Melanoma: Sebastian G

Garbe C, Hauschild A, Volkenandt M, Schadendorf D, Stolz W, Reinhold U, Kortmann RD, Kettelhack C, Frerich B, Keilholz U, Dummer R, Sebastian G, Tilgen W, Schuler G, Mackensen A, Kaufmann R. · University Department of Dermatology, Tübingen, Germany. · Melanoma Res. · Pubmed #18337653 No free full text.

Abstract: Systemic medical treatment of melanoma is administered in the adjuvant and palliative setting. Adjuvant therapy may be considered in patients with primary melanoma with more than 1.5 mm tumor thickness and with regional node metastasis. Presently no indication for systemic adjuvant chemotherapy or for adjuvant therapy with nonspecific immune-stimulatory agents outside controlled studies is seen. Interferon-alpha is the first substance in the adjuvant therapy of melanoma, which has shown to present a significant advantage to the patients in some prospective randomized studies. Good arguments for using adjuvant interferon-alpha therapy in high-risk melanoma patients exist. Both high-dose and low-dose interferon-alpha show promise. The major indications for systemic chemotherapy and chemoimmunotherapy are inoperable recurrent tumors, inoperable regional metastases and distant metastases (stage IV). As treatment in such situations is primarily palliative, the effect of any regimen on the quality of life must be carefully weighed. As a first line treatment, single agent therapy is recommended, as polychemotherapy or biochemotherapy did not show significant advantages for prolongation of survival; hence they are more toxic. An urgent need for development of new treatment modalities is necessary and general principles of experimental immunotherapy are outlined.

Garbe C, Hauschild A, Volkenandt M, Schadendorf D, Stolz W, Reinhold U, Kortmann RD, Kettelhack C, Frerich B, Keilholz U, Dummer R, Sebastian G, Tilgen W, Schuler G, Mackensen A, Kaufmann R. · University Department of Dermatology, Tübingen, Germany. · Melanoma Res. · Pubmed #18227710 No free full text.

Abstract: The primary treatment of a melanoma is surgical excision. An excisional biopsy is preferred, and safety margins of 1 cm for tumor thickness up to 2 mm and 2 cm for higher tumor thickness should be applied either at primary excision or in a two-step procedure. When dealing with facial, acral or anogenital melanomas, micrographic control of the surgical margins may be preferable to allow reduced safety margins and conservation of tissue. The sentinel lymph node biopsy should be performed in patients whose primary melanoma is thicker than 1.0 mm and this operation should be performed in centers where both the operative and nuclear medicine teams are experienced. In clinically identified lymph node metastases, radical lymph node dissection is considered standard therapy. If distant metastases involve just one internal organ and operative removal is feasible, then surgery should be seen as therapy of choice. Radiation therapy for the primary treatment of melanoma is indicated only in those cases in which surgery is impossible or not reasonable. In regional lymph nodes, radiation therapy is usually recommended when excision is not complete (R1 resection) or if the nodes are inoperable. In distant metastases, radiation therapy is particularly indicated in bone metastases, brain metastases and soft tissue metastases.

Sebastian G. · Klinik und Poliklinik für Dermatologie, Universitätsklinikum Carl Gustav Carus, Fetscherstrasse 74, 01307 Dresden. · Hautarzt. · Pubmed #16874532 No free full text.

Abstract: Excision is the treatment of choice in stage I malignant melanoma. As supported by several controlled clinical studies, reduced safety surgical margins from 0.5 to 2 cm are sufficient. Most surgical defects can be closed by simple skin flap techniques. In critical anatomic sites (e. g. face, hand, foot) micrographic surgery is the therapy of choice. Sentinel lymph node biopsy (SLNB) was proposed as a minimally-invasive procedure for the histopathologic staging of the regional lymph nodes. Today SLNB is standard in the diagnostic approach to melanomas thicker than 1 mm. The therapeutic relevance of SLNB is unclear. The most common sign of tumor progression is involvement of regional lymph nodes. The treatment of choice in patients with neck metastases is the radical, modified or selective neck dissection. In the case of axillary metastases, levels I-III of the axillary lymph nodes are excised. With groin metastases, superficial inguinal dissection is usually preferred. There are no randomized controlled trials comparing the outcome of combined inguinal and pelvic lymph node dissection and superficial inguinal lymph node dissection.

