tbuckley/cabot-search huggingface dataset:
Taxane-induced alopecia: A historical review of patients with ovarian or breast cancer treated with with paclitaxel, docetaxel or paclitaxel poliglumex
Authors: E. A. Calhoun, E. Welshman, S. Brown
Journal: Journal of Clinical Oncology (2005)

8044 Background: Data from ovarian cancer patients treated with platinum and either paclitaxel (P) or cyclophosphamide (CYC) show that alopecia is predictive of reduced quality of life (QOL). Paclitaxel poliglumex (PPX; XYOTAX) is a macromolecular drug conjugate linking paclitaxel with poly-L-glutamic acid, a biodegradable polymer. PPX is water soluble and administered as a 10-minute infusion without premedication. Preclinical and clinical findings show that PPX is relatively stable in plasma; over 95% of paclitaxel in circulation is present as the inactive conjugate. Reduced systemic exposure to high concentrations of free paclitaxel may result in a more favorable toxicity profile, including minimal alopecia. Methods: We compared rates and grades of P- or docetaxel-induced alopecia (reported in prescribing information [PI]) to PPX-induced alopecia (phase 1–2 clinical trials). Results: Pooled analysis of 10 studies of P showed that alopecia was observed in 87% of patients with ovarian (n = 493) or breast cancer (n = 319). Alopecia occurred in 74.2% of docetaxel-treated patients with breast cancer (n=965). In combination trials in previously untreated ovarian carcinoma, alopecia incidence (all grades/grade 3) was 96%/51% with P 175 mg/m2 plus cisplatin (C) 75 mg/m2 (n = 339), and 55%/6% with P 135 mg/m2 plus C 75 mg/m2 (n = 196). In a combination trial in breast cancer patients (n=744), alopecia incidence (all grades) was 97.8% with docetaxel 75 mg/m2 plus doxorubicin 50 mg/m2 and CYC 500 mg/m2. In contrast, grade ≥2 alopecia was absent in a phase 2 trial of PPX 175 mg/m2 in 99 heavily pretreated patients with recurrent ovarian cancer; hair thinning (grade 1) was reported in 7% of patients. No alopecia was reported in 17 patients with advanced breast cancer receiving PPX 235 mg/m2. Pooled analysis of phase 1–2 trials indicate that grade 3 alopecia (total hair loss) has not been observed in any patient treated with PPX (n = 275), including 47 patients receiving PPX plus C. Conclusions: PPX induces infrequent and mild alopecia compared with standard taxanes. Delivery of effective taxane therapy without the negative impact of hair loss on QOL is an important advantage for PPX. No significant financial relationships to disclose.
Concurrent chemoradiation therapy with oral etoposide and cisplatin for locally advanced inoperable non-small-cell lung cancer: radiation therapy oncology group protocol 91-06.
Authors: J S Lee, C Scott, R Komaki, F V Fossella, G S Dundas, S McDonald, R W Byhardt, W J Curran
Journal: Journal of Clinical Oncology (1996)

PURPOSE Patients with locally advanced inoperable non-small-cell lung cancer (NSCLC) have a poor clinical outcome. We conducted a prospective study to evaluate the merit of chemotherapy administered concurrently with hyperfractionated thoracic radiation therapy. PATIENTS AND METHODS Seventy-nine patients with inoperable NSCLC were enrolled onto a multicenter phase II trial of concurrent chemoradiation therapy. Treatment consisted of two cycles of oral etoposide 100 mg/d (50 mg/d if body-surface area [BSA] &lt; 1.70 m2), intravenous cisplatin 50 mg/m2 on days 1 and 8, and hyperfractionated radiation therapy 5 days per week (1.2 Gy twice daily &gt; 6 hours apart; total 69.6 Gy). RESULTS Seventy-six assessable patients with a Karnofsky performance status &gt; or = 60 and adequate organ function who had received no prior therapy were evaluated for clinical outcome and toxic effects. After a minimum follow-up duration of 21 months, the 1- and 2-year survival rates and the median survival duration were 67%, 35%, and 18.9 months overall; they were 70%, 42%, and 21.1 months for patients with weight loss of &lt; or = 5%. Toxicity was significant; 57% developed grade 4 hematologic toxicity, 53% grade 3 or 4 esophagitis, and 25% grade 3 or 4 lung toxicity. However, only 6.6% of patients had grade 4 or lethal nonhematologic toxicity, which included three treatment-related deaths (two of pneumonitis and one of renal failure). CONCLUSION Concurrent chemoradiation therapy with oral etoposide and cisplatin plus hyperfractionated radiation therapy is feasible. The survival outcome from this regimen compares favorably with that of other chemoradiation trials and even of multimodality trials that have included surgery.
Differentiation of high-grade and low-grade diffuse gliomas by intravoxel incoherent motion MR imaging
Authors: Osamu Togao, Akio Hiwatashi, Koji Yamashita, Kazufumi Kikuchi, Masahiro Mizoguchi, Koji Yoshimoto, Satoshi O. Suzuki, Toru Iwaki, Makoto Obara, Marc Van Cauteren, Hiroshi Honda
Journal: Neuro-Oncology (2015)

