tbuckley/cabot-search huggingface dataset:
A randomized phase II study comparing trabectedin (T) and best supportive care (BSC) in patients (pts) with translocation-related sarcomas (TRS).
Authors: Shunji Takahashi, Nobuhito Araki, Hideshi Sugiura, Takafumi Ueda, Mitsuru Takahashi, Hideo Morioka, Tsukasa Yonemoto, Hiroaki Hiraga, Toru Hiruma, Toshiyuki Kunisada, Akihiko Matsumine, Akira Kawai
Journal: Journal of Clinical Oncology (2014)

10524 Background: T binds to the minor groove of DNA and blocks DNA repair machinery following the inhibition of cell cycle and proliferation. In addition, T inhibits interactions of transcription factors including TRS-related transcription factors with the DNA in a competitive manner. This is the first time that the progression-free survival (PFS) of T is compared with BSC as a second or later line treatment in pts with TRS in a multi-center, open, phase II trial. Methods: Main inclusion criteria were the following: histologically proven TRS; unresponsiveness or intolerability to standard chemotherapy regimens (pts with extraskeletal Ewing sarcoma (EES), myxoid liposarcoma (ML), or synovial sarcoma (SS) should have received anthracyclines); at least 1 measurable baseline lesion (RECIST v1.1); confirmed disease progression (per RECIST) compared with the image assessment performed during the previous 6 months(m). Pts stratified by subtype (alveolar rhabdomyosarcoma, ESS, ML, SS vs other TRS) were randomly assigned 1:1 to T (1.2 mg/m2 in 24h continuous infusion every 21 days) or BSC. The primary endpoint was PFS by independent review assessment (IR). This study had 80% power for a one-sided 5% significance level test given a hazard ratio (HR) (T relative to BSC) of 0.50. Sample size goal was 74 pts with an event goal of 52 events by IR requiring a total of 60 events by investigator’s assessment (IA). PFS and overall survival (OS) were analyzed using a stratified log-rank test. Results: Data cut-off date was 8th February 2014. Total of 76 pts were enrolled. Number of pts for efficacy analysis was 73 (T: 37 pts and BSC: 36 pts). Median PFS (90% confidence interval(CI))for T and BSC were 5.6 m (4.2-7.5) and 0.9 m (0.9-1.0), respectively (p<0.0001; HR=0.07, 90% CI: 0.03-0.14). Median OS (95% CI) for T and BSC were not reached (NR) (12.8-NR) and 8.0 m (7.0-NR), respectively (p=0.025; HR=0.38, 95% CI: 0.16-0.91) under permission of crossover. Conclusions: T is an active drug in TRS pts pretreated by available chemotherapies with a significant increase in PFS and OS. Clinical trial information: JapicCTI-121850.
Encouraging Clinical Outcomes for Lymphoma Patients Participating in Early Phase Clinical Trials in the Current Era: A Single Institution and a Global Perspective
Authors: Jenny O'Nions, Anna Cowley, Hakim-Moulay Dehbi, Dima El-Sharkawi, Shirley D'Sa, Kirit M. Ardeshna, Rakesh Popat, William Townsend
Journal: Blood (2018)
Media Coverage, Forecasted Posttraumatic Stress Symptoms, and Psychological Responses Before and After an Approaching Hurricane
Authors: Rebecca R. Thompson, E. Alison Holman, Roxane Cohen Silver
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Exposure to disaster-related media coverage is associated with negative mental health outcomes. However, risk factors that render individuals vulnerable to this exposure are unknown. Hurricane-associated media exposure was expected to explain the association between forecasted posttraumatic stress (PTS) and adjustment after the hurricane. <h3>Objective</h3> To examine forecasted PTS responses and media coverage as risk factors for negative mental health outcomes in the context of media coverage of an