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Vol. 100. Issue 9.
Pages 767-779 (November 2009)
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Vol. 100. Issue 9.
Pages 767-779 (November 2009)
Practical dermatology
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Study and Treatment of Locally Advanced Melanoma
Melanoma Localmente Avanzado. Estudio y Tratamiento
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D. Moreno-Ramíreza,
Corresponding author
dmoreno@e-derma.org

Correspondence: Departamento de Dermatología Médico-Quirúrgica y Venereología, Hospital Universitario Virgen Macarena, Avda. Dr. Fedriani s/n, 41009 Sevilla, Spain.
, L. de la Cruzb, L. Ferrándiza, F.M. Camachoa
a Departamento de Dermatología Médico-Quirúrgica y Venereología, Hospital Universitario Virgen Macarena, Sevilla, Spain
b Servicio de Oncología Médica, Hospital Universitario Virgen Macarena, Sevilla, Spain
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Abstract

Locally advanced melanoma is characterized clinically by the appearance of in-transit or satellite metastases, and is considered stage IIIB or IIIC according to the 2002 classification of the American Joint Committee on Cancer. Despite the absence of distant metastases, the management of locally advanced melanoma is complicated and the disease is associated with a reduction in overall survival. The initial step in the approach to the patient with locally advanced melanoma involves restaging in order to exclude the presence of distant metastases. Positron emission tomography-computed tomography is currently accepted as the most accurate restaging technique. Surgical excision of the metastases continues to be the treatment of choice for locally advanced melanoma. In the case of unresectable metastases, hyperthermic isolated limb perfusion with melphalan with or without tumor necrosis factor has achieved complete responses in up to 60% of patients treated, with very rare severe locoregional and systemic toxic effects. Radiation therapy, chemotherapy, and biochemotherapy are options that, even though they have not been tested in patients with only in-transit metastases, may have a role in unresectable, locally advanced melanoma without distant metastases. In any case, therapeutic options for locally advanced melanoma should be individualized, and should take into consideration the availability of each of these techniques as well as the experience of the health care team.

Key words:
melanoma
locally advanced melanoma
in-transit metastasis
satellitosis
isolated limb perfusion
Resumen

El melanoma localmente avanzado representa un estadio clínico caracterizado principalmente por la presencia de metástasis en tránsito o satelitosis, estadios IIIB o IIIC de la clasificación American Joint Committee on Cancer de 2002, y que en ausencia de metástasis a distancia, representa un acortamiento en la supervivencia del paciente y un escenario clínico de manejo complejo.

La aproximación al paciente en este estadio debe iniciarse con una reestadificación que permita descartar la presencia de metástasis a distancia, para lo que se acepta como técnica con mayor validez la tomografía por emisión de positrones-tomografía computarizada. La exéresis quirúrgica de la/s metástasis continúa siendo considerada el tratamiento de primera elección en la enfermedad localmente avanzada.

En caso de metástasis irresecables la perfusión hipertérmica del miembro aislado con melfalán con o sin factor de necrosis tumoral, proporciona porcentajes de respuesta completa del 60%, con toxicidad sistémica y locorregional grave muy poco frecuente. La radioterapia, quimioterapia y bioquimioterapia son alternativas terapéuticas que, aunque no han sido estudiadas exclusivamente en el paciente con metástasis en tránsito, pueden tener un papel en la enfermedad localmente avanzada irresecable sin metástasis a distancia.

En cualquier caso, las opciones terapéuticas en el melanoma localmente avanzado clínico deben ser individualizadas para cada paciente y teniendo en cuenta la disponibilidad de cada una de las técnicas y la experiencia del equipo de profesionales con cada una de ellas.

