Wanda K. Bernreuter

Locally Advanced Breast Cancer: MR Imaging for Prediction of Response to Neoadjuvant Chemotherapy—Results from ACRIN 6657/I-SPY TRIAL

PURPOSE To compare magnetic resonance (MR) imaging findings and clinical assessment for prediction of pathologic response to neoadjuvant chemotherapy (NACT) in patients with stage II or III breast cancer. MATERIALS AND METHODS The HIPAA-compliant protocol and the informed consent process were approved by the American College of Radiology Institutional Review Board and local-site institutional review boards. Women with invasive breast cancer of 3 cm or greater undergoing NACT with an anthracycline-based regimen, with or without a taxane, were enrolled between May 2002 and March 2006. MR imaging was performed before NACT (first examination), after one cycle of anthracyline-based treatment (second examination), between the anthracycline-based regimen and taxane (third examination), and after all chemotherapy and prior to surgery (fourth examination). MR imaging assessment included measurements of tumor longest diameter and volume and peak signal enhancement ratio. Clinical size was also recorded at each time point. Change in clinical and MR imaging predictor variables were compared for the ability to predict pathologic complete response (pCR) and residual cancer burden (RCB). Univariate and multivariate random-effects logistic regression models were used to characterize the ability of tumor response measurements to predict pathologic outcome, with area under the receiver operating characteristic curve (AUC) used as a summary statistic. RESULTS Data in 216 women (age range, 26-68 years) with two or more imaging time points were analyzed. For prediction of both pCR and RCB, MR imaging size measurements were superior to clinical examination at all time points, with tumor volume change showing the greatest relative benefit at the second MR imaging examination. AUC differences between MR imaging volume and clinical size predictors at the early, mid-, and posttreatment time points, respectively, were 0.14, 0.09, and 0.02 for prediction of pCR and 0.09, 0.07, and 0.05 for prediction of RCB. In multivariate analysis, the AUC for predicting pCR at the second imaging examination increased from 0.70 for volume alone to 0.73 when all four predictor variables were used. Additional predictive value was gained with adjustments for age and race. CONCLUSION MR imaging findings are a stronger predictor of pathologic response to NACT than clinical assessment, with the greatest advantage observed with the use of volumetric measurement of tumor response early in treatment.

Ultrasound detection of bone erosions in rheumatoid arthritis: a comparison to routine radiographs of the hands and feet

PurposeTo determine if ultrasound (US) of selected joints in the hands and feet can detect more erosions than radiography and establish the presence of erosive disease in patients with rheumatoid arthritis (RA).MethodsEighty joints in ten patients with RA and 40 joints in five healthy control subjects, who were age, gender and ethnicity-matched to the patients with arthritis, were prospectively studied with radiographs and sonography. Conventional radiographs of the hands and feet were obtained. US examinations of the 2nd and 5th metacarpal-phalangeal (MCP) joints of the hands, and the 1st and 5th metatarsal-phalangeal (MTP) joints of the feet were performed. Radiographs and US exams were independently graded for the presence of erosions.ResultsNone of the control subjects had erosions. US detected erosions in 17/80, and radiographs detected erosions in 6/80 joints assessed with both modalities. US detected all erosions seen by radiographs in these selected joints. Erosive disease was present in the radiographs of seven of ten RA patients. US established erosive disease in eight of ten RA patients. US determined erosive disease in two of the three patients without radiographic erosions.ConclusionsUS of the MTP and MCP joints in RA can detect erosions not seen with radiography and may be complementary to radiography in establishing the presence of erosive disease in early RA.

Leiomyosarcoma of bone. A ciinicopathologic, immunohistochemical, and ultrastructural study of five cases

