tbuckley/cabot-search huggingface dataset:
A nationwide cohort study of surveillance for stage I seminoma.
Authors: Mette Sakso Mortensen, Maria Gry Gundgaard, Jakob Lauritsen, Mads Agerbaek, Niels Vilstrup Holm, Hans von der Maase, Gedske Daugaard
Journal: Journal of Clinical Oncology (2013)

4502 Background: The standard treatment for stage I seminoma remains a topic for discussion. Survival rates are excellent irrespective of treatment modality (radiotherapy, carboplatin or surveillance). However, late effects might differ between treatment options. Only smaller surveillance studies with limited follow-up have previously been published. We present data from a large nationwide cohort study on surveillance in stage I seminoma patients. Methods: A nationwide and population based clinical database covering germ cell cancer patients diagnosed 1984-2007 was constructed. The database included 4,683 cases. All stage I seminoma patients followed by surveillance were identified. Possible prognostic factors for relapse were collected from patient files and pathology reports. By merging our data with the national patient registry we were able to collect data on late relapses, vital status and cause of death on all patients up to December 2012. Results: 1,822 patients with stage I seminoma were followed on a surveillance program. The median follow-up time was 15.4 years. Ten year cancer specific survival (CSS) was 99.6%. A total of 355 (19.5%) patients had a relapse after a median time of 13.7 months (range 1.2-173.7 months). Within 2-5 years after orchiectomy, 72 patients (4.0 %) had a relapse and 26 patients (1.4 %) had a relapse more than 5 years after orchiectomy. Invasion of blood or lymphatic vessels, tumor size &gt; 4 cm and serum human chorionic gonadotropin &gt; 200 IU/L were all predictive factors for relapse in both univariate and multivariate analyses (p&lt;0.01). Invasion of rete testis was significant in the univariate analysis but not in the multivariate analyses (p=0.53). Conclusions: We present the largest cohort ever published of stage I seminoma patients followed on a surveillance program. The prognosis was excellent with a 10 year CSS of 99.6%. Prognostic factors for relapse were identified. The relapse rate after 5-years of follow-up was 1.4%. Surveillance should be the preferred option of management in stage I seminoma patients. Several international guidelines are now in agreement with this statement.
Adverse effects of treatment in HIV-associated tuberculosis patients in Iran
Authors: Parvaneh Baghaei Shiva, Payam Tabarsi, Majid Marjani, Mohammad Reza Masjedi
Journal: European Respiratory Journal (2011)

Background:  We intend to assess the frequency of adverse effects of tuberculosis treatment in HIV patients.   Methods:  The study was conducted at National Tuberculosis referral center in Iran, 2005-2010 including all documented TB patients with HIV co-infected. All patients received anti-TB treatment based on National TB Program. All adverse effects (AE) observed in patients were recorded in our registry.   Results:  Of the total 151 TB/HIV patients, 81 (53.6%) developed adverse effects (AE) whether major or minor. Major AE (65) included hepatitis (46), convulsion (4), thrombocytopenia (17), rash (5) that 86.2% of them had CD4   Conclusion:  This study showed that major adverse effects do not affect to outcome of TB treatment.
S9900: Surgery alone or surgery plus induction (ind) paclitaxel/carboplatin (PC) chemotherapy in early stage non-small cell lung cancer (NSCLC): Follow-up on a phase III trial
Authors: K. Pisters, E. Vallieres, P. A. Bunn, J. Crowley, K. Chansky, R. Ginsberg, D. R. Gandara
Journal: Journal of Clinical Oncology (2007)