Palabras clave:
melanoma
melanoma localmente avanzado
metástasis en tránsito
satelitosis
perfusión del miembro aislado
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References
[1.]
S. Saenz, J. Conejo-Mir, A. Cayuela.
Epidemiología del melanoma en España.
Actas Dermosifiliogr, 96 (2005), pp. 411-418
[2.]
C.M. Balch, A.C. Buzaid, S.J. Soong, M.B. Atkins, N. Cascinelli, D.G. Coit, et al.
Final version of the American Joint Committee on Cancer Staging System for Cutaneous Melanoma.
J Clin Oncol, 19 (2001), pp. 3635-3648
[3.]
A.J. Hayes, M.A. Clark, M. Harries, J.M. Thomas.
Management of in-transit metastases from cutaneous malignant melanoma.
Br J Surg, 91 (2004), pp. 673-682
[4.]
T.M. Pawlik, M.I. Ross, M.M. Johnson, C.W. Schacherer, D.M. McClain, P.F. Mansfield, et al.
Predictors and natural histor y of in-transit melanoma after sentinel lymphadenectomy.
Ann Surg Oncol, 12 (2005), pp. 587-596
[5.]
T.M. Hughes, R.P. A’Hern, J.M. Thomas.
Prognosis and surgical management of patients with palpable inguinal lymph node metastases from melanoma.
[6.]
S.E. Finkelstein, J.A. Carrasquillo, J.M. Hoffman, B. Galen, P. Choyke, D.E. White, et al.
A prospective analysis of positron emission tomography and conventional imaging for detection of stage IV metastatic melanoma in patients undergoing metastasectomy.
Ann Surg Oncol, 11 (2004), pp. 731-738
[7.]
H.C. Steinert, R.A. Huch Boni, A. Buck, R. Boni, T. Berthold, B. Marincek, et al.
Malignant melanoma: staging with whole body positron emission tomography and 2-(F-18)fluoro-2deoxy-Dglucose.
Radiology, 195 (1995), pp. 705-709
[8.]
S.A. Gulec, M.B. Faries, C.C. Lee, D. Kirgan, C. Glass, D.L. Morton, et al.
The role of fluorine-18 deoxyglucose positron emission tomography in the management of patients with metastatic melanoma: impact on surgical decision making.
Clin Nucl Med, 28 (2003), pp. 961-965
[9.]
M. Rodríguez Garrido, C. Asensio del Barrio.
PET-TAC: Indicaciones, revisión sistemática y metaanálisis. Agencia de Evaluación de Tecnologías Sanitarias (AETS).
Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III, (2004),
[10.]
C.R. Rossi, M. Foletto, S. Mocellin, P. Pilati, M. Lise.
Hyperthermic isolated limb perfusion with low-dose tumor necrosis factor and melphalan for bulky in-transit melanoma metastases.
Ann Surg Oncol, 11 (2004), pp. 173-177
[11.]
A. Brobeil, C. Berman, C.W. Cruse, R. De Conti, A. Cantor, G.H. Lyman, et al.
Efficacy of hyperthermic isolated limb perfusion for extremity-confined recurrent melanoma.
Ann Surg Oncol, 5 (1998), pp. 376-383
[12.]
D.P. Jaques, D.G. Coit, M.F. Brennan.
Major amputation for advanced malignant melanoma.
Surg Gynaecol Obstet, 169 (1989), pp. 1-6
[13.]
M.R. Kapma, B.C. Vrouenraets, O.E. Nieweg, A.N. Van Geel, E.M. Noorda, A.M. Eggermont, et al.
Major amputation for intractable extremity melanoma after failure of isolated limb perfusion.
Eur J Surg Oncol, 31 (2005), pp. 95-99
[14.]
S. Hill, J.M. Thomas.
Use of carbon dioxide laser to manage cutaneous metastases from malignant melanoma.
Br J Surg, 83 (1996), pp. 509-512
[15.]
L. Strobbe, O. Nieweg, B. Kroon.
Carbon dioxide laser for cutaneous melanoma metastases: indications and limitations.
Eur J Surg Oncol, 23 (1997), pp. 435-438
[16.]
O. Creech, E.T. Krementz, R.F. Ryan, K. Reemtsa, J.N. Winblad.
Experiences with Isolation-Perfusion Technics in the Treatment of Cancer.
Ann Surg, 149 (1959), pp. 627-639
[17.]
W.R. Cornett, L.M. McCall, R.P. Petersen, M.I. Ross, H.A. Briele, R.D. Noyes, et al.