Our aim was to assess the diagnostic performance of intravoxel incoherent motion (IVIM) MR imaging for differentiating high-grade gliomas (HGGs) from low-grade gliomas (LGGs). Forty-five patients with diffuse glioma (age 50.9 ± 20.4 y; 26 males, 19 females) were assessed with IVIM imaging using 13 b-values (0–1000 s/mm2) at 3T. The perfusion fraction (f), true diffusion coefficient (D), and pseudo-diffusion coefficient (D*) were calculated by fitting the bi-exponential model. The apparent diffusion coefficient (ADC) was obtained with 2 b-values (0 and 1000 s/mm2). Relative cerebral blood volume was measured by the dynamic susceptibility contrast method. Two observers independently measured D, ADC, D*, and f, and these measurements were compared between the LGG group (n = 16) and the HGG group (n = 29). Both D (1.26 ± 0.37 mm2/s in LGG, 0.94 ± 0.19 mm2/s in HGG; P < .001) and ADC (1.28 ± 0.35 mm2/s in LGG, 1.03 ± 0.19 mm2/s in HGG; P < .01) were lower in the HGG group. D was lower than ADC in the LGG (P < .05) and HGG groups (P < .0001). D* was not different between the groups. The f-values were significantly larger in HGG (17.5 ± 6.3%) than in LGG (5.8 ± 3.8%; P < .0001) and correlated with relative cerebral blood volume (r = 0.85; P < .0001). Receiver operating characteristic analyses showed areas under curve of 0.95 with f, 0.78 with D, 0.73 with ADC, and 0.60 with D*. IVIM imaging is useful in differentiating HGGs from LGGs.
Granulocyte Colony-Stimulating Factor After Intensive Consolidation Chemotherapy in Acute Myeloid Leukemia: Results of a Randomized Trial of the Groupe Ouest-Est Leucémies Aigues Myeloblastiques
Authors: J.L. Harousseau, B. Witz, B. Lioure, M. Hunault-Berger, B. Desablens, M. Delain, F. Guilhot, P.Y. Le Prise, J.F. Abgrall, E. Deconinck, D. Guyotat, J.P. Vilque, P. Casassus, O. Tournilhac, B. Audhuy, E. Solary
Journal: Journal of Clinical Oncology (2000)

Ten years after the first clinical studies, the clinical impact of myeloid growth factors in acute myeloid leukemia is still unclear. One of the objectives of the Groupe Ouest-Est Leucémies Aigues Myeloblastiques (GOELAM) 2 trial was to evaluate the benefit of granulocyte colony-stimulating factor (GCSF) given only after the two courses of intensive consolidation chemotherapy (ICC) used to maintain complete remission (CR).One hundred ninety-four patients who were in CR after induction treatment were randomly assigned to receive G-CSF (100 patients) or no G-CSF (94 patients) after two courses of ICC (ICC 1, high-dose cytarabine plus mitoxantrone; ICC 2, amsacrine plus etoposide). G-CSF (filgrastim) was administered from the day after chemotherapy until granulocyte recovery at a daily dose of 5 microg/kg.In the G-CSF group, the median duration of neutropenia (< 0.5 x 10(9)/L) was dramatically reduced, both after ICC 1 (12 v 19 days, P <.001) and after ICC 2 (20 v 28 days, P <.001). The median duration of hospitalization was also significantly shorter in the G-CSF group (24 v 27 days after ICC 1, P <.001; 29 v 34 days after ICC 2, P <. 001). The median duration of intravenous antibiotics was significantly reduced after ICC 1 and ICC 2, and the median duration of antifungal therapy was significantly reduced after ICC 1. However, the incidence of microbiologically documented infections, the toxic death rate, the 2-year disease-free survival, and the 2-year overall survival were not affected by G-CSF administration. Moreover, the median interval between ICC1 and ICC2 was reduced by only 2 days, and the number of patients undergoing ICC2 was not increased in the G-CSF arm.G-CSF should be administered routinely after ICC to reduce the duration of neutropenia and hospitalization. However, G-CSF did not seem to significantly increase the feasibility of this two-course program or modify overall outcome.
Hypoxic phenotype in pulmonary metastases of different primary tumors
Authors: Thomas Schweiger, Christoph Nikolowsky, Lukas Lehmann, Robert Wiebringhaus, György Lang, Peter Birner, Walter Klepetko, Hendrik-Jan Ankersmit, Konrad Hoetzenecker
Journal: European Respiratory Journal (2012)