7520 Background: Small randomized and non-randomized studies suggest induction chemotherapy may improve survival in early stage NSCLC. The primary objective of this study was to determine if induction PC could improve survival over surgery alone. Preliminary results of this trial were reported at ASCO 2005 (J Clin Oncol, ASCO Proc 23(16S) 2005:7012). Median time for patients alive at last contact is now 46 months (mos). Methods: Consenting patients with clinical stage T2N0, T1–2N1 and T3N0–1 NSCLC (excluding superior sulcus tumors) were stratified by clinical stage (IB/IIA vs. IIB/IIIA) and randomized to induction PC (P:225 mg/m 2 over 3 hours, C:AUC=6) on day 1, every 3 weeks × 3 or surgery alone. Eligible patients had a performance status 0–1, age =18 years (yrs), predicted post- resection FEV1 =1.0L. Surgery was at least a lobectomy and mediastinal nodal sampling. The primary endpoint was a 33% increase in overall survival over expected 2.7 yrs median for surgery. Planned sample size was 600 patients, 81% power, 1-sided test, 0.025 significance. Results: S9900 closed 07/04 when adjuvant chemotherapy became standard. 354 patients had accrued; 174-surgery alone, 180- induction PC; 19 were ineligible. Median age 65 yrs, 66% male, 70% IB/IIA, 30% IIB/IIIA. Major radiographic response to induction PC was 41%. Treatment-related deaths: 3 during induction PC, 11 within 30 days of surgery (7-induction PC arm, 4-control). Progression-free survival (PFS), overall (OS) survival rates and hazard ratios (HR) are shown. Conclusions: PFS and OS continue to trend in favor of induction PC with HR similar to those observed in adjuvant trials, supporting the role of chemotherapy in operable NSCLC. Randomized trials comparing induction to adjuvant chemotherapy are warranted. Supported by SWOG CA30102. [Table: see text] [Table: see text]
Population pharmacokinetics of CNTO 95, a human anti-αv integrin antibody, in patients with solid tumors
Authors: J. Ling, Y. Zhang, C. Hu, T. Jiao, Z. Lang, B. Foster, J. Marini, B. Zhong, T. Puchalski, H. Zhou
Journal: Journal of Clinical Oncology (2009)

e14593 Background: CNTO 95 is a human anti-αv integrin antibody. The dose-dependent antitumor effect of CNTO 95 has been demonstrated in multiple preclinical studies. The objective of these analyses was to characterize the population pharmacokinetics (PPK) in solid tumor cancer patients treated with CNTO 95 with and without dacarbazine. Methods: Approximately 140 patients with solid tumors from two phase I and one phase II studies were included in this analysis. CNTO 95 was administered via intravenous infusion, with 11 different regimens ranging from 0.1 to 20 mg/kg every 1–4 weeks. Serum CNTO 95 concentrations were determined using a validated enzyme-linked immunosorbent assay. Serum CNTO 95 concentration data were analyzed using noncompartmental analysis (NCA) and a PPK approach. Results: The NCA results indicated that total clearance of CNTO 95 decreased as the dose of CNTO95 increased and approached saturation at 10 mg/kg. Based on the NONMEM analysis, data were best described by a 2-compartment model with dual clearance pathways (linear and nonlinear elimination). The nonlinear elimination process is likely due to the receptor-mediated clearance. Mean estimates of central volume, peripheral compartment volume, intercompartmental clearance and linear clearance, as well as an additional nonlinear clearance, were in agreement with antibodies targeting membrane-bound receptors. No differences in the PPK of CNTO 95 were found in patients treated with and without co-administered dacarbazine. Interindividual variability was moderate (&lt;50%). Conclusions: A PPK model could adequately describe serum CNTO 95 concentration-time profiles. Extensions of this model can be used to assist in the selection of doses in diverse oncology patient populations. [Table: see text]
Density gradient of the lung parenchyma at computed tomography in patients with pulmonary hypertension
Authors: Maria Kokosi, Gregory J. Keir, Benjamin Schreiber, Jamanda Haddock, David M. Hansell, Athol U. Wells
Journal: European Respiratory Journal (2014)

Rationale.  In healthy individuals, the density of pulmonary parenchyma at computed tomography (CT) in the dependent lung is higher than the density in the nondependent lung, reflecting a gravity-dependent density gradient. Abnormal pulmonary perfusion is known to result in regional differences in CT density. We evaluated possible disturbances in the normal CT density gradient in patients with idiopathic pulmonary arterial hypertension (IPAH).   Methods.  We analyzed non-contrast enhanced thin section CTs of 7 patients with IPAH - established on right heart catheterisation - and 8 healthy controls. Regions of interest (ROI) were selected in the most dependent and nondependent areas at two levels: aortic arch and pulmonary venous confluence. The mean densities in Hounsfield Units (HU) for the ROIs in each lung region were obtained and their average was taken as the mean density for that region. Average densities were calculated for the dependent and non-dependent ROIs in each level and zonal and global density gradients were derived.   Results.  Patients with IPAH were characterized by a decreased density gradient compared to the healthy individuals, at the level of aortic arch (median, 15.3 versus 35.6, p = .04), the level of pulmonary venous confluence (median, 29.1 versus 46.3, p = .02) and globally (median, 24.6 versus 42.9, p = .03).   Conclusion.  Patients with IPAH have a significantly reduced gravity-dependent density gradient compared to healthy individuals. This observation suggests that the normal gradient is largely dependent on the structural integrity and compliance of the pulmonary vasculature.
Comparison of CAF versus CMFP in metastatic breast cancer: analysis of prognostic factors.
Authors: F J Cummings, R Gelman, J Horton
Journal: Journal of Clinical Oncology (1985)

