tbuckley/cabot-search huggingface dataset:
Higher dose per fraction and shorter overall treatment time using intensity-modulated radiation therapy versus conventional radiation therapy with concurrent carboplatin and 5-fluorouracil for locally advanced oropharyngeal carcinoma: A comparison of toxicity and efficacy
Authors: S. Clavel, D. Nguyen, P. Després, B. Fortin, G. Coulombe, D. Donath, D. Soulières, D. Charpentier, L. Guertin, P. F. Nguyen-Tan
Journal: Journal of Clinical Oncology (2009)

6038 Background: The aim of this retrospective study was to compare toxicity and efficacy of two different radiotherapy regimens, the first one using intensity-modulated radiation therapy (IMRT) to that of conventional radiotherapy (CRT) in patients treated with concomitant chemotherapy for locally advanced oropharyngeal cancer. Methods: Between January 2000 and December 2007, 249 patients with stage III-IV squamous cell oropharyngeal carcinoma were treated at our institution with definitive concurrent chemoradiation using carboplatin 70 mg/m 2 /day for four days and 5-fluorouracil 600 mg/m 2 /day as a continuous infusion every 3 weeks. One hundred patients had 70 Gy in 33 fractions using IMRT (2.12 Gy per day) and 149 received CRT at 70 gy in 35 fractions (2 Gy per day), both administered five times a week. Toxicities were compared using Fisher's exact test. Overall survival (OS), disease-free survival (DFS), and locoregional control (LRC) were estimated using the Kaplan-Meier method and compared with the log-rank test. Results: Median follow-up was 33 months. Three year actuarial rates for OS, DFS, and LRC were 95.4 vs. 75.8% (p &lt; 0.001), 89.3 vs. 71.6% (p &lt; 0.001), and 92.4 vs. 85.3% (p = 0.050) for IMRT and CRT respectively. To minimize the effect of changes in treatment paradigm over time, analyses were performed for patients treated after January 2004 and still showed OS, DFS, and LRC differences. Comparison of toxicities demonstrated that IMRT was associated with fewer dermatitis than CRT (p &lt; 0.01), but caused the same rates of mucositis, weight loss, enteral feeding, hospitalization and death during treatment. There was significantly less xerostomia at 24 and 36 months (p &lt; 0.001) following the end of treatment with IMRT. Conclusions: In this retrospective study, higher dose per fraction and shorter overall treatment time using IMRT given concurrently with chemotherapy when compared to CRT is a safe regimen with better OS, DFS, LRC, and less long term xerostomia. Altered fractionation RT with chemotherapy seems to result in better outcome and future prospective trials are needed to confirm this hypothesis. No significant financial relationships to disclose.
A rational approach for a phase I clinical study design to evaluate CNTO 95, a novel, fully human anti-a<sub>v</sub>monoclonal antibody (MAb), in patients with solid tumors
Authors: H. M. Davis, U. Prabhakar, H. Jang, Q. Jiao, M. Trikha, J. Ford, C. Joel, A. Fasanmade, M. A. Graham
Journal: Journal of Clinical Oncology (2004)

2609 Background: Centocor has developed a fully human MAb,designated CNTO 95, against avintegrin receptors, known to be essential mediators of angiogenesis. CNTO 95 is currently being evaluated in a Phase I clinical study in patients with solid tumors refractory to standard therapy. Methods: The range of doses chosen for this study (0.1–10 mg/kg) in humans was based on both the pharmacokinetic (PK) and toxicologic profile observed in primates as well as on efficacy models in rodents and in vitro studies of human endothelial cell proliferation. Results: The antiangiogenic efficacy and antitumor effects of this MAb were demonstrated in both mouse and rat tumor-cell-induced angiogenesis as well as in human melanoma xenograft models. Furthermore, the safety of this antibody is supported by toxicology studies in cynomolgus monkeys. Complete inhibition of cell growth was achieved when the concentration of CNTO 95 was >10 μg/mL. Hence, it was estimated that a serum concentration of at least 10 μg/mL of CNTO 95 would need to be maintained to observe an in vivo pharmacological response. Based on monkey PK and safety studies, doses of 3 and 10 mg/kg were predicted to maintain trough levels of CNTO 95 above 10 μg/mL for 2–3 days in humans. Conclusions: The dose range (0.1–10 mg/kg) chosen for the Phase I clinical study is expected to span sub-therapeutic and therapeutic serum levels of CNTO 95 in patients. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Centocor, Inc. Centocor, Inc. Centocor, Inc.
Sense About Science charity joins fight against bid to prevent transparency of trials
Authors: J. Wise
Journal: BMJ (2015)

The charity Sense About Science plans to intervene in a legal challenge facing the Health Research Authority (HRA) over its work to promote clinical trial transparency.

