tbuckley/cabot-search huggingface dataset:
A review of radical prostatectomy outcomes in active surveillance patients—The Sunnybrook experience.
Authors: V. Jethava, D. Vesprini, D. A. Loblaw, A. Mamedov, R. Nam, L. Klotz
Journal: Journal of Clinical Oncology (2011)

104 Background: Prostate cancer is the most prevalent non-cutaneous cancer among North American men. Approximately 50% of these are favorable risk cancers; the NCCN guideline recommends active surveillance for these patients. Patients are generally followed by serial PSAs, DREs and/or TRUS-guided biopsies with triggers identified for each test. Consequently, about 30% of these cancers will be reclassified to a higher risk and require definitive treatment. Cases treated with radical prostatectomy (rP) give important insights into the biology of these cancers. Methods: The ASURE database of active surveillance patients was used to identify cases; a retrospective chart review was completed. The following variables were extracted: primary reason for rP; % biochemical failure; % of patients requiring salvage radiation or hormone therapy; Gleason score (GS), tumor size staging and nodal status in the rP specimen; cause and rate of mortality; proportion of patients treated for PSA-doubling times less then 3 years presenting with a GS greater than 7. Descriptive statistics were used to summarize the results. Results: Of 566 patients in the ASURE database, the charts of 26 patients having an rP were extracted. The primary cause for an rP was a PSA-doubling times less than 3 years (57% of patients) followed by a biopsy indicating a GS of 4+3 or greater (19%). 7% of patients (2/26) were not reclassified but preferred to be treated with rP. 4 patients had biochemical failure (15%) all 4 had salvage therapy. There was 1 cause-specific death. 85% of rP specimens had GS 7, while the remaining had GS 6. Half of these GS 7 individuals had PSA doubling times of less than 3 years. Conclusions: Radical prostatectomy appears to be an effective deferred treatment for patients who are reclassified on active surveillance as evidenced by low prostate-cancer mortality, low rates of biochemical failure acceptable use of salvage therapy. Of interest is that the majority patients with PSAdt &lt; 3 y have Gleason 7 disease on specimen. No significant financial relationships to disclose.
Prenatal exposure to maternal bereavement and offspring psoriasis: a Danish nationwide cohort study
Authors: X. Liu, J. Chen, J. Olsen, V. Schlünssen, N. Momen, J. Li
Journal: British Journal of Dermatology (2016)

Prenatal stress may alter immune competence of the fetus. Limited data exist on the role of antenatal stress in psoriasis development.To investigate whether prenatal exposure to maternal bereavement increases the risk of offspring psoriasis.This register-based cohort study included 1 811 917 live singletons born from 1978 to 2008 in Denmark. The children were assigned to the bereaved group if their mothers lost a child, partner/spouse, parent or sibling during pregnancy or up to 12 months before pregnancy. Follow-up started at the date of birth and ended at the date of first hospital treatment for psoriasis or a prescription redeemed for topical vitamin D derivatives (often used to treat psoriasis), emigration, death or 31 December 2010, whichever came first. We evaluated the hazard ratio (HR) of psoriasis in bereaved children using Cox proportional hazards regressions, compared with the nonbereaved group.During 28 million person-years of follow-up, 7956 children were hospitalized or prescribed medications for psoriasis. By the age of 30 years, 1·54% [95% confidence interval (CI) 1·25-1·90%] of children from the bereaved group were diagnosed with psoriasis, compared with 1·34% (95% CI 1·30-1·38%) of nonbereaved children. Overall, prenatal exposure to maternal bereavement was not associated with risk of psoriasis in general (HR 1·05, 95% CI 0·91-1·20). However, children born to mothers who lost a partner/spouse or an older child had an increased risk of psoriasis (HR 1·33, 95% CI 1·02-1·73).Prenatal exposure to the most stressful life event may contribute to the development and/or exacerbation of psoriasis.
Efficacy of pancreatic enzyme replacement therapy in chronic pancreatitis: systematic review and meta-analysis
Authors: Daniel de la Iglesia-García, Wei Huang, Peter Szatmary, Iria Baston-Rey, Jaime Gonzalez-Lopez, Guillermo Prada-Ramallal, Rajarshi Mukherjee, Quentin M Nunes, J Enrique Domínguez-Muñoz, Robert Sutton
Journal: Gut (2016)

