tbuckley/cabot-search huggingface dataset:
Understanding why some people with stage III colon cancer do not receive adjuvant chemotherapy.
Authors: Valerie Heong, Hui-Li Wong, Jeanne Tie, Michael Jefford, Kathryn Maree Field, Suzanne Kosmider, Jayesh Desai, Matthew Croxford, Ian Jones, Peter Gibbs
Journal: Journal of Clinical Oncology (2013)

e14608 Background: Adjuvant chemotherapy is a standard of care for patients (pts) with stage III colon cancer. While many retrospective series have concluded that treatment is underutilised in routine clinical practice, particularly in older pts, reasons for this remain unexplored. Methods: Data was collected on all pts with stage III colon cancer attending four community hospitals in Australia between January 2003 and July 2012. Every patient was referred to a medical oncologist. For each case where adjuvant therapy was not delivered, reason(s) were prospectively documented by clinicians in a consensus database. Results: Data was collected on 875 pts. Median age 67 years (range 15 - 92). Overall, 147 (25.9%) did not receive adjuvant therapy. Comorbidity was the main reason for non-treatment in all age groups. Age alone was the reason for not recommending treatment in a small number of elderly pts (n=20, 20.4%). Risk of recurrence (N1 vs N2 disease) did not impact recommendations of clinicians (75% vs 76%) or pt acceptance (92% vs 93%). Pts with a lower socioeconomic status were less likely to be offered treatment; however this reflected greater comorbidity in these pts. Treatment acceptance was similar across all socioeconomic groups (data not shown). Conclusions: In routine clinical practice adjuvant chemotherapy should be recommended to, and can be safely delivered to a very high proportion of younger patients. Clinicians are comfortable recommending adjuvant chemotherapy to older pts, with co-morbidity the dominant reason that treatment was not recommended for pts &gt;65 years. The rate of pts declining treatment increased with age, and further study of the factors involved in treatment refusal should be pursued [Table: see text]
A prospective, multicenter, randomized clinical trial of <i>UGT1A1</i> promoter polymorphism for irinotecan dose escalation in metastatic colorectal cancer patients treated with bevacizumab plus FOLFIRI as the first-line setting (PURE FIST).
Authors: Jaw-Yuan Wang
Journal: Journal of Clinical Oncology (2017)

625 Background: The polymorphisms of genes encoding drug-metabolizing enzymes can play a crucial role in the increased susceptibility of patients to chemotherapy. This study is a prospective, multicenter, randomized clinical trial to compare the clinical outcomes and adverse events in metastatic colorectal cancer (mCRC) patients treated with bevacizumab plus 5-fluorouracil/leucovorin/irinotecan (FOLFIRI) with or without UGT1A1genotyping and irinotecan dose escalation as the first-line setting (NCT02256800). Methods: The enrolled patients were randomly assigned to one of two groups on the basis of receiving UGT1A1 genotyping or not. The study group receives a biweekly FOLFIRI plus bevacizumab, with irinotecan dose escalation based on UGT1A1 genotyping; whereas the control group receives the conventional biweekly FOLFIRI plus bevacizumab without UGT1A1 genotyping. The primary endpoint was the overall response rate (ORR), and the second endpoint was progression-free survival (PFS), overall survival (OS) and toxicities between the two groups. Results: BetweenAugust 2013 and May 2016, eighty-eight mCRC patients were enrolled, including 45 patients in the study group and 43 patients in the control group. With a median follow up time of 12.5 months (range, 5-30), the ORR was 71.4% vs. 44.2% ( P = 0.011). The PFS was 14.04 ± 1.44 vs. 9.08 ± 0.58 months in study group and control group ( P = 0.195), OS was 19.12 ± 1.24 vs. 14.16 ± 1.04 months ( P = 0.098), and ≥ Gr. III anemia was 2.2% vs. 23.3% ( P= 0.002) in study group and control group, respectively. However, there were no significant differences in ≥ Gr. III leukopenia or diarrhea even though the 1.36 fold relative dose intensity (RDI) in the study group. Conclusions: In the current study, patients with mCRC undergoing UGT1A1 genotyping may receive escalated doses of irinotecan for a potentially more favorable clinical response and outcome, in addition to acceptable toxicities. Such a personalized medicine based on genotyping may be feasible for potentially clinical practice. Clinical trial information: NCT02256800.
Gemcitabine, paclitaxel, and doxorubicin as first-line therapy for patients with advanced urothelial carcinoma and renal insufficiency: A phase II study.
Authors: Lance C. Pagliaro, Mark F. Munsell, Deborah Harris, Robert L. Carolla, Arlene O. Siefker-Radtke
Journal: Journal of Clinical Oncology (2013)

