MR spectroscopy of breast cancer for assessing early treatment response: Results from the ACRIN 6657 MRS trial.

PURPOSE: To estimate the accuracy of predicting response to neoadjuvant chemotherapy (NACT) in patients with locally advanced breast cancer using MR spectroscopy (MRS) measurements made very early in treatment. MATERIALS AND METHODS: This prospective Health Insurance Portability and Accountability Act (HIPAA)-compliant protocol was approved by the American College of Radiology and local-site institutional review boards. One hundred nineteen women with invasive breast cancer of ≥3 cm undergoing NACT were enrolled between September 2007 and April 2010. MRS measurements of the concentration of choline-containing compounds ([tCho]) were performed before the first chemotherapy regimen (time point 1, TP1) and 20-96 h after the first cycle of treatment (TP2). The change in [tCho] was assessed for its ability to predict pathologic complete response (pCR) and radiologic response using the area under the receiver operating characteristic curve (AUC) and logistic regression models. RESULTS: Of the 119 subjects enrolled, only 29 cases (24%) with eight pCRs provided usable data for the primary analysis. Technical challenges in acquiring quantitative MRS data in a multi-site trial setting limited the capture of usable data. In this limited data set, the decrease in tCho from TP1 to TP2 had poor ability to predict either pCR (AUC = 0.53, 95% confidence interval [CI]: 0.27-0.79) or radiologic response (AUC = 0.51, 95% CI: 0.27-0.75). CONCLUSION: The technical difficulty of acquiring quantitative MRS data in a multi-site clinical trial setting led to a low yield of analyzable data, which was insufficient to accurately measure the ability of early MRS measurements to predict response to NACT. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:290-302.

Results of the two incidence screenings in the National Lung Screening Trial.

BACKGROUND: The National Lung Screening Trial was conducted to determine whether three annual screenings (rounds T0, T1, and T2) with low-dose helical computed tomography (CT), as compared with chest radiography, could reduce mortality from lung cancer. We present detailed findings from the first two incidence screenings (rounds T1 and T2). METHODS: We evaluated the rate of adherence of the participants to the screening protocol, the results of screening and downstream diagnostic tests, features of the lung-cancer cases, and first-line treatments, and we estimated the performance characteristics of both screening methods. RESULTS: At the T1 and T2 rounds, positive screening results were observed in 27.9% and 16.8% of participants in the low-dose CT group and in 6.2% and 5.0% of participants in the radiography group, respectively. In the low-dose CT group, the sensitivity was 94.4%, the specificity was 72.6%, the positive predictive value was 2.4%, and the negative predictive value was 99.9% at T1; at T2, the positive predictive value increased to 5.2%. In the radiography group, the sensitivity was 59.6%, the specificity was 94.1%, the positive predictive value was 4.4%, and the negative predictive value was 99.8% at T1; both the sensitivity and the positive predictive value increased at T2. Among lung cancers of known stage, 87 (47.5%) were stage IA and 57 (31.1%) were stage III or IV in the low-dose CT group at T1; in the radiography group, 31 (23.5%) were stage IA and 78 (59.1%) were stage III or IV at T1. These differences in stage distribution between groups persisted at T2. CONCLUSIONS: Low-dose CT was more sensitive in detecting early-stage lung cancers, but its measured positive predictive value was lower than that of radiography. As compared with radiography, the two annual incidence screenings with low-dose CT resulted in a decrease in the number of advanced-stage cancers diagnosed and an increase in the number of early-stage lung cancers diagnosed. (Funded by the National Cancer Institute; NLST ClinicalTrials.gov number, NCT00047385.).

Neoadjuvant Chemotherapy for Breast Cancer: Functional Tumor Volume by MR Imaging Predicts Recurrence-free Survival-Results from the ACRIN 6657/CALGB 150007 I-SPY 1 TRIAL.

