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Corresponding author: Carmen Salvador-Coloma; Medical Oncology Department, University Hospital La Fe, Valencia, Spain.
Cite this article as: Salvador-Coloma C, Montalar J, Niño OM, Tormo A, Aparicio J. Long term survival after brain metastases from
malignant melanoma. Int J Cancer Ther Oncol. 2016; 4(4):448. DOI: 10.14319/ijcto.44.8

© Salvador-Coloma et al. ISSN 2330-4049

Long term survival after brain metastases from malignant
melanoma

Carmen Salvador-Coloma1, Joaquín Montalar1, Óscar Mauricio Niño1,
Alejandro Tormo2, Jorge Aparicio1

1Medical Oncology Department, University Hospital La Fe, Valencia, Spain
2Radiotherapy Department, University Hospital La Fe, Valencia, SpainReceived August 25, 2016; Revised December 13, 2016; Accepted December 20, 2016; Published Online December 28, 2016

Case Report
AbstractWe present the case of a 32-year-old patient with malignant melanoma whorelapsed with an unresectable brain metastases (BM). He was managed with wholebrain radiotherapy (WBRT) and temozolomide chemotherapy. A metabolicpositron emission tomography (PET-scan) complete response was achieved. He isliving disease-free more than 6 years after the diagnosis of BM. He is now 51 yearsold and remains asymptomatic and free of disease since then. However, apronounced residual image still appears on magnetic resonance imaging (MRI) antPET-scan.
Keywords: Malignant melanoma, Brain metastases, Long-term survival,Unresectable brain metastases

1. IntroductionMelanoma has a high propensity to metastasize thecentral nervous system (CNS). After breast and lungcancer, it is the third most common neoplasm causingbrain metastases (BM).1-2 Some characteristics ofmelanoma are associated with an increased risk ofsystemic disease and therefore BM: origin in mucosalsurfaces or skin of trunk, head and neck, male gender,ulcerated primary lesion, wide thickness invasion, acrallentiginous or nodular lesions, involvement of 3 or moreregional lymph nodes, and visceral metastases at thetime of diagnosis.1At 5 years, median survival for stage IV melanoma is6-10 months, but for melanoma with BM is 2-9 months.2Long-term survival after BM is very unusual because ofpoor prognosis, regardless of cancer type. Nevertheless,survival is different depending on the primaryneoplasm. Patients with ovarian tumors have the highestsurvival rate (7.8%), which is only 2.3% for patientswith melanoma.3We present the case of a patient with malignantmelanoma who relapsed with an unresectable BM. He isliving disease-free more than 6 years after the diagnosisof BM. He was managed with whole brain radiotherapy(WBRT) and temozolomide chemotherapy.

2. Case PresentationA 32 year-old man, with medical history of hypertension,diabetes and dyslipidemia, was diagnosed with acutaneous malignant melanoma (stage II-A), in his leftshoulder in 1997. He underwent wide surgery and wasrendered disease-free.In 2001, a physical exam revealed axillary lymph nodeenlargement. He was treated with surgery,complementary radiotherapy (40 Gy) and adjuvantalpha 2b interferon therapy (20 MU/m2/dayintravenously (i.v) 5 days a week for 4 weeks, then 10MU/m2 subcutaneously (s.c) three times per week for 48weeks).However, in 2002, in transit skin metastases weredetected. He underwent salvage surgery plus adjuvantchemotherapy with 6 courses of dacarbazine (250mg/m2 × 5 days, every 4 weeks), that was welltolerated.He was disease-free until 2010, when an unresectableBM relapse (5 cm in diameter, intraaxial with satellitelesions) was noticed in the right frontal lobe (Figure 1).

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Figure 1: Magnetic resonance: Melanoma metastatic lesion at diagnosis (2010).

Figure 2: Magnetic resonance: Post-treatment residual hemorrhagic injury (2016).The lesion was not studied by biopsy. He receivedconcomitant chemo-radiotherapy (temozolamide 75mg/m2 continuous during WBRT to a total dose of 30Gy). After concomitant treatment, he received eighteencycles of temozolamide (200 mg/m2 days 1-5 of 28days). The clinical tolerance was acceptable, presentingonly grade 2-3 emesis, which was controlled withstandard antiemetic therapy.

A metabolic positron emission tomography (PET-scan)complete response was achieved. He is now 51 years oldand remains asymptomatic and free of disease sincethen. However, a pronounced residual image stillappears on magnetic resonance imaging (MRI) antPET-scan (Figures 2 and 3).