approaching disaster (Hurricane Irma). <h3>Design, Setting, and Participants</h3> In a representative probability community sample of 1637 adults from Florida, respondents completed 2 online surveys: the first during the 60 hours before Hurricane Irma’s landfall (wave 1; September 8-11, 2017) and the second approximately 1 month later (wave 2; October 12-29, 2017). Poststratification weights were applied to facilitate population-based inferences. Data were analyzed from October 19 through 31, 2018. <h3>Main Outcomes and Measures</h3> Posttraumatic stress responses, psychological distress, functional impairment, and worry about future events. <h3>Results</h3> The wave 1 survey included 1637 participants (57.0% response rate); 1478 participants were retained at the wave 2 follow-up (90.3% retention) (weighted proportion of women, 62.2%; mean [SD] age, 59.1 [15.2] years). The final weighted sample closely approximated US Census benchmarks for the state of Florida. Data analyses using structural equation modeling revealed that exposure to media coverage of the hurricane (β = 0.21; 95% CI, 0.11-0.31;<i>P</i> &lt; .001) and forecasted PTS (β = 0.44; 95% CI, 0.35-0.52;<i>P</i> &lt; .001) were significantly associated with adjustment after the hurricane. In addition, a significant indirect path from forecasted PTS to adjustment after the storm occurred through exposure to hurricane-related media coverage (β = 0.07; 95% CI, 0.05-0.08;<i>P</i> &lt; .001). Covariates included demographics, mental health diagnoses before the storm, perceived evacuation zone status, and degree of hurricane exposure. <h3>Conclusions and Relevance</h3> Results of this study provide a more thorough understanding of how psychological factors before hurricanes are associated with adjustment after hurricanes via media consumption. The findings may also demonstrate the importance of considering prestorm psychological factors when assessing poststorm outcomes, with implications for the media and public health efforts.
The risk factors for severe adverse events of chemotherapy for advanced non-small cell lung cancer.
Authors: Kentaro Suina, Takehito Shukuya, Ryo Koyama, Tetsuhiko Asao, Yuichiro Honma, Motoyasu Kato, Keiko Muraki, Rina Shibayama, Naoko Shimada, Shoko Sakuraba, Kazuhisa Takahashi
Journal: Journal of Clinical Oncology (2014)

e19129 Background: Serious adverse events, which cause immediate hospitalization, prolonged hospitalization, permanent damage, or death, are clinically defined as severe adverse events (SAEs). Few studies have reported on the risk factors for SAEs for non-small cell lung cancer. Methods: The medical records of the patients treated with pemetrexed/cisplatin (PC), bevacizumab plus carboplatin/paclitaxel (BVCP), docetaxel monotherapy (DTX), pemetrexed monotherapy (PEM) at Juntendo University Hospital between January 2010 and March 2012 were retrospectively reviewed. A multivariate analysis was performed to identify the independent risk factors among the following factors; sex, age, PS, lines of previous chemotherapy, coexistence of interstitial pneumonia (IP) before chemotherapy, smoking history, and chemotherapeutic regimen. Results: A total of 252 patients received chemotherapy (male/ female, 164/ 88; median age (range), 66 (36-92) years; stage III/ stage IV/ postoperative recurrence, 53/ 145/ 54; adenocarcinoma/ squamous cell carcinoma/ NOS, 211/ 24/ 17; PC/ BVCP/ PEM/ DTX, 50/ 51/ 67/ 84). Of these, 30 (11.9%) patients experienced SAEs. The causes of SAEs were appetite loss in 10 patients, febrile neutropenia (FN) in 8 patients, occurrence or exacerbation of IP in 6 patients, infection in 3, renal failure in 1, pneumothorax in 1, and gastrointestinal hemorrhage in 1, respectively. 