tbuckley/cabot-search huggingface dataset:
Opiate detoxification under anaesthesia
Authors: J. Strang, J. Bearn, M. Gossop
Journal: BMJ (1997)

Intracytoplasmic sperm injection: offering hope for a term pregnancy and a healthy child?We need a common approach to definition and detection of birth defects O ne of the most recent techniques of assisted reproduction, intracytoplasmic sperm injection, offers hope for those suffering from subfertility, and particularly male factor infertility.This hope is tempered by worry, since couples who undergo this procedure might never become pregnant or, if they do, may not carry the pregnancy to term.Added to these known risks are theoretical risks regarding birth defects: intracytoplasmic sperm injection involves fertility drugs, chemical baths, and physical procedures, any of which could increase malformation rates.Moreover, if left to nature, the sperm manipulated by this procedure would probably not produce a pregnancy, and these sperm themselves may carry an increased risk for birth defects.Some reassurance about these theoretical concerns was offered recently when researchers from Belgium reported that major birth defects affected only 3.3% (14) of 423 children born after intracytoplasmic sperm injection, 1 a rate no higher than in the general population.In the current issue, however, Kurinczuk and Bower provide a less reassuring interpretation. 2 Using the classification scheme and data from the highly regarded Western Australia birth defects registry, they note that many major defects in the Belgian series had been incorrectly classified as minor.Reclassification yielded 31 major defects, or 7.38%; compared with the Western Australian rate of 3.78%, the risk of major defects following intracytoplasmic sperm injection was increased twofold.Although the Belgian group has expanded its experience to 877 children, with an overall major malformation rate of 2.6%, 3 these later findings are based on the same analytic approach and may similarly be called into question.On the other hand, researchers from New York recently found only nine major malformations among 578 babies born after intracytoplasmic sperm injection, 4 a rate of only 1.6%-less than half that in Western Australia.Even if the six minor defects they identified were reclassified as major, the resulting rate of 2.6% is still below the expected.Do these findings suggest that birth defect risks can be minimised if couples undergo this procedure in New York rather than Belgium, or might something else explain these discrepant results?The Western Australia researchers correctly argue that for comparisons of birth defect rates to be valid, investigators must use the same definition of what Correction Attention deficit hyperactivity disorder
A phase II study of venlafaxine for the treatment of hot flashes in men undergoing androgen deprivation for prostate cancer
Authors: A. Shafqat, M. L. Titzer, C. J. Sweeney, R. B. Giesler, A. Hanna, J. Porter, K. Selbe, J. Daggy, L. H. Einhorn
Journal: Journal of Clinical Oncology (2004)

