tbuckley/cabot-search huggingface dataset:
P01.078 Glioma surgery in the elderly, a retrospective population based registry study
Authors: D Löfgren, M Olivecrona
Journal: Neuro-Oncology (2018)

There is a trend in brain tumor treatments over time to treat patients at a higher age and to perform more advanced and radical surgery. Despite this little is known about the perioperative morbidity and mortality after intracranial tumor surgery, especially regarding the elderly. The Swedish brain tumor registry has collected data since 1999 with good coverage and is considered population based. Among the parameters registered are perioperative complications such as postoperative hematoma and thromboembolism as well as newly diagnosed epilepsy, new focal neurologic deficit and date of death. Data from the registry has been collected and analyzed in this retrospective population based study. This study includes patients in the registry at age 65 or older, with high grade glioma (GBM, astrocytoma grIII), low grade glioma (astrocytoma grI-II, oligodendroglioma grII-III and gangliogliomas) registered from 1999 to 2015. Formation of diagnose groups are in conjunction with suggestions from the Swedish National Brain Tumor Trialist Group. From this data we have excluded patients that have not undergone surgery, where surgery (or not) cannot be determined and where data on complications is unavailable. Only the national regions with a high enough coverage are included. The material contains 1467 evaluable patients. High grade gliomas were 1277 (male 59%, female 41%), median age at surgery 71 (range 65 to 86), women not older (72 VS 71; NS). 17,5% (male 16,4%, female 20,0%; NS) had WHO/ECOG-PS >2. Perioperative mortality was 7,8% (male 9,2%, female 5,9%; p=0,03), associated with WHO/ECOG-PS >2 (p<0,0001). 15,7% (male 17,3%, female 13,5%; NS) had perioperative complications. The most common complication was worsening of neurologic function (7,6%, male 8,4%, female 6,5%; NS) and most patients (10,8%, male 12,8%, female 8,0%; NS) had one recorded complication. The mortality and morbidity remains consistent regardless of year of surgery. Low grade gliomas were 190 (male 55% VS female 45%), median age 70 (65 to 83), men not significantly older (71 VS 69; NS). 16,8% (male 15,7%, female 19,5%; NS) had WHO/ECOG-PS >2. Perioperative mortality was 5,3% (male 6,7%, female 3,5%; NS). 20,0% (male 21%, female 18,8%; NS) had perioperative complications. As with high grade gliomas the most common complication was worsening of neurologic function (13,7%, male 15,2%, female 11,8%; NS) and the mortality and morbidity remains without significant changes regardless of year of surgery. In this material we can conclude that the perioperative mortality as well as morbidity is higher than in published younger patient materials for gliomas. We cannot see an increase in perioperative mortality or morbidity with higher age within the material but this could be from lack of power and we hope to be able to get a clearer view in a later comparison with the younger patients in the registry.
The effects of delayed imatinib mesylate treatment on outcome in patients with GIST.
Authors: Amina Kurtovic Kozaric, Amina Kugic, Azra Kurtovic, Semir Beslija, Timur Ceric, Anes Pasic, Semir Vranic, Mirza Kozaric, Dijana Kopric, Ermina Iljazovic, Jelena Todorovic Baruscia, Nermina Ibisevic, Sabira Kurtovic
Journal: Journal of Clinical Oncology (2016)