PURPOSE: To evaluate volumetric magnetic resonance (MR) imaging for predicting recurrence-free survival (RFS) after neoadjuvant chemotherapy (NACT) of breast cancer and to consider its predictive performance relative to pathologic complete response (PCR). MATERIALS AND METHODS: This HIPAA-compliant prospective multicenter study was approved by institutional review boards with written informed consent. Women with breast tumors 3 cm or larger scheduled for NACT underwent dynamic contrast-enhanced MR imaging before treatment (examination 1), after one cycle (examination 2), midtherapy (examination 3), and before surgery (examination 4). Functional tumor volume (FTV), computed from MR images by using enhancement thresholds, and change from baseline (ΔFTV) were measured after one cycle and before surgery. Association of RFS with FTV was assessed by Cox regression and compared with association of RFS with PCR and residual cancer burden (RCB), while controlling for age, race, and hormone receptor (HR)/ human epidermal growth factor receptor type 2 (HER2) status. Predictive performance of models was evaluated by C statistics. RESULTS: Female patients (n = 162) with FTV and RFS were included. At univariate analysis, FTV2, FTV4, and ΔFTV4 had significant association with RFS, as did HR/HER2 status and RCB class. PCR approached significance at univariate analysis and was not significant at multivariate analysis. At univariate analysis, FTV2 and RCB class had the strongest predictive performance (C statistic = 0.67; 95% confidence interval [CI]: 0.58, 0.76), greater than for FTV4 (0.64; 95% CI: 0.53, 0.74) and PCR (0.57; 95% CI: 0.39, 0.74). At multivariate analysis, a model with FTV2, ΔFTV2, RCB class, HR/HER2 status, age, and race had the highest C statistic (0.72; 95% CI: 0.60, 0.84). CONCLUSION: Breast tumor FTV measured by MR imaging is a strong predictor of RFS, even in the presence of PCR and RCB class. Models combining MR imaging, histopathology, and breast cancer subtype demonstrated the strongest predictive performance in this study.

STARD 2015: An Updated List of Essential Items for Reporting Diagnostic Accuracy Studies.

Incomplete reporting has been identified as a major source of avoidable waste in biomedical research. Essential information is often not provided in study reports, impeding the identification, critical appraisal, and replication of studies. To improve the quality of reporting of diagnostic accuracy studies, the Standards for Reporting of Diagnostic Accuracy Studies (STARD) statement was developed. Here we present STARD 2015, an updated list of 30 essential items that should be included in every report of a diagnostic accuracy study. This update incorporates recent evidence about sources of bias and variability in diagnostic accuracy and is intended to facilitate the use of STARD. As such, STARD 2015 may help to improve completeness and transparency in reporting of diagnostic accuracy studies.

STARD 2015: An Updated List of Essential Items for Reporting Diagnostic Accuracy Studies.

Incomplete reporting has been identified as a major source of avoidable waste in biomedical research. Essential information is often not provided in study reports, impeding the identification, critical appraisal, and replication of studies. To improve the quality of reporting of diagnostic accuracy studies, the Standards for Reporting of Diagnostic Accuracy Studies (STARD) statement was developed. Here we present STARD 2015, an updated list of 30 essential items that should be included in every report of a diagnostic accuracy study. This update incorporates recent evidence about sources of bias and variability in diagnostic accuracy and is intended to facilitate the use of STARD. As such, STARD 2015 may help to improve completeness and transparency in reporting of diagnostic accuracy studies.

Comparing Lung Cancer Screening Strategies in a Nationally Representative US Population Using Transportability Methods for the National Lung Cancer Screening Trial.