4528 Background: The role of cisplatin-based chemotherapy for the treatment of locally advanced or metastatic urothelial carcinoma is well established. For patients (pts) who cannot receive cisplatin owing to renal insufficiency, substitution with carboplatin was associated with inferior response rate and overall survival (OS). To address this unmet need, we conducted a phase II study of gemcitabine (Gem), paclitaxel (Tax), and doxorubicin (Adria) in this group. Methods: The primary endpoint was overall response rate (ORR); secondary endpoints were toxicity, OS, and the safety and efficacy of pegfilgrastim 6 mg (G-CSF) given immediately after chemotherapy on Day 1. A Simon 2-stage design was chosen to detect ORR of 40% and to reject ORR of 25%. Eligible pts had metastatic or unresectable urothelial carcinoma, no prior chemotherapy, performance status ≤ 2, glomerular filtration &lt; 60 ml/min, and no need for dialysis; all gave informed consent. Brain metastases were excluded, as were clinically significant heart disease, peripheral neuropathy, and liver or bone marrow dysfunction. Treatment consisted of 900 mg/m 2 Gem (fixed rate of 10 mg/m 2 /min), 135 mg/m 2 Tax, and 40 mg/m 2 Adria administered with same-day GCSF every 14 d to a maximum of 9 cycles. Tumors were evaluated after every 3 cycles. Results: Forty pts were enrolled January 2008 through November 2011, and 39 could be assessed for response. Median age was 72 (range, 51–89) and 11 pts (28.2%) were women. There were 7 complete and 15 partial responses, for an ORR of 56.4% (95% CI 39.6-72.2). Notable grade 3 and 4 nonhematologic toxicities in the first 2 cycles were dyspnea and mucositis (1 pt each). There were no treatment-related deaths and no toxicity attributed to same-day G-CSF. Median OS was 14.4 mo with median follow-up of 12.6 mo for all pts, 15.6 mo for 10 who were alive. Conclusions: Gem-Tax-Adria is effective as first-line treatment for metastatic or locally advanced urothelial carcinoma, and it can safely be given to pts with renal insufficiency. Same-day G-CSF also appears to be safe and effective in this setting. Phase III study is warranted. Clinical trial information: NCT00478361.
Multiplatform molecular profiling of 2,400 pancreatic adenocarcinomas to identify targets for therapeutic intent.
Authors: Sherri Z. Millis, David Arguello, Maeve Aine Lowery, Eileen Mary O'Reilly
Journal: Journal of Clinical Oncology (2014)

4136 Background: Pancreas adenocarcinoma (PC) is a challenging disease with overall single digit 5-year survivorship. Few validated biomarkers exist for directing treatment in PC. Only one targeted...
Assessment of liver dysfunction in hepatocellular carcinoma (HCC): An international collaborative study.
Authors: Philip James Johnson, Sarah Berhane, Chiaki Kagebayashi, Shinji Satomura, Mabel Joey Teng, Anna Skowronska, Trevor F. Cox, Daniel H. Palmer, Winnie Yeo, Frankie Mo, Paul B. S. Lai, Mercedes Iñarrairaegui, Stephen Lam Chan, Bruno Sangro, Toshifumi Tada, Hidenori Toyoda, Takashi Kumada
Journal: Journal of Clinical Oncology (2014)

4094 Background: Survival in HCC depends on tumour-related features and liver dysfunction, the latter currently characterised by Child-Pugh score (C-P.S). Since some constituents of C-P.S are interrelated and subjective and the tumour may contribute to liver dysfunction, C-P may not be ideal for HCC assessment. Aim:To assess how much discrimination in liver dysfunction is afforded by the C-P.S and develop a simpler evidence-based approach. Methods: 5,269 patients were recruited from 4 specialist HCC centres: Japan (n=2,599, predominantly HCV), Hong Kong (1 112, predominantly HBV), Spain (n=834, predominantly HCV and alcohol) and the UK (n=724, multiple aetiologies). Patients undergoing liver transplantation were excluded. A model explaining variation in survival according to liver function was developed in 1,313 Japanese subjects and then validated in the remaining 3,716 cases. Results: Overall the classification in C-P.S was A, 69%, B, 25% and C 6%; figures were similar in all ethnic groups. After allowing for tumour size the variation in survival could be accounted for by just serum bilirubin and albumin; these were incorporated into a simple Cox regression model (the ‘ALBIS’ score) which allows classification into 3 risk groups. Statistical analysis showed that the degree of discrimination was as good as, or better than, C-P.S. Irrespective of country, or tumour stage the ALBIS score showed clear survival differences among C-P. S ‘A’ patients (Table). Conclusions: The
Gastric cancer with synchronous hepatic metastases: A multicentric Italian survey.
Authors: Guido Alberto Massimo Tiberio, Vittorio D. Ferrari, Silvia Ministrini, Chiara Cipollari, Luigina Graziosi, Paolo Morgagni, Daniele Marrelli, Alberto Marchet, Luca Baiocchi, Arianna Coniglio, Annibale Donini, Franco Roviello, Giovanni De Manzoni
Journal: Journal of Clinical Oncology (2013)

