tbuckley/cabot-search huggingface dataset:
Phase III trial of nimotuzumab for the treatment of newly diagnosed diffuse intrinsic pontine gliomas in children and adolescents
Authors: U. Bode, M. Windelberg, M. Massimino, E. Khuhlaeva, M. Warmuth-Metz, R. D. Kortmann, F. Bach, G. Fleischhack
Journal: Journal of Clinical Oncology (2008)

2058 Background: Despite multimodal therapy children with newly diagnosed intrinsic pontine glioma (PG) have a dismal prognosis. Recently novel therapeutic approaches were taken in order to improve the survival of these patients while preserving a good quality of life. This multicentre phase III trial was designed following the excellent results of a phase II study in resistant diffuse intrinsic pontine gliomas (ASCO 2007; 2006) to explore the feasibility and efficacy of the monoclonal anti-EGFR antibody (Nimotuzumab) in the primary treatment of these patients. Methods: Pediatric patients with newly diagnosed PG with radiologically proven disease and a life expectancy of minimum 4 weeks were eligible to the study. The treatment consisted of an induction therapy including a weekly short infusion of 150 mg/m2 nimotuzumab for twelve weeks, concomitantly with radiotherapy at weeks 3 to 8 to a total dose of 54 Gy. In case of non-PD a consolidation therapy of 150 mg/m2 of nimotuzumab biweekly followed until disease progression. The response was documented by MRI (RECIST) in week 12, 24 and 36 and only clinically in rapidly progresssive disease. Results: Between March 2006 and August 2007 42 patients aged 3 to 16 years (median 7 years) were enrolled in this study. 41 patients were evaluable for response. Primary endpoint: Probability of a patient to survive progression free 6 months after diagnosis (Ho: p< 0.5 (one sided sign test) at level 0.025) H1: p> 0.5 or equivalent that the study population has a median PFS over 6 months. Illustration: Two-sided 95%- confidence interval on p, median survival. Secondary endpoint: Overall survival, response rate, toxcicity and quality of life. No severe side effects related to the study medication, either during induction or consolidation, have been observed thus far. Conclusions: These data suggest that the repeated application of Nimotuzumab is well tolerated and safe. Nimotuzumab in combination with radiotherapy has cytotoxic efficacy in PG. Data will be updated as final results by March 30th, 2008. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Oncoscience AG Oncoscience AG
Hyperglycemia and obesity in patients (pts) with acute lymphoblastic leukemia (ALL): Association with prevalence, response, and survival
Authors: K. D. Vu, V. R. Lavis, S. Strom, S. H. Faderl, M. Konopleva, D. A. Thomas, S. Gruschkus, M. Andreeff, H. Kantarjian
Journal: Journal of Clinical Oncology (2007)

7074 Increasing evidence suggests associations between obesity, diabetes and/or hyperglycemia (DM/HG) and solid tumors. Less is known about the relationship of these metabolic factors to the hematologic malignancies. To determine the prevalence of DM/HG and obesity in pts with ALL and whether these are predictors of response and survival, we conducted a retrospective chart review of 299 pts with newly diagnosed ALL, who were evaluated at our institution between November 1999 and May 2005 and received hyper-CVAD therapy: fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with methotrexate and high-dose cytarabine. Median age was 43 yrs (range 15–83). Sixty-one percent of pts were male, and 39% female. Seventy-four percent had a diagnosis (dx) of precursor B cell ALL (22% Ph+), 18% Burkitt's ALL, 6% lymphoblastic lymphoma, 2% other. Prior to therapy, the overall prevalence of DM/HG (diabetes based on reported dx prior to ALL-dx, and hyperglycemia based on baseline serum glucose ≥200 mg/dL) was 16%. Pts with DM/HG were significantly older than those without DM/HG (median age 57 yrs vs. 40 yrs, p&lt;0.001). Complete remission (CR) rate and the CR duration (CRD) were similar in the DM/HG vs. non-DM/HG group. However, the mean CRD was 80 wks in the HG separately group and 121 wks in the non-HG group (p=0.04). The mean CRD was 102 wks in the obese pts and 124 wks in the non-obese pts (p=.04). In univariate analysis, DM/HG, obesity, and older age were associated with shorter overall survival (OS). Mean OS of pts with DM/HG was 134 vs. 194 wks for pts without DM/HG, (p=0.2). Mean OS of obese pts was 136 vs. 199 wks for non-obese pts, (p=0.01). In a multivariable Cox regression model, the only factors that remained significant for survival were age, obesity, and white blood cell count (WBC). There was no significant difference in OS by leukemia diagnosis. In conclusion, the prevalence data suggests that DM/HG may be involved in the development of ALL. However, DM/HG has no impact on survival, probably because of its strong correlation with age. The association of obesity with shorter OS warrants further investigation. No significant financial relationships to disclose.
Long term randomised controlled trial is needed
Authors: R. Lyons
Journal: BMJ (1996)

