Scalp In-Transit Metastatic Melanoma Treated with Interleukin-2 and Pulsed Dye Laser

No particular regimen is considered standard therapy for widespread metastatic melanoma, although surgery is the primary choice for regional nodal metastases. Systemic interleukin-2 (IL-2) is an effective immunotherapy for melanoma, but standard doses are associated with severe toxicity. We report a patient who was treated with intralesional low-dose IL-2 and V-beam pulsed dye laser for the treatment of scalp melanoma metastases. This treatment resulted in rapid regression of metastatic tumors with limited adverse effects.


Introduction
No particular regimen is considered standard therapy for widespread metastatic melanoma, and effectiveness of single-agent interventions has been questioned [1]. Here, we report a new approach with intralesional interleukin-2 (IL-2) and V-beam pulsed dye laser for the treatment of scalp melanoma metastases.

Case Report
The patient was a 61-year-old man. Twenty-two years ago, a primary melanoma was removed from his neck. Eleven years later, a second primary melanoma developed on his scalp, and was surgically excised. Seven years later, a third melanoma (superficial spreading type) developed on the scalp (Clark level III, Breslow thickness 0.9 mm, and mitotic rate 2/mm 2 ), and was treated with wide local excision OPEN ACCESS and sentinel lymph node biopsy. Two lymph nodes harvested were negative. Half a year later, multiple in-transit metastases appeared on his scalp without signs of distant metastases. The lesions were surgically excised. However, multiple in-transit metastases continued to develop in the region rapidly. Thereafter, surgical excision and topical imiquimod 5% were initiated resulting in complete resolution of one lesion, whereas two others persisted.
The patient was referred to our institution ( Figure 1A). The melanoma was genetically wild-type. Treatment began with systemic granulocyte-macrophage colony-stimulating factor (GMCSF) (250 mcg/day; alternating between 2 weeks of treatments and cessations), topical imiquimod 5% (twice/day), V-beam pulsed dye laser (every 2-4 weeks; 595 nm; 10-mm spot size), and periodic punch excisions from June through November 2010. Despite improvement, new lesions continued to develop. Intralesional IL-2 injections (6 million IUs, 2-3 times/week) were then added to the therapeutic regimen. Subsequently, within 1 month, all the tumors vanished ( Figure 1A) with pathological confirmation. No severe toxicity was observed, and patient only had flu-like symptoms. Treatment was discontinued in December 2010. The patient remained clinically melanoma-free until July 2011, when a new solitary lesion appeared on vertex scalp. The 0.5 × 0.5-cm lesion was a freely mobile, subcutaneous nodule and was confirmed to be metastatic melanoma. IL-2 injections resumed with the previous protocol for a longer period, and complete response was achieved. By September 2011, biopsy showed no residual cancer in the area.

Results and Discussion
The management of recurrent melanoma remains challenging. This patient with prolonged but localized in-transit melanoma showed remarkably improved clinical outcome when intralesional IL-2 was added to the interventions. The synergistic effect of IL-2 with V-beam laser is supported by animal models that show enhanced antitumor immunity with judicious combination of immunologic stimulation and laser devitalization of tumor nodules [2]. The benefits of systemic IL-2 are offset by its toxicities, limiting its usage to selected patients with advanced metastatic melanoma. We demonstrated that intralesional administration of IL-2 in combination with V-beam laser achieved rapid regression of in-transit metastasis with limited adverse effects.
IL-2 induced vascular leakage is advantageous in localized treatment because local edema may initiate tumor necrosis that stimulates the immune response. Furthermore, intralesional injection of IL-2 achieves much higher local concentration and limits systemic adverse effects. Therefore a greater therapeutic effect could be expected. Indeed, studies indicated that intralesional IL-2 therapy was more effective than systemic, perilesional, and distant site IL-2 treatments [3]. One report showed that a complete local response was achieved in 69% of metastasized melanoma patients (33/48) by intratumorally injection of IL-2 [4].
Preferential absorption of laser radiance by hemoglobin and the subsequent conversion of light energy into thermal energy may cause blood vessel coagulation [5], which may enhance the local edematous and ischemic effect of IL-2. In addition, cancer cells are more vulnerable than normal cells to hyperthermia-induced cellular damage [6]. Considerable improvement in clinical outcome has been reported after hyperthermic therapy in tumors of many types, including melanoma [6]. Figure 1B summarizes the possible synergetic effect of intralesional IL-2 and V-beam therapy.