Tumor hypoxia has been shown to be a common feature in tumor growth and metastasis. It negatively affects the clinical outcome in patients with various malignancies. Although hypoxia is described in many primary tumor types, data on pulmonary metastases is lacking.  We determined the expression of hypoxia-related proteins in paraffin-embedded specimens of pulmonary metastases of different types of cancer (breast cancer n= 6, colo-rectal carcinoma n=29, renal cell carcinoma n=13, sarcoma n=10). All recruited patients underwent curative metastasectomy at the Department of Thoracic Surgery, MUV, between April 2009 and December 2011. Expression of carbonic anhydrase 9 (CA9), heat-shock protein 70 and HIF prolyl hydroxylase 2 was evaluated by immunohistochemistry. Metastasis free survival and estimated tumor size and overall survival was determined for all sub-groups.  Hypoxia related proteins are expressed in 66.6%, 76.9%, 7.7% and 0.0% of pulmonary metastases of breast cancer, colo-rectal carcinoma, renal cell carcinoma and sarcoma, respectively. Furthermore, metastases with highly positive CA9-staining are associated with early tumor spreading to the lung (Disease free interval: 21.8±7.0 months vs. 46.1±26.6 months; p=0.008)  This study provides first evidence for hypoxia marker expression in pulmonary metastases and its clinical relevance. These findings may be important for future therapeutic targets in the therapy of generalized malignant diseases.
Prognostic factors in adult patients with locally controlled soft tissue sarcoma. A study of 546 patients from the French Federation of Cancer Centers Sarcoma Group.
Authors: J M Coindre, P Terrier, N B Bui, F Bonichon, F Collin, V Le Doussal, A M Mandard, M O Vilain, J Jacquemier, H Duplay, X Sastre, C Barlier, M Henry-Amar, J Macé-Lesech, G Contesso
Journal: Journal of Clinical Oncology (1996)

PURPOSE To define the prognostic factors in adult patients with locally controlled soft tissue sarcoma (STS) and to determine which patients should be considered for adjuvant treatment. PATIENTS AND METHODS Five hundred forty-six patients with a nonmetastatic and locally controlled STS, collected in a cooperative data base by the French Federation of Cancer Centers (FNCLCC) Sarcoma Group from 1980 and 1989, were studied. Histologic slides of all patients were collegially reviewed. Initial treatment consisted of complete tumor resection with amputation in only 4% of the patients. Adjuvant radiotherapy was administered to 57.9% and adjuvant chemotherapy to 31%. Relationships between tumor characteristics were analyzed, and univariate and multivariate analyses were performed using Cox models for the hazards rate of tumor mortality, development of distant metastasis, and strictly local recurrence. RESULTS Unfavorable characteristics with an independent prognostic value for tumor mortality were: grade 3 (P = 3 x 10(-10)), male sex (P = 1.5 x 10(-5)), no adjuvant chemotherapy (P = 5.4 x 10(-5)), tumor size &gt; or = 5 cm (P = 3.8 x 10(-3)), and deep location (P = 4.6 x 10(-3)). Unfavorable characteristics for the development of distant metastasis were: grade 3 (P = 4 x 10(-12)), no adjuvant chemotherapy (P = 6.4 x 10(-4)), tumor size &gt; or = 10 cm (P = 9.8 x 10(-4)), and deep location (P = 1.3 x 10(-3)). For the development of local recurrence, the unfavorable characteristics were: no adjuvant radiotherapy (P = 3.6 x 10(-6)), poor surgery (local excision) (P = 2 x 10(-4)), grade 3 (P = 7.6 x 10(-4)), and deep location (P = 10(-2)). Grade, depth, and tumor size were used to define groups of patients according to the metastatic risk. Adjuvant chemotherapy was beneficial in terms of overall survival and metastasis-free survival in grade 3 tumor patients only. Despite worse characteristics concerning tumor depth, tumor-node-metastasis (TNM) and American Joint Committee (AJC)/International Union Against Cancer (UICC) classifications and grade in patients with adjuvant radiotherapy, the latter experienced significantly fewer local recurrences than patients with no radiotherapy. CONCLUSION Grade, tumor depth, and tumor size could be used to select patients with a high metastatic risk, for which adjuvant chemotherapy could be beneficial.
Adalimumab and etanercept serum (anti)drug levels are not predictive for successful dose reduction or discontinuation in rheumatoid arthritis
Authors: Noortje van Herwaarden, Chantal A M Bouman, Aatke van der Maas, Ronald F van Vollenhoven, Johannes W Bijlsma, Frank H J van den Hoogen, Alfons A den Broeder, Bart J F van den Bemt
Journal: Annals of the Rheumatic Diseases (2015)