e15148 Background: The treatment of these patients is controversial and influenced by personal, often passive, attitude. Knowledge of variables affecting outcome may promote clinical pragmatism.We surveyed the clinical approach to the subset of patients presenting with synchronous hepatic metastases as sole metastatic site at diagnosis of gastric cancer, focusing on the results achieved by different treatments and investigated the prognostic factors of major clinical relevance. Methods: Retrospective multi-centre chart review evaluating 210 patients admitted in surgical units. We studied how survival from surgery or diagnosis was influenced by different patient-related, gastric cancer-related, metastases-related and treatment-related candidate prognostic factors. Results: Seventeen patients received supportive care, 44 minor palliative surgery, 98 palliative gastrectomy in 16 cases associated to R+ hepatectomy, while 51 patients received both curative gastrectomy and hepatic resection/s (R0). Adjuvant chemotherapy was administered to 41 patients. Therapeutic approach was selected on the basis of stage of disease, patients’ general conditions and surgeon’s attitude toward the disease, without any pre-set common criteria, in absence of institutional protocols or guidelines. Surgical mortality was 4.6%, surgical morbidity 17.6%. Survival was independently influenced by the degree of hepatic involvement (p= 0.036) but therapeutic approach to the metastases was the principal prognostic variable (p&lt;0.001): 1, 3, and 5 years survival rates were 48.3%, 11.8% and 7.1%, respectively, for patients submitted to curative surgery (R0), 16%, 4.3% and 2.1% after palliative (R+) gastrectomy, 6,8%, 0% and 0% after minor palliative surgery and 0%,0% and 0% with supportive care. Chemotherapy displayed a clear prognostic role (p&lt; 0.001) with clear benefit for those receiving adjuvant treatment. Conclusions: Our data show that an aggressive multimodal approach offers the best survival chances, the best results being offered by the association of radical (R0) surgery and adjuvant chemotherapy. Upon these bases we conclude that this aggressive management must be pursued whenever possible.
Intraportal infusion of liver-mesenchymal stem cells in rats lead to transient interruption of the hepatic blood flow: intravital microscopy and anapathological analysis
Authors: L. Coppin, P. Van Der Smissen, P.-E. Dollet, C. Lombard, F. Smets, I. Scheers, E. Sokal, X. Stephenne
Journal: Journal of Hepatology (2017)
Impact of income in stage IV prostate cancer.
Authors: Aabra Ahmed, Timothy Dean Malouff, Ryan W Walters, Sydney Marsh, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2017)

244 Background: There is growing evidence of the impact of socioeconomic status on survival in cancer patients. To our knowledge, this is the largest study to examine demographics and the association between income and survival in patients with stage IV prostate cancer. Methods: Using the National Cancer Database, 50,639 patients diagnosed with stage IV prostate cancer between 2004-2011 were identified. Income was evaluated using the median income of the patient’s zip code. Between-income survival differences were estimated by the Kaplan-Meier method and associated log-rank tests; Tukey-Kramer adjusted p &lt; .05 indicated statistical significance. Results: Survival differences were indicated between all income quartiles. Median survival was highest for patients in zip codes with a median income ≥ $63,000 and lowest for patients in zip codes with an income &lt; $38,000 (46.1 months vs. 31.6 months, respectively; p &lt; .001). As such, 41% of patients in zip codes with a median income ≥ $63,000 were alive five years following diagnosis, compared to 31% of patients in zip codes with median income &lt; $38,000. Additionally, compared to patients in zip codes in which the median income was &lt; $38,000, patients in zip codes with a median income ≥ $63,000 had a higher rate of zero comorbidities (81% vs. 76%), a greater percentage of patients living in an area where &gt;93% people have a high school degree (58% vs 1%), and a lower proportion of African Americans (8% vs 41%). Conclusions: Compared to patients with a median income &lt; $38,000, patients in zip codes with a median income &gt; $63,000 had a median survival nearly 15 months longer, had 10% more patients alive after 5 years, and had fewer comorbidities. [Table: see text]
Examining the role of psychological factors in the relationship between sleep problems and suicide
Authors: D. Littlewood, S.D. Kyle, D. Pratt, S. Peters, P. Gooding
Journal: Clinical Psychology Review (2017)

