Hypofractionated Low-Dose Total Skin Electron Beam Therapy for Primary Cutaneous T-Cell Lymphoma: Analysis of Efficacy and Toxicity

Introduction

Cutaneous T-cell lymphoma (CTCL) is a rare form of lymphoma that is characterized by the localization of malignant cells to the skin. While considerable advances have been made in both the diagnosis and treatment of this disease, management and long-term disease control continue to be significant challenges. In particular, total skin electron beam therapy (TSEBT)-a technique that allows for homogenous irradiation of the entire skin-has proved to be efficacious for palliatively treating CTCL (Heumann TR et al IJROBP 2015), but a large proportion of patients continue to relapse over time with a limited possibility of retreatment due to skin toxicity (Wilson LD et al J Am Acad Dermatol 1996; Becker M et al IJROBP 1995).

Recently, low-dose TSEBT to ~12 Gy has largely replaced traditional TSEBT to ~36 Gy for the palliative treatment of CTCL due to similar high response rate with less toxicity and more room to re-treat as necessary (Hoppe et al J Am Acad Dermatol 2015). However, there is little consensus on the optimal fractionation and dose per fraction (i.e. number of total treatments needed to deliver 12 Gy).

At our institution, we have implemented a novel condensed hypofractionated scheme for low-dose TSEBT, where instead of giving ½ cycle (3 positions) per fraction, we give a full cycle (all 6 positions) per fraction, leading to half as many treatments (6 instead of 12) for the same total dose (12 Gy). We hypothesize that condensed low-dose TSEBT given in 6 fractions, compared to 12, will have similar toxicity and efficacy with the additional convenience of half as many treatments.

Methods

We conducted a single-institution retrospective review of patients with primary CTCL who received TSEBT at UT Southwestern between 2012 and 2021. We stratified patients based on whether they received high-dose TSEBT (18 Gy or above) or low-dose TSEBT (12 Gy), and among those with low-dose TSEBT substratified them between standard fractionation (12 fractions) or hypofractionation (6 fractions). We recorded each patient's primary outcomes, which included response to radiation (complete response, near complete response, partial response, stable disease, or progressive disease), time to response, duration of response, and any acute toxicities. Physician-assessed secondary outcomes, demographic information, and any systemic treatments given concurrently or adjuvantly with TSEBT were also included.

Results

Overall, 46 patients received 59 courses of TSEBT, with 39 patients receiving 52 courses of low-dose TSEBT. Of the 52 low-dose courses evaluated, median age at treatment was 62.5 years old (range, 21-91). Most patients had stage IB, IIB, or IVA disease before initiation of TSEBT. The overall response rate was 87%. Nine courses (17%) resulted in a complete response, 5 courses (9.6%) resulted in a near complete response, and 25 courses (48%) resulted in a partial response. The incidence of progression of skin disease was 17% at 6 months and 21% at 1 year.

Of the 59 total courses, 40 patients had hypofractionation (full cycle) and 8 patients had standard fractionation (half cycle). There was no significant difference in the response rate between these two groups.

The median time to response for the hypofractionation compared to the standard fractionation was 7 weeks versus 8.5 weeks, respectively, while the duration of response was 46 weeks versus 54 weeks, respectively. Concurrent treatments included bexarotene for 2 patients, brentuximab for 2 patients, interferon for 1 patient, and romidepsin for 1 patient. Importantly, no patients experienced significant toxicities including those in the hypofractionation group, with the exception of 1 patient (2.5%) who experienced grade 3 desquamation.

Conclusion

In the largest series to date of low-dose TSEBT using a hypofractionation scheme, our results suggest that it is equally safe and effective as traditional fractionation. This novel condensed low-dose TSEBT comes with the added benefits of convenience and cost-effectiveness, as well as decreased patient exposure to the healthcare system during the current pandemic, and should be considered for all CTCL patients needing TSEBT. Moving forward, we look to evaluate the impact of radiation therapy with concurrent or adjuvant treatments for patients with CTCL as alternative options for possibly supplementing the efficacy of radiotherapy and/or reducing the need for recurrent radiation altogether.