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Background Psoriasis is a disease that often requires prolonged systemic treatment. It is important to determine the safety of available therapies. There is currently little insight into sex-specific differences in the safety of systemic psoriasis therapies. Objectives To examine the real-world, long-term safety of systemic psoriasis therapies with sex stratification in drug-related adverse events (ADRs). Methods Ten-year data from adults with moderate-to-severe psoriasis requiring systemic treatment (conventional systemic therapies [CST], biologics) were obtained from the Swiss psoriasis registry (SDNTT). ADRs were categorized according to the international terminology Medical Dictionary for Regulatory Activities (MedDRA). Safety was assessed by calculating event rates per 100 patient-years (PY). We used descriptive statistics for patient and disease characteristics, and binomial and t-tests to compare treatment groups and sex. Results In total, 791 patients (290 females) were included with a mean age of 46 years. 358 (45%) received CSTs and 433 (55%) biologics; both groups had similar baseline characteristics except for more joint involvement in patients using biologics (26.86% vs. 14.8%, p < 0.0001). CSTs were associated with a 2.2-fold higher ADR rate (40.43/100 PY vs. 18.22/100 PY, p < 0.0001) and an 8.0-fold higher drug-related discontinuation rate than biologics (0.16/PY vs. 0.02/PY, p < 0.0001). Trends showed non-significant higher serious adverse event rates per 100 PY for biologics (8.19, CI 6.87–9.68) compared to CSTs (7.08, CI 5.39–9.13) (p = 0.3922). Sex stratification revealed a significantly higher overall ADR rate for all treatments in females (1.8-fold for CSTs [57.30/100 PY vs. 31.69/100 PY] and 2.0-fold for biologics [27.36/100 PY vs. 13.9/100 PY], p < 0.0001), and drug-related discontinuation rates for most CSTs in females. Conclusion Females were associated with a significantly, Background: Psoriasis is a disease that often requires prolonged systemic treatment. It is important to determine the safety of available therapies. There is currently little insight into sex-specific differences in the safety of systemic psoriasis therapies. Objectives: To examine the real-world, long-term safety of systemic psoriasis therapies with sex stratification in drug-related adverse events (ADRs). Methods: Ten-year data from adults with moderate-to-severe psoriasis requiring systemic treatment (conventional systemic therapies [CST], biologics) were obtained from the Swiss psoriasis registry (SDNTT). ADRs were categorized according to the international terminology Medical Dictionary for Regulatory Activities (MedDRA). Safety was assessed by calculating event rates per 100 patient-years (PY). We used descriptive statistics for patient and disease characteristics, and binomial and t-tests to compare treatment groups and sex. Results: In total, 791 patients (290 females) were included with a mean age of 46 years. 358 (45%) received CSTs and 433 (55%) biologics; both groups had similar baseline characteristics except for more joint involvement in patients using biologics (26.86% vs. 14.8%, p < 0.0001). CSTs were associated with a 2.2-fold higher ADR rate (40.43/100 PY vs. 18.22/100 PY, p < 0.0001) and an 8.0-fold higher drug-related discontinuation rate than biologics (0.16/PY vs. 0.02/PY, p < 0.0001). Trends showed non-significant higher serious adverse event rates per 100 PY for biologics (8.19, CI 6.87–9.68) compared to CSTs (7.08, CI 5.39–9.13) (p = 0.3922). Sex stratification revealed a significantly higher overall ADR rate for all treatments in females (1.8-fold for CSTs [57.30/100 PY vs. 31.69/100 PY] and 2.0-fold for biologics [27.36/100 PY vs. 13.9/100 PY], p < 0.0001), and drug-related discontinuation rates for most CSTs in females. Conclusion: Females were associated with a significantly higher rate of ADRs and drug-related discontinua

