National Cancer Institute®
Last Modified: May 1, 2002
UI - 11926952
AU - Lens MB; Dawes M; Goodacre T; Newton-Bishop JA
TI - Elective lymph node dissection in patients with melanoma: systematic review and meta-analysis of randomized controlled trials.
SO - Arch Surg 2002 Apr;137(4):458-61
AD - Centre for Evidence-Based Medicine, University of Oxford Nuffield Department of Clinical Medicine, the Oxford Radcliffe National Health Service Trust, Oxford OX3 9DU, England. firstname.lastname@example.org
HYPOTHESIS: Elective lymph node dissection does not improve survival in patients with melanoma without clinically detectable lymph node metastases. OBJECTIVE: To determine whether elective lymph node dissection in patients with melanoma without clinically detectable regional metastases decreases overall mortality. DESIGN: Systematic review and meta-analysis of randomized controlled trials comparing elective lymph node dissection with delayed lymphadenectomy at the time of clinical recurrence. SETTING: Randomized controlled trials available participants. INTERVENTION: Elective lymph node dissection compared with delayed lymphadenectomy or no lymphadenectomy in patients with melanoma without clinically detectable regional metastases. MAIN OUTCOME MEASURE: Overall mortality in treatment groups as compared with control groups at the end of a 5-year follow-up period. RESULTS: Three randomized controlled trials met the inclusion criteria. The pooled odds ratio for overall mortality for the 3 trials was 0.86 (95% confidence interval, 0.68-1.09). Results are statistically nonsignificant, but they have potential clinical significance. CONCLUSIONS: This systematic review of randomized controlled trials comparing elective lymph node dissection with surgery delayed until the time of clinical recurrence shows no significant overall survival benefit for patients undergoing elective lymph node dissection. Trials included in this review, however, contain significant bias. The question is not answered for all patients, and the results do not exclude the possibility that some subgroups may benefit from elective lymph node dissection. Further research is required.
UI - 11927189
AU - Capuron L; Gumnick JF; Musselman DL; Lawson DH; Reemsnyder A; Nemeroff
TI - CB; Miller AH Neurobehavioral effects of interferon-alpha in cancer patients: phenomenology and paroxetine responsiveness of symptom dimensions.
SO - Neuropsychopharmacology 2002 May;26(5):643-52
AD - Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1639 Pierce Drive, Atlanta, GA 30322, USA.
We have previously shown that the risk of major depression in patients with malignant melanoma undergoing interferon-alpha (IFN-alpha) therapy can be reduced by pretreatment with the antidepressant, paroxetine. Using dimensional analyses, the present study assessed the expression and treatment responsiveness of specific clusters of neuropsychiatric symptoms over the first three months of IFN-alpha therapy. Forty patients with malignant melanoma eligible for IFN-alpha treatment were randomly assigned to receive either paroxetine or placebo in a double-blind design. Neuropsychiatric assessments were conducted at regular intervals during the first twelve weeks of IFN-alpha therapy and included the 21-item Hamilton Depression Rating Scale, the 14-item Hamilton Anxiety Rating Scale and the Neurotoxicity Rating Scale. Neurovegetative and somatic symptoms including anorexia, fatigue and pain appeared within two weeks of IFN-alpha therapy in a large proportion of patients. In contrast, symptoms of depressed mood, anxiety and cognitive dysfunction appeared later during IFN-alpha treatment and more specifically in patients who met DSM-IV criteria for major depression. Symptoms of depression, anxiety, cognitive dysfunction and pain were more responsive, whereas symptoms of fatigue and anorexia were less responsive, to paroxetine treatment. These data demonstrate distinct phenomenology and treatment responsiveness of symptom dimensions induced by IFN-alpha, and suggest that different mechanisms mediate the various behavioral manifestations of cytokine-induced "sickness behavior."
UI - 11858976
AU - Eggermont AM; Keilholz U; Autier P; Ruiter DJ; Lehmann F; Lienard D;
TI - EORTC Melanoma Group The EORTC Melanoma Group: a comprehensive melanoma research programme by clinicians and scientists. European Organisation for Research and Treatment of Cancer.
