CORONADO, CALIF. Radiation therapy is underused as a treatment for malignant melanoma, Dr. Ray Lin said at a melanoma update sponsored by the Scripps Clinic.
"The reasons are traced back to in vitro studies which showed that melanomas are more radioresistant," explained Dr. Lin of the department of radiation oncology at the clinic in La Jolla, Calif.
Most studies actually show that malignant melanoma responds to high doses of radiation per fraction, but this approach raises concern about late effects of radiation toxicity.
"The more fractionated the treatments are, the lower the risk for late toxicity," he said. "For instance, delivering higher doses of radiation in fewer fractions for a tumor near the spinal cord could lead to late spinal cord injury. For skin cancers, late tissue injury usually involves the soft tissues, bones, and normal structures underneath the skin irradiated."
One recent study demonstrated that melanoma patients treated with conventional fractionation had similar rates of local control, compared with those who were treated with hypofractionation (Int. J. Radiat. Oncol. Biol. Phys. 2006;66:10515).
Results from this and other studies "really take out the concern for late toxicity," Dr. Lin said. "Approximately 17% of patients with locoregional disease and 51% of patients with metastatic disease will benefit from radiation therapy."
Current studies show a wide range of response to radiation therapy, sometimes with similar sensitivities to other epithelial cancers. Most melanomas "are easily seen and have a high chance of cure with surgical excision alone," he said. "Locally advanced melanomas have a propensity for local and distant recurrences with surgery alone, and local control is associated with longer survival."
One use of radiation therapy in melanoma includes treating lentigo maligna, particularly for large cancers on the face, which could be difficult to remove surgically. Radiation therapy is delivered for 3 weeks, and it takes 1824 months before most of the pigmentation resolves. Recurrences can be easily salvaged with surgery.
Radiation therapy may also be indicated after biopsy of primary melanoma for high-risk patients, including those with close or positive margins, rapid or multiple recurrences, extensive perineural invasion, and large primary tumors.
For patients with stage I-III melanoma, surgery alone without radiation therapy "is usually fine, because these patients have a higher risk of distant relapse," Dr. Lin said. "However, for these patients it's important to assess local failure risk, including margin status, head and neck site, thickness of 4 cm or greater, and history of recurrence or desmoplasia."
One trial of radiation therapy in 174 patients with head and neck melanoma found that the 5-year local regional control was 88%. The patients ranged in age from 16 to 89 years and they received a total of 30 Gy of hypofractionated radiotherapy delivered in five fractions over 2.5 weeks (Int. J. Radiat. Oncol. Biol. Phys. 1994;30:7958).
The 5-year survival rate correlated with lymph node status. Only 23% of patients who had more than three involved lymph nodes survived, while 39% of those who had one to three involved lymph nodes survived.
The 5-year survival rate also correlated with the thickness of the tumor. The rate of survival in patients with a tumor up to 1.5 mm thick was 100%, but it dropped to 72% for those with tumors 1.54 mm thick and 30% for those with tumors greater than 4 mm thick.
"Unfortunately, most patients with high-risk features have poor survival," Dr. Lin commented. "There is some controversy on whether there is a clear survival advantage with radiation therapy, but [it] should be considered for certain high-risk features," he suggested. These include melanoma patients with recurrent disease, large nodal size (3 cm or greater), multiple lymph node involvement, and extracapsular extension.
Radiation therapy also is offered to stage IV melanoma patients who have brain, bone, or skin metastases. It is used on brain metastases to prevent further growth, shrink tumors, and control neurologic defects, and on bone metastases to control pain and prevent pathologic fracture. "After several treatments, patients usually experience significant pain relief," he said.
Complete response in patients with primary malignant melanoma ranges from 14% to 57%.
Sequelae from skin irradiation "depend on size, dose, and fractionation scheme," Dr. Lin said. "Usually there's some pruritus, hair loss, and desquamation. Late reactions may include telangiectasia, hyperpigmentation, hypopigmentation, and local hair loss."
This patient with lentigo maligna is about to begin radiation therapy.
Three weeks after therapy, the treated area is back to normal coloration. Photos courtesy Dr. Ray Lin