How I treat and prevent venous thrombotic complications in patients with lymphoma.

Venous thromboembolism (VTE) is a common complication occurring in 5% to 10% of patients with lymphoma. As the complexity of lymphoma management has increased with novel therapies, so too has the treatment of VTE. Therapeutic options for the treatment of cancer-associated VTE have expanded from only warfarin and low-molecular-weight heparins (LMWHs) to include the direct oral anticoagulants (DOACs) apixaban, edoxaban and rivaroxaban. There have been no head-to-head trials comparing different DOACs in this setting, and randomized trials comparing a DOAC with LMWH dalteparin differ in trial design and results. Drug-drug interactions, drug-specific side effects, and patient selection are important considerations when prescribing anticoagulant therapy. In all patients, the relative risks of thrombosis and bleeding, the availability of the anticoagulant, and the life expectancy of the patient are vital elements in selecting the most appropriate anticoagulant (which can vary over time) for the individual patient. We describe the intricacies and challenges of treating thrombotic complications in patients with lymphoma with an emphasis on evidence and guideline-based care.

Patient characteristics and long-term outcomes beyond the first 6 months after a diagnosis of cancer-associated venous thromboembolism.

INTRODUCTION: Little is known about the clinical course and treatment decisions in patients with cancer-associated venous thromboembolism (VTE) beyond the initial treatment period of 3 to 6 months. This information is important for clinicians and patients to inform their decisions regarding duration of anticoagulation. MATERIALS AND METHODS: We reviewed health records from consecutive patients referred to our institution for cancer-associated VTE management between 2013 and 2015 to describe their clinical course and outcomes from 6 to 24 months following their index VTE. Details on patient and cancer characteristics, objectively documented recurrent venous thromboembolism (rVTE), clinically relevant bleeding (CRB) and overall mortality were captured. RESULTS: 524 patients met eligibility criteria and 322 were alive at 6 months after the index VTE. At 6 months, anticoagulation was continued in 222 patients (68.9%). During follow-up, there were 33 rVTE events in 30 patients (1-year cumulative incidence of 8.2%; 95% CI: 5.5%-11.6%), and 16 CRB events in 15 patients (1-year cumulative incidence of 4.1%; 95% CI: 2.3%-6.7%); 20 (60.6%) rVTE events and 13 (81.3%) CRB events occurred while on anticoagulation. One-year survival beyond 6 months was 73.7% (95% CI: 68.5%-78.2%). A higher proportion of patients with advanced cancer and receiving cancer treatment was found among those who continued anticoagulation beyond 6 months compared to those who stopped anticoagulation. CONCLUSIONS: Patients with cancer-associated VTE who are alive at 6 months after VTE diagnosis remain at high risk of rVTE, CRB and death.

A computational model to generate simulated three-dimensional breast masses.

PURPOSE: To develop algorithms for creating realistic three-dimensional (3D) simulated breast masses and embedding them within actual clinical mammograms. The proposed techniques yield high-resolution simulated breast masses having randomized shapes, with user-defined mass type, size, location, and shape characteristics. METHODS: The authors describe a method of producing 3D digital simulations of breast masses and a technique for embedding these simulated masses within actual digitized mammograms. Simulated 3D breast masses were generated by using a modified stochastic Gaussian random sphere model to generate a central tumor mass, and an iterative fractal branching algorithm to add complex spicule structures. The simulated masses were embedded within actual digitized mammograms. The authors evaluated the realism of the resulting hybrid phantoms by generating corresponding left- and right-breast image pairs, consisting of one breast image containing a real mass, and the opposite breast image of the same patient containing a similar simulated mass. The authors then used computer-aided diagnosis (CAD) methods and expert radiologist readers to determine whether significant differences can be observed between the real and hybrid images. RESULTS: The authors found no statistically significant difference between the CAD features obtained from the real and simulated images of masses with either spiculated or nonspiculated margins. Likewise, the authors found that expert human readers performed very poorly in discriminating their hybrid images from real mammograms. CONCLUSIONS: The authors' proposed method permits the realistic simulation of 3D breast masses having user-defined characteristics, enabling the creation of a large set of hybrid breast images containing a well-characterized mass, embedded within real breast background. The computational nature of the model makes it suitable for detectability studies, evaluation of computer aided diagnosis algorithms, and teaching purposes.