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© Salvador-Coloma et al. ISSN 2330-4049

Figure 3: PET-scan: complete response.
3. DiscussionMalignant melanomas tend to metastasize into the CNS.4This specific dissemination has a negative effect onoverall survival and in most cases represents a terminalevent.5 Patients with large (>4 cm), or numerous lesionsare difficult to treat and usually receive palliativetherapies. In contrast, smaller (<2 cm) and single lesionscan be treated more effectively.6 For patients with BM,some studies have shown favorable prognostic variablesfor extended survival: younger age, the presence of asingle lesion, surgical resection, chemotherapy andWBRT.3The treatment of choice for oligometastatic CNS diseaseis surgical resection. It depends on the number oflesions, the size and locations of the tumor, the state ofsystemic disease and performance status.7 In this groupof patients surgery has been shown to improvesurvival.8 In 60-70% of patients, WBRT has shown asurvival improvement of 1-2 months and is effective inpalliating symptoms of BM.9 A series from the SydneyMelanoma Unit report outcome of 646 melanomapatients treated for BM. Median survival was 8.7 monthsfor surgery versus 8.9 months for surgery andpostoperative WBRT and 3.4 months for patients treatedsolely with WBRT.10 Stereotactic radiosurgery can treatsmaller metastatic lesions. The benefit is that it allowsfor treatment lesions that would otherwise beinoperable.11-12 A variety of cytotoxic drugs has beentested for the treatment of BM of melanoma, includingtemozolamide. Most of the studies have shown betterresults for combination therapies as compared to WBRTalone.13-14For solitary BM, the recommended treatment is surgicalremoval of the lesion followed by WBRT or WBRT withstereotactic radiosurgery. The case reported here unde-rwent concomitant chemotherapy and radiotherapyfollowed by adjuvant chemotherapy. Stereotacticradiosurgery or surgery was not administrated due to

the lesion extension and its location. Historically, BMwere treated with WBRT followed by stereotacticradiosurgery. In recent years, however, it is suggestedthat stereotactic radiosurgery of smaller lesionsprovides long-term control as exclusively treatment, andthat many patients did not appear to require additionaltreatment.15 There are some clinical trials includingpatients with one to three BM from different kind ofcancers that have shown local control with stereotacticradiosurgery is not improved by WBRT, but thedevelopment of new BM is decreased by the addition ofWBRT.12,16,17
4. ConclusionSystemic treatment has not been shown to be effectivein melanoma BM, therefore it has uncommonly beenused as primary treatment.18 Nowadays, thedevelopment of new therapeutic agents point out animportant improvement in management options forthese patients.19 The present case suggests thattreatment of melanoma BM remains an ongoingchallenge, and advances in treatment are providingbenefit for patients. Nevertheless, we must continueinvestigating ways to develop an optimal treatment forthese patients.
Conflict of interestThe authors have no actual, potential, real or apparentinterest to declare and have no involvement that mightraise the question of bias in the work reported or in theconclusions, implications, or opinions stated.
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12. Manon R, O’Neill A, Knisely J, et al. Phase II trialof radiosurgery for one to three newlydiagnosed brain metastases from renal cellcarcinoma, melanoma, and sarcoma: an easterncooperative oncology group study (E 6397). JClin Oncol. 2005;23(34):8870-6.13. Meier S, Baumert BG, Maier T, et al. Survivaland prognostic factors in patients with brainmetastases from malignant melanoma.Onkologie 2004;27:145-9.14. Chiarion-Sileni V, Murr R, Pigozzo J, et al. Brainmetastases from malignant melanoma. Forum(Genova). 2003;13(2):170-82.15. Rao G, Klimo P, Thompson C, et al. Stereotacticradiosurgery as therapy for melanoma, renalcarcinoma, and sarcoma brainmetastases:impact of added surgical resection andwhole-brain radiotherapy. Int J Radiat OncolBiol Phys. 2006;66(4):S20-5.16. Kocher M, Soffietti R, Abacioglu U, et al.Adjuvant wholebrain radiotherapy versusobservation after radiosurgery or surgicalresection of one to three cerebralmetastases:results of the EORTC 22952–26001 study. J ClinOncol. 2011;29(2):134–41.17. Aoyama H, Shirato H, Tago M, et al. Stereotacticradiosurgery plus whole-brain radiationtherapy vs stereotactic radiosurgery alone fortreatment of brain metastases: a randomizedcontrolled trial. JAMA. 2006; 295(21):2483–91.18. Agarwala S, Kirkwood J, Gore M, et al.Temozolomide for the treatment of brainmetastases associated with metastaticmelanoma: a phase II study. J Clin Oncol.2004;22(11):2101–7.19. Goldinger SM, Panje C, Nathan P. Treatment ofmelanoma brain metastases. Curr Opin Oncol.2016;28(2):159-65.

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