tbuckley/cabot-search huggingface dataset:
Compliance with National Comprehensive Cancer Network guidelines for antiemesis in cisplatin regimens.
Authors: Terri P. Wolf, Dana Ann Little
Journal: Journal of Clinical Oncology (2016)

280 Background: The members of a network of community cancer centers affiliated with an academic medical center report following National Comprehensive Cancer Network (NCCN) guidelines. To determine guideline compliance, cisplatin regimens were audited. Cisplatin was selected because of its wide use, high emetic potential, and the impact on QOL for patients with unmanaged nausea and vomiting.The community cancer centers affiliated with an academic medical center report following National Comprehensive Cancer Network (NCCN) guidelines for treatment plans. To determine guideline compliance rates, cisplatin regimens were audited. Cisplatin was selected because of its wide use, high emetic potential, and the impact on QOL for patients with unmanaged nausea and vomiting. Methods: Prior to a chart audit, medical oncologists were surveyed on their knowledge of NCCN antiemesis guidelines, frequency of prescribing based on guidelines, and reasons for not using guidelines. Auditors identified patient charts through billing records and reviewed cycle 1 day 1 orders of cisplatin regimens. Secondary data was collected on hydration orders and home medications for antiemesis. Results: Guideline adherence varied from 0% to 76% with overall adherence at 28%. Dexamethasone doses ranged from 2-20 mg (guideline 12 mg) as did serotonin antagonists (5HT3) ordered at higher IV doses of 24-32 mg (guideline 8-16 mg). Conclusions: Although cancer centers report following the guidelines, this study did not find consistent adherence. The cancer center with the highest adherence rate works closely with a pharmacist and has built order sets with the guidelines. One cancer center had wide variances among practitioners. The variances increase the potential for error. The cancer center with lowest adherence rate used 10 mg doses of dexamethasone because the drug is delivered in 10 mg vials. This study identified multiple systems issues impacting guideline compliance. Managing nausea and vomiting is important for patient QOL and to manage costs by decreasing hospitalizations, treatment delays, and nutritional deficits. Understanding prescribing habits relative to guidelines provides an opportunity to change practice and reduce variability.
Effects of ASA404, a vascular disrupting agent, on tumor growth of gastric cancer in an experimental model.
Authors: S. A. Lang, C. Moser, E. M. Jung, K. Pfister, E. K. Geissler, H. J. Schlitt
Journal: Journal of Clinical Oncology (2011)

48 Background: A functional vascular system is essential for growth of solid malignancies including gastric cancer. For establishment and maintenance of such a vascular system endothelial cells (ECs) and pericytes (e.g. vascular smooth muscle cells, VSMC) are required. We hypothesized that targeting tumor vasculature with the vascular disrupting agent (VDA) ASA404 (Novartis Oncology) reduces tumor growth in a model of gastric cancer. Methods: Gastric cancer (GC) cell lines, ECs and VSMCs were used for experiments. Effects of ASA404 on growth of GC, EC and VSMC were assessed by MTT assays. Impact of ASA404 (20 mg/kg on day 1, 5, 9) in combination with paclitaxel (10 mg/kg on day 1 and 7) on tumor growth was assessed in a subcutaneous tumor model. Treatment was started when tumors reached a size of approximately 200 mm 3 . Tumors were measured and harvested on day 23 for IHC analyses. Effect of ASA404 on blood perfusion of tumors during therapy was monitored by contrast-enhanced ultrasound (CEUS). Results: In vitro ASA404 impaired growth of ECs and VSMCs upon stimulation with condition media from gastric cancer cells. No direct effect on tumor cells was observed. In vivo, treatment with ASA404 led to marked decrease of tumor perfusion and an increase of necrosis as determined by CEUS. Furthermore, combination of ASA404 with paclitaxel showed significant reduction of tumor growth compared to controls (p &lt; 0.05). In addition, tumor vascularisation and tumor cell proliferation were significantly reduced as determined by CD31-positive vessel area and BrdU-positive cells (p &lt; 0.05). Conclusions: Combination of the VDA ASA404 with paclitaxel impairs tumor growth and perfusion of gastric cancer in an experimental model. Hence, targeting tumor vasculature with ASA404 appears to be a promising strategy for therapy of gastric cancer. No significant financial relationships to disclose.
Correlation of high FDG uptake in PET/CT with poor prognosis in metastatic gastric adenocarcinoma.
Authors: M. Canhoroz, T. Korkmaz, S. Seber, A. Bilici, K. Okutur, T. Toptaş, G. Basaran, F. Dede, F. Yumuk, F. Dane, M. Kanitez, O. Kanat, M. Gumus, G. Demir, N. S. Turhal
Journal: Journal of Clinical Oncology (2011)