SO - Eur J Cancer 2002 Mar;38 Suppl 4():S114-9
AD - Department of Surgical Oncology, Erasmus University Medical Center-Den Hoed Cancer Center, Rotterdam, The Netherlands. email@example.com
The EORTC Melanoma Group (MG) was founded in 1969 by both clinicians and scientists from various disciplines and fields of research with a common interest in malignant melanoma. This collaborative approach has always been the foundation of the groups strength. With an interest in tumour biology and especially the immunological aspects of the disease, the group has always pursued a scientific approach to treatment development in malignant melanoma. Over the years, the group has performed many clinical trials, epidemiological studies, histopathological studies defining standards and guidelines, translational research regarding prognostic factors and various metastatic and immunological aspects of melanoma, and developed quality assurance programmes for immunological and molecular biological assays in laboratory networks. At present, the EORTC MG runs the worldwide largest clinical trial programme in stages II, III and IV melanoma involving some 140 cancer centres in and outside Europe. Each trial is associated with the appropriate translational research programmes.
UI - 11955740
AU - Yu C; Chen JC; Apuzzo ML; O'Day S; Giannotta SL; Weber JS; Petrovich Z
TI - Metastatic melanoma to the brain: prognostic factors after gamma knife radiosurgery.
SO - Int J Radiat Oncol Biol Phys 2002 Apr 1;52(5):1277-87
AD - Department of Radiation Oncology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA. firstname.lastname@example.org
PURPOSE: To identify important prognostic factors predictive of survival and tumor control in patients with metastatic melanoma to the brain who underwent gamma knife radiosurgery. METHODS AND MATERIALS: A total of 122 consecutive patients with 332 intracranial melanoma metastases underwent gamma knife radiosurgery over a 5-year period. Of these, 39 (32%) also received whole-brain irradiation (WBI). The median tumor volume was 0.8 cm(3) (range: 0.02-30.20 cm(3)), and the median prescribed dose was 20 Gy (range: 14-24 Gy). Median follow-up was 6.8 months. Univariate and multivariate analyses of survival and freedom from progression were performed using the following parameters: status of systemic disease, intracranial tumor volume, number of lesions, tumor location, Karnofsky performance status, gender, age, and WBI. RESULTS: Overall median survival was 7.0 months from time of radiosurgery and 9.1 months from the onset of brain metastasis. In multivariate analysis, improved survival was noted in patients with total intracranial tumor volume <3 cm(3) (p = 0.003) and inactive systemic disease (p = 0.0065), whereas other parameters studied were of lesser importance (tumor location, p = 0.056, and Karnofsky performance status, p = 0.086), or of no significance (number of lesions, WBI, age, and gender). Freedom from subsequent brain metastasis depended on intracranial tumor volume (p = 0.0018) and status of systemic disease (p = 0.034). CONCLUSIONS: Stereotactic radiosurgery is an effective treatment modality for patients with intracranial metastatic melanoma. Tumor volume and status of systemic disease are good independent predictors of survival and freedom from tumor progression.
UI - 11902552
AU - Fife K; Thompson J F
TI - Lymph-node metastases in patients with melanoma: what is the optimum management?
SO - Lancet Oncol 2001 Oct;2(10):614-21
AD - Addenbrooke's Hospital, Cambridge, UK.
Lymph-node metastasis is an indicator of poor prognosis for patients with melanoma. The management of regional nodes is controversial, with continuing debate about whether surgery or radiotherapy of positive lymph nodes improves long-term survival or whether nodal involvement is merely a marker of aggressive disease. However, there is general agreement that systemic chemotherapy is rarely an effective form of management. This review therefore considers surgical and radiotherapeutic aspects of lymph-node management in patients with melanoma. We discuss regional control and survival after lymph-node surgery in retrospective series, randomised trials of elective lymph-node dissection, the role of 'sentinel' lymph-node biopsy, radiobiology and radiotherapy fractionation issues in melanoma treatment, retrospective studies of adjuvant nodal radiotherapy, and finally, randomised trials of adjuvant radiotherapy after lymph-node dissection.
UI - 11310650
AU - Goldstein BG; Goldstein AO
TI - Diagnosis and management of malignant melanoma.
SO - Am Fam Physician 2001 Apr 1;63(7):1359-68, 1374
AD - University of North Carolina at Chapel Hill School of Medicine, USA.
