Contralateral prophylactic mastectomy in the American College of Radiology Imaging Network 6667 trial: effect of breast MR imaging assessments and patient characteristics.

PURPOSE: To assess which patient and magnetic resonance (MR) imaging factors are associated with the likelihood of contralateral prophylactic mastectomy (CPM) in patients with newly diagnosed breast cancer. MATERIALS AND METHODS: The American College of Radiology Imaging Network 6667 trial was compliant with HIPAA; institutional review board approval was obtained at each site. All patients provided written informed consent. This study was a retrospective review of data from 934 women enrolled in the trial who did not have a known contralateral breast cancer at the time of surgical planning. The authors assessed age, menopausal status, index breast cancer histologic results, contralateral breast histologic results, breast density, family history, race and/or ethnicity, MR imaging Breast Imaging Reporting and Data System (BI-RADS) assessment, and number of MR imaging lesions for association with CPM by using the Fisher exact test, exact χ(2) test, and multivariate logistic regression analyses. RESULTS: Eighty-six of the 934 (9.2%) women underwent CPM and were more likely to be younger (mean age, 48 years [range, 27-78 years] vs mean age, 54 years [range, 25-86 years]; P < .0001), be premenopausal (55 of 86 [64%] vs 349 of 845 [41%], P < .0001), have ductal carcinoma in situ (DCIS) in the index breast (31% [27 of 86] vs 19% [164 of 848], P = .02), have greater breast density (71 of 86 [83%] vs 572 of 848 [68%], P = .004), and have a family history of breast cancer (44 of 86 [30%] vs 150 of 488 [18%], P = .01) than those who did not undergo CPM. Distributions of race and/or ethnicity, contralateral lesion pathologic results, and number of MR imaging lesions were similar in both groups. With multivariate modeling, younger age, greater breast density, DCIS index cancer, and family history remained significant, whereas menopausal status did not. Positive MR imaging assessments were not significantly more frequent in the CPM group than in the group of women who did not undergo CPM (14 of 86 [16.3%] vs 113 of 848 [13.3%], P = .43). CONCLUSION: In patients with newly diagnosed breast cancer who underwent breast MR imaging at which a contralateral breast cancer was not identified, patient factors and not breast MR imaging BI-RADS scores were chief determinants in decisions regarding CPM. Online supplemental material is available for this article.

Intended versus inferred management after PET for cancer restaging: analysis of Medicare claims linked to a coverage with evidence development registry.

BACKGROUND: The National Oncologic PET Registry (NOPR) ascertained changes in the intended management of cancer patients using questionnaire data obtained before and after positron emission tomography (PET) under Medicare's coverage with evidence development policy. OBJECTIVE: To assess the concordance between intended care plans and care received as ascertained through administrative claims data. RESEARCH DESIGN: Analysis of linked data of NOPR participants from 2006 to 2008 and their corresponding Medicare claims. SUBJECTS: Consenting patients aged older than 65 years having their first PET for restaging of bladder, kidney, ovarian, pancreas, prostate, small cell lung, or stomach cancer. MEASURES: : Agreement (positive predictive values and κ) between NOPR post-PET intended management plans for treatment (systemic therapy, radiotherapy, surgery, or combinations), biopsy, or watching as compared to claims-inferred care 30 days after PET. RESULTS: A total of 8460 patients with linked data were assessed. A total of 43.5% had metastatic disease and 45.3% had treatment planned (predominantly systemic therapy only), 11.1% biopsy and 43.5% watching. Claims-confirmed intended plans (positive predictive value) for single-mode systemic therapy in 62.0%, radiation in 66.0%, surgery in 45.6%, and biopsy in 55.7%. A total of 25.7% of patients with a plan of watching had treatment claims. By cancer type, κ ranged for systemic therapy only from 0.17 to 0.40 and for watching from 0.21 to 0.41. Agreement rates varied by cancer types but were minimally associated with patient age, performance status, comorbidity, or stage. CONCLUSIONS: Among elderly cancer patients undergoing PET for restaging, there was moderate concordance between their physicians' planned management and claims-inferred actions within a narrow time window. When higher accuracy levels are required in future coverage with evidence development studies, alternative designs will be needed.

Use of BI-RADS 3-probably benign category in the American College of Radiology Imaging Network Digital Mammographic Imaging Screening Trial.

