Skin Cancer & Melanoma

In their article on radiotherapy forcutaneous malignant melanoma,Drs. Ballo and Ang discuss fourkey points, which we will addressbelow.

The article by Bisseck and colleagueshighlights an importantissue encountered increasinglyby physicians-melanoma in childrenand adolescents. The incidence andmortality of melanoma continues torise.[1] It is now the fifth most commoncancer in men and the seventhmost common cancer in women. Inour practice at the Johns HopkinsMelanoma Center, we have treated agrowing number of children and adolescentswith melanoma, includingmany with stage III disease identifiedby sentinel node technology, similarto that described by Bisseck andcolleagues.

The surgical management of cutaneousmelanoma remainscontroversial in part becausethere is no consensus regarding themargins of excision for the primarytumor or the therapeutic benefit ofremoving clinically normal appearingregional lymph nodes (electivelymph node dissection).[1] Intraoperativelymphatic mapping with sentinellymph node dissection hasrevolutionized the management of regionallymph nodes by allowing thesurgeon to perform a minimally invasiveprocedure instead of electivelymph node dissection, and by allowingthe pathologist to focus on one ortwo lymph nodes rather than all thenodes in a complete lymph node dissectionspecimen.[2]

The presence or absence oflymph node metastases is themost significant prognostic factorfor survival and recurrence in malignantmelanoma. Lymph node diseasedecreases the 5-year survival by 40%to 50%. The number of metastatic nodesand whether nodal metastases are clinicallyoccult or apparent are independentpredictors of survival.[1]

Head and neck melanoma is a rare and aggressive childhoodmalignancy. Surgery remains the primary treatment, with lymphaticinvolvement determined by neck dissection. In the adult population,sentinel lymph node biopsy has emerged as a less morbid yet accuratemethod of staging regional lymph nodes. This innovative technique canalso be used in the pediatric population.

NEW YORK-An antisense oligonucleotide directed against Bcl-2 is yielding "remarkable" responses in specific melanoma patients enrolled in a phase III trial, according to Anna C. Pavlick, DO, assistant professor of medicine, New York University School of Medicine.

NEW YORK-Antigenics Inc. announced positive final results from a phase II study of the company’s personalized heat shock protein cancer vaccine Oncophage (HSPPC-96) in patients with metastatic melanoma. The study included 39 evaluable patients with stage IV melanoma who underwent surgery to remove tumor tissue, which was used to produce their personalized Oncophage vaccine.

KING OF PRUSSIA, Pennsylvania-Protarga, Inc. has received comments from the FDA that allow it to proceed with two separate phase III clinical studies of its new cancer drug Taxoprexin Injection (DHA-pacli-taxel) for the treatment of metastatic melanoma and pancreatic cancer. Taxoprexin is made by linking the fatty acid docosahexaenoic acid (DHA) to paclitaxel, the company said in a news release.

Despite significant advances in the treatment of a variety of malignancies, highly effective therapies for most patients with metastatic renal cell carcinoma or metastatic melanoma are rare. Traditional oncologic treatment methods, such as

Interleukin-2 (IL-2, Proleukin) is one of the most effective agents in the treatment of metastatic renal cell carcinoma and metastatic melanoma. High-dose IL-2 therapy produces overall response rates of 15% to 20%;

Although high-dose interleukin-2 (IL-2, Proleukin), a highly toxic agent used in the treatment of renal cell carcinoma and melanoma, was initially associated with treatment-related mortality, it can, in the appropriate

NEW ORLEANS-Because of their malignant potential and their cosmetic appearance, congenital nevi elicit much concern from parents. Ashfaq A. Marghoob, MD, assistant professor of dermatology and director of the Pigmented Lesion Group, Memorial Sloan-Kettering Cancer Center, presented new insights into this disorder at a symposium on melanoma held during the American Academy of Dermatology annual meeting.

Flavopiridol [2-(2-chlorophenyl 5 ,7-dihydroxy-8-[cis-(3-hydroxy-1-methyl-4-piperidinyl)-4H-1-benzopyran-4-one, hydrochloride] is a semisynthetic flavone with a novel structure compared with that of polyhydroxylated flavones, such as quercetin and genistein.[1] It is derived from rohitukine, an alkaloid isolated from the stem bark of Dysoxylum binectariferum, a plant indigenous to India.[2] Originally synthesized and supplied by Hoechst India Limited, flavopiridol is provided to the Division of Cancer Treatment and Diagnosis of the National Cancer Institute (NCI) by Aventis Pharmaceuticals, Inc.

Two of the most important predictors of relapse (and, therefore, survival) in patients with melanoma are the Breslow thickness of the primary melanoma and regional lymph node involvement. Patients with melanomas greater than 4 mm in thickness have approximately a 50% risk of recurrence, and those with lymph node involvement have a 50% to 85% risk of recurrence depending on the number of lymph nodes involved. Thus, a group of patients can be identified who are at high risk of death from melanoma and are, therefore, appropriate candidates for postsurgical adjuvant therapy.

Despite more than 2 decades of active clinical study, the use of interferon as adjuvant therapy for high-risk melanoma remains controversial. The controversy has centered on dose, schedule, and toxicity of treatment. Agarwala and Kirkwood superbly summarize the clinical studies to date and highlight many of the salient issues relevant to clinicians.

