Radiotheranostics: a roadmap for future development.

Radiotheranostics, injectable radiopharmaceuticals with antitumour effects, have seen rapid development over the past decade. Although some formulations are already approved for human use, more radiopharmaceuticals will enter clinical practice in the next 5 years, potentially introducing new therapeutic choices for patients. Despite these advances, several challenges remain, including logistics, supply chain, regulatory issues, and education and training. By highlighting active developments in the field, this Review aims to alert practitioners to the value of radiotheranostics and to outline a roadmap for future development. Multidisciplinary approaches in clinical trial design and therapeutic administration will become essential to the continued progress of this evolving therapeutic approach.

Diffusion of Bevacizumab Across Oncology Practices: An Observational Study.

BACKGROUND: Technological advances can improve care and outcomes but are a primary driver of health care spending growth. Understanding diffusion and use of new oncology therapies is important, given substantial increases in prices and spending on such treatments. OBJECTIVES: Examine diffusion of bevacizumab, a novel (in 2004) and high-priced biologic cancer therapy, among US oncology practices during 2005-2012 and assess variation in use across practices. RESEARCH DESIGN: Population-based observational study. SETTING: A total of 2329 US practices providing cancer chemotherapy. PARTICIPANTS: Random 20% sample of 236,304 Medicare fee-for-service beneficiaries aged above 65 years in 2004-2012 undergoing infused chemotherapy for cancer. MEASURES: Diffusion of bevacizumab (cumulative time to first use and 10% use) in practices, variation in use across practices overall and by higher versus lower-value use. We used hierarchical models with practice random effects to estimate the between-practice variation in the probability of receiving bevacizumab and to identify factors associated with use. RESULTS: We observed relatively rapid diffusion of bevacizumab, particularly in independent practices and larger versus smaller practices. We observed substantial variation in use; the adjusted odds ratio (95% confidence interval) of bevacizumab use was 2.90 higher (2.73-3.08) for practices 1 SD above versus one standard deviation below the mean. Variation was less for higher-value [odds ratio=2.72 (2.56-2.89)] than lower-value uses [odds ratio=3.61 (3.21-4.06)]. CONCLUSIONS: Use of bevacizumab varied widely across oncology practices, particularly for lower-value indications. These findings suggest that interventions targeted to practices have potential for decreasing low-value use of high-cost cancer therapies.

Comparing a medical records-based and a claims-based index for measuring comorbidity in patients with lung or colon cancer.

OBJECTIVE: Ascertaining comorbid conditions in cancer patients is important for research and clinical quality measurement, and is particularly important for understanding care and outcomes for older patients and those with multi-morbidity. We compared the medical records-based ACE-27 index and the claims-based Charlson index in predicting receipt of therapy and survival for lung and colon cancer patients. MATERIALS AND METHODS: We calculated the Charlson index using administrative data and the ACE-27 score using medical records for Veterans Affairs patients diagnosed with stage I/II non-small cell lung or stage III colon cancer from January 2003 to December 2004. We compared the proportion of patients identified by each index as having any comorbidity. We used multivariable logistic regression to ascertain the predictive power of each index regarding delivery of guideline-recommended therapies and two-year survival, comparing the c-statistic and the Akaike information criterion (AIC). RESULTS: Overall, 97.2% of lung and 90.9% of colon cancer patients had any comorbidity according to the ACE-27 index, versus 59.5% and 49.7%, respectively, according to the Charlson. Multivariable models including the ACE-27 index outperformed Charlson-based models when assessing receipt of guideline-recommended therapies, with higher c-statistics and lower AICs. Neither index was clearly superior in prediction of two-year survival. CONCLUSIONS: The ACE-27 index measured using medical records captured more comorbidity and outperformed the Charlson index measured using administrative data for predicting receipt of guideline-recommended therapies, demonstrating the potential value of more detailed comorbidity data. However, the two indices had relatively similar performance when predicting survival.

Racial disparities in cancer care in the Veterans Affairs health care system and the role of site of care.