Importance: The National Lung Screening Trial (NLST) found that screening for lung cancer with low-dose computed tomography (CT) reduced lung cancer-specific and all-cause mortality compared with chest radiography. It is uncertain whether these results apply to a nationally representative target population. Objective: To extend inferences about the effects of lung cancer screening strategies from the NLST to a nationally representative target population of NLST-eligible US adults. Design, Setting, and Participants: This comparative effectiveness study included NLST data from US adults at 33 participating centers enrolled between August 2002 and April 2004 with follow-up through 2009 along with National Health Interview Survey (NHIS) cross-sectional household interview survey data from 2010. Eligible participants were adults aged 55 to 74 years, and were current or former smokers with at least 30 pack-years of smoking (former smokers were required to have quit within the last 15 years). Transportability analyses combined baseline covariate, treatment, and outcome data from the NLST with covariate data from the NHIS and reweighted the trial data to the target population. Data were analyzed from March 2020 to May 2023. Interventions: Low-dose CT or chest radiography screening with a screening assessment at baseline, then yearly for 2 more years. Main Outcomes and Measures: For the outcomes of lung-cancer specific and all-cause death, mortality rates, rate differences, and ratios were calculated at a median (25th percentile and 75th percentile) follow-up of 5.5 (5.2-5.9) years for lung cancer-specific mortality and 6.5 (6.1-6.9) years for all-cause mortality. Results: The transportability analysis included 51 274 NLST participants and 685 NHIS participants representing the target population (of approximately 5 700 000 individuals after survey-weighting). Compared with the target population, NLST participants were younger (median [25th percentile and 75th percentile] age, 60 [57 to 65] years vs 63 [58 to 67] years), had fewer comorbidities (eg, heart disease, 6551 of 51 274 [12.8%] vs 1 025 951 of 5 739 532 [17.9%]), and were more educated (bachelor's degree or higher, 16 349 of 51 274 [31.9%] vs 859 812 of 5 739 532 [15.0%]). In the target population, for lung cancer-specific mortality, the estimated relative rate reduction was 18% (95% CI, 1% to 33%) and the estimated absolute rate reduction with low-dose CT vs chest radiography was 71 deaths per 100 000 person-years (95% CI, 4 to 138 deaths per 100 000 person-years); for all-cause mortality the estimated relative rate reduction was 6% (95% CI, -2% to 12%). In the NLST, for lung cancer-specific mortality, the estimated relative rate reduction was 21% (95% CI, 9% to 32%) and the estimated absolute rate reduction was 67 deaths per 100 000 person-years (95% CI, 27 to 106 deaths per 100 000 person-years); for all-cause mortality, the estimated relative rate reduction was 7% (95% CI, 0% to 12%). Conclusions and Relevance: Estimates of the comparative effectiveness of low-dose CT screening compared with chest radiography in a nationally representative target population were similar to those from unweighted NLST analyses, particularly on the relative scale. Increased uncertainty around effect estimates for the target population reflects large differences in the observed characteristics of trial participants and the target population.

The National CT Colonography Trial: assessment of accuracy in participants 65 years of age and older.

PURPOSE: To conduct post-hoc analysis of National CT Colonography Trial data and compare the sensitivity and specificity of computed tomographic (CT) colonography in participants younger than 65 years with those in participants aged 65 years and older. MATERIALS AND METHODS: Of 2600 asymptomatic participants recruited at 15 centers for the trial, 497 were 65 years of age or older. Approval of this HIPAA-compliant study was obtained from the institutional review board of each site, and informed consent was obtained from each subject. Radiologists certified in CT colonography reported lesions 5 mm in diameter or larger. Screening detection of large (≥10-mm) histologically confirmed colorectal neoplasia was the primary end point; screening detection of smaller (6-9-mm) colorectal neoplasia was a secondary end point. The differences in sensitivity and specificity of CT colonography in the two age cohorts (age < 65 years and age ≥ 65 years) were estimated with bootstrap confidence intervals (CIs). RESULTS: Complete data were available for 477 participants 65 years of age or older (among 2531 evaluable participants). Prevalence of adenomas 1 cm or larger for the older participants versus the younger participants was 6.9% (33 of 477) versus 3.7% (76 of 2054) (P < .004). For large neoplasms, mean estimates for CT colonography sensitivity and specificity among the older cohort were 0.82 (95% CI: 0.644, 0.944) and 0.83 (95% CI: 0.779, 0.883), respectively. For large neoplasms in the younger group, CT colonography sensitivity and specificity were 0.92 (95% CI: 0.837, 0.967) and 0.86 (95% CI: 0.816, 0.899), respectively. Per-polyp sensitivity for large neoplasms for the older and younger populations was 0.75 (95% CI: 0.578, 0.869) and 0.84 (95% CI: 0.717, 0.924), respectively. For the older and younger groups, per-participant sensitivity was 0.72 (95% CI: 0.565, 0.854) and 0.81 (95% CI: 0.745, 0.882) for detecting adenomas 6 mm in diameter or larger. CONCLUSION: For most measures of diagnostic performance and in most subsets, the difference between senior-aged participants and those younger than 65 years was not statistically significant.

