tbuckley/cabot-search huggingface dataset:
Tolerability and efficacy of anti-androgen manipulation versus taxotere and anti-androgen manipulation in patients with hormone-naive, high-risk/metastatic prostate cancer: A phase II, open-labeled, randomized study.
Authors: I. D. Pedley, J. A. Frew, J. M. Wilson, A. R. Abdul Razak, A. Azzabi, R. McMenemin, J. Stockley, N. Soomro, G. Durkan, H. Leung
Journal: Journal of Clinical Oncology (2011)

147 Background: Anti-androgen manipulation (AA) is considered the standard initial therapy for high-risk/metastatic prostate cancer. The role of chemotherapy and anti-androgen manipulation (TAA) is still undefined in this group. GenTax is a phase II trial investigating clinical outcome and gene profiling in prostate cancer before and after AA or TAA. Here we present the clinical outcome data. Methods: Patients with T3/4 disease, PSA ≥ 50 ng/ml or Gleason score ≥ 8, or metastatic disease were enrolled. Patients were randomised at histological diagnosis to AA or TAA (goserelin 3.6 mgs q28 ± taxotere 75 mg/m 2 q21 for 6 cycles). TRUS biopsies were taken at randomisation and 22 weeks after treatment initiation. Clinical assessment including KPS, QOL using QLQ-C30, bloods/PSA were measured 3 weekly until 22 weeks then 3 monthly. Data was analysed for PFS, OS, toxicities and QOL. Results: 30 patients were recruited with 15 patients in each arm from 10/13/2005 to 12/02/2009. The median age was 62.2 yrs (range 48.9-75.1). All patients had a KPS of ≥ 90%. 12 (40%) and 18 (60%) of patients had stage 3 and 4 disease respectively. At randomization 10 patients had bone and 4 had visceral metastases. 29 had a Gleason score of ≥ 7. There were no statistical differences for age, KPS, disease stage or Gleason score between the two arms. Treatment was well tolerated in both groups with no G3-4 toxicity in the AA arm. In the TAA arm, 4 patients had dose delays or reductions; with one G3 incidence of neutropenia. G3-4 non-hematological toxicities were infrequent; fatigue and one episode of anaphylaxis occurring in separate patients. Median PFS and OS between the two treatments have not been reached at median follow up of 25 months. The 2-year PFS rate was not significantly different, (50% vs 60% p = 0.788) between the AA and TAA groups. There were no significant differences in QOL measures. Conclusions: Combination therapy of taxotere and anti-androgen manipulation is safe and well tolerated. The gene profiling results may provide important information in selecting patients who will benefit from more aggressive initial therapy. [Table: see text]
Time spent in the lymphedema state: Area under the curve.
Authors: J. M. Armer, B. R. Stewart, R. Madsen
Journal: Journal of Clinical Oncology (2011)

