Radiation therapy overcomes adverse prognostic role of cyclooxygenase-2 expression on Reed-Sternberg cells in early Hodgkin lymphoma

Int J Radiat Oncol Biol Phys. 2015 May 1;92(1):84-90. doi: 10.1016/j.ijrobp.2014.10.004. Epub 2014 Dec 2.

Abstract

Purpose: To analyze the role of radiation therapy (RT) on the adverse prognostic influence of cyclooxygenase-2 (COX-2) expression on Reed-Sternberg (RS) cells, in the setting of early Hodgkin lymphoma (HL) treated with ABVD (adriamycin, vinblastine, bleomycin, dacarbazine).

Methods and materials: In the present study we retrospectively investigated the prognostic value of COX-2 expression in a large (n=143), uniformly treated early HL population from the Spanish Network of HL using tissue microarrays. Univariate and multivariate analyses were done, including the most recognized clinical variables and the potential role of administration of adjuvant RT.

Results: Median age was 31 years; the expression of COX-2 defined a subgroup with significantly worse prognosis. Considering COX-2(+) patients, those who received RT had significantly better 5-year progression-free survival (PFS) (80% vs 54% if no RT; P=.008). In contrast, COX-2(-) patients only had a modest, nonsignificant benefit from RT in terms of 5-year PFS (90% vs 79%; P=.13). When we compared the outcome of patients receiving RT considering the expression of COX-2 on RS cells, we found a nonsignificant 10% difference in terms of PFS between COX-2(+) and COX-2(-) patients (P=.09), whereas the difference between the 2 groups was important (25%) in patients not receiving RT (P=.04).

Conclusions: Cyclooxygenase-2 RS cell expression is an adverse independent prognostic factor in early HL. Radiation therapy overcomes the worse prognosis associated with COX-2 expression on RS cells, acting in a chemotherapy-independent way. Cyclooxygenase-2 RS cell expression may be useful for determining patient candidates with early HL to receive consolidation with RT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Analysis of Variance
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / metabolism*
  • Bleomycin
  • Child
  • Cyclooxygenase 2 / metabolism*
  • Dacarbazine
  • Disease-Free Survival
  • Doxorubicin
  • Female
  • Hodgkin Disease / drug therapy
  • Hodgkin Disease / enzymology*
  • Hodgkin Disease / mortality
  • Hodgkin Disease / pathology
  • Hodgkin Disease / radiotherapy*
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Reed-Sternberg Cells / enzymology*
  • Retrospective Studies
  • Tissue Array Analysis
  • Tumor Burden
  • Vinblastine
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Bleomycin
  • Vinblastine
  • Dacarbazine
  • Doxorubicin
  • Cyclooxygenase 2

Supplementary concepts

  • ABVD protocol