tbuckley/cabot-search huggingface dataset:
Effect of FNCLCC grade 2 versus grade 3 on survival after neoadjuvant chemotherapy (NAC) plus or minus regional hyperthermia (RHT) in soft tissue sarcomas (STS): An analysis of the EORTC-ESHO Intergroup phase III study.
Authors: R. D. Issels, R. P. Laubender, L. Lindner, U. Mansmann, E. Kampmann, J. Verweij, P. Reichardt, B. Schem, S. Daugaard, M. Niederhagen, Z. Vujaskovic, R. Wessalowski, C. M. Wendtner, K. Jauch, H. R. Duerr, R. Windhager, W. Hiddemann, J. Blay, P. Hohenberger
Journal: Journal of Clinical Oncology (2011)

10021 Background: There is ongoing debate on the predictive value of histological grade for treatment benefit in various stages of STS. A retrospective analysis by the French Sarcoma Group suggested that patients (pts) with FNCLCC grade 3, but not grade 2, STS may benefit from adjuvant chemotherapy. Here we analyzed the predictive value of grade for NAC in a randomized phase 3 completed trial (NCT 00003052) which showed that RHT added to NAC was beneficial in terms of tumor response, local progression-free (LPFS), and disease-free (DFS) survival. Overall survival (OS) was improved in pts who completed the induction therapy with RHT (Lancet Oncol 2010). Methods: From July 97 to Nov 06, 339 pts (eligible for this analysis) (161 pts grade 2; 178 pts grade 3) were randomized to receive NAC + RHT (168 pts; 84 grade 2 (50%) and 84 grade 3 (50%)) or NAC alone (171 pts; 77 grade 2 (45%) and 94 grade 3 (55%) tumors). Grade was assessed according to the FNCLCC system. For the impact of grade, survival rates (LPFS, DFS, and OS) were estimated using the Kaplan-Meier-Method and compared by the log-rank test. Multivariate analyses were carried out by the Cox regression model including the stratification variables (primary, recurrence, prior surgery, anatomic site). Results: In the overall study grade was a prognostic factor for OS (grade 2 vs 3: HR 1.40 CI: 1.01-1.92; p=0.041). In the NAC + RHT group (168 pts), OS in grade 2 pts was significantly better (2 yr: 87%; 4 yr: 69%) than OS in grade 3 pts (2 yr: 69%; 4 yr: 49%) (HR 1.79 CI: 1.10-2.91; p=0.019). In the NAC alone group (171 pts) comparing OS in grade 2 pts (2 yr: 79%; 4 yr: 58%) with OS in grade 3 pts (2 yr: 66%; 4 yr: 54%) no association could be assessed (HR 1.22 CI: 0.76-1.94; p=0.411). The addition of RHT to NAC (NAC + RHT: 84 pts vs NAC: 77 pts) increased LPFS (HR 0.54 CI: 0.31-0.94; p=0.026) and DFS (HR 0.63 CI: 0.41-0.97; p=0.034) in grade 2 pts and to much lesser extent in grade 3 pts (NAC + RHT: 84 pts vs NAC alone: 94 pts) (LPFS: HR 0.67 CI: 0.41-1.09; p=0.104 and DFS: HR 0.74 CI 0.51-1.07; p=0.110). Conclusions: This is the first report to indicate that FNCLCC grade 2 high-risk STS preferentially benefit from NAC if RHT is added.
Combinations of the Phosphatidylinositol 3-Kinase-Delta (PI3Kδ) Inhibitor Gs-1101 (CAL-101) with Rituximab and/or Bendamustine Are Tolerable and Highly Active in Previously Treated, Indolent Non-Hodgkin Lymphoma: Results From a Phase I Study
Authors: Nathan H Fowler, Sven de Vos, Marshall T. Schreeder, John P. Leonard, Ian W. Flinn, Steve Coutre, Nina D. Wagner-Johnston, Jeff Sharman, Ralph V. Boccia, Jacqueline C. Barrientos, Thomas E. Boyd, Leanne M. Holes, Brian J. Lannutti, David Johnson, Thomas M. Jahn, Langdon L Miller, Wayne R Godfrey
Journal: Blood (2012)
Clinical recurrence post-biochemical failure of prostate cancer.
