tbuckley/cabot-search huggingface dataset:
Association of Surgical Treatment, Systemic Therapy, and Survival in Patients With Abdominal Visceral Melanoma Metastases, 1965-2014
Authors: Gary B. Deutsch, Devin C. Flaherty, Daniel D. Kirchoff, Mariel Bailey, Sarah Vitug, Leland J. Foshag, Mark B. Faries, Anton J. Bilchik
Journal: JAMA Surgery (2017)

Systemic therapy for metastatic melanoma has evolved rapidly during the last decade, and patient treatment has become more complex.To evaluate the survival benefit achieved through surgical resection of melanoma metastatic to the abdominal viscera in patients treated in the modern treatment environment.This retrospective review of the institutional melanoma database from the John Wayne Cancer Institute at Providence St Johns Health Center, a tertiary-level melanoma referral center, included 1623 patients with melanoma diagnosed as having potentially resectable abdominal metastases before (1969-2003) and after (2004-2014) advances in systemic therapy.Overall survival (OS).Of the 1623 patients identified in the database with abdominal melanoma metastases, 1097 were men (67.6%), and the mean (SD) age was 54.6 (14.6) years. Of the patients with metastatic melanoma, 1623 (320 [19.7%] in the 2004-2014 period) had abdominal metastases, including 336 (20.7%) with metastases in the gastrointestinal tract, 697 (42.9%) in the liver, 138 (8.5%) in the adrenal glands, 38 (2.3%) in the pancreas, 109 (6.7%) in the spleen, and 305 (18.8%) with multiple sites. Median OS was superior in surgical (n = 392; 18.0 months) vs nonsurgical (n = 1231; 7.0 months) patients (P < .001). The most favorable 1-year and 2-year OS was seen after surgery for gastrointestinal tract (52% and 41%) and liver (51% and 38%) metastases, respectively. Multivariable analysis found increasing age (hazard ratio [HR], 1.01; 95% CI, 1.00-1.01; P = .02) and the presence of ulceration (HR, 1.21; 95% CI, 1.01-1.45; P = .04) were associated with a worse OS. Alternatively, treatment with metastasectomy (HR, 0.59; 95% CI, 0.46-0.74; P < .001) and metastases involving the gastrointestinal tract (HR, 0.65; 95% CI, 0.48-0.87; P = .004) were associated with a better OS. The systemic treatment era did not significantly affect outcomes (HR, 0.82; 95% CI, 0.67-1.02; P = .15). Overall, patients with gastrointestinal tract metastases undergoing complete, curative resection derived the greatest benefit, with a median OS of 64 months.To our knowledge, this series is the largest single-institution experience with abdominal melanoma metastases, demonstrating that surgical resection remains an important treatment consideration even in the systemic treatment era.
Does a treatment delay affect the survival of octogenarian patient population?
Authors: Ali Mehmood Raufi, Hassaan Jafri, Todd W. Gress
Journal: Journal of Clinical Oncology (2017)

149 Background: The cancer management of the elderly patient is an increasingly important and challenging issue. The aim of this retrospective analysis is to evaluate the impact of treatment delay on survival outcome of cancer in octogenarian patients. Methods: From 2006 to 2015, established cancer patients age 80 and above who received treatment at our comprehensive cancer center were retrospectively reviewed. We evaluated the relationship between a delay in cancer treatment of more than 30 days in the octogenarian patient and survival using Kaplan-Meier survival and Cox proportional hazards models. Results: There were 235 octogenarian cancer patients available for evaluation and 115 of these had a delay in initiation of cancer treatment ( &gt; 30 days). Mean age was 83.7 years the treatment delay (TD) group and 83.9 in the no treatment delay (NTD) group (p = 0.70) Eastern Cooperative Oncology Group (ECOG) score of 2 or more was present in 22.6% of the TD group and 18.3% of the NTD group (p = 0.42). Metastatic disease was higher in the NTD group (22.5% vs. 11.3% TD group; p = 0.051). There were more breast (36.5% TD vs. 12.5% NTD group) and lung cancer (26.9% TD vs. 18.3% NTD group) in the TD group, and more genitourinary (20.8% NTD vs. 9.6% TD group) and gynecological cancer (20.8% NTD vs. 15.6% TD group) in the NTD group (p &lt; 0.001 for overall comparison). Median overall survival was higher in the TD group (50 vs. 24 months NTD group; p = 0.001). Treatment delay was still associated with improved survival even after adjusting for age, gender, ECOG, stage of disease, and type of tumor (HR 0.64, CI 0.44-0.92). Conclusions: We found that a delay in cancer treatment in the octogenarian patient was associated with better overall survivial. Bias in regards to the reasons for the treatment delay may exist and could have affected our results. We attempted to minimize this bias by adjusting for characteristics that influence treatment between our two study groups. Nevertheless, our findings suggest that a delay in cancer treatment at minimum did not adversely affect mortality in this older patient population.
Chromatin-remodeling factor SMARCD2 regulates transcriptional networks controlling differentiation of neutrophil granulocytes
Authors: Maximilian Witzel, Daniel Petersheim, Yanxin Fan, Ehsan Bahrami, Tomas Racek, Meino Rohlfs, Jacek Puchałka, Christian Mertes, Julien Gagneur, Christoph Ziegenhain, Wolfgang Enard, Asbjørg Stray-Pedersen, Peter D Arkwright, Miguel R Abboud, Vahid Pazhakh, Graham J Lieschke, Peter M Krawitz, Maik Dahlhoff, Marlon R Schneider, Eckhard Wolf, Hans-Peter Horny, Heinrich Schmidt, Alejandro A Schäffer, Christoph Klein
Journal: Nature Genetics (2017)
Redesigning care to lower episode costs in bone marrow transplantation.
Authors: Laura J. Johnston, Diana Patterson, Ning Tang, Christine McMurdo, Laura Adams, Susan Chang
Journal: Journal of Clinical Oncology (2017)