PURPOSE: To determine (a) how often the Breast Imaging Reporting and Data System (BI-RADS) category 3 was used in the American College of Radiology Imaging Network (ACRIN) Digital Mammographic Imaging Screening Trial (DMIST), either at the time of screening mammography or after work-up, (b) how often subjects actually returned for the recommended follow-up examination, and (c) the rate and stages of any malignancies subsequently found in subjects for whom short-term interval follow-up was recommended. MATERIALS AND METHODS: This study was approved by the Institutional Review Board at all institutions where subjects were enrolled. All subjects participating in DMIST gave informed consent and the study was HIPAA-compliant. A total of 47,599 DMIST-eligible and evaluable subjects, all of whom consented to undergo both digital and screen-film mammography, were included in this analysis. Cases referred for short-term interval follow-up based on digital, screen-film, or both imaging examinations were determined. Compliance with the recommendations and the final outcome (malignancy diagnosis at biopsy or no malignancy confirmed through follow-up) of each evaluable case were determined. RESULTS: A total of 1114 of the 47,599 (2.34%) subjects had tumors assigned a BI-RADS 3 category and were recommended to undergo short-interval follow-up. In this study, 791 of 1114 (71%) of the subjects were compliant with the recommendation and returned for short-interval follow-up. Of the women who did not return for short-interval follow-up, 70% (226 of 323) did return for their next annual mammography. Among all subjects whose tumors were assigned a BI-RADS 3 category either at screening mammography or after additional work-up, nine of 1114 (0.81%) were found to have cancer. Of the nine biopsy-proved cancers, six were invasive cancers and three were ductal carcinoma in situ stage Tis-T1c. The invasive cancers were all less than 2 cm in size. CONCLUSION: In DMIST, radiologists used the BI-RADS 3 classification infrequently (2.3% of patients). Tumors assigned a BI-RADS 3 category had a low rate of malignancy. The relatively high rate of noncompliance with short-interval follow-up recommendations (323 of 1114, or 29%) supports prior recommendations that radiologists thoroughly evaluate lesions before placing them in this category.

Frequency of malignancy seen in probably benign lesions at contrast-enhanced breast MR imaging: findings from ACRIN 6667.

PURPOSE: To determine the frequency of malignancy in probably benign lesions seen at magnetic resonance (MR) screening of the contralateral breast in patients with known breast cancer enrolled in American College of Radiology Imaging Network (ACRIN) protocol 6667. MATERIALS AND METHODS: ACRIN conducted a prospective multi-institutional MR imaging screening trial of the contralateral breast in women in whom breast cancer had been diagnosed recently. Each participating institution obtained institutional review board approval before patient accrual and was compliant with HIPAA. Informed consent was obtained from the patients. At enrollment, all women had negative clinical breast examination results and negative mammograms of the study breast. At image interpretation, radiologists scored lesions by using the Breast Imaging and Reporting and Data System (BI-RADS) lexicon. Of the 969 women who comprised the final study group, 106 were classified as having a BI-RADS category 3 lesion as their highest scoring lesion at MR imaging. There were 145 BI-RADS category 3 lesions in 106 patients. RESULTS: In the 106 patients with at least one BI-RADS category 3 lesion, there were 37 masses (25.5%), 59 areas of nonmass enhancement (40.7%), and 47 foci of enhancement (32.4%). In two (1.4%) of these patients, no findings were reported. Eighty-three (78.3%) of the 106 patients had no evidence of malignancy in the study breast after 2 years of follow-up; the remaining 23 (21.7%) received a tissue diagnosis. Seventeen (16.0%) of the 106 patients elected to undergo biopsy. Biopsy was recommended in the remaining six patients (5.7%) on the basis of follow-up imaging findings. The biopsy results were benign in 18 (78%) of the 23 patients, whereas they showed atypical hyperplasia in two (9%). One (4%) of the 23 patients had ductal carcinoma in situ. Overall, malignancy was diagnosed in one (0.9%) of the 106 patients. CONCLUSION: In a multi-institutional study, the frequency of malignancy in MR-detected BI-RADS category 3 lesions was 0.9% (95% confidence interval: 0.02%, 5.14%).

Utility of Diffusion-weighted Imaging to Decrease Unnecessary Biopsies Prompted by Breast MRI: A Trial of the ECOG-ACRIN Cancer Research Group (A6702).