Association Between Surgery Preference and Receipt in Ductal Carcinoma In Situ After Breast Magnetic Resonance Imaging: An Ancillary Study of the ECOG-ACRIN Cancer Research Group (E4112).

Importance: Guiding treatment decisions for women with ductal carcinoma in situ (DCIS) requires understanding patient preferences and the influence of preoperative magnetic resonance imaging (MRI) and surgeon recommendation. Objective: To identify factors associated with surgery preference and surgery receipt among a prospective cohort of women with newly diagnosed DCIS. Design, Setting, and Participants: A prospective cohort study was conducted at 75 participating institutions, including community practices and academic centers, across the US between March 25, 2015, and April 27, 2016. Data were analyzed from August 2 to September 24, 2021. This was an ancillary study of the ECOG-ACRIN Cancer Research Group (E4112). Women with recently diagnosed unilateral DCIS who were eligible for wide local excision and had a diagnostic mammogram within 3 months of study registration were included. Participants who had documented surgery and completed the baseline patient-reported outcome questionnaires were included in this substudy. Exposures: Women received preoperative MRI and surgeon consultation and then underwent wide local excision or mastectomy. Participants will be followed up for recurrence and overall survival for 10 years from the date of surgery. Main Outcomes and Measures: Patient-reported outcome questionnaires assessed treatment goals and concerns and surgery preference before MRI and after MRI and surgeon consultation. Results: Of the 368 participants enrolled 316 (86%) were included in this substudy (median [range] age, 59.5 [34-87] years; 45 women [14%] were Black; 245 [78%] were White; and 26 [8%] were of other race). Pre-MRI, age (odds ratio [OR] per 5-year increment, 0.45; 95% CI, 0.26-0.80; P = .007) and the importance of keeping one's breast (OR, 0.48; 95% CI, 0.31-0.72; P < .001) vs removal of the breast for peace of mind (OR, 1.35; 95% CI, 1.04-1.76; P = .03) were associated with surgery preference for mastectomy. After MRI and surgeon consultation, MRI upstaging (48 of 316 [15%]) was associated with patient preference for mastectomy (OR, 8.09; 95% CI, 2.51-26.06; P < .001). The 2 variables with the highest ORs for initial receipt of mastectomy were MRI upstaging (OR, 12.08; 95% CI, 4.34-33.61; P < .001) and surgeon recommendation (OR, 4.85; 95% CI, 1.99-11.83; P < .001). Conclusions and Relevance: In this cohort study, change in patient preference for DCIS surgery and surgery received were responsive to MRI results and surgeon recommendation. These data highlight the importance of ensuring adequate information and ongoing communication about the clinical significance of MRI findings and the benefits and risks of available treatment options.

Bayesian versus Empirical Calibration of Microsimulation Models: A Comparative Analysis.

Calibration of a microsimulation model (MSM) is a challenging but crucial step for the development of a valid model. Numerous calibration methods for MSMs have been suggested in the literature, most of which are usually adjusted to the specific needs of the model and based on subjective criteria for the selection of optimal parameter values. This article compares 2 general approaches for calibrating MSMs used in medical decision making, a Bayesian and an empirical approach. We use as a tool the MIcrosimulation Lung Cancer (MILC) model, a streamlined, continuous-time, dynamic MSM that describes the natural history of lung cancer and predicts individual trajectories accounting for age, sex, and smoking habits. We apply both methods to calibrate MILC to observed lung cancer incidence rates from the Surveillance, Epidemiology and End Results (SEER) database. We compare the results from the 2 methods in terms of the resulting parameter distributions, model predictions, and efficiency. Although the empirical method proves more practical, producing similar results with smaller computational effort, the Bayesian method resulted in a calibrated model that produced more accurate outputs for rare events and is based on a well-defined theoretical framework for the evaluation and interpretation of the calibration outcomes. A combination of the 2 approaches is an alternative worth considering for calibrating complex predictive models, such as microsimulation models.