e22518 Background: Cancer patients in developing and low income countries have limited access to target therapies. Many patients with gastrointestinal stromal tumors (GIST) have had to wait for extended period of time to receive imatinib mesylate (0-67 months), the standard treatment for patients with advanced/metastatic disease. Some patients never received the target therapy. We set to evaluate if delayed therapy had deleterious effects on patient outcome. Methods: We examined the relationship between delayed imatinib therapy and treatment outcome for 145 patients with GIST in period from June 2005 to December 2015 treated in three university clinical centers in Bosnia and Herzegovina. Since 58% of patients waited > 1 month for therapy, we stratified them into following groups: immediate therapy (range 0-5 months wait; median 0.5 month, n = 63), > 6 month wait (median wait 9 months, n = 17), never received imatinib (median wait 21 months, n = 25) and imatinib not indicated (low recurrence risk, n = 40). Results: At 60 months, the Kaplan-Meier estimated rate of survival was 7% for patients who never received the required therapy, 39% for immediate treatment (0-5 months), and 45% for patients who waited > 6 months (p < 0.001). There was no difference in OS in patients who waited > 6 months compared to those who received immediate treatment in a 10 year follow-up period. There was a significant difference in OS of patients who received less than one year of imatinib therapy (median 8 months) compared to patients who received more than one year of therapy (median 36.5 months) (p < 0.01). At 36 months, 35% of patients who received less than one year of therapy survived compared to 69% of patients who received more than 1 year of therapy. Since patients received delayed imatinib therapy, we found that delayed treatment had no statistically significant effect on the overall survival of patients who received imatinib for < 1 year or > 1 year of therapy. Conclusions: Even though patients in developing countries have had to wait for imatinib treatment, we found no deleterious effects on patient outcomes. The length of imatinib treatment correlated positively with better overall survival but did not significantly improve the outcome of patients with delayed therapy.
California law requires doctors to disclose serious misconduct probation to patients
Authors: Owen Dyer
Journal: BMJ (2018)

A new California law, the first of its kind in the United States, requires doctors to tell new patients if the state medical board has placed them on probation for activity involving patient harm.

Activities that must be reported under the Patient’s Right to Know Act include sexual misconduct, drug misuse that has harmed or could harm patients, a criminal conviction involving harm to patients, and inappropriate prescribing.

Doctors already had to notify employers …
Abstract 17149: Aspirin and the Risk of Cardiovascular Events in Atherosclerosis Patients With and Without Prior Ischemic Events
Authors: Anthony A Bavry, Islam Y Elgendy, Ahmed N Mahmoud, Yedid Elbez, Emmanuel Sorbets, Ph G Steg, Deepak L Bhatt
Journal: Circulation (2016)

Introduction: Aspirin is recommended after an acute ischemic event for prevention of future cardiovascular events; however, the benefit among those with stable atherosclerosis without a prior ischemic event is poorly defined. Hypothesis: In patients with stable atherosclerosis and no prior ischemic event, aspirin might not be associated with a reduction in ischemic events. Methods: This is an observational analysis of patients from the Reduction of Atherothrombosis for Continued Health (REACH) registry. Patients were divided into those with a prior ischemic event (i.e., unstable angina, acute myocardial infarction, transient ischemic attack, or acute ischemic stroke; n=21,724) and those with stable atherosclerosis, but no prior ischemic event (i.e., stable angina with documented coronary artery disease, history of coronary revascularization, ≥ 1 carotid plaque, asymptomatic carotid stenosis ≥70%, carotid revascularization, ankle brachial index < 0.9, or lower extremity revascularization or amputation; n=1...
Establishing Surrogate Kidney End Points for Lupus Nephritis Clinical Trials: Development and Validation of a Novel Approach to Predict Future Kidney Outcomes
Authors: Meggan Mackay, Maria Dall'Era, Joanna Fishbein, Kenneth Kalunian, Martin Lesser, Jorge Sanchez‐Guerrero, Deborah M. Levy, Earl Silverman, Michelle Petri, Cristina Arriens, Edmund J. Lewis, Stephen M. Korbet, Fabrizio Conti, Vladimir Tesar, Zdenka Hruskova, Eduardo F. Borba, Eloisa Bonfa, Tak Mao Chan, Manish Rathi, K. L. Gupta, Vivekanand Jha, Sarfaraz Hasni, Melissa R. West, Neil Solomons, Frederic A. Houssiau, Juanita Romero‐Diaz, Juan Mejia‐Vilet, Brad H. Rovin
Journal: Arthritis & Rheumatology (2018)