Tapering of TNF inhibitors (TNFi) is feasible in many patients with rheumatoid arthritis (RA), but sometimes leads to flaring. TNFi trough serum levels and antidrug antibodies (ADAs) have been proposed as predictors for successful dose reduction or discontinuation,1–3 suggesting that: (1) a patient with low or undetectable serum levels (with or without ADAs) should be able to successfully stop the TNFi and (2) a patient with high serum levels should be able to reduce the dose. As obtaining trough levels is often not practical, our aim was to investigate whether random timed serum drug levels and ADAs of adalimumab and etanercept are predictive for successful dose reduction or discontinuation of these TNFi in patients with RA doing well.

For these analyses 118 patients with RA from an open randomised clinical trial investigating a dose reduction strategy of adalimumab or etanercept with 18 months follow-up were included . 4 Serum samples were collected at baseline (before start of dose reduction) at a regular visit, unrelated to time …
Treatment and Prevention of Respiratory Syncytial Virus Lower Respiratory Tract Infection
Authors: ERIC A. F. SIMOES
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

The association between respiratory syncytial virus (RSV) bronchiolitis and asthma has been established for more than 30 yr. However, the question of causality remains unanswered: Does severe RSV lower respiratory tract infection (LRTI) cause long-term pulmonary morbidity or do factors that predispose a child to wheeze later in life also predispose the child to severe RSV LRTI? In several human studies (1–4), obstructive airway disease appears to occur up to 10 yr after an initial RSV infection. The Tucson Children’s Respiratory Study showed an effect at 10 yr (5) but not by 13 yr (6). Hall and coworkers prospectively monitored 29 children who were hospitalized during infancy for RSV LRTI for 8 yr (7). Six children continued to have lower respiratory tract disease and six (21%) had persistently low oxyhemoglobin levels (Sa O2 ) at follow-up. Sigurs and colleagues found that children who had experienced RSV LRTI were more likely to have asthma and recurrent wheeze for 7 yr (4). Weber and colleagues (8) determined in Gambia that RSV LRTI predisposed children to recurrent wheeze, but only for 2 yr; after 3 yr, there was no significant difference between RSV-infected children and control children with respect to wheezing episodes. Many of the patients in the Tucson study had only RSV upper respiratory tract infections and none were hospitalized (5, 6). Patients in the study by Sigurs and coworkers (4), Hall and colleagues (7), and those in the Gambia study (8) had severe RSV disease. The reason for the observed varying degree and length of long-term sequelae may lie in the differing degrees of severity of illness studied (mild versus severe), or differences in location (developed versus developing countries), or ecological differences in sensitizing allergens (desert versus temperate versus tropical), or other undetermined factors. It remains to be determined whether severe RSV LRTI causes the pulmonary sequelae observed in longitudinal studies (i.e., a causeand-effect relationship) or whether inherent genetic or structural abnormalities that predispose a child to wheeze later in life also predispose the child to severe RSV LRTI. If causality exists, reducing severe RSV LRTI would reduce subsequent wheezing; if causality does not exist, reducing severe RSV LRTI would have no effect on subsequent wheezing. This is, therefore, a key clinical issue, which has been addressed in three sets of studies: antiviral therapy for RSV LRTI, antiinflammatory therapy for RSV LRTI, and prevention of RSV LRTI.
Mean platelet volume in obstructive sleep apnea patients. Another link to cardiovascular disease
Authors: Paschalis Steiropoulos, Evangelia Nena, Panagiota Zikidou, Pavlos Zarogoulidis, Nikolaos Papanas, Konstantinos Archontogeorgis, Theodora Gkioka, Eleni Pitta, Argyrios Tzouvelekis, Stavros Anevlavis, Marios Froudarakis, Demosthenes Bouros
Journal: European Respiratory Journal (2011)

Pobjective and aims: Various studies have examined the association between Obstructive Sleep Apnea (OSA) and cardiovascular risk. Mean Platelet Volume (MPV) has been evaluated as a potential marker of cardiovascular risk in several lines of patients. The aim of this study was to evaluate MPV in relation to OSA severity, as well as to investigate the associations between MPV and anthropometric characteristics and parameters of breathing function during sleep.

