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Literatur:

Hautkrebsprävention: Risikovermeidung und Früherkennung (S. 10–15)
Kohelia Choudhury, Beate Volkmer, Henriette Bunde, Eckhard Breitbart

  1. Katalinic, A. (2017): Aktuelle Zahlen zur Epidemiologie von Melanomen und Hellem Hautkrebs, Institut für Krebsepidemiologie e.V. (IKE) der Universität zu Lübeck. (persönliche Korrespondenz)
  2. Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF): S3-Leitlinie Prävention von Hautkrebs, Langversion 1. 1, 2014, AWMF Registernummer: 032/052OL, leitlinienprogram-onkologie.de/Leitlinien.7.0.html (Zugriff am 31.08.2017)
  3. Robert-Koch Institut. Bericht zum Krebsgeschehen in Deutschland. 2016; pp 53–56
  4. Kandarr J, Reckert H, Mücke HG. Anpassung an die gesundheitlichen Risiken des Klimawandels als Aufgabe des umweltbezogenen Gesundheitsschutzes. Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz. 2014; 57(10): 1209–215 
  5. Armstrong BK, Kricker A. The epidemiology of UV induced skin cancer. J Photochem Photobiol B 2001, 63(1-3): 8–18
  6. El Ghissassi F, et al. A review of human carcinogens--part D: radiation. Lancet Oncol 2009; 10(8): 751–52 
  7. Matsumura Y, Ananthaswamy HN. Molecular mechanisms of photocarcinogenesis. Front Biosci 2002; 7: d765–83
  8. Douki T, Reynaud-Angelin A, Cadet J, Sage E. Bipyrimidine photoproducts rather than oxidative lesions are the main type of DNA damage involved in the genotoxic effect of solar UVA radiation. Biochemistry 2003; 42(30): 9221–226 
  9. Pfeifer GP, Besaratinia A. UV wavelength-dependent DNA damage and human non- melanoma and melanoma skin cancer. Photochem Photobiol Sci 2012; 11(1): 90–97 
  10. Yoshikawa T, Rae V, Bruins-Slot W, Van den Berg JW, Taylor JR, and Streilein JW. Susceptibility to effects of UVB radiation on induction of contact hypersensitivity as a risk factor for skin cancer in humans. J Invest Dermatol 1990; 95: 530–36
  11. Marshall V. Premalignant and malignant skin tumours in immunosuppressed patients. Transplantation 1974; 17(3): 272–75 
  12. Gandini S, Sera F, Cattaruzza MS, Pasquini P, Zanetti R, Masini C, Boyle P, Melchi CF. Meta-analysis of risk factors for cutaneous melanoma: III. Family history, actinic damage and phenotypic factors. Eur J Cancer 2005; 41(14): 2040–59
  13. Gallagher RP, Hill GB, Bajdik CD, Fincham S, Coldman AJ, McLean DI, Threlfall WJ. Sunlight exposure, pigmentary factors, and risk of nonmelanocytic skin cancer. I. Basal cell carcinoma. Arch Dermato 1995; 131(2): 157–63
  14. Holick MF. Environmental factors that influence the cutaneous production of vitamin D. Am J Clin Nutr 1995; 61(3 Suppl): 638S–645S
  15. Autier P, Dore JF. Influence of sun exposures during childhood and during adulthood on melanoma risk. EPIMEL and EORTC Melanoma Cooperative Group. European Organisation for Research and Treatment of Cancer. Int J Cancer 1998; 77(4): 533–37
  16. International Agency for Research on Cancer – Handbook of Cancer Prevention-Sunscreens. 2001; 5: 142–48 (http://www.iarc.fr/en/publications/pdfs-online/prev/handbook5/index.php)
  17. Eisemann N, Jansen L, Holleczek B, Waldmann A, Luttmann S, Emrich K, Hauschild A, Brenner H, Katalinic A. GEKID Survival Working Group. Up- to-date results on survival of patients with melanoma in Germany. Br J Dermatol 2012; 167: 606–12 
  18. Seidenari S, Benati E, Ponti G et al. Italian Euromelanoma Day Screening Campaign (2005–2007) and the planning of melanoma screening strategies. Eur J Cancer Prev 2012; 21: 89–95 
  19. Choudhury K, Volkmer B, Greinert R, Christophers E, Breitbart EW. Effectiveness of skin cancer screening programs. Br J Dermatol 2012; 167 Suppl 2: 94–8 
  20. Lüken F, Batz D, Kutschmann M. Evaluation der Screeninguntersuchungen auf Haut- krebs gemäß Krebsfrüherkennungs-Richtlinie des Gemeinsamen Bundesausschusses -Abschlussbericht der Jahre 2011–2013. BQS Institut füer Qualität und Patientensicherheit GmbH. 2016
  21. Breitbart EW, Waldmann A, Nolte S, Capellaro M, Greinert R, Volkmer B, Katalinic A.  Systematic skin cancer screening in Northern Germany. J Am Acad Dermatol 2012; 66: 201– 11 
  22. Eisemann N, Waldmann A, Katalinic A. Inzidenz des malignen Melanoms und Veränderung der stadienspezifischen Inzidenz nach Einführung eines Hautkrebsscreenings in Schleswig-Holstein. Bundesgesundheitsblatt 2014; 57: 77–83 
