Healthcare 2013, 1(1), 96-99; doi:10.3390/healthcare1010096

Case Report
Scalp In-Transit Metastatic Melanoma Treated with Interleukin-2 and Pulsed Dye Laser
Michael Z. Wang and Jerry D. Brewer *
Department of Dermatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA; E-Mail: wang08380@gmail.com
*
Author to whom correspondence should be addressed; E-Mail: brewer.jerry@mayo.edu; Tel.: +1-507-284-3579; Fax: +1-507-284-2072.
Received: 20 August 2013; in revised form: 16 October 2013 / Accepted: 21 October 2013 /
Published: 25 October 2013

Abstract

: 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.
Keywords:
interleukin-2; melanoma; pulsed dye laser therapy

1. 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.

2. 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/mm2), and was treated with wide local excision 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.

Healthcare 01 00096 g001 200
Figure 1. (A1) In-transit metastasis of melanoma at presentation (referral to our institution); (A2) After initial treatment with pulsed dye laser; (A3) At the initiation of interleukin-2 injections, in conjunction with continued pulsed dye laser therapy; (A4) Four and a half weeks after the addition of interlesional interleukin-2; (B) Possible mechanisms of the synergetic effects of intralesional interleukin-2 (IL-2) and local laser therapy.

Click here to enlarge figure

Figure 1. (A1) In-transit metastasis of melanoma at presentation (referral to our institution); (A2) After initial treatment with pulsed dye laser; (A3) At the initiation of interleukin-2 injections, in conjunction with continued pulsed dye laser therapy; (A4) Four and a half weeks after the addition of interlesional interleukin-2; (B) Possible mechanisms of the synergetic effects of intralesional interleukin-2 (IL-2) and local laser therapy.
Healthcare 01 00096 g001 1024

3. 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.

4. Conclusions

Our results indicate that this combined therapy is a promising strategy for the treatment of in-transit metastatic melanoma. Further study in a larger patient population is warranted.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Garbe, C.; Eigentler, T.K.; Keilholz, U.; Hauschild, A.; Kirkwood, J.M. Systematic review of medical treatment in melanoma: Current status and future prospects. Oncologist 2011, 16, 5–24.
  2. Katz, K.A.; Jonasch, E.; Hodi, F.S.; Soiffer, R.; Kwitkiwski, K.; Sober, A.J.; Haluska, F.G. Melanoma of unknown primary: Experience at Massachusetts General Hospital and Dana-Farber Cancer Institute. Melanoma Res. 2005, 15, 77–82, doi:10.1097/00008390-200502000-00013.
  3. Jacobs, J.J.; Sparendam, D.; den Otter, W. Local interleukin 2 therapy is most effective against cancer when injected intratumourally. Cancer Immunol. Immunother. 2005, 54, 647–654, doi:10.1007/s00262-004-0627-4.
  4. Weide, B.; Derhovanessian, E.; Pflugfelder, A.; Eigentler, T.K.; Radny, P.; Zelba, H.; Pföhler, C.; Pawelec, G.; Garbe, C. High response rate after intratumoral treatment with interleukin-2: Results from a phase 2 study in 51 patients with metastasized melanoma. Cancer 2010, 116, 4139–4146, doi:10.1002/cncr.25156.
  5. Babilas, P.; Shafirstein, G.; Baumler, W.; Baier, J.; Landthaler, M.; Szeimies, R.M.; Abels, C. Selective photothermolysis of blood vessels following flashlamp-pumped pulsed dye laser irradiation: In vivo results and mathematical modelling are in agreement. J. Invest. Dermatol. 2005, 125, 343–352.
  6. Van der Zee, J. Heating the patient: A promising approach? Ann. Oncol. 2002, 13, 1173–1184, doi:10.1093/annonc/mdf280.
Healthcare EISSN 2227-9032 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert