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Short German guidelines: Malignant melanoma

2008; Wiley; Volume: 6; Issue: s1 Linguagem: Holandês

10.1111/j.1610-0387.2008.06711.x

1610-0387

Claus Garbe, Dirk Schadendorf, Wilhelm Stolz, Matthias Volkenandt, Uwe Reinhold, Rolf‐Dieter Kortmann, Christoph Kettelhack, Bernhard Frerich, Ulrich Keilholz, Reinhard Dummer, Günther Sebastian, Wolfgang Tilgen, Gerold Schuler, Andréas Mackensen, Roland Kaufmann, Axel Hauschild,

bioluminescence and chemiluminescence research

JDDG: Journal der Deutschen Dermatologischen GesellschaftVolume 6, Issue s1 p. S9-S14 Free Access Short German guidelines: Malignant melanoma Claus Garbe, Claus GarbeSearch for more papers by this authorDirk Schadendorf, Dirk SchadendorfSearch for more papers by this authorWilhelm Stolz, Wilhelm StolzSearch for more papers by this authorMatthias Volkenandt, Matthias VolkenandtSearch for more papers by this authorUwe Reinhold, Uwe ReinholdSearch for more papers by this authorRolf-Dieter Kortmann, Rolf-Dieter KortmannSearch for more papers by this authorChristoph Kettelhack, Christoph KettelhackSearch for more papers by this authorBernhard Frerich, Bernhard FrerichSearch for more papers by this authorUlrich Keilholz, Ulrich KeilholzSearch for more papers by this authorReinhard Dummer, Reinhard DummerSearch for more papers by this authorGünther Sebastian, Günther SebastianSearch for more papers by this authorWolfgang Tilgen, Wolfgang TilgenSearch for more papers by this authorGerold Schuler, Gerold SchulerSearch for more papers by this authorAndreas Mackensen, Andreas MackensenSearch for more papers by this authorRoland Kaufmann, Roland KaufmannSearch for more papers by this authorAxel Hauschild, Axel HauschildSearch for more papers by this author Claus Garbe, Claus GarbeSearch for more papers by this authorDirk Schadendorf, Dirk SchadendorfSearch for more papers by this authorWilhelm Stolz, Wilhelm StolzSearch for more papers by this authorMatthias Volkenandt, Matthias VolkenandtSearch for more papers by this authorUwe Reinhold, Uwe ReinholdSearch for more papers by this authorRolf-Dieter Kortmann, Rolf-Dieter KortmannSearch for more papers by this authorChristoph Kettelhack, Christoph KettelhackSearch for more papers by this authorBernhard Frerich, Bernhard FrerichSearch for more papers by this authorUlrich Keilholz, Ulrich KeilholzSearch for more papers by this authorReinhard Dummer, Reinhard DummerSearch for more papers by this authorGünther Sebastian, Günther SebastianSearch for more papers by this authorWolfgang Tilgen, Wolfgang TilgenSearch for more papers by this authorGerold Schuler, Gerold SchulerSearch for more papers by this authorAndreas Mackensen, Andreas MackensenSearch for more papers by this authorRoland Kaufmann, Roland KaufmannSearch for more papers by this authorAxel Hauschild, Axel HauschildSearch for more papers by this author First published: 30 May 2008 https://doi.org/10.1111/j.1610-0387.2008.06711.xCitations: 71 Prof. Dr. med. Claus GarbeLeiter der Sektion DermatologischeOnkologieUniversitäts-HautklinikLiebermeister Straße 25D-72076 TübingenTel.: +49-7071-29-83678Fax: +49-7071-29-5187E-Mail: [email protected] AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Definition Malignant melanoma is a malignant tumor which arises from melanocytic cells and primarily involves the skin. For the balance of these guidelines, the terms malignant melanoma and melanoma will be used interchangeably, because there are no benign melanomas. Melanomas can also arise in the eye (conjunctiva and uvea), meninges and on various mucosal surfaces. While melanomas are usually heavily pigmented, there are also amelanotic tumors. Even small tumors have a tendency towards metastasis and thus a relatively unfavorable prognosis. Melanomas account for 90% of the deaths associated with cutaneous tumors. The incidence of melanoma is increasing worldwide in white populations, especially where fair-skinned peoples receive excessive sun exposure. In central Europe the incidence is 10–12/100,000 yearly; in the USA, 10-25/100,000 