The incidence of malignant melanoma has increased in recent years more than that of any other cancer in the United States. About one in 70 people will develop melanoma during their lifetime. Family physicians should be aware that a patient with a changing mole, an atypical mole or multiple nevi is at considerable risk for developing melanoma. Any mole that is suggestive of melanoma requires an excisional biopsy, primarily because prognosis and treatment are based on tumor thickness. Staging is based on tumor thickness (Breslow's measurement) and histologic level of invasion (Clark level). The current recommendations for excisional removal of confirmed melanomas include 1-cm margins for lesions measuring 1.0 mm or less in thickness and 2-cm margins for lesions from 1.0 mm to 4.0 mm in thickness or Clark's level IV of any thickness. No evidence currently shows that wider margins improve survival in patients with lesions more than 4.0 mm thick. Clinically positive nodes are typically managed by completely removing lymph nodes in the area. Elective lymph node dissection is recommended only for patients who are younger than 60 years with lesions between 1.5 mm and 4.0 mm in thickness. In the Eastern Cooperative Oncology Group Trial, interferon alfa-2b was shown to improve disease-free and overall survival, but in many other trials it has not been shown to be effective at prolonging overall survival. Vaccine therapy is currently being used to stimulate the immune system of melanoma patients with metastatic disease.
UI - 11486853
AU - Innet LM; Haripershad V; Van Den Berg J; Cooper L
TI - Circuit and protocol for hypoxic hyperthermic isolated limb perfusion to treat malignant melanoma.
SO - Perfusion 2001 Jul;16(4):325-30
AD - Department of Cardiothoracic Surgery-Perfusion, Waikato Hospital, Hamilton, New Zealand. email@example.com
In the treatment of cancer, isolated limb perfusion (ILP) allows what would be a lethal systemic dose of cytotoxic drugs to be administered directly to a tumour site of an extremity. Unfortunately, ILP is a complex, expensive, time-consuming treatment that requires general anaesthesia, vascular surgery and expertise with extracorporeal circuits that may not be available outside a cardiac centre. By streamlining the traditional ILP protocols and eliminating the oxygenator from the circuit, an equally safe and effective technique of hypoxic hyperthermic isolated limb perfusion has been developed.
UI - 11801787
AU - LeBoit PE
TI - Nevus, redux.
SO - Am J Dermatopathol 2001 Oct;23(5):491-3
AD - Department of Pathology, University of California, San Francisco, California 94115, USA. firstname.lastname@example.org
UI - 11928800
AU - Spanknebel K; Temple L; Hiotis S; Yeh A; Coit DG
TI - Randomized clinical trials in melanoma.
SO - Surg Oncol Clin N Am 2002 Jan;11(1):23-52, viii
AD - Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. email@example.com
Efforts to improve the survival of patients with metastatic melanoma have led to 67 prospective randomized clinical trials investigating the use of agents comprising three main areas of therapy: systemic chemotherapy-based regimens, immunotherapy, and vaccine therapy
UI - 11959101
AU - Raisova M; Goltz G; Bektas M; Bielawska A; Riebeling C; Hossini AM;
TI - Eberle J; Hannun YA; Orfanos CE; Geilen CC Bcl-2 overexpression prevents apoptosis induced by ceramidase inhibitors in malignant melanoma and HaCaT keratinocytes.
SO - FEBS Lett 2002 Apr 10;516(1-3):47-52
AD - Department of Dermatology, University Medical Center Benjamin Franklin, The Free University of Berlin, 14195, Berlin, Germany.
We examined the biological effects of the ceramide analogues (1S,2R)-2-N-myristoylamino-1-phenyl-1-propanol (D-e-MAPP) and (1R,2R)-2-N-myristoylamino-1-(4-nitrophenyl)-1,3-propandiol (D-NMAPPD) on human HaCaT keratinocytes and human melanoma cells. We could demonstrate that D-e-MAPP and D-NMAPPD are able to suppress acid ceramidase activity. The elevation of the endogenous level of ceramide is followed by induction of apoptosis and suppression of proliferation in HaCaT keratinocytes. Moreover, we recently identified a group of human melanoma cell populations which are heterogeneously susceptible to C2-ceramide-mediated apoptosis. Studies with these melanoma cells revealed correlation between ceramide-mediated apoptosis and D-NMAPPD-induced apoptosis, confirming the effect of this inhibitor on ceramide signaling in human melanoma cells. These findings suggest ceramidase inhibitors as a potential new therapeutical class of antiproliferative and cytostatic drugs.
UI - 11977016
AU - Lewis CW Jr; Harpole D
TI - Pulmonary metastasectomy for metastatic malignant melanoma.
