In postmenopausal women with estrogen receptor-positive early breast cancer, surgery is usually followed by a 5-year course of tamoxifen. This report presents results of a prospective, open-label, ...randomized study, designed to evaluate the benefits of switching to anastrozole after 2 years of tamoxifen treatment, compared with continuing on tamoxifen for 5 years.
After receiving tamoxifen treatment for 2 years, eligible patients (n = 979) were randomly assigned to switch to anastrozole (1 mg/d) or continue tamoxifen (20 or 30 mg/d) for an additional 3 years. Patients were monitored every 6 months during years 1 to 3 and annually thereafter. The primary efficacy variable was disease-free survival, including local or distant recurrence, new contralateral breast cancer, or death. Secondary variables were overall survival and assessment of safety.
Switching to anastrozole resulted in a significant reduction in the risk of disease recurrence (hazard ratio HR, 0.66; 95% CI, 0.44 to 1.00; P = .049), and improved overall survival (HR, 0.53; 95% CI, 0.28 to 0.99; P = .045) compared with continuing on tamoxifen. Fewer patients who switched to anastrozole reported serious adverse events (22.7% v 30.8%) compared with those who continued on tamoxifen, mainly due to more patients in the tamoxifen group with endometrial events. The overall safety profile for anastrozole was consistent with previous reports and no new safety issues were identified.
Postmenopausal women who have taken tamoxifen for 2 years as adjuvant therapy are less likely to experience a recurrence of breast cancer and have improved overall survival if they switch to anastrozole compared with continuing to receive tamoxifen.
Large skull-base meningiomas are difficult to treat due to their proximity or adherence to critical structures. We analyzed the long-term results of patients with skull-base meningiomas treated by a ...new approach with high-precision fractionated stereotactic radiotherapy.
One hundred eighty-nine patients with benign meningiomas were treated with conformal fractionated stereotactic radiotherapy between 1985 and 1998. Patients were undergoing a course of radiotherapy either as primary treatment, following subtotal resection, or for recurrent disease. The median target volume was 52.5 mL (range, 5.2 to 370 mL). The mean radiation dose was 56.8 Gy (+/- 4.4 Gy). Follow-up examinations, including magnetic resonance imaging, were performed at 6-month intervals thereafter.
The median follow-up period was 35 months (range, 3 months to 12 years). Overall actuarial survival for patients with World Health Organization (WHO) grade I meningiomas was 97% after 5 years and 96% after 10 years. Local tumor failure was observed in three of 180 patients with WHO grade I tumors and was significantly higher in two of nine patients with WHO grade II tumors. A volume reduction of more than 50% was observed in 26 patients (14%). Preexisting cranial nerve symptoms resolved completely in 28% of the patients. Clinically significant treatment-induced toxicity was seen in 1.6% of the patients. No treatment-related deaths occurred.
The results of this study demonstrate that fractionated stereotactic radiotherapy is safe and effective in the therapy of subtotally resected or unresectable meningiomas. The overall morbidity and incidence subacute and late side effects of this conformal radiotherapy approach were low.
To investigate, with dynamic magnetic resonance imaging (dMRI) and a fiducial marker, the influence of different breathing maneuvers on internal organ and external chest wall motion.
Lung and chest ...wall motion of 16 healthy subjects (13 male, 3 female) were examined with real-time trueFISP (true fast imaging with steady-state precession) dMRI and a small inductively coupled marker coil on either the abdomen or thorax. Three different breathing maneuvers were performed (predominantly "abdominal breathing," "thoracic breathing," and unspecific "normal breathing"). The craniocaudal (CC), anteroposterior (AP), and mediolateral (ML) lung distances were correlated (linear regression coefficient) with marker coil position during forced and quiet breathing.
Differences of the CC distance between maximum forced inspiration and expiration were significant between abdominal and thoracic breathing (p < 0.05). The correlation between CC distance and coil position was best for forced abdominal breathing and a marker coil in the abdominal position (r = 0.89 +/- 0.04); for AP and ML distance, forced thoracic breathing and a coil in the thoracic position was best (r = 0.84 +/- 0.03 and 0.82 +/- 0.03, respectively). In quiet breathing, a lower correlation was found.
