tbuckley/cabot-search huggingface dataset:
Abstract 23077: The Effects Of Prolonged Anacetrapib Therapy On First And Subsequent Occlusive Vascular Events
Authors: Emily Sammons, Louise Bowman, Martin Landray
Journal: Circulation (2017)

Background: There is definitive evidence that lowering LDL-cholesterol with statins as monotherapy, or in combination with ezetimibe or PCSK9 inhibitors, prevents not only first but also subsequent major coronary events (i.e. coronary death, myocardial infarction or coronary revascularization). Consequently, prolonged treatment produces greater absolute reductions in morbidity, mortality and economic costs. Inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib lowers LDL-cholesterol levels, as well as substantially increasing HDL-cholesterol, but it is not yet known if it produces benefits on first and subsequent occlusive vascular events and deaths. Methods: The HPS3/TIMI55-REVEAL trial has assessed the effects of adding the CETP inhibitor anacetrapib to atorvastatin on vascular morbidity and mortality in 30,449 individuals who had a history of atherosclerotic vascular disease. Study treatment was continued for a median of 4.1 years. Information was recorded on first and subsequent cardiovascular events that occurred during the scheduled treatment period. Results: The main trial results are to be presented at the European Society of Cardiology Congress in August 2017. For the American Heart Association Congress, it is proposed to present more detailed results on the effects of anacetrapib on first and subsequent occlusive vascular events. Within this high-risk population of individuals with pre-existing vascular disease, 3443 (11%) had a first major coronary event and 1097 subsequent events were reported during the scheduled treatment period. Conclusions: Unblinded results of the cumulative effects of anacetrapib on first and subsequent rates of coronary and other occlusive vascular events will be available for presentation.
Food Intake Recruits Orosensory and Post-ingestive Dopaminergic Circuits to Affect Eating Desire in Humans
Authors: Sharmili Edwin Thanarajah, Heiko Backes, Alexandra G. DiFeliceantonio, Kerstin Albus, Anna Lena Cremer, Ruth Hanssen, Rachel N. Lippert, Oliver A. Cornely, Dana M. Small, Jens C. Brüning, Marc Tittgemeyer
Journal: Cell Metabolism (2018)
Safety and Efficacy of Combined Ruxolitinib and Thalidomide in Patients with Myelofibrosis: Initial Results of a Phase II Study
Authors: Raajit K. Rampal, Srdan Verstovsek, Sean M Devlin, Eytan M. Stein, Tapan M. Kadia, Michael J. Mauro, Naveen Pemmaraju, Kelsey Alvarez, Nicole Ard, Tawni Goodman, Kelly Marek, Prithviraj Bose
Journal: Blood (2018)
Pre and postradiation lymphopenia predicts survival in management of bone metastases.
Authors: Sara R. Alcorn, Sarah Saleemi, Powell Perng, Stuart A. Grossman, Omar Y. Mian, Todd R. McNutt, Russell K. Hales, Theodore L. DeWeese, Thomas J. Smith, Susannah G. Ellsworth
Journal: Journal of Clinical Oncology (2014)

9563 Background: Radiation-induced lymphopenia (RIL) has recently been identified as an adverse prognostic factor in select solid tumors, yet its prognostic value is unknown in the management of metastatic lesions. We examine the relationship between RIL and survival in patients receiving palliative radiation (RT) for bone metastases. Methods: Palliative bone RT plans were identified through medical records at a high-volume institution from 9/1/2007-7/15/2012. Patient and treatment characteristics were recorded, including lymphocyte count (LC) ≤6 weeks before RT and within 1-3 months after RT. Comparative statistics were performed using t-tests, ANOVA, and Kaplan-Meier analyses. Results: Of 573 palliative bone RT plans, 405 plans from 251 patients with complete baseline data were analyzed; 227 