Richmond Pharmacology, a contract research organisation that runs clinical trials on behalf of drug companies, launched a judicial review against the HRA in March this year.

The HRA, a UK body established to promote and protect the interests of patients in health research, has been working to make clinical trials more transparent. In September 2013 the body made the registration of a clinical …
RUNX1 haploinsufficiency results in granulocyte colony-stimulating factor hypersensitivity
Authors: D W L Chin, M Sakurai, G S S Nah, L Du, B Jacob, T Yokomizo, T Matsumura, T Suda, G Huang, X-Y Fu, Y Ito, H Nakajima, M Osato
Journal: Blood Cancer Journal (2016)

RUNX1/AML1 is among the most commonly mutated genes in human leukemia. Haploinsufficiency of RUNX1 causes familial platelet disorder with predisposition to myeloid malignancies (FPD/MM). However, the molecular mechanism of FPD/MM remains unknown. Here we show that murine Runx1(+/-) hematopoietic cells are hypersensitive to granulocyte colony-stimulating factor (G-CSF), leading to enhanced expansion and mobilization of stem/progenitor cells and myeloid differentiation block. Upon G-CSF stimulation, Runx1(+/-) cells exhibited a more pronounced phosphorylation of STAT3 as compared with Runx1(+/+) cells, which may be due to reduced expression of Pias3, a key negative regulator of STAT3 signaling, and reduced physical sequestration of STAT3 by RUNX1. Most importantly, blood cells from a FPD patient with RUNX1 mutation exhibited similar G-CSF hypersensitivity. Taken together, Runx1 haploinsufficiency appears to predispose FPD patients to MM by expanding the pool of stem/progenitor cells and blocking myeloid differentiation in response to G-CSF.
Dose-painted intensity-modulated radiation therapy for anal cancer: A multi-institutional report of acute toxicity and response to therapy.
Authors: T. S. Hong, H. K. Tsai, J. Coen, L. S. Blaszkowsky, K. L. Hartshorn, E. L. Kwak, J. Willins, D. P. Ryan, L. A. Kachnic
Journal: Journal of Clinical Oncology (2010)

4144 Background: Chemoradiation for anal cancer yields effective tumor control, but is associated with significant acute toxicity. We report our multi-institutional experience using dose-painted IMRT (DP-IMRT), allowing for the simultaneous delivery of escalated doses to gross tumor and lower doses to normal tissues, in attempts to reduce this morbidity. Methods: From August 2005 to May 2009, 43 patients were treated with DP-IMRT and concurrent chemotherapy for biopsy-proven, squamous cell carcinoma of the anal canal at two tertiary-care academic medical centers. DP-IMRT was prescribed as follows - T2N0: 42 Gy, 1.5 Gy/fraction (fx) to elective nodal planning target volume (PTV) and 50.4 Gy, 1.8 Gy/fx to anal tumor PTV; T3-4N0-3: 45 Gy, 1.5 Gy/fx to elective nodal PTV, and 54 Gy, 1.8 Gy/fx to the anal tumor and metastatic nodal PTV > 3 cm with 50.4 Gy, 1.68 Gy/fx to nodal PTVs < 3 cm in size. All patients received concurrent chemotherapy: 5FU and MMC in 35; cisplatin was substituted for the MMC in 3, and single agent 5FU in 5 patients. Acute toxicity was scored using CTC 3.0. Late toxicity was scored using the RTOG criteria. Actuarial analysis was performed using the Kaplan-Meier method. Results: Median age was 58 years; 67% female; 16% stage I, 37% II; 42% III; 5% IV. Fourteen patients were immunocompromised: 21% HIV-positive and 12% on chronic immunosuppression. Median follow-up was 24 months (range, 0.6-114 months). Sixty percent completed chemoradiation without treatment interruption; median duration of treatment interruption was 2 days (range, 2-24 days). Acute Gr. 3+ toxicity included: heme 51%, derm 10%, GI 7% and GU 7%. Predictors of Gr. 3+ morbidity included the presence of any immunosuppressive co-morbidity and multi-agent chemotherapy. All patients achieved a clinically CR twelve weeks posttreatment. Two-year LC, OS, colostomy-free survival and metastasis-free survival was 95%, 94%, 90% and 92%, respectively. Conclusions: DP-IMRT appears effective for anal canal cancer, even in immunocompromised patients. The acute toxicity profile with DP-IMRT is favorable.Further analysis of outcomes and late morbidity will be required to validate this approach. No significant financial relationships to disclose.
A randomized study of platinum based chemotherapy with or without amifostine for the treatment of children with hepatoblastoma (HB): A report of the Intergroup Hepatoblastoma Study P9645
Authors: H. M. Katzenstein, K. Chang, M. Krailo, L. Bowman, B. Greffe, R. Castleberry, M. Malogolowkin
Journal: Journal of Clinical Oncology (2004)