OBJECTIVES: We assessed cancer care disparities within the Veterans Affairs (VA) health care system and whether between-hospital differences explained disparities. METHODS: We linked VA cancer registry data with VA and Medicare administrative data and examined 20 cancer-related quality measures among Black and White veterans diagnosed with colorectal (n = 12,897), lung (n = 25,608), or prostate (n = 38,202) cancer from 2001 to 2004. We used logistic regression to assess racial disparities for each measure and hospital fixed-effects models to determine whether disparities were attributable to between- or within-hospital differences. RESULTS: Compared with Whites, Blacks had lower rates of early-stage colon cancer diagnosis (adjusted odds ratio [AOR] = 0.80; 95% confidence interval [CI] = 0.72, 0.90), curative surgery for stage I, II, or III rectal cancer (AOR = 0.57; 95% CI = 0.41, 0.78), 3-year survival for colon cancer (AOR = 0.75; 95% CI = 0.62, 0.89) and rectal cancer (AOR = 0.61; 95% CI = 0.42, 0.87), curative surgery for early-stage lung cancer (AOR = 0.50; 95% CI = 0.41, 0.60), 3-dimensional conformal or intensity-modulated radiation (3-D CRT/IMRT; AOR = 0.53; 95% CI = 0.47, 0.59), and potent antiemetics for highly emetogenic chemotherapy (AOR = 0.87; 95% CI = 0.78, 0.98). Adjustment for hospital fixed-effects minimally influenced racial gaps except for 3-D CRT/IMRT (AOR = 0.75; 95% CI = 0.65, 0.87) and potent antiemetics (AOR = 0.95; 95% CI = 0.82, 1.10). CONCLUSIONS: Disparities in VA cancer care were observed for 7 of 20 measures and were primarily attributable to within-hospital differences.

Tumor boards and the quality of cancer care.

BACKGROUND: Despite the widespread use of tumor boards, few data on their effects on cancer care exist. We assessed whether the presence of a tumor board, either general or cancer specific, was associated with recommended cancer care, outcomes, or use in the Veterans Affairs (VA) health system. METHODS: We surveyed 138 VA medical centers about the presence of tumor boards and linked cancer registry and administrative data to assess receipt of stage-specific recommended care, survival, or use for patients with colorectal, lung, prostate, hematologic, and breast cancers diagnosed in the period from 2001 to 2004 and followed through 2005. We used multivariable logistic regression to assess associations of tumor boards with the measures, adjusting for patient sociodemographic and clinical characteristics. All statistical tests were two-sided. RESULTS: Most facilities (75%) had at least one tumor board, and many had several cancer-specific tumor boards. Presence of a tumor board was associated with only seven of 27 measures assessed (all P < .05), and several associations were not in expected directions. Rates of some recommended care (eg, white blood cell growth factors with cyclophosphamide, adriamycin, vincristine, and prednisone in diffuse large B-cell lymphoma) were lower in centers with hematologic-specialized tumor boards (39.4%) than in centers with general tumor boards (61.3%) or no tumor boards (56.4%; P = .002). Only one of 27 measures was statistically significantly associated with tumor boards after applying a Bonferroni correction for multiple comparisons. CONCLUSIONS: We observed little association of multidisciplinary tumor boards with measures of use, quality, or survival. This may reflect no effect or an effect that varies by structural and functional components and participants' expertise.

Area-level variations in cancer care and outcomes.

BACKGROUND: : Substantial regional variations in health-care spending exist across the United States; yet, care and outcomes are not better in higher-spending areas. Most studies have focused on care in fee-for-service Medicare; whether spillover effects exist in settings without financial incentives for more care is unknown. OBJECTIVE: : We studied care for cancer patients in fee-for-service Medicare and the Veterans Health Administration (VA) to understand whether processes and outcomes of care vary with area-level Medicare spending. DESIGN: : An observational study using logistic regression to assess care by area-level measures of Medicare spending. SUBJECTS: : Patients with lung, colorectal, or prostate cancers diagnosed during 2001-2004 in Surveillance, Epidemiology, and End Results (SEER) areas or the VA. The SEER cohort included fee-for-service Medicare patients aged older than 65 years. MEASURES: : Recommended and preference-sensitive cancer care and mortality. RESULTS: : In fee-for-service Medicare, higher-spending areas had higher rates of recommended care (curative surgery and adjuvant chemotherapy for early-stage non-small-cell lung cancer and chemotherapy for stage III colon cancer) and preference-sensitive care (chemotherapy for stage IV lung and colon cancer and primary treatment of local/regional prostate cancer) and had lower lung cancer mortality. In the VA, we observed minimal variation in care by area-level Medicare spending. DISCUSSION: : Our findings suggest that intensity of care for Medicare beneficiaries is not driving variations in VA care, despite some overlap in physician networks. Although the Dartmouth Atlas work has been of unprecedented importance in demonstrating variations in Medicare spending, new measures may be needed to better understand variations in other populations.