Utility of preoperative ultrasound for predicting pN2 or higher stage axillary lymph node involvement in patients with newly diagnosed breast cancer.

OBJECTIVE: The objective of our study was to report the positive predictive value (PPV) of ultrasound of the axilla to predict pN2 or higher disease in breast cancer patients. MATERIALS AND METHODS: A retrospective study of 559 patients with newly diagnosed invasive breast cancer from 2005 through 2009 was performed. All patients underwent ipsilateral axillary ultrasound for staging purposes. Ultrasound findings were considered suspicious for metastasis if cortical thickening or nonhilar blood flow to the cortex was present. Suspicious lymph nodes were classified on the basis of their features as high, intermediate, or low suspicion. The standard of truth was confirmed pathologically. RESULTS: Either pN2 or pN3 disease was found in 50 of 181 (28%) patients with positive findings on an ultrasound study and 10 of 378 (3%) patients with a negative ultrasound study (p < 0.01). When two or more lymph nodes of high suspicion or a total of three or more lymph nodes of any combination of high suspicion and intermediate suspicion were detected, patients were likely to have pN2 or pN3 disease (PPV, 82%). Either pN2 or pN3 disease was found in two of 122 (2%) patients whose primary cancers were up to 10 mm and 58 of 437 (13%) patients whose primary cancers were larger than 10 mm (p < 0.001). Ultrasound of the patient with tumors larger than 10 mm showing at least two highly suspicious nodes had a PPV of 87% for predicting pN2 or higher disease. CONCLUSION: Ultrasound was useful for predicting pN2 or higher axillary disease in breast cancer patients. Preoperative ultrasound assessment for staging of axillary lymph nodes might help avoid underestimation at sentinel lymph node biopsy.

Usefulness of presentation of similar images in the diagnosis of breast masses on mammograms: comparison of observer performances in Japan and the USA.

Computer-aided diagnosis has potential in improving radiologists' diagnosis, and presentation of similar images as a reference may provide additional useful information for distinction between benign and malignant lesions. In this study, we evaluated the usefulness of presentation of reference images in observer performance studies and compared the results obtained by groups of observers practicing in the United States and Japan. The results showed that the presentation of the reference images was generally effective for both groups, as the areas under the receiver operating characteristic curves improved from 0.915 to 0.924 for the group in the US and from 0.913 to 0.925 for the group in Japan, although the differences were marginally (p = 0.047) and not (p = 0.13) statistically significant, respectively. There was a slight difference between the two groups in the way that the observers reacted to some benign cases, which might be due to differences in the population of screenees and in the socio-clinical environment. In the future, it may be worthwhile to investigate the development of a customized system for physicians in different socio-clinical environments.

Clinically missed cancer: how effectively can radiologists use computer-aided detection?

OBJECTIVE: The purpose of this study was to determine the effectiveness with which radiologists can use computer-aided detection (CADe) to detect cancer missed at screening. MATERIALS AND METHODS: An observer study was performed to measure the ability of radiologists to detect breast cancer on mammograms with and without CADe. The images in the study were from 300 analog mammographic examinations. In 234 cases the mammograms were read clinically as normal and free of cancer for at least 2 subsequent years. In the other 66 cases, cancers were missed clinically. In 256 cases, current and previous mammograms were available. Eight radiologists read the dataset and recorded a BI-RADS assessment, the location of the lesion, and their level of confidence that the patient should be recalled for diagnostic workup for each suspicious lesion. Jackknife alternative free-response receiver operating characteristic analysis was used. RESULTS: The jackknife alternative free-response receiver operating characteristic figure of merit was 0.641 without aid and 0.659 with aid (p = 0.06; 95% CI, -0.001 to 0.036). The sensitivity increased 9.9% (95% CI, 3.4-19%) and the callback rate 12.1% (95% CI, 7.3-20%) with CADe. Both increases were statistically significant (p < 0.001). Radiologists on average ignored 71% of correct computer prompts. CONCLUSION: Use of CADe can increase radiologist sensitivity 10% with a comparable increase in recall rate. There is potential for CADe to have a bigger clinical impact because radiologists failed to recognize a correct computer prompt in 71% of missed cancer cases [corrected].

Breast cancers not detected at MRI: review of false-negative lesions.