plans had complete post-RT data. At a median follow-up of 4.3 months, 9% of patients were living. Median age and KPS were 64 years (range 22-94) and 70 (range 30-100), respectively. RT sites were 51% spine, 20% pelvis, 19% extremity, and 10% other. Median RT dose was 30 Gy (range 2-48 Gy). Prior to RT, 13% and 46% of patients had LC<500 and LC<1000, respectively; on survival analyses, baseline LC <500 was associated with lower median survival as compared to LC≥500 (1.4 vs 5.6 mo.; p<0.001), as was baseline LC<1000 vs LC≥1000 (3.1 vs 6.7 mo.; p<0.001). Mean LC was significantly higher before RT (1270, SD=1247) than after RT (903, SD=867; paired samples t-test p<0.001.) Excluding baseline LC<500, median survival was lower for patients with LC<500 vs LC≥500 after RT (4 vs 11.1 mo.; p<0.001); post-RT LC<1000 did not predict survival. Whereas daily pre-RT steroid use was associated with higher percent change in LC after RT (t-test p=0.001), steroids at the time of post-RT labs and peri-RT chemotherapy did not significantly affect LC. Histology, RT site, RT to >4 vertebral bodies, and RT dose >30 Gy were also not associated with post-RT LC. Conclusions: Lymphopenia prior to and after RT appears to be a prognostic factor in the treatment of bone metastases, and significant RIL can occur irrespective of RT characteristics such as field and dose. These data suggest for careful consideration of hematologic status during patient selection for palliative RT.
A randomized phase III trial comparing triple weekly usage with weekly usage of paclitaxel in concurrent chemoradiotherapy for patients with locally advanced non-small cell lung cancer.
Authors: Guangying Zhu, Anhui Shi, Hongmei Lin, Yuhchyau Chen, Rong Yu, Jian-Cheng Li, Hang Li, Yingjie Wang, Tingyi Xia, Linchun Feng
Journal: Journal of Clinical Oncology (2014)

7545 Background: Optimum management of clinically locally advanced non-small cell lung cancer (LANSCLC) presents challenges because of the high local recurrence rate. NCCN guidelines recommend concurrent chemoradiotherapy (CCRT) as the standard therapy for LANSCLC. A phase III study was performed to compare triple weekly usage (group 1) with weekly usage (group 2) of paclitaxel in concurrent chemoradiotherapy for patients with locally advanced non-small cell lung cancer. Methods: It is a multi-center, randomised, controlled, phase III trail. After 2 to 4 cycles of induction chemotherapy, patients with LANSCLC were randomly assigned to two groups. In group 1, chemotherapy consisted of paclitaxel (15 mg/m2, 3times/week, 270 mg/m2 over six weeks). In group 2, chemotherapy consisted of paclitaxel (45 mg/m2, 1 time/week, 270 mg/m2over six weeks). Radiotherapy consisted of 60-70Gy (2Gy per fraction and 5 fractions per week). Results: From March 2006 to February 2013, 115 patients were enrolled into the study. Sixty-three patients were enrolled in group 1, among which 3 patient had radiation esophagitis of Grade 3, 3 patients developed leucopenia of Grade 3, 12 patients had radiation pneumonitis of Grade 3, and 1 patient had radiation pneumonitis of Grade 5 and died of respiratory failure. Fifty-two patients were enrolled in group 2, 5 patient had radiation esophagitis of Grade 3, 15 patients developed leucopenia of Grade 3 or 4, 6 patients had radiation pneumonitis of Grade 3, and 2 patients had radiation pneumonitis of Grade 5 and died of respiratory failure. The response rate for the group 1 was significantly higher (87.3%) than that of the group 2 (57.7%) (p value 0.023), and the median PFS in the two groups were 11.0ms and 7.4ms (p value =0.039). Conclusions: The study results showed that triple weekly usage is more safe and effective than weekly usage of paclitaxel with CCRT for patients with LANSCLC. Clinical trial information: ChiCTR-TRC-10000786.