One hundred fifty-five eligible women with metastatic breast cancer were randomly allocated to receive monthly cycles of either CMFP (cyclophosphamide, methotrexate, 5-fluorouracil, prednisone) or CAF (cyclophosphamide, doxorubicin, 5-fluorouracil), and 12 patients were studied to evaluate the effects of additional Corynebacterium parvum immunotherapy. Overall response rates of 53% were seen with CMFP and CAF. CAF was associated with significantly more complete responses than CMFP (17% v 5%). However, CAF therapy was administered for eight months and CMFP for six months. Only 13% of the CAF patients had a complete response during the first six months of chemotherapy, and this was not significantly different from the complete response rate on CMFP. The median response durations (CMFP, 6.3 months; CAF, 11.0 months), times to treatment failure (CMFP, 5.7 months; CAF, 7.8 months), and survival times (CMFP, 15.8 months; CAF, 18.6 months) were not statistically different. Other investigators who have compared CAF to CMF-containing regimens have reported a large advantage in CAF therapy among patients with "good risk" sites of metastases (local-regional recurrence, bone, lung nodules). Such a finding was not confirmed by our study: in multivariate analyses the groups associated with an advantage for CAF tended to have a poorer prognosis than the groups associated with an advantage for CMFP. There was significantly more nausea and vomiting after CAF treatment, and CMFP treatment was associated with significantly more edema, Cushingoid features, fever, and eye symptoms.
IFCT0401-bio trial: Predictive biological markers for disease control (DC) of patients with non-resectable, adenocarcinoma with bronchioloalveolar carcinoma features (ADC-BAC) treated with gefitinib
Authors: M. Wislez, M. Antoine, V. Poulot, J. F. Morere, M. Perol, P. J. Souquet, M. P. Lebitasy, G. Zalcman, F. Coulet, J. Cadranel
Journal: Journal of Clinical Oncology (2007)

7653 Background: A French prospective multicentric phase II trial (IFCT0401) evaluated gefitinib as first-line treatment in non- resectable ADC-BAC. Tissue samples were collected for central pathological review and molecular analysis in attempt to identify biological markers associated with DC by gefitinib. Methods: Tumor samples were classified as BAC variants or ADC-other types according to the 2004 WHO histological classification and as non-mucinous or mucinous/mixed according to cytology. Immunohistochemistry was performed using antibodies against TTF1, Ki67, phosphorylated AKT, erbB2, and EGFR. Polysomy/amplification was examined for EGFR and erbB2. EGFR 18–21 and K-ras 2 exons were amplified and sequenced. Results: Tissue specimen were collected from 65 of the 88 eligible participants. This subgroup did not differ from the overall trial population in terms of sex ratio, proportion of non-smokers and DC rate. DC was achieved in 22/64 patients (DCR=34.4%, CI=[22–41]). 81% were BAC variants (n=50) and 19% ADC other types. Of the 50 BAC variants, half were non-mucinous and half mucinous. EGFR high polysomy/amplification was present in 6/40 samples (15%). EGFR exon 19, 20 and 21 mutations were detected in 6/57 (10.5%), 1/49 (2%) and 0/58 samples, respectively and K- ras mutation in 11/53 (20.7%). Expression of TTF1 (p&lt;0.0001) and EGFR (p=0.04) as well as polysomy/amplification of EGFR (p=0.04) were significantly higher in the non-mucinous than in the mucinous type. There was also a trend for more frequent detection of EGFR mutations among non-mucinous than mucinous type (p=0.08). DC with gefitinib was significantly associated with female gender (p=0.02), non- smoker status (p=0.03), non-mucinous subtype (p=0.006), high TTF1 expression (p=0.02) and EGFR mutation (p=0.0003). K-ras mutation was associated with progression (p=0.04). Conclusions: Among patients with histologically proven ADC-BAC who received gefitinib, female gender, non-smoker status, non-mucinous subtype, high TTF1 expression, and EGFR mutation are associated with DC, while K-ras mutation is associated with disease progression. Multivariate analysis will be released at ASCO meeting. No significant financial relationships to disclose.
Fluoxetine, Cognitive-Behavioral Therapy, and Their Combination for Adolescents With Depression
Authors: John March, Susan Silva, Stephen Petrycki, John Curry, Karen Wells, John Fairbank, Barbara Burns, Marisa Domino, Steven McNulty, Benedetto Vitiello, Joanne Severe
Journal: JAMA (2004)