e14668 Background: Gastric cancer (GC) is one of the leading causes of cancer mortality worldwide. 18F-FDG PET may have a role in predicting patient prognosis on the basis of the metabolic activity of primary tumors (PT). We retrospectively evaluated prognostic value of FDG-PET/CT in metastatic gastric cancer. Methods: This was a retrospective analysis of 75 patients with metastatic G who attended chemotherapy units of the participating centers from January 2007 to June 2010 and underwent FDG PET/CT imaging before the first line chemotherapy. Results: Median age in our study group was 62 and 25 of them were women. Median follow-up was 10 months. The patients received either ECF (n=16) or TCF (n=47) or cisplatin and capesitabine (n=12). Both PFS and OS were significantly higher in the ECOG PS 0 and 1 group of patients (n=58) compared to ECOG PS 2 (n=17; 6 vs 4 months, p= 0.032) and 13 vs 8 months, p= 0.002 respectively). 57 patients were adenocarcinoma while signet ring cell type were diagnosed in 18 patients. Median PFS and OS were 5 and 11 months respectively. Median SUV max value (>8.6) for the PT was significantly associated with both PFS (6 vs 4 months, , p= 0.04, HR: 0.45 (0.21-0.98) and OS (16 vs 8 ay, HR: 0.40 [0.17-0.90] p= 0.03). Median highest SUV max value (>7) for distant metastasis (DM) was not correlated with PFS (p= 0.7) and OS (p= 0.1). When the correlation between median SUV max for each metastatic site with PFS and OS were assessed, only liver metastasis had a significant association with OS; (15 vs 7.5 months, HR: 0.18 [0.07-0.46] p= 0.0003). In multivariate analysis ECOG PS (p=0.0015), SUV max of the primary tumor sites (p=0.02) and metastatic liver lesions (p= 0.00001) remained as significant predictors for poor OS. Conclusions: In metastatic gastric cancer PET CT is a useful instrument for predicting poor prognosis. High FDG uptake of primary tumor site and metastatic liver lesions are significantly associated with shorter OS.
Does performing en bloc versus piecemeal mucosal resections affect outcomes in patients with intramucosal adenocarcinoma?
Authors: Chuanlian Chu, Cadman Leggett, Kname Uno, Lori Lutzke, Kenneth WANG
Journal: Journal of Clinical Oncology (2014)

1 Background: Endoscopic resection (ER) is used to treat early esophageal cancers (EAC). With the advent of techniques such as ESD that can remove large lesions en bloc, it is important to determine if performing piecemeal resections of intramucosal cancers is detrimental. Aim: To evaluate the response rates in patients with esophageal intramucosal adenocarcinoma (IMC) who had a single ER (SR) compared to those treated with piecemeal resection (PR). Methods: This is a cohort study of patients being followed in our BE unit. Patients in a prospectively maintained database with EAC from Jan 1998 to Apr 2012 were assessed. IMC was defined as lesions that were intramucosal without extension into the submucosa. All T1a cancers were verified by two expert gastrointestinal pathologists. We compared the tumor characteristics and recurrence rate between the two groups of SR and PR of IMC. Results: A total of 197 IMC (T1a) lesions in 138 patients were identified. 88(44.7%) lesions were performed SR and 109(55.3%) were PR. Mean follow up time were 45 months (IQR 24-70.5) in SR and 39 months (IQR 26-52, P=0.067) in PR. Complete remission were found of 92.1% (81) in SR and of 93.6% (102) in PR (P=0.788) patients. The recurrence rate was 7.9% in the SR patients, and 6.4% in the PR patients (P=0.699). Median time to progression was 12 months in the SR group (IQR 8-23.5) and 11 months in the PR (IQR 8-22) (P=0.765) group. The mean survival duration was 116.3 months in the SR and 89 months in the PR (P=0.079). No statistical difference in 5-year survival rates was found between SR (83.2%) and PR (80.9%) (P=0.082). Cox proportional hazard model analysis showed local recurrence after EMR was not related to number of specimen resected or technique. Conclusions: PR appears to be as effective a therapy as en bloc for esophageal IMC. Using PR does not appear to affect clinical outcomes.
A single-institution phase II trial of five fractions of radiotherapy followed by four courses of FOLFOX chemotherapy as preoperative therapy for rectal adenocarcinoma.
Authors: Robert J. Myerson, Parag J Parikh, Benjamin Tan, Steven Hunt, James W Fleshman, Elisa H Birnbaum, Matthew G Mutch, Ira J Kodner, Bashar Safar, Michael Naughton, Joel Picus, Steven Sorscher, Albert Craig Lockhart, Caron Rigden, Rama Suresh, Andrea Wang-Gillam, Lannis Hall
Journal: Journal of Clinical Oncology (2012)