Results of a Phase 1, Dose-Escalation Study of FF-10501-01 in Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML) or Hypomethylating Agent (HMA)-Resistant Myelodysplastic Syndrome (MDS)
Authors: Guillermo Garcia-Manero, Michael R. Kurman, Courtney D. DiNardo, Naveen Pemmaraju, Yesid Alvarado, Kiran Naqvi, Farhad Ravandi, Elias J. Jabbour, Ricardo Delumpa, Timothy Madden, Gary Maier, Hiroyuki Iwamura, Hagop M. Kantarjian
Journal: Blood (2018)
Focal bone marrow processes and early bone lesions in patients with multiple myeloma (MM) precursor diseases: A prospective study using molecular imaging.
Authors: Manisha Bhutani, Baris Turkbey, Esther Tan, Neha Korde, Mary Kwok, Elisabet E. Manasanch, Nishant Tageja, Sham Mailankody, Mark J. Roschewski, Marcia Mulquin, Elizabeth Lamping, Brendan M. Weiss, Esther Mena, Liza Lindenberg, Katherine R. Calvo, Irina Maric, Peter L. Choyke, Karen A. Kurdziel, Ola Landgren
Journal: Journal of Clinical Oncology (2014)

8587 Background: The incidence and impact ofbone marrow processes and/or early bone lesions in patients with MM precursor diseases is largely unknown. We prospectively compared the sensitivity of several imaging modalities among patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) and MM. Methods: Ninety-one patients were evaluated: Thirty (10 each with MGUS, SMM and MM) had skeletal survey, [18F]-FDG PET/CT, [18F]-NaF PET/CT, and lumbosacral dynamic contrast enhanced (DCE)-MRI. Sixty-one newly diagnosed patients (16 high risk SMM and 45 MM) had skeletal surveys and FDG PET/CT. Results: Among ten patients with MGUS, MRI found only one unifocal marrow process; all other evaluations were negative. Among 26 SMM patients who by definition had negative skeletal surveys, 11(42%) had abnormalities on FDG PET/CT including four with lytic bone lesions on CT, one with a biopsy-confirmed intramedullary lesion that was negative on both CT and NaF PET/CT and six with unifocal or diffuse marrow process; DCE-MRI was negative in those assessed. Among 55 MM patients, 35 (70%) and 47 (85%) had lytic lesions on skeletal survey and CT, respectively, with 15 and five having >7 sites on CT and skeletal survey, respectively. Marrow involvement was observed on FDG PET/CT in seven (31%), and on DCE-MRI in 6/9 (67%). NaF uptake was observed only in patients with lytic lesions on CT, and provided no additional information. The normal vertebral FDG or NaF SUVmean was not correlated with marrow plasmacytosis and did not increase from MGUS>SMM>MM. Conclusions: Using sensitive molecular imaging tools we detected bone and marrow changes not present on skeletal surveys in SMM patients, consistent with the concept of a disease continuum leading to MM. These results provide a framework to include molecular imaging in trials with SMM and MM patients with the hope of improving risk/prognosis categorization. Molecular image-guided biopsies will also allow longitudinal evaluation of bone marrow processes. By integrating modern imaging and molecular profiling, we may be able to develop more precise treatment strategies for precursors to myeloma. Clinical trial information: NCT01237054; NCT01402284; NCT01572480.
Comprehensive Immune Profiling from Peripheral Blood and Bone Marrow in Newly Diagnosed and Relapsed/Refractory Multiple Myeloma Patients Reflects Differences in Immune Subsets and Activation Status
Authors: Greg E. Pietz, Mark Tometsko, Wilbert B. Copeland, Elizabeth Whalen, Frank Schmitz, Ethan G. Thompson, Amit Agarwal, Teresa Foy, Lauren Buchholz, Vitalina Komashko, Justine Dell'Aringa, Brian A. Fox, Kathryn Newhall
Journal: Blood (2018)
Randomized phase II study of personalized peptide vaccination with cyclophosphamide pretreatment in refractory advanced biliary tract cancer patients.