Initial treatment of major depressive disorder in adolescents may include cognitive-behavioral therapy (CBT) or a selective serotonin reuptake inhibitor (SSRI). However, little is known about their relative or combined effectiveness.To evaluate the effectiveness of 4 treatments among adolescents with major depressive disorder.Randomized controlled trial of a volunteer sample of 439 patients between the ages of 12 to 17 years with a primary Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of major depressive disorder. The trial was conducted at 13 US academic and community clinics between spring 2000 and summer 2003.Twelve weeks of (1) fluoxetine alone (10 to 40 mg/d), (2) CBT alone, (3) CBT with fluoxetine (10 to 40 mg/d), or (4) placebo (equivalent to 10 to 40 mg/d). Placebo and fluoxetine alone were administered double-blind; CBT alone and CBT with fluoxetine were administered unblinded.Children's Depression Rating Scale-Revised total score and, for responder analysis, a (dichotomized) Clinical Global Impressions improvement score.Compared with placebo, the combination of fluoxetine with CBT was statistically significant (P =.001) on the Children's Depression Rating Scale-Revised. Compared with fluoxetine alone (P =.02) and CBT alone (P =.01), treatment of fluoxetine with CBT was superior. Fluoxetine alone is a superior treatment to CBT alone (P =.01). Rates of response for fluoxetine with CBT were 71.0% (95% confidence interval [CI], 62%-80%); fluoxetine alone, 60.6% (95% CI, 51%-70%); CBT alone, 43.2% (95% CI, 34%-52%); and placebo, 34.8% (95% CI, 26%-44%). On the Clinical Global Impressions improvement responder analysis, the 2 fluoxetine-containing conditions were statistically superior to CBT and to placebo. Clinically significant suicidal thinking, which was present in 29% of the sample at baseline, improved significantly in all 4 treatment groups. Fluoxetine with CBT showed the greatest reduction (P =.02). Seven (1.6%) of 439 patients attempted suicide; there were no completed suicides.The combination of fluoxetine with CBT offered the most favorable tradeoff between benefit and risk for adolescents with major depressive disorder.
Serum Steroid Binding Proteins and the Bioavailability of Estradiol in Relation to Breast Diseases2
Authors: Mark S. Langley, Geoffrey L. Hammond, Alan Bardsley, Ronald A. Sellwood, David C. Anderson
Journal: JNCI Journal of the National Cancer Institute (1985)

Journal Article Serum Steroid Binding Proteins and the Bioavailability of Estradiol in Relation to Breast Diseases Get access Mark S. Langley, Mark S. Langley Search for other works by this author on: Oxford Academic PubMed Google Scholar Geoffrey L. Hammond, Geoffrey L. Hammond Search for other works by this author on: Oxford Academic PubMed Google Scholar Alan Bardsley, Alan Bardsley Search for other works by this author on: Oxford Academic PubMed Google Scholar Ronald A. Sellwood, Ronald A. Sellwood Search for other works by this author on: Oxford Academic PubMed Google Scholar David C. Anderson David C. Anderson Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 75, Issue 5, November 1985, Pages 823–829, https://doi.org/10.1093/jnci/75.5.823 Published: 01 November 1985 Article history Received: 17 December 1984 Revision received: 10 July 1985 Accepted: 05 August 1985 Published: 01 November 1985
Irinotecan (I), carboplatin (C), and radiotherapy (RT) followed by maintenance bevacizumab (B) in the treatment (tx) of limited-stage small cell lung cancer (LS-SCLC): Update of a phase II trial of the Minnie Pearl Cancer Research Network
Authors: J. F. Patton, D. R. Spigel, F. A. Greco, W. H. Liggett, J. D. Zubkus, M. Baskette, M. Schreeder, D. Woytowitz, E. Nelson, J. D. Hainsworth
Journal: Journal of Clinical Oncology (2006)