We sought to conduct the first systematic review of empirical evidence investigating the role of psychological factors in the relationship between sleep problems and suicidal thoughts and behaviours. Twelve studies were identified which examined psychological factors grouped into four categories of cognitive appraisals, psychosocial factors, emotion regulation strategies, and risk behaviours. Although there was substantial heterogeneity across studies with respect to measurement, sampling, and analysis, preliminary evidence indicated that negative cognitive appraisals, perceived social isolation, and unhelpful emotion regulation strategies may contribute to the association between sleep problems and suicidal thoughts and behaviours. Given that findings in this area are currently restricted to studies with cross-sectional designs, the directionality of the interrelationships between these psychological factors, sleep problems and suicidality, remains unclear. We integrate the findings of our review with contemporary psychological models of suicidal behaviour to develop a clear research agenda. Identified pathways should now be tested with longitudinal and experimental designs. In addition, a more thorough investigation of the complexities of sleep, psychological factors, and suicidal thoughts and behaviours is crucial for the development of targeted psychological interventions.
A phase 1 study of AMG 900, an orally administered pan-aurora kinase inhibitor, in adult patients with acute myeloid leukemia
Authors: Hagop M. Kantarjian, Michael W. Schuster, Nitin Jain, Anjali Advani, Elias Jabbour, Erick Gamelin, Erik Rasmussen, Gloria Juan, Abraham Anderson, Vincent F. Chow, Gregory Friberg, Florian D. Vogl, Mikkael A. Sekeres
Journal: American Journal of Hematology (2017)

Abstract Aurora kinases are involved in the pathophysiology of several cancers including acute myeloid leukemia (AML). In this phase 1 study, we investigated the safety and efficacy of AMG 900, an orally administered, highly potent, selective, small‐molecule inhibitor of both Aurora kinase A and B, in patients with AML . Patients with pathologically documented AML who either declined standard treatments or had relapsed from or were refractory to previous therapies were enrolled. Two every‐2‐week dose‐escalation schedules using a modified 3 + 3 + 3 design were evaluated AMG 900 given daily for 4 days with 10 days off (4/10 schedule), and AMG 900 given daily for 7 days with 7 days off (7/7 schedule). Thirty‐five patients were enrolled at 9 different dose levels: 22 patients on the 4/10 schedule (doses from 15 to 100 mg daily), and 13 patients on the 7/7 schedule (doses from 30 to 50 mg daily). Both schedules were tolerated; nausea (31%), diarrhea (29%), febrile neutropenia (29%), and fatigue (23%) were the most common treatment‐related adverse events. Three patients (9%) achieved complete response with incomplete count recovery. Patients with higher baseline expression of a set of specific pathway‐related genes ( BIRC5 , AURKA , TTK , CDC2 , and CCNB1 ) were more likely to respond in an exploratory biomarker analysis. AMG 900 was tolerated in a general AML population, and pathway‐specific biomarkers identified a potential target population. Future research efforts will be directed toward further exploration of biomarkers of response and combination of AMG 900 with other anticancer agents.
GEINO-11: A prospective multicenter, open label, phase II pilot clinical trial to evaluate safety and efficacy of PF-299804 (dacomitinib), a pan-HER irreversible inhibitor, in patients with recurrent glioblastoma with EGFR amplification or presence of EGFRvIII mutation.
Authors: Juan Manuel Sepúlveda, M. Angeles Vaz, Aurelio Hernandez-Lain, Miquel Gil, Pilar Sanhez, Ramos Ana, Oscar Gallego, Gaspar Reynes, Maria Victoria Bolós, Raquel Luque, M. Quindos, Maria Martinez Garcia, Pedro Pérez Segura, Manuel Benavides, Carmen Balañá
Journal: Journal of Clinical Oncology (2014)