End points currently used in lupus nephritis (LN) clinical trials lack uniformity and questionably reflect long-term kidney survival. This study was undertaken to identify short-term end points that predict long-term kidney outcomes for use in clinical trials.
NCI9782: A phase 1 study of talazoparib in combination with carboplatin and paclitaxel in patients with advanced solid tumors.
Authors: Anita Ahmed Turk, Ticiana Leal, Nancy Chan, Robert Wesolowski, Kristen Renee Spencer, Jyoti Malhotra, Joshua Michael Lang, Douglas G. McNeel, Ruth O'Regan, Janice M. Mehnert, Jens C. Eickhoff, Glenn Liu, Kari Braun Wisinski
Journal: Journal of Clinical Oncology (2019)

e14640 Background: Poly(ADP-ribose) polymerase (PARP) enzymes are involved in DNA repair and activated by DNA strand breaks. DNA damage from carboplatin is associated with activation of PARP. Preclinical data indicate that PARP inhibition and trapping potentiates the anti-tumor effect of platinum chemotherapy. Talazoparib (T) is an oral, selective PARP inhibitor. This phase I study combines T with carboplatin (C) and paclitaxel (P). Methods: Two dosing schedules are being investigated. C is administered on day 1 and P on days 1, 8, and 15 of a 21-day cycle. T (100-1000mcg) is dosed once daily for days 1-7 (schedule A) or days 1-3 (schedule B). Dose escalation is by 3+3 design. Patients (pts) must have tumor type that is expected to respond to C + P or have BRCA germline or somatic mutation and adequate organ function. After 4-6 cycles of combination therapy, pts may continue the combination, change to C and intermittent T without P or change to T alone. Each schedule will have a 6 pt dose expansion at the MTD. The dose level (DL) 1 for schedule B is the previously reported MTD from schedule A (T 250mcg with C AUC 6 + P 80mg/m 2 ). Results: Schedule B results are reported: 15 pts (median age 56 yrs [range 43-76]) have been enrolled. Primary malignancies include colorectal (4), pancreas (4), prostate (2), urothelial (2), and other (3). Dose was initiated at Schedule A MTD. DL2 (T 350mcg with C AUC 6 + P 80mg/m 2 ) exceeded the MTD with 2 of 6 pts experiencing hematologic dose limiting toxicities (DLTs). DL1 is the confirmed schedule B MTD. Dose expansion to 6 pts is ongoing. Of the 11 pts with measurable disease, 3 (27%) had PR and 5 (45%) had SD. Pts were on study a median of 10 weeks (range 5-36+). Most common grade 3/4 AEs include leukopenia (53%), neutropenia (47%), and anemia (47%). One grade 5 AE of intracranial hemorrhage occurred, possibly related to therapy in the setting of grade 3 thrombocytopenia and concern for CNS disease. Conclusions: The schedule B MTD and RP2D is T 250 mcg with C AUC 6 and P 80mg/m 2 . Data from the full dose expansion will be presented. This combination was tolerated with prolonged responses seen at lower dose T in combination with C+P. Clinical trial information: NCT02317874.
Lymphoma-associated mortality in the German HIV-lymphoma cohort study.
Authors: Marcus Hentrich, Christoph Wyen, Daniel Gillor, Markus Mueller, Albrecht Stoehr, Alexander Schultze, Bjoern Jensen, Jan-Christian Wasmuth, Timo Wolf, Jan M. Siehl, Mark Oette, Ninon Taylor, Manfred Hensel, Gerd Fätkenheuer, Philipp Schommers, Christian Hoffmann
Journal: Journal of Clinical Oncology (2016)

