Meta-analysis in metastatic uveal melanoma to determine progression free and overall survival benchmarks: an international rare cancers initiative (IRCI) ocular melanoma study.

BACKGROUND: Despite the completion of numerous phase II studies, a standard of care treatment has yet to be defined for metastatic uveal melanoma (mUM). To determine benchmarks of progression free survival (PFS) and overall survival (OS), we carried out a meta-analysis using individual patient level trial data. METHODS: Individual patient variables and survival outcomes were requested from 29 trials published from 2000 to 2016. Univariable and multivariable analysis were carried out for prognostic factors. The variability between trial arms and between therapeutic agents on PFS and OS was investigated. RESULTS: OS data were available for 912 patients. The median PFS was 3.3 months (95% CI 2.9-3.6) and 6-month PFS rate was 27% (95% CI 24-30). Univariable analysis showed male sex, elevated (i.e. > versus ≤ upper limit of normal) lactate dehydrogenase (LDH), elevated alkaline phosphatase (ALP) and diameter of the largest liver metastasis (≥3 cm versus <3 cm) to be substantially associated with shorter PFS. Multivariable analysis showed male sex, elevated LDH and elevated ALP were substantially associated with shorter PFS. The most substantial factors associated with 6-month PFS rate, on both univariable and multivariable analysis were elevated LDH and ALP. The median OS was 10.2 months (95% CI 9.5-11.0) and 1 year OS was 43% (95% CI 40-47). The most substantial prognostic factors for shorter OS by univariable and multivariable analysis were elevated LDH and elevated ALP. Patients treated with liver directed treatments had statistically significant longer PFS and OS. CONCLUSION: Benchmarks of 6-month PFS and 1-year OS rates were determined accounting for prognostic factors. These may be used to facilitate future trial design and stratification in mUM.

Swollen joint count in psoriatic arthritis is associated with progressive radiological damage in hands and feet.

OBJECTIVES: Psoriatic arthritis (PsA) may progress to joint damage. Determining clinical predictors of joint damage assessed by radiography is important. The aim of this study was to determine clinical factors as possible predictors for radiological damage in hands and feet of PsA patients with a 12-month follow-up. METHODS: We conducted a retrospective study on 53 PsA patients who were taking disease-modifying anti-rheumatic drugs (DMARDs) and/or tumour necrosis factor (TNF)-alpha-blockers at a fixed dosage. The patients were observed in 118 follow-up visits (intervals of 12 months ± 3 months), according to a clinical and radiological protocol which included the documentation of the number of swollen and tender joints in hands and feet, the applied therapy, psoriasis, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and global health assessment. Outcome was defined as radiographic damage of hands and feet (Ratingen score). For the statistical analysis the Chi-Square test for 2x2 crosstables (with Fisher's correction, as required) was used. RESULTS: Progressive radiological damage was more frequent among patients with an increasing swollen joint count (8 of 26 visits; 30.8%) than among those with a stable or decreased number of swollen joints (5 of 89 visits; 5.6%; p=0.001). The analysis of the patients stratified into the different treatment modalities resulted in a significant higher rate of radiological progress (20.8%) in patients on DMARD therapy compared with TNF-alpha blocking agents (0%) (p=0.009). CONCLUSIONS: During a 12-month follow-up of PsA patients, an increasing number of swollen joints heralds progression of radiological damage. TNF-alpha-blocker therapy appears to be superior to DMARDs in the protection from radiological progress.