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Xiang J.,University of Washington | Hurchla M.A.,University of Washington | Fontana F.,University of Washington | Su X.,University of Washington | And 16 more authors.
Molecular Cancer Therapeutics | Year: 2015

The SDF-1 receptor CXCR4 has been associated with early metastasis and poorer prognosis in breast cancers, especially the most aggressive triple-negative subtype. In line with previous reports, we found that tumoral CXCR4 expression in patients with locally advanced breast cancer was associated with increased metastases and rapid tumor progression. Moreover, high CXCR4 expression identified a group of bone marrow-disseminated tumor cells (DTC)-negative patients at high risk for metastasis and death. The protein epitope mimetic (PEM) POL5551, a novel CXCR4 antagonist, inhibited binding of SDF-1 to CXCR4, had no direct effects on tumor cell viability, but reduced migration of breast cancer cells in vitro. In two orthotopic models of triplenegative breast cancer, POL5551 had little inhibitory effect on primary tumor growth, but significantly reduced distantmetastasis. When combined with eribulin, a chemotherapeutic microtubule inhibitor, POL5551 additively reduced metastasis and prolonged survival inmice after resection of the primary tumor compared with single-agent eribulin. Hypothesizing that POL5551 may mobilize tumor cells from their microenvironment and sensitize them to chemotherapy, weused a "chemotherapy framing" dosing strategy. When administered shortly before and after eribulin treatment, three doses of POL5551 with eribulin reduced bone and liver tumor burden more effectively than chemotherapy alone. These data suggest that sequenced administration of CXCR4 antagonists with cytotoxic chemotherapy synergize to reduce distant metastases. © 2015 American Association for Cancer Research.

Youland R.S.,Mayo Medical School | Khwaja S.S.,Mayo Medical School | Schomas D.A.,Saint Lukes Cancer Institute | Keating G.F.,Mayo Medical School | And 2 more authors.
Journal of Pediatric Hematology/Oncology | Year: 2013

BACKGROUND:: This study reports changes in long-term survival after the introduction of modern imaging in pediatric patients with low-grade gliomas (LGGs). METHODS:: Records from 351 consecutive pediatric patients diagnosed with LGG between 1970 and 2009 at Mayo Clinic Rochester were reviewed and divided into diagnosis before (group I: 1970 to 1989) and after (group II: 1990 to 2009) postoperative magnetic resonance imaging became regularly used in pediatric LGG. RESULTS:: Median progression-free survival (PFS) and overall survival (OS) were not reached. Overall, 10-year PFS was 62% and OS was 90%. On multivariate analysis, improved PFS was associated with gross total resection (GTR; P<0.0001) and postoperative radiation therapy (RT; P<0.0001). In those undergoing less than GTR, PFS was improved with RT, nearing rates of patients receiving GTR (P=0.12). On multivariate analysis, higher OS was associated with GTR (P<0.0001) and pilocytic histology (P=0.03). Group II had fewer headaches, fewer sensory/motor symptoms, less postoperative RT, and more GTRs. OS and PFS were not different between the groups. CONCLUSIONS:: This large series of pediatric LGG patients with long-term follow-up found no significant changes in OS or PFS over time. Overall, GTR was associated with improved OS and PFS. RT was associated with an improvement in PFS, with the greatest benefit seen in patients undergoing less than GTR. Copyright © 2012 by Lippincott Williams & Wilkins.

Adrada B.E.,University of Texas M. D. Anderson Cancer Center | Miranda R.N.,515 Holcombe Blvd. | Rauch G.M.,University of Texas M. D. Anderson Cancer Center | Arribas E.,University of Texas M. D. Anderson Cancer Center | And 12 more authors.
Breast Cancer Research and Treatment | Year: 2014