252 Background: The experience of lymphedema (LE) is variable as related to the pattern of LE emergence, with characteristics related to time since diagnosis, duration of the LE episode, frequency of limb volume change (LVC) events, and overall time spent in the state defined as LE. Recognition of these characteristics, examination of trajectories, and application of the ability to quantify LE state through calculation of Area Under the Curve provide an opportunity to explore new ways to quantify LE occurrence to better examine the impact of LE on survivorship outcomes. Further, through these findings researchers and clinicians will better understand the potential variations in lymphedema experience, including patterns of emergence, duration of each episode, frequency of events, and time spent in the lymphedema state. Methods: Participants were enrolled following BC diagnosis and followed every 6 months through 60 months. The criterion of 10% LVC (LePCT) by perometry was chosen to demonstrate use of trajectories and utility of calculating Area Under the Curve (AUC). We examined times when a participant met the criterion as a means of following the trajectory of LE and quantified the proportion of (calendar) time that a participant appeared to have LE by looking at the AUC determined by the individual’s graph. As study time differed, rather than look at AUC alone, we looked at the percent of time that a participant met the LE criterion by dividing AUC by total study time. Results: Over the 60-month time-stamps of data collection points, we examined trajectories or patterns of events where participants met the LE criterion of interest. An individual may have a single LVC “spike” or may have multiple “spikes.” These cases may be acute, transient, or chronic. Further, individuals may experience the LVC early or late in the survivorship trajectory. These variations contribute to varying AUC and percent of the (calendar) time that a participant meets the LE criterion. Conclusions: These approaches provide an opportunity to further examine the association of LVC with psychosocial and functional outcomes of interest in cancer survivorship. They also provide preliminary data for exploring phenotypic differences in presentation and progression of post-breast cancer lymphedema.
Fear Erasure Facilitated by Immature Inhibitory Neuron Transplantation
Authors: Wu-Zhou Yang, Ting-Ting Liu, Jun-Wei Cao, Xuan-Fu Chen, Xiao Liu, Min Wang, Xin Su, Shu-Qing Zhang, Bin-Long Qiu, Wen-Xiang Hu, Lin-Yun Liu, Lan Ma, Yong-Chun Yu
Journal: Neuron (2016)
Time from Relapse to Donor Leukocyte Infusion in Allogeneic Stem Cell Transplantation Patients Is Longer for Recipients of Unrelated DLI Compared to Matched Sibling DLI, with Similar Incidence of Graft Versus Host Disease (GVHD) and Survival
Authors: Anita J. Kumar, Pavel Vassilev, Alison W. Loren, Selina M. Luger, Ran Reshef, Saar I. Gill, Jacqueline Smith, Steven C. Goldstein, Elizabeth Hexner, Edward A. Stadtmauer, David Porter, Noelle V. Frey
Journal: Blood (2014)
Bone Marrow Lymphocytic Status during Tyrosine Kinase Inhibitor Therapy and Its Relation to Therapy Response in Chronic Phase Chronic Myeloid Leukemia Patients
Authors: Mohamed El Missiry, Shady Adnan, Hanna Rajala, Ahmed Al-Samadi, Marja Ekblom, Berit Markevän, Ingbritt Åstrand-Grundström, Maren Wold, Birgitte Ravn Juhl, Ole Weis Bjerrum, Inger Haulin, Kimmo Porkka, Ulla Olsson-Strömberg, Henrik Hjorth-Hansen, Satu Mustjoki
Journal: Blood (2015)
Preliminary results of perioperative outcomes and oncologic efficacy from a single-institution randomized controlled trial of open versus robotic-assisted radical cystectomy.
Authors: Jamie Christopher Messer, John Patrick Fitzgerald, Barbara Ercole, Robert Scott Svatek, Dipen J. Parekh
Journal: Journal of Clinical Oncology (2012)

305 Background: In the past decade minimally invasive robotic assisted approaches have emerged as a viable option for the treatment of many urologic malignancies. Robotic-assisted radical cystectomy (RARC) for bladder cancer has been reported with the potential for lower blood loss, less transfusion requirement, and shorter hospital stay in prior studies. We present preliminary data from a single institution prospective randomized clinical trial of open radical cystectomy (ORC) versus RARC. Methods: Prospective randomized single institution series evaluating the feasibility of ORC versus RARC for consecutive patients was performed from July 2009 to June 2011. Oncologic efficacy was assessed based on the surrogates of total number of lymph nodes removed and positive surgical margins. Perioperative morbidity was assessed evaluating for estimated blood loss, transfusion requirements, length of stay and perioperative morbidity. Results: To date 46 patients have been randomized with data available on 39 patients for analysis. Each group was similar with regards to age, sex, race, BMI, comorbidities, and previous abdominal procedures, operative time, and final pathologic stage. We observed no significant difference between oncologic outcomes of positive surgical margins (5% vs 5.263%, p 0.48) or number of LN removed (11 vs 23, p 0.40) for the RARC versus ORC groups respectively. The RARC group was noted to have decreased estimated blood loss (400 mL vs 800 mL, p 0.008) and a trend towards decreased rate of excessive length of stay (&gt;5 days) (65% vs 84%, p 0.17) for the RARC versus ORC groups. The robotic group had a trend towards decreased rate of transfusion however this was not statistically significant (40% versus 53%, p 0.26). Conclusions: Our preliminary findings from a single institution randomized trial of RARC versus ORC indicates that RARC has equivalent oncologic outcomes as measured by positive surgical margins and total number of lymph node removed. RARC demonstrates Perioperative benefits of decreased blood loss, fewer excessive hospital stays, and a trend toward fewer transfusions that was not significant.
Planning outcomes and acute toxicity of intensity-modulated radiotherapy (IMRT) for treatment of bladder and pelvic lymph nodes.
Authors: V. Harris, F. McDonald, V. Hansen, H. Taylor, R. A. Huddart
Journal: Journal of Clinical Oncology (2011)

