Health-related quality of life (HRQoL) in real-world patients with cutaneous T cell lymphoma (CTCL): Evaluation of patient reported outcomes using the Skindex-16 in a multidisciplinary CTCL clinic

Abstract                                                             Background                      Cutaneous T-cell lymphomas (CTCLs) are a rare group of heterogenous lymphomas that affect the skin and blood, causing significant symptom burden due to skin itching, rash, and peeling. CTCL negatively affects the HRQoL of patients and their care partners, with profound impacts on physical, social, and emotional functioning. Although CTCL guidelines recommend evaluation of patient-reported outcomes (PROs) when selecting treatment and assessing symptomatic response to therapy, these studies are scant in real-world patients treated outside of the clinical trial setting. At the University of Colorado, patients evaluated in our multidisciplinary CTCL clinic complete serial Skindex-16 PRO questionnaires as part of routine clinical care. In this study, we evaluated Skindex-16 scores and treatment information to examine symptom burden and HRQoL in real-world patients with CTCL.                        Methods                      In this cross-sectional, retrospective study, we extracted demographics, staging, and treatment information at the time of patients' first visit with recorded Skindex-16 scores. The Skindex-16 is a validated PRO questionnaire that addresses HRQoL in patients with skin disease in symptom, emotional, and functional domains (Chren 2011), with published norms for mild, moderate, and severe scores (Prinsen 2011). Patients with a diagnosis of CTCL (mycosis fungoides [MF], Sezary syndrome [SS], lymphomatoid papulosis [LyP], and subcutaneous panniculitis-like T-cell lymphoma [SPTCL]) and with Skindex-16 scores at a multidisciplinary CTCL clinic visit between January 1, 2024 and June 30, 2025 were included. Patients with B-cell lymphomas and anaplastic large cell lymphomas were excluded. Two-tailed t-tests and multiple regression analyses were utilized to compare Skindex-16 scores and to determine associations between clinical variables and HRQoL.                     Results                     There were 132 patients: mean age 64 years (range 19-93), 44% female, 80% White, 5% Black, 3% American Indian/Alaska Native, 12% other, and 11% Hispanic. Most had Medicare (51%), followed by private insurance (40%). Most patients had MF (76%), followed by SS (9%), LyP (8%), SPTCL (5%), and other CTCL types (2%). At the time of their visit, 26% had advanced-stage disease, although 38% previously had advanced-stage CTCL. Most (52%) were on systemic therapy (oral, intravenous, or extracorporeal photopheresis), and 48% were on skin-directed therapy only (topical or ultraviolet).                     For the entire cohort, total Skindex-16 mean score was 33 (SD 28), indicating a moderate impact on HRQoL. Skin-related symptoms were rated as mild (mean 32, SD 30), as was functional impact of CTCL (mean 23, SD 29). However, patients reported severe emotional burden related to CTCL (mean 43, SD 34). Highest individual items within the emotional domain were worry about persistence/recurrence (mean 3.3 out of 6, SD 2.3), worry about disease (mean 2.4, SD 2.4), and annoyance at disease (mean 2.8, SD 2.4). Participants rated depression (mean 1.8, SD 2.1) and embarrassment (mean 2.2, SD 2.4) as less bothersome.                     There were no significant differences in total Skindex-16 scores or symptom, emotional, or functional domain scores between early- vs advanced-stage CTCL. Patients on systemic therapy had worse symptom domain scores (β 15.6, p=.05, SD 30), including hurting (β 1.1, p=0.04, SD 1.7), as well as difficulty showing affection in the functional domain (β 1.1, p=0.02, SD 1.9). We also found that patients on Medicaid had worse total Skindex-16 scores than those on Medicare (β 48.8, p=0.004, SD 28.1).                     Conclusions                     Our cross-sectional analysis of Skindex-16 scores in a cohort of CTCL patients highlights a substantial emotional burden associated with the disease, even when physical symptoms and functional impairments are rated as mild to moderate. The emotional burden of CTCL is high, even for those with early-stage disease and on skin-directed therapy only. Individual items rated highest within the emotional domain were fear of recurrence, as well as worry about disease. These findings emphasize the importance of routinely integrating HRQoL assessments into CTCL care. Further, the psychological effects of CTCL may be an unmet need requiring tailored supportive interventions to address emotional distress as well as fear of recurrence. Future prospective studies are needed to examine how HRQoL scores change over time with different treatment options in this rare disease.