A fiducial marker coil external to the thorax in combination with dMRI is a new technique to yield quantitative information on the correlation of internal organ and external chest wall motion. Correlations are highly dependent on the breathing maneuver.
OBJECTIVES:To evaluate relative cerebral blood flow (rCBF) in normal brain tissue using arterial spin-labeling (ASL) methods and first-pass dynamic susceptibility-weighted contrast-enhanced (DSC) ...magnetic resonance imaging (MRI).
METHODS:Sixty-two patients with brain metastases were examined on a 1.5 T-system up to 6 times during routine follow-up after stereotactic radiosurgery. Perfusion values in normal gray and white matter were measured using the ASL techniques ITS-FAIR in 38 patients, Q2TIPS in 62 patients, and the first-pass DSC echo-planar (EPI) MRI after bolus administration of gadopentetate dimeglumine in 42 patients. Precision of the ASL sequences was tested in follow-up examinations in 10 healthy volunteers.
RESULTS:Perfusion values in normal brain tissue obtained by all sequences correlated well by calculating Pearson’s correlation coefficients (P < 0.0001) and remained unchanged after stereotactic radiosurgery as shown by analysis of variance (P > 0.05).
CONCLUSION:Both ASL and DSC EPI MRI yield highly comparable perfusion values in normal brain tissue.
A dysregulated secretion of contra-inflammatory cytokines such as interleukin-10 (IL-10) could play a role in the pathogenesis of inflammatory bowel disease (IBD). We have investigated the expression ...of IL-10 in gut tissues from patients with Crohn's disease (CD), ulcerative colitis (UC) and controls by mRNA
in situhybridization and immunohistochemistry. Intestinal epithelial cells were found to express IL-10 mRNA and IL-10 protein in all of the tissues investigated without any major differences in the expression patterns. However, compared with noninflamed gut, significantly increased numbers of mononuclear cells (MNCs) producing IL-10 were present in inflamed gut, both in CD and UC. This cytokine was expressed most prominently by inflammatory infiltrates enriched in macrophages, although T cells seem to contribute to its production as well. Elevated IL-10 expression in IBD was mainly detected in the submucosa, whereas IL-10 production by lamina propria cells remained comparably low. In contrast, the expression of IL-1β mRNA was preferentially increased in the lamina propria. Our data argue against a general deficiency in IL-10 production in IBD. The results suggest rather that the local production of IL-10 by mucosal MNCs in IBD is insufficient to down-regulate pro-inflammatory cytokines such as IL-1β in the lamina propria compartment.
To evaluate outcome after fractionated stereotactic radiotherapy (RT) of patients with World Health Organization Grade 2 astrocytoma in terms of progression-free survival, overall survival, toxicity, ...quality of life, and prognostic factors.
Between 1984 and 2000, 143 patients with histologically proven Grade 2 astrocytoma were treated with fractionated stereotactic RT at our institution. The evaluation of the quality of life and toxicity was based on neurologic examinations and the Karnofsky performance score. Univariate analysis was performed on seven potential prognosticators and multivariate analysis on four prognosticators.
The median follow-up was 44 months. The actuarial overall survival and progression-free survival was 58% and 39% at 5 years, respectively. Out-of-field recurrences occurred in 1 patient (1.2%). We did not observe a dose–response relationship. Overall survival and progression-free survival were significantly correlated with the absence of contrast media enhancement before RT (
p <0.01). Toxicity was mild and included severe side effects of European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group Grade 3 in only 4 patients (2.8%). The Karnofsky performance score improved in most patients.
Fractionated stereotactic RT is effective and has low toxicity in the treatment of Grade 2 gliomas. The rate of field border recurrences was not increased compared with after conventional RT. Exceeding the tumor dose did not improve the tumor control rate but did enhance toxicity. Pretherapeutic contrast media enhancement should be interpreted as a sign of higher grade tumor elements.
