Oncologists are often reluctant to recommend radiotherapy (RT) to palliate metastatic melanoma due to a perception that this tumor is radioresistant. The Mayo Clinic experience was analyzed to determine the efficacy of palliative RT. Eighty-four consecutive patients with 114 lesions that were not metastatic to the central nervous system (CNS) were evaluated for the response of the presenting symptom, the duration of response, and survival after RT. The median dose delivered was 30 grays (Gy) and the median biologic effective dose (BED) was 39.0 Gy₁₀. Performance status was not uniformly available for all patients.

RESULTS. Complete resolution of the presenting symptom occurred in 10 lesions (9%). Of the lesions treated, there was partial improvement in 86 (75%), no change in 12 (11%), and worsening in 6 (5%) lesions. The median survival was 3.8 months and freedom from disease progression (FFP) for individual lesions was 6 months. Patients treated with >30 Gy had significantly longer FFP compared with patients given 30 Gy (P = .01). In addition, patients treated with >30 Gy had a significantly longer survival than those given a lesser dose (median of 2 months vs 8 months; P < .0001). Similarly, patients receiving a BED >39.0 Gy₁₀ also were found to have longer FFP (P = .03) and survival (median of 2 months vs 8 months; P < .0001) compared with those receiving a BED 39.0 Gy₁₀. The dose per fraction, number of previous therapies, and location of the lesions did not appear to impact the effectiveness of RT.

CONCLUSIONS. RT was found to provide effective palliation of non-CNS metastasis from malignant melanoma and should be considered for symptomatic patients. RT doses >30 Gy and a BED >39.0 Gy₁₀ were found to be associated with longer palliation.

RT provided some degree of palliation in 84% of patients in the current study. This study is not the first to note good palliation in patients with metastatic melanoma. Seegenschmiedt reviewed their 20-year experience using RT for the palliation of melanoma and noted a 100% response rate (CR rate of 64% and PR rate of 46%) in 121 patients with metastases in all sites, including the CNS. Other authors have recorded more modest rates of palliation, ranging from 67% to 85%.The findings of the current analysis corroborate the results of these studies.

There is controversy regarding the importance of dose-related factors when treating patients with metastatic melanoma. The studies of Kirova  failed to find a correlation between dose and the rate of palliation in patients with metastatic melanoma. Conversely, Katz and Seegenschmiedt  both reported that the rate of palliation improved with RT doses 30 Gy and 40 Gy, respectively.

The Radiation Therapy Oncology Group (RTOG) conducted a prospective phase 3 randomized trial (83-05) to address the question of dose and, specifically, dose per fraction in patients with metastatic melanoma. A total of 137 patients were randomized to receive either a hypofractionated regimen of 32 Gy (8 Gy given in 4 fractions) or a more traditional fractionation regimen of 50 Gy (2.5 Gy given in 20 fractions). There was no significant difference noted between the 2 regimens. The rates of CR and PR were 23.8% and 34.9%, respectively. No response was noted in 36.5% of patients. FFP and survival were not addressed in the study.

In addition, Overgaard et al. reported on 35 tumors in 14 patients with metastatic or recurrent melanoma who were randomized to receive either 9 Gy given in 3 fractions or 5 Gy given in 8 fractions, delivered twice weekly. Complete and persistent regression was found in 24 of 35 tumors (69%) and PR was noted in 10 of the tumors. The overall response rate was 97%. No difference was observed between the 2 treatment regimens.

An important point is that the findings of the current study addressed a very different RT dose-related question than the studies previously described. Although the other studies correlated the dose and dose per fraction with the initial response rate, to our knowledge none of them addressed the durability of response as related to RT dose or BED. FFP is a direct measure of the durability of response and, in the current series, FFP was found to be improved in patients who received >30 Gy or a BED >39.0 Gy₁₀. The finding that survival was improved with RT dose and BED was unexpected and may be an artifact of the study design.

The retrospective nature of the current study makes it unable to address unrecognized or undocumented biases that may have influenced the association between dose and survival. For example, the performance status of each patient was not recorded in each patient chart before RT and therefore this variable could not be evaluated. It is possible that patients with a better performance status were given higher doses of RT than patients with a poor performance status. Despite the potential for biases in the current study, investigators have documented similar findings in controlled randomized trials that have found that the dose of palliative RT can influence patient survival. The proper dose for palliative lung RT has been studied extensively. One such study was the Dutch National Study conducted by Kramer which compared a dose of 16 Gy (8 Gy given in 2 fractions) with a dose of 30 Gy (3 Gy given in 10 fractions). In this randomized controlled trial, there was no difference noted with regard to symptom palliation between the regimens, but the 30-Gy regimen was found to be associated with a prolonged palliation (P < .001) and improved 1-year survival (P < .03). Bezjak et al. also reported similar findings in a phase 3 trial comparing 10-Gy, single-fraction RT with 20 Gy given in 5 fractions for the palliation of symptoms from lung cancer. Patients who received 5 fractions survived an average of 2 months longer (P = .0305) than patients who received 1 fraction.

Melanoma is widely believed to be a radioresistant tumor, a misconception that has historically led to the limited use of RT for its treatment. However, as we and others have shown, RT provides effective palliation in patients with metastatic malignant melanoma. Doses >30 Gy (or a BED >39.0 Gy₁₀) were found to be associated with prolonged palliation and is the notable finding of the current study. These findings should be viewed with caution because the lack of data regarding performance status as well as other unknown confounding factors limit the applicability of this retrospective study. Common RT regimens for palliation include 8 Gy given in a single fraction or 30 Gy given in 10 fractions. Neither of these regimens would have as durable a response as a higher dose regimen based on this retrospective study. The finding of prolonged survival with increased dose is possibly an artifact of the retrospective study design, and should be confirmed with a prospective randomized trial. We recommend that higher doses of RT be considered when using RT for the palliation of patients with metastatic melanoma and a performance status that could tolerate such therapy. For patients with a longer expected survival, a dose of 37.5 Gy given in 15 fractions (2.5 Gy per fraction) may be a reasonable regimen that is sufficiently short and would deliver an effective BED (46.87 Gy₁₀).