Authors: C. A. Reddy, J. P. Ciezki, E. A. Klein
Journal: Journal of Clinical Oncology (2011)

195 Background: The purpose of this study is to evaluate the role of salvage therapy (STx) after biochemical failure (bF) for prostate cancer (CaP) and to determine what factors are associated with the development of clinical recurrence (cR). Methods: From 1996-2009, 7,585 patients (pts) with CaP were treated with prostatectomy (RP), brachytherapy (PI), or external beam radiotherapy (RT). For RP patients (pts), bF was defined as a postoperative PSA &gt;0.3 and for PI and RT pts the Phoenix definition was used. bF was documented in 927 pts. cR was defined as any image-based or pathological diagnosis of disease recurrence after bF. Cox proportional hazards regression was used to examine if the use of STx after bF, the time of bF, along with disease characteristics were associated with cR after bF. Results: The median follow-up after bF was 31months (mo; range: 0-131). Thirty percent of pts had a cR after bF, and the 5-year rate of cR free survival was 58%. STx within 1 year after bF (early) was given to 46% of pts, STx more than 1 year after bF (late) was given to 11% of pts, and 43% of pts did not receive STx. On univariate analysis, factors found to be significantly associated (p-value &lt;0.05) with cR were a short interval between initial treatment and bF (bFTime), no use of STx, early initiation of STx, biopsy Gleason Score (bGS), clinical stage, older age at bF, the use of PI or RT, and increased frequency of PSA follow-up after bF (PSAfreq). In multivariable analysis, bFTime, no use of STx, early initiation of STx, bGS, the use of PI or RT, and PSAfreq remained significant. To better evaluate the effect the timing of initiation of STx had on the development of cR, a second analysis was preformed, limited to the 529 pts who did receive STx after bF. In multivariable analysis, early use of STx remained significant for cR (HR=2.09, 95%CI=1.24- 3.51). As a continuous variable, in a second multivariable analysis, delayed use of STx resulted in a reduced risk of developing cR (HR=0.98, 95%CI=0.96-1.00). Conclusions: This study suggests that while the use of STx after bF reduces the risk of subsequently developing cR, early use of STx after bF is not beneficial. Other factors such as the time interval between initial treatment and bF need to be evaluated when determining when to initiate STx after bF. No significant financial relationships to disclose.
CyberKnife for prostate cancer: Is it cost-effective?
Authors: A. Parthan, N. Pruttivarasin, D. Taylor, D. Davies, G. Yang, V. Pawar, M. C. Weinstein
Journal: Journal of Clinical Oncology (2011)

87 Background: The study assessed the cost-effectiveness of CyberKnife (CK) compared to surgery and radiation therapy for the treatment of prostate cancer (PC) from a third-party and societal perspective. Methods: For patients &gt; 65 yrs with localized PC, a Markov model compared treatment with CK, intensity modulated radiation therapy (IMRT), surgery or proton therapy (PT). Following treatment, patients were at risk of long-term toxicity: genitourinary (GU); gastrointestinal (GI); and sexual dysfunction (SD). Long-term toxicity was defined as adverse events &gt;grade 2 on Radiation Therapy Oncology Group scale occurring at least 12 months following treatment. Markov states included all possible combinations of GI, GU, and SD long-term toxicities, no toxicity, and death. During each year patients remained in the same Markov state or died. Costs and utilities were assigned using published sources. Toxicity probabilities were derived using meta-analytical techniques to pool results from multiple studies. It was assumed that long-term disease control would not differ across treatments. The model projected expected lifetime costs and quality adjusted life years (QALYs) for each treatment and incremental cost-effectiveness of CK vs comparators as cost per QALY gained. Costs from societal perspective included lost productivity. Extensive sensitivity analyses were conducted. Results: Surgery was the least expensive treatment option followed by CK. CK patients had higher expected QALYs (8.11) than other treatment options (7.72- 8.06). From a payer perspective, total lifetime costs were $25,904, $22,295, $38,915, and $58,100 for CK, surgery, IMRT and PT, respectively. Incremental cost per QALY gained for CK versus Surgery was $9,200/QALY. Compared to IMRT and PT, CK was less costly and resulted in higher QALYs (dominance). At a threshold of $50,000/QALY, CK was cost effective in 86%, 79%, and 91% of simulations compared to surgery, IMRT, and PT, respectively. From a societal perspective, CK costs $4,200/QALY compared to surgery and remained dominant vs IMRT and PT. Results were most sensitive to costs of surgery and CK. Conclusions: Initial CK costs are higher than surgery, but CK patients have better quality of life. CK patients have lower lifetime costs and higher QALYs than IMRT and PT patients. [Table: see text]
Pulmonary Mortality after High-Dose Oral Busulfan and Autologous Stem Cell Transplant (ASCT) in Patients with Non-Hodgkin Lymphoma (NHL).
