Pattern of follow-up care and early relapse detection in breast cancer patients.

Routine breast cancer follow-up aims at detecting second primary breast cancers and loco regional recurrences preclinically. We studied breast cancer follow-up practice and mode of relapse detection during the first 5 years of follow-up to determine the efficiency of the follow-up schedule. The Netherlands Cancer Registry provided data of 6,509 women, operated for invasive non-metastatic breast cancer in 2003-2004. In a random sample including 144 patients, adherence to follow-up guideline recommendations was studied. Mode of relapse detection was studied in 124 patients with a second primary breast cancer and 160 patients with a loco regional recurrence. On average 13 visits were performed during the first 5 years of the follow-up, whereas nine were recommended. With one, two and three medical disciplines involved, the number of visits was 9, 14 and 18, respectively. Seventy-five percent (93/124) of patients with a second primary breast cancer, 42 % (31/74) of patients with a loco regional recurrence after breast conserving surgery and 28 % (24/86) of patients with a loco regional recurrence after mastectomy had no symptoms at detection. To detect one loco regional recurrence or second primary breast cancer preclinically, 1,349 physical examinations versus 262 mammography and/or MRI tests were performed. Follow-up provided by only one discipline may decrease the number of unnecessary follow-up visits. Breast imaging plays a major and physical examination a minor role in the early detection of second primary breast cancers and loco regional recurrences. The yield of physical examination to detect relapses early is low and should therefore be minimised.

Computer-aided detection in full-field digital mammography in a clinical population: performance of radiologist and technologists.

The purpose of the study was to evaluate the impact of a computer-aided detection (CAD) system on the performance of mammogram readers in interpreting digital mammograms in a clinical population. Furthermore, the ability of a CAD system to detect breast cancer in digital mammography was studied in comparison to the performance of radiologists and technologists as mammogram readers. Digital mammograms of 1,048 consecutive patients were evaluated by a radiologist and three technologists. Abnormalities were recorded and an imaging conclusion was given as a BI-RADS score before and after CAD analysis. Pathology results during 12 months follow up were used as a reference standard for breast cancer. Fifty-one malignancies were found in 50 patients. Sensitivity and specificity were computed before and after CAD analysis and provided with 95% CIs. In order to assess the detection rate of malignancies by CAD and the observers, the pathological locations of these 51 breast cancers were matched with the locations of the CAD marks and the mammographic locations that were considered to be suspicious by the observers. For all observers, the sensitivity rates did not change after application of CAD. A mean sensitivity of 92% was found for all technologists and 84% for the radiologist. For two technologists, the specificity decreased (from 84 to 83% and from 77 to 75%). For the radiologist and one technologist, the application of CAD did not have any impact on the specificity rates (95 and 83%, respectively). CAD detected 78% of all malignancies. Five malignancies were indicated by CAD without being noticed as suspicious by the observers. In conclusion, the results show that systematic application of CAD in a clinical patient population failed to improve the overall sensitivity of mammogram interpretation by the readers and was associated with an increase in false-positive results. However, CAD marked five malignancies that were missed by the different readers.

Strategies for digital mammography interpretation in a clinical patient population.

Mammography is the basic imaging modality for early detection of breast cancer. The aim of this prospective study was to evaluate the impact of different mammogram reading strategies on the diagnostic yield in a consecutive patient population referred for digital mammography to a hospital. First, the effect of using computer-aided detection (CAD) software on the performance of mammogram readers was studied. Furthermore, the impact of employing technologists as either prereaders or double readers was assessed, as compared to the conventional strategy of single reading by a radiologist. Digital mammograms of 1,048 consecutive patients were evaluated by a radiologist and 3 technologists with and without the use of CAD software. ROC analysis was used to study the effects of the different strategies. In the conventional strategy, an overall area under the curve (AUC) of 0.92 was found, corresponding to a sensitivity of 84% and specificity of 94%. When applying CAD software, the AUCs were similar before and after CAD for all readers (mean of 0.95). Employing technologists in prereading and double reading of mammograms resulted in a mean AUC of 0.91 and 0.96, respectively. In the prereading strategy, the corresponding sensitivity and specificity were 81 and 96%; in the double reading strategy they were 96 and 79%, respectively. Concluding, in this clinical population, systematic application of CAD software by either radiologist or technologists failed to improve the diagnostic yield. Furthermore, employing technologists as double readers of mammograms was the most effective strategy in improving breast cancer detection in daily clinical practice.