PURPOSE: Conventional breast MRI is highly sensitive for cancer detection but prompts some false positives. We performed a prospective, multicenter study to determine whether apparent diffusion coefficients (ADCs) from diffusion-weighted imaging (DWI) can decrease MRI false positives.Experimental Design: A total of 107 women with MRI-detected BI-RADS 3, 4, or 5 lesions were enrolled from March 2014 to April 2015. ADCs were measured both centrally and at participating sites. ROC analysis was employed to assess diagnostic performance of centrally measured ADCs and identify optimal ADC thresholds to reduce unnecessary biopsies. Lesion reference standard was based on either definitive biopsy result or at least 337 days of follow-up after the initial MRI procedure. RESULTS: Of 107 women enrolled, 67 patients (median age 49, range 24-75 years) with 81 lesions with confirmed reference standard (28 malignant, 53 benign) and evaluable DWI were analyzed. Sixty-seven of 81 lesions were BI-RADS 4 (n = 63) or 5 (n = 4) and recommended for biopsy. Malignancies exhibited lower mean in centrally measured ADCs (mm2/s) than benign lesions [1.21 × 10-3 vs.1.47 × 10-3; P < 0.0001; area under ROC curve = 0.75; 95% confidence interval (CI) 0.65-0.84]. In centralized analysis, application of an ADC threshold (1.53 × 10-3 mm2/s) lowered the biopsy rate by 20.9% (14/67; 95% CI, 11.2%-31.2%) without affecting sensitivity. Application of a more conservative threshold (1.68 × 10-3 mm2/s) to site-measured ADCs reduced the biopsy rate by 26.2% (16/61) but missed three cancers. CONCLUSIONS: DWI can reclassify a substantial fraction of suspicious breast MRI findings as benign and thereby decrease unnecessary biopsies. ADC thresholds identified in this trial should be validated in future phase III studies.

Repeatability of 18F-FDG PET/CT in Advanced Non-Small Cell Lung Cancer: Prospective Assessment in 2 Multicenter Trials.

UNLABELLED: PET/CT with the glucose analog (18)F-FDG has several potential applications for monitoring tumor response to therapy in patients with non-small cell lung cancer (NSCLC). A prerequisite for many of these applications is detailed knowledge of the repeatability of quantitative parameters derived from (18)F-FDG PET/CT studies. METHODS: The repeatability of the (18)F-FDG signal was evaluated in 2 prospective multicenter trials. Patients with advanced NSCLC (tumor stage III-IV) underwent two (18)F-FDG PET/CT studies while not receiving therapy. Tumor (18)F-FDG uptake was quantified by measurement of the maximum standardized uptake value within a lesion (SUVmax) and the average SUV within a small volume of interest around the site of maximum uptake (SUVpeak). Analysis was performed for the lesion in the chest with the highest (18)F-FDG uptake and a size of at least 2 cm (target lesion) as well as for up to 6 additional lesions per patient. Repeatability was assessed by Bland-Altman plots and calculation of 95% repeatability coefficients (RCs) of the log-transformed SUV differences. RESULTS: Test-retest repeatability was assessed in 74 patients (34 from the ACRIN 6678 trial and 40 from the Merck MK-0646-008 trial). SUVpeak was 11.57 ± 7.89 g/mL for the ACRIN trial and 6.89 ± 3.02 for the Merck trial. The lower and upper RCs were -28% (95% confidence interval [CI], -35% to -23%) and +39% (95% CI, 31% to 54%) in the ACRIN trial, indicating that a decrease of SUVpeak by more than 28% or an increase by more than 39% has a probability of less than 2.5%. The corresponding RCs from the Merck trial were -35% (95% CI, -42% to -29%) and +53% (95% CI, 41% to 72%). Repeatability was similar for SUVmax of the target lesion, averaged SUVmax, and averaged SUVpeak of up to 6 lesions per patient. CONCLUSION: The variability of repeated measurements of tumor (18)F-FDG uptake in patients with NSCLC is somewhat larger than previously reported in smaller single-center studies but comparable to that of gastrointestinal malignancies in a previous multicenter trial. The variability of measurements supports the definitions of tumor response according to PET Response Criteria in Solid Tumors.

Consequences of false-positive screening mammograms.