Patient-Reported Testing Burden of Breast Magnetic Resonance Imaging Among Women With Ductal Carcinoma In Situ: An Ancillary Study of the ECOG-ACRIN Cancer Research Group (E4112).

Importance: The use of magnetic resonance imaging (MRI) in pretreatment planning of ductal carcinoma in situ (DCIS) remains controversial. Understanding changes in short-term health-related quality of life associated with breast MRI would allow for a more complete comparative effectiveness assessment. Objective: To assess whether there are changes in patient-reported quality of life associated with breast MRI among women diagnosed with DCIS. Design, Setting, and Participants: This cohort study was a substudy of a nonrandomized clinical trial conducted at 75 participating US institutions from March 2015 to April 2016. Women recently diagnosed with unilateral DCIS who were eligible for wide local excision and had a diagnostic mammogram within 3 months of study registration were included. A total of 355 women met the eligibility criteria and underwent the study MRI. Data analysis was performed from June 3, 2020, to July 1, 2021. Exposures: Participants underwent bilateral breast MRI within 30 days of study registration and before surgery. Information on patient-reported testing burden for breast MRI was collected after MRI and before surgery. Main Outcomes and Measures: The primary outcome of this substudy was the patient-reported testing burden of breast MRI, measured by the Testing Morbidities Index (TMI) summated scale score. The TMI is a 7-item instrument that evaluates the temporary changes in quality of life associated with imaging before, during, and after the test (0 represents the worst possible, 100 the hypothetical ideal test experience). Results: Of the 355 women who met the eligibility criteria, 244 (69%) completed both questionnaires and were included in this analysis. The median age was 59 years (range, 34-85 years). The mean MRI TMI summated scale score was 85.9 (95% CI, 84.6-87.3). Of the 244 women, 142 (58%) experienced at least some fear and anxiety before the examination, and 120 women (49%) experienced fear and anxiety during the examination. A total of 156 women (64%) experienced pain or discomfort during the examination. In multivariable analyses, greater test-related burden was associated with higher levels of cancer worry (regression coefficient, -2.75; SE, 0.94; P = .004). Conclusions and Relevance: In this cohort study, a clinically meaningful breast MRI testing burden among women with DCIS was revealed that was significantly associated with cancer worry. Understanding the potential quality-of-life reduction associated with MRI, especially when used in combination with mammography, may allow development of targeted interventions to improve the patient experience.

Prenatal exposure to cigarette smoke and benign breast disease.

BACKGROUND: Experimental studies have indicated that cigarette smoke contains potential human breast toxins and that the toxic influence during the prenatal period is greater than that of later life. METHODS: The study sample includes 810 women whose mothers enrolled in the Collaborative Perinatal Project between 1959 and 1966 in Boston and Providence. These women have been followed from gestation until middle-age. Information on maternal smoking during pregnancy was prospectively collected during prenatal visits. We identified 146 women who had been told by a health professional that they had benign breast disease. Log-binomial regression models with Generalized Estimating Equation methods were employed to quantify the association between maternal smoking and benign breast disease among offspring. RESULTS: There was a positive association between maternal smoking during pregnancy and the risk of benign breast disease among offspring. In particular, women whose mother smoked 1 pack or more per day were 1.7 times more likely to develop benign breast disease (relative risk = 1.7 [95% confidence interval = 1.2-2.5]) in comparison with women whose mother never smoked during pregnancy. The association was independent of women's age, race, education, age at menarche, parity, obesity, birth weight, and maternal age at pregnancy. CONCLUSIONS: Exposure to heavy cigarette smoking during the prenatal period was associated with an increased risk of benign breast disease in adulthood.

MRI Evaluation of the Contralateral Breast in Women with Recently Diagnosed Breast Cancer: 2-Year Follow-up.

