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Scottsdale, AZ, United States

Kuske R.,Virginia per Cancer Center
Journal of Contemporary Brachytherapy

Purpose: To describe a breast-conserving technique using interstitial brachytherapy after lumpectomy and axillary nodal sampling in selected women who are diagnosed with breast cancer in the presence of augmentation mammoplasty. Material and methods: Over the past 20 years, we have developed and improved a technique of "pinch view" image-guided catheter insertion that avoids implant puncture. Selection criteria include: 1) women of any age with either subpectoral or retroglandular, augmentation implants (silicone or saline) who were diagnosed with stages Tis, T1, T2, N0, or N1 breast cancer; 2) any pathologic subtype of malignant breast cancer was accepted; 3) microscopic tumor extent < 3 cm; 4) axillary node negative or metastasis to 1 to 3 nodes without extracapsular extension; and 5) surgical margins clear by the NSABP "no ink on tumor" definition. More than 250 women have been successfully treated. Patients were treated with high dose rate Iridium-192 brachytherapy to 34 Gy in 10 or 32 Gy in 8 twice daily fractions. The target volume was the surgical cavity edge with 1.5 to 2 cm margin using 3-D treatment planning systems. Results: The implant technique as currently employed is described. There have been no implant ruptures, and the Planning Treatment Volume (PTV-eval) exhibited at least 90% coverage by the 90% isodose line in the vast majority of cases. Dose Homogeneity Index exceeded 70% in most cases. The maximum skin dose was below the prescription dose in every case. Other than some patients with pre-existing capsular contracture, less than 5% experience new capsular contracture after interstitial brachytherapy. Conclusions: A technique of reliable and reproducible accelerated partial breast irradiation is described that minimizes the risk of capsular contracture by avoiding circumferential dose to the foreign body in the breast. Source

Borazanci E.,Translational Genomics Research Institute | Von Hoff D.D.,Virginia per Cancer Center
Expert Review of Gastroenterology and Hepatology

Adenocarcinoma of the pancreas or pancreatic cancer as we will refer to it here, is a cancer of poor prognosis with a high mortality, particularly in the advanced or metastatic setting. Until 2011 and the Phase III results of FOLFIRINOX, standard treatment options were limited to gemcitabine. Combination therapy had shown either a lack of or very limited improvement versus monotherapy with gemcitabine. With the positive results of the MPACT study in 2013 showing improved survival with nab-paclitaxel plus gemcitabine combination therapy, there are now more options for oncologists to treat patients with advanced pancreatic cancer. This paper will highlight the Phase I/II and Phase III trials of nab-paclitaxel plus gemcitabine along with discussing their biology and further possible development in treating patients with pancreatic cancer. © 2014 Informa UK, Ltd. Source

Goldstein D.,University of New South Wales | El-Maraghi R.H.,Royal Victoria Regional Health Center | Heinemann V.,Ludwig Maximilians University of Munich | Kunzmann V.,Universitatsklinikum Wurzburg | And 11 more authors.
Journal of the National Cancer Institute

Background: Positive findings from the phase III MPACT trial led to the regulatory approval of nab-paclitaxel plus gemcitabine as a treatment option for patients with metastatic pancreatic cancer. This report is an update of overall survival (OS) based on longer follow-up. Methods: Patients (n = 861) with metastatic pancreatic cancer and a Karnofsky performance status of 70 or greater were randomly assigned one to one to receive nab-paclitaxel + gemcitabine or gemcitabine alone. Efficacy data for this post hoc analysis were collected through May 9, 2013. Exploratory analyses of carbohydrate antigen 19-9 (CA19-9) and neutrophil-to-lymphocyte ratio (NLR) were conducted. The primary efficacy endpoint was OS, which was analyzed for all randomly assigned patients by the Kaplan-Meier method. All statistical tests were two-sided. Results: The median OS was statistically significantly longer for nab-paclitaxel plus gemcitabine vs gemcitabine alone (8.7 vs 6.6 months, hazard ratio [HR] = 0.72, 95% confidence interval [CI] = 0.62 to 0.83, P <. 001). Long-term (>three-year) survivors were identified in the nab-paclitaxel plus gemcitabine arm only (4%). In pooled treatment arm analyses, higher CA19-9 level and NLR at baseline were statistically significantly associated with worse OS. There appeared to be a treatment effect for OS favoring nab-paclitaxel plus gemcitabine over gemcitabine alone in poor-prognosis subgroups defined by these factors (HR = 0.612, P <. 001 for CA19-9 level ≥ median and HR = 0.81, P =. 079 for NLR > 5). Conclusions: These data confirm and extend the primary report of OS, supporting the superior efficacy of nab-paclitaxel plus gemcitabine over gemcitabine alone. Subgroup analyses support the relevance of CA 19-9 and NLR as prognostic markers in metastatic pancreatic cancer. © The Author 2015. Published by Oxford University Press. All rights reserved. Source

