Mangold, Aaron R.

Importance Lichen planus is a chronic, highly pruritic, inflammatory disease that affects the skin and other tissues. Objective To evaluate the efficacy and safety of ruxolitinib, 1.5%, cream in patients with cutaneous lichen planus. Design, Setting, and Participants This phase 2, 16-week, randomized, double-blind, vehicle-controlled trial with a 16-week open-label extension was conducted from November 2022 to February 2024. Patients were enrolled from 19 sites in the US and Canada. The trial included adults with predominantly cutaneous lichen planus, an Investigator’s Global Assessment (IGA) score of 3 or 4, an Itch Numerical Rating Scale score of 4 or greater, and an affected body surface area of 20% or less were enrolled. Data were analyzed from February to August 2024. Interventions Patients were randomized 1:1 to ruxolitinib, 1.5%, twice daily cream or vehicle cream for 16 weeks, after which eligible patients applied ruxolitinib cream twice daily as needed in a 16-week, open-label extension. Main Outcomes and Measures The primary end point was IGA treatment success (IGA score of 0 or 1 [clear/almost clear skin] with a ≥2-grade improvement from baseline) at week 16. Results Among 64 randomized patients, 46 (72%) were female, 18 (28%) were male, 18 (28%) were African American/Black, 4 (6%) were Asian, 40 (63%) were White, and the median (range) age was 57.0 (18-78) years. Significantly more patients who applied ruxolitinib, 1.5%, cream vs vehicle achieved IGA treatment success (50.0% [95% CI, 31.9%-68.1%] vs 21.9% [95% CI, 9.3%-40.0%], respectively; response rate difference, 29.4% [95% CI, 7.6%-51.3%]; P = .01; primary end point) at week 16, with further improvement to week 32. Similar results were observed in the proportion of patients who achieved a 4 or greater–point improvement from baseline in Itch Numerical Rating Scale score (week 16, 48.4% [95% CI, 30.2%-66.9%] vs 16.1% [95% CI, 5.5%-33.7%]; response rate difference, 33.5%; 95% CI, 12.2%-54.9%; P = .004; secondary end point). No serious treatment-emergent adverse events or discontinuations due to an adverse event were observed with ruxolitinib cream. Conclusions and Relevance The results of this randomized clinical trial suggest that ruxolitinib cream significantly reduced lesions and itch in patients with lichen planus. Therefore, ruxolitinib cream represents a potential treatment option for patients with cutaneous lichen planus. Trial Registration ClinicalTrials.gov Identifier: NCT05593432

ABSTRACT Background Current staging systems for head and neck cutaneous squamous cell carcinoma (HNCSCC), such as AJCC8 and BWH, often fail to adequately stratify high‐risk patients, particularly due to the exclusion of important biological and host factors. This study aimed to identify independent prognostic factors for HNCSCC outcomes in the largest multi‐institutional retrospective series to date. Methods De‐identified data from 8,610 primary HNCSCC tumors, treated with curative intent surgery across multiple international centers, were analyzed. Outcomes included local recurrence (LR), locoregional metastasis (LM), distant metastasis (DM), and disease‐specific death (DSD). Multivariable Fine–Gray subdistribution hazard regression models with robust standard errors clustered at the patient level were fitted to generate exploratory hypotheses regarding independent hazard determinants. Results During a median follow‐up of 31.4 months (IQR 14.2–52.8), the cumulative incidence was 3.3% for LR, 2.7% for LM, 0.5% for DM, and 1.2% for DSD. Multivariable analysis confirmed that tumor diameter, poor differentiation, deep invasion, and large‐caliber perineural invasion (LCPNI) were the strongest predictors, being significantly associated with at least three of the four outcomes. Notably, factors currently excluded from or weighted differently in staging systems also proved critical: Immunosuppression was significantly associated with LR (SHR 2.03) and DSD (SHR 1.70); and lymphovascular invasion (LVI) was independently associated with LM (SHR 3.00). Poor differentiation demonstrated high prognostic impact, being a significant predictor for all four endpoints. Conclusion Tumor diameter, poor differentiation, deep invasion, LCPNI, immunosuppression status, and LVI are the most critical independent factors for HNCSCC prognosis. Our multi‐institutional data provide a robust framework for hypothesis generation, highlighting that incorporating host biological features and non‐anatomic variables could significantly refine future staging system discussions.

Importance Hypopigmented mycosis fungoides (HMF) is uncommon in adults, and data on clinicopathologic features and long-term outcomes remain sparse. Objective To investigate the clinicopathologic features and outcomes of adults with HMF in a large multicenter cohort. Design, Setting, and Participants This retrospective multicenter cohort study conducted from January 2011 to October 2023 at 6 US tertiary referral centers and included adults (18 years or older at diagnosis) with biopsy-confirmed HMF and hypopigmentation documented at diagnosis, with a median (range) follow-up of 39 (1-347) months. Data were analyzed from February to December 2025. Exposures Clinical variant, immunophenotype predominance, and polymerase chain reaction–based T-cell receptor ( TCR ) gene rearrangement in peripheral blood and/or skin. Main Outcomes and Measures Best overall response, defined as complete response, partial response, stable disease, or progressive disease, and progression to a higher stage. Results The cohort included 224 adults with HMF (median [range] age, 44 [18-74] years), of whom 164 (73%) were women (60 men [27%]), 5 (2%) were Asian individuals, 1 (0.4%) was a Hispanic/Latino individual, 1 (0.4%) was a Middle Eastern individual, 19 (8%) were White individuals, and 186 (83%) were Black individuals; 219 (98%) presented with early-stage disease. Most had hypopigmented lesions only (159 [71%]), whereas 65 (29%) exhibited mixed-variant mycosis fungoides; outcomes were similar between groups. Among 141 patients with available immunophenotyping, 88 (63%) had CD8-positive predominance. Among 207 treated patients, most (179 [90%]) received skin-directed therapy alone. Among 198 evaluable patients, the best overall response was complete response for 52 (26%), partial response for 101 (51%), stable disease for 34 (17%), and progressive disease for 11 (6%). Over a median (range) follow-up of 39 (1-347) months, 14 of 224 patients (6%) experienced progression to a higher stage, including 5 of 219 patients (2%) with early-stage disease at baseline who experienced progression to advanced-stage disease. Peripheral blood TCR monoclonality was detected in 23 of 85 tested patients (27%) and was associated with poorer treatment response but not with disease progression. Conclusions and Relevance The finding of this cohort study suggest that adult HMF demonstrated a generally indolent course, with favorable response to skin-directed therapy, irrespective of immunophenotype or mixed-variant presentation. Peripheral blood TCR monoclonality was associated with lower treatment response but not disease progression.