Survival of older patients with cancer in the Veterans Health Administration versus fee-for-service Medicare.

PURPOSE: The Veterans Health Administration (VHA) provides high-quality preventive chronic care and cancer care, but few studies have documented improved patient outcomes that result from this high-quality care. We compared the survival rates of older patients with cancer in the VHA and fee-for-service (FFS) Medicare and examined whether differences in the stage at diagnosis, receipt of guideline-recommended therapies, and unmeasured characteristics explain survival differences. PATIENTS AND METHODS: We used propensity-score methods to compare all-cause and cancer-specific survival rates for men older than age 65 years who were diagnosed or received their first course of treatment for colorectal, lung, lymphoma, or multiple myeloma in VHA hospitals from 2001 to 2004 to similar FFS-Medicare enrollees diagnosed in Surveillance, Epidemiology, and End Results (SEER) areas in the same time frame. We examined the role of unmeasured factors by using sensitivity analyses. RESULTS: VHA patients versus similar FFS SEER-Medicare patients had higher survival rates of colon cancer (adjusted hazard ratio [HR], 0.87; 95% CI, 0.82 to 0.93) and non-small-cell lung cancer (NSCLC; HR, 0.91; 95% CI, 0.88 to 0.95) and similar survival rates of rectal cancer (HR, 1.05; 95% CI, 0.95 to 1.16), small-cell lung cancer (HR, 0.99; 95% CI, 0.93 to 1.05), diffuse large-B-cell lymphoma (HR, 1.02; 95% CI, 0.89 to 1.18), and multiple myeloma (HR, 0.92; 95% CI, 0.83 to 1.03). The diagnosis of VHA patients at earlier stages explained much of the survival advantages for colon cancer and NSCLC. Sensitivity analyses suggested that additional adjustment for the severity of comorbid disease or performance status could have substantial effects on estimated differences. CONCLUSION: The survival rate for older men with cancer in the VHA was better than or equivalent to the survival rate for similar FFS-Medicare beneficiaries. The VHA provision of high-quality care, particularly preventive care, can result in improved patient outcomes.

Understanding variation in primary prostate cancer treatment within the Veterans Health Administration.

OBJECTIVE: To examine the variation in prostate cancer treatment in the Veterans Health Administration (VHA)--a national, integrated delivery system. We also compared the care for older men in the VHA with that in fee-for-service Medicare. METHODS: We used data from the Veterans Affairs Central Cancer Registry linked with administrative data and Surveillance, Epidemiology, and End Results-Medicare data to identify men with local or regional prostate cancer diagnosed during 2001 to 2004. We used multinomial logistic and hierarchical regression models to examine the patient, tumor, and facility characteristics associated with treatment in the VHA and, among older patients, used propensity score methods to compare primary therapy between the VHA and fee-for-service Medicare. RESULTS: The rates of radical prostatectomy and radiotherapy varied substantially across VHA facilities. Among the VHA patients, older age, black race/ethnicity, and greater comorbidity were associated with receiving neither radical prostatectomy nor radiotherapy. Facilities with more black patients with prostate cancer had lower rates of radical prostatectomy, and those with less availability of external beam radiotherapy had lower radiotherapy rates. The adjusted rates of radiotherapy (39.7% vs 52.0%) and radical prostatectomy (12.1% vs 15.8%) were lower and the rates of receiving neither treatment greater (48.2% vs 32.2%) in the VHA versus fee-for-service Medicare (P < .001). CONCLUSIONS: In the VHA, the treatment rates varied substantially across facilities, and black men received less aggressive prostate cancer treatment than white men, suggesting factors other than patient preferences influence the treatment decisions. Also, primary prostate cancer therapy for older men is less aggressive in the VHA than in fee-for-service Medicare.