yearly; and in Australia the highest incidence, 50-60/100,000 yearly. In individuals with more pigmentation (Asians, Africans) melanomas are uncommon and almost always found on either acral or mucosal surface. Individuals with large numbers of melanocytic nevi and those with melanoma precursors (dysplastic nevi, congenital nevi) are at greater risk. The inheritance of melanoma is polygenic; 5-10% of melanomas appear in melanoma-prone families. In addition to these genetic and constitutional factors, the most important exogenous factor is exposure to UV irradiation. The relative roles of toxic substances, medications and hormones (pregnancy, oral contraceptives) are controversial. The immune status of the patient plays a major role in determining the course of melanoma, as numerous examples of spontaneous regression or of rapid progression in immunosuppressed individuals bear testimony. A number of different types of melanomas can be identified clinically and histologically. Some tumors either represent mixed forms or are not classifiable. Examples of special forms are amelanotic melanomas, mucosal melanomas, and other extracutaneous melanomas, which together account for about 5% of all melanomas. Superficial spreading melanoma (SSM) starts with an intraepidermal horizontal or radial growth phase, starting as macule and slowly evolving into a plaque, often with multiple colors and pale areas of regression. Secondary nodular areas may also develop. A characteristic histologic feature is pagetoid spread of clear malignant melanocytes throughout the epidermis. Nodular melanoma in contrast is a primarily nodular, exophytic brown-black, often eroded or bleeding tumor, which has only short horizontal growth phase and then an aggressive vertical phase. Thus early identification in an intraepidermal stage is almost impossible. Lentigo maligna melanoma arises often after many years from a lentigo maligna (melanoma in-situ) almost exclusively on the face of elderly individuals. Acral-lentiginous melanoma is usually palmoplantar, or sub- or periun-gual. In its early intraepidermal phase, there is irregular, poorly circumscribed pigmentation; later a nodular region signals the invasive growth pattern. Preoperative and Staging Evaluation Required Examinations • Dermatoscopy to enhance differential diagnosis of pigmented tumors. • Clinical evaluation of draining lymphatic pathways and to exclude the presence of a second melanoma or other melanoma precursors. • Lymph node sonography for lesions thicker than 1 mm. • Confirmation of diagnosis with an excisional biopsy. • Histopathologic diagnosis should include type of melanoma, tumor thickness (Breslow depth), Clark level, and presence or absence of ulceration. • Sentinel lymph node biopsy should be performed as part of routine staging in melanomas thicker than 1 mm. When the tumor is located on face, elective lymph node dissection or parotid gland excision should be considered. • Laboratory evaluation includes sed rate, CBC, LDH, alkaline phosphates and serum S100 protein for tumors thicker than 1 mm. • Chest X-ray in two planes. • Sonography of the abdomen including the pelvis and retroperitoneum. Useful in Selected Cases • High-resolution sonography to measure tumor depth preoperatively. • CT, MRI or PET evaluation as alternative or supplement to above-mentioned staging examinations. Prognosis and Staging About 90% of melanomas are diagnosed as primary tumors without any evidence for metastasis. The tumor-specific 10-year-survival for all such tumors is around 75–80%. The most important prognostic factors for primary melanoma without metastases are: • Vertical tumor thickness (Breslow depth) measured on histological specimen • Presence of a histologically recognizable ulceration • Clark level Melanomas can metastasize either by the lymphatic or hematogenous routes. About two-thirds of metastases are originally confined to the drainage area of regional lymph nodes. A regional metastasis can appear as: • Satellite metastases (up to 2 cm from the primary tumor), as well as local recurrence