16 Background: Increased scrutiny over costs of cancer care has led to the introduction of episode-based payment by federal and commercial insurers. National average billed charges for autologous and allogeneic transplant episodes of care are approximately $375K and $925K, respectively. Through comprehensive analysis of claims data, we identified leading drivers of cost in BMT episodes (which span 30 days before transplant through 60-100 days post-transplant) and cost reduction opportunities. By redesigning care delivery, we can reduce post-transplant admissions and potentially improve the health and patient experience for this population. Methods: From September 1, 2013 – February 28, 2015, SHC performed 221 allogeneic and 241 autologous transplants. We analyzed internal claims data to map costs of BMT episodes, including pre-transplant, transplant (index), and post-transplant phases of care using standardized cost categories including room accommodations, medications, medical and surgical supplies, imaging, and labs. Results: 67% of episode cost was associated with pre-transplant and index phases. In both phases, patients’ treatment closely matched defined protocols. Imaging, medications, and blood utilization met clinical indications. The largest opportunity was seen in the post-transplant phase for patients with multiple myeloma who received autologous transplants. On average, episodes with post-transplant admissions were 35% more costly than episodes without post-transplant admissions. Many of these patients are admitted 5-9 days after transplant due to neutropenic fever, have short LOS, and receive empiric antibiotics. An estimated 37% of post-transplant admissions, totaling $790,000 in annualized cost, may be prevented with additional outpatient support. Conclusions: A multidisciplinary team proposed redesigning care to safely shift treatment from the inpatient to outpatient setting. Strategies include expanding Infusion Treatment Area and home pharmacy capacity and partnering with home health agencies.
구연 : 클라벨홀 ; 황달을 동반한 알코올간경변증 환자의 단기 예후인자
Authors: 김진동, 손덕승, 양진모, 최종영, 장우임, 유샃란, 장정원, 김창욱, 조세현, 한준열, 이영석
Journal: Clinical and Molecular Hepatology (2008)
Are we choosing wisely? Operationalizing Choosing Wisely in the Ontario cancer system.
Authors: Simron Singh, Craig Earle, Nicole Mittmann, Natalie G. Coburn, Farah Rahman, Ning Liu, Matthew C. Cheung
Journal: Journal of Clinical Oncology (2017)