OBJECTIVE: The objective of our study was to determine the sensitivity of cancer detection at breast MRI using current imaging techniques and to evaluate the characteristics of lesions with false-negative examinations. MATERIALS AND METHODS: Two hundred seventeen patients with 222 newly diagnosed breast cancers or highly suspicious breast lesions that were subsequently shown to be malignant underwent breast MRI examinations for staging. Two breast imaging radiologists performed a consensus review of the breast MRI examinations. The absence of perceptible contrast enhancement at the expected site was considered to be a false-negative MRI. Histology of all lesions was reviewed by an experienced breast pathologist. RESULTS: Enhancement was observed in 213 (95.9%) of the 222 cancer lesions. Of the nine lesions without visible enhancement, two lesions were excluded because the entire tumor had been excised at percutaneous biopsy performed before the MRI examination and no residual tumor was noted on the final histology. The overall sensitivity of MRI for the known cancers was 96.8% (213/220); for invasive cancer, 98.3% (176/179); and for ductal carcinoma in situ, 90.2% (37/41). CONCLUSION: In a population of 220 sequentially diagnosed breast cancer lesions, we found seven (3.2%) MRI-occult cancers, fewer than seen in other published studies. Small tumor size and diffuse parenchymal enhancement were the principal reasons for these false-negative results. Although the overall sensitivity of cancer detection was high (96.8%), it should be emphasized that a negative MRI should not influence the management of a lesion that appears to be of concern on physical examination or on other imaging techniques.

Presentation of similar images as a reference for distinction between benign and malignant masses on mammograms: analysis of initial observer study.

The effect of the presentation of similar images for distinction between benign and malignant masses on mammograms was evaluated in the observer performance study. Images of masses were obtained from the Digital Database for Screening Mammography. We selected 50 benign and 50 malignant masses by a stratified randomization method. For each case, similar images were selected based on the size of masses and the similarity measures. Radiologists were shown images with unknown masses and asked to provide their confidence level that the lesions were malignant before and after the presentation of the similar images. Eleven observers, including three attending breast radiologists, three breast imaging fellows, and five residents, participated. The average areas under the receiver operating characteristic curves without and with the presentation of the similar images were almost equivalent. However, there were many cases in which the similar images caused beneficial effects to the observers, whereas there were a small number of cases in which the similar images had detrimental effects. From a detailed analysis of the reasons for these detrimental effects, we found that the similar images would not be useful for diagnosis of rare and very difficult cases, i.e., benign-looking malignant and malignant-looking benign cases. In addition, these cases should not be included in the reference database, because radiologists would be confused by these unusual cases. The results of this study could be very important and useful for the future development and improvement of a computer-aided diagnosis system.

MR-directed ("Second-Look") ultrasound examination for breast lesions detected initially on MRI: MR and sonographic findings.

OBJECTIVE: The objective of our study was to assess the clinical utility of MR-directed ("second-look") ultrasound examination to search for breast lesions detected initially on MRI. MATERIALS AND METHODS: A retrospective review was performed of the records of 158 consecutive patients (202 lesions) with breast abnormalities initially detected on MRI between July 2003 and May 2006. All lesions were detected as enhancing findings on a dynamic contrast MR study and were subsequently evaluated with ultrasound. Ultrasound was performed using MR images as a guide to lesion location, size, and morphology. Pathology findings were confirmed by subsequent percutaneous biopsy or lesion excision. Imaging follow-up was used for probably benign lesions, which were not biopsied. RESULTS: Of the 202 MRI-detected lesions, ultrasound correlation was made in 115 (57%) including 33 malignant lesions and 82 benign lesions. The remaining 87 lesions were not sonographically correlated and included 11 malignant lesions and 76 nonmalignant lesions. Mass lesions identified on MRI were more likely to have a sonographic correlate than nonmasslike lesions (65% vs 12%, respectively); malignant mass lesions were more likely to show an ultrasound correlation (85%). The malignant lesions with successful sonographic correlation tended to present with subtle sonographic findings. CONCLUSION: MR-directed ultrasound of MRI-detected lesions was useful for decision making as part of the diagnostic workup. Malignant lesions were likely to have an ultrasound correlate, especially when they presented as masses on MRI. However, the sonographic findings of these lesions were often subtle, and careful scanning technique was needed for successful MRI-ultrasound correlation.