following the removal of the primary tumor with an inadequate excision margin • In-transit metastases (in the skin between the site of the primary tumor and the first lymph node) • Regional lymph node metastases In 2001, the AJCC proposed a new TNM classification and staging for melanoma; it has now also been accepted by the UICC. This new system now forms the cornerstone for classifying melanomas and is summarized in Tables 1–4. A new version of the TMN classification is currently being developed. Table 1. T classification of primary tumor for melanoma. T classification Tumor thickness Additional prognostic parameters Tis No information Melanoma in situ, no tumor invasion Tx Stage cannot be determined* T1 < = 1.0 mm a: No ulceration, Level II–III b: Ulceration or Level IV–V T2 1.01–2.0 mm a: No ulceration b: Ulceration T3 2.01–4.0 mm a: No ulceration b: Ulceration T4 >4.0 mm a: No ulceration b: Ulceration *Tumor thickness or information on ulceration not available, or unknown primary tumor. Table 2. N classification of the regional lymph nodes for melanoma. N classification Number of involved lymph nodes (LN) Extent of lymph node metastases N1 1 LN a: Micrometastases b: Macrometastases N2 2–3 LN a: Micrometastases b: Macrometastases c: Satellite or in-transit metastases N3 ≥4 LN, satellite or in-transit metastases plus node involvement Table 3. M classification of distant metastases for melanoma. M classification Type of distant metastasis LDH M1a Skin, subcutaneous tissue or lymph node Normal M1b Lungs Normal M1c All other distant metastases Normal Any distant metastasis Elevated Table 4. Staging of melanoma. Stage Primary tumor (pT) Regional lymph node metastases (N) Distant metastases (M) 0 In situ tumor None None IA ≤1.0 mm, no ulceration None None IB ≤1.0 mm with ulceration or Clark None None Level IV or V 1.01–2.0 mm, no ulceration None None IIA 1.01–2.0 mm with ulceration None None 2.01–4.0 mm, no ulceration None None IIB 2.01–4.0 mm with ulceration None None >4.0 mm, no ulceration None None IIC >4.0 mm with ulceration None None IIIA Any tumor thickness, no ulceration Micrometastases None IIIB Any tumor thickness with ulceration Micrometastases None Any tumor thickness, no ulceration Up to three macrometastases None Any tumor thickness ± ulceration None but satellite and/ or in-transit metastases None IIIC Any tumor thickness with ulceration Up to three macrometastases None Any tumor thickness ± ulceration Four or more macrometastases, or lymph node None involvement extending beyond capsule, or satellite and/or intransit metastases with lymph node involvement IV Distant metastases Therapy Curative Surgical Therapy The primary treatment of a biopsy-proven Stage I melanoma is surgical excision with the goal of cure. The safety margin of the excision is variable and based on the risk of metastasis. In patients with thin melanomas extensive procedures are not needed; conversely in those with thick tumors, radical surgery does little to influence the risk of distant metastases. Too narrow margins are most likely associated with an increased risk of local recurrence. All these factors combine to produce the excision strategy shown in Table 5. Most procedures can be performed under local anesthesia with primary closure of defect. Table 5. Recommended excision margins for melanoma. Tumor thickness (Breslow) Safety margin in situ 0.5 cm ≤2 mm 1 cm >2 mm 2 cm When dealing with lentigo maligna melanoma and acral melanoma, micrographic surgery using permanent sections may allow a narrower margin of safety. Radiation therapy is a possible alternative to surgery for facial lentigo maligna. Sentinel lymph node biopsy should be performed for all tumors thicker than1 mm. If other unfavorable signs are present (Clark level IV/V, ulceration of primary tumor), sentinel lymph node biopsy should be considered for thinner tumors. Sentinel lymph node biopsies should be performed in centers experienced in both the nuclear medicine and operative aspects of the procedure. The sentinel lymph node biopsy is a histologic staging procedure and not a