<h3>Objective</h3> The benefits of pancreatic enzyme replacement therapy (PERT) in chronic pancreatitis (CP) are inadequately defined. We have undertaken a systematic review and meta-analysis of randomised controlled trials of PERT to determine the efficacy of PERT in exocrine pancreatic insufficiency (EPI) from CP. <h3>Design</h3> Major databases were searched from 1966 to 2015 inclusive. The primary outcome was coefficient of fat absorption (CFA). Effects of PERT versus baseline and versus placebo, and of different doses, formulations and schedules were determined. <h3>Results</h3> A total of 17 studies (511 patients with CP) were included and assessed qualitatively (Jadad score). Quantitative data were synthesised from 14 studies. PERT improved CFA compared with baseline (83.7±6.0 vs 63.1±15.0, p&lt;0.00001; I<sup>2</sup>=89%) and placebo (83.2±5.5 vs 67.4±7.0, p=0.0001; I<sup>2</sup>=86%). PERT improved coefficient of nitrogen absorption, reduced faecal fat excretion, faecal nitrogen excretion, faecal weight and abdominal pain, without significant adverse events. Follow-up studies demonstrated that PERT increased serum nutritional parameters, improved GI symptoms and quality of life without significant adverse events. High-dose or enteric-coated enzymes showed a trend to greater effectiveness than low-dose or non-coated comparisons, respectively. Subgroup, sensitive and meta-regression analyses revealed that sample size, CP diagnostic criteria, study design and enzyme dose contributed to heterogeneity; data on health inequalities were lacking. <h3>Conclusions</h3> PERT is indicated to correct EPI and malnutrition in CP and may be improved by higher doses, enteric coating, administration during food and acid suppression. Further studies are required to determine optimal regimens, the impact of health inequalities and long-term effects on nutrition.
Prognostic Significance of DNA Methyltransferase 3A Mutations in Cytogenetically Normal Acute Myeloid Leukemia: A Study by the Acute Leukemia French Association
Authors: Aline Renneville, Nicolas Boissel, Olivier Nibourel, Céline Berthon, Nathalie Helevaut, Claude Gardin, Jean-Michel Cayuela, Sandrine Hayette, Oumedaly Reman, Nathalie Contentin, Dominique Bordessoule, Cécile Pautas, Stephane de Botton, Thierry De Revel, Christine Terre, Pierre Fenaux, Xavier Thomas, Sylvie Castaigne, Herve Dombret, Claude Preudhomme
Journal: Blood (2011)
Cancer-Selective Targeting of the NF-κB Survival Pathway in Multiple Myeloma with the GADD45β/MKK7 Inhibitor, DTP3
Authors: Laura Tornatore, Gary Acton, Nigel Adams, Elizabeth A Campbell, James Kelly, Richard M Szydlo, Mike Tarbit, Salina Bannoo, Daniel D'Andrea, Daria Capece, Annamaria Sandomenico, Julian Dyson, Antonio Leonardi, Christoph Driessen, Menotti Ruvo, Ishara Anees, Metod Oblak, Sheena Quaid, Magda J Al-Obaidi, Holger Auner, Reuben Benbenjamin, Richard S Kaczmarski, Martin F Kaiser, Atul Mehta, Heather E Oakervee, Stephen A Schey, Ashutosh Wechalekar, Jane F. Apperley, Guido Franzoso
Journal: Blood (2015)
The Multiple Myeloma Research Consortium (MMRC) Model: Reduced Time to Trial Activation and Improved Accrual Metrics.
Authors: Sandra Wear, Paul G. Richardson, Carolyn Revta, Ravi Vij, Mark Fiala, Sagar Lonial, Dixil Francis, David Samuel diCapua Siegel, Alex Schramm, Andrzej J. Jakubowiak, Colleen K. Harvey, Donna E. Reece, Engin Gul, Sundar Jagannath, Lisa La, Craig C. Hofmeister, Buffy Jansak, Keith Stewart, Rachel Hagerty, Jeffrey L. Wolf, Beth Davis, Amrita Krishnan, Lupe Duarte, Todd M. Zimmerman, Angela Cisneros, Shaji Kumar, Ann Birgin, Robert Ott, Leah Tasca, Susan L. Kelley, Kenneth C. Anderson, Kathy Giusti
Journal: Blood (2010)
Effect of dual inhibition of the Src and insulin-like growth factor-1 receptor (IGF-1R) pathways on antitumor effects in prostate cancer (PCa).
Authors: F. Dayyani, N. Parikh, J. H. Song, J. C. Araujo, J. M. Carboni, M. M. Gottardis, G. C. Trudel, C. Logothetis, G. E. Gallick
Journal: Journal of Clinical Oncology (2011)