It is not necessary for Toozs-Hobson and Car- dozo to claim that the whole female population is diseased in order to recommend prophylaxis; we recommend supplementation with folic acid for women before conception and in the first trimester without believing that they all have a dietary deficiency.There may well be a very good argu- ment for all postmenopausal women to take hormone replacement therapy, based on evidence of a favourable ratio of benefits to risks.For the women who are being recommended lifelong hormone replacement therapy, convincing arguments of this sort will be more persuasive than labelling a universal life event as a disease.
Potential head of Food Standards Agency would treat antimicrobial resistance as priority
Authors: Adrian O’Dowd
Journal: BMJ (2016)

The proposed new chair of the Food Standards Agency will treat antimicrobial resistance as a priority, MPs have been told.

Heather Hancock, who is the government’s chosen candidate for the position, explained her plans for the role during a pre-appointment hearing session held on 5 January jointly by the parliamentary health committee and the environment, food, and rural affairs committee.

Hancock joined the agency as deputy chair in September last year. She has served as private secretary to three home secretaries, set up the Millennium Commission as its chief executive, headed the Yorkshire Dales National Park authority, and been on the board at the professional services firm Deloitte.

During the session MPs raised the issue …
Abstract 18375: Prognostic Value of Unipolar vs Bipolar Electroanatomic Voltage Mapping in Patients with Arrhythmogenic Right Ventricular Cardiomyopathy/dysplasia
Authors: Federico Migliore, Alessandro Zorzi, Maria Silvano, Michela Bevilacqua, Martina Perazzolo Marra, Barbara Bauce, Ilaria Rigato, Giuseppe Tarantini, Cristina Basso, Gateano Thiene, Sabino Iliceto, Domenico Corrado
Journal: Circulation (2012)