8148 \(\underline{\mathrm{Background:}}\)Vasomotor hot flashes are a common and distressing problem in men undergoing androgen deprivation therapy (ADT) for prostate cancer. Venlafaxine reduces both the incidence and severity of hot flashes in women with breast cancer. Data in men with prostate cancer on ADT are scarce. \(\underline{\mathrm{Methods:}}\) Eligible patients underwent ADT and had at least 14 hot flashes per week of sufficient severity to desire intervention. The initial daily dose was 75 mg, but the study was amended after enrolling the first 4 patients to 37.5 mg because of grade 2 toxicity by one patient. Data was collected by daily questionnaires during an initial 1-week baseline period and then weekly for the first 4 weeks during treatment with venlafaxine. Primary end point was reduction of greater than 50% in the weekly hot flash score (a composite score of number of hot flashes and severity), during the last week as compared to baseline. Toxicity data was collected each week. Patients completed a Beck Depression Inventory (BDI) and a single-item global quality-of-life (QOL) question each week. All outcomes were analyzed using repeated measures analysis of variance models. \(\underline{\mathrm{Results:}}\) Twenty patients were enrolled. Three patients did not complete any of the weekly questionnaires and were inevaluable. Of the 17 evaluable patients, 12 (70.6%) had more than 50% reduction in the hot flash score. Weekly hot flash scores were reduced by an average of 58% (95% C.I. 0.49–0.66) from baseline to end of study. The average weekly frequency of hot flashes was 58.6 at baseline and was reduced to 29 by end of study (p<.0001). Overall QOL data was available for 15 patients, and increased from baseline to end of study by an average of 1.3 points (p=.01). BDI scores were available for 11 patients and improved by an average of 3.5 points (p=.011). Only one patient had grade 2 dizziness and fatigue toxicity. Thirteen of the 17 patients (76.4%) said they would wish to continue the medication at the end of the study. \(\underline{\mathrm{Conclusions:}}\) Venlafaxine was well tolerated and effective in mitigating hot flashes in this patient population. No significant financial relationships to disclose.
A phase I study of the anti-IGF-1R monoclonal antibody (MoAb), IMC-A12 (I), and everolimus (E) in well-differentiated neuroendocrine tumors (WD NET).
Authors: Arvind Dasari, Alexandria Phan, Sanjay Gupta, Kenneth R. Hess, Kirk Salvatore Culotta, Asif Rashid, S. J. Yeung, Helen X. Chen, Mei Dong, Daniel M. Halperin, Ishwaria Mohan Subbiah, Funda Meric-Bernstam, James C. Yao
Journal: Journal of Clinical Oncology (2014)

232 Background: Octreotide LAR (LAR) and E have well known anti-cancer effects in WD NETs. Preclinical data also show that inhibition of the insulin like growth factor receptor (IGF-1R) may sensitize NETs to mTOR inhibitors such as E. Methods: Patients (pts) with WD NETs, ECOG performance status ≤ 2 and adequate organ function were treated with LAR 20 mg IM q 21days (d), E 10 mg po daily and escalating doses of I iv q 21 d in 21 d cycles in cohorts of 6 until maximum tolerated dose (MTD). Recommended phase II dose (RP2D) was defined as dose level below MTD. An expansion cohort of 9 pts was planned at RP2D. Plasma samples for everolimus pharmacokinetics (PK), IGF, mTOR pathway pharmacodynamics (PD) in addition to paired tissue biopsies were obtained. Results: 19 pts with previously treated (median prior systemic therapy, 1, range 0-3) WDNET (4 pancreatic NET, 11 carcinoid, 4 unknown primary) were enrolled in this single institution study. Ten pts in dose escalation and 9 in expansion phases received a median of 8.5 cycles (range, 3-19+). Dose limiting toxicities (DLTs) were grade (g) 3 mucositis in 2 pts at 2 nd dose level of I 15 mg/m2 q 21 d. Most frequent adverse events (AEs) observed while on study were fatigue, hyperlipidemia, weight loss (74%), dysguesia (68%), hyperglycemia and mucositis (63%). Most common g3 AEs were fatigue (21%), mucositis, transaminitis and electrolyte disturbances (all 11%). Other g 3 AEs included anorexia, anemia, injury, retinal detachment, dehydration and thromboembolism. One g 4 AE of hyperglycemia was noted during the expansion phase. One pt with pancreatic NET had confirmed partial response and 17 had stable disease as best response. The median progression free survival was 34+ weeks. Conclusions: The RP2D of this combination is I 10 mg/m2, LAR 20 mg IM q 21 d, E 10 mg po daily. PK, PD and other correlative analyses are ongoing and will be presented at the meeting. Although adequate safety and a sign of activity were noted in this study, these will need to be reconciled with data from larger studies of anti-IGF-1R MoAb in NET and other cancers that have been disappointing. Clinical trial information: NCT01204476.
Gene profiling of tumor tissue in the diagnosis of patients with carcinoma of unknown primary site (CUP): Evaluation of the Veridex 10-gene molecular assay
Authors: J. D. Hainsworth, D. Talantov, T. Jatkoe, C. Meng, J. Baden, D. R. Spigel, A. Mazumder, Y. Wang, F. A. Greco
Journal: Journal of Clinical Oncology (2007)