Costs and effects of using specialized breast technologists in prereading mammograms in a clinical patient population.

OBJECTIVES: The aim of this study was to assess the costs and effects of using specialized breast technologists in prereading mammograms to reduce the increasing workload of radiologists in daily clinical practice. Mammography is the most widely used imaging modality for early detection and diagnosis of breast cancer. METHODS: A total of 1389 mammograms of consecutive patients were evaluated by two technologists trained in mammogram interpretation. The costs and effects of four different experimental strategies of prereading mammograms by technologists were analyzed by decision analytic modeling and compared with the conventional strategy of standard evaluation by the radiologist on duty. RESULTS: Overall, the employment of technologists in this patient population resulted in a potential time saving up to 73 percent (1019/1389) for the radiologist. No additional false-negative imaging results were found as compared to the conventional strategy. The total diagnostic costs in the conventional strategy were determined at euro150,602. The experimental strategies resulted in cost savings up to 17.2 percent (range, euro122,494-euro139,781). CONCLUSIONS: The employment of technologists in prereading mammograms in a clinical patient population could be effective to reduce the workload of radiologists without jeopardizing the detection of malignancies. Furthermore, diagnostic costs can be reduced considerably.

Validation of a prediction rule for renal artery stenosis.

OBJECTIVES: We previously developed a prediction rule to estimate the probability of renal artery stenosis. This rule should be validated before it can be used reliably to select hypertensive patients for renal angiography. We determined the validity of the prediction rule in recent patients and in other settings. DESIGN: We studied three aspects of validity (agreement between predicted and observed probability of stenosis, discriminative ability, and clinical usefulness) in 180 consecutive patients with drug-resistant hypertension and normal or mildly impaired renal function, who visited six hypertension clinics of academic and community hospitals in the Netherlands. Thirty-five patients (19%) had a significant stenosis. RESULTS: The clinical characteristics in the rule (age, sex, vascular disease, recent onset of hypertension, smoking, body mass index, abdominal bruit, serum creatinine concentration, and hypercholesterolemia) had similar predictive value in the validation sample and development sample. The predicted probabilities of stenosis agreed well with the observed frequencies (Hosmer-Lemeshow goodness-of-fit test, P = 0.87). The prediction rule discriminated reasonably between patients with and without stenosis in the validation sample with an area under the receiver operating characteristic curve of 0.71. If only patients with predicted probabilities of stenosis of 5% or more were referred for renal angiography, the number of referrals was reduced by 20%, while 9% of patients with a stenosis were missed. CONCLUSIONS: The prediction rule was valid in more recently treated patients in other settings. If used conservatively, the rule can reliably exclude a small proportion of patients from angiography.

The additional diagnostic value of ultrasonography in the diagnosis of breast cancer.