  23. Katalinic A, Eisemann N, Waldmann A. Skin cancer screening in Germany – documen- ting melanoma incidence and mortality from 2008 to 2013. Dtsch Arztebl Int 2015; 112: 629–34 
  24. Anders MP, Nolte S, Waldmann A, Capellaro M, Volkmer B, Greinert R, Breitbart EW. The German SCREEN project - design and evaluation of the communication strategy. Eur J Public Health 2015; 25(1): 150–55


Aktueller Überblick zur Diagnostik des malignen Melanoms (S. 21–29)
Christina Kellner

  1. Krebs in Deutschland 2007/2008. 8. Ausgabe. Robert-Koch-Institut (Hrsg) und die Gesellschaft der epidemiologischen Krebsregister in Deutschland e.V. (Hrsg). Berlin, 2012
  2. American Cancer Socity, Cancer Facts&Figures 2015. Atlanta : American Cancer Socitety ; 2015 
  3. Zentrum für Krebsregisterdaten im Robert Koch-Institut (2016) : Datensatz des ZfKD auf Basis der epidemiologischen Landeskrebsregisterdaten, verfügbare Diagnosejahre bis 2013. Version : Epi2015_1
  4. Gesellschaft der epidemiologischen Krebsresgister in Deutschland e.V. Atlas der Krebsinzidenz und -mortalität in Deutschland (GEKID-Atlas). Datenlieferung : Dezember 2011, Lübeck, 2013. Verfügbar über : http : //www.gekid.de
  5. Gesellschaft der epidemiologischen Krebsregister in Deutschland/ Robert-Koch Institut : Krebs in Deutshcland 2005-2006, Häufigkeiten und Trends : Malignes Melanom der Haut, 7. Auflage : 60 – 63, 2012
  6. Balch C M, Gershenwald J E, Soong S et al.. Final Version of 2009 AJCC Melanoma Staging and Classification. Journal of Clinical Oncology 2009 ; 27(36), 6199–6206 doi.org/10.1200/JCO.2009.23.4799
  7. Bafounta M L, et al. Is dermoscopy (epiluminescence microscopy) useful for the diagnosis of melanoma? Results of a meta-analysis using techniques adapted to the evaluation of diagnostic tests. Archives of Dermatology 2001 ; 137(10): p. 1343–1350
  8. Kittler H, et al. Compliance with follow-up and prognosis among patients with thin melanomas. European Journal of Cancer 2001; 37(12): p. 1504–1509 
  9. Goodson AG, et al. Comparative analysis of total body and dermatoscopic photographic monitoring of nevi in similar patient populations at risk for cutaneous melanoma. Dermatol Surg 2010 ; 36(7): p. 1087–98 
  10. Rajadhyaksha M, Grossman M, Esterowitz D, Webb RH, Anderson RR: In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast. J Invest Dermatol 1995; 104: 946–52
  11. Halpern A, Rajadhyaksha M, Toledo-Crow R. Bringing histology to the bedside. J Invest Dermatol 2005; 124; 8–10
  12. Rajadhyaksha M, Gonzalez S, Zavislan JM, Anderson RR, Web RH. In vivo confocal laser microscopy of human skin II: advances in instrumentation and comparison with histology. J Invest Dermatol 1999; 113: 293–303
  13. Pellacani G, Cesinaro A, Seidenari S: Reflectance-mode confocal microscopy of pigmented skin lesions – improvement in melanoma diagnostic specificity. J Am Acad Dermatol 2005; 53(6): 979–85
  14. Pellacani G, Guitera P, Longo C, Avramidis M, Seidenari S, Menzies S: The Impact of In Vivo Reflectance Confocal Microscopy for the Diagnostic Accuracy of Melanoma and Equivocal Melanocytic Lesions. J Invest Dermatol 2007; doi: 10.1038/sj.jid.5700993
  15. Pellacani G, Longo C, Malvehy J, Puig S, Carrera C, Segura S, Bassoli S, Seidenari S: In Vivo Confocal Microscopic and Histopathologic Correlations of Dermoscopic Features in 202 Melanocytic Lesions. Arch Dermatol 2008; 144(12): 1597–1608
  16. Reflectance Confocal Microscopy of Cutaneous Tumors, An Atlas with Clinical, Dermoscopic and Histological Correlations; Edited by González S., Gill M., Halpern A.C., informa healthcare, London 2008
  17. Guitera P et al.,Improving management and patient care in Lentigo maligna by mapping with in vivo confocal microscopy.JAMA Dermatol 2013
  18. Sattler E et al., How long does protection last? – in vivo fluorescence confocal laser scanning imaging fort he evaluation of the kincetics of a topically applied lotion in an everyday setting.  Skin Res Technol 2012; 18(3): 370–377
  19. Aberg P, Birgersson U, Elsner P, Mohr P, Ollmar S. Electrical impedance spectroscopy and the diagnostic accuracy for malignant melanoma. Exp. Dermatol 2011 Aug; 20(8): 648–52 doi: 10.1111/j.1600-0625.2011.01285.x. Epub 2011 May 4
  20. scibase.se/de/the-nevisense-product/clinical-studies-results/  2028734436
  21. Mohr P, Birgersson U, Berking C et al. Electrical impedance spectroscopy as a potential adjunct diagnostic tool for cutaneous melanoma. Skin Res Technol 2013 May; 19(2): 75–83. doi: 10.1111/srt.12008. Epub 2013 Jan 27 