IMPORTANCE: False-positive mammograms, a common occurrence in breast cancer screening programs, represent a potential screening harm that is currently being evaluated by the US Preventive Services Task Force. OBJECTIVE: To measure the effect of false-positive mammograms on quality of life by measuring personal anxiety, health utility, and attitudes toward future screening. DESIGN, SETTING, AND PARTICIPANTS: The Digital Mammographic Imaging Screening Trial (DMIST) quality-of-life substudy telephone survey was performed shortly after screening and 1 year later at 22 DMIST sites and included randomly selected DMIST participants with positive and negative mammograms. EXPOSURE: Mammogram requiring follow-up testing or referral without a cancer diagnosis. MAIN OUTCOMES AND MEASURES: The 6-question short form of the Spielberger State-Trait Anxiety Inventory state scale (STAI-6) and the EuroQol EQ-5D instrument with US scoring. Attitudes toward future screening as measured by women's self-report of future intention to undergo mammographic screening and willingness to travel and stay overnight to undergo a hypothetical new type of mammography that would identify as many cancers with half the false-positive results. RESULTS: Among 1450 eligible women invited to participate, 1226 (84.6%) were enrolled, with follow-up interviews obtained in 1028 (83.8%). Anxiety was significantly higher for women with false-positive mammograms (STAI-6, 35.2 vs 32.7), but health utility scores did not differ and there were no significant differences between groups at 1 year. Future screening intentions differed by group (25.7% vs 14.2% more likely in false-positive vs negative groups); willingness to travel and stay overnight did not (9.9% vs 10.5% in false-positive vs negative groups). Future screening intention was significantly increased among women with false-positive mammograms (odds ratio, 2.12; 95% CI, 1.54-2.93), younger age (2.78; 1.5-5.0), and poorer health (1.63; 1.09-2.43). Women's anticipated high-level anxiety regarding future false-positive mammograms was associated with willingness to travel overnight (odds ratio, 1.94; 95% CI, 1.28-2.95). CONCLUSIONS AND RELEVANCE: False-positive mammograms were associated with increased short-term anxiety but not long-term anxiety, and there was no measurable health utility decrement. False-positive mammograms increased women's intention to undergo future breast cancer screening and did not increase their stated willingness to travel to avoid a false-positive result. Our finding of time-limited harm after false-positive screening mammograms is relevant for clinicians who counsel women on mammographic screening and for screening guideline development groups.

Intended versus inferred care after PET performed for initial staging in the National Oncologic PET Registry.

UNLABELLED: The National Oncologic PET Registry (NOPR) collected data on intended management before and after PET in cancer patients. We have previously reported that PET was associated with a change in intended management of about one third of patients and was consistent across cancer types. It is uncertain if intended management plans reflect the actual care these patients received. One approach to assess actual care received is using administrative claims to categorize the type and timing of clinical services. METHODS: NOPR data from 2006 to 2008 were linked to Medicare claims for consenting patients aged 65 y or older undergoing initial-staging PET scanning for bladder, ovarian, pancreatic, small cell lung, or stomach cancers. We determined the 60-d agreement between claims-inferred care and NOPR treatment plans. RESULTS: Patients (n = 4,661) were assessed, and 30%-52% had metastatic disease. Planned treatments were about two-thirds monotherapy, of which 46% was systemic therapy only, and one-third combinations. Claims paid by 60 d confirmed the NOPR plan of any systemic therapy, radiotherapy, or surgery in 79.3%, 64.7%, and 63.6%, respectively. Single-mode plans were much more often confirmed: systemic therapy in more than 85% of patients with ovarian, pancreatic, and small cell lung cancers and surgery in more than 73% of those with bladder, pancreatic, and stomach cancers. Intended combination treatments had claims for both in only 28% of patients receiving surgery-based combinations and in 55% receiving chemoradiotherapy. About 90% of patients with NOPR-planned systemic therapy had evaluation or management claims from a medical oncologist. An age of less than 75 y was associated more often with confirmation of chemotherapy, less often for radiotherapy but not with confirmation of surgery. Performance status or comorbidity did not explain confirmation rates within action categories, but confirmation rates were higher if the referrer specialized in the planned treatment. CONCLUSION: Claims confirmations of NOPR intent for initial staging were widely variable but were higher than previously reported for restaging PET, suggesting that measuring change in intended management is a reasonable method for assessing the impact diagnostic tests have on actual care.

PET and PET/CT reports: observations from the National Oncologic PET Registry.

UNLABELLED: Our objective was to identify core elements for inclusion in oncologic PET reports and to evaluate a sample of reports in the National Oncologic PET Registry database. METHODS: A list of desirable elements in PET reports was compiled from American College of Radiology and Society of Nuclear Medicine guidelines. A training set of 20 randomly selected reports was evaluated by the 4-physician panel, and the results were used to formulate a consensus approach for assessing report content and quality. Each reviewer then scored 65 randomly selected reports-20 common to all reviewers. The scores were tabulated, and interrater variability was measured for the common cases. RESULTS: Each report was assessed for 34 elements-21 primary and 11 additional questions related to 6 of these primary elements. Among the common cases, there was strong (> or = 0.70) interrater agreement for 30 of 34 elements. Among the unique cases, only 9 elements were included in more than 90% of the reports. Several important elements were not included in more than 40% of the reports: the reason for the study, a description of treatment history, a statement about comparison to other imaging, and time from radiopharmaceutical injection to imaging. CONCLUSION: Essential elements that should be included in oncologic PET reports were missing from many reports. These deficiencies may render the reports less helpful to referring physicians, may lead to misdiagnoses, and may cause coding and billing errors. Interpreting physicians should audit their reports to ascertain that they include appropriate elements necessary for billing compliance and for effective communications with referring physicians.