therapeutic measure with a proven positive effect on overall survival. The sentinel lymph node biopsy increases the length of recurrence-free status in the regional lymph nodes and may be used to help decide on adjuvant systemic therapy. For melanomas thicker than 1 mm in the head and neck region, lymph node staging can also be accomplished with an elective neck dissection or parotid gland excision, depending on the site of the tumor. If there is no indication of involvement of the sentinel lymph node, no further surgical procedures are indicated on the lymph nodes. If a micrometastasis is identified, a radical lymph node dissection is typically performed. There is not convincing evidence that this procedure improves the overall survival. Palliative Surgical Therapy When the patient has satellite and/or in transit metastases, complete excision of metastases is performed. When a single limb is involved with multiple satellite and/or in transmit metastases, hyper-thermic perfusion of cytostatic agents can be considered. For regional lymph node metastases, a radical lymph node dissection (or a modified or selective neck dissection) is a curative attempt. If a tumor-free status cannot be obtained or if the operation is not appropriate for the patient, then radiation therapy is recommended. In Stage IV diseases if the metastases are potentially completely resectable (R0 intention), this surgical approach should be undertaken. Further recommendations in this setting are unclear and should be decided on an individual basis by a multidisciplinary team. Adjuvant Therapy Interferon- is the first substance for ad-juvant therapy of melanoma which has been shown in prospective randomized studies to significantly improve the recurrence-free interval. Thus adjuvant therapy with IFN-α should be offered to all patients with an increased risk of metastasis, as long as there are no contraindications. The two available substances IFN-α-2a and IFN-α-2b differ in the molecular structure at only two amino acids and are identical in regards to receptor binding, efficacy, and side effects. Both are available in pegylated forms with a prolonged half-life, making weekly administration possible. In melanoma patients with tumor thickness ≥1.50 mm without evidence of metastasis, three prospective randomized studies have been carried out with low-dose IFN-α. All studies used IFN-α 3 million IU 3 times weekly for 6–18 months, and in all studies there was a significant prolongation of the recurrence-free time. In the largest study where patients were treated for 18 months, there was a clear trend towards a prolonged overall survival. Thus patients in this risk group should be offered IFN-α 3 million IU 3 times weekly for 18 months, as long as there are no contraindications. Based on the current AJCC/UICC classification with consideration of the sentinel node status, adjuvant IFN-α therapy is offered to all patients with above stage IIA (≥ 2.0 mm tumor thickness, with or without ulceration). There is no certain data proving efficacy in this lower risk group, so consideration is being given to first offering adjuvant therapy to patients in Stage IIB (≥2.0 mm tumor thickness with ulceration, ≥4.0 mm tumor thickness without ulceration). A variety of randomized studies using varying dosages of IFN-α have been performed in patients with lymph node metastases. The clearest results are available for high-dose IFN-α -2b. Two prospective randomized studies both show an improved recurrence-free survival in contrast to control patients. This therapy has been accepted as standard in the USA and Canada; in Europe because of the toxicity of high-dose INF-α and the fact that only a subgroup of patients benefit, other interferon regimens are being considered. A large prospective randomized study of pegylated IFN-α -2b showed a significant increase in recurrence-free survival. Patients with micrometastases profit the most; they also have an increased time free of distant metastases. Low-dose IFN-α- 2a and IFN-α -2b have achieved conflicting results in prospective randomized studies in