2, 1 and 1 patients died of drug-induced IP, FN and severe infection, respectively. Multivariate analysis revealed that IP before chemotherapy (OR=4.99; p=0.0011) and chemotherapeutic regimen (p=0.0019) were significantly associated with SAEs. Conclusions: IP associated with lung cancer and chemotherapeutic regimen is the risk factors in the prediction of SAEs in clinical practice. Total SAEs % P value Total n=252 n=30 11.9% Sex N.S* male 164 26 15.9% female 88 4 4.5% Regimen 0.0019* PC 50 9 18.0% BVCP 51 8 15.7% DTX 84 11 13.1% PEM 67 2 3.0% Age(year) N.S* ≥75 51 7 13.7% <75 201 23 11.4% PS N.S* 3- 22 4 18.2% 1 and 2 230 26 11.3% line N.S* 1/2 line 194 25 12.9% 3~line 58 5 8.6% B.I. N.S* ≥600 117 20 17.1% <600 135 10 7.4% IP 0.0011* + 52 14 26.9% − 200 16 8.0% * multivariate analysis
Promoter hypermethylation of GPX3 correlates with chemoresistance and is a strong predictor for poor prognosis in head and neck cancer
Authors: Zhongmin Guo, Zhaorong Chen, Zejia Yang, Lisa Schumaker, Kevin Cullen
Journal: Cancer Research (2007)

1629  Cisplatin and its analogues are widely used in the treatment of a broad range of solid tumors including head and neck cancer. However, intrinsic and acquired resistance of cancer cells to this group of drugs is the major limitation in clinical application of cisplatin-based chemotherapy. Despite intensive efforts for more than a quarter century, the mechanisms by which cancer cells develop or acquire resistance to the drugs are still unclear, and there is no way currently to predict the drug resistance status of individual tumors. To elucidate the role of epigenetic changes in cisplatin-based resistance and identify novel methylation markers for predicting chemoresistance and patient prognosis in head and neck cancer, we performed genome-wide scanning of hypermethylated genes on a cisplatin sensitive and resistant isogenic head and neck cell model. We identified a series of candidate genes whose promoter hypermethylation may be associated with head and neck chemoresistance and could be potential predictive markers for chemoresistance and prognosis of head and neck cancer patients. One of the strong candidate targets from the list is glutathione peroxidase 3 (GPX3), an enzyme involved in metabolism of reactive oxygen species (ROS). Loss of GPX3 expression was observed in 4 out of 8 head and neck cancer cell lines in consistence with their cisplatin resistance. Demethylating treatment of the cell lines negative for GPX3 expression significantly restored its expression, implicating the role of promoter hypermethylation in regulation of GPX3 expression in head and neck cancer. Bisulfite DNA sequencing showed that the 5’ flanking promoter region of GPX3 was heavily hypermethylated in all cell lines with expression-silencing of the gene.  Using realtime Methylation Specific PCR (MSP), GPX3 methylation was quantitatively assessed in tumors from 46 patients in which chemotherapy response and survival were known. In the 46 tested cases, 15 out of 23 non-responding cases (65%) showed GPX3 methylation while 4 of 23 complete and partial response cases (17%) contained low levels of GPX3 methylation (Relative Risk 3.343, two sided Fisher exact test, P=0.002). Kaplan-Meier survival analysis showed a relative risk of death of 1.942 in patients with GPX3 methylation. Our findings suggest that GPX3 methylation and expression silencing may play an important role in the development of cisplatin resistance and are strong candidate predictors for chemoresistance and prognosis of head and neck cancer patients.