OBJECTIVE: The American College of Radiology Imaging Network Trial 6667 showed that MRI can detect cancer in the contralateral breast that is missed by mammography and clinical examination at the time of the initial breast cancer diagnosis, based on 1-year follow-up. This study is a continuation of the trial that evaluates the diagnostic accuracy of MRI for contralateral breast cancer after 2 years of follow-up. METHODS: In total, 969 women with a diagnosis of unilateral breast cancer and no clinical or imaging abnormalities in the contralateral breast underwent breast MRI. The cancer status of all participants was monitored for 2 years after the initial MRI. Follow-up included documentation of any clinical, imaging, or interventional procedures performed. A study participant was considered positive for cancer if she had a tissue diagnosis of in situ or invasive breast cancer in the contralateral breast within 730 days of her initial MRI. RESULTS: Three additional cancers were diagnosed in the study population in the second year of the trial. The diagnostic yield for MRI for the 2-year period was 3% (31/969). After 2 years of follow-up, breast MRI has a sensitivity of 86% and specificity of 88% for detection of contralateral breast cancer. Its negative predictive value was 99%, and its positive predictive value was 22%. These values did not change significantly from the 1-year data. CONCLUSION: A negative contralateral breast MRI has a very high and reliable negative predictive value over 2 years, and, therefore, is helpful in managing and counseling patients during the period of initial diagnosis and early treatment.

Integrated platform for manual and high-throughput statistical validation of tandem mass spectra.

As proteomic data sets increase in size and complexity, the necessity for database-centric software systems able to organize, compare, and visualize all the proteomic experiments in a lab grows. We recently developed an integrated platform called high-throughput autonomous proteomic pipeline (HTAPP) for the automated acquisition and processing of quantitative proteomic data, and integration of proteomic results with existing external protein information resources within a lab-based relational database called PeptideDepot. Here, we introduce the peptide validation software component of this system, which combines relational database-integrated electronic manual spectral annotation in Java with a new software tool in the R programming language for the generation of logistic regression spectral models from user-supplied validated data sets and flexible application of these user-generated models in automated proteomic workflows. This logistic regression spectral model uses both variables computed directly from SEQUEST output in addition to deterministic variables based on expert manual validation criteria of spectral quality. In the case of linear quadrupole ion trap (LTQ) or LTQ-FTICR LC/MS data, our logistic spectral model outperformed both XCorr (242% more peptides identified on average) and the X!Tandem E-value (87% more peptides identified on average) at a 1% false discovery rate estimated by decoy database approach.

Micronodules Detected on Computed Tomography During the National Lung Screening Trial: Prevalence and Relation to Positive Studies and Lung Cancer.

INTRODUCTION: In the National Lung Screening Trial (NLST) all cases with a 4-mm nodule (micronodule) and no other findings were classified as a negative study. The prevalence and malignant potential of micronodules in the NLST is evaluated to understand if this classification was appropriate. METHODS AND MATERIALS: In the NLST a total of 53,452 participants were enrolled with 26,722 undergoing low-dose computed tomography (CT) screening. To determine whether a micronodule developed into a lung cancer, a list from the NLST database of those participants who developed lung cancer and had a micronodule recorded was selected. The CT images of this subset were reviewed by experienced, fellowship-trained thoracic radiologists (R.F.M., C.C., P.M.B., and D.R.A.), all of whom participated as readers in the NLST. RESULTS: There were 26,722 participants who underwent CT in the NLST, of which 11,326 (42%) participants had at least one CT with a micronodule. Five thousand five hundred sixty (49%) of these participants had at least one positive CT examination, of which 409 (3.6%) subsequently were diagnosed with lung cancer. Of the 409 lung cancer cases with a micronodule recorded, there were 13 cases in which a micronodule developed into lung cancer. Considering the 13 cases, they represent 1.2% (13 of 1089) of the lung cancers diagnosed in the CT arm of the NLST and 0.11% (13 of 11,326) of the total micronodule cases. Additionally they represent 0.23% (13 of 5560) of the micronodule and at least one positive CT examination cases and 3.2% (13 of 409) of the micronodule cases diagnosed with lung cancer. The average size of the nodule at baseline (recorded as maximum diameter by perpendicular diameter) was 3.0 × 2.5 mm (ranges 2 x 4 mm and 2 x 4 mm) and at the positive CT the nodule was 11.1 × 8.6 mm (ranges, 6 x 20 mm and 5 x 14 mm); a difference of average change in size of 8.1 × 6.1 mm. The average number of days from first CT with a micronodule recorded to positive CT was 459 days (range, 338 - 723 days), the mean time from first CT with micronodule to lung cancer diagnosis was 617 days (range, 380 - 1140 days) and the mean time from positive CT to lung cancer diagnosis was 160 days (range, 18 - 417 days). Histologically, there was one small cell carcinoma and 12 non-small cell with stages of IA in 8 (62%), stage IB in 2 (15%), and 1 each stage IIIA, IIIB, and IV. The overall survival of NSCLC cases with a micronodule was not significantly different than the survival of the CT subset diagnosed with NSCL (p = 0.36). CONCLUSIONS: Micronodules are common among lung cancer-screened participants and are capable of developing into lung cancer; however, following micronodules by annual CT screening surveillance is appropriate and does not impact overall survival or outcome.