Authors: Tetsuro Sasada, Shigeru Yutani, Satoko Matsueda, Takashi Shirahama, Akira Yamada, Kyogo Itoh
Journal: Journal of Clinical Oncology (2014)

3087 Background: We previously demonstrated the feasibility of personalized peptide vaccination (PPV), in which appropriate vaccine peptides are individually selected for each patient to boost anti-cancer immunity, in advanced biliary tract cancer (BTC) patients. This study was conducted to assess whether cyclophosphamide (CYP) pretreatment could improve the clinical efficacy of PPV in refractory advanced BTC patients. Methods: We conducted a randomized phase II study to examine the effect of CYP pretreatment (100 mg, daily for 7 days before each cycle of 6 vaccinations) on PPV for advanced BTC patients, who failed or progressed after standard chemotherapy regimens. For PPV treatment, a maximum of 4 peptides were selected from 31 candidate peptides based on the HLA class I types and antigen-specific humoral immune responses before vaccination, and subcutaneously administered (6 vaccinations, weekly; thereafter, by-weekly). The primary and secondary endpoints were to examine the immunological responses to vaccine antigens and overall survival (OS), respectively, after PPV with and without CYP pretreatment (PPV plus CYP and PPV alone, respectively). Results: Thirty-four BTC patients were randomly assigned; 16 and 18 patients were assigned to the PPV plus CYP and PPV alone groups, respectively. No severe adverse events were observed in the treated patients. There were no statistically significant differences between the two groups with regard to the numbers of patients, who showed increased peptide-specific CTL or IgG responses. However, CTL frequencies in the patients with positive CTL responses were significantly higher in the PPV plus CYP group, compared to those in the PPV alone group. OS in the PPV plus CYP group was significantly longer than that in the PPV alone group (P = 0.03 by Fleming-Harrington test). The median OS was 397 and 190 days in the PPV plus CYP and PPV alone groups, respectively. Conclusions: Pretreatment with CYP did not enhance antigen-specific immune responses, but might improve the prognosis after PPV in refractory advanced BTC patients. Further larger scale, randomized trials would be needed to confirm this encouraging result. Clinical trial information: 000006249.
Low-dose abiraterone (abi) with food in men with metastatic castration-resistant prostate cancer (mCRPC): The Princess Margaret Cancer Centre experience.
Authors: Raya Leibowitz-Amit, Eshetu G. Atenafu, Jo-An Seah, Arnoud J. Templeton, Francisco Emilio Vera-Badillo, Nimira S. Alimohamed, Jennifer J. Knox, Srikala S. Sridhar, Ian Tannock, Anthony M. Joshua
Journal: Journal of Clinical Oncology (2014)

5077 Background: Abiraterone (abi) prolongs survival in men with mCRPC [de Bono et al. NEJM 2011; 364:1995.]. Initial studies showed that abi plasma concentrations are higher when administered with a high-fat meal vs the fasting state, and similar maximal plasma drug concentrations and areas under the curve were reported after administration of 250 or 500 mg of abi in the fed-state (‘low dose’) as after 1000 mg in the fasting state (‘full dose’) [Attard. JCO 2008; 26:4563. Ryan. JCO 2010; 28:1481.]. Two phase III trials assessed full-dose abi [de Bono et al. NEJM 2011; 364:1995., Ryan. NEJM 2012; 368:138.], and this dose was approved for both pre- and post-chemotherapy. At the Princess Margaret (PM) Cancer Centre, low-dose abi in the fed-state is sometimes prescribed to men who otherwise cannot access the drug due to funding constraints, particularly in the pre-chemotherapy setting. Methods: All men treated with abi at PM until Mar-2013 were reviewed. Associations between dose (full vs. low) and PSA response rate (PSA-RR), progression free survival (PFS), and overall survival (OS) were assessed using chi-square and log rank tests, respectively. PSA-RR was defined as a confirmed PSA decrease ≥50%, PFS was from start of