High frequency of brain metastases after adjuvant therapy for high-risk melanoma

Cancer Med. 2017 Nov;6(11):2576-2585. doi: 10.1002/cam4.1223. Epub 2017 Oct 10.

Abstract

The incidence of CNS progression in patients with high-risk regional melanoma (stages IIIAN2a-IIIC) is not well characterized. Data from the S0008 trial provided an opportunity to examine the role of CNS progression in treatment failure and survival. All patients were surgically staged. Following wide excision and full regional lymphadenectomy, patients were randomized to receive adjuvant biochemotherapy (BCT) or high-dose interferon alfa-2B (HDI). CNS progression was retrospectively identified from data forms. Survival was measured from date of CNS progression. A total of 402 eligible patients were included in the analysis (BCT: 199, HDI: 203). Median follow-up (if alive) was over 7 years (range: 1 month to 11 years). The site of initial progression was identifiable in 80% of relapsing patients. CNS progression was a component of systemic melanoma relapse in 59/402 patients (15% overall). In 34/402 patients (9%) CNS progression represented the initial site of treatment failure. CNS progression was a component of initial progression in 27% of all patients whose melanoma relapsed (59/221). The risk of CNS progression was highest within 3 years of randomization. The difference in CNS progression rates between treatment arms was not significant (BCT = 25, HDI = 34, P = 0.24). Lymph node macrometastases strongly associated with CNS progression (P = 0.001), while ulceration and head and neck primaries were not significant predictors. This retrospective analysis of the S0008 trial identified a high brain metastasis rate (15%) in regionally advanced melanoma patients. Further studies are needed to establish whether screening plus earlier treatment would improve survival following CNS progression.

Keywords: Biochemotherapy; brain metastases; interferon; lymph node metastases; melanoma; ulceration.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Brain Neoplasms / secondary*
  • Cisplatin / administration & dosage
  • Dacarbazine / administration & dosage
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / therapeutic use*
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • Male
  • Melanoma / complications
  • Melanoma / secondary*
  • Melanoma / therapy*
  • Neoplasm Staging
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / therapeutic use
  • Retrospective Studies
  • Skin Neoplasms / complications
  • Skin Neoplasms / pathology*
  • Skin Neoplasms / therapy*
  • Skin Ulcer / etiology
  • Survival Rate
  • Vinblastine / administration & dosage

Substances

  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Vinblastine
  • Dacarbazine
  • Cisplatin

Grants and funding