tbuckley/cabot-search huggingface dataset:
Predictive value of ERCC1 and KRAS in colorectal cancer patients with FOLFOX chemotherapy.
Authors: In Kyu Lee, Sung-Bong Choi, DaeYoung Cheung, Jin Il Kim
Journal: Journal of Clinical Oncology (2016)

588 Background: To determine the clinical significance of KRAS mutation and ERCC1 overexpression as a predictive factor of resistance in oxaliplatin based treatment. Methods: We retrospectively analyzed the clinicopathologic features, status of KRAS mutation and ERCC1 overexpression of 386 colorectal cancer patients who received curative intent surgery. Among them 84 patients were treated by FOLFOX regimen as the first line. Their disease-free survival and overall survival according to the KRAS and ERCC1 were analyzed. Results: About a quarter of patients (25.5%) were represented KRAS wild type with ERCC1 overexpression. Among the patients who treated by FOLFOX regimen, 73 patients were evaluated both of the KRAS and ERCC1. There were no significant differences of disease-free survival and overall survival according to KRAS status and ERCC1 expression each. Under the subgroup analysis, overall survival of ERCC1 overexpression group in wild type KRAS was poor than ERCC1 negative group (p=.029), but no significant difference was in mutant KRAS group (p=.671). Conclusions: Our results suggest that the KRAS wild type with ERCC1 overexpression would be associated with the resistance of oxaliplatin.If oxaliplatin based chemotherapy would beconsidered, status of KRAS mutation and ERCC1 overexpression should be evaluated.
Inflammation is independent of steatosis in a murine model of steatohepatitis
Authors: Wei Wang, Ming‐Jiang Xu, Yan Cai, Zhou Zhou, Haixia Cao, Partha Mukhopadhyay, Pal Pacher, Shusen Zheng, Frank J. Gonzalez, Bin Gao
Journal: Hepatology (2017)

Obesity and alcohol consumption synergistically promote steatohepatitis, and neutrophil infiltration is believed to be associated with steatosis. However, the underlying mechanisms remain obscure. Peroxisome proliferator–activated receptor gamma (PPARγ) plays a complex role in lipid metabolism and inflammation; therefore, the purpose of this study was to dissect its role in regulating steatosis and neutrophil infiltration in a clinically relevant mouse steatohepatitis model of 3‐month high‐fat diet (HFD) feeding plus a binge of ethanol (HFD‐plus‐binge ethanol). Hepatocyte‐specific Pparg disruption reduced liver steatosis but surprisingly increased hepatic neutrophil infiltration after HFD‐plus‐binge ethanol. Knockout or knockdown of the PPARγ target gene, fat‐specific protein 27, reduced steatosis without affecting neutrophil infiltration in this model. Moreover, hepatocyte‐specific deletion of the Pparg gene, but not the fat‐specific protein 27 gene, markedly up‐regulated hepatic levels of the gene for chemokine (C‐X‐C motif) ligand 1 ( Cxcl1 , a chemokine for neutrophil infiltration) in HFD‐plus‐binge ethanol‐fed mice. In vitro, deletion of the Pparg gene also highly augmented palmitic acid or tumor necrosis factor alpha induction of Cxcl1 in mouse hepatocytes. In contrast, activation of PPARγ with a PPARγ agonist attenuated Cxcl1 expression in hepatocytes. Palmitic acid also up‐regulated interleukin‐8 (a key chemokine for human neutrophil recruitment) expression in human hepatocytes, which was attenuated and enhanced by cotreatment with a PPARγ agonist and antagonist, respectively. Finally, acute ethanol binge markedly attenuated HFD‐induced hepatic PPARγ activation, which contributed to the up‐regulation of hepatic Cxcl1 expression post–HFD‐plus‐binge ethanol. Conclusion : Hepatic PPARγ plays an opposing role in controlling steatosis and neutrophil infiltration, leading to dissociation between steatosis and inflammation; acute ethanol gavage attenuates hepatic PPARγ activation and subsequently up‐regulates hepatic CXCL1/interleukin‐8 expression, thereby exacerbating hepatic neutrophil infiltration. (H epatology 2017;66:108–123).
The role of HE4 in predicting surgical outcome in recurrent ovarian cancer (ROC).
Authors: E. I. Braicu, C. Fotopoulou, R. Richter, R. Chekerov, K. Pietzner, C. Hall, W. Lichtenegger, J. Sehouli
Journal: Journal of Clinical Oncology (2011)

