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Childs S.K.,Harvard University | Chen Y.-H.,Dana-Farber Cancer Institute | Duggan M.M.,Faulkner Hospital | Duggan M.M.,Dana-Farber Cancer Institute | And 5 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2013

Purpose: To examine the rate of local recurrence according to the margin status for patients with pure ductal carcinoma in situ (DCIS) treated by mastectomy. Methods and Materials: One hundred forty-five consecutive women who underwent mastectomy with or without radiation therapy for DCIS from 1998 to 2005 were included in this retrospective analysis. Only patients with pure DCIS were eligible; patients with microinvasion were excluded. The primary endpoint was local recurrence, defined as recurrence on the chest wall; regional and distant recurrences were secondary endpoints. Outcomes were analyzed according to margin status (positive, close (≤2 mm), or negative), location of the closest margin (superficial, deep, or both), nuclear grade, necrosis, receptor status, type of mastectomy, and receipt of hormonal therapy. Results: The primary cohort consisted of 142 patients who did not receive postmastectomy radiation therapy (PMRT). For those patients, the median follow-up time was 7.6 years (range, 0.6-13.0 years). Twenty-one patients (15%) had a positive margin, and 23 patients (16%) had a close (≤2 mm) margin. The deep margin was close in 14 patients and positive in 6 patients. The superficial margin was close in 13 patients and positive in 19 patients. One patient experienced an isolated invasive chest wall recurrence, and 1 patient had simultaneous chest wall, regional nodal, and distant metastases. The crude rates of chest wall recurrence were 2/142 (1.4%) for all patients, 1/21 (4.8%) for those with positive margins, 1/23 (4.3%) for those with close margins, and 0/98 for patients with negative margins. PMRT was given as part of the initial treatment to 3 patients, 1 of whom had an isolated chest wall recurrence. Conclusions: Mastectomy for pure DCIS resulted in a low rate of local or distant recurrences. Even with positive or close mastectomy margins, the rates of chest wall recurrences were so low that PMRT is likely not warranted. © 2013 Elsevier Inc. All rights reserved. Source

Vaz-Luis I.,Dana-Farber Cancer Institute | Vaz-Luis I.,Institute Medicina Molecular | Zeghibe C.A.,Dana-Farber Cancer Institute | Frank E.S.,Dana-Farber Cancer Institute | And 10 more authors.
Breast Cancer Research and Treatment | Year: 2013

There are ethical concerns regarding the performance of biopsies in patients for research purposes. We examined our single-institution experience regarding acceptance, safety, and success rate with research biopsies in patients with breast cancer. Among patients with data from paired samples, receptor status agreement between primary and metastatic samples was examined, either on first recurrence or after progression on one or more lines of therapy. An IRB-approved prospective study at the Dana-Farber Cancer Institute collects research biopsies as additional passes at the time of a clinical biopsy (AB, additional biopsy) or as a separate procedure for banking purposes (RPOB, research purposes only biopsy). Biopsies are not linked to a specific therapeutic or correlative trial. Grade 2-5 adverse events are prospectively collected. 151 patients were included in the analytic cohort (total procedures = 161); 80.8 % underwent AB, 17.2 % underwent RPOB, and 2.0 % underwent both AB and RPOB. Most patients were white (88.7 %) with a performance status of 0-1 (94.0 %). 96.0 % of patients underwent a biopsy in the setting of known or suspected metastatic disease. Receptor status between primary cancer and recurrent research biopsies differed in 43.2 % of patients with available data (18.8 % among patients who underwent the research biopsy before any systemic treatment, 48.1 % after treatment). Tissue was successfully collected in 92.3 % of patients undergoing AB and 100 % patients undergoing RPOB. Only three (2.0 %) patients had adverse events ≥grade-2: one grade-2 pain; one grade-2 pneumothorax; and one grade-3 pain. Our experience suggests research biopsies can be performed safely with a high rate of successful tissue collection. Consistent with previous reports we found a high rate of discordance between primary and metastatic samples, which was even higher among treated patients. This supports continued efforts to study tissue samples at multiple points in a patient's disease course. © 2013 The Author(s). Source

Buck M.,Veterans Affairs San Diego Healthcare System | Buck M.,University of California at San Diego | Garcia-Tsao G.,Veterans Affairs Connecticut Healthcare System | Garcia-Tsao G.,Yale University | And 9 more authors.
Hepatology | Year: 2014