7550 Background: Since the introduction of combination antiretroviral therapy (ART) the outcome of HIV-associated lymphoma has significantly improved. However, aggressive lymphomas remain the most frequent AIDS-defining event leading to death. We aimed to analyse lymphoma-related mortality in the German HIV-Lymphoma Cohort Study. Methods: This prospective multicenter cohort study includes adult HIV- 1 infected patients with biopsy or cytologically proven HIV-related lymphoma diagnosed at 33 participating centers in Germany and Austria since January 2005. Data on HIV-infection and lymphoma characteristics, treatments and outcomes recorded until December 2014 were analyzed. Pts with T-cell lymphomas, indolent lymphomas and primary central nervous system lymphomas were excluded from the present analysis. Results: Of 499 pts (463 males, 36 females) 394 had aggressive NHL and 105 HL. At the time of lymphoma diagnosis the median age was 44.7 years (range, 22–74.7) and the median CD4-cell count was 210/μl (0–1586). 344 of 499 pts (69%) were diagnosed with advanced stage (III/IV) disease. 214 pts (43%) were ART-naïve, 175 pts (35%) had a viral load below the detection limit of < 50 HIV RNA copies/ml at lymphoma diagnosis while on ART, and 110 pts (22%) had a viral load > 50 copies/ml while on ART or while discontinuing ART. After a median follow-up of 1.8 years 25 of 105 HL (24%) and 122 of 394 NHL pts (31%) have died with an overall death rate of 30% (147/499). 84 of 147 pts (57%) died of relapsed/refractory lymphoma, 75 of 122 pts with NHL (62%) and 9 of 25 pts with HL (36%). In 30 of 147 pts (20%) the cause of death were infections during or shortly after primary chemotherapy (7/25 pts with HL [28%] and 23/122 of pts with NHL [19%]). CD4-cell count was 164/μl in pts who died of infections compared to 293/μl in pts alive (P< 0.001). Further causes of death were secondary malignancies (n = 6; 4%), AIDS-defining events other than NHL (n = 6; 4%) including 4 cases of progressive multifocal leukoencephalopathy, and miscellaneous (n = 21; 14%). Conclusions: HIV-related lymphomas mainly occur in ART-naïve or insufficiently treated patients. The major cause of death is relapsed/refractory lymphoma followed by infections during or shortly after primary chemotherapy.
Abstract 17348: Clinical Associations and Treatment Strategy of Iron Deficiency in the Daily Care of Heart Failure
Authors: Niels Grote Beverborg, Wouter C Meijers, Peter van der Meer, Rudolf A de Boer
Journal: Circulation (2016)

Introduction: Iron deficiency (ID) is a prevalent co-morbidity in heart failure (HF) and iron supplementation has been reported to reduce HF symptoms and rehospitalisations. We evaluated the clinic...
Identification of potential oncogenic LncRNA RP11-474D1.3 in colorectal cancer.
Authors: Jialin Yang, Meihua Chen, Jie Wang, Jin Yi Lang, Ming Fan, Li Pan, Jichuan Wang
Journal: Journal of Clinical Oncology (2018)

e15611 Background: Colorectal cancer (CRC) is the most common type of gastrointestinal cancer and is the third leading cause of cancer patient’s death worldwide. Long noncoding RNAs (lncRNAs) are a novel class of RNA molecules defined as transcripts longer than 200 nucleotides that lack protein coding potential. Evidence is growing that lncRNAs are important regulatory molecules involved in various cellular processes and many lncRNAs are deregulated in cancer and some of them can be important drivers of malignant transformation. Methods: In this study, we identified differentially expressed lncRNAs between CRC and adjacent normal tissues based on two TCGA database (GEPIA and circlncRNAnet). CRC specific-expressed lncRNAs were selected for further analysis. With the lncRNA database TANRIC, The clinical importance and correlated genes of candidate lncRNAs were analyzed. Then the GO and KEGG Pathway enrichment analysis were carried as well as the functional analysis of lncRNA correlated genes. Results: Over 6000 differentially expressed lncRNAs between CRC and adjacent normal tissues were obtained, and 72 lncRNAs (FC > = 2, Log2 (TPM+1) > 1, p < 0.05) was selected for further analysis. RP11-474D1.3, one of these lncRNAs, was only expressed in CRC, and RP11-474D1.3 is up-regulated in MSS-CRC and MSI-L-CRC, but down-regulated in MSI-H-CRC; is up-regulated in CIN and INVASIVE, but down-regulated in MSI/CIMP; which suggest that RP11-474D1.3 maybe correlated with CRC worse prognosis. Moreover, based on the correlation analysis, we found that RP11-474D1.3 has high coefficient with many oncogenes (CTNNB1, NODAL, PLCG1, RNF43, SGK2 and ZNRF3) and oncogenes pathway, especially EMT related signaling pathways, such as WNT and TGF-β signaling pathway. And also has high coefficient with SCNA for genes in TGF-β signaling pathway. GO and KEGG pathway enrichment analysis confirmed that SCNA related genes mainly involved in TGF-β signaling pathway. Conclusions: These findings suggest that RP11-474D1.3 is a potential oncogenic lncRNA in colorectal cancer, which can be used as a therapeutic target for colorectal cancer. It could provide novel insights to understand the mechanisms and functions of lncRNAs in colorectal cancers.
miR-221 to modulate tumor growth in vivo and as a regulator of TGF.
Authors: Martin Spahn, Eugenio Zoni, Markus Krebs, Philip Herreiner, Charis Kalogirou, Lanpeng Chen, Ewa Snaar-Jagalska, George N. Thalmann, Marianna Kruithof-de Julio, Hubertus Riedmiller, Burkhard Kneitz
Journal: Journal of Clinical Oncology (2017)