e15556 Background: The value of secondary tumordebulking in ROC remains unclear. Retrospective analyses indicate that patient’s survival is positively affected only when complete macroscopic tumor resection is achieved, so that efforts are internationally focussed on prediction of operability and postoperative tumor residuals. HE4 constitutes a novel biomarker in ovarian cancer, showing so far promising results in the early diagnosis. Primary aim was to evaluate the predictive role of HE4 on surgical outcome and platinum response in 2nd line systemic treatment. Secondary aims were prognostic role of HE4 for overall- (OAS) and progression free survival (PFS). Methods: Plasma was obtained before secondary cytoreductive surgery from 76 patients with ROC. HE4 was detected using ELISA technique Results: In 64.5% of the patients a complete macroscopical tumor debulking could be obtained. A total of 85.5% patients were primary platinum sensitive. Mean HE4 plasma concentration was 195,05 pg/ml (range 36.8-900pg/mLl). HE4 correlated significantly with the presence of peritoneal carcinomatosis (p<0.001) and residual tumor mass after surgery (p= 0.001, HR 12, 61, 95% CI 2.77-57.39). At a HE4 cut off value of 70pg/ml surgical outcome in terms of postoperative residuals could be predicted with a sensitivity of 44.9% and a specificity of 88.9% (95%CI 0.618-0.865). Even though HE4 expression in plasma significantly correlated with OAS (p=0.019, HR=2.77, 95%CI 1.18-6.50) in univariate analysis, it could not retain prognostic significance in multivariate setting. Independent factors for OAS were presence of ascites, residual tumor mass, and initial platinum response. The latter two were also independent prognostic factors for PFS. Conclusions: HE4 appears to be a novel predictive marker for postoperative tumor residuals at secondary tumor debulking in ROC. Larger population studies are warranted to validate these first results.
A study of genes and microRNAs that may predict clinical responses to anti-CTLA-4 therapy.
Authors: Jianjun Gao, Hong Chen, Derek Ng Tang, Padmanee Sharma
Journal: Journal of Clinical Oncology (2013)

285 Background: Blockade of T cell co-inhibitory receptor CTLA-4 with a monoclonal antibody, Ipilimumab (BMS), has led to augmented anti-tumor immune responses, clinical benefit, and FDA approval of Ipilimumab for the treatment of metastatic melanoma. Only a subset of patients benefit from anti-CTLA-4 therapy. In order to identify genes, microRNAs, and signaling pathways that are modulated by anti-CTLA-4, which may be used for potential correlation with clinical outcomes or provide additional targets for therapy, we purified and analyzed CD4 + T cells from patients treated with anti-CTLA-4 for changes in gene and microRNA expression profiles. Methods: On an IRB-approved Phase Ia presurgical clinical trial, 6 patients with localized bladder cancer were treated with two doses of Ipilimumab at 10 mg/kg at weeks 1 and 4. Pre-therapy and post-therapy blood samples were collected for CD4 + T cell enrichment by using the T cell isolation kit from Miltenyi Biotec (Auburn, CA). RNA and microRNA were isolated from purified CD4 + T cells using Qiagen RNA isolation kits for Affymetrix microarray and micoRNA array analyses. Microarray data were then analyzed using Ingenuity iReport (Redwood City, CA). RT-PCR and Western blot were used to confirm significant changes in genes or pathways identified in microarray analyses. Results: Ipilimumab treatment resulted in modulation of differentially expressed genes (DEGs). After two doses of treatment, Ipilimumab significantly changed expression of a total of 289 DEGs. Further pathway analyses indicated that Ipilimumab induced a variety of pathways involved in cell proliferation and immune modulation, including PI3K/AKT, MAP/ERK, and IFN/JAK-STAT pathways. We have also identified 9 microRNAs that potentially regulate the expression of genes changed by anti-CTLA-4 therapy. Conclusions: Ipilimumab treatment results in modulation of multiple genes, microRNAs, and pathways, which likely play important roles in anti-tumor immune responses. We are currently testing a number of these identified genes and microRNAs as potential predictive biomarkers for anti-CTLA-4 therapy in a small cohort of patients who had complete response vs. progression of disease after anti-CTLA-4 therapy.
Treatment strategy for obstructive colorectal cancer.
Authors: Shiro Iwagami, Nobutomo Miyanari, Tatsuo Kubota, Yousuke Nakao, Takanobu Yamao, Hidetaka Sugihara, Hiroshi Sawayama, Takao Mizumoto, Yuuki Kitano, Hideo Baba
Journal: Journal of Clinical Oncology (2016)