Breast implant-associated anaplastic large cell lymphoma (BIA ALCL) is a newly described clinicopathologic entity. The purpose of this study is to describe the imaging findings of patients with BIA ALCL and determine their sensitivity and specificity in the detection of the presence of an effusion or a mass related to BIA ALCL. A retrospective search was performed of our files as well as of the world literature for patients with pathologically proven BIA ALCL who had been assessed by any imaging study including ultrasound (US), computerized tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET)-CT, as well as mammography. The sensitivity and specificity of each imaging modality in the detection of an effusion or a mass around breast implants was determined. We identified 44 patients who had BIA ALCL and imaging studies performed between 1997 and 2013. The sensitivity for detecting an effusion was 84, 55, 82, and 38 %, and for detecting a mass was 46, 50, 50, and 64 %, by US, CT, MRI, and PET, respectively. The sensitivity of mammography in the detection of an abnormality without distinction of effusion or mass was 73 %, and specificity 50 %. Progression-free survival was worse in patients with an implant-associated mass (p = 0.001). Conclusions: Current imaging with US, CT, MR, and PET appears suboptimal in the detection of an imaging abnormality associated with BIA ALCL. This under diagnosis may reflect a lack of awareness of this rare entity suggesting the need for better understanding of the spectrum of imaging findings associated with BIA ALCL by breast imagers. © 2014 Springer Science+Business Media.

Miranda R.N.,University of Houston | Aladily T.N.,University of Jordan | Prince H.M.,University of Melbourne | Kanagal-Shamanna R.,University of Houston | And 31 more authors.
Journal of Clinical Oncology | Year: 2014

Purpose: Breast implant-associated anaplastic large-cell lymphoma (ALCL) is a recently described clinicopathologic entity that usually presents as an effusion-associated fibrous capsule surrounding an implant. Less frequently, it presents as a mass. The natural history of this disease and long-term outcomes are unknown. Patients and Methods: We reviewed the literature for all published cases of breast implant-associated ALCL from 1997 to December 2012 and contacted corresponding authors to update clinical follow-up. Results: The median overall survival (OS) for 60 patients was 12 years (median follow-up, 2 years; range, 0-14 years). Capsulectomy and implant removal was performed on 56 of 60 patients (93%). Therapeutic data were available for 55 patients: 39 patients (78%) received systemic chemotherapy, and of the 16 patients (28%) who did not receive chemotherapy, 12 patients opted for watchful waiting and four patients received radiation therapy alone. Thirty-nine (93%) of 42 patients with disease confined by the fibrous capsule achieved complete remission, compared with complete remission in 13 (72%) of 18 patients with a tumor mass. Patients with a breast mass had worse OS and progression-free survival (PFS; P = .052 and P = .03, respectively). The OS or PFS were similar between patients who received and did not receive chemotherapy (P = .44 and P = .28, respectively). Conclusion: Most patients with breast implant-associated ALCL who had disease confined within the fibrous capsule achieved complete remission. Proper management for these patients may be limited to capsulectomy and implant removal. Patients who present with a mass have a more aggressive clinical course that may be fatal, justifying cytotoxic chemotherapy in addition to removal of implants. © 2013 by American Society of Clinical Oncology.

Youland R.S.,Rochester College | Schomas D.A.,Saint Lukes Cancer Institute | Brown P.D.,University of Houston | Brown P.D.,Mayo Medical School | And 5 more authors.
Neuro-Oncology | Year: 2013

BackgroundTo identify changes in patient presentation, treatment, and outcomes of low-grade gliomas (LGGs) over the past 50 years.MethodsRecords of 852 adults who received a diagnosis at Mayo Clinic from 1960 through 2011 with World Health Organization grade II LGGs were reviewed and grouped by those who received a diagnosis before (group I: 1960-1989) and after (group II: 1990-2011) the routine use of postoperative MRI.ResultsMedian follow-up was 23.3 and 8.7 years for groups I and II, respectively. Patients in group I more often presented with seizures, headaches, sensory/motor impairment, and astrocytoma histology. Over time, more gross total resections (GTRs) were achieved, fewer patients received postoperative radiotherapy (PORT), and more received chemotherapy.Median progression-free survival (PFS) and overall survival (OS) were 4.4 and 8.0 years, respectively. Although PFS was similar, 10-year OS was better in group II (47%) than in group I (33%; P <. 0001). Improved PFS in multivariate analysis was associated with group I patients, nonastrocytoma histology, small tumor size, successful GTR, or radical subtotal resection (rSTR), PORT, and postoperative chemotherapy. Factors associated with improved OS in multivariate analysis were younger age, nonastrocytoma histology, small tumor size, and GTR/rSTR.ConclusionsOS for LGG has improved over the past 50 years, despite similar rates of progression. In the modern cohort, more patients are receiving a diagnosis of oligodendroglioma and are undergoing extensive resections, both of which are associated with improvements in OS. Because of risk factor stratification by clinicians, the use of PORT has decreased and is primarily being used to treat high-risk tumors in modern patients. © The Author(s) 2013. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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