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UCLA researchers increase survival among melanoma patients

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Los Angeles, with its Sunbelt location, offers many advantages; however, a disadvantage of our sunny clime is an increased risk of skin cancer, including deadly melanomas. On February 13, UCLA researchers published a study in The New England Journal of Medicine that reported on their progress regarding reducing the spread (metastasis) of melanomas.

A long-term research project was begun in 2001 by researchers at UCLA’s Jonsson Comprehensive Cancer Center. The study involved lymphatic mapping and sentinel-node biopsy, techniques that could detect the early metastasis of melanoma; to evaluate the success of the project, the subjects underwent 10 years of follow-up. (A sentinel node is a lymph node that is likely to contain cancerous cells at an early stage of metastasis.) They found that, compared to the traditional “watchful waiting” approach, their treatment protocol significantly increased the patients’ disease-free and melanoma-specific survival. The study authors noted that their findings offer a new standard for detecting melanoma metastasis to the lymph nodes because it allows physicians to quickly determine which patients actually have metastasis (approximately 20% in the study group). Thus, these patients may benefit from having their non-sentinel lymph nodes removed, while avoiding the surgery and its possible complications, as well as significant cost, for the many patients who probably will not benefit from surgery (approximately 80% of patients).

One of the significant findings of the study was that the thickness of the initial melanoma tumor correlated to the effectiveness of these treatments in managing metastases to lymph nodes and other areas. If patients with primary melanoma tumors of intermediate thickness (1.20 to 3.5 millimeters thick) undergo sentinel-node biopsies and then have immediate complete removal of the lymph nodes if the sentinel node contained cancer cells, they had an overall disease-free survival of 71.3% compared with 64.7% for those whose nodes were observed without sentinel biopsy. In addition, the investigators found that this group with cancer cells in their sentinel nodes had prolonged distant disease-free survival (survival without disease spread to distant organs such as the brain, lungs, or liver) and melanoma-specific survival (survival without development of additional metastases).

At their initial diagnosis, approximately 20% of melanoma patients have disease spread to nearby (regional) lymph nodes. Traditional treatment for these patients was surgical removal of the primary tumor and a rim of surrounding normal tissue; subsequently, the patients underwent a period of lymph node observation. If signs of cancer spread to the lymph nodes was found, the nodes were surgically removed. This spared 80% of the patients from unnecessary surgery; however, it was possibly too late to prevent the spread of the cancer in the 20% who had metastasis. An alternative treatment was to remove all patients’ lymph nodes, with the rationale that every patient was potentially at risk of metastasis.

Study leader Dr. Donald L. Morton and colleagues searched for and eventually perfected a method to specifically identify the 20% of patients whose tumors had already spread to the lymph nodes. Before cancer cells spread to the lymph nodes, they travel through the lymphatic system, first entering the lymph node most directly connected to the tumor (the sentinel lymph node). A combination of blue dye and radioactive tracer is injected into the tissues surrounding the primary tumor; this locates the lymphatic channels that lead to the first tumor-draining lymph node. The mixture follows the same lymphatic path used by the melanoma cells to spread to the sentinel node. The sentinel node is removed and microscopically evaluated in detail; the process allows detection of even a single melanoma cell. If tumor cells are not found in the sentinel node it is extremely unlikely that tumor will be present in other non-sentinel nodes; thus, further nodal surgery is deemed unnecessary. If cancer cells are present in the sentinel node, all the other lymph nodes in the nodal group are immediately removed.

The study authors note that their results confirm that for patients with intermediate thickness melanomas, early sentinel node biopsy reduces the risk of cancer recurring in the lymph nodes, and decreases the patients’ risk of dying from the disease. Some patients with thick primary tumors benefit from having their lymph nodes removed; however, the study findings suggest that the timing of the intervention is not as crucial for them as it is for patients with intermediate thickness primary tumors. The study group did not contain enough patients with thin melanomas to allow conclusions regarding their benefit from the technique. The researchers note that this group of patients will be a focus of a future study.

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