Background: electroanatomic voltage mapping (EVM) allows to identify and quantify low-voltage right ventricular (RV) areas, which may represent the electroanatomic scar substrate of life-threatening RV tachyarrhythmias. We prospectively assessed the prognostic value of EVM in a consecutive series of patients witharrhythmogenic right ventricular cardiomyopathy (ARVC). Methods: the study population included 69 consecutive patients (47 male; age 37±14 years) fulfilling the International Task Force diagnostic criteria. All patients underwent electrophysiological study and high density EVM (195±22 points), using both bipolar and unipolar map techniques. The extent area of confluent bipolar (&lt;1.5 mV) and unipolar (&lt;6.0 mV) low-voltage electrograms was calculated with the CARTO software. Results: Fifty-three patients (77%) showed ≥1 RV electroanatomic scar regions with an estimated burden of bipolar vs unipolar low-voltage areas of 25.5±12.7% and 66.5±18.4%, respectively (P&lt;0.009). In all the remaining patients with normal bipolar-EVM (n=16; 23%) the use of unipolar EVM technique unmasked ≥1 region of low-voltage electrogram abnormality affecting 27.3±13.8% of RV wall. During 49±13 months of follow-up, 19 (27.5%) patients experienced major arrhythmic events, such as sudden death (n=1), appropriate ICD interventions (n=7) or sustained ventricular tachycardia (n=11). Univariate predictors of arrhythmic outcome included syncope (HR=2.4;95%CI:1.1-6.7;P=0.03), previous cardiac arrest (HR=3.7;95%CI:1.4-8.9;P=0.02), right precordial T-wave inversion (HR=9.3;95%CI:1.7-29) and extent of bipolar low-voltage areas (HR=1.7/5%;95%CI=1.5-2; P&lt;0.001), while the only independent predictor was the bipolar low-voltage electrogram burden (HR=1.5/5%;95% CI:1.4-1.6;P&lt;0.001). All patients with normal bipolar EVM had an uneventful clinical course despite the presence of unipolar scar areas. Conclusions: The extent of bipolar RV endocardial low-voltage area is a powerful predictor of malignant arrhythmic events in ARVC/D, independently of medical history and RV datation/dysfunction. Non-transmural RV electroanatomic scar involvement (abnormal unipolar/normal bipolar EVM) characterized a low-risk subgroup of patients.
Use of Chest Computed Tomography for Staging and Treatment of Wilms’ Tumor in Children
Authors: Daniel M. Green
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.12.2763 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12065550 Use of Chest Computed Tomography for Staging and Treatment of Wilms' Tumor in Children Daniel M. GreenxDaniel M. GreenSearch for articles by this author Show More Roswell Park Cancer Institute, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY https://doi.org/10.1200/JCO.2002.20.12.2763 Full Text PDF Figures and Tables "Use of Chest Computed Tomography for Staging and Treatment of Wilms' Tumor in Children." Journal of Clinical Oncology, 20(12), pp. 2763–2764© 2002 by American Society of Clinical Oncology
Influence of Orotic Acid on Liver Tumorigenesis in Rats Ingesting Ethionine, &lt;italic&gt;N-2&lt;/italic&gt;-Fluorenylacetamide, and 3′-Methyl-Dimethylaminoazobenzene&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: H Sidransky, E Verney
Journal: JNCI Journal of the National Cancer Institute (1970)
Feasibility of breast conservation after neoadjuvant taxae-based chemotherapy in locally advanced breast cancer
Authors: M. A. Aboziada, M. I. El-Sayed, D. W. Maximous, M. E. Abdel-Wanis, M. M. Bakr
Journal: Journal of Clinical Oncology (2009)

e11627 Background: Neoadjuvant chemotherapy is the standard of care of locally advanced cancer breast. Our study was aiming to evaluate the feasibility of breast conversation (BC) after neoadjuvant chemotherapy. Methods: Forty five patients had stage IIB and stage IIIA were selected to 3 cycles taxane-based neoadjuvant chemotherapy. Patient who had tumours ≤ 5cm underwent BC while patients who had tumour size &gt;5cm underwent radical surgery. Negative margin is essential for BC. Adjuvant chemotherapy and 3-D radiotherapy ± hormonal treatment were given to all patients. Results: Thirty four patients had BC. Response to chemotherapy was the only statistically significant factor which influences the BC. Incidence of local recurrence was 5.9% for patients who had BC at a median follow up 24 months. Conclusions: Breast conservation is feasible in selected cases of locally advanced, non metastatic cancer breast. We recommend that patients who have tumour size ≤ 4cm after chemotherapy are the best candidates for BC. No significant financial relationships to disclose.
Improved survival with cyclic chemotherapy for nonseminomatous germ cell tumors of the testis.
Authors: C J Logothetis, M L Samuels, D Selig, D Swanson, D E Johnson, A C von Eschenbach
Journal: Journal of Clinical Oncology (1985)