Improved outcomes associated with higher surgery rates for older patients with early stage nonsmall cell lung cancer.

BACKGROUND: Although surgery offers the greatest chance of a cure for patients with early stage nonsmall cell lung cancer (NSCLC), older and sicker patients often fail to undergo resection. The benefits of surgery in older patients and patients with multiple comorbidities are uncertain. METHODS: The authors identified a national cohort of 17,638 Medicare beneficiaries aged ≥66 years living in Surveillance, Epidemiology, and End Results (SEER) areas who were diagnosed with stage I or II NSCLC during 2001 to 2005. Areas with high and low rates of curative surgery for early stage lung cancer were compared to estimate the effectiveness of surgery in older and sicker patients. Logistic regression models were used to assess mortality according to the quintile of area-level surgery rates, adjusting for potential confounders. RESULTS: Less than 63% of patients underwent surgery in low-surgery areas, whereas >79% underwent surgery in high-surgery areas. High-surgery areas operated on more patients of advanced age and patients with chronic obstructive pulmonary disease than low-surgery areas. The adjusted all-cause 1 year mortality was 18% in high-surgery areas versus 22.8% in low-surgery areas (adjusted odds ratio [OR], 0.89; 95% confidence interval [CI], 0.86-0.93) for each 10% increase in the surgery rate).The 1-year lung-cancer-specific mortality similarly was lower in high-surgery areas (12%) versus low-surgery areas (16.9%; adjusted OR, 0.86; 95% CI, 0.82-0.91) for each 10% increase in the surgery rate. CONCLUSIONS: Higher rates of surgery for stage I/II NSCLC were associated with improved survival, even when older patients and sicker patients underwent resection. The authors concluded that more work is needed to identify and reduce barriers to surgery for early stage NSCLC.

Location of cancer surgery for older veterans with cancer.

OBJECTIVE: Many veterans undergo cancer surgery outside of the Veterans Health Administration (VHA). We assessed to what extent these patients obtained care in the VHA before surgery. DATA SOURCES: VHA-Medicare data, VHA administrative data, and Veterans Affairs Central Cancer Registry data. STUDY DESIGN: We identified patients aged ≥65 years in the VHA-Medicare cohort who underwent lung or colon cancer resection outside the VHA and assessed VHA visits in the year before surgery. PRINCIPAL FINDINGS: Over 60% of patients in the VHA-Medicare cohort who received lung or colon cancer surgeries outside the VHA did not receive any care in VHA before surgery. CONCLUSIONS: Veterans' receipt of major cancer surgery outside the VHA probably reflects usual private sector care among veterans who are infrequent VHA users.

Reasons for underuse of recommended therapies for colorectal and lung cancer in the Veterans Health Administration.

BACKGROUND: Many studies have documented low rates of effective cancer therapies, particularly in older or minority populations. However, little is known about why effective therapies are underused in these populations. METHODS: The authors examined medical records of 584 patients with cancer diagnosed or treated in Department of Veterans Affairs facilities to assess reasons for lack of 1) surgery for stage I/II nonsmall cell lung cancer, 2) surgery for stage I/II/III rectal cancer, 3) adjuvant radiation therapy for stage II/III rectal cancer, and 4) adjuvant chemotherapy for stage III colon cancer. They also assessed differences in reasons for underuse by patient age and race. RESULTS: Across the 4 guideline-recommended treatments, 92% to 99% of eligible patients were referred to the appropriate cancer specialist; however, therapy was recommended in only 74% to 92% of eligible cases. Poor health was cited in the medical record as the reason for lack of therapy in 15% to 61% of underuse cases; patient refusal explained 26% to 58% of underuse cases. African American patients were more likely to refuse surgery. Older patients were more likely to refuse treatments. CONCLUSIONS: Recommendation against therapy was a primary factor in underuse of effective therapies in older and sicker patients. Patients' refusal of therapy contributed to age and racial disparities in care. Improved data on the effectiveness of cancer therapies in community populations and interventions aimed at improved communication of known risks and benefits of therapy to cancer patients could be effective tools to reduce underuse and lingering disparities in care.

Quality of care for older patients with cancer in the Veterans Health Administration versus the private sector: a cohort study.

