arch Dermatol. 2006;142(2):166-72. [Crossref]  [PubMed] 
  49. Rivera N, Boada A, Bielsa MI, Fernández-Figueras MT, Carcereny E, Moran MT, et al. Hair repigmentation during immunotherapy treatment with an anti-programmed cell death 1 and anti-programmed cell death ligand 1 agent for lung cancer. JAMA Dermatol. 2017;153(11):1162-5. [Crossref]  [PubMed]  [PMC] 
  50. Dorr VJ. A practitioner's guide to cancer-related alopecia. Semin Oncol. 1998;25(5):562-70. [PubMed] 
  51. Rossi A, Fortuna MC, Caro G, Pranteda G, Garelli V, Pompili U, et al. Chemotherapy-induced alopecia management: Clinical experience and practical advice. J Cosmet Der matol. 2017;16(4):537-41. [Crossref]  [PubMed]  [PMC] 
  52. Breed WPM, van den Hurk CJG, Peerbooms M. Presentation, impact and prevention of chemotherapy-induced hair loss: Scalp cooling potentials and limitations. Expert Rev Dermatol. 2011;6(1):109-25. [Crossref] 
  53. Vendelbo Johansen L. Scalp hypothermia in the prevention of chemotherapy-induced alopecia. Acta Radiol Oncol. 1985;24(2):113-6. [Crossref]  [PubMed] 
  54. Shin H, Jo SJ, Kim DH, Kwon O, Myung SK. Efficacy of interventions for prevention of chemotherapy-induced alopecia: a systematic review and meta-analysis. Int J Cancer. 2015;136(5):E442-54. [Crossref]  [PubMed] 
  55. Betticher DC, Delmore G, Breitenstein U, Anchisi S, Zimmerli-Schwab B, Müller A, et al. Efficacy and tolerability of two scalp cooling systems for the prevention of alopecia associated with docetaxel treatment. Support Care Cancer. 2013;21(9):2565-73. [Crossref]  [PubMed] 
  56. Komen MM, Breed WP, Smorenburg CH, van der Ploeg T, Goey SH, van der Hoeven JJ, et al. Results of 20- versus 45-min post-infusion scalp cooling time in the prevention of docetaxel-induced alopecia. Support Care Cancer. 2016;24(6):2735-41. [Crossref]  [PubMed] 
  57. Hillen HF, Breed WP, Botman CJ. Scalp cooling by cold air for the prevention of chemotherapy-induced alopecia. Neth J Med. 1990; 37(5-6):231-5. [PubMed] 
  58. Munzone E, Bagnardi V, Campennì G, Mazzocco K, Pagan E, Tramacere A, et al. Preventing chemotherapy-induced alopecia: a prospective clinical trial on the efficacy and safety of a scalp-cooling system in early breast cancer patients treated with anthracyclines. Br J Cancer. 2019;121(4):325-31. [Crossref]  [PubMed]  [PMC] 
  59. van den Hurk CJ, van de Poll-Franse LV, Breed WP, Coebergh JW, Nortier JW. Scalp cooling to prevent alopecia after chemotherapy can be considered safe in patients with breast cancer. Breast. 2013;22(5):1001-4. [Crossref]  [PubMed] 
  60. Lemieux J, Amireault C, Provencher L, Maunsell E. Incidence of scalp metastases in breast cancer: a retrospective cohort study in women who were offered scalp cooling. Breast Cancer Res Treat. 2009;118(3):547-52. [Crossref]  [PubMed] 
  61. Komen MM, Smorenburg CH, van den Hurk CJ, Nortier JW. Factors influencing the effectiveness of scalp cooling in the prevention of chemotherapy-induced alopecia. Oncologist. 2013;18(7):885-91. [Crossref]  [PubMed]  [PMC] 
