The performance of human papillomavirus high-risk DNA testing in the screening and diagnostic settings.

OBJECTIVE: We sought to evaluate the performance of the human papillomavirus high-risk DNA test in patients 30 years and older. MATERIALS AND METHODS: Screening (n=835) and diagnosis (n=518) groups were defined based on prior Papanicolaou smear results as part of a clinical trial for cervical cancer detection. We compared the Hybrid Capture II (HCII) test result with the worst histologic report. We used cervical intraepithelial neoplasia (CIN) 2/3 or worse as the reference of disease. We calculated sensitivities, specificities, positive and negative likelihood ratios (LR+ and LR-), receiver operating characteristic (ROC) curves, and areas under the ROC curves for the HCII test. We also considered alternative strategies, including Papanicolaou smear, a combination of Papanicolaou smear and the HCII test, a sequence of Papanicolaou smear followed by the HCII test, and a sequence of the HCII test followed by Papanicolaou smear. RESULTS: For the screening group, the sensitivity was 0.69 and the specificity was 0.93; the area under the ROC curve was 0.81. The LR+ and LR- were 10.24 and 0.34, respectively. For the diagnosis group, the sensitivity was 0.88 and the specificity was 0.78; the area under the ROC curve was 0.83. The LR+ and LR- were 4.06 and 0.14, respectively. Sequential testing showed little or no improvement over the combination testing. CONCLUSIONS: The HCII test in the screening group had a greater LR+ for the detection of CIN 2/3 or worse. HCII testing may be an additional screening tool for cervical cancer in women 30 years and older

Ipilimumab, Pembrolizumab, or Nivolumab in Combination with BBI608 in Patients with Advanced Cancers Treated at MD Anderson Cancer Center

Background: BBI608 is an investigational reactive oxygen species generator that affects several molecular pathways. We investigated BBI608 combined with immune checkpoint inhibitors in patients with advanced cancers. Methods: BBI608 (orally twice daily) was combined with ipilimumab (3 mg/kg IV every 3 weeks); pembrolizumab (2 mg/kg IV every 3 weeks); or nivolumab (3 mg/kg IV every 4 weeks). We assessed the safety, antitumor activity and the pharmacokinetic profile of BBI combined with immunotherapy. Results: From 1/2017 to 3/2017, 12 patients were treated (median age, 54 years; range, 31–78; 6 men). Treatment was overall well tolerated. No dose-limiting toxicity was observed. The most common adverse events were diarrhea (5 patients: grade (G)1–2, n = 3; G3, n = 2) and nausea (4 patients, all G1). Prolonged disease stabilization was noted in five patients treated with BBI608/nivolumab lasting for 12.1, 10.1, 8.0, 7.7 and 7.4 months. The median progression-free survival was 2.73 months. The median overall survival was 7.56 months. Four patients had prolonged overall survival (53.0, 48.7, 51.9 and 48.2 months). Conclusions: Checkpoint inhibitors combined with BBI608 were well tolerated. Several patients had prolonged disease stabilization and overall survival. Prospective studies to elucidate the mechanisms of response and resistance to BBI608 are warranted

The Accuracy of the Papanicolaou Smear in the Screening and Diagnostic Settings

Objective. We evaluated the performance of the Papanicolaou smear in screening and diagnostic settings. Study Design. We analyzed Papanicolaou smear results of 1,850 women recruited into a clinical trial to evaluate an emerging technology for the detection of cervical cancer. Screening and diagnosis groups were based on the history of previous Papanicolaou smear results. We calculated sensitivities, specificities, positive and negative likelihood ratios (LR+ and LRj), receiver operating characteristic curves, and areas under the receiver operating characteristic curve (AUC). Results. In the screening group, by defining disease as cervical intraepithelial neoplasia (CIN) 2,3/cancer or worse and using high-grade squamous intraepithelial lesion (HSIL) as the test cutpoint, the AUC was 0.689, and the LR+ and LRj were 39.25 and 0.67, respectively. In the diagnosis group, the AUC was 0.764, and the LR+ and LRj were 3.79 and 0.56, respectively. By defining disease as human papillomavirus/CIN 1 or worse and HSIL as the test cutpoint, the AUC was 0.586, and the LR+ and LRj were 17.01 and 0.92 in the screening group; in the diagnosis group, the AUC was 0.686, and the LR+ and LRj were 2.77 and 0.75, respectively. Conclusions. In a screening setting, a Papanicolaou smear result of HSIL or worse is 39 times more likely in a patient with CIN 2,3/cancer than in a patient without it. This compares to 4 times more likely in the diagnostic setting. The magnitude of the positive likelihood ratio observed in the screening group indicated that abnormal Papanicolaou smear results obtained in the screening setting should have more impact on clinical decision making than those from results obtained in the diagnostic setting.

Patient Characteristics and Outcomes in Adolescents and Young Adults (AYA) With Acute Myeloid Leukemia (AML)

BackgroundLittle is known about outcomes of acute myeloid leukemia (AML) in adolescents and young adults (AYA). The purpose of this study is to determine the characteristics and outcomes of AYA AML patients in comparison to older adult patients with AML.Patients and methodsWe retrospectively analyzed all AML patients treated at our institution from 1965 to 2009 who were aged 16 to 29 years.ResultsAmong 3922 adult AML patients treated during this period, 432 (11%) were identified as AYA. Median age was 23 years (range, 16-29 years); 73 (17%) patients had core binding factor (CBF)-AML [inversion (16), translocation (8:21)], and 51 (12%) had acute promyelocytic leukemia. Complete remission (CR) rates were 93% for CBF AML, 78% for APL, 77% with diploid karyotype, and 68% for other AML. Univariate analysis demonstrated higher rates of CR, CR duration, and overall survival (OS) in the AYA group compared with older patients. On multivariate analysis, AYA age group was independently associated with improved CR rate and CR duration, with a trend for longer OS (P = .085).ConclusionOutcome of AYA AML patients is overall better than for older adults with AML. Despite improvements in treatments and outcomes over time, there is still need for improvement in AYA with AML particularly for those with AML other than CBF and APL