BACKGROUND: The Veterans Health Administration (VHA) is the largest integrated health care system in the United States. Studies suggest that the VHA provides better preventive care and care for some chronic illnesses than does the private sector. OBJECTIVE: To assess the quality of cancer care for older patients provided by the VHA versus fee-for-service Medicare. DESIGN: Observational study of patients with cancer that was diagnosed between 2001 and 2004 who were followed through 2005. SETTING: VHA and non-VHA hospitals and office-based practices. PATIENTS: Men older than 65 years with incident colorectal, lung, or prostate cancer; lymphoma; or multiple myeloma. MEASUREMENTS: Rates of processes of care for colorectal, lung, or prostate cancer; lymphoma; or multiple myeloma. Rates were adjusted by using propensity score weighting. RESULTS: Compared with the fee-for-service Medicare population, the VHA population received diagnoses of colon (P < 0.001) and rectal (P = 0.007) cancer at earlier stages and had higher adjusted rates of curative surgery for colon cancer (92.7% vs. 90.5%; P < 0.010), standard chemotherapy for diffuse large B-cell non-Hodgkin lymphoma (71.1% vs. 59.3%; P < 0.001), and bisphosphonate therapy for multiple myeloma (62.1% vs. 50.4%; P < 0.001). The VHA population had lower adjusted rates of 3-dimensional conformal or intensity-modulated radiation therapy for prostate cancer treated with external-beam radiation therapy (61.6% vs. 86.0%; P < 0.001). Adjusted rates were similar for 9 other measures. Sensitivity analyses suggest that if patients with cancer in the VHA system have more severe comorbid illness than other patients, rates for most indicators would be higher in the VHA population than in the fee-for-service Medicare population. LIMITATION: This study included only older men and did not include information about performance status, severity of comorbid illness, or patient preferences. CONCLUSION: Care for older men with cancer in the VHA system was generally similar to or better than care for fee-for-service Medicare beneficiaries, although adoption of some expensive new technologies may be delayed in the VHA system. PRIMARY FUNDING SOURCE: Department of Veterans Affairs.

End-of-life care for older cancer patients in the Veterans Health Administration versus the private sector.

BACKGROUND: Treatment of older cancer patients at the end of life has become increasingly aggressive, despite the absence of evidence for better outcomes. We compared aggressiveness of end-of-life care of older metastatic cancer patients treated in the Veterans Health Administration (VHA) and those under fee-for-service Medicare arrangements. METHODS: Using propensity score methods, we matched 2913 male veterans who were diagnosed with stage IV lung or colorectal cancer in 2001-2002 and died before 2006 with 2913 similar men enrolled in fee-for-service Medicare living in Surveillance, Epidemiology, and End Result (SEER) areas. We assessed chemotherapy within 14 days of death, intensive care unit (ICU) admissions within 30 days of death, and >1 emergency room visit within 30 days of death. RESULTS: Among matched cohorts, men treated in the VHA were less likely than men in the private sector to receive chemotherapy within 14 days of death (4.6% vs 7.5%, P<.001), be admitted to an ICU within 30 days of death (12.5% vs 19.7%, P<.001), or have >1 emergency room visit within 30 days of death (13.1 vs 14.7, P=.09). CONCLUSIONS: Older men with metastatic lung or colorectal cancer treated in the VHA healthcare system received less aggressive end-of-life care than similar men in fee-for-service Medicare. This may result from the absence of financial incentives for more intensive care in the VHA or because this integrated delivery system is better structured to limit potentially overly aggressive care. Additional studies are needed to assess whether men undergoing less aggressive end-of-life care also experience better outcomes.

Does oral antiandrogen use before leuteinizing hormone-releasing hormone therapy in patients with metastatic prostate cancer prevent clinical consequences of a testosterone flare?