For more than 20 years, tamoxifen has been the mainstay of adjuvant endocrine therapy for women with hormone-sensitive early-stage breast cancer. However, not only does tamoxifen have potential ...side-effects such as an increased risk of endometrial cancer and thromboembolic events, but patients can also develop resistance to the drug. We aimed to investigate whether switching treatment of postmenopausal women with such breast cancer to anastrozole after 2–3 years of tamoxifen would be more effective than continuing on tamoxifen for a total of 5 years.
We did a meta-analysis of three clinical trials—the Austrian Breast and Colorectal Cancer Study Group (ABCSG 8), Arimidex-Nolvadex (ARNO 95), and the Italian Tamoxifen Anastrozole (ITA) studies—in which postmenopausal women with histologically confirmed, hormone-sensitive early-stage breast cancer were randomised to 1 mg/day anastrozole (n=2009) after 2–3 years of tamoxifen treatment or to continued 20 or 30 mg/day tamoxifen (n=1997). We analysed the data with a stratified Cox proportional hazards model with the covariates of age, tumour size, nodal status, grade, surgery, and chemotherapy.
Patients who switched to anastrozole had fewer disease recurrences (92
vs 159) and deaths (66
vs 90) than did those who remained on tamoxifen, resulting in significant improvements in disease-free survival (hazard ratiro 0·59 95% CI 0·48–0·74; p<0·0001), event-free survival (0·55 0·42–0·71; p<0·0001), distant recurrence-free survival (0·61 0·45–0·83; p=0·002), and overall survival (0·71 0·52–0·98; p=0·04).
Our results show that the clinical benefits in terms of event-free survival seen in individual trials for those patients who switched to anastrozole translate into a benefit in overall survival. These findings confirm that clinicians should consider switching postmenopausal women who have taken adjuvant tamoxifen for 2–3 years to anastrozole.
This phase II trial evaluated the efficacy and safety of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib, in combination with first-line chemotherapy in advanced ...urothelial cancer.
Chemotherapy-naïve patients with advanced or metastatic urothelial carcinoma were randomized 1:1:1 to receive six cycles of chemotherapy (gemcitabine 1,250 mg/m2 on days 1 and 8, and cisplatin 70 mg/m2 on day 1 of every cycle) concomitantly with gefitinib 250 mg/day (arm A); or with sequential gefitinib (arm B); or alone (arm C). The primary endpoint was the time to progression (TTP).
A total of 105 patients received study treatment. Median TTP for arms A, B, and C were 6.1, 6.3, and 7.8 months, respectively. There were no significant differences between treatment arms for any outcomes measured. The most common adverse events were nausea and vomiting.
Gefitinib in combination with chemotherapy did not improve efficacy in advanced urothelial cancer.
This study demonstrates the value of a fast fluid‐attenuated inversion‐recovery (FLAIR) technique in the assessment of primary intraaxial brain tumors. Twenty‐one patients with primary intraaxial ...brain tumors were examined by T2‐weighted, proton‐density‐weighted fast spin echo, fast FLAIR, and contrast‐enhanced T1‐weighted spin echo using identical slice parameters. The images were evaluated using quantitative and qualitative criteria. Quantitative criteria were tumor‐to‐background and tumor‐to‐cerebrospinal fluid (CSF) contrast and contrast‐to‐noise ratio (CNR). The qualitative evaluation was performed as a multi‐reader analysis concerning lesion detection, lesion delineation, and image artifacts. In the qualitative evaluation, all readers found the fast FLAIR to be superior to fast spin echo in the exact delineation of intraaxial brain tumors (P < .001) and the delineation of enhancing and nonenhancing tumor parts. Fast FLAIR was superior in the delineation of cortically located and small lesions but was limited in lesions adjacent to the ventricles. Fast FLAIR provided a significantly better tumor‐to‐CSF contrast and tumor‐to‐CSF CNR (P < .001). The tumor‐to‐background contrast and tumor‐to‐background CNR of the fast FLAIR images were lower than those of T2‐weighted spin‐echo images but higher than those of proton‐density‐weighted spin‐echo images. FLAIR images had more image artifacts influencing the image interpretation in only two patients. Signal hyperintensities at the ventricular border were present in 92% of the patients. They are common findings in fast FLAIR and should be included into the image interpretation.
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