The rationale for screening inflammatory serum biomarkers of the hepatic vein pressure gradient (HVPG) is based on the fact that portal hypertension is pathogenically related to liver injury and fibrosis, and that in turn these are associated with the activation of inflammatory pathways. This was a nested cohort study in the setting of a randomized, clinical trial to assess the development of gastroesophageal varices (GEV) (N Engl J Med 2005;353:2254). Patients had cirrhosis and portal hypertension but did not have GEV. A total of 90 patients who had baseline day-1 sera available were enrolled in the present study. The objective of this study was to determine whether inflammatory biomarkers in conjunction with clinical parameters could be used to develop a predictive paradigm for HVPG. The correlations between HVPG and interleukin (IL)-1β (P=0.0052); IL-1R-α (P=0.0085); Fas-R (P=0.0354), and serum VCAM-1 (P=0.0007) were highly significant. By using multivariate logistic regression analysis and selected parameters (transforming growth factor beta [TGFβ]; heat shock protein [HSP]-70; at-risk alcohol use; and Child class B) we could exclude HVPG ≥12 mmHg with 86% accuracy (95% confidence interval [CI]: 67.78 to 96.16%) and the sensitivity was 87.01% (95% CI: 69.68 to 96.34%). Therefore, the composite test could identify 86% of compensated cirrhosis patients with HVPG below 12 mmHg and prevent unnecessary esophagogastroduodenoscopy with its associated morbidity and costs in these patients. Our diagnostic test was not efficient in predicting HVPG ≥12 mmHg. Conclusion: A blood test for HVPG could be performed in cirrhosis patients to prevent unnecessary esophagogastroduodenoscopy. © 2014 by the American Association for the Study of Liver Diseases. Source

Masciari S.,Dana-Farber Cancer Institute | Dillon D.A.,Brigham and Womens Hospital | Rath M.,Dana-Farber Cancer Institute | Robson M.,Sloan Kettering Cancer Center | And 10 more authors.
Breast Cancer Research and Treatment | Year: 2012

Breast cancer is the most common tumor in women with Li-Fraumeni Syndrome (LFS), an inherited cancer syndrome associated with germline mutations in the TP53 tumor suppressor gene. Their lifetime breast cancer risk is 49% by age 60. Breast cancers in TP53 mutation carriers recently have more often been reported to be hormone receptor and HER-2 positive by immunohisto-chemistry and FISH in small series. We seek to complement the existing small literature with this report of a histopath-ologic analysis of breast cancers from women with documented LFS. Unstained slides and paraffin-embedded tumor blocks from breast cancers from 39 germline TP53 mutation carriers were assembled from investigators in the LFS consortium. Central histology review was performed on 93% of the specimens by a single breast pathologist from a major university hospital. Histology, grade, and hormone receptor status were assessed by immunohistochemistry; HER-2 status was defined by immunohistochemistry and/or FISH. The 43 tumors from 39 women comprise 32 invasive ductal carcinomas and 11 ductal carcinomas in situ (DCIS). No other histologies were observed. The median age at diagnosis was 32 years (range 22-46). Of the invasive cancers, 84% were positive for ER and/or PR; and 81% were high grade. Sixty three percent of invasive and 73% of in situ carcinomas were positive for Her2/neu (IHC 3+ or FISH amplified). Of the invasive tumors, 53% were positive for both ER and HER2+; other ER/PR/HER2 combinations were observed. The DCIS were positive for ER and HER2 in 27% of the cases. This report of the phenotype of breast cancers from women with LFS nearly doubles the literature on this topic. Most DCIS and invasive ductal carcinomas in LFS are hormone receptor positive and/or HER-2 positive. These findings suggest that modern treatments may result in improved outcomes for women with LFS-associated breast cancer. © 2012 Springer Science+Business Media, LLC. Source

Reddy P.,HealthCare Partners | Atay J.K.,Brigham and Womens Hospital | Selbovitz L.G.,Newton Wellesley Hospital | Connors J.M.,Brigham and Womens Hospital | And 11 more authors.
Critical Pathways in Cardiology | Year: 2011

Dabigatran etexilate is the first commercially available oral direct thrombin inhibitor. A single trial has studied patients at risk for stroke associated with nonvalvular atrial fibrillation; in this trial, dabigatran 150 mg twice a day met the criteria for superiority over warfarin in preventing stroke and systemic embolism while reducing the rate of hemorrhagic stroke with a similar risk of major bleeding. For the treatment of venous thromboembolism, dabigatran 150 mg twice a day had comparable efficacy and safety versus warfarin. In contrast, dabigatran was less effective than enoxaparin 30 mg twice a day in venous thromboembolism prevention in orthopedic surgery. Advantages of dabigatran over warfarin include its lack of need for routine laboratory monitoring, a fixed-dose regimen, and potentially fewer clinically important drug interactions. Concerns include higher incidences of dyspepsia and gastrointestinal bleeding, twice-daily dosing, and lack of effective antidote. Additional drawbacks include higher drug cost versus warfarin, accumulation in case of renal impairment, higher discontinuation rates due to adverse events, and limited long-term safety and trial data. From a payer perspective, overall costs will be higher with dabigatran compared with warfarin, but dabigatran does meet the threshold to be considered a cost-effective therapy. In addition, the lack of need for regular laboratory monitoring is a quality of life advantage for patients on dabigatran. These observations suggest that dabigatran is a valuable addition to the therapeutic armamentarium for stroke prevention in selected patients with atrial fibrillation although caution should be exercised given the limited data on this agent and higher cost. Copyright © 2011 by Lippincott Williams & Wilkins. Source

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