21 research outputs found
Vaginal recurrence of endometrial cancer: MRI characteristics and correlation with patient outcome after salvage radiation therapy
Purpose To evaluate MRI characteristics in vaginal recurrence of endometrial cancer (EC) including tumor volume shrinkage during salvage radiotherapy, and to identify imaging features associated with survival. Methods Patients with vaginal recurrence of EC treated with external beam radiotherapy (EBRT) followed by brachytherapy (BT), and with available pelvic MRI at two time points: baseline and/or before BT were retrospectively identified from 2004 to 2017. MRI features including recurrence location and tissue characteristics on T2- and T1-weighted images were evaluated at baseline only. Tumor volumes were measured both at baseline and pre-BT. Survival rates and associations were evaluated by Cox regression and Fisher's exact test, respectively. Results Sixty-two patients with 36 baseline and 50 pre-BT pelvic MRIs were included (24/62 with both MRIs). Vaginal recurrence of EC was most commonly located in the vaginal apex (27/36, 75%). Tumors with a post-contrast enhancing peripheral rim or low T2 signal rim at baseline showed longer recurrence-free survival (RFS) (HR 0.2, 95% CI 0.1-0.9, P < 0.05 adjusted for histology; HR 0.2, 95% CI 0.1-0.8, P < 0.05, respectively). The median tumor shrinkage at pre-BT was 69% (range 1-99%). Neither absolute tumor volumes nor volume regression at pre-BT were associated with RFS. Lymphovascular space invasion (LVSI) at hysterectomy and adjuvant RT were associated with recurrence involving the distal vagina (both P < 0.05). Conclusion Vaginal recurrences with rim enhancement at baseline MRI predicted improved RFS, while tumor volume shrinkage at pre-BT did not. Distal vaginal recurrence was more common in patients with LVSI and adjuvant RT at EC diagnosis
Impact of Poxvirus Vector Priming, Protein Coadministration, and Vaccine Intervals on HIV gp120 Vaccine-Elicited Antibody Magnitude and Function in Infant Macaques
ABSTRACT Despite success in reducing vertical HIV transmission by maternal antiretroviral therapy, several obstacles limit its efficacy during breastfeeding, and breast-milk transmission is now the dominant mode of mother-to-child transmission (MTCT) of HIV in infants. Thus, a pediatric vaccine is needed to eradicate oral HIV infections in newborns and infants. Utilizing the infant rhesus macaque model, we compared 3 different vaccine regimens: (i) HIV envelope (Env) protein only, (ii) poxvirus vector (modified vaccinia virus Ankara [MVA])-HIV Env prime and HIV Env boost, and (iii) coadministration of HIV Env and MVA-HIV Env at all time points. The vaccines were administered with an accelerated, 3-week-interval regimen starting at birth for early induction of highly functional HIV Env-specific antibodies. We also tested whether an extended, 6-week immunization interval using the same vaccine regimen as in the coadministration group would enhance the quality of antibody responses. We found that pediatric HIV vaccines administered at birth are effective in inducing HIV Env-specific plasma IgG. The vaccine regimen consisting of only HIV Env protein induced the highest levels of variable region 1 and 2 (V1V2)-specific antibodies and tier 1 neutralizing antibodies, whereas the extended-interval regimen induced both persistent Env-specific systemic IgG and mucosal IgA responses. Antibody-dependent cell-mediated cytotoxicity (ADCC) antibodies in plasma were elicited by all vaccine regimens. These data suggest that infant immunizations beginning at birth are effective for the induction of functional HIV Env-specific antibodies that could potentially protect against breast milk transmission of HIV and set the stage for immunity prior to sexual debut
Evaluation of Fecal Immunochemical Tests for Colorectal Cancer Screening
Background: Colorectal cancer (CRC) screening reduces the mortality due to CRC. It is important for health care providers to be aware of the variation in the products available for CRC screening. Purpose: The purpose of this study was to summarize the accuracy of results of individual fecal immunochemical test (FIT) products across pathology proficiency testing programs. Methods: Secondary data analysis of proficiency testing programs’ FIT results. Results: Four of 7 proficiency testing program’s FIT evaluations were obtained for a 2-year period. Fourteen unique FIT brands were evaluated by at least 1 of the 4 proficiency testing programs. Five of the products performed similarly with sensitivities ranging from 98.1% to 98.8% and specificities from 98.1% to 99.6%. Ninety-three percent of the FIT tests completed were manual Clinical Laboratory Improvement Amendments–waived FITs. Conclusions: About two thirds of the commonly used FIT products performed acceptably on spiked samples of human hemoglobin. However, some had low sensitivity and specificity and probably should not be used for population-based or other screening. Further investigation to determine appropriate, reliable products for fecal occult blood testing is warranted
Incidence and Cause of Delirium in Hospitalized Patients between the Ages of 18 and 56: A Retrospective Chart Review
Background. Delirium is a common and devastating condition which has been well characterized in elderly cancer patients, but little is known about delirium in cancer patients under the age of 65. Aim. A pilot study to explore the incidence and potential causes of delirium in hospitalized advanced cancer patients at the age of 18–56 years. Design. A retrospective chart review using validated instruments was used to examine the charts of hematology-oncology admissions in a large academic institution. Data was collected as to the likelihood of delirium and potential precipitants. Results. Delirium incidence was 29% among advanced cancer patients. The associated precipitants of delirium were multifactorial, the most common being medications and infection. Delirium was more common in patients admitted for either acute symptom management or the presence of a lung malignancy. Patients with delirium demonstrated significantly increased total hospital cost and a borderline significant result for increased mortality compared to those without delirium. Conclusions. Delirium is common in hospitalized advanced cancer patients (age 18–56 years) and the cause is typically multifactorial. Delirium results in a more complicated hospital course and likely increased mortality. Further research is needed to define strategies to prevent and treat this common and distressing condition
