The MOTION study: a randomized, phase III study of vimseltinib for the treatment of tenosynovial giant cell tumor.

Tenosynovial giant cell tumor (TGCT) is a rare, locally aggressive neoplasm that occurs in the synovium of joints, bursae, or tendon sheaths and is caused by upregulation of the CSF1 gene. Vimseltinib is an oral switch-control tyrosine kinase inhibitor specifically designed to selectively and potently inhibit the CSF1 receptor. Here, we describe the rationale and design for the phase III MOTION trial (NCT05059262), which aims to evaluate the efficacy and safety of vimseltinib in participants with TGCT not amenable to surgical resection. In part 1, participants are randomized to receive vimseltinib 30 mg twice weekly or matching placebo for ≤24 weeks. Part 2 is a long-term treatment phase in which participants will receive open-label vimseltinib.

Tenosynovial giant cell tumor (or TGCT) is a rare, noncancerous tumor that grows in the soft tissue lining the spaces of joints and bursae (fluid-filled sacs that work to reduce friction in the joints). These tumors are linked to increased levels of a protein called CSF1. While this condition is typically treated with surgery, some patients may not be candidates for surgical removal of the tumor due to factors such as location or complexity of the tumor; therefore, drug treatments are needed to help these patients. Vimseltinib is an investigational oral drug specifically designed to inhibit the receptor to which the CSF1 protein binds. In this article, we describe the rationale and design for a phase III clinical trial that will test how well vimseltinib works in participants with TGCT who are not candidates for surgery. In the first part of the study, participants are randomly assigned to receive vimseltinib 30 mg twice weekly or a matching placebo (inactive substance) for up to 24 weeks. This first part is blinded, so participants will not know if they are receiving vimseltinib or the placebo. The second part of the study is a long-term treatment phase in which all participants will receive vimseltinib (unblinded). Clinical Trial Registration: NCT05059262 (ClinicalTrials.gov).

Correlation of FIBROSpect II with histologic and morphometric evaluation of liver fibrosis in chronic hepatitis C.

BACKGROUND & AIMS: Accurate disease staging in chronic hepatitis C (CHC) infection helps guide treatment and may provide prognostic information. Liver biopsies are invasive, costly, and associated with morbidity. We hypothesized that a noninvasive test of liver fibrosis can accurately stage liver fibrosis. We prospectively evaluated the FIBROSpect II (FSII) biomarker panel versus pathology assessment and a quantitative measure of fibrosis. METHODS: Liver biopsy specimens and serum were obtained from 252 CHC patients, including 50 posttransplant, from 3 tertiary centers. Biopsy specimens were scored centrally and independently at each site, along with central quantification of fibrosis by digitized morphometry. Serum tests were performed blinded to clinical or histologic evaluation. RESULTS: The mean biopsy specimen length was 1.95 +/- 0.87 cm; prevalence of stage F2 through F4 fibrosis was 77%. Agreement between central and site readings for individual stages was modest (k = 0.674), with concordant readings in 106 of 248 (43%) biopsy specimens. The area under the receiver operating characteristic curve for FSII and morphometry for stages F2 through F4 for concordant biopsy specimens were 0.823 and 0.728, respectively. Sensitivity and specificity for FSII were 83.5% and 66.7%, respectively, with an accuracy of 80.2%. The aspartate aminotransferase to platelet ratio index sensitivity and specificity for predicting F2 through F4 were 30.4% and 100%, respectively, the indeterminate rate was 40.4%, and the accuracy rate was 48.4%. The accuracy of FSII in concordant biopsy specimens in the posttransplant cohort was 73%. CONCLUSIONS: Serum biomarkers can differentiate mild from moderate-to-severe fibrosis. This prospective study validates the performance characteristics of FSII in CHC patients and a posttransplant cohort. Assessing the diagnostic utility of biomarkers is limited by variability in methods to quantify fibrosis and poor interobserver agreement for histologic staging.

Serum insulin levels and the prevalence of adenomatous and hyperplastic polyps in the proximal colon.

BACKGROUND & AIMS: Obesity and diabetes mellitus are associated with an increased incidence of proximal colon cancer. Colonic adenoma that has been reported to be associated with elevated serum insulin levels and subsets of hyperplastic polyps might serve as a precursor of colon cancer. In this study, we sought to determine segment-specific associations between serum insulin levels and the prevalence of adenoma and hyperplastic polyps in the proximal and distal colon. METHODS: We studied 343 consecutive patients who underwent colonoscopy in our hospital. All medical information, including fasting serum insulin, was obtained at colonoscopy. We performed multinomial logistic regression models by using the outcome categories of none (reference), proximal-only, distal-only, and both-segment lesions for the presence of adenoma/hyperplastic polyp with serum insulin, age, gender, lifestyle characteristics, and the presence of other types of lesions as predictors. Odds ratios (ORs) and 95% confidence intervals (CIs) are provided for a 5-muU/mL increase in serum insulin. RESULTS: Overall, serum insulin levels were significantly associated with adenoma (OR, 1.5; 95% CI, 1.1-2.0; P = .005) and borderline associated with hyperplastic polyps (OR, 1.3; 95% CI, 1.0-1.7; P = .075). In multinomial logistic regression models, elevated serum insulin levels were significantly associated with proximal-only adenoma (OR, 1.8; 95% CI, 1.2-2.5; P = .002), both-side hyperplastic polyp (OR, 1.7; 95% CI, 1.1-2.5; P = .015), and proximal-only hyperplastic polyp (OR, 1.5; 95% CI, 1.0-2.1; P = .048) and borderline associated with distal-only adenoma (OR, 1.5; 95% CI, 1.0-2.1; P =.059) but not with distal-only hyperplastic polyp. CONCLUSIONS: Serum insulin levels directly correlate with the presence of adenoma and hyperplastic polyps in the proximal colon and might also less strongly correlate with the presence of distal adenoma.

The impact of steatosis on disease progression and early and sustained treatment response in chronic hepatitis C patients.

BACKGROUND/AIMS: Questions remain regarding the etiology of steatosis in hepatitis C, and its impact on disease progression and treatment outcomes. METHODS: We evaluated liver biopsies from 574 patients with chronic hepatitis C from a single center. RESULTS: Severity of steatosis was associated with body mass index, HCV genotype 3 infection, age, and duration of infection (P

A Bayesian approach to case-control studies with errors in covariables.

We develop Bayesian methodology for the analysis of case-control data with covariate imprecision. The pretense that the distribution of the imprecisely measured covariate is discrete on a heuristically chosen support set leads to a method which is reasonably simple to implement, and can be applied to different study designs. The methodological development emphasizes the interplay between retrospective and prospective analysis. We illustrate the method on simulated data, and on data from a cancer study where smoking history is the imprecisely measured covariate.