8518 Background: Platinum-based therapy has improved the outcome for children with HB, however this therapy is associated with an increased risk of ototoxicity. Amifostine is a chemoprotectant developed to protect normal tissues from chemotherapy-induced side effects without adversely affecting anti-tumor activity. One of the goals of the P9645 study was to estimate the efficacy of Amifostine in reducing the toxicity associated with platinum agents in children with HB by randomizing patients to receive chemotherapy with or without Amifostine. Methods: A total of 203 patients were entered onto this study. Stage I/II patients received treatment with 4 cycles of Cisplatin-5-Fluorouracil-Vincristine (C5V) +/- Amifostine and patients with Stage III/IV were randomized to receive 4–6 cycles of C5V +/- Amifostine or Carboplatin alternating with Cisplatin (CC) +/- Amifostine. Amifostine (740 mg/m2/dose) was given intravenously prior to the platin agent in every cycle. Audiometric data was assessed in a cohort of surviving patients who had not progressed, and therefore had not received additional therapy off protocol. Results: The disease outcome for patients receiving Amifostine was not different from those treated without Amifostine. Audiometric data was available for 116 eligible patients, and fully evaluable in 82. Amifostine did not prevent ototoxicity as significant hearing loss (> 40 dB extending to 2 kHz) was seen in 14% (5/37) of the patients receiving Amifostine versus 9% (4/45) of the patients who did not receive Amifostine (p=0.72 ). Other organ toxicities (renal/bone marrow) were not different for patients who did or did not receive Amifostine, however, the use of Amifostine was associated with a higher incidence of hypocalcemia (5% vs. 0.5%, p=0.00006). Conclusion: Amifostine in the dose and schedule used in this study does not protect against the ototoxicity associated with platinum agents used for the treatment of children with HB. No significant financial relationships to disclose.
SAT0383 Using MRI synovitis to count involved joints in the ACR/EULAR 2010 RA criteria increases their sensitivity and specificity
Authors: A. Duer-Jensen, K. Hørslev-Petersen, L. Bak, J.S. Johansen, M.S. Hansen, M.L. Hetland, B.J. Ejbjerg, H.M. Lindegaard, H. Vinterberg, J. Møller, M. Østergaard
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> In a prospective cohort study of patients with undifferentiated arthritis (UA) to investigate the ability of ACR/EULAR 2010 criteria with or without different MRI variables to diagnose RA, considering ACR 1987 criteria as gold standard reference <h3>Methods</h3> 119 pts (≥2 tender/swollen joints in MCP, PIP, wrist or MTP joints for &gt;6 wks but &lt;24 mths) without a rheumatological diagnosis, underwent clinical (68SJC/68TJC), biochemical, X-ray and MRI (unilateral wrist, MCP, PIP and MTP, scored by OMERACT RAMRIS (MTP not scored for synovitis (syn))) examinations and were followed for &gt;12 mths. Sensitivity, specificity, accuracy, positive/negative predictive value (PPV/NPV) for diagnosing RA by 1) using ACR/EULAR 2010 criteria with and without including MRI syn, 2) substituting 68SJC/68TJC with MRI syn or 3) incorporating MRI bone oedema (BE) in the criteria are shown in Table. <h3>Results</h3> ACR/EULAR criteria <i>with</i> MRI syn variables included, gave a slight increase in sensitivity (Table, row 2-4) compared to <i>without</i> MRI (row 1). BE increased the sensitivity even more, highest with BE in wrist and/or MTP joint (row 5-8). Highest sensitivity, specificity, agreement and PPV were demonstrated when 68SJC/68TJC was replaced with counting only joints with MRI syn (row 9-11). Using syn ≥1 as cut-off (row 9) the sens, spec, accuracy, PPV and NPV were all higher than using the criteria based on clinical examination (row 1). <h3>Conclusions</h3> When fulfilment of the ACR 1987 criteria at follow-up is considered the gold standard reference, substituting IJC with MRI synovitis in joints of one hand, markedly increases the sensitivity and specificity of the ACR/EULAR 2010 criteria in UA. <h3>Disclosure of Interest</h3> None Declared
Association between standard clinical and pathological breast cancer characteristics and the 21-gene recurrence score: A population-based study
Authors: I. Wolf, N. Ben-Baruch, R. Shapira-Frommer, S. Rizel, H. Goldberg, N. Yaal-Hahoshen, B. Klein, D. B. Geffen, B. Kaufman
Journal: Journal of Clinical Oncology (2007)