553 Background: Preoperative radiotherapy (RT) with 5FU chemotherapy (CT) is a standard of care for cT3-4 rectal cancer. Studies incorporating additional cytotoxic agents have resulted in increased morbidity with little benefit. We evaluate a template that seeks to (1) include the known benefits of preoperative RT on local response/control, (2) provide for preoperative multi-drug CT, (3) avoid the morbidity of concurrent RT and multi-drug CT. Methods: Patients with cT3-4, any N, any M rectal cancer were eligible. Patients were confirmed to be candidates for surgery, provided the response was sufficient. Preoperative treatment was 5 fractions RT (25 Gy to involved mesorectum, 20 Gy to elective nodes), followed by 4 cycles of mFOLFOX6. Postoperative CT was at the discretion of the medical oncologist. The principal objectives are to demonstrate that this regimen can achieve T stage down staging (ypT &lt; cT) and acute grade 3+ gastrointestinal (GI) morbidity equal to or better than historical controls. Results: Accrual opened late 2009, with 60 patients enrolled through 8/2011. Forty-six have had sufficient time to proceed to surgery with 4 having grade 3 preoperative GI morbidity. Two cases are inevaluable for response: one withdrew consent prior to CT and one received no surgery due to progression of cM1 disease (with local response). The 44 evaluable cases included 4 cT4 and 40 cT3; 32 (73%) cN+, 4 cM1. At surgery 33 (75%) had ypT0-2 residual disease including 13 (30%) ypT0, 14 (32%) were ypN+. Cases were sub-analyzed by whether disease was too advanced for the upcoming ACOSOG preoperative FOLFOX vs. 5FU-RT trial. By ACOSOG eligibility, response rates were (eligible first, ineligible second) ypT0: 10/22 (45%) vs. 3/22 (14%) (p = 0.05), ypT0-2: 19/22 (86%) vs. 14/22 (64%) (p = NS). Conclusions: This regimen achieves high response rates with acceptable morbidity. The response for ACOSOG eligible cases meets pre-determined stopping criteria for proceeding to a randomized trial. Our successor study will randomize to this regimen vs. FOLFOX alone for ACOSOG eligible cases, while initially continuing as a single arm trial for ACOSOG ineligible cases.
The histone deacetylase inhibitor FK228 increases the efficacy of adenovirus-mediated p53 family gene therapy in <i>in Vitro</i> and <i>in Vivo</i> human cancer models
Authors: Y. Sasaki, Y. Oshima, H. Mita, Y. Naishiro, M. Toyota, K. Imai, T. Tokino
Journal: Journal of Clinical Oncology (2005)

3160 Background: p53 gene therapy is being tested clinically for the treatment of human cancer, however some cancer models (in vivo and in vitro) are resistant to p53. We have shown that p73/p63, the newly discovered p53 family members, is effective in some of colorectal cancer cells resistant to p53-mediated apoptosis. FK228 is a natural histone deacetylase inhibitors that is known to enhance adenovirus transgene expression. Before testing whether a combination of the adenovirus (Ad)-mediated transfer of the p53 family genes with FK228 could be developed in clinical trials, preclinical experiments were performed. Methods: The effect of FK228 on adenoviral transduction, coxsakie-adenovirus receptor (CAR) expression, and acetylation of exogenous p53 family proteins were investigated. Apoptosis was examined by flow cytometry, PARP cleavage, and TUNEL analyses. The Induction of p53-target genes in FK228-treated cells was measured using Western blot. The in vivo effects of FK228 on the anti-tumor activity of Ad-mediated transfer of the p53 family genes were determined by using human cancer xenograft models. Results: Cells treated with FK228 prior to infection had a 3–7-fold increase in transgene expression from a beta-galactosidase- or GFP-expressing Ad. The enhanced viral transduction was due in part to the up-regulation of the CAR protein. Pretreatment with FK228 enhanced apoptosis induced by p53 family through increased expression of exogenous proteins. Additionally, FK228 induced hyperacetylation of exogenous p53 or p63. The levels of certain p53-targets, including NOXA and PIG3, were significantly increased compared with treated with Ad alone. Together, the combination of FK228 and Ad-p53 or Ad-p63 induced Bax translocation to the mitochondria. In human cancer xenograft models, FK228 significantly increased the therapeutic effectiveness of p53 gene therapy. Conclusions: FK228 increased expression of exogenous p53 family gene transfer, apoptosis, and antitumor mechanisms. These results support a clinical combination of FK228 with p53 gene therapy in cancer patients. No significant financial relationships to disclose.
Building an oncology community of practice.
Authors: Anne Willis, Deena R. Loeffler, Mandi Pratt-Chapman
Journal: Journal of Clinical Oncology (2016)