Authors: Matt Kalaycio, Brad Pohlman, Lisa Rybicki, Ronald Sobecks, Elizabeth Kuczkowski, Steven Andresen, Stacey Brown, Brian Bolwell
Journal: Blood (2005)
Econimic burden of reoperative renal surgery: Do the means justify the ends?
Authors: N. Agochukwu, W. Linehan, G. Bratslavsky
Journal: Journal of Clinical Oncology (2011)

364 Background: Despite the high morbidity of reoperative renal surgery (RRS) most patients are able to preserve adequate renal function to obviate the need for dialysis. Nevertheless, the economic burden of RRS has not been evaluated so far. We aim to provide cost analysis for patients requiring RRS on a solitary kidney and patients needing completion nephrectomy and dialysis. Methods: We reviewed the charts of patients treated at the NCI requiring RRS from 1989 to 2010. The data extracted included total time in the OR, ICU stay, total hospital stay, need for additional procedures, blood products, laboratory evaluation, and surveillance imaging until the next intervention on the operated unit or most recent follow up. The hospitalization cost was calculated based on current Medicare reimbursement rates based on current procedural terminology (CPT) codes. Those costs were compared to the estimated cost of completion of uncomplicated nephrectomy, AV fistula placement, and hemodialysis. Results: We identified 30 patients treated with RRS on a solitary renal unit. The average procedure lasted 7.76 hours (4.25-11 hours) requiring an average of 7.16 units of blood transfused (0-32 units). The average time of hospitalization was 9.56 days (6-30 days), with the average ICU stay of 4.03 days (range 1-12 days), and an average floor stay of 6.64 (2-18 days). The estimated cost for hospitalization per patient was $52,058, while the estimated cost for uncomplicated nephrectomy, AV fistula placement, and a year of dialysis was $59,572. The financial benefit of RRS is reached at 0.9 years. At our median follow up of 4 years, the average cost saving per patient is estimated to be greater than $100,000 with the numbers likely to increase as these patients continue to avoid dialysis. Conclusions: While associated with high morbidity, the RRS on the solitary unit may provide an opportunity for the majority of patients to retain their native renal remnants, preserve quality of life, and allow for savings for the healthcare system. These benefits are in addition to savings not included in our analysis that are associated with the morbidity and complications associated with dialysis in addition to the costs of care required for patients on dialysis. No significant financial relationships to disclose.
The primary (dis)function of consciousness: (Non)Integration
Authors: Liad Mudrik
Journal: Behavioral and Brain Sciences (2016)

Morsella et al. put forward an interesting theory about the functions of consciousness. However, I argue that this theory is more about showing what is not the function of consciousness, and claiming that it does not integrate, than vice versa - as opposed to its proclaimed goal. In addition, the question of phenomenality and its relations with integration is still left open.