  62. Witman G, Cadman E, Chen M. Misuse of scalp hypothermia. Cancer Treat Rep. 1981;65(5-6):507-8. [PubMed] 
  63. Glaser DA, Hossain P, Perkins W, Griffiths T, Ahluwalia G, Weng E, et al. Long-term safety and efficacy of bimatoprost solution 0?03% application to the eyelid margin for the treatment of idiopathic and chemotherapy-induced eyelash hypotrichosis: a randomized controlled trial. Br J Dermatol. 2015;172(5):1384-94. [Crossref]  [PubMed]  [PMC] 
  64. Jimenez JJ, Yunis AA. Vitamin D3 and chemotherapy-induced alopecia. Nutrition. 1996;12(6):448-9. [Crossref]  [PubMed] 
  65. Hidalgo M, Rinaldi D, Medina G, Griffin T, Turner J, Von Hoff DD. A phase I trial of topical topitriol (calcitriol, 1,25-dihydroxyvitamin D3) to prevent chemotherapy-induced alopecia. Anticancer Drugs. 1999;10(4):393-5. [Crossref]  [PubMed] 
  66. Rodriguez R, Machiavelli M, Leone B, Romero A, Cuevas MA, Langhi M, et al. Minoxidil (Mx) as a prophylaxis of doxorubicin--induced alopecia. Ann Oncol. 1994;5(8):769-70. [Crossref]  [PubMed] 
  67. Duvic M, Lemak NA, Valero V, Hymes SR, Farmer KL, Hortobagyi GN, et al. A randomized trial of minoxidil in chemotherapy-induced alopecia. J Am Acad Dermatol. 1996;35(1):74-8. [Crossref]  [PubMed] 
  68. Rozner RN, Freites-Martinez A, Shapiro J, Geer EB, Goldfarb S, Lacouture ME. Safety of 5α-reductase inhibitors and spironolactone in breast cancer patients receiving endocrine therapies. Breast Cancer Res Treat. 2019; 174(1):15-26. [Crossref]  [PubMed]  [PMC] 
  69. Soref CM, Fahl WE. A new strategy to prevent chemotherapy and radiotherapy-induced alopecia using topically applied vasoconstrictor. Int J Cancer. 2015;136(1):195-203. [Crossref]  [PubMed]  [PMC] 
  70. Davis ST, Benson BG, Bramson HN, Chapman DE, Dickerson SH, Dold KM, et al. Prevention of chemotherapy-induced alopecia in rats by CDK inhibitors. Science. 2001; 291(5501):134-7. Retraction in: Davis ST, Benson BG, Bramson HN, Chapman DE, Dickerson SH, Dold KM, et al. [Crossref]  [PubMed] 
  71. Jimenez JJ, Wong GH, Yunis AA. Interleukin 1 protects from cytosine arabinoside-induced alopecia in the rat model. FASEB J. 1991;5(10):2456-8. [Crossref]  [PubMed] 
  72. Shirai A, Tsunoda H, Tamaoki T, Kamiya T. Topical application of cyclosporin A induces rapid-remodeling of damaged anagen hair follicles produced in cyclophosphamide administered mice. J Dermatol Sci. 2001;27(1):7-13. [Crossref]  [PubMed] 
  73. Jimenez JJ, Yunis AA. Protection from 1-beta-D-arabinofuranosylcytosine-induced alopecia by epidermal growth factor and fibroblast growth factor in the rat model. Cancer Res. 1992;52(2):413-5. [PubMed] 
  74. Dueland S, Sauer T, Lund-Johansen F, Ostenstad B, Tveit KM. Epidermal growth factor receptor inhibition induces trichomegaly. Acta Oncol. 2003;42(4):345-6. [Crossref]  [PubMed] 