abi to PSA progression, clinical progression, drug cessation, or death, and OS from start of treatment to death. Results: 90 and 21 men were treated with full or low dose abi, respectively. PSA-RR was non-significantly lower in chemo-naive men treated with low doses compared to full doses (p=0.09), but there were no significant differences in PFS or OS for both the entire cohort and the chemo-naïve cohort (table). Conclusions: Administration of low dose abi after a high-fat meal is not associated with shorter PFS or OS despite a trend to lower PSA-RR. These results may be relevant in resource-limited settings and warrant further prospective clinical research. Dose N PSA-RR % (95% CI) P value median PFS, months (95% CI) P value Median OS, months (95% CI) P value All men Full 90 43 (32-54) 0.36 4.4 (2.8-5.7) 0.3 18.7 (14.8-22.1) 0.25 Low 21 32 (13-57) 5.6 (2.1-8.0) 16.6 (13.4- nr) Chemo-naive Full 34 53 (35-71) 0.09 5.5 (4.4-6.5) 0.9 18.8 (14.8-32.1) 0.49 Low 16 27 (8-55) 4.6 (2.0-8.0) nr (15.3-nr)
Long-term dexamethasone treatment diminishes store-operated Ca2+ entry in salivary acinar cells
Authors: Yuichiro Kusuda, Yusuke Kondo, Yuta Miyagi, Takashi Munemasa, Yusuke Hori, Fumiko Aonuma, Shintaro Tsuka, Taro Mukaibo, Chihiro Masaki, Ryuji Hosokawa
Journal: International Journal of Oral Science (2019)

Corticosteroids are used in the treatment of many diseases; however, they also induce various side effects. Dexamethasone is one of the most potent corticosteroids, and it has been reported to induce the side effect of impaired salivary gland function. This study aimed to evaluate the effects of dexamethasone on mouse submandibular gland function to gain insight into the mechanism of dexamethasone-induced salivary hypofunction. The muscarinic agonist carbachol (CCh) induced salivary secretion and was not affected by short-term dexamethasone treatment but was decreased following long-term dexamethasone administration. The expression levels of the membrane proteins Na+-K+-2Cl− cotransporter, transmembrane member 16A, and aquaporin 5 were comparable between the control and long-term dexamethasone treatment groups. The CCh-induced increase in calcium concentration was significantly lower in the presence of extracellular Ca2+ in the long-term dexamethasone treatment group compared to that in the control group. Furthermore, CCh-induced salivation in the absence of extracellular Ca2+ and Ca2+ ionophore A23187-induced salivation was comparable between the control and long-term dexamethasone treatment groups. Moreover, salivation induced by the Ca2+-ATPase inhibitor thapsigargin was diminished in the long-term dexamethasone treatment group. In summary, these results demonstrate that short-term dexamethasone treatment did not impair salivary gland function, whereas long-term dexamethasone treatment diminished store-operated Ca2+ entry, resulting in hyposalivation in mouse submandibular glands. Long-term corticosteroid use causes dry mouth by inhibiting calcium movement into salivary gland cells. Corticosteroid use is associated with multiple systemic side effects including salivary inhibition, prompting Yusuke Kondo and a research team from Japan's Kyushu Dental University to elucidate the reasons why. Submandibular glands taken from mice after six weeks' treatment with the corticosteroid dexamethasone produced significantly less saliva in ten minutes than a group given just one week's treatment, or no treatment at all. Further investigation revealed that long-term dexamethasone treatment inhibited the ability of salivary gland cells, known as acinar cells, to transport calcium ions from the exterior to the interior of the cells—an essential mechanism enabling salivation. The study improves our understanding of corticosteroid-induced dry mouth and reveals potential pharmacological targets to enable treatment.
Population-based evaluation of treatment patterns and survival of localized prostate cancer (CaP) patients with high prostate-specific antigen (PSA).