Authors identified five leiomyosarcomas (LMS) in a review of 13 nonmatrix‐producing spindle cell sarcomas of bone. Only two were initially recognized as LMS; the others had been diagnosed as malignant fibrous histiocytoma (two) and fibrosarcoma (one). The patients, four of whom were women, ranged in age from 32 to 70 years. Sites included proximal humerus (two), distal femur (two), and rib (one). All tumors presented with clinical and radiographic features consistent with a diagnosis of primary bone neoplasms, although one probably represented a solitary metastasis from a primary uterine LMS. Radiographs showed lytic bone destruction with a moth‐eaten appearance, and three cases had soft tissue extension. Histologically, all tumors showed broad, interlacing fascicles of spindle cells with pleomorphic nuclei, frequent mitoses, and necrosis. Two cases had a focal storiform pattern and bizarre multinucleated cells, and two other cases had focally prominent osteoclast‐like giant cells. Extensive immunoreactivity for muscle actin was seen in all cases and for desmin in three. In each case, electron microscopy showed definite smooth muscle differentiation including cytoplasmic filaments with densities. At this writing, two patients are free of disease (including the patient with a presumed metastasis), one is alive with locally recurrent disease, and two are dead of disease. Experience suggests that LMS of bone is a distinct clinicopathologic entity that may be more common than previously recognized. Application of immunohistochemistry and electron microscopy to nonmatrix‐producing bone sarcomas should facilitate diagnosis of additional cases.

Cartilage imaging in osteoarthritis

Osteoarthritis (OA) is the most common articular disorder encountered worldwide. Its successful evaluation (and eventual treatment) depends on establishing a set of criteria for measuring disease progression. An ideal measurement would evaluate changes in articular cartilage, where the primary pathology of the disease takes place. Plain radiographs are the simplest and most readily employable means of joint evaluation, and now microfocal radiographs have been developed, which magnify the radiograph and help portray the joint space more accurately. However, radiography, along with nuclear medicine scans, arthrography, and computed tomography (CT) scans, are limited in their use because they are unable to detect early cartilage abnormalities. Magnetic resonance imaging (MRI) has the advantages of multiplanar imaging, soft tissue contrast, and noninvasiveness. Like radiography, MRI can underestimate the extent of cartilage abnormality. The most sensitive technique for measuring superficial articular abnormalities is arthroscopy, and small-bore arthroscopes are being used to assess knee damage in conscious, nonsedated patients. However, it is not yet clear if arthroscopy can detect subtle changes over time, and vision can be blocked by cloudy synovial fluid. Finally, although it is usually well tolerated, arthroscopy is an invasive technique.

Reducing the cost of diagnosis of breast carcinoma

The objective of this study was to determine whether the use of ultrasound and percutaneous breast biopsies in patients with screen‐detected nonpalpable abnormalities can reduce benign open surgical biopsies of the breast without increasing cost or sacrificing detection of potentially curable breast carcinomas.

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

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

Pilot trial of preoperative (neoadjuvant) letrozole in combination with bevacizumab in postmenopausal women with newly diagnosed estrogen receptor- or progesterone receptor-positive breast cancer.

INTRODUCTION Tumor content or expression of vascular endothelial growth factor (VEGF) is associated with impaired efficacy of antiestrogen adjuvant therapy. We designed a pilot study to assess the feasibility and short-term efficacy of neoadjuvant letrozole and bevacizumab (anti-VEGF) in postmenopausal women with stage II and III estrogen receptor/progesterone receptor-positive breast cancer. PATIENTS AND METHODS Patients were treated with a neoadjuvant regimen of letrozole orally 2.5 mg/day and bevacizumab intravenously 15 mg/kg every 3 weeks for a total of 24 weeks before the surgical treatment of their breast cancer. Patients were followed for toxicity at 3-week intervals, and tumor assessment (a physical examination and ultrasound) was performed at 6-week intervals. Positron emission tomography (PET) scans were performed before therapy and 6 weeks after the initiation of therapy. RESULTS Twenty-five evaluable patients were treated. The regimen was well-tolerated, except in 2 patients who were taken off the study for difficulties controlling their hypertension. An objective clinical response occurred in 17 of 25 patients (68%), including 16% complete responses (CRs) and 52% partial responses. The 4 patients with clinical CRs manifested pathologic CRs in their breasts (16%), although 1 patient had residual tumor cells in her axillary nodes. Eight of 25 patients (32%) attained stage 0 or 1 status. The PET scan response at 6 weeks correlated with clinical CRs and breast pathologic CRs at 24 weeks (P < .0036). CONCLUSION Combination neoadjuvant therapy with letrozole and bevacizumab was well-tolerated and resulted in impressive clinical and pathologic responses. The Translational Breast Cancer Research Consortium has an ongoing randomized phase II trial of this regimen in this patient population.