Observer study for evaluating potential utility of a super-high-resolution LCD in the detection of clustered microcalcifications on digital mammograms.

We evaluated the potential utility of a newly developed liquid-crystal display (LCD), which used an independent sub-pixel drive (ISD) technique for increasing the spatial resolution of a standard LCD three times in one direction, by use of receiver operating characteristic (ROC) analysis and a two-alternative-forced-choice (2AFC) method to determine improvement in radiologists' accuracy in the detection of clustered microcalcifications (MCLs) on digital mammograms. We used a standard LCD without and with the ISD technique, which can increase the spatial resolution of the LCD three times in one direction from three mega- to nine megapixels without changes in the size of the display. We used 60 single views of digital mammograms (30 with and 30 without clustered MCLs) for ROC studies and 60 regions of interest (ROIs) with clustered MCLs for 2AFC studies. In the ROC study, seven radiologists attempted to detect clustered MCLs without and with the ISD on the same LCD. In the 2AFC study, the same observer group compared the visibility of MCLs by use of the LCD without and with the ISD. Our institutional review board approved the use of this database and the participation of radiologists in this study. The accuracy in detecting clustered MCLs in the ROC study was improved by use of the LCD with the ISD, but the improvement was not statistically significant (p = 0.08). However, the superiority of the LCD with the ISD was demonstrated as significant (p < 0.001) in the 2AFC study. An LCD with ISD can improve the visibility of clustered MCLs when high-resolution digital mammograms are available.

Determination of similarity measures for pairs of mass lesions on mammograms by use of BI-RADS lesion descriptors and image features.

RATIONALE AND OBJECTIVES: To determine similarity measures for selection of pathology-known similar images that would be useful for radiologists as a reference guide in the diagnosis of new breast lesions on mammograms. MATERIALS AND METHODS: The images were obtained from the Digital Database for Screening Mammography developed by the University of South Florida. For determination and evaluation of similarity measures, the "gold standard" of similarities for 300 pairs of masses was determined by 10 breast radiologists. For determining similarity measures that would agree with radiologists' similarity determination, an artificial neural network (ANN) was trained with the radiologists' subjective similarity ratings and the image features. The image features were determined subjectively using the Breast Imaging Reporting and Data System (BI-RADS) lesion descriptors and objectively by computerized image analysis. The similarity measures determined by the ANN were compared to the gold standard and evaluated in terms of the correlation coefficient. RESULTS: The similarity measures determined using the BI-RADS descriptors only were not as useful as those determined by use of the image features only. When the BI-RADS margin ratings were combined with the image features, the correlation coefficient between the subjective ratings and the objective measures improved slightly (r = 0.76) compared to those based on the image features alone (r = 0.74). CONCLUSIONS: The inclusion of the BI-RADS margin descriptors may be useful for determination of similarity measures, especially when it is difficult to obtain the manual outlines of the masses and if the BI-RADS descriptors were provided consistently by radiologists.

Axillary lymph nodes suspicious for breast cancer metastasis: sampling with US-guided 14-gauge core-needle biopsy--clinical experience in 100 patients.

PURPOSE: To study the clinical usefulness of ultrasonography (US)-guided core-needle biopsy (CNB) of axillary lymph nodes and the US-depicted abnormalities that may be used to predict nodal metastases. MATERIALS AND METHODS: This retrospective study was HIPAA compliant and institutional review board approved; the requirement for informed patient consent was waived. US-guided 14-gauge CNB of abnormal axillary lymph nodes was performed in 100 of 144 patients with primary breast cancer who underwent US assessment of axillary lymph nodes. A biopsy needle with controllable action rather than a traditional throw-type needle was used. US findings were considered suspicious for metastasis if cortical thickening and/or nonhilar blood flow (NHBF) to the lymph node cortex was present. The absence of any discernible fatty hilum was also noted. RESULTS: Nodal metastases were documented at CNB in 64 (64%) of the 100 patients. All 36 patients with negative biopsy results underwent subsequent sentinel lymph node biopsy (SLNB), which yielded negative findings in 32 (89%) patients and revealed metastasis in four (11%). All 44 patients who did not undergo CNB because of negative US results subsequently underwent SLNB, which revealed lymph node metastasis in 12 (27%) patients. Cortical thickening was found in 63 (79%) of the total of 80 metastatic nodes, but only a minority (n = 26 [32%]) of the nodes had an absent fatty hilum. NHBF to the cortex was detected in 52 (65%) metastatic nodes. Both absence of a fatty hilum (metastasis detected in 26 [93%] of 28 nodes) and cortical thickening combined with NHBF (metastasis detected in 52 [81%] of 64 nodes) had a high positive predictive value. No clinically important complications were encountered with the biopsy procedures. CONCLUSION: Axillary lymph nodes with abnormal US findings can be sampled with high accuracy and without major complications by using a modified 14-gauge CNB technique.