21 Background: The Src and IGF-1R axes are aberrantly activated in both PCa and the microenvironment of bone metastases. Dasatinib and BMS-754807 are clinically promising small molecule inhibitors with high potency against Src family kinases and IGF-1R, respectively. The aim of this study was to establish antitumor co-operativity by combining IGF-1R and Src blockade in a preclinical PCa model. Methods: LNCaP and PC3 cells were used as models for androgen-dependent and independent PCa, respectively. Inhibition of Src and IGF-1R pathways was accomplished by pharmacologic agents (dasatinib against Src and BMS-754807 against IGF-1R) as well as by shRNA. Serum IGF-1 levels were measured in patients (pts) with castration-resistant PCa (CRPC) treated with dasatinib and docetaxel in a phase II trial. Results: Src inhibition decreased proliferation of PCa cells, and migration in modified Boyden Chamber and wound assays. In contrast, IGF-1R blockade induced apoptosis (increased Sub-G1 fraction cells, Annexin-V(+) cells and PARP cleavage). Phosphorylation of Akt was partially inhibited by either drug alone and almost completely abrogated by the combination. Intraprostatic injection of shIGF-1R or shSrc PC3 cells in nude mice led to an 83% and 60% decrease in tumor size compared to control shRNA, respectively. In both cell lines, all observed antitumor effects were enhanced when dual blockade was used, relative to blocking the Src or IGF-1R pathway alone. In 9/19 (47%) pts with CRPC, treatment with dasatinib resulted in a compensatory increase of serum IGF-1 levels. Conclusions: Dual inhibition of Src and IGF-1R is effective and complementary in PCa, mediated, in part, through inhibition of the downstream target Akt. In about half of pts treated with dasatinib, an increase in soluble IGF-1 levels was observed, indicating there is a compensatory upregulation of survival pathways that might be abrogated by dual inhibition of Src and IGF-1R. The combination of dasatinib and BMS-754807 may be a rational therapeutic approach in PCa by blocking complementary processes of tumor growth and progression. [Table: see text]
Overall survival with everolimus, sunitinib, and placebo for advanced pancreatic neuroendocrine tumors: A matching-adjusted indirect comparison of randomized trials.
Authors: James E. Signorovitch, Elyse Swallow, Evan Kantor, Xufang Wang, Tomas Hass, Judith Klimovsky, Peter Metrakos
Journal: Journal of Clinical Oncology (2012)