Accuracy of Breast Magnetic Resonance Imaging in Predicting Pathologic Response in Patients Treated With Neoadjuvant Chemotherapy

BACKGROUND Prior studies of the ability of magnetic resonance imaging (MRI) to predict pathologic response to neoadjuvant chemotherapy have shown conflicting results that vary depending on baseline molecular characteristics. This study examines the ability of MRI to predict pathologic complete response (pCR) and explores the influence of tumor molecular profiles on MRI sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). METHODS Eighty-one patients with invasive breast cancer treated with neoadjuvantsystemic therapy between 2002 and 2009 who were imaged with breast MRI pre- and post-treatment were reviewed. Patient, tumor, and treatment characteristics were recorded. Comparisons of molecular subsets and their influence on MRI sensitivity, specificity, PPV, and NPV were made using χ(2)contingency tables. RESULTS The sensitivity, specificity, PPV, and NPV of MRI for predicting pCR for the total group were 92%, 50%, 74%, and 80%, respectively. Patients had the following molecular subtypes: 33/81 (41%) HR+Her2-, 23/81 (28%) HR+/-Her2 +, and 25/81(31%) triple receptor negative (TN). Molecular subtype did not demonstrate a significant correlation of radiographic and pathologic response, although MRI NPV was highest in the TN subset (100%) followed by those with HR+/-Her2+ disease (87.5%). Multivariate analysis did not show that tumor characteristics (estrogen receptor status, progesterone receptor status, HER2 status) or neoadjuvant treatment (doxorubicin, cyclophosphamide, paclitaxel versus other or trastuzumab) had any effect on MRI sensitivity or specificity. CONCLUSIONS In patients receiving neoadjuvant systemic therapy for invasive breast cancer, molecular subtype and systemic regimen administered did not significantly influence the sensitivity, specificity, PPV, or NPV of MRI in predicting pathologic response.

PACS and CR implementation in a Level I Trauma Center Emergency Department

Implementation of a picture archive and communication system (PACS) at a large teaching hospital is an expensive and daunting endeavor. The approach taken at the University of Alabama Hospitals has been to assemble an institution-wide system through focused integration of smaller mini-PACS. Recently a mini-PACS using Computed Radiography (CR) has been placed in the Emergency Department (ED) of a Level I Trauma Center completely replacing conventional screen-film radiography. This area of the hospital produces approximately 250 images per day and provides many challenging requirements: the need for rapid radiography; providing good image quality for difficult examinations with potentially uncooperative patients; reproduction of lost films to maintain availability of images to multiple consulting teams; and frequently unknown patient demographics. The PACS includes both vendor-supplied and in-house developed devices for image storage, distribution, and display. Digital images are produced using two photostimulable phosphor CR systems. Currently, all radiographic examinations are acquired digitally with production of a hard copy film as well as electronic distribution via the PACS. Interpretation of images is done primarily via hard copy with a goal of transition to soft copy interpretation. This paper discusses the functional requirements of the PACS and solutions to workflow issues arising in the ED.

A Pilot Trial of Pre-Operative (Neoadjuvant) Letrozole in Combination with Bevacizumab in Post-Menopausal Women with Newly Diagnosed Estrogen and/or Progesterone Receptor Positive Breast Cancer.

Purpose Tumor content or expression of vascular endothelial growth factor (VEGF) is associated with impaired efficacy of anti-estrogen adjuvant therapy. We designed a pilot study of neoadjuvant letrozole and bevacizumab (anti-VEGF) to assess feasibility and short term efficacy in post-menopausal women with stage II/III, ER/PR positive breast cancer. Patients and Methods Patients were treated with a neo-adjuvant regimen of letrozole, 2.5mg/day (P.O.) and bevacizumab 15mg/kg Q3 weeks (I.V.) for a total of 24 weeks prior to surgical treatment of their breast cancer. Patients were followed for toxicity at 3 week intervals and tumor assessment (physical exam and tumor ultrasound) at 6 week intervals. PET scans were carried out prior to therapy and 6 weeks after initiation of therapy. Surgery was done 4 weeks after the last dose of bevacizumab. Results Twenty five evaluable patients were treated. The regimen was well tolerated except for 2 patients who were taken off-study for difficult to control hypertension. Objective clinical response occurred in 17/25 patients (68%) including 16% CR and 52% PR. The 4 patients with clinical CR had pathologic CR in their breasts (16%) although one had residual tumor cells in axillary nodes. 8/25 patients (32%) attained stage 0 or 1 status. PET scan response at 6 weeks correlated with clinical CR and breast pathologic CR at 24 weeks (p Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1088.