Authors: Fan Ye, Laura H. Hendrix, Mark Raymond Waddle, Ronald C. Chen
Journal: Journal of Clinical Oncology (2014)

e16008 Background: Overtreatment of patients with indolent CaP is widely reported, but many patients have aggressive and potentially life-threatening CaP. We examined patterns of primary treatment and survival outcomes in a recent population-based cohort of non-metastatic CaP patients with high PSA. Methods: We included 19,036 patients in the SEER database diagnosed from 2004-10 with N0 M0 CaP and PSA ≥25 ng/mL. Primary treatment was examined by PSA levels: 25-49.9, 50-74.9, 75-97.9, and ≥98. Logistic regression assessed factors associated with use of definitive therapy (prostatectomy/radiation). Kaplan-Meier estimates of cancer-specific survival were calculated in patients receiving radical prostatectomy (RP), external beam radiation (RT), and conservative management (CM). Results: Definitive therapy decreased in patient groups with higher PSA levels (from 25-49.9 to ≥98): RP (22% to 8%), RT (33% to 20%), brachytherapy (4% to 1%); with corresponding increases in CM (34% to 59%) and ablative techniques (7% to 12%). Logistic regression showed older age at diagnosis, Gleason score ≥8, PSA >90, nonwhite race, and being unmarried were associated with lower odds of definitive therapy (Table 1). 5-year cancer specific survival for RP, RT, and CM patients were 98.4, 94.6, and 81.3%, respectively. Conclusions: 41-71% of patients (in PSA groups) with aggressive but potentially curable CaP do not receive definitive therapy. Ironically, treatment decreased for patients with higher PSA and Gleason scores. This suggests possible nihilism in patients and physicians regarding aggressive CaP, and demonstrates significant undertreatment. Table. Logistic regression for receipt of definitive treatment OR P-value Age (REF: <60) 60-69 0.82 0.07 70-79 0.43 * 80+ 0.14 * Race (REF: White) Nonwhite 0.68 * Marital Status (REF: Married) Unmarried 0.56 * Clinical T stage (REF: T1) T2 1.0 0.95 T3-T4 1.4 0.03 Gleason (REF: ≤6) 7 1.2 0.09 ≥8 0.75 0.01 PSA (REF: 25-29.9) 30-39.9 0.94 0.62 40-49.9 0.96 0.76 50-59.9 0.99 0.93 60-69.9 0.74 0.08 70-79.9 0.98 0.94 80-89.9 1.2 0.50 90-97.9 0.56 0.01 ≥98.0 0.33 * Also controlled for diagnosis year, regional income and education, urban/rural, and SEER region. *p-value <0.0001
A multicenter audit of the incidence of febrile neutropenia and neutropenia associated with docetaxel and cyclophosphamide (TC) chemotherapy for early breast cancer.
Authors: Roopa Lakhanpal, Robin Stuart-Harris, Arlene Chan, Dusan Kotasek, Jane McNeil Beith, Katharine Cuff, Patricia A. Bastick, Clara Inkyung Lee
Journal: Journal of Clinical Oncology (2013)

1079 Background: A 2006 US Oncology trial reported that four cycles of docetaxel and cyclophosphamide (TC) resulted in better disease free and overall survival than four cycles of doxorubicin and cyclophosphamide (AC) in women with early breast cancer (EBC) and TC is now a frequently used adjuvant chemotherapy regimen for EBC. The 2006 trial reported that TC was associated with a 5% incidence of febrile neutropenia (FN), but others have noted a higher incidence of FN. Methods: We have conducted a multicentre retrospective audit of women with EBC treated with TC between January 2010 and July 2011, recruited from seven Australian centres. The primary endpoints of the study were the incidence of FN associated with the use of TC and also the incidence of grade 3 or 4 neutropenia during cycle one of TC. Patients receiving prophylactic granulocyte colony stimulating factor (G–CSF) or prophylactic antibiotics were excluded. Results: Of a total of 368 previously untreated women with EBC who received TC, 300 were evaluable for FN. The median age of the patients was 57 years. Overall, 73 (24.3%) patients developed FN. The highest incidence of FN was seen after cycle one (91.8%) of TC and the incidence of FN appeared higher in women under the age of 65 years. Of 304 patients evaluable for neutropenia during cycle one, eight (2.6%) developed grade 3 neutropenia and 191 (62.8%) developed grade 4 neutropenia. Conclusions: This is the largest study to date which reveals that TC is associated with a high incidence of grade 4 neutropenia and a high incidence of FN. The incidence of FN is above the 20% threshold for the use of G-CSF as primary prophylaxis as recommended by The EORTC and The National Comprehensive Cancer Network. Therefore, we recommend that G-CSF be considered as primary prophylaxis when TC is used as adjuvant chemotherapy for EBC.