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Monson J.R.T.,University of Rochester | Probst C.P.,University of Rochester | Wexner S.D.,Cleveland Clinic | Remzi F.H.,Cleveland Clinic | And 4 more authors.
Annals of Surgery | Year: 2014

Objective: This study examines recent adherence to recommended neoadjuvant chemoradiotherapy guidelines for patients with rectal cancer across geographic regions and institution volume and assesses trends over time. CopyrightBackground: A recent report by the Institute of Medicine described US cancer care as chaotic. Cited deficiencies included wide variation in adherence to evidencebased guidelines even where clear consensus exists.Methods: Patients operated on for clinical stage II and III rectal cancer were selected from the 2006-2011 National Cancer Data Base.Multivariable logistic regressions were used to assess variation in chemotherapy and radiation use by cancer center type, geographical location, and hospital volume. The analysis controlled for patient age at diagnosis, sex, race/ethnicity, primary payer, average household income, average education, urban/rural classification of patient residence, comorbidity, and oncologic stage.Results: There were 30,994 patients who met the inclusion criteria. Use of neoadjuvant radiation therapy and chemotherapy varied significantly by type of cancer center. The highest rates of adherence were observed in highvolume centers compared with lowvolume centers (78% vs 69%; adjusted odds ratio =1.46; P0.001). This variation ismirrored by hospital geographic location. Primary payer and year of diagnosiswere not predictive of rates of neoadjuvant chemoradiotherapy.Conclusions: Adherence to evidencebased treatment guidelines in rectal cancer is suboptimal in the United States, with significant differences based on hospital volume and geographic regions. Little improvement has occurred in the last 5 years. These results support the implementation of standardized care pathways and a Centers of Excellence program for US patients with rectal cancer. © 2014 by Lippincott Williams & Wilkins. Source

Garcia-Garcia C.,Vall dHebron Institute of Oncology VHIO | Rivas M.A.,Vall dHebron Institute of Oncology VHIO | Ibrahim Y.H.,Vall dHebron Institute of Oncology VHIO | Calvo M.T.,Vall dHebron Institute of Oncology VHIO | And 24 more authors.
Clinical Cancer Research | Year: 2015

Purpose: PI3K pathway activation occurs in concomitance with RAS/BRAF mutations in colorectal cancer, limiting the sensitivity to targeted therapies. Several clinical studies are being conducted to test the tolerability and clinical activity of dual MEK and PI3K pathway blockade in solid tumors. Experimental Design: In the present study, we explored the efficacy of dual pathway blockade in colorectal cancer preclinical models harboring concomitant activation of the ERK and PI3K pathways. Moreover, we investigated if TP53 mutation affects the response to this therapy. Results: Dual MEK and mTORC1/2 blockade resulted in synergistic antiproliferative effects in cell lines bearing alterations in KRAS/BRAF and PIK3CA/PTEN. Although the on-treatment cellcycle effects were not affected by the TP53 status, a marked proapoptotic response to therapy was observed exclusively in wild-type TP53 colorectal cancer models. We further interrogated two independent panels of KRAS/BRAF- and PIK3CA/PTENaltered cell line- and patient-derived tumor xenografts for the antitumor response toward this combination of agents. A combination response that resulted in substantial antitumor activity was exclusively observed among the wild-type TP53 models (two out of five, 40%), but there was no such response across the eight mutant TP53 models (0%). Interestingly, within a cohort of 14 patients with colorectal cancer treated with these agents for their metastatic disease, two patients with long-lasting responses (32 weeks) had TP53 wild-type tumors. Conclusions: Our data support that, in wild-type TP53 colorectal cancer cells with ERK and PI3K pathway alterations, MEK blockade results in potent p21 induction, preventing apoptosis to occur. In turn, mTORC1/2 inhibition blocks MEK inhibitor- mediated p21 induction, unleashing apoptosis. © 2015 American Association for Cancer Research. Source

Kelly K.J.,Sloan Kettering Cancer Center | Yoon S.S.,Sloan Kettering Cancer Center | Yoon S.S.,Massachusetts General Hospital | Kuk D.,Memorial SloanKettering Cancer Center | And 7 more authors.
Annals of Surgery | Year: 2015

