Comparative Outcomes of Single- and Split-Fraction Low-Dose Radiation in Mycosis Fungoides

Localized radiation is a cornerstone therapy for early-stage mycosis fungoides (MF), with low-dose regimens achieving high response rates. However, the optimal fractionation schedule remains unclear. Single-fraction (8 Gy × 1) and split-fraction (4 Gy × 2) regimens are widely used, but comparative data are limited. Reducing treatment burden may be particularly important in rural settings, where travel distance can limit access.

This study aims to compare lesion-level response, recurrence, and durability between 8 Gy × 1 and 4 Gy × 2 low-dose radiation regimens in MF. We performed a retrospective review of 136 lesions from 27 adults with biopsy-confirmed MF treated with localized electron beam radiation at a rural multidisciplinary cutaneous lymphoma clinic (2014-2025). Lesions were categorized as patch or plaque. The primary outcome was complete response (CR) at 6 months. Secondary outcomes included overall response rate, local recurrence, time to next therapy, and toxicity. Analyses included χ²/Fisher's exact tests, Kaplan-Meier survival, Cox regression, and inverse-probability weighting.

Of 136 lesions, 119 (87.5%) received 4 Gy × 2 and 17 (12.5%) received 8 Gy × 1. Six-month CR was 81.5% versus 82.4%, respectively (P = 1.0). Overall response rate was 98.3% versus 100%, respectively (P = 1.0). Six-month local recurrence occurred in 3.4% versus 11.8% of lesions (P = .17), and additional local treatment within 6 months was required in 12.6% versus 5.9% of lesions (P = .69). No grade ≥2 toxicities occurred. Median patient travel distance was 86.2 miles versus 71.0 miles (P = .069). Multivariable and inverse-probability weighting analyses showed no association between regimen and CR at 6 months.

Limitations of this study include retrospective design and small single-fraction sample. Single-fraction 8 Gy was associated with similar short-term outcomes and excellent tolerability, supporting its use as an effective, logistically advantageous option, particularly in rural practice.