297 Background: We implemented an IMRT protocol for simultaneous treatment of bladder and pelvic lymph nodes (LN) and report the planning outcomes and acute toxicity of patients treated using this technique. Methods: 13 patients were treated with a 5-field step and shoot IMRT technique. Inclusion criteria were: radiological evidence of pelvic LN metastases; stage T3/T4; high risk pathology or post-cystectomy with persistent/recurrent disease. Anisotropic margins were applied to the whole bladder CTV (0.5 cm laterally/inferiorly, 1 cm posteriorly, 1.5 cm superiorly/anteriorly) to create PTV1. 0.5 cm margins were applied to the pelvic LN CTV to create PTV2. PTVs 1/2 were prescribed 52 Gy in 32 fractions. 1 cm margins were applied to the involved bladder to create PTV3 (prescribed 64Gy). 0.5 cm margins were applied to the involved LN volumes to create PTV4 (prescribed 60 Gy). Post cystectomy patients were planned using PTVs 2/4 only. Dose volume histograms for organs at risk (rectum, femoral heads and other bowel) were calculated and compared with local dose constraints. Acute toxicity was assessed according to common toxicity criteria v3.0 and recorded weekly during treatment. Treatment verification was performed by cone beam CT. Results: All treatment plans achieved target coverage of &gt; 95% volume to &gt; 95% prescription dose for each PTV. All patients achieved rectal and femoral head dose constraints. 2 patients did not meet V45 other bowel constraints but proceeded with treatment as all other dose limits were achieved. At the time of abstract submission 13 patients had completed treatment. 2 were treated for relapse post-cystectomy and did not have GU toxicities recorded. Maximum experienced acute toxicities were recorded. 9/11 patients experienced acute GU toxicity (G1=3, G2=1, G3=5). 6/13 patients experienced acute GI toxicity (G1=3, G2=3). 9/13 patients developed other acute toxicities (G1=7, G2=2). No patients developed ≥G3 non-GU toxicity. Conclusions: Bladder and pelvic LN IMRT allows patients with high risk locoregional bladder cancer to meet preset dose constraints, appears feasible and has a comparable rate of acute toxicity to conventional bladder-only radiotherapy treatment. No significant financial relationships to disclose.
Association of baseline risk factors with cardiovascular (CV) events during long-term degarelix therapy in men with prostate cancer.
Authors: M. R. Smith, L. Klotz, E. van der Meulen, E. Colli, L. B. Tanko
Journal: Journal of Clinical Oncology (2011)