Cost-Effectiveness of Alirocumab
Authors: Dhruv S. Kazi, Joanne Penko, Pamela G. Coxson, David Guzman, Pengxiao C. Wei, Kirsten Bibbins-Domingo
Journal: Annals of Internal Medicine (2018)

Background: The ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial included participants with a recent acute coronary syndrome. Compared with participants receiving statins alone, those receiving a statin plus alirocumab had lower rates of a composite outcome including myocardial infarction (MI), stroke, and death. Objective: To determine the cost-effectiveness of alirocumab in these circumstances. Design: Decision analysis using the Cardiovascular Disease Policy Model. Data Sources: Data sources representative of the United States combined with data from the ODYSSEY Outcomes trial. Target Population: U.S. adults with a recent first MI and a baseline low-density lipoprotein cholesterol level of 1.81 mmol/L (70 mg/dL) or greater. Time Horizon: Lifetime. Perspective: U.S. health system. Intervention: Alirocumab or ezetimibe added to statin therapy. Outcome Measures: Incremental cost-effectiveness ratio in 2018 U.S. dollars per quality-adjusted life-year (QALY) gained. Results of Base-Case Analysis: Compared with a statin alone, the addition of ezetimibe cost $81 000 (95% uncertainty interval [UI], $51 000 to $215 000) per QALY. Compared with a statin alone, the addition of alirocumab cost $308 000 (UI, $197 000 to $678 000) per QALY. Compared with the combination of statin and ezetimibe, replacing ezetimibe with alirocumab cost $997 000 (UI, $254 000 to dominated) per QALY. Results of Sensitivity Analysis: The price of alirocumab would have to decrease from its original cost of $14 560 to $1974 annually to be cost-effective relative to ezetimibe. Limitation: Effectiveness estimates were based on a single randomized trial with a median follow-up of 2.8 years and should not be extrapolated to patients with stable coronary heart disease. Conclusion: The price of alirocumab would have to be reduced considerably to be cost-effective. Because substantial reductions already have occurred, we believe that timely, independent cost-effectiveness analyses can inform clinical and policy discussions of new drugs as they enter the market. Primary Funding Source: University of California, San Francisco, and Institute for Clinical and Economic Review.
The impact of prothrombotic mutations, PSGL-1 VNTR polymorphism, tissue factor, and soluble P-selectin on venous thromboembolism in cancer patients with adenocarcinoma.
Authors: Mustafa Bozkurt, Kerem Okutur, Kubra Aydin, Esat Namal, Akin Ozturk, Kezban Nur Planci, Veysel Sabri Hancer, Coskun Tecimer, Reyhan Diz Kucukkaya, Gokhan Demir
Journal: Journal of Clinical Oncology (2014)

e22049 Background: Inherited factors such as factor V Leiden (FVL), prothrombin G20210A (PT) mutations and psgl-1 vntr polymorphism (PSGL-1 VNTR) are shown to be related with venous thromboembolism (VTE). Factors assumed acquired with carcinogenesis like tissue factor (TF) and soluble p-selectin (sP-selectin) are also shown to be related with venous thromboembolism (VTE).We evaluated inherited factors and factors assumed acquired with carcinogenesis such as tissue factor (TF) and soluble p-selectin (sP-selectin) in cancer patients with adenocarcinoma. Methods: This is a retrospective observational study held with patients followed by Istanbul Bilim University Department of Medical Oncology between October 2007 and March 2012. Of 1,838 patients 63 (3.4%) with adenocarcinoma histology, experienced VTE. The diagnosis of VTE was confirmed by radiology and the patients were treated accordingly. We defined VTE by sites as deep venous thrombosis (DVT), pulmonary embolism (PE), other vascular territories (subclavian, jugular and pelvic veins), and central venous catheter related (CVC-R). Blood drawn at any time, during active treatment or follow-up, at any stage with VTE (n=63) and without VTE (n=38) as a control grup.This study is approved by Istanbul Bilim University Ethics Commitee. Results: Results were shown at table. sP-selectin levels were higher at patients with thrombosis (p=0.036). PSGL-1 VNTR polymorfism was related with site of thrombosis. AB and AC types were more frequent in patients with CVC-R and other vein thrombosis (p=0.02). Besides heterozygosity (AB+AC) relationship was more prominent in this group (p=0.007). Tissue factor was higher at pancreatic carcinoma than the others. (800 (16-800) vs 99 (13-800); p=0.047). Conclusions: Although this is a retrospective observational study held with blood samples delivered randomly,we confirmed the data regarding the levels of TF and sP-selectin were higher in thrombosis. It is shown for the first time that a relationship between PSGL-1 VNTR polymorfism and sites of VTE, of which is unknown with clinical relevance.
Polymorphism <i>BCL2 </i>c(-717)a and prognosis in diffuse large B-cell lymphoma patients.