21109 Background: Standard treatment for most patients with CUP involves empiric chemotherapy. Since specific treatment now exists for most types of advanced carcinoma, precise identification of the primary site could lead to improved therapy. Veridex developed an optimized set of 10 gene markers, for a qRTPCR assay to identify tissue of origin of metastatic carcinoma in formalin-fixed, paraffin-embedded (FFPE) tissue samples (J Mol Diagn 8:320, 2006). The assay includes markers for 6 primary sites: lung, pancreas, colon, breast, ovary, and prostate. In this retrospective study, we evaluated the Veridex assay in patients with CUP. Methods: We obtained FFPE tissue from diagnostic biopsies on 69 CUP patients previously enrolled in empiric chemotherapy studies. The Veridex assay was performed as previously described. Assay results were correlated with clinical features, pathologic features, and response to treatment. Results: The Veridex assay yielded provisional diagnoses in 42 of 69 patients (61%): lung (15), pancreas (11), colon (12 ), ovary (4), breast (0), and prostate, (0 ). Most patients with diagnoses of lung and pancreas cancer had clinical and pathologic features compatible with these diagnoses; response rates to empiric chemotherapy (usually taxane/platinum-based) in patients with these diagnoses were 29% and 9%, respectively. The 12 patients with colon cancer diagnoses had predominantly intra-abdominal metastases (liver, peritoneum); response rate to therapy (usually taxane/platinum- based) was low (8%). The 4 patients with ovarian cancer had atypical clinical and pathologic features, and only 1 of 4 had PR to first-line taxane/platinum therapy. Conclusions: In this retrospective study, the Veridex 10-gene molecular assay was feasible and provided provisional diagnoses in a majority of patients with CUP. The diagnoses made using this assay (except ovarian cancer) were compatible with clinicopathologic features. The efficacy of cancer-specific treatment in patients diagnosed by this assay will be evaluated in prospective studies. No significant financial relationships to disclose.
Double CEBPA Mutations Are Not Associated With Favorable Clinical Outcome In Pediatric AML: A Report From The Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG)
Authors: Hidemasa Matsuo, Mio Kajihara, Daisuke Tomizawa, Tomoyuki Watanabe, Akiko Moriya Saito, Junichiro Fujimoto, Keizo Horibe, Mayu Tokumasu, Hiroshi Itoh, Hideki Nakayama, Akitoshi Kinoshita, Takashi Taga, Akio Tawa, Tomohiko Taki, Souichi Adachi
Journal: Blood (2013)
Comparison of validity of methacholine and mannitol bronchial challenges in asthma diagnosis
Authors: Konstantinos Porpodis, Kaliopi Domvri, Theodoros Kontakiotis, Dimitrios Latsios, Dimitrios Ioannidis, Pashalina Giouleka, Konstantinos Zarogoulidis, Despoina Papakosta
Journal: European Respiratory Journal (2012)

Background: Detection of BHR with methacholine or mannitol have been highly sensitive tests to identify asthma diagnosis.

Purpose: The purpose of this study was to demonstrate the diagnostic validity of the two bronchial challenges and their correlation with symptoms, atopy and inflammatory markers.

Methods: Eighty-eight patients, 47 women and 41 men, aged 14-75 years who presented with asthma related symptoms and were not on any anti-asthma medication, were challenged with mannitol and methacholine. Medical history, physical examination, skin prick tests, Asthma Control Test (ACT) and FeNO levels were also assessed. The clinical diagnosis of asthma was based on bronchodilator reversibility test.