190 Background: GnRH agonists have been associated with a greater incidence of CV events in men with prostate cancer. Less is known about GnRH antagonists and CVD. We used prospective data to evaluate the relationships of baseline CV risk, dosing regimen and duration of degarelix therapy, and CV events. Methods: Data from 16 phase II/III and one extended phase III trial was pooled (n=1,704). Maintenance doses and exposure time varied between 20-480 mg and 1-66 months, respectively. Baseline CV risk was assessed based on established CVD, BMI (&gt;30 kg/m 2 ), smoking, hypertension, type 2 diabetes, and hyperlipidemia. Patients were stratified into 3 groups: 1) no CV risk factors (n=337), 2) ≥1 CV risk factors without CVD (n=803), 3) established CVD (n=564). Acute CV events were collected prospectively. Results: The incidence of CV events in patients with established CVD, ≥1 CV risk factors, and no CV risk factors was 20% (n=112), 8% (n=57) and 7% (n=28), respectively. Established CVD was associated with a 3.1-fold increased risk for CV events (p&lt;0.0001), whereas presence of ≥1 CV risk factors with 1.3-fold (p=0.28). The cumulative hazard curve indicated no increases in hazards with increasing duration of treatment. Hazards of primary CV events during degarelix treatment (0.049) were not statistically different from that during the 2 years prior treatment (0.48, p=0.85). In multivariate models, age, established CV disease, high BMI and no alcohol consumption were independently associated with greater risk for CV events (Table); type 2 diabetes (p=0.13) and smoking (p=0.08) were of borderline significance. Degarelix dose and schedule were not associated with CV risk (p=0.78) in the model. Conclusions: CV events during degarelix treatment were largely confined to those with established CVD and further modulated by aging and modifiable risk factors. Rates of CV events were similar before and after degarelix treatment. [Table: see text] [Table: see text]
Testing and clinical implications for non‐V600 <i>BRAF</i> mutations in metastatic <i>NRAS</i> <sup> <i>mt</i> </sup> melanoma
Authors: G. Richtig, E. Richtig, K. Kashofer, L. Koch, G. Winter, G. Hoefler, M. Pichler, B. Ehall, M.R. Grübler, A. Heinemann, A. Aigelsreiter
Journal: British Journal of Dermatology (2016)
Talens-Mediated DLEU1 Gene Silencing in Burkitt Lymphoma (BL): Implication of Lncrna DLEU1 Gene As a Potential Tumor Suppressor Gene in BL.
Authors: Sanghoon Lee, Changhong Yin, Janet Ayello, Carmella van de Ven, Henry Hwang, Charles Biggar, James Pao, Erin Mulvey, Mitchell S. Cairo
Journal: Blood (2012)
Amrubicin as second- or third-line treatment for patients with HER2-negative metastatic breast cancer (MBC): A Sarah Cannon Research Institute phase I trial.
Authors: J. H. Barton, K. C. Shih, E. Raefsky, D. W. Haines, B. Strike, J. D. Hainsworth, H. A. Burris, D. A. Yardley
Journal: Journal of Clinical Oncology (2011)

1116 Background: Anthracyclines demonstrate significant activity in breast cancer; however, cumulative cardiotoxicity limits their use. Amrubicin is a novel anthracycline with broad-spectrum antitumor activity and low potential for cardiotoxicity. We initiated a phase I/II trial of amrubicin in patients with MBC. Results from the phase I portion are presented. Methods: Women with HER2-negative MBC, ≤2 prior chemotherapy regimens for metastatic disease, normal LVEF, and measurable disease were eligible. Amrubicin was administered IV every 3 weeks; doses were escalated in sequential cohorts of patients, using standard phase I methodology. Four amrubicin dose levels were evaluated: 90 mg/m2, 100 mg/m2, 110 mg/m2, and 120 mg/m2. The MTD was defined as the highest dose producing ≤2 DLTs in a patient cohort. Prophylactic GCSF support was strongly encouraged due to previous reports of complicated neutropenic events. Cardiac monitoring with serial ECHOs or MUGAs was performed every 4 cycles. Response assessments were performed every 2 cycles. Results: Fifteen patients were treated at 4 amrubicin dose levels; data is available for 12 patients. Grade 3/4 toxicity is summarized in the table. No cardiotoxicity was evident. At the 120 mg/m2 dose level, 2 patients had grade 4 neutropenia in spite of GCSF support; 1 pt had neutropenia > 7 days and one pt had her dose delayed by one week due to neutropenia. Due to these events, the MTD of amrubicin in this pt population (and recommended phase II dose) was 110 mg/m2 with GCSF support. Conclusions: Amrubicin 110 mg/m2 was tolerable as 2nd/3rd-line treatment in women with MBC. Myelosuppression was the most common grade 3/4 toxicity and the DLT, despite the use of prophylactic GCSF support. The phase II portion of this trial is proceeding. Amrubicin dose G3/4 toxicity 90 mg/m2 100 mg/m2 110 mg/m2 120 mg/m2 (n=3) (n=3) (n=3) (n=3) Neutropenia 1 (33%) 1 (33%) 3 (100%) 2 (66%)* Thrombocytopenia 0 0 0 1 (33%) Leukopenia 1 (33%) 1 (33%) 3 (100%) 1 (33%) Anemia 0 0 0 0 Fatigue 1 (33%) 0 0 1 (33%) Nausea/vomiting 0 0 0 2 (66%) Number of DLTs 0 0 0 1 (33%) * One toxicity did not meet DLT criteria due to duration <7 days.
High Prevalence of FLT3 - ITD Mutations in Patients (pts) with Acute Myeloid Leukemia (AML) Who Present with Central Nervous System (CNS) Relapse.
Authors: Fabio P S Santos, Hagop Kantarjian, Tapan Kadia, Carol Bivins, Susan Obrien, Farhad Ravandi, Jorge Cortes, Guillermo Garcia Manero, Stefan Faderl, Sherry Pierce, Elias Jabbour
Journal: Blood (2009)
Something must be done—but chemotherapy isn’t the only option
Authors: Caroline Mawer
Journal: BMJ (2016)