741 Background: The number of patients with colorectal cancer has been increasing in all over the world. Approximately 10 percent of CRC is complicated by obstructive symptoms at the time of their diagnosis. Obstructive colorectal cancer (OCRC) could be a fatal because of perforation peritonitis or sepsis, and it is necessary to immediate treatment. The aim of this study was to explore the treatment strategies for patients with OCRC. Methods: Between April 2008 and December 2014, six hundred seventy two patients underwent surgery in out institute. The numbers of OCRC were 82 cases (12.2%). We evaluated the feasibility and effectiveness of our treatments for OCRC. Results: Treatment strategies were adopted according to the location of CRC. For patients with right-sided OCRC, we performed one-stage surgery. They underwent primary tumor resection and anastomosis at the same time. For left-sided OCRC, patients were treated by two-stage surgery. At first, they were managed by decompression of their colon with colostomy or transanal ileus tube, and then, underwent colectomy. The cases of right-side OCRC were 23 cases, and all of them underwent one-stage surgery. We could find no cases of anastomotic leakage in these cases. The cases of left-side OCRC were 59 cases, and 50 patients (86%) of them were treated two-stage surgery. Stage IV OCRC patients tended to undergo colostomy only. Conclusions: One-stage surgery was feasible for patients with right-sided OCRC. For left-sided OCRC cases, two-stage surgery was effective to prevent perioperative complications.
Catumaxomab treatment of malignant ascites in patients with chemotherapy-refractory ovarian cancer: A phase II study.
Authors: J. S. Berek, R. P. Edwards, L. Parker, L. R. DeMars, T. J. Herzog, S. S. Lentz, R. Morris, W. L. Akerley, R. W. Holloway, M. Method, S. C. Plaxe, J. L. Walker, T. Schindler, E. Schulze, C. N. Krasner
Journal: Journal of Clinical Oncology (2011)

5048 Background: Malignant ascites (MA) in ovarian carcinoma (OC) patients (pts) is associated with a poor prognosis and reduced quality of life due to symptoms from ascites. In 2009, catumaxomab was approved in the EU for the intraperitoneal (IP) treatment of MA. Methods: In this single-arm, open-label, US, multicenter, phase II study, 32 chemotherapy-refractory and heavily pretreated (median of 4.5 prior chemotherapies) OC pts with MA were treated with catumaxomab. Pts received 4 IP infusions (10, 20, 50, and 150 µg) over 3 hours on days 0, 3, 7, and 10. The primary endpoint was the proportion of pts with at least a 4-fold increase in the puncture-free interval (PuFI) relative to their pretreatment interval. Main secondary endpoints were puncture-free survival (PuFS), overall survival (OS), MA symptoms based on patient-assessed FACIT-AI scores, safety, and tolerability. Results: 22.6% pts achieved at least a 4-fold increase in the PFI after catumaxomab treatment, which was below the predefined threshold of 60%. In median, the PFI was prolonged 2.0 fold in the full-analysis set (from median of 1.7 to 3.9 weeks) and 2.9 fold in the per-protocol set (from median of 2.6 to 7.1 weeks). 19 (59.4%) pts required paracentesis after catumaxomab treatment. The other pts died or were lost to follow up. The median PuFS was 4.2 weeks and median OS was 3.6 months. After catumaxomab treatment, patients’ symptoms improved in the majority of 13 predefined categories or remained stable. At repuncture, most symptoms were still improved compared with screening. The most frequent adverse events, pyrexia, nausea, and vomiting, are related to cytokine release. Transient increases in liver parameters and transient decreases in blood lymphocytes were regularly observed but were generally without clinical relevance. Conclusions: The study demonstrates an overall prolongation of PuFI and improvement of MA symptoms in these heavily pretreated patients. The median OS of 3.6 months support a therapeutic effect of catumaxomab. The safety profile of catumaxomab was acceptable, consistent with its mode of action and similar to that in previous clinical studies.
Disseminated tumor cells in the bone marrow of ductal carcinoma in situ patients.
Authors: N. Sänger, K. E. Effenberger, S. Riethdorf, E. Ruckhäberle, L. C. Hanker, I. Wiegratz, K. Strebhardt, K. Pantel, M. Kaufmann
Journal: Journal of Clinical Oncology (2011)