Forty-eight patients with advanced nonseminomatous germ cell tumors of the testis received a combination of cyclophosphamide, doxorubicin, and cisplatin (CISCAII) and a modified combination of vinblastine and bleomycin (VBIV) cyclic chemotherapy. Forty-four (92%) have achieved a complete remission. No patient in complete remission has relapsed with a mean follow-up of 139.0 weeks (SEM 7.0 weeks). The patients were stratified according to the modified Samuels clinical staging criteria. Thirty-seven (77%) had advanced disease (stage III-B3 to III-B5), ten of whom had advanced visceral non-lung disease (stage III-B5). Chemotherapy was individualized by tumor volume and response to therapy. Two courses were delivered after complete remission or the development of a stable mass with negative serum biomarkers. Twenty-four patients (50%) were explored for a persistent and stable mass. No viable cancer was found; 15 (62%) had mature teratomas and nine (38%) had scar. No patients suffered from doxorubicin cardiotoxicity, clinical pulmonary bleomycin toxicity, or persistent cisplatin renal failure. Four patients died. One patient, an unrecognized drug abuser, died of toxicity. Three with far-advanced tumors died of progressive disease. CISCAII/VBIV cyclic chemotherapy is superior to chemotherapy with vinblastine, bleomycin, and cisplatin, resulting in a 92% complete remission rate and a significant reduction in long-term toxicity.
Taste and Smell in Disease
Authors: Franklin H. Epstein, Susan S. Schiffman
Journal: New England Journal of Medicine (1983)

Taste, Smell, and Food IntakeTaste and smell have a potent role in the control of intake, although the relation is not a simple one. It is clear that the ability to identify sodium chloride properly by taste in order to correct a salt deficiency is innate; however, preferences for specific foods containing other basic nutrients, including other minerals, appear to be learned through the association of taste with a state of need.100 In addition to sodium chloride, specific appetites have been reported for thiamine, calcium, potassium, and sugar in response to nutritional and metabolic imbalances. Overall, taste and smell . . .
Rapid, effective, and sustained control of breakthrough pain (BTP) in cancer patients treated with BEMA (BioErodible MucoAdhesive) fentanyl
Authors: R. Kapoor, A. Finn, D. Blum, E. Giefer
Journal: Journal of Clinical Oncology (2008)

9600 Background: Transmucosal delivery of fentanyl can provide prompt control of breakthrough pain (BTP) in patients taking stable doses of opioids for chronic pain. The BEMA drug delivery system was designed for fast oral transmucosal drug delivery with dose to dose reliability of plasma concentrations, and ease of patient use. BEMA fentanyl consists of a small, dissolvable, polymer disc formulated with the opioid narcotic fentanyl for application to the buccal (inner lining of cheek) membranes. The mucoadhesive polymers adhere to the membrane and rapidly deliver fentanyl across the capillary-rich mucosa. Methods: Eighty adult cancer patients on stable opioid doses who achieved adequate control of BTP with BEMA fentanyl (200 to 1,200μg) in an open-label titration phase were treated for up to 9 BTP episodes with the previously determined BEMA fentanyl dose (6 episodes) and placebo (3 episodes) in a double-blind, multiple crossover study (FEN-201). Subjects recorded pain intensity (PI; 11-point scale) at treatment and at 5, 10, 15, 30, 45, and 60 minutes after treatment. The primary outcome measure was the sum of PI differences (SPID) at 30 minutes. In an open-label study (FEN-202), 173 cancer patients on stable opioid doses (including patients who successfully completed FEN-201) were treated with an open-label BEMA fentanyl dose (200 to 2,400μg) determined in a titration phase. Results: A total of 394 BTP episodes were treated with BEMA fentanyl and 197 with placebo in FEN-201; SPID values for BEMA fentanyl-treated episodes were statistically significantly greater than placebo-treated episodes at 15 minutes (12.7 ± 0.88 vs. 10.6 ± 1.06; p=0.047), 30 minutes (49.1 ± 2.40 vs. 39.0 ± 2.95, p=0.004), and through 60 minutes. In FEN-202, in which more than 56,000 BTP episodes were treated, rescue medication was required for only 10.2% of all episodes treated, and the study medication performance was rated as ’Good’ or better for 84.8% of all BTP episodes treated. Conclusions: BEMA fentanyl provides patients with a rapid, reliable treatment for BTP that is easy to use and provides a continued benefit over an extended duration of use. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration BioDelivery Sciences International BioDelivery Sciences International BioDelivery Sciences International BioDelivery Sciences, BioDelivery Sciences International
Reducing the health inequalities associated with employment conditions
Authors: Joan Benach, Carles Muntaner, Haejoo Chung, Orielle Solar, Vilma Santana, Sharon Friel, Tanja A.J. Houweling, Michael Marmot
Journal: BMJ (2010)