Wise challenges the usefulness of chemotherapy drugs in patients with metastatic cancer,1 and Hewlett “gets it” that a survival benefit of only a few months may not be fundable from a health economist’s point of view.2 Understandably, though, Hewlett highlights the potential personal benefit of chemotherapy. 

So …
Additional Value of Early-Phase 18F-FP-CIT PET Image for Differential Diagnosis of Atypical Parkinsonism
Authors: Soyoung Jin, Minyoung Oh, Seung Jun Oh, Jungsu S. Oh, Sang Ju Lee, Sun Ju Chung, Jae Seung Kim
Journal: Clinical Nuclear Medicine (2016)

Regional cerebral perfusion is coupled to metabolism in general. Early perfusion dominant imaging using F-FP-CIT PET (pCIT) may provide complementary information to delayed dopamine transporter dominant images. We investigated the ability of pCIT to differentiate atypical Parkinson disorder from Parkinson disease (PD) compared to FDG and the image quality for optimizing the acquisition time.Sixty-seven subjects [PD, 23 subjects; multiple system atrophy-cerebellar type (MSA-C), 27 subjects; MSA-Parkinson type (MSA-P), 12 subjects; and progressive supranuclear palsy (PSP), 5 subjects] underwent F-FP-CIT and FDG PET. Using dynamic PET data acquired during the first 10 minutes after F-FP-CIT administration, we generated potential perfusion images of 0 to 5 (pCIT-5m), 0 to 7 (pCIT-7m), and 0 to 10 (pCIT-10m) minutes. We compared regional uptake between groups in pCIT and FDG images and image quality among pCIT images using visual, quantitative, or statistical parametric mapping analyses.Regional cerebral uptake of pCITs correlated well to that of the FDG images (R > 0.5, all). Multiple system atrophy-cerebellar type and MSA-P groups show different regional uptake patterns compared with PD group on pCITs in quantitative and statistical parametric mapping analyses, analogous to FDG images, but not in the PSP group. In visual analysis, concordance rates between each pCIT and FDG image were high (92.3%-96.0%, regional; 86.2%-93.1%, diagnostic), and there was no significant difference among pCITs. However, pCIT-10m discriminated PSP better than others and showed higher signal-to-noise ratio (P = 0.001).F-FP-CIT PETs with the first 10 minutes could be useful for the differential diagnosis of atypical Parkinson disorder by providing complementary FDG-like information to the dopamine transporter binding on late-phase FP-CIT images.
Evaluation of (18F) FDG-PET-CT for preoperative lymph-node staging of bladder cancer.
Authors: Julius van Essen, Joachim Grosse, David J. K. P. Pfister, Robin Epplen, Axel Heidenreich
Journal: Journal of Clinical Oncology (2012)