TPS2110 Background: Recurrent GBM has a very poor prognosis and there is an unmet need for new treatment options. EGFR is an attractive therapeutic target for GBM, due to high rates of amplifcation and the growing evidence linking the activation of the EGFR and tumor proliferation, survival, angiogenesis and invasion. Amplification of EGFR is reported in approximately 50% of GBM and approximately 50% of these cases are associated with deletion of the extracellular ligand binding domain, the constitutively active mutant protein EGFRvIII. Dacomitinib (DA) is a second-generation, oral, irreversible, pan-HER tyrosine kinase inhibitor active in erlotinib and gefitinib-resistant nonclinical models of lung cancer. Methods: This multicenter, 2-stage, open-label, phase II trial aims to assess the efficacy and safety of DA in pts with recurrent GBM with EGFR gene amplification with or without EGFRvIII mutation. DA will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end. Pts at first recurrence will be enrolled onto 1 of 2 cohorts that will be recruited and analysed independently. Cohort A will include patients who have EGFR gene amplification and EGFRvIII mutations. Cohort B will include patients who have EGFR gene amplification but no EGFRvIII mutations. The primary endpoint is progression-free survival at six months (PFS6m) according to RANO criteria and each cohort will follow a Simon´s 2-stage optimal design (P0 = 15% PFS6m; P1=35% PFS6m; a, b error = 0.1, 0.1). For each cohort, 17 patients will be accrued in the stage 1. Additional 15 patients per cohort will be enrolled in stage 2 if the predetermined PFS6m of at least 3 patients is met in that cohort in stage 1. Secondary endpoints include safety, response rate, OS, duration of response and changes in steroid use. In December 2011 the study protocol received institutional review board approval and in April 2012 the trial commenced enrolment in 12 Spanish institutions members of GEINO.
Sensing of Bacterial Cyclic Dinucleotides by the Oxidoreductase RECON Promotes NF-κB Activation and Shapes a Proinflammatory Antibacterial State
Authors: Adelle P. McFarland, Shukun Luo, Fariha Ahmed-Qadri, Meghan Zuck, Elizabeth F. Thayer, Young Ah Goo, Kevin Hybiske, Liang Tong, Joshua J. Woodward
Journal: Immunity (2017)
Pancreatic polypeptide as a biomarker for pancreatic neuroendocrine tumors.
Authors: Angela Tatiana Alistar, Erin L. Moshier, Michelle Kim, Richard Warner, Randall F. Holcombe
Journal: Journal of Clinical Oncology (2012)

e21109 Background: Pancreatic neuroendocrine tumors (PNETs) represent tumors that secrete numerous proteins that could be used as biomarkers. We present a retrospective analysis of patients with PNETs who have had Pancreatic Polypeptide (PP) testing in an attempt to better define PP producing tumors as an entity and the role of PP as a biomarker. To our knowledge, this is the first single center comprehensive review of Pancreatic Polypeptide producing tumors. Methods: A retrospective study of patients with PNETs seen at Mount Sinai from 1980 to 2011. All patients that have had PP concentrations measured at least once were evaluated. Data relating to diagnosis, pathology, surgery, liver directed therapies, chemotherapy and survival outcome were noted. 71 patients with PNETs fulfilled the inclusion criteria. The 71 patients formed 4 subgroups. The 4 subgroups were evaluated and compared for survival: all 71 PP tested patients, 30 patients with PP producing tumors, 8 patients with PPomas, 22 patients with PP producing tumors that were non PP-omas and 41 patients with PP non-producing tumors Results: We identified a trend towards better survival for PNETs patients with PP producing tumors vs. non- PP producing tumors (p=0.19). There was no correlation between survival and a diagnosis of PPoma in relation to other PP producing tumors (p= 0.59) or non-PP producing tumors (p=0.58). Conclusions: Pancreatic Polypeptide is a biomarker that is worth prospective investigation and a standardized assay. Our analysis investigating Pancreatic Polypeptide as a prognostic and or predictive biomarker reveals a trend towards showing these characteristics. Using a standardized test and investigating this biomarker prospectively could lead to the validation of Pancreatic Polypeptide as a biomarker.
The Ubiquitin Binding Protein TAX1BP1 Mediates Autophagosome Induction and the Metabolic Transition of Activated T Cells
Authors: Michael I. Whang, Rita M. Tavares, Daniel I. Benjamin, Michael G. Kattah, Rommel Advincula, Daniel K. Nomura, Jayanta Debnath, Barbara A. Malynn, Averil Ma
Journal: Immunity (2017)