Results: Sixty seven patients were diagnosed with asthma and 21 without asthma. Both methacholine (p<0,014) and mannitol (p<0.000) challenges were significant in diagnosing asthma. The sensitivity/specificity was 62,68%/85,71% for methacholine, 64,17%/95,23% for mannitol and 64,70%/93,75% for both methods together, whereas the positive/negative predictive value was 93,33%/41.86%, 97,72%/45,45% and 97,05%/45,45%, respectively. There was a negative correlation between PC20 of methacholine and the FeNO level p<0,001, and positive with the PD15 of mannitol p<0,001 and the pre-test FEV1% pred p<0,005, whereas PD15 of mannitol was negatively correlated with the FeNO level p<0,001. Furthermore, dyspnoea was the only asthmatic symptom associated with FeNO level p<0,035 and the positivity of mannitol p<0,014 and methacholine p<0,04.

Conclusions: Both provocation methods were equivalent in diagnosing asthma, although sensitivity/specificity values appeared to be slightly higher in mannitol challenge.
Time-varying prognostic impact of hormone receptors for breast cancer patients
Authors: W. Yin, J. Lu, G. Liu, G. Di, J. Wu, Z. Shen, Z. Shao
Journal: Journal of Clinical Oncology (2008)

22131 Background: In most studies, the effect of steroid hormone receptor (HR) on prognosis was illustrated by survival analysis, which may obscure the changes of event probability over time. However, such information is highlighted using the hazard function. We sought to investigate the time-varying prognostic impact of HR for breast cancer patients by use of hazard function. Similar data is still not available at present. Methods: We performed a retrospective study of 2143 female unilateral breast cancer patients undergoing surgery in our hospital from 1992 to 2003. The primary endpoint was recurrence-free survival (RFS), defined as the time from surgery to the earliest occurrence of local-regional or distant relapse (including contralateral breast cancer), or death from any cause. Results: According to different HR status, patients were categorized into the three subgroups as follows: double-positive (ER+/PR+), single-positive (ER+/PR− and ER−/PR+) and double-negative (ER−/PR−). Both univariate and multivariate survival analysis indicated that tumor size, axillary nodal status, HR status were prognostic factors for RFS (P <0.05). Annual recurrence hazard curve showed double-peaked pattern irrespective of HR status. In different subgroups, however, discrepancies existed regarding the time of hazard peaks. Double-negative patients showed an early major surge peaking at the 2nd year after surgery and a slight increase at the 8.5th year. As to double-positive patients, bimodal pattern was indicated by a gradual increase in risk until 2.5 years after surgery, followed by a modest decline until year 7.5, and then a second rise to a maximum at 9.5 years. The corresponding peaks for the single-negative patients were at the 1.5th year and at the 10th year. In other words, double-negative breast cancers were more likely to recur early compared with double-positive ones, while the recurrence pattern for single-negative tumors was intermediate between double-negative and double-positive counterparts. Conclusions: According to the prognostic impact of HR on time distribution, we could formulate different strategies for different patients in the treatment and follow-up, which provides the possibility of delaying the recurrence hazard to improve the therapeutic effect. No significant financial relationships to disclose.
Quality-of-life concordance between patients with malignant gliomas (MG) and their caregivers.
Authors: D. Jacobs, S. A. Grimm, A. Rademaker, L. Rice, J. Chandler, K. Muro, M. H. Marymont, I. B. Helenowski, L. I. Wagner, J. J. Raizer
Journal: Journal of Clinical Oncology (2010)