Objective: To compare outcomes of patients with retroperitoneal or pelvic sarcoma treated with perioperative radiation therapy (RT) versus those treated without perioperative RT. Background: RT for retroperitoneal or pelvic sarcoma is controversial, and few studies have compared outcomes with and without RT. Methods: Prospectively maintained databases were reviewed to retrospectively compare patients with primary retroperitoneal or pelvic sarcoma treated during 2003-2011. Multivariate Cox regression modelswere used to assess associations with the primary endpoints: local recurrence-free survival (LRFS) and disease-specific survival. Results: At 1 institution, 172 patients were treated with surgery alone, whereas at another institution 32 patients were treated with surgery and perioperative proton beam RT or intensity-modulated RT with or without intraoperative RT. The groups were similar in age, tumor size, grade, and margin status (all P > 0.08). The RT group had a higher percentage of pelvic tumors (P = 0.03) and a different distribution of histologies (P = 0.04). Perioperative morbidity was higher in the RT group (44% vs 16% of patients; P = 0.004). After a median follow-up of 39 months, 5-year LRFS was 91% (95% confidence interval, 79%-100%) in the RT group and 65% (57%-74%) in the surgery-only group (P = 0.02). On multivariate analysis, RT was associated with better LRFS (hazard ratio, 0.26; P = 0.03). Five-year disease-specific survival was 93% (95% confidence interval, 82%-100%) in the RT group and 85% (78%-92%) in the surgery-only group (P = 0.3). Conclusions: The addition of advanced-modality RT to surgery for primary retroperitoneal or pelvic sarcoma was associated with improved LRFS, although this did not translate into significantly better disease-specific survival. This treatment strategy warrants further investigation in a randomized trial. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Source

Rebeiz K.,American University of Beirut | Shamseddine A.,American University of Beirut | Hachem R.,American University of Beirut | Brown K.,Memorial SloanKettering Cancer Center | And 7 more authors.
Clinical Imaging | Year: 2016

Gastroduodenal artery (GDA) aneurysm is a very rare condition. It is divided into false aneurysms (pseudoaneurysms) associated with pancreatitis and true aneurysms secondary to celiac trunk stenosis. We report a 24-year-old patient who was diagnosed with pancreatic head neuroendocrine tumor and was incidentally found to have multiple GDA aneurysms in the absence of celiac artery stenosis. The aneurysms were embolized because of the presumed high risk of bleeding. The procedure was successful with no recurrence on follow-up computed tomography scan. © 2015 Elsevier Inc.. Source

Lee S.Y.,Sloan Kettering Cancer Center | Lee S.Y.,The Surgical Center | Konstantinidis I.T.,Sloan Kettering Cancer Center | Eaton A.A.,Memorial SloanKettering Cancer Center | And 7 more authors.
HPB | Year: 2014

Background: The reliable prediction of hepatocellular carcinoma (HCC) recurrence patterns potentially allows for the prioritization of patients for liver resection (LR) or transplantation. Objectives: The aim of this study was to analyse clinicopathological factors and preoperative Milan criteria (MC) status in predicting patterns of HCC recurrence. Methods: During 1992-2012, 320 patients undergoing LR for HCC were categorized preoperatively as being within or beyond the MC, as were recurrences. Results: After a median follow-up of 47 months, 183 patients developed recurrence, giving a 5-year cumulative incidence of recurrence of 62.5%. Patients with preoperative disease within the MC had better survival outcomes than those with preoperative disease beyond the MC (median survival: 102 months versus 45 months; P < 0.001). Overall, 31% of patients had preoperative disease within the MC and 69% had preoperative disease beyond the MC. Estimated rates of recurrence-free survival at 5 years were 61.8% for all patients and 53.8% for patients with initial beyond-MC status. Independent factors for recurrence beyond-MC status included preoperative disease beyond the MC, the presence of microsatellite or multiple tumours and lymphovascular invasion (all: P < 0.001). A clinical risk score was used to predict survival and the likelihood of recurrence beyond the MC; patients with scores of 0, 1, 2 and 3 had 5-year incidence of recurring beyond-MC of 9.0%, 29.5%, 48.8% and 75.4%, respectively (P < 0.0001). Conclusions: Regardless of initial MC status, at 5 years the majority of patients remained disease-free or experienced recurrence within the MC after LR, and thus were potentially eligible for salvage transplantation (ST). Incorporating clinicopathological parameters into the MC allows for better risk stratification, which improves the selection of patients for ST and identifies patients in need of closer surveillance. © 2014 International Hepato-Pancreato-Biliary Association. Source

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