47 Background: Oncology patient-centered outcomes research (PCOR) helps stakeholders, including patients, clinicians and policymakers, make decisions about care; yet, research findings may take years to be put into practice. With the increasing availability of survivorship PCOR, better methods are needed to disseminate and implement findings quickly and effectively. Engaging multiple stakeholders is essential to meet this need, and Communities of Practice (CoP) are effective in increasing collaboration across organizations and stakeholders. Methods: The George Washington University (GW) Cancer Institute created a CoP as a knowledge management approach to break down professional and organizational barriers, support learning for people new to the field and facilitate collaboration within and across organizations. The goal of the CoP is to create stronger links across researchers, healthcare professionals and patients by facilitating the sharing of survivorship information and resources. These linkages will result in enhanced dissemination of evidence-based practices. Results: The CoP is housed within the Generation and Translation of Evidence (GATE) website. The site features user-generated content, including descriptions of research findings and evidence-based interventions to succinctly provide information for a variety of stakeholders to guide decision-making as well as descriptions of best practices and lessons learned to capture practice-based efforts that can drive research. GATE features a question-and-answer bank with evidence-based responses by survivorship experts. The CoP includes Ask the Expert sessions to provide researchers an opportunity to interact with clinicians and patients to guide research dissemination. It also includes Special Interest Groups for researchers to create collaborations and advance research agendas. An e-newsletter highlights new GATE content and opportunities to collaborate. Conclusions: There is a clear need to better disseminate and implement survivorship PCOR evidence to improve cancer care delivery. The GATE website will aid in more rapid implementation of survivorship PCOR evidence into clinical practice and foster collaborative dissemination and implementation efforts.
A gene expression signature to predicit overall, prostate cancer, and non–prostate cancer survival.
Authors: Chunde Li, Zhuochun Peng, Lambert Skoog, Henrik Hellborg, Inga-lill Wingmo, Marie Hjelm-Eriksson, Ulrika Harmenberg, Gabriella Cohn-Cedermark, Lars Ährlund-Richter, Setia Pramana, Yudi Pawitan, Monica Nistér, Sten Nilsson
Journal: Journal of Clinical Oncology (2013)

51 Background: For prostate cancer patients, prostate cancer specific and non-prostate cancer specific survival have the same importance. This study aimed at identifying expression biomarkers that can predict prostate cancer specific, non-prostate cancer specific and overall survival at diagnosis. Methods: Selected ESCGPs (embryonic stem cell gene predictors) and control genes were analyzed by multiplex quantitative PCR using prostate fine-needle aspiration samples taken at diagnosis from a Swedish cohort of 189 prostate cancer patients diagnosed between 1986 and 2000. Of all patients, 97.9% had overall and cancer-specific survival data and 77.9% were primarily treated only by hormone therapy. The cohort was divided into one discovery and two validation subsets. Univariate and multivariate Cox proportional hazard ratios and Kaplan-Meier plots were used for the survival analysis. A published dataset was used for external validation. Results: An expression signature of F3, VGLL3 and IGFBP3, was sufficient to categorize the patients into high-risk, intermediate-risk and low-risk subtypes. The median overall survival of the subtypes was 3.23, 4.00 and 9.85 years respectively. The difference corresponded to HRs of 5.86 (95% CI 2.91-11.78, P&lt;0.001) for the high-risk and 3.45 (95% CI 1.79-6.66, P&lt;0.001) for the intermediate-risk compared to the low-risk subtype. This signature is significant in correlation to overall, cancer-specific and non-cancer specific survival in both univariate and multivariate analyses including common clinical parameters. Conclusions: These results suggest that these novel expression biomarkers and the expression signature could be used to improve the accuracy of the currently available clinical tools for predicting overall, cancer-specific and non-cancer specific survival and selecting patients with potential survival benefit from hormone treatment.
Correlation of abnormal upper tract cytology and tumor histology in patients who have undergone a nephroureterectomy for urothelial carcinoma with disease recurrence in the bladder.
Authors: Einar Freyr Sverrisson, Timothy Kim, Patrick Espiritu, Wade Jeffers Sexton, Julio Pow-Sang, Jasreman Dhillon, Philippe E. Spiess
Journal: Journal of Clinical Oncology (2013)