Randomized multicenter trial of hyperthermic isolated limb perfusion with melphalan alone compared with melphalan plus tumor necrosis factor: American College of Surgeons Oncology Group Trial Z0020.
J ClinOncol, 24 (2006), pp. 4196-4201
[18.]
E.M. Noorda, B.C. Vrouenraets, O.E. Nieweg, F. Van Coevorden, B.B. Kroon.
Isolated limb perfusion: what is the evidence for its use?.
Ann Surg Oncol, 11 (2004), pp. 837-845
[19.]
A.L. Feldman, H.R. Alexander, D.L. Bartlett, D.L. Fraker, S.K. Libitti.
Management of extremity recurrences after complete responses to isolated limb perfusion in patients with melanoma.
Ann Surg Oncol, 6 (1999), pp. 562-567
[20.]
E.M. Noorda, B.C. Vrouenraets, O.E. Nieweg, A.N. van Geel, A.MM. Eggermont, B.BR. Kroon.
Repeat isolated limb perfusion with TNFa and melphalan for recurrent limb melanoma after failure of previous perfusion.
Eur J Surg Oncol, 32 (2006), pp. 318-324
[21.]
Moreno-Ramírez D, de la Cruz L, Ferrándiz L,Villegas-Portero R. Perfusión del miembro aislado en el tratamiento del melanoma y sarcoma de partes blandas. Informe técnico de evaluación. Agencia de evaluación de Tecnologías Sanitarias. In press, 2008.
[22.]
M. Sigüenza, A. Pizarro, M. Mayor, C. Vidaurrázaga, L. Miralles, M. González-Beato, et al.
Tratamiento tópico de las metástasis cutáneas de melanoma con imiquimod.
Actas Dermosifiliogr, 96 (2005), pp. 111-115
[23.]
A. Steinmann, J.O. Funk, G. Schuler, P. von den Driesch.
Topical imiquimod treatment of a cutaneous melanoma metastasis.
J Am Acad Dermatol, 43 (2000), pp. 556
[24.]
S. Ugurel, A. Wagner, C. Pföhler, W. Tilgen, U. Reinhold.
Topical imiquimod eradicates skin metastases of malignant melanoma but fails to prevent rapid lymphogenous metastatic spread.
Br J Dermatol, 147 (2002), pp. 621-624
[25.]
A.B. Bong, B. Bonnekoh, I. Franke, M.P. Schön, J. Ulrich, H. Gollnick.
Imiquimod, a topical immune response modifier, in the treatment of cutaneous metastases of malignant melanoma.
Dermatology, 205 (2002), pp. 135-138
[26.]
I.H. Wolf, J. Smolle, B. Binder, L. Cerroni, E. Richtig, H. Kerl.
Topical imiquimod in the treatment of metastatic melanoma to skin.
Arch Dermatol, 139 (2003), pp. 273-276
[27.]
P. Vereecken, A. Mathieu, M. Laporte, M. Petein, T. Velu, A. Awada, et al.
Management of cutaneous locoregional recurrences of melanoma: a new therapeutic perspective with imiquimod.
Dermatology, 206 (2003), pp. 279-280
[28.]
C. Hesling, M. D’Incan, S. Mansard, F. Franck, A. Corbin-Duval, C. Chèvenet, et al.
In vivo and in situ modulation of the expression of genes involved in metastasis and angiogenesis in a patient treated with topical imiquimod for melanoma skin metastases.
Br J Dermatol, 150 (2004), pp. 761-767
[29.]
E. Nagore, O. Sanmartín, R. Botella-Estrada, C. Guillén.
Imiquimod para el tratamiento de las metástasis cutáneas de melanoma.
Actas Dermosifiliogr, 96 (2005), pp. 549-550
[30.]
D.S. Green, M.D. Bodman-Smith, A.G. Dalgleish, M.D. Fischer.
Phase I/II study of topical imiquimod and intralesional interleukin-2 in the treatment of accessible metastases in malignant melanoma.
Br J Dermatol, 156 (2007), pp. 337-345
[31.]
P. Radny, U.M. Carola, J. Bauer, T. Paul, C. Schlegel, T.K. Eigentler, et al.
Phase II trial of intralesional therapy with interleukin-2 in soft-tissue melanoma metastases.
Br J Cancer, 89 (2003), pp. 1620-1626
[32.]
C. Hoeller, B. Jansen, E. Heere-Ress, T. Pustelnik, U. Mossbacher, H. Schlagbauer-Wadl, et al.
Perilesional injection of R-GM-CSF in patients with cutaneous melanoma metastases.
J Invest Dermatol, 117 (2001), pp. 371-374
[33.]
C. Gaudy, M.A. Richard, G. Folchetti, J.J. Bonerandi, J.J. Grob.
