No abstract

Antiangiogenic therapies, despite initial encouragement, have demonstrated a limited benefit in ovarian cancer. Laboratory studies suggest antiangiogenic therapy-induced hypoxia can induce tumor "stemness" as resistance to antiangiogenic therapy develops and limits the therapeutic benefit. Resistance to antiangiogenic therapy and an induction of tumor stemness may be mediated by proangiogenic tumor-associated macrophages (TAM). As such, TAMs have been proposed as a therapeutic target. We demonstrate here that ovarian TAMs express high levels of the folate receptor-2 (FOLR2) and can be selectively targeted using G5-dendrimer nanoparticles using methotrexate as both a ligand and a toxin. G5-methotrexate (G5-MTX) nanoparticles deplete TAMs in both solid tumor and ascites models of ovarian cancer. As a therapeutic agent, these nanoparticles are more effective than cisplatin. Importantly, these nanoparticles could (i) overcome resistance to antiangiogenic therapy, (ii) prevent antiangiogenic therapy-induced increases in cancer stem-like cells in both murine and human tumor cell models, (iii) prevent antiangiogenic therapy-induced increases in VEGF-C, and (iv) prevent antiangiogenic therapy-induced BRCA1 gene expression. Combined, this work strongly supports the development of TAM-targeted nanoparticle therapy. .

Key Points Question Is maintenance therapy after first-line treatment of ovarian cancer cost-effective in the United States? Findings In this economic evaluation of maintenance strategies after first-line ovarian cancer therapy, no maintenance regimen—including olaparib, olaparib-bevacizumab, bevacizumab, and niraparib—was cost-effective when using a willingness-to-pay threshold of $100 000 per progression-free life-year saved, even when stratified by molecular signatures. Olaparib monotherapy became cost-effective for patients with a BRCA variant when current olaparib pricing was reduced by half. Meaning Various frontline maintenance therapies for ovarian cancer may have clinical benefit but may not be considered cost-effective, even with reductions in drug pricing.

Female first authorship and senior authorship in academic obstetrics and gynecology has increased over time but gender-specific publishing data are lacking within gynecologic oncology. We examined contribution by gender to the subspecialty's flagship journal, Gynecologic Oncology, over five decades, from 1972 to 2014, to identify trends in gender representation. Chi-square tests were used to compare gender distributions within and between the first and last years studied (1972–73 and 2014) as well as linear regression to model trends over time. Female first and senior authorship increased significantly from 1972 to 2014 (first: χ2 = 20.9, p < .01; senior: χ2 = 9.9, p < .01). The number of female first authors increased markedly after 2000. Male senior authors still outnumber female senior authors. Papers with senior female authors were more likely to have female first authors, suggesting a mentorship role. Subspecialty-wide gender equity initiatives should encourage continued mentorship of women by female colleagues.