  22. Huang D, Swanson EA, Lin CP et al. Optical coherence tomography. Science 1991; 254; 1178–81
  23. Welzel J, Lankenau E, Birngruber R, Engelhardt R. Optical cohérence tomography of the human skin. J Am Acad Dermatol 1997; 37(6): 958–63
  24. Longo C, Pellacani G. Relfectance confocal microscopy. In : Katsambas AD, Lotti TM, Dessinioti C, D`Erme AM, editors. European handbook of dermatological treatments. Berlin: Springer 2015 ; P. 1129–37
  25. Welzel J. Optical coherence tomography in dermatology: a review. Skin Res Technol 2001; 7: 1–9
  26. Ulrich M, von Braunmuehl T, Kurzen H, Dirschka T, Kellner C, Sattler EC, et al. The sensitivity and specificity of optical cohérence tomography for the assited diagnosis of nonpigmented basal cell carcinoma : an observational study. Br J Dermatol. 2015; 173(2): 428–35
  27. Mariampillai A, Standish BA, Moriyama EH, Khurana M, Munce NR, Leung MK, et al. Speckle variance détection of microvasculature usin swept-source Optical cohérence tomography. Opt Lett 2008; 33(13): 1530–2
  28. Schuh S, Holmes J, Ulrich M, Themstrup L, Jemec GBE, De Carvalho N, Pellacani G, Welzel J. Imaging Blood Vessel Morphology in Skin : Dynamic Optical Coherence Tomography as a Novel Potential Diagnostic Tool in Dermatology. Dermatol Ther (Heidelb) 2017 Jun; 7(2): 187–202. Doi : 10.1007/s13555-017-0175-4.Epub 2017 Mar 3
  29. Ulrich M, Themstrup L, de Carvalho N, Manfredi M, Grana C, Ciardo S, et al. Dynamic Optical cohérence tomography in dermatology. Dermatology 2016; 232(3): 298–311
  30. Gambichler T, Plura I, Schmid-Wendtner M, et al. High-definition Optical cohérence tomography of melanocyctic skin lesions. J Biophotonics 2015; 8(8): 681–686
  31. Picard A, Tsilika K, Long-Mira E, et al. Use of high-definition Optical cohérent tomography (HD-OCT) for Imaging of melanoma. Br J Dermatol 2013; 169(4): 950–952
  32. Coleman AJ, Richardson TJ, Orchard G, Uddin A, Choi MJ, Lacy KE. Histological correlates of optical coherence tomography in non-melanoma skin cancer. Skin Res Technol 2013 Feb; 19(1): 10–9. doi: 10.1111/j.1600-0846.2012.00626.x. Epub 2012 Jun 28
  33. Banzhaf CA, Themstrup L, Ring HC, Mogensen M, Jemec GB. Optical coherence tomography imaging of non-melanoma skin cancer undergoing imiquimod therapy. Skin Res Technol 2014 May; 20(2): 170–6. doi: 10.1111/srt.12102. Epub 2013 Sep 16
  34. Tomatis S, Bono A, Bartoli C, et al. Automated melanoma détection : multispectral Imaging and neutral network approach for classification. Med Phys 2003; 30(2): 212–221
  35. Tehari H, Walls J, Price G, Cotton S, Sassoon E, Hall P. A novel Imaging technique as an adjunct to the in vivo diagnosis of nonmelanoma skin cancer. Br J Dermatol 2006 Dec; 155(6): 1177–83
  36. Moncrieff M., Cotton S. Claridge E, Hall P. Spectrophotometric intracutaneous analysis : a new technique for Imaging pigmented skin lesions. Br J Dermatol 2002; 146(3): 448–457
  37. Alexander H, Miller DL. Determining skin thickness with pulsed ultra sound. J Invest Dermatol 1979; 72(1): 17–19
  38. Jasaitiene D, Valiukeviciene S, Linkevicuiute G, Raisutis R, Jasiuniene E, Kazys R. Principles of high-frequency ultrasonography for investigation of skin pathology. J Eur Acad Dermatol Venerol 2011; 25(4): 375–382
  39. Kleinerman R, Whang TB, Bard RL, Marmur ES. Ultrasound in dermatology : principles and applications. J Am Acad Dermatol 2012; 67(3): 478–487
  40. Lassau N, Lamuraglia M, Koscielny S, et al. Prognostic value of angiogenesis evaluated with high-frequency and colour Doppler sonography for preoperative assessement of primary cutaneous melanomas : corrélation with récurrence after a 5 year follow-up period. Cancer Imaging 2006 ;p. 24–29
  41. Pellacani G, Seidenari S. Preoperative melanoma thickness détermination by 20 MHz sonography and digital videomicroscopy in combination. Arch Dermatol 2003; 139(3): 293–298
  42. Harland CC, Kale SG, Jackson P, Mortimer PS, Bamber JC. DIfferentiation of common benign pigmented skin lesions from melanoma by high-resolution ultrasound. Br J Dermatol 2000; 143(2): 281–289
  43. Eigentler, T. K., Mühlenbein, C., Follmann, M., Schadendorf, D. and Garbe, C. (2017), S3-Leitlinie Diagnostik, Therapie und Nachsorge des Melanoms – Update 2015/2016, Kurzversion 2.0. JDDG: Journal der Deutschen Dermatologischen Gesellschaft, 15: e1–e41. doi:10.1111/ddg.13247