Randomized controlled study of electrochemotherapy in the local treatment of skin metastases of melanoma.
J Cutan Med Surg, 10 (2006), pp. 115-121
[34.]
C.M. Byrne, J.F. Thompson, H. Johnston, P. Hersey, M.J. Quinn, T. Michael Hughes, et al.
Treatment of metastatic melanoma using electroporation therapy with bleomycin (electrochemotherapy).
Melanoma Res, 15 (2005), pp. 45-51
[35.]
G. Stevens, M.J. McKay.
Dispelling the myths surrounding radiotherapy for treatment of cutaneous melanoma.
Lancet Oncol, 7 (2006), pp. 575-583
[36.]
M.J. McKay, R.F. Kefford.
The spectrum of in vitro radiosensitivity in four human melanoma cell lines is not accounted for by differential induction or rejoining of DNA double strand breaks.
Int J Radiat Oncol Biol Phys, 31 (1995), pp. 345-352
[37.]
J. Overgaard, D. González González, M.C. Hulshof, G. Arcangeli, O. Dahl, O. Mella, et al.
Randomised trial of hyperthermia as adjuvant to radiotherapy for recurrent or metastatic malignant melanoma.
Lancet, 345 (1995), pp. 540-543
[38.]
W.T. Sause, J.S. Cooper, S. Rush, C.T. Ago, D. Cosmatos, C.T. Coughlin, et al.
Fraction size in external beam radiation therapy in the treatment of melanoma.
Int J Radiat OncolBiol Phys, 20 (1991), pp. 429-432
[39.]
G. Stevens, J.F. Thompson, I. Firth, C.J. O’Brien, W.H. McCarthy, M.J. Quinn.
Locally advanced melanoma: results of postoperative hypofractionated radiation therapy.
Cancer, 88 (2000), pp. 88-94
[40.]
Y. Li, E.F. McClay.
Systemic chemotherapy for the treatment of metastatic melanoma.
Semin Oncol, 29 (2002), pp. 413-426
[41.]
A.M.M. Eggermont, J.M. Kirkwood.
Re-evaluating the role of dacarbazine in metastatic melanoma: what have we learned in 30 years?.
Eur J Cancer, 40 (2004), pp. 1825-1836
[42.]
H.J. Gogas, J.M. Kirkwood, V.K. Sondak.
Chemotherapy for metastatic melanoma. Time for a change?.
Cancer, 109 (2007), pp. 455-464
[43.]
M.R. Middleton, J.J. Grob, N. Aaronson, G. Fierlbeck, W. Tilgen, S. Seiter, et al.
Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma.
J Clin Oncol, 18 (2000), pp. 158-166
[44.]
P.B. Chapman, L. Einhorn, M.L. Meyers, S. Saxman, A.N. Destro, K.S. Panageas, et al.
Phase III multicenter randomized trial of Dartmouth regimen versus dacarbazine in patients with metastatic melanoma.
J Clin Oncol, 17 (1999), pp. 2745-2761
[45.]
J. Atzpodien, K. Neuber, D. Kamanabrou, M. Fluck, E.B. Bröcker, C. Neumann, et al.
Combination chemotherapy with or without s.c. IL-2 and IFN-α: results of a prospectively randomized trial of the Cooperative Advanced Malignant Melanoma Chemoimmunotherapy Group.
Br J Cancer, 86 (2002), pp. 179-184
[46.]
M.B. Atkins, K.R. O’ Boyle, J.A. Sosma, G.R. Weiss, K.A. Margolin, M.L. Ernest, et al.
Multiinstitutional Phase II trial of intensive combination chemoimmunotherapy for metastatic melanoma.
J Clin Oncol, 12 (1994), pp. 1553-1560
[47.]
S.S. Legha, S. Ring, O. Eton, A. Bedikian, A.C. Buzaid, C. Plager, et al.
Development of a biochemotherapy regimen with concurrent administration of cisplatin, vinblastine, dacarbazine, interferon alfa, and interleukin-2 for patients with metastatic melanoma.
J Clin Oncol, 16 (1998), pp. 1752-1759
[48.]
L.E. Flaherty, W. Robinson, B.G. Redman, R. González, S. Martino, M. Kraut, et al.
A Phase II study of dacarbazine and cisplatin in combination with outpatient administered interleukin-2 in metastatic malignant melanoma.
Cancer, 71 (1993), pp. 3520-3525
Copyright © 2009. Academia Española de Dermatología y Venereología and Elsevier España, S.L.
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