Recurrence Patterns of Non-Mycosis Fungoides Cutaneous Lymphoma Following Various Treatment Modalities.
Authors: Confer Michael E. , Tward Jonathan D. , Perkins Sherrie L. , Bowen Glen M. , Lee Robert J. , Glenn Martha J. , Gaffney David K. 
Published: April 2020

INTRODUCTION: Non-mycosis fungoides (MF) primary cutaneous lymphoma (PCL) is rare, and the more indolent forms seldom progress to fatal, systemic lymphoma. Nevertheless, frequent relapses are common. Although several therapies exist, no standard of care has been established for initial treatment.

OBJECTIVES: To compare the role of radiotherapy to other initial treatment options and to evaluate clinicopathologic factors affecting overall, cause-specific, and relapse-free survival

METHODS: Thirty-eight patients from 1985 to 2006 were retrospectively identified and reviewed with non-MF PCLs including: primary cutaneous anaplastic large cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, primary cutaneous marginal zone B-cell lymphoma, primary cutaneous follicle-center lymphoma, primary cutaneous diffuse large B-cell lymphoma, leg type, or primary cutaneous intravascular large B-cell lymphoma. Regression-free, cause-specific, and overall survival was estimated using the methods of Kaplan and Meier. Outcomes were compared with the log-rank test and Cox regression analysis.

RESULTS: 38 patients were included in the analysis with a median follow-up time of 34.6 months (range 2 – 138 months). The distribution of initial treatment was: surgery - 29%, topical therapy - 16%, systemic therapy - 18%, and radiation - 63%. Three patients never received radiation.

For the entire cohort, the 5-year overall (OS), cause-specific (CSS), and relapse free survival (RFS) was 86.2%, 88.9%, and 29.5% respectively. Subjects who received radiation therapy (n=24) as part of their initial treatment course had a significantly longer median time to first relapse of 57 months compared to 3.2 months for the 14 subjects who did not receive radiotherapy (log-rank p &lt; 0.0001). Overall survival was significantly improved for subjects whose International Prognostic Index (IPI) score was 0–1 (n=25) versus those whose score was 2 or greater (n=13, p=0.05).

Multivariate analysis for RFS revealed that the absence of radiation as part of initial treatment (Hazard Ratio (HR) = 22.2, 95% CI 2.1 – 238.5, p=0.01) and aggregate size less than 10cm (HR 0.04, 95% CI 0.0 – 0.3, p&lt;0.01) significantly altered the risk of relapse.

No relapses were observed within the radiation therapy treatment field in 31/35 (89%) subjects following their first course of radiation therapy. Of the 15/35 (43%) of patients that relapsed anywhere following radiation, only 2/15 (13%) relapsed in-field exclusively, 2/15 (13%) relapsed both in and out-of-field, and the remaining 11/15 (73%) relapsed exclusively outside the area treated. No patient relapsed within the treatment field of after 24 months.

CONCLUSION: An initial course of radiation therapy significantly delays relapse compared to other therapies for non-MF PCL and provides excellent local control of plaques. Our findings also extend the IPI as prognostic for overall survival for this rare disease. Bulky lesions greater than 10cm in any one dimension are more strongly correlated with relapse.