Diagnostic accuracy of digital versus film mammography: exploratory analysis of selected population subgroups in DMIST.

PURPOSE: To retrospectively compare the accuracy of digital versus film mammography in population subgroups of the Digital Mammographic Imaging Screening Trial (DMIST) defined by combinations of age, menopausal status, and breast density, by using either biopsy results or follow-up information as the reference standard. MATERIALS AND METHODS: DMIST included women who underwent both digital and film screening mammography. Institutional review board approval at all participating sites and informed consent from all participating women in compliance with HIPAA was obtained for DMIST and this retrospective analysis. Areas under the receiver operating characteristic curve (AUCs) for each modality were compared within each subgroup evaluated (age < 50 vs 50-64 vs >or= 65 years, dense vs nondense breasts at mammography, and pre- or perimenopausal vs postmenopausal status for the two younger age cohorts [10 new subgroups in toto]) while controlling for multiple comparisons (P < .002 indicated a significant difference). All DMIST cancers were evaluated with respect to mammographic detection method (digital vs film vs both vs neither), mammographic lesion type (mass, calcifications, or other), digital machine type, mammographic and pathologic size and diagnosis, existence of prior mammographic study at time of interpretation, months since prior mammographic study, and compressed breast thickness. RESULTS: Thirty-three centers enrolled 49 528 women. Breast cancer status was determined for 42,760 women, the group included in this study. Pre- or perimenopausal women younger than 50 years who had dense breasts at film mammography comprised the only subgroup for which digital mammography was significantly better than film (AUCs, 0.79 vs 0.54; P = .0015). Breast Imaging Reporting and Data System-based sensitivity in this subgroup was 0.59 for digital and 0.27 for film mammography. AUCs were not significantly different in any of the other subgroups. For women aged 65 years or older with fatty breasts, the AUC showed a nonsignificant tendency toward film being better than digital mammography (AUCs, 0.88 vs 0.70; P = .0025). CONCLUSION: Digital mammography performed significantly better than film for pre- and perimenopausal women younger than 50 years with dense breasts, but film tended nonsignificantly to perform better for women aged 65 years or older with fatty breasts.

STARD 2015 guidelines for reporting diagnostic accuracy studies: explanation and elaboration.

Diagnostic accuracy studies are, like other clinical studies, at risk of bias due to shortcomings in design and conduct, and the results of a diagnostic accuracy study may not apply to other patient groups and settings. Readers of study reports need to be informed about study design and conduct, in sufficient detail to judge the trustworthiness and applicability of the study findings. The STARD statement (Standards for Reporting of Diagnostic Accuracy Studies) was developed to improve the completeness and transparency of reports of diagnostic accuracy studies. STARD contains a list of essential items that can be used as a checklist, by authors, reviewers and other readers, to ensure that a report of a diagnostic accuracy study contains the necessary information. STARD was recently updated. All updated STARD materials, including the checklist, are available at http://www.equator-network.org/reporting-guidelines/stard Here, we present the STARD 2015 explanation and elaboration document. Through commented examples of appropriate reporting, we clarify the rationale for each of the 30 items on the STARD 2015 checklist, and describe what is expected from authors in developing sufficiently informative study reports.