Evaluation of Risk Prediction with Hierarchical Data: Dependency Adjusted Confidence Intervals for the AUC
The area under the true ROC curve (AUC) is routinely used to determine how strongly a given model discriminates between the levels of a binary outcome. Standard inference with the AUC requires that outcomes be independent of each other. To overcome this limitation, a method was developed for the estimation of the variance of the AUC in the setting of two-level hierarchical data using probit-transformed prediction scores generated from generalized estimating equation models, thereby allowing for the application of inferential methods. This manuscript presents an extension of this approach so that inference for the AUC may be performed in a three-level hierarchical data setting (e.g., eyes nested within persons and persons nested within families). A method that accounts for the effect of tied prediction scores on inference is also described. The performance of 95% confidence intervals around the AUC was assessed through the simulation of three-level clustered data in multiple settings, including ones with tied data and variable cluster sizes. Across all settings, the actual 95% confidence interval coverage varied from 0.943 to 0.958, and the ratio of the theoretical variance to the empirical variance of the AUC varied from 0.920 to 1.013. The results are better than those from existing methods. Two examples of applying the proposed methodology are presented
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Persistent inter-observer variability of breast density assessment using BI-RADS® 5th edition guidelines
Due to most states' legislation, mammographic density categorization has potentially far-reaching implications, but remains subjective based on BIRADS® guidelines. We aimed to determine 1) effect of BI-RADS® 5th edition (5th-ed) vs 4th-edition (4th-ed) guidelines on reader agreement regarding density assessment; 2) 5th-ed vs 4th-ed density distribution, and visual vs quantitative assessment agreement; 3) agreement between experienced vs less experienced readers.
In a retrospective review, six breast imaging radiologists (BIR) (23–30 years' experience) visually assessed density of 200 screening mammograms performed September 2012–January 2013 using 5th-ed guidelines. Results were compared to 2016 data of the same readers evaluating the same mammograms using 4th-ed guidelines after a training module. 5th-ed density categorization by seven junior BIR (1–5 years' experience) was compared to eight experienced BIR. Nelson et al.'s kappas (κm, κw), Fleiss' κF, and Cohen's κ were calculated. Quantitative density using Volpara was compared with reader assessments.
Inter-reader weighted agreement using 5th-ed is moderately strong, 0.73 (κw, s.e. = 0.01), similar to 4th-ed, 0.71 (κw, s.e. = 0.03). Intra-reader Cohen's κ is 0.23–0.34, similar to 4th-ed. Binary not-dense vs dense categorization, using 5th-ed results in higher dense categorization vs 4th-ed (p < 0.001). 5th-ed density distribution results in higher numbers in categories B/C vs 4th-ed (p < 0.001). Distribution for 5th-ed does not differ based on reader experience (p = 0.09). Reader vs quantitative weighted agreement is similar (5th-ed, Cohen's κ = 0.76–0.85; 4th-ed, Cohen's κ = 0.68–0.83).
There is persistent subjectivity of visually assessed mammographic density using 5th-ed guidelines; experience does not correlate with better inter-reader agreement.
•Mammographic density inter-reader agreement remains variable and persistently subjective.•Using BI-RADS® 5th edition compared to the 4th edition, breast imagers assess more mammograms as dense.•No difference in breast density distribution is observed based on experience level
A Pilot Study of Multidimensional Diffusion MRI for Assessment of Tissue Heterogeneity in Prostate Cancer
OBJECTIVES: The objectives of this exploratory study were to investigate the feasibility of multidimensional diffusion magnetic resonance imaging (MddMRI) in assessing diffusion heterogeneity at both a macroscopic and microscopic level in prostate cancer (PCa).MATERIALS AND METHODS: Informed consent was obtained from 46 subjects who underwent 3.0-T prostate multiparametric MRI, complemented with a prototype spin echo-based MddMRI sequence in this institutional review board-approved study. Prostate cancer tumors and comparative normal tissue from each patient were contoured on both apparent diffusion coefficient and MddMRI-derived mean diffusivity (MD) maps (from which microscopic diffusion heterogeneity [MKi] and microscopic diffusion anisotropy were derived) using 3D Slicer. The discriminative ability of MddMRI-derived parameters to differentiate PCa from normal tissue was determined using the Friedman test. To determine if tumor diffusion heterogeneity is similar on macroscopic and microscopic scales, the linear association between SD of MD and mean MKi was estimated using robust regression (bisquare weighting). Hypothesis testing was 2 tailed; P values less than 0.05 were considered statistically significant.RESULTS: All MddMRI-derived parameters could distinguish tumor from normal tissue in the fixed-effects analysis (P < 0.0001). Tumor MKi was higher (P < 0.05) compared with normal tissue (median, 0.40; interquartile range, 0.29-0.52 vs 0.20-0.18; 0.25), as was tumor microscopic diffusion anisotropy (0.55; 0.36-0.81 vs 0.20-0.15; 0.28). The MKi could not be predicted (no significant association) by SD of MD. There was a significant correlation between tumor volume and SD of MD (R2 = 0.50, slope = 0.008 ÎĽm2/ms per millimeter, P < 0.001) but not between tumor volume and MKi.CONCLUSIONS: This explorative study demonstrates that MddMRI provides novel information on MKi and microscopic anisotropy, which differ from measures at the macroscopic level. MddMRI has the potential to characterize tumor tissue heterogeneity at different spatial scales