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4. GENERAL PROVISIONS

4.1. "Turkiye Klinikleri" is completely free to determine which of the services and contents provided in the "SITE" will be charged.

4.2. People benefiting from the services provided by "Turkiye Klinikleri" and using the website can use the "SITE" only according to the law and only for personal reasons. Users have the criminal and civil liability for every process and action they take in the "SITE". Every USER agrees, declares and undertakes that they will not proceed by any function or action infringement of rights of "Turkiye Klinikleri"s and/or other third parties', they are the exclusive right holder on usage, processing, storage, made public and revealing any written, visual or auditory information reported to Turkiye Klinikleri" and/or "SITE" to the third parties. "USER" agrees and undertakes that s/he will not duplicate, copy, distribute, process, the pictures, text, visual and auditory images, video clips, files, databases, catalogs and lists within the "SITE", s/he will not be using these actions or with other ways to compete with "Turkiye Klinikleri", directly or indirectly.

4.3. The services provided and the context published within the "SITE" by third parties is not under the responsibility of "Turkiye Klinikleri", institutions collaborated with "Turkiye Klinikleri", "Turkiye Klinikleri" employee and directors, "Turkiye Klinikleri" authorized salespeople. Commitment to accuracy and legality of the published information, context, visual and auditory images provided by any third party are under the full responsibility of the third party. "Turkiye Klinikleri" does not promise and guarantee the safety, accuracy and legality of the services and context provided by a third party.

4.4. "USER"s cannot act against "Turkiye Klinikleri", other "USER"s and third parties by using the "SITE". "Turkiye Klinikleri" has no direct and/or indirect responsibility for any damage a third party suffered or will suffer regarding "USER"s actions on the "SITE" against the rules of the hereby "Terms of Use" and the law.

4.5. "USER"s accept and undertake that the information and context they provided to the "SITE" are accurate and legal. "Turkiye Klinikleri" is not liable and responsible for promising and guaranteeing the verification of the information and context transmitted to "Turkiye Klinikleri" by the "USER"s, or uploaded, changed and provided through the "SITE" by them and whether these information are safe, accurate and legal.

4.6. "USER"s agree and undertake that they will not perform any action leading to unfair competition, weakening the personal and commercial credit of "Turkiye Klinikleri" and a third party,  encroaching and attacking on personal rights within the "SITE" in accordance with the Turkish Commercial Code Law.

4.7. "Turkiye Klinikleri" reserves the right to change the services and the context within the "SITE"  anytime. "Turkiye Klinikleri" may use this right without any notification and timelessly. "USER"s have to make the changes and/or corrections "Turkiye Klinikleri" required immediately. Any changes and/or corrections that are required by "Turkiye Klinikleri", may be made by "Turkiye Klinikleri" when needed. Any harm, criminal and civil liability resulted or will result from changes and/or corrections required by "Turkiye Klinikleri" and were not made on time by the "USER"s belongs completely to the users.

4.8. "Turkiye Klinikleri" may give links through the "SITE" to other websites and/or "CONTEXT"s and/or folders that are outside of their control and owned and run by third parties. These links are provided for ease of reference only and do not hold qualification for support the respective web SITE or the admin or declaration or guarantee for the information inside. "Turkiye Klinikleri" does not hold any responsibility over the web-sites connected through the links on the "SITE", folders and context, the services or products on the websites provided through these links or their context.

4.9. "Turkiye Klinikleri" may use the information provided to them by the "USERS" through the "SITE" in line with the terms of the "PRIVACY POLICY" and "USER CONTRACT". It may process the information or classify and save them on a database. "Turkiye Klinikleri" may also use the USER's or visitor's identity, address, e-mail address, phone number, IP number, which sections of the "SITE" they visited, domain type, browser type, date and time information to provide statistical evaluation and customized services.

5. PROPRIETARY RIGHTS

5.1. The information accessed through this "SITE" or provided by the users legally and all the elements (including but not limited to design, text, image, html code and other codes) of the "SITE" (all of them will be called as studies tied to "Turkiye Klinikleri"s copyrights) belongs to "Turkiye Klinikleri". Users do not have the right to resell, process, share, distribute, display or give someone permission to access or to use the "Turkiye Klinikleri" services, "Turkiye Klinikleri" information and the products under copyright protection by "Turkiye Klinikleri". Within hereby "Terms of Use" unless explicitly permitted by "Turkiye Klinikleri" nobody can reproduce, process, distribute or produce or prepare any study from those under "Turkiye Klinikleri" copyright protection.