221 Background: The Choosing Wisely (CW) campaign aims to initiate conversations about unnecessary treatments contributing to the rising cost of cancer care. We aim to develop a data linkage research platform to operationalize CW recommendations within administrative health care databases and the population-based performance of these recommendations. We initiated testing with the CW recommendiation against routine surveillance imaging in patients with aggressive histology lymphoma and pancreatic/gastric (P/G) cancer treated with curative intent. Methods: We used population-based administrative databases from Ontario, Canada to examine a cohort of adult patients with diffuse large B-cell lymphoma (DLBCL) (2004-2011) and P/G cancer post-surgical resection (2003-2013). For the DLBCL cohort, we defined an index date of 2-years after the last dose of R-CHOP as the time-frame beyond which surveillance CT imaging would be inappropriate. For the P/G cohort, the index date was 6 months post-resection. The primary outcome was cumulative incidence of CT scans within 3 years of the index date. To ensure that only surveillance scans were captured, we censored 6 months prior to development of recurrent disease, a new cancer diagnosis, or death. Results: The cohort consisted of 2,838 DLBCL and 2,930 P/G patients. The cumulative incidence of receiving CT imaging in the three years post index date was 55.6% (95% CI 53.7%-57.5%) among DLBCL and 82.8% (95% CI 81.3%-84.3%) among P/G patients. DLBCL patients ≥65 were more likely to receive imaging (p&lt;0.01) as were those with more comorbidities (p&lt;0.01). Younger patients with P/G were more likely to receive imaging (p&lt;0.01) as were men (p&lt;0.01). Income and rurality did not predict for increased imaging in either cohort. Surveillance CT imaging decreased over time among DLBCL patients (p&lt;0.01), but increased among P/G cancer patients (p&lt;0.001). Conclusions: During a time-frame in which surveillance imaging is deemed unnecessary by the CW campaign, the practice in Ontario remains excessive. This study represents a real-world demonstration that CW statements can be operationalized within population-based administrative databases and used as quality indicators in cancer care.
GLIOSTRY (GLIOblastoma regiSTRY) of the AINO (Italian Association of Neuro-Oncology): Analysis of factors influencing survival in glioblastoma patients receiving the nitrosourea fotemustine at first relapse following Stupp regimen.
Authors: Roberta Ruda, Giuseppe Lombardi, Silvia Scoccianti, Maria Grazia Fabrini, Matteo Santoni, Andrea Pace, Antonio Silvani, Alfredo Marinelli, Ivan Lolli, Mario Balducci, Mauro Arcicasa, Maurizio Salvati, Andrea Sponghini, Simona Vallarelli, Manuela Caroli, Francesca Imbesi, Domenico Bilancia, Marina Faedi, Stefano Cascinu, Riccardo Soffietti
Journal: Journal of Clinical Oncology (2015)

2054 Background: patients with glioblastoma failing radiotherapy plus temozolomide are treated in Europe with nitrosourea-based regimens, but factors influencing survival are not entirely known.We investigated the factors influencing survival in a large cohort of Italian glioblastoma patients who received the nitrosourea fotemustine (FTM) at first relapse following the Stupp regimen. Methods: survival data and information on demographics, clinical, radiological, molecular and treatments factors were collected in 34 Italian Institutions. PFS and OS curves were constructed using the Kaplan-Meier method and both univariate and multivariate analysis were performed . Results: Since 2005, 921 (587 M 334 F, median age 56 yrs) patients were enrolled , and up to date 897 are evaluable. Median PFS following FTM was 103 days. Factors of prognostic significance in univariate analysis were: MGMT methylation (129 d methylated vs 90 d unmethylated tumors, p < 0.001) and association with bevacizumab (148 d the association vs 97 d FTM alone, p < 0.0001). Both MGMT status with an HR of 0.64 (0.52-0.79), p < 0,001, and association with bevacizumab with an HR of 0.71 (0.56-0.92), p < 0,008, remained significant after multivariate analysis. Median OS following FTM was 197 days. Factors of prognostic significance in univariate analysis were age (200 d < 65 yrs vs 182 d > 65 yrs, p = 0.0102), Karnofsky Performance Score (213 d KPS 90-100 vs 182 d KPS ≤ 80), extent of initial surgery (213 d gross total vs 184 d partial removal, p = 0.0022), MGMT status (246 d methylated vs 176 unmethylated tumors, p < 0.001) and association with bevaizumab (238 d association with bev vs 187 d FTM alone, p = 0.0297). MGMT status with HR of 0.60 (0.48-0.76), p < 0.001, and association with bevacizumab with HR of 0.73 (0.56-0.95), p = 0.022, remained significant after multivariate analysis. MGMT methylation was the strongest factor influencing OS from initial diagnosis. Conclusions: MGMT is a strong prognostic and predictive factor in GBM patients following FTM. The association of bevacizumab with FTM could be superior over FTM alone.
Understanding the landscape and challenges of end-of-life measurement among comprehensive cancer centers.
Authors: Denise Morse, Delinda Pendleton
Journal: Journal of Clinical Oncology (2017)

