Episodic excursions of low-mass protostars on the Hertzsprung-Russell diagram

Following our recent work devoted to the effect of accretion on the pre-main-sequence evolution of low-mass stars, we perform a detailed analysis of episodic excursions of low-mass protostars in the Hertzsprung-Russell (H-R) diagram triggered by strong mass accretion bursts typical of FU Orionis-type objects (FUors). These excursions reveal themselves as sharp increases in the stellar total luminosity and/or effective temperature of the protostar and can last from hundreds to a few thousands of years, depending on the burst strength and characteristics of the protostar. During the excursions, low-mass protostars occupy the same part of the H-R diagram as young intermediate-mass protostars in the quiescent phase of accretion. Moreover, the time spent by low-mass protostars in these regions is on average a factor of several longer than that spent by the intermediate-mass stars in quiescence. During the excursions, low-mass protostars pass close to the position of most known FUors in the H-R diagram, but owing to intrinsic ambiguity the model stellar evolutionary tracks are unreliable in determining the FUor properties. We find that the photospheric luminosity in the outburst state may dominate the accretion luminosity already after a few years after the onset of the outburst, meaning that the mass accretion rates of known FUors inferred from the bolometric luminosity may be systematically overestimated, especially in the fading phase.Comment: 15 pages, 12 figure

Phase Ib/II Study of the Safety and Efficacy of Combination Therapy with Multikinase VEGF Inhibitor Pazopanib and MEK Inhibitor Trametinib In Advanced Soft Tissue Sarcoma.

Purpose: Pazopanib, a multireceptor tyrosine kinase inhibitor targeting primarily VEGFRs1–3, is approved for advanced soft tissue sarcoma (STS) and renal cell cancer. Downstream of VEGFR, trametinib is an FDA-approved MEK inhibitor used for melanoma. We hypothesized that vertical pathway inhibition using trametinib would synergize with pazopanib in advanced STS. Experimental Design: In an open-label, multicenter, investigator-initiated National Comprehensive Cancer Network (NCCN)-sponsored trial, patients with metastatic or advanced STS received pazopanib 800 mg and 2 mg of trametinib continuously for 28-day cycles. The primary endpoint was 4-month progression-free survival (PFS). Secondary endpoints were overall survival, response rate, and disease control rate. Results: Twenty-five patients were enrolled. The median age was 49 years (range, 22–77 years) and 52% were male. Median PFS was 2.27 months [95% confidence interval (CI), 1.9–3.9], and the 4-month PFS rate was 21.1% (95% CI, 9.7–45.9), which was not an improvement over the hypothesized null 4-month PFS rate of 28.3% (P ¼ 0.79). Median overall survival was 9.0 months (95% CI, 5.7–17.7). A partial response occurred in 2 (8%) of the evaluable patients (95% CI, 1.0–26.0), one with PIK3CA E542K-mutant embryonal rhabdomyosarcoma and another with spindle cell sarcoma. The disease control rate was 14/25 (56%; 95% CI, 34.9–75.6). The most common adverse events were diarrhea (84%), nausea (64%), and fatigue (56%). Conclusions: The combination of pazopanib and trametinib was tolerable without indication of added activity of the combination in STS. Further study may be warranted in RAS/RAF aberrant sarcomas. ©2017 AACR