Radiotherapy Eradicates Malignant T Cells and Is Associated with Improved Survival in Early-Stage Mycosis Fungoides

Clin Cancer Res. 2020 Jan 15;26(2):408-418. doi: 10.1158/1078-0432.CCR-18-4147. Epub 2019 Oct 21.

Abstract

Purpose: Mycosis fungoides is the most common subtype of cutaneous T-cell lymphoma. Skin-directed treatments often improve but do not cure mycosis fungoides skin lesions. The purpose of this study was to (i) assess whether remission was associated with malignant T-cell clone depletion at treated sites using either low-dose radiotherapy (LDRT, 8 Gy) or topical steroids and (ii) assess whether a clone-ablative therapy, like LDRT, is associated with overall survival in patients with high-risk early-stage CTCL.

Experimental design: Pre- and posttreatment biopsies from 20 lesional skin samples of 18 patients with mycosis fungoides who received either 8 Gy LDRT (n = 16) or topical steroids (n = 4) underwent high-throughput T-cell receptor sequencing of the TCRB gene to quantify the malignant T-cell clone. For the retrospective chart review, overall survival of 47 high-risk early-stage patients was compared between patients who did or did not receive radiation.

Results: LDRT eradicated the clone in 5 of 16 lesions and reduced it >90% in 11 of 16; there were no recurrences in these lesions. Patients treated with topical steroids appeared to clinically improve, but the malignant clone persisted. We found that the number of residual malignant T cells predicted lesion recurrence. A retrospective review showed that early-stage high-risk patients who received radiation as part of their treatment regimen had prolonged overall survival compared with patients who did not.

Conclusions: These findings demonstrate that LDRT can eradicate malignant T cells in mycosis fungoides, provides robust disease control, and is associated with improved survival in high-risk early-stage patients.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Female
  • Humans
  • Lymphoma, T-Cell, Cutaneous / mortality*
  • Lymphoma, T-Cell, Cutaneous / pathology
  • Lymphoma, T-Cell, Cutaneous / radiotherapy
  • Male
  • Middle Aged
  • Mycosis Fungoides / mortality*
  • Mycosis Fungoides / pathology
  • Mycosis Fungoides / radiotherapy
  • Neoplasm Recurrence, Local / mortality*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / radiotherapy
  • Prospective Studies
  • Radiotherapy / mortality*
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Retrospective Studies
  • Skin Neoplasms / mortality*
  • Skin Neoplasms / pathology
  • Skin Neoplasms / radiotherapy
  • Survival Rate
  • T-Lymphocyte Subsets / radiation effects*
  • Treatment Outcome
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Receptors, Antigen, T-Cell, gamma-delta