Preoperative steroid pulse therapy for invasive thymoma: clinical experience and mechanism of action

Cancer. 2006 May 1;106(9):1901-7. doi: 10.1002/cncr.21875.

Abstract

Background: Glucocorticoid was used in thymomas. The purpose of the study was to evaluate the efficacy of intravenous high-dose glucocorticoid (steroid pulse) therapy in patients with previously untreated advanced thymoma. Causes were also sought for a possible underlying mechanism of the effect of steroid on thymoma.

Methods: Seventeen patients with invasive thymoma who had not received previous chemotherapy or radiation therapy were enrolled in the study. All cases were treated with 2 courses of glucocorticoid therapy before surgery. Tumor response was assessed by computed tomography (CT) scan 1 week after the steroid pulse therapy. Lymphocytes associated with thymoma were analyzed for their CD4/CD8 phenotype and glucocorticoid receptor (GR). TdT-mediated dUTP-biotin nick-end labeling (TUNEL) staining was used to analyze the apoptotic lymphocytes and epithelial cells.

Results: The overall response rate to the steroid pulse therapy was 47.1% (8 of 17). The reduction in tumor size was most prominent in type B1 thymomas; there were significant differences between type AB and type B1 thymomas (P = .0234) and type B1 and type B3 thymomas (P = .0068). The reduction in tumor size was accompanied with a marked reduction in the CD4+8+ double-positive immature thymocytes that expressed higher levels of glucocorticoid receptor. Apoptotic changes were observed in both neoplastic epithelial cell and lymphocyte components after glucocorticoid therapy.

Conclusions: The efficiency of preoperative steroid pulse therapy in type B1 thymoma was most prominent, which is probably related to the specific effect on GR-rich CD4+8+ double-positive immature lymphocytes, which are abundant in this type of thymoma.

MeSH terms

  • Adult
  • Aged
  • CD4 Antigens / analysis
  • CD8 Antigens / analysis
  • Combined Modality Therapy
  • Female
  • Flow Cytometry
  • Glucocorticoids / adverse effects
  • Glucocorticoids / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Thymoma / drug therapy*
  • Thymoma / immunology
  • Thymoma / pathology
  • Thymus Neoplasms / drug therapy*
  • Thymus Neoplasms / immunology
  • Thymus Neoplasms / pathology

Substances

  • CD4 Antigens
  • CD8 Antigens
  • Glucocorticoids