Clonal Evolution of Multiple TET2 mutations In the Transformation of Chronic Myelomonocytic Leukemia to Acute Myeloid Leukemia and Its Subsequent Relapse
Authors: Robert D. Petty, Farideh Miraki-Moud, Tracy Chaplin, Grossmann Vera, Daverio Andrea, Finlay Macdougall, Maria Ronayne, Bryan D Young, Manoj Raghavan
Journal: Blood (2010)
Direct induction of neural progenitor cells transiently passes through a partially reprogrammed state
Authors: Rui Gao, Wenchao Xiu, Linfeng Zhang, Ruge Zang, Lei Yang, Chenfei Wang, Min Wang, Mingzhu Wang, Li Yi, Yuanyuan Tang, Yawei Gao, Hong Wang, Jiajie Xi, Wenqiang Liu, Yixuan Wang, Xuejun Wen, Yongchun Yu, Yong Zhang, Liang Chen, Jiayu Chen, Shaorong Gao
Journal: Biomaterials (2016)
Use of Blue Citrus, a Chinese herbal remedy, to reduce side effects of aromatase inhibitors.
Authors: K. Massimino, M. Glissmeyer, T. Wagie, K. Karamlou, R. M. Look, L. Sorenson, C. Turner, N. Johnson
Journal: Journal of Clinical Oncology (2011)

170 Background: Aromatase inhibitors are widely used in treatment of estrogen receptor positive breast cancer. Many patients experience significant arthralgias, which may lead to early cessation of therapy. Blue Citrus, a mix of Chinese herbs formulated in our community, had anecdotal reports of success in alleviating these symptoms. We objectively evaluated its activity in symptomatic patients. Methods: Breast cancer patients with significant arthralgia on aromatase inhibitors were enrolled in a prospective fashion to a double blind crossover placebo controlled trial. Each patient received either Blue Citrus (BC+P) or a placebo (P+BC) for three months and then crossed over to the opposite treatment for an additional three months. Symptoms were measured over the course of treatment. Results: A total of 37 patients enrolled on the study. There were 6 early withdrawals, which left 31 evaluable patients. Visual Analogue Score (VAS) for both groups was similar at baseline at 4.9 and 5.1 for the BC+P and P+BC groups, respectively. At 30 days the BC+P score was 3.4 vs. the P+BC of 4.7 showing clearly improved symptom control in the BC+P group. The P+BC group did however approach the BC+P group by 90 days. At crossover the BC+P group experienced a spike in symptomology when changed to placebo that didn’t appear for the P+BC group. When compared to baseline, mean VAS score on Blue Citrus was 2.98 (p=0.001) versus mean VAS score on placebo 3.92 (p=0.0203). By study end (180 days) the VAS scores for both groups were closer at 2.6 BC+P vs. 3.0 for P+BC but BC+P still maintained lower VAS scores. Conclusions: Blue Citrus improved symptoms associated with aromatase inhibitor use. Patients who received Blue Citrus in the first arm had rapid improvement in symptoms and experienced return of symptoms when converted to placebo. All patients averaged lower VAS scores on Blue Citrus however at 6 months the difference between the arms became less pronounced.
Association of Selective Serotonin Reuptake Inhibitors With the Risk for Spontaneous Intracranial Hemorrhage
Authors: Christel Renoux, Sarah Vahey, Sophie Dell’Aniello, Jean-François Boivin
Journal: JAMA Neurology (2016)

Selective serotonin reuptake inhibitors (SSRIs) may increase the risk for spontaneous intracranial hemorrhage (ICH), an effect that is in theory linked to the strength of inhibition of serotonin reuptake of an antidepressant. However, whether antidepressants that are strong inhibitors of serotonin reuptake actually increase the risk for ICH and the effect of concomitant use of antithrombotics are unknown.To assess the risk for ICH associated with the use of SSRIs compared with tricyclic antidepressants (TCAs) among new users of antidepressants and according to the relative affinity of the antidepressant for the serotonin transporter and to assess whether concomitant use of antithrombotics modifies this risk.This population-based cohort study included new users of antidepressants 18 years or older from January 1, 1995, to June 30, 2014. More than 650 general practices in the United Kingdom contributing to the Clinical Practice Research Datalink enrolled patients. with use of a nested case-control approach, each case of a first ICH identified during follow-up was matched with as many as 30 control individuals by age, sex, calendar time, and duration of follow-up. Follow-up was completed on October 31, 2014.Current use of SSRIs compared with TCAs and strong compared with weak serotonin reuptake inhibitors.Incidence rate ratios (RRs) of ICH.Among a cohort of 1 363 990 incident users of antidepressants (36.8% male; 63.2% female; mean [SD] age, 47.9 [18.5] years), 3036 cases of ICH were identified during follow-up and matched to 89 702 controls. Current SSRI use was associated with an increased risk for ICH (RR, 1.17; 95% CI, 1.02-1.35) relative to TCAs, highest during the first 30 days of use (RR, 1.44; 95% CI, 1.04-1.99), and translating in very few additional events. Similarly, the risk was increased by 25% with strong inhibitors (RR, 1.25; 95% CI, 1.01-1.54) and highest during the first 30 days of use (RR, 1.68; 95% CI, 0.90-3.12). Concomitant use of anticoagulants may increase the risk substantially (RR, 1.73; 95% CI, 0.89-3.39).The use of SSRIs and more generally of antidepressants with strong inhibition of serotonin reuptake are associated with an increased risk for ICH, particularly in the first 30 days of use and when used concomitantly with oral anticoagulants.