SO - Semin Thorac Cardiovasc Surg 2002 Jan;14(1):45-8
AD - Duke University Medical Center, Durham, NC 27710, USA.
Melanoma is the most deadly of skin cancers, and metastatic disease most commonly first appears in the lungs. Because most patients with early metastatic pulmonary disease are asymptomatic, routine screening with chest radiographs is the most cost-effective method of discovery. The therapy for pulmonary metastatic melanoma has drastically changed over the years. Even today there is no curative immunotherapy or chemotherapy available. The long-term overall survival for these patients is still very poor, but early detection and surgery offers the only hope for control in a small number of patients. Copyright 2002, Elsevier Science (USA). All rights reserved.
UI - 11920589
AU - Jager E; Hohn H; Necker A; Forster R; Karbach J; Freitag K; Neukirch C;
TI - Castelli C; Salter RD; Knuth A; Maeurer MJ Peptide-specific CD8+ T-cell evolution in vivo: response to peptide vaccination with Melan-A/MART-1.
SO - Int J Cancer 2002 Mar 20;98(3):376-88
AD - Medizinische Klinik II, Hamatologie-Onkologie, Krankenhaus Nordwest, Frankfurt, Germany.
Monitoring of CD8+ T-cell responses in cancer patients during peptide vaccination is essential to provide useful surrogate markers and to demonstrate vaccine efficacy. We have longitudinally followed CD8+ T-cell responses in 3 melanoma patients who were immunized with peptides derived from Melan-A/MART-1. Recombinant HLA-A2 tetramers loaded with the naturally presented Melan-A/MART-1 nonamer peptide (AAGIGILTV) and the Melan-A/MART-1 analog (ELAGIGILTV) were used in combination with phenotypical analysis for different T-cell subsets including naive T cells, effector T cells, "true memory" T cells and "memory effector" T cells, based on CD45RA/RO and CCR7-expression. At least in a single patient, T cells binding to the AAGIGILTV epitope were detected in naive, precursor (CD45RA+/CCR7+) CD8+ T cells, and CD8+ T cells binding to the analog ELAGIGILTV peptide were identified in the terminally differentiated (CD45RA+/CCR7-) T-cell subset. Molecular and functional analysis of tetramer-binding T cells revealed that the T-cell receptor (TCR) repertoire was oligo/polyclonal in AAGIGILTV-reactive T cells, but different and restricted to a few TCR clonotypes in ELAGIGILTV-reactive T cells prior to vaccination. The TCR repertoire reactive with Melan-A/MART-1 peptide epitopes was broadened during vaccination and exhibited a different profile of cytokine release after specific stimulation: tetramer-binding T cells from 2/3 patients secreted granulocyte/macrophage colony-stimulating factor (GM-CSF) and interferon-gamma but not interleukin-2 (IL-2) in response to Melan-A/MART-1 peptides. In the third patient, tetramer-binding T cells secreted IL-2 exclusively. Our results show that T-cell responses to peptide vaccination consist of different T-cell subsets associated with different effector functions. Complementary analysis for TCR CDR3 and cytokine profiles may be useful to define the most effective CD8+ T-cell population induced by peptide vaccination. Copyright 2002 Wiley-Liss, Inc.
UI - 11928697
AU - Schadendorf D
TI - Is there a standard for the palliative treatment of melanoma?
SO - Onkologie 2002 Feb;25(1):74-6
AD - Skin Cancer Unit of the German Cancer Research Center at the Department of Dermatology, University Hospital Mannheim. firstname.lastname@example.org
UI - 11896440
AU - Carsana M; Tragni G; Nicolini G; Bersani I; Parmiani G; Anichini A; Sun
TI - YS; Moller P; Schadendorf D; Sensi ML Comparative assessment of TCRBV diversity in T lymphocytes present in blood, metastatic lesions, and DTH sites of two melanoma patients vaccinated with an IL-7 gene-modified autologous tumor cell vaccine.