Melanoma is almost 100% curable when diagnosed early, but when metastatic to distant organs, it is associated with a poor survival. The interferons have shown the most promise in the treatment of melanoma and interferon

The authors are to be complimented on a thoughtful and complete review of the application of the sentinel node paradigm to colorectal cancer. This paradigm is inherently quite different for colorectal cancer because, except for the occasional demonstration of variant anatomy, the technique will not alter the extent of surgery as it has done in melanoma and breast cancer.

The role of sentinel lymph node identification has been investigated over the past decade in a variety of malignancies. It has become part of standard care for melanoma. Its role in breast cancer is evolving, but with the completion of two large randomized clinical trials, it will probably be added to the surgical armamentarium for the management of most breast cancers. Studies have been proposed or are under way to evaluate sentinel node mapping in head and neck cancer, penile and vulvar cancer, and gastrointestinal cancers.

BOSTON-Excessive sun exposure is a known risk factor for the development of skin cancer, but sun exposure appears to have a protective effect against a variety of other cancers, according to speakers at a symposium on sunlight at the 168th National Meeting of the American Association for the Advancement of Science (AAAS).

NEW YORK-In patients with metastatic cutaneous melanoma who have already failed or are refractory to standard treatment, Allovectin-7, a targeted gene therapy using a nonviral delivery system, can induce both local and systemic responses in tumors injected weekly, results of a multicenter phase II study suggest.

NEW YORK-A potential chemopreventive agent against melanoma stopped metastatic spread in some patients in a phase I clinical trial, according to a report presented at the Chemotherapy Foundation Symposium XIX (abstract 69). The agent,

In 2001, the American Joint Committee on Cancer Melanoma Staging Committee proposed and created a new staging system for melanoma. This new system will become official in 2002, with the publication of the sixth

Intraoperative lymphatic mapping and sentinel lymphadenectomy has become an increasingly popular technique for staging the regional lymph nodes in early-stage melanoma. This operative technique allows for detailed pathologic analysis of the first (or sentinel) lymph node in direct connection with the primary tumor, and provides a unique opportunity for assessing potential immunologic interactions between the primary tumor and regional lymph node basin. We performed lymphatic mapping and sentinel lymphadenectomy on 25 patients with early-stage melanoma and resected an additional nonsentinel node in each case. Sentinel and nonsentinel nodes were evaluated by routine pathologic analysis. A portion of each node was processed for expression of the dendritic markers of activation CD80, CD86, and CD40, and their corresponding T-cell receptors CTLA-4 and CD28. Of 25 patients undergoing lymphatic mapping and sentinel lymphadenectomy, 20 (80%) had matched sentinel and nonsentinel nodes. A total of 26 matched lymph node sets were obtained: three pairs from one patient and two from an additional two patients. Reverse transcription polymerase chain reaction analyses of corresponding sections of the sentinel and nonsentinel nodes demonstrated a marked reduction in semiquantitative expression of CD80 (77%), CD86 (77%), and CD40 (85%), as well as CTLA-4 (88%) and CD28 (85%) in sentinel as compared to nonsentinel nodes. The diminished expression of the dendritic cell markers appeared to be unrelated to the B-cell (CD20) and T-cell (CD2) expression. Lymphatic mapping and sentinel lymphadenectomy allows for detailed pathologic and molecular characterization of sentinel nodes. Our results suggest a quantitative reduction in dendritic cell markers in sentinel as compared to nonsentinel nodes, which may be important in the immunologic interaction between the primary site and regional lymph node basin and may also serve as useful criteria for identifying sentinel nodes. [ONCOLOGY 16(Suppl 1):27-31, 2002]

MIAMI BEACH-Heat shock protein peptide complex-96 (HSPPC-96, Oncophage), an individualized cancer vaccine, produced complete responses in two patients with metastatic melanoma and long-term stable disease in several others during an Italian phase I-II trial.

SAN DIEGO--The results of a series of five free annual skin cancer screenings has demonstrated that community education and early detection are valuable tools in addressing cancer prevention, said Rosemary Giuliano, ARNP, MSN. She is national clinical research coordinator in the Cutaneous Oncology Program’s Department of Surgery at the H. Lee Moffitt Cancer Center & Research Institute, University of South Florida, Tampa.

A study published in the Journal of the American Academy of Dermatology (44:807-813, 2001) reported an almost 90%

NEW YORK-Among men over age 50 with an additional melanoma risk factor, diagnostic yield of melanoma screening is 1 in 219, data from the American Academy of Dermatology (AAD) National Skin Cancer Screening Program show. That yield is high, suggesting the potential cost-effectiveness of this intervention, according to Barbara A. Gilchrest, MD, professor and chairman of dermatology, Boston University.

NEW YORK-A variety of simple dietary interventions could prove effective in inhibiting carcinogenesis and reducing the incidence of skin cancers, said James M. Spencer, MD, associate professor of dermatology, Mount Sinai School of Medicine, New York.

NEW YORK-Many persons who apply sunscreen before spending time outdoors are nevertheless increasing their risk of skin cancer by not applying sunscreen frequently enough to prevent sunburn, recent studies involving skiers at high altitudes suggest.

WASHINGTON-Node-negative patients with intermediate-to-thick melanomas who underwent node staging by sentinel lymph node (SLN) biopsy had a significant survival advantage over those staged by elective lymph node dissection (ELND) or clinical examination, said Sophie Dessureault, MD, of the University of South Florida H. Lee Moffitt Cancer Center, Tampa. She spoke on behalf of the AJCC (American Joint Committee on Cancer) Melanoma Staging Committee.