5.2. Within hereby "Terms of Use", "Turkiye Klinikleri" reserves the rights for "Turkiye Klinikleri" services, "Turkiye Klinikleri" information, the products associated with "Turkiye Klinikleri" copyrights, "Turkiye Klinikleri" trademarks, "Turkiye Klinikleri" trade looks or its all rights for other entity and information it has through this website unless it is explicitly authorized by "Turkiye Klinikleri".

6. CHANGES IN THE TERMS OF USE

"Turkiye Klinikleri" in its sole discretion may change the hereby "Terms of Use" anytime announcing within the "SITE". The changed terms of the hereby "Terms of Use" will become valid when they are announced. Hereby "Terms of Use" cannot be changed by unilateral declarations of users.

7. FORCE MAJEURE

"Turkiye Klinikleri" is not responsible for executing late or never of this hereby "Terms of Use", privacy policy and "USER Contract" in any situation legally taken into account as force majeure. Being late or failure of performance or non-defaulting of this and similar cases like this will not be the case from the viewpoint of "Turkiye Klinikleri", and "Turkiye Klinikleri" will not have any damage liability for these situations. "Force majeure" term will be regarded as outside of the concerned party's reasonable control and any situation that "Turkiye Klinikleri" cannot prevent even though it shows due diligence. Also, force majeure situations include but not limited to natural disasters, rebellion, war, strike, communication problems, infrastructure and internet failure, power cut and bad weather conditions.

8. LAW AND AUTHORISATION TO FOLLOW

Turkish Law will be applied in practicing, interpreting the hereby "Terms of Use" and managing the emerging legal relationships within this "Terms of Use" in case of finding element of foreignness, except for the rules of Turkish conflict of laws. Ankara Courts and Enforcement Offices are entitled in any controversy happened or may happen due to hereby contract.

9. CLOSING AND AGREEMENT

Hereby "Terms of Use" come into force when announced in the "SITE" by "Turkiye Klinikleri". The users are regarded to agree to hereby contract terms by using the "SITE". "Turkiye Klinikleri" may change the contract terms and the changes will be come into force by specifying the version number and the date of change on time it is published in the "SITE".

 

30.03.2014

Privacy Policy

We recommend you to read the terms of use below before you visit our website. In case you agree these terms, following our rules will be to your favor. Please read our Terms of Use thoroughly.

www.turkiyeklinikleri.com website belongs to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. and is designed in order to inform physicians in the field of health

www.turkiyeklinikleri.com cannot reach to user’s identity, address, service providers or other information. The users may send this information to the website through forms if they would like to. However, www.turkiyeklinikleri.com may collect your hardware and software information. The information consists of your IP address, browser type, operating system, domain name, access time, and related websites. www.turkiyeklinikleri.com cannot sell the provided user information (your name, e-mail address, home and work address, phone number) to the third parties, publish it publicly, or keep it in the website. Gathered information has a directing feature to be a source for the website’s visitor profile, reporting and promotion of the services.

www.turkiyeklinikleri.com uses the taken information:

-To enhance, improve and maintain the quality of the website

-To generate visitor’s profile and statistical data

-To determine the tendency of the visitors on using our website

-To send print publications/correspondences

-To send press releases or notifications through e-mail

-To generate a list for an event or competition

By using www.turkiyeklinikleri.com you are considered to agree that;

-Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. cannot be hold responsible for any user’s illegal and immoral behavior,

-Terms of use may change from time to time,

-It is not responsible for other websites’ contents it cannot control or the harms they may cause although it uses the connection they provided.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. may block the website to users in the following events:

-Information with wrong, incomplete, deceiving or immoral expressions is recorded to the website,

-Proclamation, advertisement, announcement, libelous expressions are used against natural person or legal identity,

-During various attacks to the website,

-Disruption of the website because of a virus.

Written, visual and audible materials of the website, including the code and the software are under protection by legal legislation.

Without the written consent of Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. the information on the website cannot be downloaded, changed, reproduced, copied, republished, posted or distributed.

All rights of the software and the design of the website belong to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. will be pleased to hear your comments about our terms of use. Please share the subjects you think may enrich our website or if there is any problem regarding our website.

info@turkiyeklinikleri.com