DCEMRI of breast lesions: is kinetic analysis equally effective for both mass and nonmass-like enhancement?

To perform a pilot study investigating whether the sensitivity and specificity of kinetic parameters can be improved by considering mass and nonmass breast lesions separately. The contrast media uptake and washout kinetics in benign and malignant breast lesions were analyzed using an empirical mathematical model (EMM), and model parameters were compared in lesions with mass-like and nonmass-like enhancement characteristics. 34 benign and 78 malignant breast lesions were selected for review. Dynamic MR protocol: 1 pre and 5 postcontrast images acquired in the coronal plane using a 3D T1-weighted SPGR with 68 s timing resolution. An experienced radiologist classified the type of enhancement as mass, nonmass, or focus, according to the BI-RADS lexicon. The kinetic curve obtained from a radiologist-drawn region within the lesion was analyzed quantitatively using a three parameter EMM. Several kinetic parameters were then derived from the EMM parameters: the initial slope (Slope(ini)), curvature at the peak (kappa(peak)), time to peak (T(peak)), initial area under the curve at 30 s (iAUC30), and the signal enhancement ratio (SER). The BI-RADS classification of the lesions yielded: 70 mass lesions, 38 nonmass, 4 focus. For mass lesions, the contrast uptake rate (alpha), contrast washout rate (beta), iAUC30, SER, Slope(ini), T(peak) and kappa(peak) differed substantially between benign and malignant lesions, and after correcting for multiple tests of significance SER and T(peak) demonstrated significance (p < 0.007). For nonmass lesions, we did not find statistically significant differences in any of the parameters for benign vs. malignant lesions (p > 0.5). Kinetic parameters could distinguish benign and malignant mass lesions effectively, but were not quite as useful in discriminating benign from malignant nonmass lesions. If the results of this pilot study are validated in a larger trial, we expect that to maximize diagnostic utility, it will be better to classify lesion morphology as mass or nonmass-like enhancement prior to kinetic analysis.

An investigation of radiologists' perception of lesion similarity: observations with paired breast masses on mammograms and paired lung nodules on CT images.

RATIONALE AND OBJECTIVES: We conducted an observer study to investigate whether radiologists can judge similarities in pairs of breast masses and lung nodules consistently and reproducibly. MATERIALS AND METHODS: Institutional review board approval and informed observer consent were obtained. This study was compliant with the Health Insurance Portability and Accountability Act. We used eight pairs of breast masses on mammograms and eight pairs of lung nodules on computed tomographic images, for which subjective similarity ratings ranging from 0 to 1 were determined in our previous studies. From these, four sets of image pairs were created (ie, a set of eight mass pairs, a set of eight nodule pairs, and two mixed sets of four mass and four nodule pairs). Eight radiologists, including four breast radiologists and four chest radiologists, compared all combinations of the eight pairs in each set using a two-alternative forced-choice (2AFC) method to determine the similarity ranking scores by identifying which pair was more similar than the other pair based on the overall impression for diagnosis. RESULTS: In the mass set and nodule set, the relationship between the average subjective similarity ratings and the average similarity ranking scores by 2AFC indicated very high correlations (r = 0.91 and 0.88). Moreover, in the two mixed sets, the correlations between the average subjective similarity ratings and the average similarity ranking scores were also very high (r = 0.90 and 0.98). Thus, radiologists were able to compare the similarities for pairs of lesions consistently, even in the unusual comparison of pairs of completely different types of lesions. CONCLUSION: The subjective similarity of a pair of lesions in medical images can be quantified consistently by a group of radiologists. The concept of similarity of lesions in medical images can be subjected to rigorous scientific research and investigation in the future.

