Safety of Total Skin Electron Therapy with Concurrent Systemic Therapy
Authors: Chelius Monica , Cohen Leah , Jiang Cecilia , Mallon John , Greisz Justin , Tierney Ann , Hossain Nasheed , Rook Alain , Villasenor-Park Jennifer , Samimi Sara , Kim Ellen , Plastaras John , Barta Stefan K. , Lariviere Michael 
Published: December 2023

Introduction:
Mycosis fungoides has a long, waxing and waning course. Multimodality therapy is needed to control disease. Total skin electron beam therapy (TSE) is an effective means of controlling cutaneous disease, though response duration is limited necessitating incorporation of additional therapeutics. There are limited data informing the safety of systemic agents used concurrently with TSE. We characterize acute toxicities of patients undergoing TSE +/- concurrent or recent systemic therapy.
Methods:
We retrospectively analyzed 114 patients comprising a total of 121 consecutive courses of full body TSE from 2013-2023. Median follow up was 1.75 years from start of TSE. Toxicities occurring up to 3 months following radiation were recorded and graded per CTCAEv5 criteria when applicable; grade was characterized as low (grades 1-2) and high (3-4). Given conflating cutaneous symptoms prior to TSE, toxicities were further characterized as “new or worsened” (N/W) from baseline. Incidence of N/W toxicity was further categorized by class of systemic therapy: interferon, retinoic acid derivative, immunotherapy, systemic steroid, histone deacetylase inhibitor, folic analogue antimetabolite, and other. Recent systemic therapy included receipt of therapy within 1 and 3 months preceding TSE given multi-month half lives of some systemics.
Results:
During 75 courses, patients received systemic therapy concurrently with TSE (CS), and 46 had no concurrent systemic therapy (NCS). The majority of concurrent systemic therapies were interferons (49, 41%) and retinoic acid derivatives (32, 27%); “other” concurrent systemics included lenalidomide, imatinib, and ibrutinib. TSE dose included 36Gy (5%), 24Gy (6%), 12Gy (84%), and other (5%). Most patients had ECOG performance status 0-1 (88% overall). Patient characteristics were well balanced, excepting stage at TSE (stage III/IV CS 45.3% vs NCS 26.1%, p&lt;0.05), though T stage and blood involvement were evenly distributed. At baseline among CS and NCS patients, 29% vs 30% had skin ulceration, 27% vs 35% had large cell transformation, and 12% vs 13% had concurrent infection, respectively (all p&gt;0.05). Incidence of any N/W toxicity was 98.7% and 100% ( p&gt;0.05)among CS and NCS patients, respectively (95% vs 94% low grade and 13% vs 26% high grade, both p&gt;0.05).
Prior to TSE, baseline rates of common symptoms among CS vs NCS courses were as follows: dermatitis 96% vs 94%, hyperpigmentation 28% vs 28%, edema 15% vs 24%, pruritus 97% vs 87%, and skin pain 32% vs 45%, respectively (all p&gt;0.05). From start of TSE through 3 month follow up, the overall incidences of CS vs NCS N/W common toxicities included the following: N/W dermatitis 73% vs 83%, N/W hyperpigmentation 33% vs 37%, and N/W edema 21% vs 24% (all p&gt;0.05). Twenty-five percent of CS patients experienced skin pain flare during TSE vs 13% NCS, and 20% of CS patients vs 11% NCS experienced pruritus flare (all p&gt;0.05). At end of treatment, 59% of CS patients with baseline pruritus experienced improvement compared to 68% NCS, with 73% vs 70% experiencing improvement at 1-3 months in follow up (all p&gt;0.05). One patient received a known concurrent radiosensitizer - methotrexate - and developed N/W grade 3 dermatitis (baseline grade 3), new grade 2 hyperpigmentation, worsened grade 1 anorexia, new grade 2 superficial soft tissue fibrosis, and pain flare.
The median number of all reported N/W toxicities among systemic classes when given concurrently was low and well balanced. This persisted when the number of toxicities per class were assessed among systemics administered within 1 month preceding TSE, and within 3 months preceding TSE.
Conclusions:
Concurrent or recent receipt of systemic therapy can be safe among most commonly used concurrent agents that are not radiosensitizers. There was no notable increase in incidence of low or high grade toxicity, or median number of low or high grade toxicities recorded in CS vs NCS patients. Most patients experienced some acute toxicity, which is not unexpected given radiation to a tissue with high cell turnover, and the interplay of toxicity with expected disease response to TSE. High rates of baseline dermatitis and high rates of N/W dermatitis highlight this observation. Notably most systemic therapies included interferons and retinoic acid derivatives. Additional data is needed to better characterize the toxicity profile of other systemic therapies used concurrently with TSE.