OBJECTIVES: To investigate whether oral antiandrogen therapy before initiation of leuteinizing hormone-releasing hormone (LHRH) agonists was associated with fewer clinical flares. LHRH agonists are associated with initial testosterone rises that may cause clinical disease flares in men with metastatic prostate cancer. METHODS: We identified newly diagnosed metastatic prostate cancer patients treated in Veterans Affairs Hospitals from 2001-2004 with LHRH agonists with or without prior antiandrogen therapy. We assessed spinal cord compression, radiation therapy, fractures, bladder outlet obstruction, and narcotic prescriptions for pain within 30 days of starting LHRH therapy. RESULTS: Of 1566 metastatic prostate cancer patients treated with LHRH agonists, 1245 (79.5%) patients received oral antiandrogens before initiating LHRH agonist treatment. Hispanic men, married patients, and those without prior cancer were treated less often with oral antiandrogens (all P < or = .05). Complication rates did not differ by receipt of oral antiandrogens (all P > or = .17). Spinal cord compression and pathologic fractures were extremely rare whether antiandrogens were used or not. In adjusted analysis, there was no decrease in odds of any event for treatment with an antiandrogen within 6 days (OR, 1.04, 95% CI, 0.78-1.40) or > or = 7 days (OR, 0.95, 95% CI, 0.72-1.25) before LHRH agonist treatment. CONCLUSIONS: Antiandrogen therapy before LHRH agonists in metastatic prostate cancer was not associated with differences in fractures, spinal cord compression, bladder outlet obstruction, or narcotic prescriptions. Rates of spinal cord compression or fracture were < 1% in the first 30 days after beginning LHRH agonist therapy regardless of antiandrogen use.

Differences in clinical trial patient attributes and outcomes according to enrollment setting.

PURPOSE: During the last 25 years, National Cancer Institute (NCI) cooperative trial groups have extended trial networks from academic centers to include certain community and Veterans Health Administration (VHA) centers. We compared trial patients' attributes and outcomes by these enrollment settings. PATIENTS AND METHODS: Studying 2,708 patients on one of 10 cooperative group, randomized lung trials at 272 institutions, we compared patient attributes by enrollment setting (ie, academic, community, and VHA affiliates). We used adjusted Cox regression to evaluate for survival differences by setting. RESULTS: Main member institutions enrolled 44% of patients; community affiliates enrolled 44%; and VHAs enrolled 12%. Patient attributes (ie, case-mix) of age, ethnicity, sex, and performance status varied by enrollment setting. After analysis was adjusted for patient case-mix, no mortality differences by enrollment setting were noted. CONCLUSION: Although trial patients with primarily advanced-stage lung cancer from nonacademic centers were older and had worse performance statuses than those from academic centers, survival did not differ by enrollment setting after analysis accounted for patient heterogeneity. An answer for whether long-term outcomes for patients at community and VHA centers affiliated with cooperative trial groups are equivalent to those at academic centers when care is delivered through NCI trials requires additional research among patients with longer survival horizons.

Survival and changes in comorbidities after bariatric surgery.

OBJECTIVE: To evaluate survival rates and changes in weight-related comorbid conditions after bariatric surgery in a high-risk patient population as compared with a similar cohort of morbidly obese patients who did not undergo surgery. SUMMARY BACKGROUND DATA: Morbid obesity is increasingly becoming a major public health issue. Existing studies are limited in their ability to assess the risks and benefits of bariatric surgery because few studies compare surgical patients to a similar, morbidly obese, nonsurgical cohort, especially in high-risk populations like the elderly and disabled. METHODS: A retrospective cohort analysis using Medicare fee-for-service patients from 2001 to 2004. Survival rates and diagnosed presence of 5 conditions commonly comorbid with morbid obesity were examined for morbidly obese patients who did and did not undergo bariatric surgery, with up to 2 years follow-up. RESULTS: Morbidly obese Medicare patients who underwent bariatric surgery had increased survival rates over the 2 years of this study when compared with a similar morbidly obese nonsurgical group (P < 0.001). For patients under the age of 65, this survival advantage started at 6 months postoperatively and for patients over age 65, at 11 months. The surgical group also experienced significant improvements in the diagnosed prevalence of 5 weight-related comorbid conditions (diabetes, sleep apnea, hypertension, hyperlipidemia, and coronary artery disease) relative to the nonsurgical cohort after 1 year postsurgery (P < 0.001). CONCLUSIONS: Bariatric surgery appears to increase survival even in the high-risk, Medicare population, both for individuals aged 65 and older and those disabled and under 65. In addition, the diagnosed prevalence of weight-related comorbid conditions declined after bariatric surgery relative to a control cohort of morbidly obese patients who did not undergo surgery.