Bussey K.J.,Translational Genomics Research Institute | Demeure M.J.,Translational Genomics Research Institute | Demeure M.J.,Virginia per Cancer Center
Current Opinion in Oncology

Purpose of review: Adrenocortical carcinoma is an aggressive, lethal malignancy of the adrenal cortex. The rarity of the disease has stymied therapeutic development. Recent work toward understanding the molecular pathogenesis of the disease has identi?ed several potential new diagnostic and therapeutic targets. Recent ?ndings: The molecular characterization of adrenocortical carcinoma has identi?ed dysregulation of the Gap 2/mitosis transition and the insulin-like growth factor 1 receptor signaling cascade as two major pathways for therapeutic development. These studies have also highlighted an unappreciated heterogeneity of the disease at the gene level that nevertheless seems to converge onto common cellular pathways. Additionally, the characterization of Wnt signaling through b-catenin in adrenal development, the demonstration of the involvement of BMP signaling in adrenocortical carcinoma growth regulation, and the discovery that ERCC1 expression levels can predict therapeutic response to platinum are just a few of the recent advances that promise to shed light on adrenocortical carcinoma biology. Summary: Short-term, therapeutic development should target the Gap 2/mitosis transition and the downstream signaling of the insulin-like growth factor 1 receptor receptor. Long-term, additional characterization of patient samples, particularly at the sequence level, is required to fully understand adrenocortical carcinoma biology and apply that knowledge to clinical practice. © 2010 Wolters Kluwer Health | Llpplncott Williams & Wilkins. Source

Von Hoff D.D.,Translational Genomics Research Institute | Von Hoff D.D.,Virginia per Cancer Center | Ervin T.,Cancer Specialists | Arena F.P.,Arena Oncology Associates | And 20 more authors.
New England Journal of Medicine

BACKGROUND: In a phase 1-2 trial of albumin-bound paclitaxel (nab-paclitaxel) plus gemcitabine, substantial clinical activity was noted in patients with advanced pancreatic cancer. We conducted a phase 3 study of the efficacy and safety of the combination versus gemcitabine monotherapy in patients with metastatic pancreatic cancer. METHODS: We randomly assigned patients with a Karnofsky performance-status score of 70 or more (on a scale from 0 to 100, with higher scores indicating better performance status) to nab-paclitaxel (125 mg per square meter of body-surface area) followed by gemcitabine (1000 mg per square meter) on days 1, 8, and 15 every 4 weeks or gemcitabine monotherapy (1000 mg per square meter) weekly for 7 of 8 weeks (cycle 1) and then on days 1, 8, and 15 every 4 weeks (cycle 2 and subsequent cycles). Patients received the study treatment until disease progression. The primary end point was overall survival; secondary end points were progression-free survival and overall response rate. RESULTS: A total of 861 patients were randomly assigned to nab-paclitaxel plus gemcitabine (431 patients) or gemcitabine (430). The median overall survival was 8.5 months in the nab-paclitaxel-gemcitabine group as compared with 6.7 months in the gemcitabine group (hazard ratio for death, 0.72; 95% confidence interval [CI], 0.62 to 0.83; P<0.001). The survival rate was 35% in the nab-paclitaxel- gemcitabine group versus 22% in the gemcitabine group at 1 year, and 9% versus 4% at 2 years. The median progression-free survival was 5.5 months in the nab-paclitaxel-gemcitabine group, as compared with 3.7 months in the gemcitabine group (hazard ratio for disease progression or death, 0.69; 95% CI, 0.58 to 0.82; P<0.001); the response rate according to independent review was 23% versus 7% in the two groups (P<0.001). The most common adverse events of grade 3 or higher were neutropenia (38% in the nab-paclitaxel-gemcitabine group vs. 27% in the gemcitabine group), fatigue (17% vs. 7%), and neuropathy (17% vs. 1%). Febrile neutropenia occurred in 3% versus 1% of the patients in the two groups. In the nab-paclitaxel-gemcitabine group, neuropathy of grade 3 or higher improved to grade 1 or lower in a median of 29 days. CONCLUSIONS: In patients with metastatic pancreatic adenocarcinoma, nab-paclitaxel plus gemcitabine significantly improved overall survival, progression-free survival, and response rate, but rates of peripheral neuropathy and myelosuppression were increased. Copyright © 2013 Massachusetts Medical Society. Source

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