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. · Universitäts-Hautklinik Tübingen. · J Dtsch Dermatol Ges. · Pubmed #16638065 No free full text.

This publication has no abstract.

Kaufmann R, Spieth K, Leiter U, Mauch C, von den Driesch P, Vogt T, Linse R, Tilgen W, Schadendorf D, Becker JC, Sebastian G, Krengel S, Kretschmer L, Garbe C, Dummer R, Anonymous00054. · Department of Dermatology, J.W. Goethe-University, Frankfurt am Main, Germany. · J Clin Oncol. · Pubmed #16260697 No free full text.

Abstract: PURPOSE: Temozolomide (TMZ) has shown efficacy in metastatic melanoma equal to that of dacarbazine (DTIC), the standard chemotherapeutic agent for melanoma. As the combination with interferon-alfa (IFN-alpha) appears superior to single-agent DTIC regarding response rates, the purpose of this study was to compare TMZ alone and TMZ plus IFN-alpha in terms of objective response (OR), overall survival, and safety in a prospective, randomized, multicenter trial. PATIENTS AND METHODS: Two hundred ninety-four patients with untreated stage IV metastatic melanoma (American Joint Committee on Cancer staging system) were randomly assigned to receive either oral TMZ alone (200 mg/m2/day; days 1 through 5 every 28 days) or in combination with subcutaneous IFN-alpha (5 MU/m2; days 1, 3, and 5 every week). RESULTS: Two hundred eighty-two patients were eligible for an intent-to-treat analysis, 271 patients were treated per protocol. In the TMZ + IFN-alpha arm, 33 (24.1%) of 137 patients responded to therapy (partial or complete remission) whereas in the monotherapy arm, in 18 (13.4%) of 134 patients, a response was evident. Thus, the response rate was significantly higher in the combination arm (P = .036). Median survival time was 8.4 months for patients treated with TMZ (95% CI, 7.07 to 9.27) and 9.7 months for those treated with the combination (95% CI, 8.26 to 11.18; P = .16). Dose modifications and interval prolongations due to hematologic toxicity were significantly more frequent in the TMZ + IFN-alpha arm (P < .001). CONCLUSION: In metastatic melanoma treatment with TMZ + IFN-alpha leads to a significantly superior OR rate compared to treatment with TMZ alone, which did not translate into prolonged survival in our study population.

Oratz R, Hauschild A, Sebastian G, Schadendorf D, Castro D, Bröcker EB, Orenberg EK. · Department of Medical Oncology, New York University Medical Center, New York City, New York 10016, USA. · Melanoma Res. · Pubmed #12569286 No free full text.

Abstract: Local therapies have been highly effective in the treatment of melanoma. The objective of this study was to evaluate the use of a novel intralesional chemotherapy - cisplatin/adrenaline injectable gel - for the treatment of refractory or recurrent cutaneous and soft tissue melanoma metastases. The gel is injected directly into the lesion and delivers high concentrations of cisplatin at the injection site, where it is retained for extended periods, with little systemic exposure. A total of 28 patients with refractory or recurrent melanoma were enrolled in this open-label, multicentre study. Of these, 25 patients with 244 lesions were evaluable for efficacy. Lesions were injected with 0.5 ml (2 mg cisplatin + 0.05 mg adrenaline) of gel/cm(3) of tumour. Patients received up to six weekly treatments within an 8 week period. The objective response rate (complete responses [CRs] plus partial responses [PRs]) for all the tumours treated (1-72 per patient) was 53% (130 out of 244; 114 CRs, 16 PRs). The response rate for the target tumours (i.e. each patient's single, most symptomatic, largest or most threatening tumour) was 44%. The median response duration for all tumours was 347 days (range 30-783 days) and median number of treatments per tumour was five (range one to twelve). Systemic toxicity was negligible; local adverse reactions such as erythema, necrosis or pain occurred frequently, but were easily managed in most cases. In conclusion, cisplatin/adrenaline injectable gel was well tolerated, easy to administer, and effective in treating metastatic melanoma confined to the skin or soft tissues.