10582 Background: The detection of disseminated tumor cells (DTC) in the bone marrow (BM) of primary breast cancer (BC) patients documents the presence of a generalized disease and has been demonstrated as an independent factor for a poor prognosis. This proof-of-principle investigation has focused on early micrometastatic cell spread in patients with ductal carcinoma in situ (DCIS) as a localized, precursor lesion of invasive BC. Methods: In 28 female DCIS patients who were preoperatively screened by stereotactic core biopsy, bone marrow aspirates were taken at the time of primary surgery. DTC detection was performed according to established protocols using monoclonal anti-cytokeratin antibodies A45-B/B3 and AE1/AE3. Results: DTC were detected in 4/19 patients with pure DCIS and in 6/9 patients with DCIS and microinvasion of the basement membrane. After a median follow-up time of 33 months, two initially DTC-positive patients suffered from contralateral carcinoma and contralateral DCIS, whereas the remaining patients were relapse-free. Conclusions: These results indicate that haematogenous dissemination of tumor cells appears as an early event in BC development. Additional to significant prognostic factors like tumor size, comedo necrosis, surgical margins and radiation therapy, DTC may contribute to local relapse or invasive recurrence in DCIS patients.
Doctor, what do I have? Limited-English–proficient patients and cancer diagnosis knowledge.
Authors: J. C. F. Leng, L. Yogendran, D. Massie, J. Ramirez, T. Lee, I. Lobach, F. Gany
Journal: Journal of Clinical Oncology (2011)

6100 Background: Screening, diagnosis and treatment have significantly reduced the cancer burden of several cancers in the US for certain populations. Incorrect knowledge of cancer diagnosis can hinder treatment. Immigrant minorities and the underserved face unique challenges in the receipt of appropriate cancer care. Barriers to understanding cancer diagnoses include language, culture, and health literacy. This study investigates knowledge of cancer diagnosis among immigrant minorities. Methods: Patients were recruited at ten hospital-based cancer clinics in New York City between September 2008 and December 2010. Bilingual staff administered a survey for a sample of 471 patients with a clinical cancer diagnosis. Demographic and self-reported diagnosis and treatment information were collected. Patient charts were reviewed to ascertain cancer diagnosis. Results: 92% of patients were foreign-born. 81% preferred to speak a language other than English in the health care setting. 64% of foreign-born patients had resided in the US for 15 years or less. 25% were uninsured. Among those who were insured, 50% had Medicaid only, and 39% had Medicaid for Emergency Services only. 60% did not have a primary care provider, and 84% did not have a social worker assisting them with their care. The most common cancer diagnoses were breast (28%), colorectal (9%), cervical (8%), and lung (7%). 14% had incorrect knowledge of their cancer diagnosis. An additional 6 participants reported the correct metastatic site, but wrong primary cancer, or correct site, but wrong type of cancer. Of the 68 patients with incorrect knowledge of their diagnosis, 91% preferred a non-English language in the health care setting. Conclusions: Among this cohort of predominantly immigrant cancer patients, a considerable proportion were unaware of their correct cancer diagnoses. This may have a significant impact on subsequent cancer treatment and care. Language discordance likely has an important role in this miscommunication between patients and the health care system. Limited English proficient patients may be at particular risk for suboptimal cancer care. More research is needed to better understand cancer care in the language discordant encounter.
From evidence to impact: Determining the vital few indicators for systemic treatment computerized prescriber order entry systems (ST CPOE).
Authors: Sara Lankshear, Marc Theriault, Annie Cheung, Sherrie Hertz, Leonard Kaiser, Vishal Kukreti
Journal: Journal of Clinical Oncology (2012)

258 Background: It is important to demonstrate that delivery systems contribute to patient outcomes. Quality indicators provide a quantitative, evidence based (EB) foundation for clinicians, organizations, researchers, and administrators to monitor and evaluate performance of these systems. Technologies, such as ST CPOE systems are costly, impact clinician practice and therefore, would benefit from accountability through quality measures. The process for the identification of EB indicators for measuring the impacts of ST CPOE systems is described. Methods: The indicators were developed alongside the ST CPOE Best Practice Guideline. A multi-phased approach included the development of a conceptual framework, defining quality dimensions, literature review, environmental scans, and key informant interviews. An initial list of indicators was identified and aligned with the relevant quality dimensions (i.e. safety, effectiveness, efficiency, integration). A Modified Delphi methodology, involving internal and external content experts in oncology practice, technology, informatics, and human factors, was undertaken to obtain consensus on the vital few. Results: Three rounds of Modified Delphi exercises were conducted with the initial list of 118 indicators. 15 clinical practice indicators (CPI) were deemed as relevant for overall evaluation and research purposes specific to ST CPOE systems. Within this group, four indicators were identified as being valuable for reporting quality monitoring at the organizational, regional and provincial levels. In addition to CPI, 74 system functionality (e.g. usability, alert features, system integration) indicators were identified. Conclusions: Through engagement of experts and evidence review, we have identified a set of quality indicators for ST CPOE systems which will facilitate appropriate evaluation of systems and implementation processes. Operationalizing these indicators for automatic data flow through is planned in a large geographic area.
Utilizing TQM and CQI prinicples in establishing a Type 1 observation unit in a comprehensive cancer center.
Authors: Josiah Halm
Journal: Journal of Clinical Oncology (2014)