Differentiation between benign and malignant breast lesions detected by bilateral dynamic contrast-enhanced MRI: a sensitivity and specificity study.

The purpose of this study was to apply an empirical mathematical model (EMM) to kinetic data acquired under a clinical protocol to determine if the sensitivity and specificity can be improved compared with qualitative BI-RADS descriptors of kinetics. 3D DCE-MRI data from 100 patients with 34 benign and 79 malignant lesions were selected for review under an Institutional Review Board (IRB)-approved protocol. The sensitivity and specificity of the delayed phase classification were 91% and 18%, respectively. The EMM was able to accurately fit these curves. There was a statistically significant difference between benign and malignant lesions for several model parameters: the uptake rate, initial slope, signal enhancement ratio, and curvature at the peak enhancement (at most P=0.04). These results demonstrated that EMM analysis provided at least the diagnostic accuracy of the kinetic classifiers described in the BI-RADS lexicon, and offered a few key advantages. It can be used to standardize data from institutions with different dynamic protocols and can provide a more objective classification with continuous variables so that thresholds can be set to achieve desired sensitivity and specificity. This suggests that the EMM may be useful for analysis of routine clinical data.

Pure ductal carcinoma in situ: kinetic and morphologic MR characteristics compared with mammographic appearance and nuclear grade.

PURPOSE: To retrospectively compare the kinetic and morphologic characteristics of pure ductal carcinoma in situ (DCIS) lesions depicted on dynamic contrast material-enhanced magnetic resonance (MR) images with the nuclear grade and conventional mammographic appearance of these lesions. MATERIALS AND METHODS: This HIPAA-compliant retrospective study was institutional review board approved, and informed patient consent was waived. Seventy-eight patients with 79 histologically proved pure DCIS lesions were selected. There were 17 low-nuclear-grade, 26 intermediate-nuclear-grade, 30 high-nuclear-grade, and six unclassified lesions. Sixty-five lesions were classified as fine pleomorphic, fine linear, or fine linear-branching calcifications (n = 31); amorphous or indistinct calcifications (n = 18); noncalcified mass (n = 10); or occult (n = 6) at conventional (x-ray) mammography. One experienced radiologist analyzed lesion morphology and kinetic curve shape according to the Breast Imaging Reporting and Data System lexicon. Initial enhancement percentage, time to peak enhancement (T(peak)), and signal enhancement ratio (a measure of washout) were calculated for each lesion. RESULTS: Of the 79 pure DCIS lesions, 20 (25%) exhibited enhancement plateau curves and 35 (44%) exhibited washout curves. The lesions with a masslike appearance on mammograms exhibited more suspicious kinetic characteristics (mean T(peak) approximately 2 minutes) than did the lesions with amorphous or indistinct calcifications (mean T(peak) = 4.4 minutes). There was no significant difference in enhancement kinetic properties across the nuclear grades. Lesion morphology was predominantly nonmass, with clumped or heterogeneous enhancement in a segmental or linear distribution. CONCLUSION: The pure DCIS lesions exhibited washout, plateau, and persistent enhancement curves. Enhancement kinetic characteristics varied with mammographic appearance but not with nuclear grade. SUPPLEMENTAL MATERIAL: http://radiology.rsnajnls.org/cgi/content/full/245/3/684/DC1.

Determination of subjective similarity for pairs of masses and pairs of clustered microcalcifications on mammograms: comparison of similarity ranking scores and absolute similarity ratings.