Materials and methods: This study included 699 subjects with suspected sleep apnea, who were all evaluated by Epworth Sleepiness Scale (ESS), physical examination and polysomnography. According to Apnea-Hypopnea Index (AHI), patients were divided into 4 groups: Group A (n=156) with AHI<5/h; Group B (n=137) AHI: 5-14.9/h; Group C (n=100) AHI: 15-29.9/h and Group D (n=303) AHI ≥30/h. MPV (blood samples anticoagulated with sodium citrate) was measured in two blood cell counters (Sysmex SF-3000 and Sysmex XE 2100).

Results: MPV was significantly higher in group D (mean value 11.7±1.2) than in groups A (9.9±1.2), B (9.9±1.6), and C (10.8±1.8) (p <0.001). In all patients, significant correlations were shown between MPV and AHI (p<0.001), average SpO2 (p<0.001), minimum SpO2 (p<0.001), t<90 (p<0.001), Arousal Index (p<0.001) and ESS (p=0.002), while regression analysis revealed no association between MPV and BMI (p=0.855) or age (p=0.774).

Conclusions: MPV is higher in patients with severe OSA and is correlated with various indices of breathing function during sleep, suggesting a role in the pathogenesis of cardiovascular risk in OSA patients.
Cisplatin and etoposide as first-line chemotherapy for metastatic breast carcinoma: a prospective randomized trial of the Italian Oncology Group for Clinical Research.
Authors: G Cocconi, G Bisagni, M Bacchi, C Boni, R Bartolucci, G Ceci, M A Colozza, V De Lisi, R Lottici, A M Mosconi
Journal: Journal of Clinical Oncology (1991)

In this prospective randomized study, first-line treatment with the combination of cisplatin (P) and etoposide (E) was compared with the standard cyclophosphamide, methotrexate, and fluorouracil (CMF) combination in 140 patients. Complete remissions were obtained in 11% of 65 assessable patients on CMF and in 12% of 65 assessable patients on PE. Complete plus partial remission rates were 48% on CMF and 63% on PE (P = .08). Time to progression (median, 32 v 31 weeks), duration of response (48 v 39 weeks), and survival (75 v 76 weeks) were not different. Hematologic toxicity was significantly higher with PE, and gastrointestinal side effects were frequent with this treatment. This study demonstrated that the PE combination is effective as front-line chemotherapy. As far as response rate is concerned, a trend of superiority over CMF was observed, which was of borderline significance. Due to the lack of survival advantage and to toxicity, this combination is not recommended for routine clinical use. However, its high level of activity should be taken into account for further research.
The recent multi-ethnic global lung initiative 2012 (GLI2012) reference values don't reflect contemporary Mediterranean spirometry
Authors: Helmi Ben Saad, Mohamed Nour Elattar, Khaoula Hadj Mabrouk, Chiraz Maatoug, Sonia Rouatbi
Journal: European Respiratory Journal (2013)

Introduction. The applicability of the recent Multi-ethnic reference values derived by the GLI2012 in interpreting spirometry data in Tunisian subjects has not been studied. Aims. To see if GLI2012 Multi-ethnic and Tunisian prediction equations can be used interchangeably while interpreting routine spirometric data. Methods. Spirometric data were recorded from 1192 consecutive spirometry procedures in adults aged 18-63 years. Predicted values and lower limits of normality (LLN) were calculated using both regression equations. Applied d efinitions : large airway obstructive ventilatory defect (LAOVD): FEV1/FVC   LLN and FVC > LLN and FEF25-75% < LLN. Tendency through a restrictive ventilatory defect (TRVD): FEV1 and FVC < LLN. Mixed VD (MVD): FEV1/FVC and FEV1 and FVC < LLN and FEV1 < LLN. Z-scores for spirometry from Mediterranean healthy subjects (n=489) were calculated. If the average z-score deviated by < ±0.40 from the overall mean, the GLI2012 reference values will be considered as reflective of contemporary Mediterranean spirometry.

Results : According to Tunisian and GLI2012 reference equations, the percentages of subjects with normal spirometry data, or having LAOVD, or SAOVD or a TRVD or a MVD, were significantly different, respectively, 35% vs 84%, 7% vs 4%, 37% vs 2%; 19% vs 9% and 3% vs 2%. The mean±SD Z-scores of the healthy group were -0.55±0.87 for FEV1, -0.62±0.86 for FVC, 0.10±0.73 for FEV1/FVC, 4.43±0.69 for FEF75% and 0.07±0,93 for FEF25-75%).

Conclusion . Our results don’t support the use of the GLI2012 reference ranges to interpret spirometry in Mediterraneans.