SO - Cancer Gene Ther 2002 Mar;9(3):243-53
AD - Human Tumor Immunobiology Unit, Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
A phase I clinical trial using autologous, IL-7 gene-modified tumor cells in patients with disseminated melanoma has been recently completed. Although no major clinical responses were observed, increased antitumor cytotoxicity was measured in postvaccine peripheral blood lymphocytes in a subset of treated patients. To analyze the in situ immune response, the T cell receptor beta-chain variable region (BV) repertoire of T cells infiltrating postvaccine lesions was studied in two patients, and compared with that of T cells present in prevaccine ones, in peripheral blood lymphocytes, and, in one patient, in delayed type hypersensitivity (DTH) sites of autologous melanoma inoculum. A relative expansion of T cells expressing few BVs was observed in all postvaccine metastases, and their intratumoral presence was confirmed by immunohistochemistry. Length pattern analysis of the complementarity determining region 3 (CDR3) indicated that the repertoire of T cells expressing some of these BVs was heterogeneous. At difference, CDR3, beta-chain joining region usage, and sequence analysis enabled us to demonstrate, within a T-cell subpopulation commonly expanded at DTH sites and at the postvaccine lesion of patient 1, that both DTH sites contained identical dominant T-cell clonotypes. One of them was also expressed at increased relative frequency in the postvaccine lesion compared to prevaccine specimens. These results provide evidence for immunological changes, including in situ clonally expanded T cells, in metastases of patients vaccinated with IL-7 gene-transduced cells.
UI - 11935312
AU - Margolin K; Atkins B; Thompson A; Ernstoff S; Weber J; Flaherty L; Clark
TI - I; Weiss G; Sosman J; II Smith W; Dutcher P; Gollob J; Longmate J; Johnson D Temozolomide and whole brain irradiation in melanoma metastatic to the brain: a phase II trial of the Cytokine Working Group.
SO - J Cancer Res Clin Oncol 2002 Apr;128(4):214-8
AD - Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, 1500 E. Duarte Rd., Duarte, CA 91010, USA. email@example.com
PURPOSE: To evaluate the antitumor effects and toxicities of whole brain irradiation (WBI) with temozolomide (TMZ) administered by prolonged oral dosing in patients with melanoma metastatic to the brain. BACKGROUND: Patients with melanoma metastatic to the central nervous system (CNS) have an extremely poor prognosis and appear to benefit little from WBI. TMZ is an alkylating agent chemically similar to dacarbazine (DTIC) with good oral bioavailability and CNS penetration. TMZ has broad preclinical antitumor activity which in melanoma is comparable to that of DTIC. The combination of TMZ and WBI may provide enhanced antitumor activity against CNS metastasis from melanoma. PATIENTS AND METHODS: Patients with measurable CNS metastases with or without systemic disease were treated with WBI, 30 Gray over ten fractions (days 1-5 and 8-12). TMZ, 75 mg small middle dotm(2 small middle dot)day, was started on day 1, continued daily for 6 weeks and repeated every 10 weeks. RESULTS: Thirty-one patients were treated. There was one CNS complete response of 4.5 months and two CNS partial responses of 2 months and 7 months duration; the latter patient also had a 4-month complete remission of systemic metastases. Toxicities were limited to a single episode of grade 3 transaminase elevation and two episodes of grade 3 neutropenia, one complicated by fatal sepsis. The median progression-free interval for both CNS and extracranial sites was 2 months (range 1 week-11 months), and median survival 6 months (range 2-12 months). CONCLUSIONS: WBI has lower than expected activity in CNS metastasis of malignant melanoma. Although TMZ can be safely administered with WBI, the combination has limited anti-tumor activity.
UI - 11905765
AU - Wolchok J D; Livingston P O
TI - Vaccines for melanoma: translating basic immunology into new therapies.
SO - Lancet Oncol 2001 Apr;2(4):205-11
AD - Clinical Immunology Service, Hematologic Department of Medicine, Memorial Sloan-Kettering Cancer Center, NY 10021, USA.
Advances in molecular biology and immunology in the past 10-15 years have allowed for a greater understanding of the molecules present on melanoma cells that are recognised by the immune system. The rising incidence of melanoma, combined with lack of efficacy of cytotoxic therapies, means there is a significant need for the development of effective immunotherapies. We discuss three types of vaccine for melanoma, which are currently in phase III clinical trials: allogeneic and autologous cellular vaccines, and carbohydrate vaccines. We also discuss several new areas of vaccine development, including DNA vaccines, dendritic-cell-based vaccines, peptide vaccines, and heat-shock protein vaccines. Although initial clinical trials have shown the safety and immunological efficacy of vaccines for melanoma, the true clinical benefit of these strategies will only be revealed in large randomised trials.
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