  44. Griewank KG et al. Genetic altérations and personalized médicine in melanoma : progress and future prospects. J Natl Cancer Inst 2014; 106(2): djt435
  45. Griewank KG et al. Molekulare Diagnostik bei melanozytären Tumoren. Pathologe 2015 ; 36: 30–36
  46. Cancer Genome Atlas Network. Genomic classification of cutaneous melanoma. Cell 2015; 161(7): 1681–1696
  47. Samatar AA, Poulikeakos PI. Targeting RAS-ERK signalling in cancer: promisses and challenges, Nat Rev Drug Discov 2014; 13(12): 928–942
  48. Lee SJ et al. Phase II trial of Nilotinib in pathients with metastatic malignant melanoma harboring KIT gene aberration : A multicenter trial of korean cancer study group (UN 10-06). Oncologist 2015; 20(11): 1312–1319
  49. Tetzlaff MT et al. Utility of BRAF V600E immunohistochemistry expression pattern as a surrogate of BRAF mutation status in 154 patients with Advanced melanoma. Hum Pathol 2015; 46(8): 1101–1110
  50. Agairny A et al. Metastatic maligngnat melanoma with complete loss of différentiation markers (undifferentiated/ dedifferentiated melanoma): analysis of 14 patients emphasizing phenotypic plasticity and the value of molecular testing as surrogate diagnostic marker. Am J Surg pathol 2016; 40(2): 181–191
  51. Topalian SL et al. Safety, activity and immune corrélâtes of anti-PD-1 antibody in cancer. N Engl J Med 2012; 366(26): 2443–2454
  52. Tumeh PC et al. PD-1 blockade induces responses by inhibiting adaptive immune résistance. Nature 2014; 515(7528): 568–571
  53. Spranger S et al. Up-regulation of PD-L1, IDO, and T(regs) in the melanoma tumor microenvironment is driven by CD8(+) T cells. Sci Transl Med 2013; 5(200): 200ra116
  54. Taube JM et al. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive résistance mechanism of immune escape. Sci Transl Med 2012; 4(127): 127
  55. Carbognin L et al. Differential activity of NIvolumab, pembrolizumab and MPDL3280A according to the tumor expression of programmed death-ligand-1 (PD-L1): sensitivity analysis of trials in melanoma, lung and genitourinary cancers. PloS ONE 2015; 10(6): 0130142
  56. Larkin J et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 2015; 373(1): 23–34
  57. Daud A et al. Long-term efficacy of pembrolizumab (pembro; MK-3475) in a pooled analysis of 655patients (pts) with advanced melanoma (MEL) enrolled in KEYNOTE-001. J Clin Oncol 2015; 33(suppl.): abstr 9005
  58. Brunner G, Reitz M, HeineckeA et al. J Cancer Res Clin Oncol.2013; 139: 249 
  59. Brunner G (2017). Sonderdruck aus DERMAforum  – Nr. 01/2017, Seite 10–11


Aktuelle Therapie des malignen Melanoms – Entwicklung innovativer Behandlungsschemata (S. 30–37)
Christina Kellner 

  1. Mocellin S, Pasquali S, Rossi CR, Nitti D. Interferon alpha adjuvant therapy in patients with high-risk melanoma: systematic review and méta-analysis. J Natl Cancer Inst; 102: 493–501, 2010. DOI:10.1093/jnci/djq009
  2. Eggermont A, Suciu S, Testori A et al. Ulceration and stage are prédictive of interféron efficacy in melanoma : results of the phase III adjuvant trials EORTC 18952 and EORTC 18991. Eur J Cancer 2012; 48: 218–225
  3. Eggermont AM, Chiarion-Sileni V, Grob JJ et al. Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial. Lancet Oncol 2015; 16(6): e262
  4. Pflugfelder A, Kochs C, Blum A et al. S3-Leitlinie ,,Diagnostik, Therapie und Nachsorge des Melanoms” – Kurzfassung, JDDG: Journal der Deutschen Dermatologischen Gesellschaft, 11 (2013) 563–594
  5. Davies H, Bignell GR, Cox C et al. Mutations of the BRAF gene in human cancer. Nature 2002; 417; 949–54
  6. Long GV, Menzies AM, Nagrial AM et al.  Prognostic and clinicopathologic associations of oncogenic BRAF in metastatic melanoma. J Clin Oncol 2011; 29: 1239–46
  7. Flaherty KT. Is it good or bad to find a BRAF mutation? J Clin Oncol 2011; 29: 1229–30
  8. Flaherty KT, Puzanov I, Kim KB et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N Eng J Med 2010; 363: 809–19
  9. B. Homet, A. Ribas. New drug targets in metastatic melanoma, J pathol 2014; 232: 134–141
  10. P B Chapman, Hauschild A, Robert C et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation.N Eng J Med 2011; 364: 2507–2516
  11. Sosman JA, Kim KB, Schuchter L et al.  Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Eng J  Med 2012; 366: 707–714
  12. Gutzmer R, Hassel JC, Kähler KC et al. Kutane Nebenwirkungen der medikamentösen Tumortherapie mit BRAF- und MEK-Inhibitoren.
