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Background: A phase 2, randomized, placebo-controlled trial was conducted in women with recurrent epithelial ovarian carcinoma to evaluate the efficacy and safety of motolimod--a Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses--combined with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces immunogenic cell death. Patients and methods: Women with ovarian, fallopian tube, or primary peritoneal carcinoma were randomized 1 : 1 to receive PLD in combination with blinded motolimod or placebo. Randomization was stratified by platinum-free interval (≤6 versus >6-12 months) and Gynecologic Oncology Group (GOG) performance status (0 versus 1). Treatment cycles were repeated every 28 days until disease progression. Results: The addition of motolimod to PLD did not significantly improve overall survival (OS; log rank one-sided P = 0.923, HR = 1.22) or progression-free survival (PFS; log rank one-sided P = 0.943, HR = 1.21). The combination was well tolerated, with no synergistic or unexpected serious toxicity. Most patients experienced adverse events of fatigue, anemia, nausea, decreased white blood cells, and constipation. In pre-specified subgroup analyses, motolimod-treated patients who experienced injection site reactions (ISR) had a lower risk of death compared with those who did not experience ISR. Additionally, pre-treatment in vitro responses of immune biomarkers to TLR8 stimulation predicted OS outcomes in patients receiving motolimod on study. Immune score (tumor infiltrating lymphocytes; TIL), TLR8 single-nucleotide polymorphisms, mutational status in BRCA and other DNA repair genes, and autoantibody biomarkers did not correlate with OS or PFS. Conclusions: The addition of motolimod to PLD did not improve clinical outcomes compared with placebo. However, subset analyses identified statistically significant differences in the OS of motolimod-treated patients on the basis of ISR and in vitro immune responses. Collectively, these data may provide important clues for identifying patients for treatment with immunomodulatory agents in novel combinations and/or delivery approaches. Trial registration: Clinicaltrials.gov, NCT 01666444. [ABSTRACT FROM AUTHOR]

In order to constrain the evolutionary state of the red supergiant Betelgeuse (α Orionis), we have produced a suite of models with zero-age main sequence masses from 15 to 25 M☉ in intervals of 1M☉ including the effects of rotation. The models were computed with the stellar evolutionary code MESA. For non-rotatingmodels, we find results that are similar to other work. It is somewhat difficult to find models that agree within 1σ of the observed values of R, Teff and L, but modestly easy within 3σ uncertainty. Incorporating the nominal observed rotational velocity, ~15 km s-1, yields significantly different and challenging constraints. This velocity constraint is only matched when the models first approach the base of the red supergiant branch (RSB), having crossed the Hertzsprung gap, but not yet having ascended the RSB and most violate even generous error bars on R, Teff and L. Models at the tip of the RSB typically rotate at only ~0.1 kms-1, independent of any reasonable choice of initial rotation. We discuss the possible uncertainties in our modelling and the observations, including the distance to Betelgeuse, the rotation velocity and model parameters. We summarize various options to account for the rotational velocity and suggest that one possibility is that Betelgeuse merged with a companion star of about 1 M☉ as it ascended the RSB, in the process producing the ring structure observed at about 7 arcmin away. A past coalescence would complicate attempts to understand the evolutionary history and future of Betelgeuse. [ABSTRACT FROM AUTHOR]

Focuses on the outcomes of stage I uterine papillary serous carcinoma patients with or without adjuvant therapy after comprehensive surgical staging. Information on the results relating to adjuvant therapy; Disease-free survival rates for the observation and radiation therapy groups.