e14621 Background: No randomized trial has compared everolimus (EVE) and sunitinib (SUN) for treatment of advanced pancreatic neuroendocrine tumors (pNET). This study indirectly compared overall survival (OS) with EVE vs. placebo (PBO), and OS and progression-free survival (PFS) with EVE vs. SUN. Methods: Individual patient data were used from the RADIANT-3 trial of EVE 10 mg/day vs. PBO (cutoff: April 2010); published summary data were used from the A6181111 trial of SUN 37.5 mg/day vs. PBO (cutoff: June 2010). To adjust for cross-trial differences, RADIANT-3 patients were subjected to A6181111 exclusion criteria and weighted to match A6181111 baseline demographics, performance status, time since diagnosis, disease sites, distant metastases and prior therapy. After matching, OS was compared between balanced trial populations for EVE vs. the PBO arm from A6181111 (which had access to SUN after progression or early stopping) and vs. the SUN arm. PFS was also compared. Analyses did not adjust for early stopping of A6181111, which may bias towards longer PFS and OS with SUN vs. PBO. Results: 394 patients from RADIANT-3 (after excluding 15 with worse performance status than allowed in A6181111 and 1 missing baseline data) and all 171 patients in A6181111 were included. RADIANT-3 patients differed from A6181111 patients in baseline performance status, prior use of somatostatin analogues, and prior use of systemic chemotherapy before matching. After matching, all baseline characteristics were well-balanced between trials. EVE was associated with significantly prolonged OS vs. PBO in A6181111 (hazard ratio [HR] for death = 0.61, 95% CI = 0.38-0.98, p=0.04), corresponding to a 1-year number needed to treat of 8.3 patients to prevent 1 death. OS and PFS were longer, but not statistically different, with EVE vs. SUN (HR for death = 0.81, 95%CI=0.49-1.31, HR for progression = 0.84, 95% CI=0.46-1.53). Conclusions: After adjusting for cross-trial differences, treatment of advanced pNET with everolimus was associated with significantly prolonged OS compared to placebo. OS and PFS were longer, but not statistically different, with everolimus compared to sunitinib.
Volumetric modulated arctherapy (VMAT) compared with sliding window intensity-modulated radiotherapy (IMRT) for whole pelvis irradiation (WPI) of locally advanced prostate cancer (LAPC).
Authors: Olivier Riou, Pauline Regnault de la Mothe, David Azria, Sabine Vieillot, Norbert Ailleres, Jean-Bernard Dubois, Pascal Fenoglietto
Journal: Journal of Clinical Oncology (2012)

171 Background: Concurrent radiotherapy to the pelvis plus a prostate boost with long term androgen deprivation is a standard of care for LAPC. IMRT has the ability to deliver highly conformal dose to the target while lowering the irradiation of critical organs around the prostate. However, delivery time is signicantly prolonged with static gantry IMRT. VMAT is able to reduce treatment time but results concerning organ sparing are controversial when compared to static gantry IMRT. Methods: 10 patients with locally advanced prostate cancer were included in this dosimetric study. The planning target volumes (PTV) 1 was defined as the pelvic lymph nodes, the prostate and the seminal vesicles plus set up margins. The PTV 2 consisted of the prostate with set up margins. The aimed dose to PTV1 was 54 Gy in 37 fractions and to PTV2, 74 Gy in 37 fractions, in a single plan using the integrated boost method, by means of a 7 coplanar static split fields IMRT, a one arc (RA1) and a two arc (RA2) Rapidarc planification. Results: All three techniques allow a very good coverage of both PTVs with an acceptable homogeneity. Static IMRT enables a better homogeneity for PTV 2 than Rapidarc techniques. Sliding-window IMRT and VMAT permitted to maintain doses to OAR within acceptable levels with a low risk of side-effects for each organ. Nevertheless, VMAT plans result in clinically and statistically significant reduction in doses to bladder (IMRT Vs RA2: Mean dose: 50.1 ± 4.6 Vs 47.1 ± 3.9 Gy, p = 0.037), rectum (Mean dose: 44 ± 4.5 Vs 41.6 ± 5.5 Gy, p = 0.006) and small bowel (V30: 76,47 ± 14,91% Vs. 47,49 ± 16,91%, p = 0.002). Conclusions: VMAT allows for better OAR sparing as compared to sliding-window IMRT while maintining PTV coverage into acceptable levels for WPI of LAPC.
Efficient Gene Transfer into Human CD34+ Peripheral Blood Progenitor Cells Using Pseudotyped Recombinant Adeno-Associated Viral Vectors
Authors: Leopold Sellner, Marlon Veldwijk, Marius Stiefelhagen, Jurgen A. Kleinschmidt, Stephanie Laufs, Julian Topaly, W. Jens Zeller, Frederik Wenz, Stefan Fruehauf
Journal: Blood (2008)
Preprogrammed Long‐Term Systemic Pulsatile Delivery of Parathyroid Hormone to Strengthen Bone
Authors: Ming Dang, Amy J. Koh, Theodora Danciu, Laurie K. McCauley, Peter X. Ma
Journal: Advanced Healthcare Materials (2016)