  13. Gibney GT, Zager JS. Clinical development of dabrafenib in BRAF mutant melanoma and other malignancies, Expert opinion on drug metabolism & toxicology 2013, 9: 893–899
  14. Shi H, Hugo W, Kong X et al. Acquired resistance and clonalevolution in melanoma during BRAF inhibitor therapy. Cancer discovery 2014; 4: 80–93
  15. A. Russo, B. Ficili, S. Candido, F.M. Pezzino, C. Guarneri, A. Biondi, S. Travali, J.A. McCubrey, D.A. Spandidos, M. Libra, Emerging targeted therapies for melanoma treatment (review), International journal of oncology, 45 (2014) 516–524
  16. Flaherty KT, Infante JR, Daud A, Gonzalez R, Kefford RF, Sosman J, Hamid O, Schuchter L, Cebon J, Ibrahim N. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. New England Journal of Medecine. 2012; 367: 1694–703
  17. K.T. Flaherty, C. Robert, P. Hersey, P. Nathan, C. Garbe, M. Milhem, L.V. Demidov, J.C. Hassel, P.
  18. Rutkowski, P. Mohr, R. Dummer, U. Trefzer, J.M. Larkin, J. Utikal, B. Dreno, M. Nyakas, M.R. Middleton, J.C. Becker, M. Casey, L.J. Sherman, F.S. Wu, D. Ouellet, A.M. Martin, K. Patel, D. Schadendorf, Improved survival with MEK inhibition in BRAF-mutated melanoma, The New England journal of medicine, 367 (2012) 107–114
  19. E. Shtivelman, M.Q. Davies, P. Hwu, J. Yang, M. Lotem, M. Oren, K.T. Flaherty, D.E. Fisher, Pathways and therapeutic targets in melanoma, Oncotarget, 5 (2014) 1701–1752
  20. McArthur GA et al. Eur J Cancer 2015; 51: 720–23
  21. Larkin J et al. New Engl J Med 2014; 37(118): 67–76
  22. Albino A P et al (1984) Transforming ras genes from human melanoma: a manifestation of tumour heterogeneity? Nature 308(5954): 69–72
  23. Padua RA, Barrass NC, Currie GA (1985) Activation of N-ras in a human melanoma cell line. Mol Cell Biol 5(3): 582–585
  24. Omholt K, Platz A, Kanter L et al. (2003). NRAS and BRAF mutations arise early during melanoma pathogenesis and are preserved throughout tumor progression. Clin Cancer Res 9 :6483-6488
  25. Carvaial RD, Antonescu CR, Wolchok JD et al (2011) : KIT as a therapeutic target in metastatic melanoma. JAMA 305: 2327–2334
  26. C. Robert, L. Thomas, I. Bondarenko, S. O'Day, D.J. M, C. Garbe, C. Lebbe, J.F. Baurain, A. Testori, J.J. Grob, N. Davidson, J. Richards, M. Maio, A. Hauschild, W.H. Miller, Jr., P. Gascon, M. Lotem, K. Harmankaya, R. Ibrahim, S. Francis, T.T. Chen, R. Humphrey, A. Hoos, J.D. Wolchok, Ipilimumab plus dacarbazine for previously untreated metastatic melanoma, The New England journal of medicine, 364 (2011) 2517–2526
  27. F.S. Hodi, S.J. O'Day, D.F. McDermott, R.W. Weber, J.A. Sosman, J.B. Haanen, R. Gonzalez, C. Robert, D. Schadendorf, J.C. Hassel, W. Akerley, A.J. van den Eertwegh, J. Lutzky, P. Lorigan, J.M. Vaubel, G.P. Linette, D. Hogg, C.H. Ottensmeier, C. Lebbe, C. Peschel, I. Quirt, J.I. Clark, J.D. Wolchok, J.S. Weber, J. Tian, M.J. Yellin, G.M. Nichol, A. Hoos, W.J. Urba, Improved survival with ipilimumab in patients with metastatic melanoma, The New England journal of medicine, 363 (2010) 711–723
  28. P.A. Ott, F.S. Hodi, C. Robert, CTLA-4 and PD-1/PD-L1 blockade: new immunotherapeutic modalities with durable clinical benefit in melanoma patients, Clinical cancer research : an official journal of the American Association for Cancer Research, 19 (2013) 5300–5309
  29. Postow MA, Chesney J, Pavlick AC et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med 2015; 372: 2006–17
  30. Robert C, Schachter J, Long GV et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 2015; 372(26): 2521–32
  31. O. Hamid, C. Robert, A. Daud, F.S. Hodi, W.J. Hwu, R. Kefford, J.D. Wolchok, P. Hersey, R.W. Joseph, J.S. Weber, R. Dronca, T.C. Gangadhar, A. Patnaik, H. Zarour, A.M. Joshua, K. Gergich, J. Elassaiss-Schaap, A. Algazi, C. Mateus, P. Boasberg, P.C. Tumeh, B. Chmielowski, S.W. Ebbinghaus, X.N. Li, S.P. Kang, A. Ribas, Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma, The New England journal of medicine, 369 (2013) 134–144
