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

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 ILDRT (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 ear ly-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.