Hauschild A, Garbe C, Stolz W, Ellwanger U, Seiter S, Dummer R, Ugurel S, Sebastian G, Nashan D, Linse R, Achtelik W, Mohr P, Kaufmann R, Fey M, Ulrich J, Tilgen W. · Department of Dermatology, Christian-Albrechts-University, Kiel. · Br J Cancer. · Pubmed #11308250 links to  free full text

Abstract: In several phase II-trials encouraging tumour responses rates in advanced metastatic melanoma (stage IV; AJCC-classification) have been reported for the application of biochemotherapy containing interleukin 2. This study was designed to compare the efficacy of therapy with dacarbazine (DTIC) and interferon alpha (IFN-alpha) only to that of therapy with DTIC and IFN-alpha with the addition of interleukin 2 (IL-2) in terms of the overall survival time and rate of objective remissions and to provide an elaborated toxicity profile for both types of therapy. 290 patients were randomized to receive either DTIC (850 mg/m(2)every 28 days) plus IFN-alpha2a/b (3 MIU/m(2), twice on day 1, once daily from days 2 to 5; 5 MIU/m(2)3 times a week from week 2 to 4) with or without IL-2 (4.5 MIU/m(2)for 3 hours i.v. on day 3; 9.0 MIU/m(2) i.v. day 3/4; 4.5 MIU/m(2) s.c. days 4 to 7). The treatment plan required at least 2 treatment cycles (8 weeks of therapy) for every patient. Of 290 randomized patients 281 were eligible for an intention-to-treat analysis. There was no difference in terms of survival time from treatment onset between the two arms (median 11.0 months each). In 273 patients treated according to protocol tumour response was assessable. The response rates did not differ between both arms (P = 0.87) with 18.0% objective responses (9.7% PR; 8.3% CR) for DTIC plus IFN-alpha as compared to 16.1% (8.8% PR; 7.3% CR) for DTIC, IFN-alpha and IL-2. Treatment cessation due to adverse reactions was significantly more common in patients receiving IL-2 (13.9%) than in patients receiving DTIC/IFN-alpha only (5.6%). In conclusion, there was neither a difference in survival time nor in tumour response rates when IL-2, applied according to the combined intravenous and subcutaneous schedule used for this study, was added to DTIC and IFN-alpha. However, toxicity was increased in melanoma patients treated with IL-2. Further phase III trials with continuous infusion and higher dosages must be performed before any final conclusions can be drawn on the potential usefulness of IL-2 in biochemotherapy of advanced melanoma.

Garbe C, Schadendorf D, Stolz W, Volkenandt M, Reinhold U, Kortmann RD, Kettelhack C, Frerich B, Keilholz U, Dummer R, Sebastian G, Tilgen W, Schuler G, Mackensen A, Kaufmann R, Hauschild A. · Sektion Dermatologische Onkologie, Universitäts-Hautklinik, Liebermeister Strasse 25, D-72076 Tübingen, Germany. · J Dtsch Dermatol Ges. · Pubmed #18801142 No free full text.

This publication has no abstract.

Garbe C, Hauschild A, Volkenandt M, Schadendorf D, Stolz W, Reinhold U, Kortmann RD, Kettelhack C, Frerich B, Keilholz U, Dummer R, Sebastian G, Tilgen W, Schuler G, Mackensen A, Kaufmann R. · University Department of Dermatology, Tübingen, Germany. · Melanoma Res. · Pubmed #17992123 No free full text.