Stereotactic and sonographic large-core biopsy of nonpalpable breast lesions: results of the Radiologic Diagnostic Oncology Group V study.

RATIONALE AND OBJECTIVES: To determine the diagnostic accuracy of stereotactically and sonographically guided core biopsy (CB) for the diagnosis of nonpalpable breast lesions. MATERIALS AND METHODS: Twenty-two institutions enrolled 2,403 women who underwent imaging-guided fine needle aspiration followed by imaging-guided large-CB of nonpalpable breast abnormalities. All mammograms were reviewed for study eligibility by one of two breast imaging radiologists. The protocol for image-guided biopsy, using either ultrasound (USCB) or stereotactic (SCB) guidance, was standardized at all institutions and all biopsy specimens were over-read by one of three expert pathologists. Patients with atypical ductal hyperplasia (ADH), atypical lobular hyperplasia, or lobular neoplasia on CB underwent surgical excision. Those with negative CB but suspicious ("discordant") pre-biopsy mammography also underwent surgical excision. Patients having a negative CB that was concordant with the pre-biopsy mammography suspicion were assigned to follow-up mammography at 6, 12, and 24 months following CB. RESULTS: A gold standard diagnosis based on definitive histopathologic diagnosis, mammography follow-up, or an imputed gold standard diagnosis was established for 1,681 patients. Of 310 cases with a gold standard diagnosis of invasive breast carcinoma, 261 (84.2%) were invasive carcinoma, 31 (10%) were ductal carcinoma in situ (DCIS), four (1.3%) were ADH, one (0.3%) was a non-breast cancer, and 13 (4.2%) were benign on CB. For 138 cases with a gold standard diagnosis of DCIS, 113 (81.9%) were DCIS, 20 (14.5%) were ADH, and five (3.6%) were benign on CB. For 57 cases (13 masses, 44 calcifications) with an initial CB diagnosis of ADH, atypical lobular hyperplasia or lobular neoplasia, 20 (35.1%) had a gold standard diagnosis of DCIS (4 masses, 16 calcifications) and four (7.0%) had a gold standard diagnosis of invasive cancer (4 calcifications). Of 144 cases (22 masses, 122 calcifications) with an initial CB diagnosis of DCIS, 31 (21.5%) had a gold standard diagnosis of invasive cancer (10 masses, 21 calcifications). The sensitivity, specificity and accuracy for CB by either imaging guidance method in this trial were .91, 1.00, and .98, respectively. The sensitivity, predictive value negative, and accuracy of CB for diagnosing masses (.96, .99, and .99, respectively) were significantly greater (P < .001) than for calcifications (.84, .94, and .96, respectively). The sensitivity (.89) of SCB for diagnosing all lesions was significantly lower (P = 0.029) than that of USCB (.97) because of the preponderance of calcifications biopsied by SCB versus USCB. There was no difference between USCB and SCB in sensitivity, predictive value negative, or accuracy for the diagnosis of masses (97.3, 98.9, and 99.2, respectively for USCB; 95.6, 98.5, and 98.9 respectively for SCB). CONCLUSION: Percutaneous, imaged-guided core breast biopsy is an accurate diagnostic alternative to surgical biopsy in women with mammographically detected suspicious breast lesions.

Diagnostic agreement in the evaluation of image-guided breast core needle biopsies: results from a randomized clinical trial.