Authors: Angelo Borsarelli Carvalho Brito, Cristiane Oliveira, Marcia Torresan Delamain, Carmino Antonio De Souza, Jose Vassallo, Carmen Silvia Passos Lima
Journal: Journal of Clinical Oncology (2014)

8573 Background: High expression of the anti-apoptotic BCL-2 protein was previously described as a predictor of poor prognosis in diffuse large B cell lymphoma (DLBCL). The BCL2 gene is polymorphic in humans and the single BCL2 C(-717)A nucleotide polymorphism (SNP) has its variant AA genotype associated with increased Bcl2 expression. The aim of this study was to evaluate whether the BCL2 C(-717)A SNP influence the outcome of DLBCL patients. Methods: Our prospective analysis included 122 consecutive DLBCL patients at diagnosis seen at the Hematology and Hemotherapy Center, between December 2007 and October 2013. Median age of patients was 57 years old (range: 17-89), 63 patients (51.6%) were females, 89 patients (72.9%) had B symptoms, 21 patients (17.2%) had bone marrow involvement (BMI), and 73 (59.8%) patients had advanced tumors (Ann Arbor stage III or IV). Genomic DNA from peripheral blood of all individuals was analysed by polymerase chain reaction followed by enzymatic digestion for discrimination of distinct BCL-2 C (-717)A genotypes. Patients received 6 cycles of R-CHOP as treatment. Overall survival (OS) time was calculated using the Kaplan-Meier estimate probabilities, and differences between survival curves were analysed by the log-rank test. OS was calculated from date of diagnosis until the date of death or last follow-up. Results: The median of observation of patients enrolled in the study was 23 months (range: 1-68). On univariate analysis, B symptoms (68% versus 86%, P=0.04), BMI (52% versus 77%, P=0.01), stage IV (59% versus 82% P=0.01), and BCL2 -717 CA+AA genotype (68% versus 88%, P=0.04) were predictive of worse outcome of DLBCL patients at 24 months of follow up. Conclusions: The data present, for the first time, preliminary evidence that inherited abnormality in intrinsic pathway of apoptosis, related to the SNP BCL2 C(-717)A, influence the outcome of DLBCL patients treated with conventional chemotherapy regimen.
Abstract 19214: Inverse Relationships of Cardio-Ankle Vascular Index and Body Mass Index in Children
Authors: Ranjit Philip
Journal: Circulation (2013)

Objective: The epidemic of childhood obesity, with early onset of adult-type diseases like diabetes and hypertension, is creating a national health crisis. Cardio-ankle vascular index (CAVI), a non-invasive measure of vascular function, reflects the stiffness of arteries independently of changes in blood pressure (BP). There are currently no CAVI scores available for children. We hypothesized that CAVI, by providing an objective measure of vascular health, may help identify children at increased risk for cardiovascular disease. Methods: Study subjects were 292 Non- Hispanic White, Non- Hispanic Black, or Hispanic children 10-18 years old, normal weight (BMI85th percentile for age). CAVI values were measured using the VaSera VS-1500N device. Results: CAVI was measured in 292 children, with 133 males and 159 females, including 89 Black, 100 White and 103 Hispanic children. After controlling for age, sex, and body weight, normal weight Black males had a higher CAVI score in comparison to Hispanic males and White males (5.53±0.15 vs. 5.13±0.15 vs. 5.02±0.15, p=0.04). In univariate analyses, mean BP showed a positive correlation with BMI (r=0.4, p&lt;0.001). Interestingly, BMI had a negative effect on the CAVI score (r= -0.335, p&lt;0.0001). In multivariate analysis, raw BMI and average CAVI scores were significant predictors of the other (R2=0.34, p&lt;0.001, R2=0.21,p&lt;0.001 respectively). No correlation occurred between the CAVI and resting BP values, confirming that CAVI scores were independent of concurrent BP values. Conclusions: Significant differences in vascular function exist among ethnic groups. Obese children had lower CAVI scores, suggestive of possible vascular adaptation to obesity in early life. CAVI may be useful measure in long-term intervention studies using diet and exercise, and may be a cost-effective, non-invasive method for examining vascular health in children.
