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OBJECTIVE Bevacizumab is an antiangiogenic agent under investigation for use in patients with high-grade glioma. It produces a high rate of radiological response; however, this response should be interpreted with caution because it may reflect normalization of the tumor vasculature and not necessarily a true antitumor effect. The authors previously demonstrated that 4 hypoxia-mediated microRNAs (miRNA)-miR-210, miR-21, miR-10b, and miR-196b-are upregulated in glioma as compared with normal brain tissue. The authors hypothesized that the regulation and expression of these miRNAs would be altered in response to bevacizumab treatment. The object of this study was to perform longitudinal monitoring of circulating miRNA levels in patients undergoing bevacizumab treatment and to correlate it with tumor response. METHODS A total of 120 serum samples from 28 patients with high-grade glioma were prospectively collected prior to bevacizumab (n = 15) or temozolomide (TMZ; n = 13) treatment and then longitudinally during treatment. Quantification of the 4 miRNAs was evaluated by real-time polymerase chain reaction using total RNA extracted from the serum. At each time point, tumor response was assessed by Response Assessment in Neuro-Oncology criteria and by performing MRI using fluid attenuated inversion recovery (FLAIR) and contrast-enhanced images. RESULTS As compared with pretreatment levels, high levels of miR-10b and miR-21 were observed in the majority of patients throughout the bevacizumab treatment period. miR-10b and miR-21 levels correlated negatively and significantly with changes in enhancing tumor diameters (r = -0.648, p < 0.0001) in the bevacizumab group but not in the TMZ group. FLAIR images and the RANO assessment did not correlate with the sum quantification of these miRNAs in either group. CONCLUSIONS Circulating levels of miR-10b and miR-21 probably reflect the antiangiogenic effect of therapy, but their role as biomarkers for tumor response remains uncertain and requires further investigation.

PURPOSE Endometrial cancer (EC) incidence has been rising over the past 10 years. Delays in diagnosis reduce survival and necessitate more aggressive treatment. We aimed to develop and validate a simple, noninvasive, and reliable triage test for EC to reduce the number of invasive diagnostic procedures and improve patient survival. METHODS We developed a test to screen and triage women with suspected EC using 726 cervical smear samples from women with and without EC, and validated the test in 562 cervicovaginal samples using three different collection methods (cervical smear: n = 248; vaginal swab: n = 63; and self-collection: n = 251) and four different settings (case/control: n = 388; cohort of women presenting with postmenopausal bleeding: n = 63; a cohort of high-risk women with Lynch syndrome: n = 25; and a nested case/control setting from a screening cohort and samples taken up to 3 years before EC diagnosis: n = 86). RESULTS We describe the Women's cancer risk IDentification – quantitative polymerase chain reaction test for Endometrial Cancer (WID-qEC), a three-marker test that evaluates DNA methylation in gene regions of GYPC and ZSCAN12. In cervical, self-collected, and vaginal swab samples derived from symptomatic patients, it detected EC with sensitivities of 97.2% (95% CI, 90.2 to 99.7), 90.1% (83.6 to 94.6), and 100% (63.1 to 100), respectively, and specificities of 75.8% (63.6 to 85.5), 86.7% (79.3 to 92.2), and 89.1% (77.8 to 95.9), respectively. The WID-qEC identified 90.9% (95% CI, 70.8 to 98.9) of EC cases in samples predating diagnosis up to 1 year. Test performance was similar across menopausal status, age, stage, grade, ethnicity, and histology. CONCLUSION The WID-qEC is a noninvasive reliable test for triage of women with symptoms suggestive of ECs. Because of the potential for self-collection, it could improve early diagnosis and reduce the reliance for in-person visits.

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