Electron Spatially Fractionated Radiation Therapy for Mycosis Fungoides

Introduction: The tumor microenvironment of mycosis fungoides is involved in disease progression and immune evasion. The presence of regulatory T-cells and progressive lack of cytotoxic T-cells fosters an immunosuppressive environment contributing to proliferation and resistance to immunotherapy. Understanding the mechanisms behind immune cell dysfunction in mycosis fungoides is vital for developing therapies that can restore immune responses and synergize with immunotherapy. Photon based spatially fractionated radiation therapy (SFRT) has been shown to have immunomodulatory effects on the tumor microenvironment, but there is a need to develop radiation strategies for cutaneous tumors. Electron radiation therapy is widely utilized for the palliative treatment of mycosis fungoides. Currently there are no clinical studies of electron SFRT (eSFRT) or evaluation of the immunomodulatory effects of eSFRT in mycosis fungoides to potentially synergize with immunotherapy. The first step is to assess the feasibility and dosimetry of GRID collimators designed for eSFRT delivery.Methods: The 3 mm and 1.5 mm lead GRID collimators were placed on a solid water phantom and the percentage depth doses (PDD) and lateral dose profiles were measured for 6, 9 and 12 MeV electron beams with Gafchromic EBT3 films. At the lateral dose profile, the peak to valley dose ratios (PVDR) and output factors were evaluated.Results: The dmax values with the 3 mm thick lead GRID collimator at 6, 9, and 12 MeV were 1.3, 2.1, and 2.9 cm, respectively. The output factors at dmax for 6, 9, and 12 MeV using a 10x10 cm field size were 0.815, 0.723, and 0.700, respectively. The PVDRs for 6 MeV at dmax and d90 for the 1.5 mm thick lead GRID collimator were 8.9 and 3.0, respectively.Conclusions: It is feasible for a lead GRID collimator to deliver a dose distribution amenable for eSFRT. Further research is warranted to evaluate preclinical models of eSFRT for mycosis fungoides to assess tumor microenvironment immune effects alone and in combination with immunotherapy.

Yaghmour:Blueprint: Speakers Bureau; Astellas: Speakers Bureau; Secura Bio: Speakers Bureau; Incyte: Speakers Bureau; SOBI: Speakers Bureau; Kite: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau; Jazz: Speakers Bureau; Servier: Speakers Bureau; Rigel: Speakers Bureau; GSK: Speakers Bureau; Astazeneca: Other: Advisory Board; Daiichi: Other: Advisory Board; Abbvie: Other: Advisory Board; Pharmacyclics: Research Funding; USC Keck School of Medicine: Current Employment; ABBVie: Speakers Bureau; Stemline therapeutic: Speakers Bureau; Alexion: Other: consult.