11002 Background: The 21-gene recurrence score (RS) aims to quantify chemotherapy benefit in lymph node-negative, estrogen receptor (ER)-positive breast cancer (BC) patients. We aimed to elucidate the association between the RS and clinical-pathological features in a population-based Israeli cohort. Methods: Study population included all Israeli BC female patients referred to the RS assay from October 2004 until October 2006. Clinical and pathology data were collected upon referral, RS risk was categorized as previously defined (low &lt; 18, intermediate 18–30, high = 31) and chemotherapy benefit was also assessed for each patient using NCCN guidelines, St. Gallen recommendations and Adjuvant! Online. Results: 300 patients were referred to the assay by 70 physicians from 16 institutions. Low, intermediate and high RS were noted in 109 (36 %), 134 (45 %) and 57 (19%) of the patients respectively, compared to 54%, 21% and 25% respectively, in the validation study (JCO;24:3726). Median age was 54 and median tumor size was 1.6 cm. Similar age distribution, tumor size and ER staining intensity were noted in all risk categories. Interestingly, no association has been identified between the RS and the presence of lymph nodes micrometastases. High tumor grade was noted in 15%, 20% and 56%; progesterone expression in 88% 72% 43%; non-infiltrative ductal carcinoma (IDC) 24%, 12% and 6%; and Her2 expression in 2%, 3% and 19% of the low, intermediate and high risk categories respectively (p&lt;0.0001 for all variables). Risk assessment according to clinical guidelines or Adjuvant! Online correlated poorly with the RS. Conclusions: Risk stratification of referred Israeli patients differs from that of the validation study population. Moreover, the RS did not correlate with age, tumor size and ER intensity. The RS correlated with histology, grade, PR and Her2 expression and may be predicted, in specific subsets of patients, using these features. However, RS categorization cannot be predicted by commonly-used clinical predicting tools. No significant financial relationships to disclose.
Improved communication and referral process may be a better use of resources
Authors: E. Carlin, S. Mann, S. E Barton, F. C Boag
Journal: BMJ (1995)

title.Other titles were not well favoured.Omitting the terms "sex" and "genito" may reduce potential embarrassment, and we currently favour the title clinic IA-department of GU medicine.The next step must be to educate, at a national level, both the lay public and some of
Pharmacogenomic prediction of breast cancer treatment outcome with adjuvant tamoxifen in postmenopausal women with estrogen receptor-positive breast cancer
Authors: O. Pribylova, L. B. Petruzelka, S. Argalaczova, B. Konopasek, J. Drazdakova, O. Slanar, O. Slanar, T. Zima
Journal: Journal of Clinical Oncology (2009)

e11501 Background: The clinical outcome of tamoxifen-treated breast cancer patients may be influenced by the activity of cytochrome P450 enzymes that catalyze the formation of antiestrogenic metabolites endoxifen and 4-hydroxytamoxifen. Methods: The AmpliChip CYP450 Test was used to identify CYP2D6 genotypes which have an impaired ability to metabolize tamoxifen into the active metabolite, endoxifen. Results: Our aim is to determine the share of ultrarapid (UM), extensive (EM), intermediate (IM) and poor (PM) metabolizers in the group of postmenopausal women with estrogen receptor-positive breast cancer. We are presenting first 72 results as the part of long term study on 180 women. It is evident that EM and UM have significantly lower percentage of disease progression (22% respectively 0%) compare to IM (67%). No progression observed at PM needs further monitoring and investigation. Conclusions: The results tentatively support the hypothesis, that the genetic variants associated with activity of CYP2D6 could help to clinicians in determining the therapeutic strategy. [Table: see text] No significant financial relationships to disclose.
Anticancer Teamwork: Cross-Presenting Dendritic Cells Collaborate with Therapeutic Monoclonal Antibodies
Authors: Céline Robert-Tissot, Daniel E. Speiser
Journal: Cancer Discovery (2016)

Abstract Summary: Cross-presentation of tumor antigens represents a key pathway in antitumor immune responses that can be exploited to synergize not only with the already prominent “checkpoint blockade,” but also with newer attempts to use T-cell stimulatory monoclonal antibodies in immunotherapy. Cancer Discov; 6(1); 17–9. ©2016 AACR. See related article by Sánchez-Paulete et al., p. 71.
Exercise improves quality of life in patients with cancer: a systematic review and meta-analysis of randomised controlled trials
Authors: Jasper K W Gerritsen, Arnaud J P E Vincent
Journal: British Journal of Sports Medicine (2015)