patients with lymph node metastases. Two meta-analyses have shown a significant improvement of 7% in the recurrence-free survival, and a positive trend for a 3% improvement in overall survival, using 5-year survival statistics (Table 6). Table 6. Dosage schedules for adjuvant therapy of melanoma with IFN-α. Schedule Dose Frequency Duration Indication Low dose 3 million IU s.c. Days 1,3 & 5 every week 18–24 months Stage II – III High dose Initiation 20 million IU/m2 iv. rapid infusion Day 1–5 every week 4 weeks Stage III Maintenance 10 million IU/m2 s.c Days 1,3 & 5 every week 11 months Stage III Pegylated IFN-α -2b Initiation 6 μg/kg/week Day 1 every week 8 weeks Stage III Maintenance 3 μg/kg/week Day 1 every week 5 years Stage III Radiation Therapy Radiation therapy is only indicated for the primary treatment of melanoma in those cases in which surgery is impossible or not reasonable. Local control of the tumor is somewhat less satisfactory with radiation therapy, but still acceptable. When a macroscopic tumor is present, it should be irradiated with a 3cm margin with 70 Gy, fractionated as 2 Gy 5× weekly. When microscopic residual tumor (R1) is present, 60 Gy are recommended. To optimize the dose to the tumor and spare normal tissue, electron beam therapy is recommended. In-transit metastases which are inoperable and where extremity perfusion does not come into question can also be treated with radiation therapy alone. Electron beam therapy with electron energies of 6–8 MeV is employed. Using conventional fractionation, a total dose of 50–60 Gy should be employed. Regional lymph node metastases can also be irradiated if they are inoperable or if surgery has failed to effect complete removal (R1 resection). Single doses of 1.8–2.0 Gy are used with a total dose of 50–54 Gy using conventional fractionation. Bone metastases can be effectively palliated with radiation therapy. The response rate is 67–85%; improvement is often noted during the therapy. The major indications are pain, loss of structural stability (fracture risk), and compression of the spinal canal with or without neurological symptoms. A total dose of 35–36 Gy with individual doses of 2.5–3.0 Gy is recommended. In cases with a limited life expectancy and no threat to structural stability, considerably higher single doses (up to 8 Gy) can be used to shorten the total treatment time. For patients with solitary brain metastases, either surgery or stereotactic single dose radiation therapy are recommended. The radiation therapy is less toxic. The combination of local therapy (operation or stereotactic radiation) and whole brain irradiation has been effective for other tumors with a marked improvement in mean survival time (from 4 months to 10 months). Multiple brain metastases in melanoma are also an indication for radiation therapy. 30 Gy are given in 10 fractions over 2 weeks. Higher doses appear to improve the median survival, so that in individual cases local enhancement should be considered. The combination of radiation therapy with hyperthermia (thermoradiotherapy) may be a reasonable therapeutic option, but it is still under study. The results from retrospective and prospective clinical studies all show that the combined procedure is more effective than radiation therapy alone. Local tumor control is improved with combined therapy. Palliative Chemotherapy and hemoimmunotherapy The main indications for systemic chemotherapy or chemoimmunotherapy are inoperable recurrences, inoperable regional metastases and distant metastases (Stage IV). Since the treatment is primarily palliative, careful attention should be paid to its effect on quality of life. In Stage IV one should distinguish between the limited disease and extensive disease patterns of metastasis. Patients with limited disease (metastases in the skin, soft tissues, lymph nodes, and lungs) respond better and survive longer with a variety of regimens than do those with extensive disease (metastases in the liver, skeleton, brain or generalized visceral metastases). A number of agents with comparable effectiveness