7085 Background: Targeting VEGF has proven to be an effective tx strategy in many solid tumors including non-small cell lung cancer. VEGF expression in SCLC provides rationale for studying B in addition to chemoradiotherapy. Methods: The endpoints of this multicenter community-based study were to assess the safety, response rate (RR), and progression-free survival (PFS) of I/C/RT followed by B in patients (pts) with LS-SCLC. Tx included: C AUC = 5 IV D1, I 50mg/m 2 IV D1,8 Q 21D x 4 cycles, and RT 1.8 Gy daily to a total of 61.2 Gy, beginning with the 3rd cycle. 3rd and 4th cycles were 28D each. Pts were restaged after 4 cycles. If no progressive disease (PD) pts received B 10 mg/kg IV Q 14D x 10 doses. Eligibility included: measurable disease, ECOG PS 0–1, informed consent, and no new brain metastases or bleeding. Results: Fifty-seven pts were enrolled from 8/03 to 10/04. Forty-five pts (79%) and 41 pts (72%) received planned tx with I/C/RT and B, respectively. The range of follow-up is 14–28 months. Baseline features: median age 65 years (42–80); male/female, 37%/63%; ECOG PS 0,1: 26%/74%. Grade (G) 3/4 non-hematologic toxicity: diarrhea (9%), DVT (4%), vomiting (11%), and fatigue (9%). G3/4 hematologic toxicity: neutropenia (37%), anemia (5%), and thrombocytopenia (13%). Only 9% of pts experienced G3/4 toxicity during B tx (1 pt each: DVT, hypokalemia, depression, pain, and colon perforation). There were 2 tx-related deaths (both from respiratory failure; 1 and 2 doses of B had been administered). Complete/partial responses were observed in 15 pts (26%)/31 pts (54%), respectively, for an overall RR of 80% (95% CI 70%-90%). Four pts had stable disease, and 5% had PD (4 pts were unevaluable.) 1- and 2-year PFS rates were 63% and 54%, respectively. 1- and 2- year overall survival (OS) rates were 71% and 29%, respectively. Median OS was 15 months. Conclusions: The safety, RR, and 1- and 2-year survival results of I/C/RT followed by B compare favorably with standard tx for LS-SCLC; and B may improve PFS. Assessing the role of B as maintenance tx in improving OS in this setting will require randomized trials. [Table: see text]
Safety, pharmacokinetics, and pharmacodynamics of ivacaftor in patients aged 2–5 years with cystic fibrosis and a CFTR gating mutation (KIWI): an open-label, single-arm study
Authors: Jane C Davies, Steve Cunningham, William T Harris, Allen Lapey, Warren E Regelmann, Gregory S Sawicki, Kevin W Southern, Sarah Robertson, Yulia Green, Jon Cooke, Margaret Rosenfeld
Journal: The Lancet Respiratory Medicine (2016)
Chemotherapy in non-selected elderly patients: Factors influencing dose-intensity and toxicity
Authors: F. Lemare, C. Mateus, S. Camps, V. Montheil, E. Henguelle, W. Cacheux, E. Bezian, R. Di Loreto, A. Dauphin, F. Goldwasser
Journal: Journal of Clinical Oncology (2007)

19585 Background: Chemotherapy (CT) is the treatment of choice for most metastatic cancers. Frequent functional impairment and comorbidities in the elderly increase the risk of chemotherapy-related acute complications. The applicability of clinical trials data to the elderly population is exposed to multiple bias. Informations extracted from non-selected treated patients (pts) may be useful. Methods: A serie of consecutive elderly cancer pts (&gt;73 years) treated over 3 years in the oncology outpatient unit, and receiving CT were included for analysis and assessed using prechemotherapy evaluation of cancer in the elderly (including performance status, comorbidities, glomerular filtration rate, liver tests, hemogram, nutritional status, inflammation tests). Relationship between preCT evaluation and acute complications, unscheduled hospitalisation, mortality were investigated by univariate analyses. Comparison between planned and realised dose- intensity of CT protocols could be extracted for the CT prescription software. Results: 108 pts with a median age of 78 years (73- 89; 44% over 80) were identified. Characteristics included performance status (PS) ≥ 2 (44%), chronic renal insufficiency (47%) ; ≥2 comorbidities (75%). Primary tumour was urologic (31%), gastro-intestinal (29%), mammary and gynaecologic (20%); pulmonary (16%) or other (4%). Disease stage was metastatic for 82% of pts. Most CT regimens contained a platinum derivative (55%), gemcitabine (25%), 5-FU (20%), taxanes (17%), vinorelbine (15%). Transfusion requirements were higher in PS≥2 pts (p&lt;0.0001). Febrile neutropenia correlated with PS, lymphocytopenia and PINI =(CRP×AAG)/(albumin×pre-albumin)&gt;10 (p&lt;0. 05). Unscheduled hospitalisation correlated with PS, lymphocytopenia, PINI, more than 2 co-morbidities, more than 4 co-medications. Oxaliplatin- and paclitaxel-containing CT protocols were associated with significant reduction of dose-intensity because of reduced number of cycles due to neurosensory toxicity (p=0.01). Conclusions: Lymphocytopenia, PS, and PINI were the most relevant prognosticators of short-term CT outcome. Elderly pts characteristics are associated with higher risk of acute toxicity and increased sensitivity to neurosensory cumulative toxicity. No significant financial relationships to disclose.