BACKGROUND: The use of ultrasonography (US) in diagnostic breast imaging is increasing. Restricting US to subgroups of patients who benefit most would result in a more efficient and effective application. This study assessed the diagnostic value of US as an adjunct to mammography (MAM) and a clinical examination (CE) in the diagnosis of breast cancer and the feasibility of selecting subgroups of patients who benefit the most. METHODS: Between October 1, 1999, and August 1, 2000, all consecutive patients referred for breast imaging underwent additional US after MAM and a CE. Results were scored on a 5-point grading scale of increasing suggestion of malignancy. Pathologic results during 12 months of follow-up were used as the criterion standard. Receiver-operating characteristic curve analysis assessed the diagnostic value of US in the whole population and in subgroups of patients according to indication for referral and age. RESULTS: A total of 3835 breasts were examined in 2020 patients, with a 6.3% prevalence of breast cancer. Breast US detected 8 extra malignancies and correctly downgraded 332 cases from a positive to a negative diagnosis (ie, from a suggested malignancy to no malignancy). Receiver-operating characteristic curves showed a significant improvement in diagnostic value by adding US to MAM and a CE (area under the curve for CE + MAM + US vs CE + MAM, 0.99 vs 0.95; P =.002). The diagnostic yield improved significantly in patients referred for palpable breast lumps (P =.004) or referred from the National Breast Cancer Screening Program (P =.05). Less pronounced was the value in patients referred for other symptoms or for follow-up of a prior breast malignancy. When breast imaging of the contralateral breast or of asymptomatic patients referred for reassurance or follow-up of a prior benign lesion was performed, the value of additional US remained undefined because of the few malignancies found. CONCLUSIONS: The systematic application of breast US improved the overall diagnostic yield. The diagnostic value increased most in patients with palpable breast lumps and in patients referred with abnormal screening MAM results.

Chlamydia pneumoniae seropositivity and systemic and renovascular atherosclerotic disease.

BACKGROUND: Patients with hypertension may be vulnerable to vascular Chlamydia pneumoniae and/or cytomegalovirus (CMV) infection because of increased expression of adhesion molecules. OBJECTIVE: To determine whether C pneumoniae or CMV is associated with the presence of atherosclerotic lesions in hypertensive patients. METHODS: Ninety-six angiographic studies on 100 consecutive patients with of clinical signs or symptoms suggestive of renovascular hypertension were reviewed for the presence or absence of atherosclerotic lesions at the level of the renal arteries as well and abdominal aorta. Also, the presence of a hemodynamically notable renal artery stenosis and antibodies to C pneumoniae (IgG and IgA) and CMV (IgG and IgM) was determined, and all classic risk factors were recorded. RESULTS: Atherosclerotic lesions were documented in 67 patients (70%), and in 49 patients (51%) such lesions were present at the level of the renal artery. In the univariate analysis, significant associations between IgG (odds ratio, 3.8; 95% confidence interval, 1.2-11.7; P =.02) as well as IgA (odds ratio, 2.6; 95% confidence interval, 1.1-6.7; P =.03) antibodies to C pneumoniae and the presence of atherosclerosis were found for both the aorta and the renal arteries. Seroprevalence (IgG) to C pneumoniae in the 23 patients with a hemodynamically notable renal artery stenosis was 100% and differed (P =.01) from those without a notable renal artery stenosis (78%). In the multivariate analysis, IgG seropositivity to C pneumoniae was significantly associated with atherosclerosis (odds ratio, 6.0; 95% confidence interval, 1.33-27.5; P =.02), and age. There was no association between CMV seropositivity and atherosclerosis. CONCLUSION: The presence of antibodies to C pneumoniae was significantly associated with atherosclerosis and renovascular disease in hypertensive patients in whom a renal artery stenosis was strongly suspected.

Accuracy of computed tomographic angiography and magnetic resonance angiography for diagnosing renal artery stenosis.