BACKGROUND AND INTRODUCTION Brain metastasis velocity (BMV) has been proposed as a prognostic factor for overall survival (OS) in patients with brain metastases (BMs). In this study, we conducted an external validation and comparative assessment of the performance of all three BMV scores. MATERIALS AND METHODS Patients treated with intracranial stereotactic radiotherapy (SRT) for BM at a single center between 2014 and 2018 were identified. Where possible, all three BMV scores were calculated. Log-rank tests and linear, logistic and Cox regression analysis were used for validation and predictor identification of OS. RESULTS For 333 of 384 brain metastasis patients, at least one BMV score could be calculated. In a sub-group of 187 patients, "classic" BMV was validated as categorical (p<0.0001) and continuous variable (HR 1.02; 95% CI 1.02-1.03; p<0.0001). In a sub-group of 284 patients, "initial" BMV was validated as categorical variable (high-risk vs. low-risk; p<0.01), but not as continuous variable (HR 1.02; 95% CI 0.99-1.04; p=0.224). "Volume-based" BMV could not be validated in a sub-group of 104 patients. On multivariable Cox regression analysis, iBMV (HR 1.85; 95% CI 1.01-3.38; p<0.05) and cBMV (HR 2.32; 95% CI 1.15 4.68; p<0.05) were predictors for OS for intermediate-risk patients after first SRT and first DBFs, respectively. cBMV proved to be the dominant predictor for OS for high-risk patients (HR 2.99; 95% CI 1.30-6.91; p<0.05). CONCLUSION This study externally validated cBMV and iBMV as prognostic scores for OS in patients treated with SRT for BMs whereas validation of vBMV was not achieved.

Background: Numerous prognostic scores (PS) for patients with brain metastases (BM) have been developed. Recently, PS based on laboratory parameters were introduced to better predict overall survival (OS). A comprehensive comparison of the wide range of scores in a modern patient collective is still missing. Materials and methods: Twelve PS considering clinical parameters only at the time of BM diagnosis were calculated for 470 patients receiving upfront SRS between January 2014 and March 2020. In a subcohort of 310 patients where a full laboratory dataset was available five additional prognostic scores were compared. Restricted mean survival time (RMST), partial likelihood and c-index were calculated as metrics for performance evaluation. Univariable and multivariable analysis were used to identify prognostic factors for OS. Results: The median OS of the whole cohort was 15.8 months (95% C.I.: 13.4–20.1). All prognostic scores performed well in separating patients into different prognostic groups. RPA achieved the highest c-index, whereas GGS achieved highest partial likelihood with evaluation in the total cohort. With incorporation of the laboratory scores the recently suggested EC-GPA achieved highest c-index and highest partial likelihood. A prognostic score solely based on the assessment of performance status achieved considerable high performance as either 3- or 4-tiered score. Multivariable analysis revealed performance status, systemic disease status and laboratory parameters to be significantly associated with OS among variates included in prognostic scores. Conclusion: Although recent PS incorporating laboratory parameters show convincing performance in predicting overall survival, older scores relying on clinical parameters only are still valid and appealing as they are easier to calculate, and as overall performance is almost equal. Moreover, a score just based on performance status is not significantly inferior and should at least be assessed for inf

Stereotactic radiosurgery (SRS) is the preferred primary treatment option for patients with a limited number of asymptomatic brain metastases. In case of relapse after initial SRS the optimal salvage treatment is not well defined. Within this retrospective analysis, we investigated the feasibility of repeated courses of SRS to defer Whole-Brain Radiation Therapy (WBRT) and aimed to derive prognostic factors for patient selection. From 2014 until 2017, 42 patients with 197 brain metastases have been treated with multiple courses of SRS at our institution. Treatment was delivered as single fraction (18 or 20 Gy) or hypo-fractionated (6 fractions with 5 Gy) radiosurgery. Regular follow-up included clinical examination and contrast-enhanced cMRI at 3-4 months' intervals. Besides clinical and treatment related factors, brain metastasis velocity (BMV) as a newly described clinical prognostic metric was included and calculated between first and second treatment. A median number of 1 lesion (range: 1-13) per course and a median of 2 courses (range: 2-6) per patient were administered resulting in a median of 4 (range: 2-14) metastases treated over time per patient. The median interval between SRS courses was 5.8 months (range: 0.9-35 months). With a median follow-up of 17.4 months (range: 4.6-45.5 months) after the first course of treatment, a local control rate of 84% was observed after 1 year and 67% after 2 years. Median time to out-of-field-brain-failure (OOFBF) was 7 months (95%CI 4-8 months). WBRT as a salvage treatment was eventually required in 7 patients (16.6%). Median overall survival (OS) has not been reached. Grouped by ds-GPA (≤ 2 vs. >2) the survival curves showed a significant split ( = 0.039). OS differed also significantly between BMV-risk groups when grouped into low vs. intermediate/high risk groups ( = 0.025). No grade 4 or 5 acute or late toxicity was observed. In selected patients with relapse after SRS for brain metastases, repeat courses of SRS were