Fair and efficient government policies on labour and welfare can reduce health inequalities that accompany poor employment conditions and unemployment, explain Joan Benach and colleagues.
Five-year survival analysis of interferon-a plus sorafenib versus sorafenib monotherapy as first-line treatment for metastatic clear cell renal cell carcinoma.
Authors: Ye Ding-Wei, Zhang Hai-Lang
Journal: Journal of Clinical Oncology (2015)

486 Background: We compared the short- and long-term efficacy and safety of interferon-a plus sorafenib with sorafenib monotherapy as first-line treatment in metastatic clear cell renal cell carcinoma (mRCC) patients. Methods: mRCC patients who had not received systemic treatment were administered either interferon-a (300 MIU IM every other day) plus sorafenib (400 mg bid n=24, Group A) or sorafenib monotherapy (400 mg bid; n=24, Group B). Objective responses (OR; RECIST criterion ver 1.0) and differences in OR, progression-free survival (PFS), overall survival (OS) and toxicity were compared. Results: Sixty eight percent males were present in both the groups with comparable baseline demographic characteristics. After a median follow-up of 68 months, the OR was comparable (p=0.726) in Group A vs B; complete remission (1 vs 0 cases), partial remission (6 vs 7 cases), stable disease (14 vs 15 cases), and progressive disease (3 vs 3 cases). No significant difference was observed in the median PFS (p=0.965) and median OS (p=0.223) between both groups [9.4 months (95% CI: 5.8-17.4), Group A vs 14.0 months (95% CI: 9.9-18.0), Group B] and [32.9 months (95% CI: 8.2-87.1), Group A vs 20.4 months (95% CI: 16.2-24.6), Group B], respectively. The 5-year survival rate was higher in Group A vs B (46% vs 25%). Toxicity symptoms like fever (13 vs 3 cases), fatigue (15 vs 9 cases) and neutropenia (6 vs 1 cases) were more pronounced in Group A vs B. The incidence of hand and foot skin reactions, alopecia, rash, hypertension, liver dysfunction, hypophosphatemia, anemia, and other toxicities was similar in both groups. There were 14 (58.3%) and 8 (33.3%) cases of dosage reduction or suspension in Groups A and B, respectively. Conclusions: Short-term effect of interferon-a plus sorafenib as first-line treatment for mRCC was comparable to sorafenib monotherapy in terms of OR and PFS. Although higher toxicity was reported for interferon-a plus sorafenib, the combination holds promise for improving long-term OS.
A phase II study of neoadjuvant docetaxel/carboplatin with or without trastuzumab in locally advanced breast cancer: Response and cardiotoxicity
Authors: H. R. Chang, D. Slamon, R. Prati, J. Glaspy, M. D. Pegram, F. C. Kass, L. D. Bosserman, J. Taguchi, R. Dichmann, D. Chung
Journal: Journal of Clinical Oncology (2006)