207 Background: Quality at the end of life is vitally important to providing patient and family centered care, however the measurement of end of life care is challenging. Numerous metrics have been fully endorsed by the NQF, however benchmark data is difficult to obtain and clinicians question the usability and reliability of these existing measures. Methods: The Comprehensive Cancer Center Consortium for Quality Improvement (C4QI) convened an End of Life workgroup comprised of members from 21 cancer centers across the country. The first task of the workgroup was to collate existing end of life metrics that are in the public domain. Once the measures were collated, a survey was sent out to the membership for feedback on current utilization of measures and obtain baseline data where available. Data was pulled using the Vizient Clinical Database to look at the ability to pull end of life data within the database. The organizations were able to compare data on ICU Utilization, Chemotherapy, Length of Stay, and Cost. Results: The results of the C4QI End of Life survey showed that there challenges exist with interpretation and analysis. Even within ASCO QOPI, each center had their own issues with capturing the same population of cases and including/excluding the same criteria. Although we had received ASCO QOPI results from numerous centers, the comparison between the centers proved to be not as accurate of a comparison as desired. The Vizient data on inpatient mortalities and discharges to hospice showed differences among centers. The data led to additional discussions about the additional data needs especially as it relates to outpatient data capture both at each individual center as well as at other centers, and the need for more clarifying information about hospital makeup. Conclusions: The C4QI End of Life workgroup has agreed to focus on Advance Directive, Management of Pain at the End of Life, Palliative Care Referrals, and Hospice Enrollment. These 4 areas are the first step towards measuring advance care planning and quality at the end of life. The project shows the challenges of metric analysis, data sharing and benchmarking that collaborative groups face especially around potentially charged topics like End of Life.
Epigenome and genome alterations in platinum resistant ovarian cancer.
Authors: Daniela Matei, Fang Fang, Horacio Cardenas, David F Miller, Aaron Buechlein, Qing Yu, Susan M. Perkins, Yunlong Liu, Guanglong Jiang, Pietro Taverna, Harold N. Keer, Douglas B Rusch, Kenneth P Nephew
Journal: Journal of Clinical Oncology (2015)

5555 Background: Epigenetic changes, particularly DNA methylation aberrations have been implicated in acquired resistance to platinum in ovarian cancer (OC). Methods: An ongoing phase I/II multi-institutional clinical trial uses the novel DNA methyl transferase inhibitor (DNMTI) SGI-110 to re-sensitize platinum resistant OC to carboplatin. Patients enrolled in this trial had recurrent, platinum resistant OC and multiple lines of prior therapy. Tumor biopsies were collected at baseline and after two cycles of SGI-110 administered daily for 5 days (30mg/m2). The objectives of the study were to analyze and integrate global RNA expression and DNA methylation profiles of platinum resistant tumors and to measure genomic and epigenomic changes induced by the DNMTI. RNA and DNA were extracted from 48 and 57 baseline tumors and analyzed using next generation sequencing (RNA-seq) and Infinium HM450 BeadChip array, respectively. Differential gene expression and DNA methylation profiles were generated and used for Ingenuity Pathway Analysis (IPA) to identify significantly altered pathways in response to SGI-110. Results: Analysis of a limited number of paired samples before and after treatment (n = 8) revealed significant changes in global gene expression profiles induced by SGI-110, with 960 significantly altered genes representing immunopathway enrichment, including cytokine production in macrophages and T helper cells by IL-17A and IL-17F, granulocyte/agranulocyte adhesion and inflammation, IL-8 signaling, p38 MAPK signaling, cAMP-mediated signaling, and innate immunity. HM450 analysis showed a significantly greater number of hypermethylated genes in baseline tumors compared to primary OC samples in the Cancer Genome Atlas (TCGA) and demethylation (decreased beta-values relative to baseline) of a large number of loci (381 gene promoters) after SGI-110 treatment. IPA analysis of baseline tumor transcriptome and methylome demonstrated significant enrichment in pathways associated with cancer, stem cells, inflammation and the immune system. Conclusions: These data suggest that SGI-110 induces reactivation of immune responses in OC. Correlations between methylation changes and expression profiles are being explored. Clinical trial information: NCT01696032.
Development of a tailored, computerized, breast cancer risk assessment and decision support tool: What do clinicians want?
Authors: Ian M. Collins, Louise A. Keogh, Emma Steel, Bruce Mann, Jon Emery, Marie Pirotta, Jane Moreton, Phyllis Butow, Alison Trainer, Antonis C. Antoniou, Jack M. Cuzick, John L. Hopper, Kelly-Anne Phillips
Journal: Journal of Clinical Oncology (2013)