BACKGROUND: Timely, accurate detection of renal artery stenosis is important because this disorder may be a potentially curable cause of hypertension and renal impairment. OBJECTIVE: To determine the validity of computed tomographic angiography (CTA) and magnetic resonance angiography (MRA) compared with digital subtraction angiography (DSA) for detection of renal artery stenosis. DESIGN: Prospective multicenter comparative study conducted from 1998 to 2001. Two panels of 3 observers judged CTA and MRA image data and were blinded to all other results. Digital subtraction angiography images were evaluated by consensus. SETTING: 3 large teaching hospitals and 3 university hospitals in the Netherlands. PATIENTS: 402 hypertensive patients with suspected renal artery stenosis were included. A group of 356 patients who underwent all 3 diagnostic tests was used for analysis. MEASUREMENTS: Reproducibility was assessed by calculating interobserver agreement. Diagnostic performance was evaluated in terms of sensitivity, specificity, and other diagnostic variables. Atherosclerotic stenoses of 50% or greater and fibromuscular dysplasia were considered clinically relevant. RESULTS: Twenty percent of patients who underwent all 3 tests had clinically relevant renal artery stenosis. Moderate interobserver agreement was found, with kappa values ranging from 0.59 to 0.64 for CTA and 0.40 to 0.51 for MRA. The combined sensitivity and specificity were 64% (95% CI, 55% to 73%) and 92% (CI, 90% to 95%) for CTA and 62% (CI, 54% to 71%) and 84% (CI, 81% to 87%) for MRA. LIMITATIONS: Eighteen percent of the patients were included nonconsecutively. Digital subtraction angiography may be an imperfect reference test. CONCLUSION: Computed tomographic angiography and MRA are not reproducible or sensitive enough to rule out renal artery stenosis in hypertensive patients. Therefore, DSA remains the diagnostic method of choice. *For a list of the other investigators and research coordinators who participated in RADISH, see the Appendix.

Clinical impact of the use of additional ultrasonography in diagnostic breast imaging.

The degree of adherence with evidence-based guidelines for the use of breast ultrasonography was determined in clinical practice of radiologists in six hospitals. Additional ultrasonography was performed in 2,272 (53%) of all 4,257 patients referred for mammography. High adherence rates (mean: 95%) were observed for guidelines recommending ultrasonography in patients referred for palpable breast masses and abnormal screening and diagnostic mammograms. Lower adherence rates (mean: 81%, Pearson correlation coefficient= -0.57; p=0.001) were found for guidelines advising against additional ultrasonography in patients referred for breast symptoms, a known benign abnormality, a family history or anxiety of breast cancer. The overuse of ultrasonography in 442 patients and underuse in 95 patients led to five additional false-positive results. It was concluded that the guidelines seem workable and feasible in clinical practice and that the current daily routine of diagnostic breast imaging corresponded to a great extent to the guidelines proposed.

Peripheral arterial disease: clinical and cost comparisons between duplex US and contrast-enhanced MR angiography--a multicenter randomized trial.

PURPOSE: To prospectively determine the clinical and economic consequences of replacing duplex ultrasonography (US) with contrast material-enhanced magnetic resonance (MR) angiography for the initial imaging work-up of patients with peripheral arterial disease (PAD). MATERIALS AND METHODS: This randomized multicenter study was approved by the institutional review board of each hospital, and all patients signed written informed consent prior to randomization. Patients with PAD who needed to undergo imaging work-up and who had an ankle-brachial pressure index (ABPI) of less than 0.90 were recruited by vascular surgeons between January 2002 and September 2003. Patients were randomly assigned to undergo contrast-enhanced MR angiography or duplex US. The primary outcome measure was cost. Secondary outcome measures included therapeutic confidence, changes in disease severity, and changes in quality of life (QOL) assessed during 6 months of follow-up. Indicators for disease severity were based on the Rutherford classification, treadmill walking distance, ABPI at rest, and ABPI after exercise. QOL was assessed with the Rating Scale, Short Form 36, EuroQol-5D, and VascuQol questionnaires. The cost of (additional) imaging procedures, therapeutic interventions, and outpatient visits were calculated from a hospital perspective (ie, all costs incurred inside the hospital were estimated, including physician costs). Data were evaluated by using the Student t test and a multivariable linear regression analysis. RESULTS: At 6 months, 352 patients (239 [68%] men, 113 [32%] women; mean age, 65 years) were analyzed. The use of contrast-enhanced MR angiography versus duplex US reduced the number of additional vascular imaging procedures by 42%; contrast-enhanced MR angiography was also associated with higher therapeutic confidence. Diagnostic costs for contrast-enhanced MR angiography were 167 euros (186 dollars) higher than those for duplex US (P < .001). No statistically significant differences were found for total cost, changes in disease severity, or changes in QOL between patients examined with duplex US and those examined with contrast-enhanced MR angiography (P > .05). CONCLUSION: Replacing duplex US with contrast-enhanced MR angiography for the initial imaging work-up of patients with PAD reduces the need for additional imaging, although diagnostic costs are higher.