Targeted combinatorial therapy of androgen receptor in androgen-independent prostate cancer cells.
Authors: A. Gomez-Pinillos, X. Liu, A. C. Ferrari
Journal: Journal of Clinical Oncology (2011)

29 Background: Gain of function of androgen receptor (AR) and PI3K/Akt/mTOR pathway due to loss of PTEN function are interrelated determinants of AIPC progression and resistance to antiandrogens. We determined that histone deacetylase inhibitors (HDACi), known to regulate AR expression and transcriptional activity, restore sensitivity to bicalutamide (Bic) of AIPC cells and the combination is synergistic. We postulate that adding a dual inhibitor of PI3K/mTOR would potentiate growth inhibition and apoptotic response. Methods: Androgen-independent, PTEN null AI-LNCaP (AI-cells) and wt PTEN RV1-cell lines were treated for 72h with the HDACi Panobinostat (PAN), the dual PI3K/mTOR inhibitor BEZ235 (E) and Bic as single agents or in doublet or triplet combinations. Growth was measured by MTT assay, Akt/mTOR pathway target proteins p-Akt, p-4EBP1 and p-S6K by western blot. Activation of ligand-independent AR downstream targets: CDC20, IDI1, CDK1, UBE2C, PRDM4 by qRT-PCR. Apoptosis by oligonucleosome quantification by ELISA was compared to docetaxel. Results: In both cell lines, the IC50s were markedly reduced in response to the doublet combinations and further decreased by the triplet. The isobolograms showed synergy. The apoptosis response increased by two fold in AI and RV1 cells in response to the doublet PAN+E and by four fold with the addition of Bic in AI cells. Only E decreased the protein levels of p473-akt, p-4EBP1, p-S6K markedly while only PAN decreased AR and these levels were not affected by the combinations. However, the triplet but not the doublets decreased by 2-fold the expression of AR targets in AI-cells but not in RV1 cells. Conclusions: The combination of PAN+E is highly effective in AIPC cells regardless of PTEN status but the addition of Bic is essential to maximize the effect in PTEN null AI-cells, suggesting they are more dependent on aberrant activation of AR. [Table: see text] No significant financial relationships to disclose.
Effect of oral cyclophosphamide use on pathologic complete response rate in the neoadjuvant treatment of breast cancer.
