LY11 Proposal for a UK prospective trial evaluating the outcomes of low-dose radiotherapy in cutaneous B-cell and T-cell lymphomas

Abstract

Indolent non-Hodgkin lymphomas (NHLs) are highly radiosensitive. The standard of care for radiotherapy (RT) delivered to localized B-cell lymphomas remains 24 Gy in 12 fractions. Reducing the dose and fractionation could improve the patient experience by reducing toxicity, inconvenience and costs. Currently, data are limited regarding the use of low-dose RT in the NHL types cutaneous B-cell lymphoma (CBCL) and cutaneous T-cell lymphoma (CTCL). This proposed national, prospective multicentre trial aims to evaluate the clinical and translational outcome of low-dose RT in CBCL and CTCL. The primary objective is to evaluate clinical response rates and response duration of low-dose RT in CBCL and CTCL. Secondary objectives include assessing patient-reported outcomes, investigating radiotherapy failure and the influence of the tumour microenvironment (TME) in local RT failures. The study aims to establish a national biobank to support translational research. Patients will undergo a baseline skin biopsy and blood sample. Patients with CBCL will receive 4 Gy in a single fraction, and selected patients with CTCL will receive 8 Gy in two fractions. A repeat skin biopsy and blood sample will be obtained 72 h after RT. Clinical response will be assessed 8–12 weeks post-­treatment. In the case of partial response, stable disease or progression, a biopsy from the treated site will be performed. If persistent disease is confirmed, patients will be offered further RT. Tissue samples will be analysed for predictive biomarkers within the TME at baseline. In nonresponders, TME and gene profiling before and after RT will help determine whether a specific immune or gene signature can be developed, aimed at a more personalized treatment approach of higher RT doses in those more likely to not respond to LDRT. This proposed trial aims to investigate a national cohort of patients with LDRT, to identify patients requiring higher-dose RT and to establish a national biobank of cutaneous lymphomas to support translational research.