Parathyroid hormone (PTH) is the only US Food and Drug Administration (FDA)‐approved anabolic agent for the treatment of osteoporosis. The anabolic action of PTH depends on the mode of PTH administration. Pulsatile administration promotes bone formation, however continuous PTH exposure results in bone resorption. In addition, the therapeutic effect of PTH is optimal when the dose and duration fit the therapeutic window. Current PTH treatment requires daily injection, which is neither a convenient nor a favorable choice of patients. Here, an implantable and biodegradable device capable of long‐term pulsatile delivery of PTH is developed as a patient‐friendly alternative. The advanced materials and fabrication techniques developed in this work enable us to preprogram a pulsatile delivery device to systemically deliver 21 daily pulses of PTH that build bone in vivo. In addition, the device is biodegradable and absorbable in vivo so that no retraction procedure is needed. Therefore, this implantable and biodegradable pulsatile device holds promise to promote bone growth and treat various conditions of bone loss without the burden of daily injections or secondary surgeries.
Ulrich Erich Otto Schirrmacher
Authors: Robert Spires
Journal: BMJ (2016)

Ulrich Erich Otto Schirrmacher (“Sherry”) was born in Turgau, Germany, and came to England with his parents in 1947. He went to school in Farnborough and then trained in medicine at St George’s Hospital Medical School in London.

He worked at the Royal Marsden Hospital for a while but then found his calling in general practice. In 1970 he joined the Birmingham Road Practice in Bromsgrove, which later became Davenal House Surgery. …
Return-to-work after radiotherapy for prostate cancer.
Authors: Joen Sveistrup, Peter Meidahl Petersen, Ole Steen Mortensen, Svend Aage Engelholm
Journal: Journal of Clinical Oncology (2012)

218 Background: Returning to work following cancer treatment is a sign of recovery. The purpose of this study was to determine how many patients return to work following definitive intensity-modulated radiotherapy for prostate cancer (PCa). Methods: The Danish DREAM-database contains information on all social benefits paid out to Danish citizens. The data are recorded prospectively every week. Based on the DREAM-database it is possible to assess whether a patient is working, on sick leave, or retired. Data on 410 of the 451 Danish citizens, treated with definitive intensity-modulated radiotherapy for PCa at our center between January 1 2006 and May 1 2010, were obtained from the DREAM-database one year prior to radiotherapy, at the start and at the end of the radiotherapy, and finally one year after radiotherapy was completed. The median age was 66 (age range, 49–76). Patients were divided into five different categories. The categories were “Working or unemployed”, “Sick leave”, “Disability pension”, “Retirement” and “Dead”. Results: The results are shown in the table. Nearly 30% of the patients are working or available for work one year prior to the radiotherapy. This number is reduced to about 12 % at the time of both the start and the end of the radiation treatment. One year after treatment nearly 20% are working. Conclusions: This study shows that a substantial proportion of patients return to work following definitive radiotherapy for PCa. This indicates that the treatment in many cases does not affect the patients’ ability to work. Further research should be on why some patients stop working after completion of definitive radiotherapy for PCa. [Table: see text]
Correlation of efficacy between rash and lapatinib/capecitabine therapy in Japanese HER2-positive metastatic breast cancer patients.
Authors: S. E. Nagai, K. Inoue, S. Kaneko, S. Uchida, T. Higuchi, Y. Hayashi, T. Yoshida, H. Takei, M. Kurosumi, T. Tabei
Journal: Journal of Clinical Oncology (2011)