BACKGROUND: Image-guided core needle biopsies (CNBs) are commonly used as the initial sampling method for nonpalpable, mammographically detected breast lesions. Although prior studies have shown that this procedure is a highly sensitive and accurate method for the detection of breast cancer, the level of diagnostic agreement between pathologists in the analysis of CNB has not been previously studied in detail. METHODS: To address this, we reviewed the pathologic findings in 2004 CNB from patients enrolled in the Radiologic Diagnostic Oncology Group 5 study, a randomized, multicenter trial designed to determine the role of CNB and fine needle aspiration biopsy in the evaluation of nonpalpable breast lesions. Slides of CNB specimens were initially diagnosed by pathologists at the 22 participating institutions (local diagnosis) and were then sent to the study pathologists for central review (central diagnosis). Local and central diagnoses were compared. RESULTS: Overall, the central diagnosis and local diagnosis were concordant in 1925 cases (96%), indicating an excellent level of agreement by kappa statistic analysis (kappa = 0.90; 95% confidence interval 0.88-0.92). The level of agreement between local and central pathologists did not vary with the image guidance system (stereotactic mammography vs. ultrasound) or with the mammographic findings (soft tissue density vs. microcalcifications). The level of diagnostic agreement observed for CNB was comparable to that observed among 596 open surgical biopsies obtained from patients in this study and subjected to central pathology review (93% agreement; kappa = 0.89, 95% confidence interval 0.86-0.92). CONCLUSIONS: The level of diagnostic agreement in interpretation of breast CNB is extremely high among pathologists and is comparable to that seen for open surgical biopsy.

Understanding individual and small area variation in the underuse of coronary angiography following acute myocardial infarction.

BACKGROUND: Underuse of coronary angiography is common among patients with acute myocardial infarction (AMI) and the magnitude of underuse varies across geographic areas. OBJECTIVES: To examine the influence of patient demographic, clinical and hospital characteristics on underuse of coronary angiography, and the contribution of these factors to variation in underuse across geographic regions. RESEARCH DESIGN: Cohort study using data from the Cooperative Cardiovascular Project. SUBJECTS: Nine thousand four hundred fifty-eight patients in 95 hospital referral regions (HRRs) hospitalized for AMI in 1994 to 1995 and for whom angiography was rated necessary. MEASURES: Odds ratios (95% confidence intervals) associated with underuse of angiography according to patient and hospital characteristics. The difference between low and high rates of underuse of angiography across regions after controlling for regional differences in patient and hospital characteristics. RESULTS: Of those for whom angiography was rated necessary, 42% did not undergo the procedure. Underuse of angiography was associated with several patient demographic and hospital attributes (eg, female gender, black race, treatment in a hospital without angiography, treatment by a general practitioner) as well as with prevalent clinical characteristics, such as renal insufficiency, congestive heart failure, prior coronary artery bypass surgery, and chronic obstructive pulmonary disease. Across HRRs, variation in underuse ranged from 24.0% to 58.3%. The difference between low and high rates did not decline significantly after controlling for regional differences in patient or hospital characteristics. CONCLUSIONS: At the patient-level, rates of necessary angiography may be improved if we address disparities in care related to sociodemographic characteristics and to the technological capabilities of hospitals. In addition, practice guidelines should be updated to reflect clinical concerns about the risks and benefits of angiography and subsequent revascularization in certain patient sub-groups, both to provide appropriate guidance to physicians and to facilitate better estimates of underuse. The causes of regional variation in underuse do not appear to be related to regional differences in patient or hospital characteristics, and therefore, require further study.

Staging of neuroblastoma at imaging: report of the radiology diagnostic oncology group.

PURPOSE: To compare the accuracies of computed tomography (CT), magnetic resonance (MR) imaging, and bone scintigraphy in staging disease in patients with neuroblastoma. MATERIALS AND METHODS: Ninety-six children with newly diagnosed neuroblastoma were enrolled in a multicenter prospective cohort study. CT, MR, and bone scintigraphy were used to evaluate tumor stage. Sensitivity and specificity values and receiver operating characteristic (ROC) curve analyses were used to compare the accuracy of CT, MR, and scintigraphy for tumor staging. RESULTS: Eighty-eight patients were eligible for staging analysis, and 45 patients who underwent surgery at initial diagnosis were eligible for analysis of local tumor extent. CT and MR had sensitivities of 43% and 83%, respectively (P <.01), and specificities of 97% and 88%, respectively (P >.05), for detection of stage 4 disease. Areas under the ROC curves for CT and MR were 0.81 and 0.85, respectively (P =.06); that for scintigraphy was 0.83. Addition of scintigraphy to both CT and MR increased the areas under the ROC curves to 0.90 and 0.88, respectively. Accuracy of CT and MR for staging disease confined to the chest or abdomen (stages 1, 2, and 3) was poor. CONCLUSION: MR alone and CT and MR combined with bone scintigraphy enable the accurate detection of stage 4 disease. Both CT and MR perform poorly for local tumor staging.