Comparison of generic and disease-specific questionnaires for the assessment of quality of life in patients with peripheral arterial disease.

OBJECTIVE: This study compared the ability of generic and disease-specific questionnaires to assess quality of life (QOL) at baseline and to detect change in QOL after treatment in patients with peripheral arterial disease (PAD). METHODS: This prospective multicenter trial recruited 514 patients with PAD who needed an imaging workup and had an ankle brachial pressure index of less than 0.90. Patients with severe comorbidity were excluded, leaving a study population of 450 patients. Patients completed two generic questionnaires, the Short Form 36 (SF-36) and the European Quality of Life 5D (EuroQol-5D), and one disease-specific questionnaire, the Vascular Quality of Life (VascuQol) at baseline and after 6 months of follow-up. Rutherford classification and treadmill walking distance were determined at baseline and after 6 months of follow-up and were considered indicators of disease severity. Receiver operating characteristic (ROC) curves and areas under the curves (AUCs) were used to evaluate each of the three questionnaires for its ability to discriminate between severe and mild disease at baseline and to discriminate between a large and small change in disease severity after follow-up. The underlying assumption was that disease severity is a major determinant of QOL. This implies that the validity of a QOL questionnaire is reflected by its ability to discriminate between mildly and severely diseased patients. RESULTS: At baseline, 443 patients and after follow-up, 386 patients completed questionnaires. At baseline, no significant ( P >.05) differences were observed among AUCs for the total scores of the three questionnaires, indicating that all three questionnaires assessed the disease severity equally well. After follow-up, the AUCs for the VascuQol were significantly higher than the AUCs for the SF-36 and EuroQol-5D with respect to detection of improvement in Rutherford classification ( P < .05), indicating that change in disease severity after follow-up was best detected by the VascuQol. CONCLUSION: The VascuQol is the preferred questionnaire as outcome measure for QOL in future trials and clinical follow-up of patients with PAD.

Costs and effects of ultrasonography in the evaluation of palpable breast masses.

OBJECTIVE: To study the costs and effects of incorporating ultrasonography in the triple assessment of palpable breast masses. METHODS: A decision analytic model was designed to compare a conventional strategy of performing fine-needle aspiration cytology after clinical examination and mammography, with three different experimental strategies of preceding ultrasonography. Empirical data were used from a prospective study in 522 breasts in 492 patients with a palpable mass, including 93 malignancies. In strategy 1, cases with probably benign, suspect malignant, and malignant ultrasonography results were referred for fine-needle aspiration cytology; in strategy 2, benign cases were also referred for fine-needle aspiration cytology; and in strategy 3, ultrasonography was only performed in patients with benign results on clinical examination and mammography, whereas immediate fine-needle aspiration cytology was performed in patients with suspicious lesions. Outcome variables included the total costs and the expected number of life years. Sensitivity analysis was performed on all parameters in the model. RESULTS: All strategies reported a similar life expectancy of 31.0 years. Cost-minimization demonstrated that experimental strategy 3 was the least expensive strategy (3013 Euro). Experimental strategy 2 was the most costly one (3512 Euro). Compared with the conventional strategy of immediate fine-needle aspiration cytology (3087 Euro), both ultrasonography strategies 1 and -3 were preferred. CONCLUSIONS: Incorporating ultrasonography in the triple assessment of palpable breast masses can result in a reduction of the total costs for the diagnosis and treatment of breast cancer.