  32. Larkin J, Chiarion-Sileni V, Gonzalez R et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med 2015; 373(1): 23–34
  33. Mir LM, Orlowski S, Belehradek Jr J et al. Electrochemotherapy potentiation of antitumour effect of bleomycin by local electric pulses. Eur J Cancer 1991; 27: 68–72
  34. Reinhold U. Electrochemotherapy of skin tumors. Hautarzt 2011; 62: 549–559
  35. Miklavčič D, Mali B, Kos B et al. Electrochemotherapy: from the drawing board into medical practice. Biomed Eng Online 2014; 13: 29
  36. Okino M, Mohri H. Effects of a high-voltage electrical impulse and an anticancer drug on in vivo growing tumors. Jpn J Cancer Res 1987; 78: 1319–1321
  37. Sersa G, Stabuc B, Cemazar M et al. Electrochemotherapy with cisplatin: potentiation of local cisplatin antitumour effectiveness by application of electric pulses in cancer patients. Eur J Cancer 1998; 34: 1213–1218
  38. Mir LM, Gehl J, Sersa G et al. Standard operating procedures of the electrochemotherapy: instructions for the use of bleomycin or cisplatin administered either systematically or locally and electric pulses delivered by the Clinicoporator by means of invasive or non-invasive electrodes. Eur J Cancer 2006; 4: 14–25
  39. Sersa G. The state-of-the-art of electrochemotherapy before ESOPE study; advantages and clinical uses. Eur J Cancer Suppl 2006; 4: 52–59
  40. Byers, B. A., Temple-Oberle, C. F., Hurdle, V. and McKinnon, J. G. (2014), Treatment of in-transit melanoma with intra-lesional interleukin-2: A systematic review. J. Surg. Oncol., 110: 770–775
  41. Kaufman HL1, Bines SD.OPTIM trial: a Phase III trial of an oncolytic herpes virus encoding GM-CSF for unresectable stage III or IV melanoma. Future Oncol. 2010 Jun; 6(6): 941–9
  42. Strahlentherapeutische Behandlungsoptionen des Merkelzellkarzinoms (S. 38–42)


Strahlentherapeutische Behandlungsoptionen des Merkelzellkarzinoms (S. 38–42)
Christian Dietzel, Dirk Vordermark

  1. Smith DF, Messina JL, Perrott R et al. Clinical approach to neuroendocrine carcinoma of the skin (Merkel cell carcinoma). Cancer Control 2000; 7(1): 72–83
  2. Goessling W, McKee PH, Mayer RJ. Merkel cell carcinoma. J Clin Oncol 2002; 20(2): 588–98
  3. Hodgson NC. Merkel cell carcinoma: changing incidence trends. J Surg Oncol 2005; 89(1): 1–4
  4. Moshiri AS, Nghiem P. Milestones in the staging, classification, and biology of Merkel cell carcinoma. J Natl Compr Canc Netw 2014; 12(9): 1255–62
  5. Assouline A, Tai P, Joseph K et al. Merkel cell carcinoma of skin-current controversies and recommendations. Rare Tumors 2011; 3(2): e23
  6. Popp S, Waltering S, Herbst C et al.UV-B-type mutations and chromosomal imbalances indicate common pathways for the development of Merkel and skin squamous cell carcinomas. Int J Cancer 2002; 99(3): 352–60
  7. Ma JE, Brewer JD. Merkel cell carcinoma in immunosuppressed patients. Cancers (Basel) 2014; 6(3): 1328–50
  8. Feng H, Shuda M, Chang Y, Moore PS. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 2008; 319(5866): 1096–100
  9. Lemos BD, Storer BE, Iyer JG, et al. Pathologic nodal evaluation improves prognostic accuracy in Merkel cell carcinoma: analysis of 5823 cases as the basis of the first consensus staging system. J Am Acad Dermatol 2010; 63(5): 751–61
  10. Leonard JH, Ramsay JR, Kearsley JH, Birrell GW. Radiation sensitivity of Merkel cell carcinoma cell lines. Int J Radiat Oncol Biol Phys 1995; 32(5): 1401–7
  11. Becker JC   AC, Vordermark D,   Reske S  et al. S2K Kurzleitlinie Merkelzellkarzinom  [Available from: www.awmf.org/uploads/tx_szleitlinien/032-023l_S2k_Merkelzellkarzionom_2012-abgelaufen.pdf
  12. Takagishi SR, Marx T, Lewis C  et al. Role of Postoperative Radiation Therapy in Stage IA Merkel Cell Carcinoma of the Head and Neck. Int J Rad Oncol • Biol• Physics; 94(4): 947
  13. Medina-Franco H, Urist MM, Fiveash J, Heslin MJ, Bland KI, Beenken SW. Multimodality treatment of Merkel cell carcinoma: case series and literature review of 1024 cases. Ann Surg Oncol. 2001;8(3):204-8.