e23008 Background: Despite the advances in cancer therapy, when Prostate Cancer (PCa) progress to castration resistant phase, patients develop incurable bone metastases. Understanding the processes that regulate homing and survival of metastatic cancer cells in the bone is crucial for the identification of new therapies. TGF-β signaling plays a major role in bone remodeling and according to the “vicious cycle hypothesis” is a master regulator of maintenance of prostate cancer cells in lytic bone lesions. microRNAs (miRs) are a class of small non-coding RNAs that regulates many biological process. miR-221 expression has been previously associated with prostate cancer progression. Here we studied the effect of miR-221 on TGF-β signaling and the impact of miR-221 on tumor growth in vivo Methods: miR-221 was overexpressed in PC3 and RWPE-1 cells and PMEPA was monitored by RT-qPCR and western blot. Expression of miR-221 in PC3 and RWPE-1 cells was assessed by RT-qPCR. Luciferase assay was used to investigate the interaction between miR-221 and PMEPA1. For zebrafish experiment, fluorescently labelled PC-3M-Pro4 cells overexpressing miR-221 were injected in the Duct of Cuvier (DC) of zebrafish embryos. Results: miR-221 overexpression resulted in decreased PMEPA1 mRNA and protein in PC-3 cells. Luciferase reporter assay indicated that miR-221 can directly interact with PMEPA1 3’ UTR. We show an enhancement of the proliferative effect of TGF-β in PC-3 cells, following miR-221 overexpression. In conclusion, we observed increased Smad2 activation upon TGF-β treatment in miR-221 overexpressing PC-3 cells. Inoculation of PC-3M-Pro4 cells overexpressing miR-221 in the DC of zebrafish embryos resulted reduced tumor burden compared to control. Finally, we observed inverse correlation between miR-221 and PMEPA1 expression in normal vs. tumor tissue collected from PCa patients. Conclusions: Our results indicate that miR-221 is a regulator of TGF-β signaling via modulation of PMEPA1 and miR-221 overexpression can reduce tumor growth in vivo.
Relationship between time to trastuzumab initiation and overall survival among young commercially insured women with metastatic breast cancer.
Authors: Christine Leopold, Fang Zhang, Anita K. Wagner, Christine Y. Lu, Craig Earle, Dennis Ross-Degnan, James Frank Wharam
Journal: Journal of Clinical Oncology (2016)