e20660 Background: End user input into the design of decision support tools is critical to enhance integration and future routine use in clinical practice. As part of the development of an evidence-based, tailored, computerized breast cancer (BC) risk assessment and management tool, we examined clinicians’ requirements. Methods: Australian breast surgeons (BSs) and primary care clinicians (PCCs) were recruited through local professional networks. Facilitated focus group discussions about current practice of assessing and managing BC risk and perceptions of the proposed tool were audiotaped transcribed and managed using QSR NVivo. A coding framework was developed based on the transcripts, data were coded and each code further analyzed to identify key themes. Results: Four focus groups, involving 12 BSs, 17 PCCs (12 doctors, 5 practice nurses) were conducted. 55 % were male, mean age 45yrs (range 25-67), mean of 14yrs in practice (range1-25+). Clinicians identified difficulties assessing and managing BC risk and lack of available tools to standardise their current inconsistent approach to risk assessment and management. Most felt confident identifying high risk women, but found differentiating women at population risk from those at moderately increased risk more difficult. They felt a tool would help them reassure anxious low to moderate risk women and avoid unnecessary onward referral or investigations and better identify and refer or manage high risk women. Desirable features in a tool included: evidence-based, accessible (web-based), visual, simple data entry process, displays absolute risk (rather than relative) and mutable risk and risk reduction estimates in multiple formats (words, pictographs, graphs) to improve comprehension, printable summary sheets. Clinicians felt that women could input risk factors before the clinic visit but that joint consumer and clinician data entry was preferable and women should only receive a risk estimate with a clinician present. Conclusions: Development of tools for BC risk assessment and management should address these clearly identified needs of end users in order to optimise translation of current and future knowledge into clinical practice.
Increased sensitivity to ZD1839 in chemoresistant tumor cells is associated with enhanced EGF-mediated signaling and ZD1839-induced Akt inactivation
Authors: Tiziana Servidei, Anna Riccardi, Cristiano Ferlini, Daniela Meco, Gabriella Cusano, Riccardo Riccardi
Journal: Cancer Research (2006)

3791   Aberrant signaling by EGFR and/or HER2 tyrosine kinases correlates with more aggressive disease, chemoresistance, and a poor prognosis. The EGFR inhibitor ZD1839 (IRESSA, gefitinib) has shown efficacy in non small-cell lung cancer patients previously treated with multiple cytotoxic agents. To address whether pretreated tumors may become more sensitive to ZD1839 because of enhanced dependence on the EGFR pathway, we compared ZD1839 antiproliferative effects in matched chemosensitive and cisplatin-selected, chemoresistant cell lines. In short term assays, the chemoresistant neuroblastoma cells SK-N-DZ/Pt were as responsive to ZD1839 as their parental cells, whereas a 2-fold increase in growth-inhibition was observed in the chemoresistant human ovarian carcinoma cells A2780/Pt and glioma cells U87/Pt, with A2780/Pt being more sensitive than U87/Pt (IC 50  2.7±1.3 vs 12.6±2.2 μM). A 10-day exposure to 1 μM ZD1839 resulted in 20% and 93% growth inhibition in A2780 and A2780/Pt, respectively. Sensitization to ZD1839 in the chemoresistant cells correlated with higher basal HER2 expression, and enhanced and/or prolonged EGFR and HER2 activation upon EGF stimulation. No change in EGFR level was observed. ZD1839 prevented EGF-induced EGFR and HER2 phosphorylation in both chemosensitive and chemoresistant cells. However, it completely abrogated phospho-Akt only in the resistant cells. In 10% FCS-containing medium, ZD1839 decreased phospho-Akt in both chemoresistant, but not chemosensitive, cell lines. Blockade of Akt pathway by the PI3K inhibitor LY294002 resulted in a dose-dependent growth inhibition similar in each pair of cell lines, suggesting that the reconnection of EGFR and Akt pathway might be responsible for sensitization of cells to ZD1839. In A2780/Pt, ZD1839-induced Akt inactivation was associated with upregulation of p27 and correlated with a G 0 /G 1  arrest at the IC 50 . No cell cycle perturbation was observed at equitoxic concentrations in the other cell lines. The combination of ZD1839 and two second-line drugs used in ovarian carcinoma (doxorubicin and topotecan) exerted a more marked synergistic effect in A2780/Pt than A2780. We suggest that chemoresistance in some tumor cells is associated with increased expression of HER2, and enhanced and/or prolonged activation of EGF-dependent signaling, likely through stabilization of HER2-containing heterodimers. Increased dependence on the EGF signaling might sensitize chemoresistant cells to ZD1839 antiproliferative effects and explain the increased synergism we observed. ZD1839 may be worth investigation as second- or third-line treatment in ovarian carcinoma and glioma pretreated patients. Supported by  Fondazione per l’Oncologia Pediatrica, Roma.  ZD1839 is a trademark of the AstraZeneca group of companies.