  14. Mojica P, Smith D, Ellenhorn JD. Adjuvant radiation therapy is associated with improved survival in Merkel cell carcinoma of the skin. J Clin Oncol 2007; 25(9): 1043–7
  15. Bhatia S, Storer BE, Iyer JG et al. Adjuvant Radiation Therapy and Chemotherapy in Merkel Cell Carcinoma: Survival Analyses of 6908 Cases From the National Cancer Data Base. J Natl Cancer Inst 2016; 108(9)
  16. Jabbour J, Cumming R, Scolyer RA et al. Merkel Cell Carcinoma: Assessing the Effect of Wide Local Excision, Lymph Node Dissection, and Radiotherapy on Recurrence and Survival in Early-Stage Disease—Results From a Review of 82 Consecutive Cases Diagnosed Between 1992 and 2004. Annals of Surgical Oncology 2007; 14(6): 1943
  17. Tsang G, O'Brien P, Robertson R et al. All delays before radiotherapy risk progression of Merkel cell carcinoma. Australas Radiol 2004; 48(3): 371–5
  18. Khan L, Barnes EA. Radiotherapy for metastatic merkel cell carcinoma: a review of the literature. J Skin Cancer 2012; 2012: 654981
  19. Jouary T, Leyral C, Dreno B et al. Adjuvant prophylactic regional radiotherapy versus observation in stage I Merkel cell carcinoma: a multicentric prospective randomized study. Ann Oncol 2012; 23(4): 1074–80
  20. Hoeller U, Mueller T, Schubert T et al. Regional nodal relapse in surgically staged Merkel cell carcinoma. Strahlenther Onkol 2015; 191(1): 51–8
  21. Gupta SG, Wang LC, Peñas PF et al. Sentinel lymph node biopsy for evaluation and treatment of patients with Merkel cell carcinoma: The Dana-Farber experience and meta-analysis of the literature. Arch Dermatol 2006; 142(6): 685–90
  22. Howle J, Veness M. Sentinel lymph node biopsy in patients with Merkel cell carcinoma: an emerging role and the Westmead hospital experience. Australas J Dermatol 2012; 53(1): 26–31
  23. Hruby G, Scolyer RA, Thompson JF. The important role of radiation treatment in the management of Merkel cell carcinoma. Br J Dermatol 2013; 169(5): 975–82
  24. Veness MJ, Perera L, McCourt J et al. Merkel cell carcinoma: improved outcome with adjuvant radiotherapy. ANZ J Surg 2005; 75(5): 275–81
  25. Mortier L, Mirabel X, Fournier C, Piette F, Lartigau E. Radiotherapy alone for primary Merkel cell carcinoma. Arch Dermatol 2003; 139(12): 1587–90
  26. Pape E, Rezvoy N, Penel N et al. Radiotherapy alone for Merkel cell carcinoma: a comparative and retrospective study of 25 patients. J Am Acad Dermatol 2011; 65(5): 983–90
  27. Veness M, Howle J. Radiotherapy alone in patients with Merkel cell carcinoma: the Westmead Hospital experience of 41 patients. Australas J Dermatol 2015; 56(1): 19–24
  28. Fang LC, Lemos B, Douglas J et al. Radiation monotherapy as regional treatment for lymph node-positive Merkel cell carcinoma. Cancer 2010; 116(7): 1783–90
  29. Stevens W, Philipson TJ, Khan ZM et al. Cancer mortality reductions were greatest among countries where cancer care spending rose the most, 1995-2007. Health Aff (Millwood) 2015; 34(4): 562–70
  30. Iyer JG, Parvathaneni U, Gooley T et al. Single-fraction radiation therapy in patients with metastatic Merkel cell carcinoma. Cancer Med 2015; 4(8): 1161–70
  31. Garibyan L, Cotter SE, Hansen JL et al. Palliative treatment for in-transit cutaneous metastases of Merkel cell carcinoma using surface-mold computer-optimized high-dose-rate brachytherapy. Cancer J 2013; 19(4): 283–7


UPDATE
Therapie des fortgeschrittenen Urothelkarzinoms der Harnblase (S. 50–56)
Mark Thalgott, Robert Tauber, Jürgen E. Gschwend, Katharina Hauner 

  1. Thalgott M et al. Operative Therapie des Harnblasenkarzinoms Uro-News 2016, 20(12) 42–47
  2. S3-Leitlinie Früherkennung, Diagnose, Therapie und Nachsorge des Harnblasenkarzinoms, Langversion 1.0 – September 2016,  AWMF-Registernummer: 032/038O 