Authors: M. Luque, P. Garcia-Teijido, Y. Fernandez, T. Sampedro, V. Reguero
Journal: Journal of Clinical Oncology (2011)

276 Background: Continuous exposure to cyclophosphamide (C) can result in selective cytotoxicity for endothelial cells, followed by antiangiogenic effects on tumor cells. In this study we analyzed the pathological complete response (pCR) rate in a cohort of patients (p) diagnosed with locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy (CT) based on anthracyclines and taxanes, depending on the route of administration of C (intravenous (IV) and oral arms). Methods: We retrospectively studied a consecutive series of p. with LABC treated with neoadjuvant CT in 2 hospitals in Asturias. The regimens used were CE100F, AC (regimens with IV C) or oral CAF (C 100mg/m2/day orally x 14 days, doxorubicin 30 mg/m2 day 1 and 8 and 5-FU 500 mg/m2 days 1 and 8 every 28 days) x 4 cycles. The anthracycline regimen was followed by weekly paclitaxel or docetaxel every 3 weeks. If HER2 overexpression, trastuzumab was given in combination with the taxane. Results: We identified 105 p., 65 of them treated with oral C and 40 with IV C (CEF 3 patients and AC 37 patients). The median age was slightly higher in the p. treated with C IV (52.2 vs. 47.7, p = 0.022), which also received a higher number of cycles (7.1 vs. 6.7, p = 0.025), although there were no significant differences in the anthracycline dose intensity (93% vs 89%, p = 0.093). There were no significant differences in tumor size, lymph node involvement, grade, estrogen receptor (ER) or HER2. The rate of pCR was significantly higher in p. receiving oral C (33.8% vs 10%, p = 0.004). Grade 3, negative estrogen receptors and HER2 were also significantly associated with a higher rate of pCR. On multivariate analysis only oral C was an independent factor associated with pCR. With a median follow up of 27.3 months (95% CI 24 to 30.6), there have been 10 recurrences (15.4%) in the continuous arm and 9 (22.5%) in the standard arm, without significant differences in disease free survival. Conclusions: Our results suggest that the pCR rate can be higher using oral C in the neoadjuvant treatment of LABC based on anthracyclines and taxanes. This hypothesis should be confirmed in a randomized and prospective study.
Periodic Treatment Regimens With Inhaled Steroids in Asthma or Chronic Obstructive Pulmonary Disease
Authors: Constant P. van Schayck
Journal: JAMA (1995)

<h3>Objective.</h3> —To determine whether inhaled corticosteroids can be discontinued in the stable phase of asthma or chronic obstructive pulmonary disease (COPD) or if this therapy should be continued. <h3>Design.</h3> —Nonrandomized open uncontrolled 5-year trial. <h3>Setting.</h3> —Prospective study in general practice. <h3>Patients.</h3> —Forty-eight patients with steroid-dependent asthma or COPD who had shown a decline in forced expiratory volume in 1 second (FEV<sub>1</sub>) of at least 80 mL per year and at least one exacerbation per year during the first 2 years of bronchodilator treatment. Subjects were treated additionally with inhaled steroids for another 2 years and were finally given the option to stop using steroids. Sixteen patients were willing to stop using beclomethasone and were studied for another year. No recruitment bias took place in this consecutive sample in the fifth year of follow-up. Two of 16 patients developed carcinomas and dropped out. <h3>Interventions.</h3> —Two years of bronchodilator treatment alone (400 μg of salbutamol or 40 μg of ipratropium bromide four times daily), followed by 2 years of additional inhaled corticosteroid treatment (400 μg of beclomethasone two times daily), and finally 1 year of bronchodilator treatment alone. <h3>Main Outcome Measures.</h3> —Decline in lung function (FEV<sub>1</sub>), change in bronchial hyperresponsiveness, indicated by a provocative concentration of histamine causing a 20% fall in FEV<sub>1</sub>(PC<sub>20</sub>), morning peak expiratory flow rate (PEFR), diurnal PEFR, week-to-week variation of PEFR, bronchial symptoms, and exacerbations. <h3>Results.</h3> —The course of FEV<sub>1</sub>during the year in which beclomethasone was discontinued was not significantly different when compared with the 2-year period of beclomethasone treatment. Neither did the course of PC<sub>20</sub>, morning PEFR, diurnal PEFR, symptom score, and exacerbation rate change. Only the week-to-week variation of the PEFR increased after discontinuing steroids. <h3>Conclusions.</h3> —Discontinuing inhaled steroids is possible in some patients with asthma or COPD after 2 years of regular treatment. This might indicate that for certain groups of patients with mild asthma or COPD, periodic treatment schedules with inhaled steroids is the treatment policy for the future. (<i>JAMA</i>. 1995;274:161-164)