62 Background: Lapatinib (L) is an oral dual-tyrosine kinase inhibitor with specificity for both EGFR and HER2. A phase III randomized trial (EGF100151) demonstrated that L+ capecitabine (C) is superior to C alone in patients with HER2-positive advanced breast cancer that progressed following prior therapy including trastuzumab. Although, Japanese phase I/II trial (EGF109749) demonstrated better response rate and higher rate of rash over a previous phase III trial. Recent reports demonstrated the correlation of efficacy between EGFR targeted therapy and rash in colon cancer. In lung cancer EGFR mutation, which are predominantly found in patients of East Asia origin are highly sensitive to EGFR-TKI. Analyzing correlation of efficacy between rash and EGFR targeted therapy is important in breast cancer. Methods: From June 2009 to February 2010, we treated 28 HER2-positive MBC patients who developed progression after anthracyclines, taxanes and trastuzumab based regimens with L 1,250 mg p.o. daily plus C 2,000 mg/m 2 p.o. days 1-14 q 21 in Saitama Cancer Center. EGFR status was evaluated by immunohistochemistry. We analyzed the correlation among rash, clinical outcome and EGFR status. Results: Fourteen (50%) patients experienced rash, which were two grade 3, four grade 2 and eight grade 1. Rash experienced group showed superior response rate (77% : 24%, p&lt;0.05) and median survival time (N/A: 259 days, p&lt;0.05) over non-rash group. EGFR status has no correlation between rash and clinical outcome. Conclusions: According to our single institute experience, rash might be predictive factor in Japanese HER2 positive breast cancer patients treated with L+C therapy.
Low-dose gemcitabine and paclitaxel combination therapy as second- or third-line treatment in patients with advanced urothelial cancer: Pain relief and tolerability.
Authors: Yasuyoshi Miyata, Kojiro Ohba, Tomohiro Matsuo, Hideki Sakai
Journal: Journal of Clinical Oncology (2012)

310 Background: Pain is the most devastating symptom of advanced urothelial cancer (UC). In addition, analgesics often decrease quality of life. So, pain relief and reduction of dosage are important goals for patients with such advanced UC. Cisplatin (CDDP)-containing chemotherapy is most effective regimen in patients with metastatic or recurrent UC. On the other hand, there is no established regimen for advanced UC after CDDP-containing chemotherapy. We performed low-dose combined therapy of gemcitabine (GEM) and paclitaxel (PTX), named GP therapy, as second- or third-line treatment for these patients. Methods: Thirty-three patients with metastatic and/or recurrent urothelial cancer (upper urinary tract = 13 and bladder =20 patients) previously treated with CDDP-containing chemotherapy were treated with GP therapy (GEM = 70 mg/m2 and PTX = 700 mg/m2 on day 1 and 8, repeated every 28 days). Survival was calculated from judgment of tumor progression. Pain was measured on a visual analog scale of 0–10. Positive effects for pain relief were defined as a decrease in analgesic consumption or a decrease in pain grade according to the visual analog scale, without increasing the dose of analgesics. Regulation of analgesics was performed by independent team that did not know this study. Pain relief and survival were compared with other chemotherapy (control; GEM alone = 9 and PTX-based chemotherapy except for GP therapy = 14). Results: At the start of this treatment, 31 patients had abdominal or back pain due to UC. In addition, 3 patients also had bone pain of metastatic tumors. In GP therapy, 28 patients (84.8%) were judged as positive in pain and only 1 patient needed to increase analgesics. On the other hand, control group showed 13 of 23 patients (56.5%) were stable and 7 (30.4%) were judged as positive in pain. Kaplan-Meier survival curves showed overall survival periods in patients with GP therapy were better compared to control group (p=0.023). All patients were received in the outpatient setting because severe side effect was not occurred. Conclusions: Low-dose GP therapy is feasible and well-tolerated as second/third-line chemotherapy in patients with advanced UC.
A Practical Approach for Achieving Clinical Immunotherapy of CLL with hCD40L- and hIL-2-Expressing Autologous Tumor Cells.
Authors: Joseph C. Fratantoni, Linhong Li, Linda N. Liu, Madhusudan V. Peshwa, Malcolm Brenner, Eric Yvon, George Carrum, Ettore Biagi
Journal: Blood (2005)