275 Background: Radical cystectomy with extended pelvic lymphadenectomy (EPLA) is the treatment of choice for muscle-invasive bladder cancer. For preoperative staging computed tomography and magnetic resonance imaging of the abdomen and the small pelvis are most commonly used in daily routine.Since the aforementioned methods, have a low sensitivity to detect local lymph node metastasis (LNM) we have prospectively evaluated the role of FDG – PET/CT for locoregional staging. Methods: In 27 patients (n = 27) with known invasive urothelial carcinoma or squamous cell carcinoma of the bladder a staging FDG – PET - CT was performed 1-2 days prior to radical cystectomy with EPLA. Subsequently, the results of the histopathological work-up of lymph node specimens and their anatomical localisations were correlated to the FDG-PET/CT findings. Total of 452 lymph nodes were removed, on average ≈ 16.7 per patient. Results: In 3/27 (11.1%) patients LNM were detected in histopathology. 2 patients showed one positive lymph node, 1 patient had two LNM. In two of these patients, the FDG-PET/CT showed an increased enrichment of FDG in projection to the corresponding histologically positive LN. One false negative and one false positive result of FDG-PET/CT were found. Calculated based on the patient population, the following statistics were calculated: Sensitivity (SENS) 66%, specificity (SPEC) 95.8%, positive predictive value (PPV) 66%, negative predictive value (NPV) 95.8%. Related to the absolute number of LN (n = 452), the following numbers were calculated: SENS 75% SPEC 98.7, PPV 37.5%, NPV 99.7%. Conclusions: To date, few studies have been conducted with regard to FDG-PET/CT and its role in locoregional staging. The reported specificity and NPV was between 86% and 100%, sensitivity and PPV were between 50% and 100%. Our results demonstrate specificity and NPV values of larger than 90% and make FDG-PET/CT a valuable staging tool to potentially identify patients with negative nodes in whom EPLA could be safely ommitted. Curently, routine use of PET CT scans can not be recommended and it is currently tested in a prospective multicenter study including a larger patient cohort.
Cost-effectiveness of zoledronic acid (ZOL) versus denosumab (Dmab) in prevention of skeletal-related events (SREs) in metastatic breast cancer (mBC).
Authors: J. A. Carter, S. J. Snedecor, S. Kaura, M. Botteman
Journal: Journal of Clinical Oncology (2011)

294 Background: Dmab has been approved in the US for prevention of SREs in mBC on the basis of the results of a phase III trial comparing Dmab vs. ZOL in mBC. In this trial, overall survival, disease progression, and serious adverse events (SAEs) were similar across treatments. The cost of a Dmab injection ($1650) is nearly 2x that of ZOLs ($887). This analysis assessed the cost effectiveness of Dmab vs. ZOL in mBC from a US managed care perspective. Methods: A literature-based Markov model was developed to estimate the survival, quality-adjusted life-years (QALYs), number and costs of SREs, and drug and administration (Dmab=$32.46; ZOL=$153.86) costs for patients (pts) receiving Dmab or ZOL. Inputs were selected to reproduce the phase III trial outcomes up to 28 months. QALYs were estimated by assigning utilities to health states (prior to SRE; SRE; post-SRE, and death). SRE-related costs and utilities were obtained from the literature. Per-event SRE costs ranged from $4,039 (vertebral fracture) to $20,734 (bone surgery). In sensitivity analysis, SAEs were included ($15,441/pt with a SAE). Future outcomes were discounted at 3%/year. Results: Dmab resulted in fewer SREs, more QALYs, and lower SRE-related costs, but higher drug-related and total costs vs. ZOL, resulting in an incremental cost of $6,884/pt (TABLE). The cost per QALY gained was $644,000 when excluding SAEs ($613,000/QALY when including SAEs). Conclusions: Dmab is predicted to result in an incremental cost/QALY gained &gt;$600,000. This high cost/QALY is due to the higher drug acquisition cost of Dmab, combined with the limited prevention of SREs and lack of overall survival/disease progression benefits vs. ZOL. The cost/QALY of Dmab is far higher than what is considered to be good value for a medical intervention ($50,000 to $100,000/QALY), thus raising questions regarding Dmab's value in mBC. [Table: see text]