Abstract: Melanoma is a malignant tumor that arises from melanocytic cells and primarily involves the skin. The most important exogenous etiological factor is exposure to ultraviolet irradiation. Diagnosis of melanoma is based primarily on its clinical features, and the A-B-C-D rule is useful in identifying pigmented lesions, which are suspicious for melanoma (Asymmetry, Border irregular, Color inhomogeneous and Diameter more than 5 mm). Dermoscopy is very helpful in clarifying the differential diagnosis of pigmented lesions. 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 about 75-85%. The most important prognostic factors for primary melanoma without metastases are vertical tumor thickness (Breslow depth) as measured on the histological specimen, presence of histopathologically recognized ulceration, invasion level (Clark level) and identification of micrometastases in the regional lymph nodes via sentinel lymph node biopsy. The current tumor node metastasis classification for the staging of primary melanoma is based on these factors. Melanomas can metastasize either by the lymphatic or by the hematogenous route. 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 intransit metastases in the skin between the site of the primary tumor and the first lymph node and as regional lymph node metastases. In the stage of regional metastasis, the differentiation between micrometastasis and macrometastasis and the number of lymph nodes involved are crucial. As soon as distant metastasis develops, prognosis depends on the site of the metastasis and on the lactate dehydrogenase levels in the blood. The frequency and extent of follow-up examinations is based on the initial tumor parameters. In thin primary melanomas up to 1-mm tumor thickness, clinical examinations at 6-month intervals are sufficient and in thicker primary melanomas, at 3-month intervals. Lymph node sonography as well as determination of the tumor marker protein S100beta are recommended. Additionally, in the stage of regional metastasis, whole body imaging should be performed every 6 months; in the stage of distant metastasis, surveillance has to be scheduled individually.

Sebastian G. · Klinik und Poliklinik für Dermatologie, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Dresden, Deutschland. · Hautarzt. · Pubmed #17569020 No free full text.

Abstract: The term "problem site" is based on a constellation of factors including the disease itself, the anatomic site, the resulting excision defect and choice of the most appropriate wound closure technique. Typical problem sites are the nose, eyelids, hands (fingers and nails) and the anogenital region, each of which is a functional-aesthetic entity. As dermatologic surgeons become even more experienced in plastic and reconstructive surgery, the term"problem sites" will be used less often.

Walther U, Kron M, Sander S, Sebastian G, Sander R, Peter RU, Meurer M, Krähn G, Kaskel P. · Department of Dermatology, Technical University of Dresden, Dresden, Germany. · Br J Dermatol. · Pubmed #15270887 No free full text.

Abstract: BACKGROUND: There are very few data regarding sun exposure behaviour of patients with basal cell carcinoma (BCC) in central Europe. OBJECTIVES: A case-control study of patients with sporadic BCC was conducted to assess the risk of occupational and leisure-time sun exposure behaviour, precursor lesions for skin cancer and phenotypic factors on the development of sporadic BCC in Ulm and Dresden, Germany. METHODS: A comparison was made of 213 patients with BCC (128 from Ulm, 85 from Dresden; 103 men and 110 women; median age at diagnosis 69 years) and 411 controls (237 from Ulm, 174 from Dresden; 197 men and 214 women; median age 58 years). Crude odds ratios (ORs) and corresponding 95% confidence intervals for all of 64 possible risk factors revealed strong associations in 33 items. Selection of important risk factors was performed in a multiple logistic regression. RESULTS: For sporadic BCC, an increased risk was shown for persons with actinic cheilitis (OR 7.1), actinic keratosis (OR 2.7) and solar lentigo (OR 2.5). The only phenotypic factor indicating risk of sporadic BCC was hair colour, with a higher risk for red/fair than brown/black hair (OR 4.3). There was an increased risk for persons with BCC in first-degree relatives (OR 5.1) and those with sunburn 20 years before sporadic BCC was diagnosed (OR 3.6). Additionally, occupational ultraviolet (UV) exposure appeared to be a risk factor (OR 2.4). In contrast, clinical actinic elastosis showed a protective effect (OR 0.1). CONCLUSIONS: In contrast to earlier reports, clinical actinic elastosis turned out to be the only protective factor for sporadic BCC. A special relationship between wrinkling and BCC risk could not be shown. For basic research, future work should be aimed at elucidating further the different forms of collagen repair processes after intermittent and/or chronic UV exposure. The data strongly support the recommendation that a change in recreational UV exposure habits in individuals, and sunburn avoidance in particular, are necessary not only because of the increased long-term risk of melanoma, but also because of the risk of other skin cancers such as sporadic BCC.