are available for monoche-motherapy of advanced melanoma. Palliative monochemotherapy may achieve regression of the tumor and thus an improvement in tumor-related signs and symptoms. The medications recommended for monotherapy of melanoma are summarized in Table 7. The combination of cytostatic agents and cytokines can improve the response rate. Unfortunately none significantly improves the overall survival. Both the objective and subjective tolerability of monochemo-therapy is worsened by concomitant administration of IFN or IL-2. Table 7. Monotherapy of advanced cutaneous melanoma. Medication Dose Response rate Dacarbazine 250 mg/m2 i.v. daily for 5 days every 3–4 weeks or 12.1–17.6% 800–1200 mg/m2 i.v. daily on one day every 3–4 weeks 5.3–23% Temozolomide 150–200 mg/m2 p.o. daily for 5 days every 4 weeks 13.5–21% Fotemustine 100 mg/m2 i.v. on days 1, 8 and 15; then 5 week pause, then repeat single dose every 3 weeks 7.4–24.2% Vindesine 3 mg/m2 i.v. every 14 day 12–26% Interferon-α 9–18 million IU/m2 s.c. 3 × weekly 13–25% Interleukin-2 6 million IU/kg as 15 min. every 8 hours infusion i.v. for 5 days (total of 14 doses). 16–21.6% Repeat every 2 weeks. Similarly, multiple-drug chemotherapy regimen (polychemotherapy) or chemotherapy agents combined with cytokines (polychemoimmunotherapy) produce higher remission rates than monotherapy but fail to prolong the overall survival. The combined regimens are more toxic than monotherapy. Using polychemotherapy or polychemoimmu-notherapy may in special cases offer better palliation or more effectively control tumor-associated signs and symptoms. The established combination regimens for melanoma are given in Table 8. Because of the potential toxicity of polychemotherapy, particular attention must be paid to supportive care to maximize the patient's quality of life while receiving this treatment. Regimens containing DTIC require highly effective anti-emetic therapy. If bony metastases are present, bisphosphonates should be employed; dental consultation should be obtained regarding oral hygiene measures to reduce the risk of biphosphonate-related jaw necrosis. Table 8. Polychemotherapy and chemoimmunotherapy of advanced cutaneous melanoma. Regimen Dose Response rate BHD BCNU 150 mg/m2 i.v. day 1 in every other cycle; 12.7–30.4% Hydroxyurea 1500 mg/m2 p.o. days 1–5 DTIC 150 mg/m2 i.v. days 1–5 every 4 weeks BOLD Bleomycin 15 mg i.v. days 1 + 4 22–40% Vincristine 1 mg/m2 i.v. days 1 + 5 CCNU 80 mg/m2 p.o. day 1 DTIC 200 mg/m2 i.v. days 1–5 every 4–6 weeks DVP DTIC 250 mg/m2 i.v. days 1–5 31.4–45% Vindesine 3 mg/m2 i.v. day 1 Cisplatin 100 mg/m2 i.v. day 1 every 3–4 weeks DVP DTIC 450 mg/m2 i.v. days 1 + 8 24% Vindesine 3 mg/m2 i.v. days 1 + 8 Cisplatin 50 mg/m2 i.v. days 1 + 8 every 3–4 weeks CarboTax Carboplatin AUC6 i.v. day 1, after four cycles reduce to AUC4 12.1% Paclitaxel 225 mg/m2 i.v. day 1 every 3 weeks, (second line) after four cycles reduce to 175 mg/m2 GemTreo Gemcitabine 1000 mg/m2 i.v. days 1 and 8 33.3% Treosulfan 3500 mg/m2 i.v. days 1 and 8 every 4 weeks (PR + SD, uveal melanoma) Follow-up The frequency and extent of follow-up examinations depends on the initial tumor parameters, just as does the treatment. The first 5 years following surgery are most important, as 90% of all metastases occur during this time period. On the other hand, melanoma does have a tendency towards late metastases so the total follow-up period should extend for 10 years. Finally, patients who have had a melanoma have an increased risk of a second melanoma, adding increased importance to regular re-evaluation. Follow-up of melanoma patients has the following goals: 1 Confirming that the tumor has not recurred or identifying disease progression at the early possible stage 2 Looking for melanoma precursors and second melanomas 3 Offering psychosocial support 4 Documenting the disease course 5 Administering and monitoring adjuvant therapy, where appropriate Current recommendations for follow-up are shown in Table 9. Table 9. Recommendations for the follow-up of melanoma patients (intervals in months). Stage