e18013 Background: Our ongoing research suggests a secular trend of improved OS for younger women diagnosed with mbc in 2005-2008 versus 2000-2004. Trastuzumab is the first line treatment for women with HER2 positive mbc and has known beneficial effects on OS. We examined whether improved survival in 2005-2008 was related to shorter time to trastuzumab initiation. Methods: We examined administrative data (Optum; Eden Prairie, MN) of members insured through a large national US health insurer. Women with mbc who received trastuzumab were drawn from an open cohort of members aged 25 to 64 years enrolled between November 1, 2000, and December 31, 2008. Outcomes were time from incident mbc diagnosis to trastuzumab initiation and to all-cause death, with up to 3 years of follow-up. We stratified outcomes by race, age at diagnosis, US region, urban/rural residence, socio-economic status, Adjusted Clinical Groups (ACG) morbidity score, and time of diagnosis. We constructed Kaplan-Meier survival plots and analyzed OS using multivariate Cox proportional hazard models. Results: We included 652 women with mbc who received trastuzumab (74% white, 2% black, 24% other). Nearly all women initiated trastuzumab in the first year after metastatic diagnosis and 141 (22%) died within 3 years. We detected earlier trastuzumab initiation among women aged 40-49 versus 50-64 years (adjusted hazard ratio, HR: 1.21; 95% confidence interval, CI: 1.01-1.44) and later initiation among women diagnosed between 2000-2004 versus 2005-2008 (HR: 0.68, 95% CI: 0.57-0.82, respectively). Time to death was accelerated among women with high versus low morbidity (HR: 1.98; 95% CI: 1.03-3.80) and women who were diagnosed between 2000-2004 versus 2005-2008 (HR: 2.63; 95% CI: 1.44-4.82). Conclusions: Younger women diagnosed with mbc between 2005-2008 had shorter time to trastuzumab initiation and improved OS at 3 years versus women diagnosed between 2000-2004. Future studies should further explore the relationship between early trastuzumab initiation and survival among younger women with mbc, in light of clinical, patient, and other care characteristics not available in administrative data.
Changes in the detection and recognition thresholds of three basic tastes in patients with non-small cell lung cancer receiving cisplatin- and paclitaxel-based chemotherapy and its association with nutritional and quality of life parameters.
Authors: Jenny Turcott, Martha de la Torre, Eva Juarez-Hernandez, Karla Sanchez-Lara, Julissa Luvian-Morales, Oscar Arrieta
Journal: Journal of Clinical Oncology (2016)

e21658 Background: We evaluated the effects of cisplatin and paclitaxel on taste acuity and its association to nutritional and health-related quality of life (HRQL) in patients with advanced non-small cell lung cancer (NSCLC). Methods: Forty chemotherapy (CT) naïve patients were assessed at baseline and after two cycles of paclitaxel and cisplatin. The taste evaluation was performed using a rinsing technique to identify detection and recognition thresholds (DT and RT) of bitter, sweet and umami tastes. The protocol was registered at clinicaltrials.gov (NCT01540045). Results: At baseline, 37.5% of the patients reported dysgeusia. After CT, the patients showed lower medians DT (p = 0.017) and RT (p = 0.028) for umami taste. These decreases were associated with clinical neuropathy, worse HRQL and a tendency of increased appetite loss. Additionally, CT did not significantly reduce the median DT to sweet (p = 0.09), which is associated with lower intakes of protein (p = 0.015), animal protein (p = 0.010), fats (p = 0.004) and iron (p = 0.047). CT decreased the median DT to bitter (p = 0.035); however, this decrease was not associated with nutritional parameters or with HRQL. Conclusions: Sensitivity to taste increased with paclitaxel and cisplatin CT, making foods more unpleasant, and is associated with neuropathy, worse HRQL and reduced nutrient intake in advanced NSCLC patients. Food having unpleasant taste Food being tasteless Bitter taste in mouth yes no p yes no p yes no p Weight (kg) 43.3± 4.8 62.6± 13 0.007 58.05± 12 61.9± 14 0.389 54.5± 1.4 64.7± 13.8 0.01 BMI (kg/m2) 20.5± 2.9 24.4± 3.8 0.03 23.4± 4.0 24.3± 3.9 0.515 22.8± 4.1 24.7± 3.6 0.129 Anorexia* 22.5± 7.5 32.8± 5.7 0.002 28.3± 7.3 33.9± 5.2 0.007 29.5± 7.22 33.4± 5.7 0.065 HRQL global^ 33.33 (16.66- 62.5) 75 (50- 83.33) 0.028 54.1 (31.2- 83.3) 75 (50- 83.3) 0.04 50 (33.33- 75) 75 (50- 91.6) 0.01 Neuropathyᶧ 33.33 (0-100) 33.33 (0- 58.33) 0.651 33.33 (0-100) 33.33 (0- 33.33) 0.07 33.33 (33.33- 66.67) 16.66 (0- 41.66) 0.06 FAACT Questionnaire ᶧCTCAE criteria ^ Median(Interquartile range), U de Mann Whitney