Ivosidenib or Enasidenib Combined with Induction and Consolidation Chemotherapy in Patients with Newly Diagnosed AML with an IDH1 or IDH2 Mutation Is Safe, Effective, and Leads to MRD-Negative Complete Remissions
Authors: Eytan M. Stein, Courtney D. DiNardo, Amir T. Fathi, Alice S. Mims, Keith W. Pratz, Michael R. Savona, Anthony S. Stein, Richard M. Stone, Eric S. Winer, Christopher S. Seet, Hartmut Döhner, Daniel A Pollyea, James K McCloskey, Olatoyosi Odenike, Bob Lowenberg, Gert J. Ossenkoppele, Prapti A. Patel, Mikhail Roshal, Frederik Lersch, Salah Nabhan, Sung Choe, Hongfang Wang, Lei Hua, Caroline Almon, Michael Cooper, Martin S. Tallman
Journal: Blood (2018)
Osteosarcoma of the head and neck (OHN): A multicenter case series of 79 adult patients in the Netherlands.
Authors: Eline Boon, Winette T.A. Van Der Graaf, Hans Gelderblom, Margot Et Tesselaar, Robert J.J. van Es, Sjoukje Oosting, Remco De Bree, Esther Van Meerten, Ann Hoeben, Uta E. Flucke, Judith V.M.G. Bovée, Carla M.L.- Van Herpen
Journal: Journal of Clinical Oncology (2014)

10542 Background: OHN is rare and behaves differently from osteosarcoma in the extremities. There is an ongoing debate about the value of (neo-) adjuvant chemotherapy in OHN. In this study we describe the general practice and outcome of patients (pts) treated for OHN in the Netherlands, with special attention to the efficacy of chemotherapy on overall survival (OS). Methods: A retrospective cohort study was conducted within the Dutch Head and Neck Society. All pts >16 years of age treated for OHN between 1993-2013 were included in this analysis. Review of pathology for tumors with uncertain grading was performed. Kaplan-Meier survival analysis and log rank testing were performed. Results: Seventy-nine pts with OHN were included, 42 (53%) female, median age 46 years (range 16-95). Twenty-five (32%) pts had a prior malignancy, 19 (24%) pts received previous radiotherapy to the head and neck region. Most common tumor location was the jaw, with 32 (40%) mandibular and 26 (33%) maxillary tumors. A total of 17 (22%) pts received (postoperative) radiotherapy. All 12 (15%) low grade OHN pts underwent a resection, without chemotherapy and had a 5 year OS of 90%. Fifty-six (71%) pts had a high grade OHN; 50/56 (89%) were operated and 25/50 (50%) received (neo-) adjuvant chemotherapy. In the 50 resected high grade OHN pts, 5 year OS was 73% versus 36% for pts treated with or without (neo-) adjuvant chemotherapy, respectively (p = 0.004). The 5 years local recurrence rate in high grade resected OHN pts was 15% versus 63% in pts treated with and without (neo-) adjuvant chemotherapy, respectively (p = 0.006), whereas the risk of distant metastases was not significantly different (13% versus 39%, respectively p = 0.08). The 5 year OS of the 56 high grade OHN was 30% versus 56% in pts with or without a prior malignancy, respectively (p = 0.08). Conclusions: Pts with high grade resected OHN have a better OS when treated with (neo-) adjuvant chemotherapy. Remarkably, local recurrence rate is significantly lower in resected OHN pts treated with (neo-) adjuvant chemotherapy, whereas no significant difference in distant metastases rate was shown.
Outcomes of Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma Included in Phase I Clinical Trials
Authors: Marion Brault, Maxime Annereau, Alina Danu, Julien Lazarovici, Claude Chahine, Andrea Varga, Capucine Baldini, Stéphane Champiat, Malik Berhoune, Christophe Massard, François Lemare, Vincent Ribrag, Jean-Marie Michot
Journal: Blood (2018)