96 Background: CMS defines Observation Services as outpatient care ordered by a physician and provided in a hospital bed to determine the need for inpatient admission or discharge. Recent CMS rules on Observation stay and 2-midnight rule has created confusion amongst Medicare beneficiaries, providers and hospitals. Two-thirds of US hospitals deliver observation care without using an observation unit. Review of our hospital observation care and a survey of Cancer Centers within the Alliance of Dedicated Cancer Centers revealed that observation care was provided in a bed anywhere in the hospital with unstructured care provided at the discretion of the treating physician. This leads to less favorable outcomes compared to protocol driven and closed observation units (Type 1). Methods: Plan- Institutional stakeholders consisting of administrators, hospitalists, ED physicians, case managers and nurse managers developed an observation services guideline policy and project team. Do- pilot initiated with ED admitting Observation patients to dedicated hospitalist providers and unit. Order sets were developed, education and staff training was provided and target start date set. Baseline and performance measures were developed. Study- impact on ED flow, admissions, ED length of stay, provider satisfaction, diagnoses, patient case-mix, and financial costs. Act– Implemented changes and lessons learned from pilot Results: Before implementation of pilot less than 10 patient per month were placed in observation status (Sept 2011- Aug 2012). After pilot average of 30 patient per month were initially placed in Observation (Sept 2012-April 2014). Approximately 73% of patients placed on observation are discharged and not admitted. Observation counts for approximately 25,000 dollars in professional charges per month. ED LOS decreased to less than 6-hours. Patient satisfaction and ED provider satisfaction scores have improved. Conclusions: Majority of Observation patients are not admitted thus avoiding the higher cost associated with inpatient stays with resulting cost saving. ED wait times have improved leading to less over-crowding with ED physicians having time to see more patients.
Stereotactic body radiation therapy and patient-reported quality of life prospectively evaluated in patients with unresectable or recurrent pancreatic cancer.
Authors: Lauren M. Rosati, Zhi Cheng, Scott P. Robertson, Megan N. Kummerlowe, Amy Hacker-Prietz, Christopher Lee Wolfgang, Timothy M. Pawlik, Dung T Le, Lei Zheng, Dan Laheru, Joseph M. Herman
Journal: Journal of Clinical Oncology (2015)

92 Background: The impact of fractionated stereotactic body radiation therapy (SBRT) on patient-reported quality of life (QOL) and physician-reported toxicity in patients with recurrent or locally advanced pancreatic cancer (PCA) was prospectively evaluated. Methods: Forty-two PCA patients were treated with 25-33 Gy using SBRT in 5 fractions on a single-institution study. Both patient- and physician-reported outcomes were evaluated prior to SBRT and 4-6 weeks post-SBRT. Eight outcomes were consistently evaluated among both groups—performance status, fatigue, pain, anorexia, nausea, vomiting, constipation, and diarrhea. Patient-reported QOL metrics were assessed using a 4-point Likert scale on the EORTC QLQ-C30 and QLQ-PAN26, while physician-reported toxicities were graded using the NCI CTCAE version 4.0. Comparisons between those with paired patient- and physician-reported outcomes collected prior to and 4-6 weeks after SBRT were made using the Wilcoxon signed-rank test. Results: Of the 42 patients currently enrolled onto the study, 29 had both patient- and physician-reported outcomes collected prior to and 4-6 weeks after SBRT. Fifty-five percent were female and 83% were Caucasian. The median age at diagnosis was 65.6 years (range, 40.8-86.6). There was no significant impairment of any of the 8 physician-reported toxicities, nor were significant changes observed in patient-reported overall health (p = 0.66) or QOL (p = 0.18) scores following SBRT. Patients felt less worried about their future health (mean change [mD] = -0.45, p = 0.02), and an improvement in feeling less attractive as a result of disease and treatment reached borderline significance (mD= 0.31, p = 0.09). However, patients felt limited in planning activities in advance (mD= 0.45, p = 0.02) and were more constipated (mD= 0.38, p = 0.01) 4-6 weeks post-SBRT. Conclusions: Although the numbers are small, patients with unresectable or locally recurrent PCA do not appear to suffer any detriment of overall health or QOL after receiving a five-day course of SBRT. Moreover, this regimen may lead to a more optimistic point of view on future health and/or level of physical attraction. Clinical trial information: NCT01781728.