  3. Sternberg CN, Skoneczna I, Kerst JM et al. Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3–pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994). Lancet Oncol 2015; 1: 76–86
  4. Hautmann RE, Gschwend JE, Petriconi RC de et al. Cystectomy for transitional cell carcinoma of the bladder: results of a surgery only series in the neobladder era. J Urol 2006; 2: 486–92; discussion 491–2
  5. Kitamura H, Tsukamoto T, Shibata T et al. Randomised phase III study of neoadjuvant chemotherapy with methotrexate, doxorubicin, vinblastine and cisplatin followed by radical cystectomy compared with radical cystectomy alone for muscle-invasive bladder cancer: Japan Clinical Oncology Group Study JCOG0209. Ann Oncol 2014; 6:1192–1198
  6. von der Maase H et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol 2000; 18(17): p 3068–77
  7. De Santis M, Bellmunt J, Mead G et al.  Randomized phase II/III trial assessing gemcitabine/carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy: EORTC study 30986. J Clin Oncol 2012; 30: 191–199
  8. Balar AV, Galsky MD, Rosenberg JE et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet 2016.
  9. Balar A, Bellmunt J, O'donnell PH et al. Pembrolizumab (pembro) as first-line therapy for advanced/unresectable or metastatic urothelial cancer: Preliminary results from the phase 2 KEYNOTE-052 study. ESMO 2016
  10. Grimm MO [Immunooncology in Urologic Cancers: Current Status]. Aktuelle Urol 2016; 47: 374–377
  11. Massard C, Gordon MS, Sharma S et al. Safety and Efficacy of Durvalumab (MEDI4736), an Anti-Programmed Cell Death Ligand-1 Immune Checkpoint Inhibitor, in Patients With Advanced Urothelial Bladder Cancer. J Clin Oncol 34: 3119–3125
  12. Powles T, Eder JP, Fine GD et al.  MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature 2014; 515: 558–562
  13. Kulkarni GS, Hakenberg OW, Gschwend JE et al. An updated critical analysis of the treatment strategy for newly diagnosed high-grade T1 (previously T1G3) bladder cancer. Eur Urol 2010; 57: 60–70
  14. Witjes JA, Comperat EM, Cowan NC et al Guidelines on Muscle-invasive and metastatic Bladder Cancer Arnheim: Euroopean Association of Urology 2015 
  15. Retz M, Gschwend JE, Schmid SC. [Update 2016 - Immunotherapy for urothelial carcinoma]. Urologe A 2016; 55: 246–252
  16. Hautmann RE et al ICUD-EAU International Consultation on Bladder Cancer 2012: Urinary diversion Eur Urol 2013; 63(1): p 67–80
  17. Sharma P, Callahan MK, Bono P et al. Nivolumab monotherapy in recurrent metastatic urothelial carcinoma (CheckMate 032): a multicentre, open-label, two-stage, multi-arm, phase 1/2 trial. Lancet Oncol 2016; 17: 1590–1598
  18. Hautmann RE, de Petriconi RC, et al Radical cystectomy for urothelial carcinoma of the bladder without neoadjuvant or adjuvant therapy: long-term results in 1100 patients. Eur Urol 2012; 61(5): 1039–47
  19. Rödel C, Grabenbauer GG, Kühn R et al. Combined-modality treatment and selective organ preservation in invasive bladder cancer: long-term results. J Clin Oncol 2002; 20(14): 3061–71
  20. Galsky MD, Retz M, Siefker-Radtke AO et al. Efficacy and safety of nivolumab monotherapy in patients with metastatic urothelial cancer (mUC) who have received prior treatment: Results from the phase II CheckMate 275 study. ESMO 2016
  21. J. Bellmunt, De Wit R, Vaughn DJ et al. Pembrolizumab as SEcon-Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med 2017,  Mar 16; 376(11): 1015–1026
  22. Rosenberg JE, Hoffman-Censits J, Powles T et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet 2016; 387:1909–1920
  23. Tauber R, Gschwend JE, Retz M.  Update 2017 – Immuntherapie beim Urothelkarzinom