The presentation of images that are similar to that of an unknown lesion seen on a mammogram may be helpful for radiologists to correctly diagnose that lesion. For similar images to be useful, they must be quite similar from the radiologists' point of view. We have been trying to quantify the radiologists' impression of similarity for pairs of lesions and to establish a "gold standard" for development and evaluation of a computerized scheme for selecting such similar images. However, it is considered difficult to reliably and accurately determine similarity ratings, because they are subjective. In this study, we compared the subjective similarities obtained by two different methods, an absolute rating method and a 2-alternative forced-choice (2AFC) method, to demonstrate that reliable similarity ratings can be determined by the responses of a group of radiologists. The absolute similarity ratings were previously obtained for pairs of masses and pairs of microcalcifications from five and nine radiologists, respectively. In this study, similarity ranking scores for eight pairs of masses and eight pairs of microcalcifications were determined by use of the 2AFC method. In the first session, the eight pairs of masses and eight pairs of microcalcifications were grouped and compared separately for determining the similarity ranking scores. In the second session, another similarity ranking score was determined by use of mixed pairs, i.e., by comparison of the similarity of a mass pair with that of a calcification pair. Four pairs of masses and four pairs of microcalcifications were grouped together to create two sets of eight pairs. The average absolute similarity ratings and the average similarity ranking scores showed very good correlations in the first study (Pearson's correlation coefficients: 0.94 and 0.98 for masses and microcalcifications, respectively). Moreover, in the second study, the correlations between the absolute ratings and the ranking scores were also very high (0.92 and 0.96), which implies that the observers were able to compare the similarity of a mass pair with that of a calcification pair consistently. These results provide evidence that the concept of similarity for pairs of images is robust, even across different lesion types, and that radiologists are able to reliably determine subjective similarity for pairs of breast lesions.

Breast cancer detection rate: designing imaging trials to demonstrate improvements.

PURPOSE: To estimate the extent of variability in screening mammography cancer detection rates and its effect on a hypothetical clinical trial of a new screening modality used to measure changes in cancer detection rate. MATERIALS AND METHODS: Each registry and the statistical coordinating center received institutional review board approval along with approval for consenting processes or a waiver of consent to enroll participants, link data, and perform analytic studies. This study was HIPAA compliant. The authors estimated the distribution of individual radiologists' breast cancer detection rates for 2,289,132 screening mammograms (9030 cancers) read by 510 radiologists in the United States who participated in the Breast Cancer Surveillance Consortium from 1996 through 2002. They then computed the distributions of breast cancer detection rates expected from a trial of screening mammography and multiple radiologists, as well as similar distributions for a hypothetical new modality that depicts one additional cancer per reader per 1000 screening examinations. Statistical power was calculated. RESULTS: The mean screening mammography cancer detection rate for individual radiologists was 3.91 cancers (standard deviation, 1.93; range, 0.25-13.75) per 1000 examinations. To achieve 80% power to detect a hypothetical increase of one additional cancer detected per reader per 1000 screening examinations, a trial in which a new modality was compared with standard mammography would require at least 25 radiologists each reading the images of at least 8000 screening examinations or 91 radiologists each reading the images of 1000-2000 examinations. CONCLUSION: The low breast cancer prevalence in an average-risk screening population and the large interradiologist variability in the observed cancer detection rate suggest that for new technologies to demonstrate significant improvement in cancer detection rate in a clinical trial, very large samples of both radiologists and patients will be required.

Independent evaluation of computer classification of malignant and benign calcifications in full-field digital mammograms.

RATIONALE AND OBJECTIVES: To evaluate whether a computer-aided diagnosis (CADx) technique can accurately classify breast calcifications in full-field digital mammograms (FFDMs) as malignant or benign. The computer technique was developed previously on screen-film mammograms (SFMs) in which individual calcifications were identified manually. The present study evaluated the computer technique independently on a new database of FFDM images with automatic detection of the individual calcifications. MATERIALS AND METHODS: We analyzed 49 consecutive FFDM cases (19 cancers) that showed suspicious calcifications. Four mammography radiologists read soft-copy mammograms retrospectively and electronically indicated the region of calcifications in each image. The computer then automatically detected the individual calcifications within the indicated region and analyzed eight features of calcification morphology and distribution to arrive at an estimated likelihood of malignancy. The radiologists entered Breast Imaging Report and Data System assessments before and after seeing the computer results. Performance was analyzed using receiver operating characteristic analysis. RESULTS: Despite variability in radiologist-indicated regions of calcifications, the computer achieved consistently high performance taking input from the four radiologists (receiver operating characteristic curve area, A(z): 0.80, 0.80, 0.78, and 0.77; differences not statistically significant). Previous results showed that the computer technique achieved an A(z) value of 0.80 on SFMs, which improved radiologists' performance significantly. CONCLUSIONS: The computer technique appears to maintain consistently high performance in classifying calcifications in FFDMs as malignant or benign without requiring substantial modification from its initial development on SFMs. The computer performance appears to be robust with respect to variations in radiologists' input.