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.
...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.
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.
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.
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).
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.
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).
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.
Abstract 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.
To 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).
Eighty 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.
None 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.
US 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.
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.
Using a computerized mammography database and consecutive logs of needle localization procedures and fine- and large core needle biopsies of a single university-based breast imaging practice, the authors determined the breast carcinoma yield and cost of diagnosis over a 14-year period and the changes that occurred over time with the sequential introduction of ultrasound, ultrasound-guided biopsies, and stereotactic biopsies.
The overall breast carcinoma yield for needle localization biopsies of nonpalpable lesions increased from 21% in 1984 to 68% in 1998 (P < 0.0001). The yield for nonpalpable masses increased from 21% to 87% (P < 0.0001) over the same period. The selective use of ultrasound alone and percutaneous fine- and large core needle biopsy resulted in a substantial reduction in benign open surgical biopsies. A cost analysis showed a 50% reduction in the average expense of discovering breast carcinoma. The breast carcinomas detected after introduction of these methods were prognostically favorable with 88% measuring 1.5 cm or less in size and 66% measuring less than 1 cm.
Selective use of ultrasound and imaging-guided percutaneous biopsies can significantly reduce the number of benign open surgical biopsies generated by mammographic screening. This can result in substantial cost savings without decreasing the sensitivity for detecting small potentially curable lesions.
To investigate the dose response relationships of methotrexate (MTX) therapy in rat adjuvant arthritis (AA), an animal model of rheumatoid arthritis (RA).
Female Lewis rats were fed a defined diet ...and were treated with 0, 0.3, 1, 2, 3, 5, and 10 mg MTX per week beginning 3 days after adjuvant injection and lasting 6 weeks. The presence or absence of arthritis, and its degree were measured by hindpaw edema scores, ankle widths, and radiographic and histopathologic scores.
The 2, 3, 5, and 10 mg MTX per week doses resulted in deaths before the end of the protocol and suppressed normal body weight gain. Tissue destruction, measured by radiographic and histopathologic scores, was reduced in a dose dependent manner with increasing MTX dose. Suppression of inflammation, measured by ankle widths and radiographic and histopathologic scores, reached a maximum at the 1 mg MTX dose and declined at higher doses.
Suppression of tissue destruction and inflammation in rat AA does not occur in a concerted fashion as the dose of MTX increases. The implications of these findings to human disease remain to be determined.
To determine the effect of a selective core biopsy program on the yield at needle-localization biopsy (NLB) of nonpalpable lesions.
Two hundred consecutive core biopsy samples of the breast were ...evaluated in an ongoing consecutive series of 1,172 NLB samples.
Before implementation of the core biopsy program, the yield at NLB improved from 21% at 100 cases to 35% just before the introduction of core biopsy. After implementation, the yield increased gradually to 55% at 200 cases. The yield in masses increased from 21% at 100 cases to 43% just before the initiation of the core biopsy program and then increased dramatically to 72% at 200 cases. The percentage of small lesions detected did not change with implementation: 88% of invasive cancers measured less than 1.5 cm and 60% measured less than 1 cm in the last 100 cases.
Appropriate selection of cases for core biopsy can more than double the yield of cancer in NLB samples without a decrease in the percentage of small cancers detected.
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 provided 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 photo-stimulable 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.
This study compared the condyle/disk relationships on magnetic resonance images (MRIs) in a group of subjects with completely silent temporomandibular joints (TMJ) when tested clinically with those ...in subjects with readily discernible TMJ sounds. The sounds were recorded with an accelerometer as the transducer. Selected degrees of jaw separation were electronically determined and recorded with interocclusal wafers for use with the imaging process. Of the "silent joints" 89% were found to have sounds when tested with the accelerometer. These "subclinical" sounds tended to be of shorter duration and occurred at a greater degree of vertical opening than the clinically discernable sounds. The MRIs of the group with clinically discernable sounds tended to show a change in the relationship between the head of the condyle and the intermediate zone of the disk, at the degree of jaw separation of the sound occurrence, whereas no condyle/disk change occurred in the group with "clinically silent joints." It is likely that all joints create sound during function. The different characteristics of the subclinical sounds versus the clinical sounds may indicate differing sound origins.
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