Updating standards for reporting diagnostic accuracy: the development of STARD 2015.

BACKGROUND: Although the number of reporting guidelines has grown rapidly, few have gone through an updating process. The STARD statement (Standards for Reporting Diagnostic Accuracy), published in 2003 to help improve the transparency and completeness of reporting of diagnostic accuracy studies, was recently updated in a systematic way. Here, we describe the steps taken and a justification for the changes made. RESULTS: A 4-member Project Team coordinated the updating process; a 14-member Steering Committee was regularly solicited by the Project Team when making critical decisions. First, a review of the literature was performed to identify topics and items potentially relevant to the STARD updating process. After this, the 85 members of the STARD Group were invited to participate in two online surveys to identify items that needed to be modified, removed from, or added to the STARD checklist. Based on the results of the literature review process, 33 items were presented to the STARD Group in the online survey: 25 original items and 8 new items; 73 STARD Group members (86 %) completed the first survey, and 79 STARD Group members (93 %) completed the second survey.Then, an in-person consensus meeting was organized among the members of the Project Team and Steering Committee to develop a consensual draft version of STARD 2015. This version was piloted in three rounds among a total of 32 expert and non-expert users. Piloting mostly led to rewording of items. After this, the update was finalized. The updated STARD 2015 list now consists of 30 items. Compared to the previous version of STARD, three original items were each converted into two new items, four original items were incorporated into other items, and seven new items were added. CONCLUSIONS: After a systematic updating process, STARD 2015 provides an updated list of 30 essential items for reporting diagnostic accuracy studies.

Towards complete and accurate reporting of studies of diagnostic accuracy: The STARD Initiative.

BACKGROUND: To comprehend the results of diagnostic accuracy studies, readers must understand the design, conduct, analysis, and results of such studies. That goal can be achieved only through complete transparency from authors. OBJECTIVE: To improve the accuracy and completeness of reporting of studies of diagnostic accuracy in order to allow readers to assess the potential for bias in the study and to evaluate its generalizability. METHODS: The Standards for Reporting of Diagnostic Accuracy (STARD) steering committee searched the literature to identify publications on the appropriate conduct and reporting of diagnostic studies and extracted potential items into an extensive list. Researchers, editors, methodologists and statisticians, and members of professional organizations shortened this list during a 2-day consensus meeting with the goal of developing a checklist and a generic flow diagram for studies of diagnostic accuracy. RESULTS: The search for published guidelines on diagnostic research yielded 33 previously published checklists, from which we extracted a list of 75 potential items. The consensus meeting shortened the list to 25 items, using evidence on bias whenever available. A prototypical flow diagram provides information about the method of patient recruitment, the order of test execution, and the numbers of patients undergoing the test under evaluation, the reference standard, or both. CONCLUSIONS: Evaluation of research depends on complete and accurate reporting. If medical journals adopt the checklist and the flow diagram, the quality of reporting of studies of diagnostic accuracy should improve to the advantage of the clinicians, researchers, reviewers, journals, and the public.

The STARD statement for reporting studies of diagnostic accuracy: explanation and elaboration.

The quality of reporting of studies of diagnostic accuracy is less than optimal. Complete and accurate reporting is necessary to enable readers to assess the potential for bias in the study and to evaluate the generalizability of the results. A group of scientists and editors has developed the STARD (Standards for Reporting of Diagnostic Accuracy) statement to improve the reporting the quality of reporting of studies of diagnostic accuracy. The statement consists of a checklist of 25 items and flow diagram that authors can use to ensure that all relevant information is present. This explanatory document aims to facilitate the use, understanding, and dissemination of the checklist. The document contains a clarification of the meaning, rationale, and optimal use of each item on the checklist, as well as a short summary of the available evidence on bias and applicability. The STARD statement, checklist, flowchart, and this explanation and elaboration document should be useful resources to improve reporting of diagnostic accuracy studies. Complete and informative reporting can only lead to better decisions in health care.