and tumor thickness Physical examination Years 1–5 Physical examination Years 6–10 Lymph node sonography Years 1–5 Serum S100 protein levels Years 1–5** Imaging studies Years 1–5*** I, < 1 mm 6 12 None None None I + II, > 1 mm 3 6–12 6 3–6 None**** III* 3 6 3–6 3–6 6 IV Individual *Stage III includes all forms of local and regional metastasis. The new AJCC Stage IIC (>4 mm tumor thickness and ulceration) should be followed as Stage III, since the prognosis is similar. **S100 protein is the only parameter suited for detecting recurrences. ***Abdominal sonography and chest x-ray, or CAT, MRI or PET. ****Patients receiving adjuvant therapy should receive imaging studies every 6–12 months. Consensus-building Process and Participants This current short guideline was written between July and September 2007 in interdisciplinary cooperation between the German Cancer Society and the German Dermatologic Society, based on the full-length guidelines published as "Interdisziplinären Leitlinien zur Diagnostik und Behandlung von Hauttumoren" (C. Garbe, ed.), Kapitel "Deutsche Leitlinie: Malignes Melanoma" with the authors Claus Garbe, Tübingen; Axel Hauschild, Kiel, Matthias Volkenandt, München, Dirk Schadendorf, Mannheim; Wilhelm Stolz, München; Rolf- Dieter Kortmann, Leipzig, Christoph Kettelhack, Basel, Bernhard Frerich, Leipzig; Ulrich Keilholz, Berlin; Reinhard Dummer, Zürich; Günter Sebastian, Dresden; Wolfgang Tilgen, Homburg; Gerold Schuler, Erlangen; Andreas Mackensen, Regensburg; Roland Kaufmann, Frankfurt. Guideline coordinator: Prof. Dr. C. Garbe, Universitäts-Hautklinik Tübingen. Authors: Claus Garbe, Universitäts-Hautklinik Tübingen; Dirk Schadendorf, Universitäts-Hautklinik Mannheim; Wilhelm Stolz, Hautklinik München Schwabing; Matthias Volkenandt, Universitäts-Hautklinik der LMU München; Uwe Reinhold, Fachbereich Dermatologie, Medizinisches Zentrum Bonn Friedensplatz; Rolf-Dieter Kort-mann, Universitäts-Klinik für Strahlentherapie und Radioonkologie Leipzig; Christoph Kettelhack, Allgemein-Chirurgie, Universitäts-Spital Basel; Bernhard Frerich, Universitäts-Klinik für Mund-, Kiefer- und Plastische Gesichtschirurgie Leipzig; Ulrich Keilholz, Medizinische Universitäts-Klinik III, Campus Benjamin Franklin, Charité Berlin; Reinhard Dummer, Dermatologische Klinik, Universitäts-Spital Zürich; Günther Sebastian, Universitäts-Hautklinik Dresden; Wolfgang Tilgen, Universitäts-Hautklinik Homburg; Gerold Schuler, Universitäts-Hautklinik Erlangen; Andreas Mackensen, Universitäts-Klinik für Hämatologie und Internisti-sche Onkologie Erlangen; Roland Kaufmann, Universitäts-Hautklinik Frankfurt; Axel Hauschild, Universitäts-Hautklinik Kiel. Next update planned: Spring 2010. The guideline coordinator is queried yearly by ISTO (Information Center for Standards in Oncology) about required updates. In case these are needed, the updated version of the guidelines will be published at http://www.krebsgesellschaft.de, http://www.ado-homepage.de and http://www.awmf.org. Conflict of interest Axel Hauschild declares the following conflict of interest: In the past 2 years he has acted as a consultant for or accepted lecture fees from: • MEDA Pharma (Germany) • Abraxis Oncology (USA) • BayerSchering (Germany/USA) • BMS (USA, Europe) • Celgene (Europe) • essex pharma/Schering-Plough (Germany, USA) • Galderma Deutschland • Genta (USA) • GSK (USA, Europe) • Hermal (Germany) • La Roche-Posay (Germany) • Merck (Germany) • Onyx (USA) • Pfizer (USA, Germany) • Roche Pharma (Germany) • Synta (USA) All remaining authors have not declared any conflict of interests. References 1 Garbe C, Hauschild A, Volkenandt M, Schadendorf D, Stolz W, Kortmann RD, Kettelhack C, Frerich B, Keilholz U, Dummer R, Sebastian G, Tilgen W, Schuler G, Mackensen A, Kaufmann R (2005) Deutsche Leitlinie: Malignes Melanoma. In: C Garbe (Hrsg.) Interdisziplinäre Leitlinien zur Diagnostik und Behandlung von Hauttumoren. Stuttgart , New York : Georg Thieme Verlag: 23– 55. Citing Literature Volume6, Issues1Special Issue: Onkologische LeitlinienMay 2008Pages S9-S14 ReferencesRelatedInformation