288 Background: 15-50% of patients with upper tract urothelial carcinomas (UTUC) will have a bladder recurrence. Abnormal upper tract cytology (UTC) is an indicator of higher grade tumors but has not been associated with bladder recurrence. We were interested in investigating the role of UTC as a predictor of bladder cancer recurrences in patients with no prior history of bladder cancer presenting with UTUC. Methods: Of 67 patients who had an UTC collected prior to their nephroureterectomy (NU) in 2004-2012, we identified 17 patients with a recurrent disease in the bladder who met the criteria of having no previous history of bladder cancer at the time of their NU. UTC and histology were reviewed and analyzed with the bladder pathology data. Positive or suspicious cytology was defined as abnormal and atypical or reactive as benign. Results: 15 (88%) of 17 patients (11 men and 6 women) who met our criteria were diagnosed with bladder cancer within one year after their NU (average 7.5 months (range 2-26)). 10 (59%) of 17 patients had abnormal UTC with a calculated sensitivity and specificity of 59% and 22%, respectively. 7 (70%) of 10 patients with abnormal UTC compared to 5 (71%) of 7 patients with benign cytology had high grade (HG) bladder cancer (p=1.0). Muscle invasive tumors were found in 5 (29%) of 17 patients and 3 (60%) of those had abnormal UTC. All six women had HG bladder cancer compared to 6 of 10 men (p=0.23). HG tumors were slightly more common in the bladder compared to the upper tract (75% vs 65%, p=0.70) and 14 (87.5%) of 16 bladder tumors had the same tumor grade in the upper tract. Conclusions: Abnormal UTC is a poor predictor of bladder recurrence in patients with a history of UTUC. The majority of patients who developed bladder recurrence presented within one year from NU with HG disease which underscores the importance of aggressive surveillance and the consideration of prophylactic intravesical therapy at the time of NU in this patient cohort.
A population-based study of expectant management utilization and its predictors for low-risk prostate cancer.
Authors: Matthew J. Maurice, Robert Abouassaly, Hui Zhu
Journal: Journal of Clinical Oncology (2014)

68 Background: Expectant management (EM), including active surveillance and watchful waiting, is a strategy to minimize prostate cancer overtreatment. We sought to evaluate contemporary trends in EM utilization and to identify factors associated with its uptake. Methods: Using the National Cancer Database, a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society, we identified men with biopsy-proven low-risk (Gleason score 6 or lower, no Gleason pattern 4 or 5, cT1-cT2a) prostate cancer diagnosed between 2004 and 2011. We then classified men within this cohort as having undergone EM (no first-course surgery, radiation, hormone therapy, or chemotherapy) or active treatment. Patient and provider variables were analyzed using univariate and multivariate logistic regression models to determine predictors of EM selection. Results: Of 287,562 men with low-risk prostate cancer, we identified 34,132 patients (11.9%) who received EM. Beginning in 2008, we observed a significant and steady rise in EM usage with time (range, 9.8% to 18.6%). Compared to 2004, patients diagnosed in 2011 had 2.5 times the odds of receiving EM (odds ratio [OR] 2.52, confidence interval [CI] 2.39-2.64, p&lt;0.0001). Aside from year of diagnosis, age, and Charlson score were strong predictors of EM usage (p&lt;0.0001). Other strong predictors of EM included hospital type and insurance provider. Specifically, patients who were treated at comprehensive cancer centers or who had personal health insurance were significantly less likely to receive EM (OR 0.63, 0.60-0.66, p&lt;0.0001 or OR 0.90, CI 0.88-0.93, p&lt;0.0001, respectively). Patient race, income, and area of residence as well as hospital location were significantly but weakly associated with EM. Conclusions: In recent years, low-risk prostate cancer has been increasingly managed with EM, especially in older patients or patients with multiple comorbidities, who are least likely to benefit from active treatment. Unexpectedly, hospital type and insurance provider also predict EM usage, calling into question whether non-clinical factors are influencing EM selection.