10515 Background: A phase II clinical trial was conducted to study the safety and efficacy of neoadjuvant docetaxel/carboplatin (T/C) with or without trastuzumab (H) in women with stage III breast cancer. Methods: Forty-eight of 75 planned primary breast cancer patients (T3 or T4, any N, M0), age between 18 and 80 have been enrolled. Four cycles of T (75 mg/m 2 ) + C (AUC 6) were given every 3 weeks preoperatively. Patients with HER-2 amplified tumors (FISH +) were randomized to receive either weekly concurrent H or T/C alone preoperatively and T/C plus H postoperatively. Tumors were assessed clinically at baseline and after neoadjuvant therapy. Cardiac assessment consisted of medical history, EKG and LVEF (by echocardiogram or MUGA) at baseline and at the end of neoadjuvant chemotherapy. Results: Available data from 45 of 48 enrolled patients showed 49% (22 cases) with complete clinical response, with 54.5% being HER-2 (+) (12 cases). Stable disease was seen in one patient who was HER-2 (−) (2.2%). Of 37 with complete pathology verification, 11 (29.7%) showed pathologic complete response (pCR) of the primary tumor with 5 cases being HER-2 (+). Of the 22 HER-2 (+) cases that completed neoadjuvant treatment, 11 received T/C/H and 11 received T/C. pCR was noted in 36.4% of the T/C/H group and 9% of the T/C group. LVEF data is available from 43 patients during the neoadjuvant phase, showing 18.6% (8 cases) with decrease of ≥ 10% (5 patients in the T/C arm and 3 patients in the T/C/H arm), although none had cardiac symptoms or LVEF below the normal limit. Conclusions: T/C ± H is clinically active in patients with locally advanced breast cancer including a 30% pCR rate. The cardiotoxicity rates were comparable between patients who received T/C and T/C/H. No significant financial relationships to disclose.
Phase II clinical trial of mutant Ras peptide vaccine in combination with GM-CSF and IL-2 in advanced cancer patients
Authors: M. S. Achtar, A. Toubaji, V. Herrin, B. Gause, M. Hamilton, R. Berhens, F. Grollman, S. Bernstein, S. Khleif
Journal: Journal of Clinical Oncology (2007)

3067 Background: Mutant ras oncogenes produce novel proteins that are processed and displayed through HLA molecules on tumor cells. Therefore, mutant ras is an attractive target for vaccine therapy. We have shown in a previous phase I trial that vaccination with mutant ras peptides produced specific immune responses (IR). Here we tested in a phase II trial the use of specific mutant ras peptides in combination with GM-CSF and IL-2 in advanced cancer patients carrying the ras mutation in their tumors. Methods: We treated 17 patients with advanced cancers (14 CRC, 1 NSCLC and 2 pancreatic) with 5000μg of the corresponding mutant ras peptide given SQ along with GM-CSF and IL-2. GM-CSF was given SQ on days -1,0,1,2 followed by ten days of low dose SQ IL-2. Vaccines were repeated every 5 weeks for a maximum of 15 cycles or until disease progression. Results: 11 patients who received 3 or more vaccinations were tested for immune response by measuring IFN-γ mRNA copies in PBMCs pre and post vaccination. 6/11 patients generated specific IR to the corresponding mutant ras vaccine. The median overall survival and the median progression-free survival for all patients were 25.8 and 13.1 months respectively. However, in the 6 patients with positive IR, it was 39.9 and 17.9 months compared to 18.5 and 15.6 months in the 5 patients who showed no IR. No grade IV toxicity occurred. Most adverse events were Grade I-II toxicities and resolved spontaneously. Grade III toxicities led to IL-2 dose reduction in 3/17 patients (18%). Conclusions: The study showed that vaccination of advanced cancer patients with mutant ras peptides in combination with GM-CSF and IL-2 is safe and can induce specific immune responses. Furthermore, those patients who generated IR showed better clinical outcome, as reflected by PFS and OS. So we believe that this vaccine may form a potentially promising approach in combination with other therapeutic modalities in advanced solid tumors. No significant financial relationships to disclose.