Purpose Exercise may be associated with increased health-related quality of life (QoL) in patients with cancer, but it is not prescribed as standard care during or after cancer treatment. We systematically reviewed the methodological quality of, and summarised the evidence from, randomised controlled trials (RCTs). A meta-analysis was performed to examine the effectiveness of exercise in improving the QoL in patients with cancer, during and after medical treatment. Methods RCTs that met the PICO (Patient Intervention Control Outcome) format were included in this study. 16 RCTs were identified through a search of Embase, Medline (OvidSP) and the Cochrane Library. These trials were reviewed for substantive results and the methodological quality was assessed using the Delphi criteria list. Results Exercise interventions differed widely in content, frequency, duration and intensity. Based on the meta-analysis, exercise improved QoL significantly in patients with cancer as compared to usual care (mean difference 5.55, 95% CI (3.19 to 7.90), p&lt;0.001). Other outcomes closely related to QoL, such as fatigue and physical functioning, also improved. Conclusions Exercise has a direct positive impact on QoL in patients with cancer, during and following medical intervention. Exercise is a clinically relevant treatment and should be an adjunct to disease therapy in oncology.
A simple mathematical approach to deciding the dosage of vaccine against pandemic H1N1 influenza
Authors: H Nishiura, K Iwata
Journal: Eurosurveillance (2009)

Results from early clinical trials have shown that a single dose of pandemic H1N1 influenza vaccine may generate sufficient antibody response, but the relevance of this fact to public health decision making has yet to be clarified. The present study compares the risk of clinical attack (i.e. clinical attack rate) between one- and two-dose vaccination schemes. If the efficacies do not greatly vary between one- and two -dose schemes, one-dose vaccination may well be supported. Nevertheless, two-dose vaccination is shown to result in less morbidity if the vaccine efficacies are greatly diminished by reducing the dose. As long as the detailed efficacy estimates rest on theoretical assumptions, single-dose vaccination may only be sufficiently justified in a specific setting where the number of vaccines is extremely limited.
Dose-intensified rechallenge with temozolomide: One week on/one week off versus 3 weeks on/one week off in patients with progressive or recurrent glioblastoma (DIRECTOR).
Authors: Ghazaleh Tabatabai, Wolfgang Wick, Guido Reifenberger, Joachim Peter Steinbach, Oliver Schnell, Peter Hau, Ulrich Herrlinger, Michael Sabel, Ralf Ketter, Uwe S. Schlegel, Christine Marosi, Roland Goldbrunner, Krisztian Homicsko, Guido Nikkhah, Josef Pichler, Peter Vajkoczy, Juergen Meixensberger, Michael Weller
Journal: Journal of Clinical Oncology (2013)

TPS2103 Background: No standard of care has been defined for patients with glioblastoma who relapse or progress on or after standard temozolomide (TMZ)-based radiochemotherapy. Rechallenge with TMZ using various dose-intensified regimens is a common approach for recurrent glioblastoma. O6-methylguanylmethyltransferase (MGMT) promoter methylation is a strong prognostic marker in newly diagnosed glioblastoma. However, in recurrent glioblastoma, the prognostic value of the MGMT status has remained unclear. Methods: The DIRECTOR trial is an open-label prospectively randomized phase II trial investigating 2 different TMZ rechallenge regimens, i.e. 1 week on/1 week off (Arm A, 120-150 mg/m 2 per day for 7 days) versus 3 weeks on/1 week off (Arm B, 80-100 mg/m 2 per day for 21 days) in recurrent glioblastoma. Patients were enrolled at first progression after having completed the first-line TMZ radiochemotherapy and at least 2 adjuvant TMZ cycles. At randomization, MGMT gene promoter methylation status from the primary or recurrent tumor was mandatory. The study treatment was monitored every 2 months by MRI using MacDonald criteria. Translational studies included blood biomarker (e.g. regulatory T cell counts, MGMT activity in peripheral blood). In addition, quality-of-life was evaluated by QLQ-C30 and QLQ-BN20 EORTC scores. Neurocognitive testing using the NeuroCogFx was optional. The primary endpoint is median time-to-treatment failure that was defined as progression, toxicity or death from any cause. Secondary endpoints are progression-free survival, overall survival, response and MGMT correlations. The trial was performed in 16 sites in Austria, Germany, and Switzerland. 105 of 166 patients have been enrolled (53 patients in Arm A and 52 patients in Arm B) before the enrollment was prematurely stopped on 30 June 2012. The database will be closed on 30 June 2013. Clinical trial information: NCT00941460.