Kropp J, Stein A, Hackert I, Sebastian G, Meurer M, Grüning T, Liepe K, Pinkert J, Franke WG. · Department of Nuclear Medicine, University Hospital Carl Gustav Carus, Technical University Dresden, Deutschland. · Nuklearmedizin. · Pubmed #11475078 No free full text.

Abstract: AIM: For optimized logistics for the sentinel lymphadenectomy (SL) it might be helpful for the clinics involved if a longer time period between the lymphoscintigraphy (LS) and surgery is possible. Therefore, we investigated if a precise localization of the sentinel lymph node is possible 24 hours after LS. METHODS: 78 patients with primary malignant melanoma (MM; n = 44) or with MM pre-operated by excisional biopsy (n = 34) were investigated. In 40 cases the tumor was localized on the trunk and in 38 cases on the extremities. Mean MM thickness was 2.68 mm (range: 0.29 to 12 mm). In all patients a lymphoscintigraphy (LS) with an average of 85 MBq of Tc-99m nanocolloid was performed one day prior to surgery. Immediately after tracer application dynamic data acquisition was started at a LFOV gamma camera followed by a whole body scan. With a hand-held gamma detector (C-Trak) 2, 4, 6, 8, and 24 hours after tracer administration the SLN was identified and the counts registered. RESULTS: 94 SLNs were identified in 87 lymphatic basins from which 86 could be resected. Nine MM showed two draining channels. After 24 hours 15.5% (as an average) of the initial counts could be measured in the SLN. The uptake in the SLN in pre-operated versus patients with primary tumor was statistically not significant (p = 0.4). In 16 cases (20.5%) the SLN was tumor positive. Four of those patients developed distant metastases and two died within the first year. None of the patients with negative SLN developed distant metastases or died. CONCLUSION: The remaining activity in the SLN up to 24 hours after administration is sufficient for their intra operative localization. The method of lymphoscintigraphy and localization of the SLN by a hand-held gamma detector optimizes the intra operative identification of the SLN in patients with malignant melanoma.

Köhler U, Jacobi T, Sebastian G, Nagel M. · Klinik und Poliklinik für Dermatologie, Medizinischen Fakultät, Technischen Universtät Carl Gustav Carus, Dresden. · Chirurg. · Pubmed #11195075 No free full text.

Abstract: Metastasized malignant melanomas can affect all organs of the human body. However, isolated metastatic spreading into the gallbladder is rare. We treated two asymptomatic patients who had undergone primary curative resection of a melanoma. Gallbladder structures suggesting the presence of tumors were noticed in the follow-up investigations. The two patients underwent laparoscopic cholecystectomy to clarify their pathological relevance. Histologically, the tumor was a metastasis of the malignant melanoma in each case. Surgery is indicated in stage IV in isolated metastatic spreading to the gallbladder in order to avoid symptoms or tumor complications. Since the vast majority of melanoma metastases of the gallbladder are located intraluminally and lymphadenectomy in the region of the hepatoduodenal ligament does not appear to be appropriate, the operation should be carried out laparoscopically. The value of postadjuvant chemoimmunotherapy after metastasis resection is being investigated in numerous studies at present.