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High-Risk Melanoma: Radiation Shown to Offer Substantial Benefits

Laino, Charlene

doi: 10.1097/01.COT.0000365652.58986.75

CHICAGO—With results repeatedly referred to as practice-changing by experts here at the American Society for Radiation Oncology Annual Meeting, researchers reported that radiation of the lymph nodes of high-risk melanoma patients significantly reduces the risk that cancer will recur in those nodes.

“This is the first real advance in the management of melanoma in 15 years—since interferon came out,” said lead investigator Bryan H. Burmeister, MD, Associate Professor of Radiation Oncology at Princess Alexandra Hospital in Brisbane, Australia.

“Results of this trial confirm the place of radiation therapy in the management of patients who have high-risk features following surgery for melanoma involving the lymph nodes. It's important that clinicians discuss and offer” metastatic melanoma patients with nodal involvement the option of radiation after surgery if they are at high risk for local recurrence.

“Adding radiation to the treatment of high-risk melanoma patients is a viable option,” he said, adding that 80% of patients who have lymph node dissection are at high risk of recurrence.

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Radiation Currently Not Routine

Speaking at the plenary session here, Dr. Burmeister explained that some institutions routinely offer radiation therapy to melanoma patients with nodal involvement, while others do not.



“In some institutions, radiation treatment is routine protocol, while in others, the protocol has been either for patients to just be observed, or to receive some type of adjuvant chemotherapy or immunotherapy.”

The new Phase II study was designed to determine the value of adjuvant radiotherapy in patients at significant risk of lymph node relapse or recurrence. Included were 209 patients at 16 centers in Australia, New Zealand, Brazil, and the Netherlands.

To be eligible, patients had to have completely resected palpable, nodal metastatic melanoma; no previous or concurrent local, in transit or distant metastatic relapse; and be at significant risk for lymph node field relapse.

Patients were considered to be at significant risk for lymph node field relapse if pathologists discovered:

  • At least one parotid lymph node, two neck or axilla nodes, or three positive lymph nodes;
  • A minimum metastatic node diameter of 3 cm in the neck or axilla or 4 cm in the groin.
  • Extranodal spread of tumor.

After lymphadenectomy, patients were randomized in a one-to-one fashion to receive external-beam radiotherapy at a dose of 48 Gy in 20 fractions over four weeks, or initial observation. The radiation treatment was given within 12 weeks of surgery.

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Radiation Groups Less Likely to Relapse

At a median follow-up of 27 months, 19% of patients treated with radiation after surgery experienced recurrence of melanoma in the lymph nodes, compared with 31% of patients who did not have radiation. The difference was statistically significant.

There was also a statistically significant improvement in lymph node field control with radiotherapy, Dr. Burmeister reported.

The median overall survival time of the patients undergoing surgery alone was 47 months, compared with 31 months for patients who received surgery plus radiation. The difference did not reach statistical significance.

The early acute adverse effects of radiation were minimal, with radiation dermatitis being the most common Grade 3 event at two weeks, he said. No patients experienced Grade 4 toxicities at two or six weeks, Dr. Burmeister added.

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Practice-Changing Findings

Study discussant Matthew T. Ballo, MD, a radiation oncologist at the University of Texas M. D. Anderson Cancer Center, said the use of radiation following lymphadenectomy “may be the new standard of care” for melanoma patients with lymph node involvement.

It provided “dramatic improvement in local control,” he told the audience.

While Dr. Ballo said that the lack of an overall survival benefit in the radiation arm “cannot be ignored,” he said that the strict eligibility criteria may explain why patients in the radiation arm did not live significantly longer than those in the observation arm.

“The disease burden may have been too high,” he said.

“This is a practice-changing study,” agreed Benjamin Movsas, MD, Chairman of the Department of Radiation Oncology at Henry Ford Hospital.

“Our goal as radiation oncologists is to prevent local recurrence of cancer, and this is what radiation in high-risk melanoma cases appears to do. Whether to radiate these lymph nodes had been an ongoing controversy…and now there are some objective data that this benefits patients.”

Outgoing ASTRO president Tim R. Williams, MD, a private practitioner at Boca Raton Community Hospital, echoed his colleagues’ statements, telling a news conference that the findings will change how he treats patients with melanoma.

“The use of interferon has been a big issue. It can help, but it is very toxic. Now we can know we can reduce recurrences in the lymph nodes if we radiate. This is the first good thing I'll be able to tell my melanoma patients in a long, long time,” he said.

© 2009 Lippincott Williams & Wilkins, Inc.
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