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

Background 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. Objective To compare lesion-level response, recurrence, and durability between 8 Gy × 1 and 4 Gy × 2 low-dose radiation regimens in MF. Methods 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 (ORR), local recurrence, time to next therapy, and toxicity. Analyses included χ²/Fisher's exact tests, Kaplan–Meier survival, Cox regression, and inverse-probability weighting (IPW). Results 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). ORR was 98.3% versus 100%, respectively (p = 1.0). Six-month local recurrence occurred in 3.4% versus 11.8% lesions (p = 0.17), and additional local treatment within 6 months was required in 12.6% versus 5.9% lesions (p = 0.69). No grade ≥2 toxicities occurred. Median patient travel distance was 86.2 miles vs 71.0 miles (p = 0.069). Multivariable and IPW analyses showed no association between regimen and CR at 6 months. Limitations Retrospective design and small single-fraction sample. Conclusions 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.