2041 Background: Quality of life (QOL) in patients with malignant gliomas (MG) is important. Patients often minimize many aspects of QOL; hence, caregiver input is valuable. The purpose of this study was to investigate QOL concordance between patient and caregiver, in order to identify relevant discrepancies. Methods: Patients with MG within 6 months of diagnosis or relapse were eligible for this study if they had an involved caregiver. The Functional Assessment of Cancer Therapy-Brain (FACT-Br) was given to patients and caregivers at baseline and then on the day MRIs were done for tumor assessment and continued until tumor progression. Patients were asked to fill out the FACT-Br and their caregiver was asked to fill out the same questionnaire as they perceived the patient would respond. MRI was done approximately every 2 months and questionnaires were given prior to disclosure of MRI results. Results: 51 pairs of FACT-Br scales were collected over the course of the study from 19 patient- caregiver pairs. A consistent discrepancy between patient and caregiver was seen. Patients reported their overall QOL to be better than perceived by their caregivers by an average of 9.9 points on the 200 point scale (p = 0.004). This difference was observed similarly for patients with newly diagnosed and recurrent MG and their caregivers. Significant differences were found within subscales of physical (p = 0.02), emotional (p = 0.01), and functional (p = 0.02) well-being, as well as brain cancer-specific items (p = 0.03). Social well-being was the only subscale where a significant discrepancy was not noted. The average score for the FACT-General was 76.1 in this sample of MG patients, significantly lower than the national average of 80.1 across all cancers. Conclusions: Results indicate patients consistently report their QOL to be more favorable than perceived by their caregivers. This finding underscores the importance of including caregivers in clinical assessments to obtain a comprehensive view of patient QOL and functional status. Physician-caregiver communication is essential to ensure quality care for patients with MG. No significant financial relationships to disclose.
Human plasma pharmacokinetics of thiotepa following administration of high-dose thiotepa and cyclophosphamide.
Authors: S P Ackland, K E Choi, M J Ratain, M J Egorin, S F Williams, J A Sinkule, J D Bitran
Journal: Journal of Clinical Oncology (1988)

Thiotepa is an established alkylating agent whose pharmacokinetics in standard doses are well defined. In order to ascertain whether dose-dependent variations in pharmacokinetics occur, we have undertaken an analysis of plasma thiotepa levels in 16 patients entered on a phase I-II study of bialkylator chemotherapy. High-dose thiotepa (1.8 to 7.0 mg/kg) and cyclophosphamide (2.5 g/m2) were administered intravenously (IV) on days -6, -4, and -2 followed by autologous marrow reinfusion on day 0. Plasma and urinary thiotepa was assayed by gas chromatography. Biexponential plasma decay curves were seen in ten patients, with a t 1/2 alpha of 10.0 +/- 6.4 minutes, a t 1/2 beta of 174 +/- 61 minutes and a total body clearance of 379 +/- 153 mL/h/kg (mean +/- SD). Six patients displayed monoexponential plasma decay curves with a terminal t 1/2 of 137 +/- 83 minutes and a total body clearance of 440 +/- 195 mL/h/kg. Although there was a trend toward reduced plasma clearance in the three patients treated at the highest dose level, the available data suggest that metabolic clearance mechanisms for thiotepa were not saturated with the doses used in this study. By stepwise regression analysis, linear functions using only 15-minute and four-hour postinfusion plasma levels were derived that correlated closely with area under the plasma concentration X time curves (AUC) (P less than .002). We conclude that high-dose thiotepa results in similar pharmacokinetic values to conventional doses with no apparent dose-dependent variation. The value of specific time points to predict AUC and clearance will require prospective evaluation.
GOFURTGO trial (GFG): An AGITG multicenter phase II study of fixed dose rate gemcitabine-oxaliplatin (Gem-Ox) integrated with concomitant 5FU and 3-D conformal radiotherapy (5FU-3DRT) for the treatment of locally advanced pancreatic cancer (LAPC)
Authors: D. Goldstein, G. van Hazel, S. Selva-Nayagam, S. Ackland, J. Shapiro, S. Carroll, M. Cummins, C. Brown, R. J. Simes, N. Spry
Journal: Journal of Clinical Oncology (2009)

4616 Background: Our previous study of Gem with sandwich 5FU-3DRT for LAPC was encouraging (Br J Cancer 2007: 97, 464–471). Gem-Ox has higher response rate than Gem, improved progression free survival (PFS) but not overall survival (OS). Its use in LAPC may improve local control (LC) and delay systemic spread. GFG is a study of induction (ind) Gem-Ox, then 5FU-3DRT, then consolidation (con) Gem-Ox. Primary outcome is feasibility using proportion of patients (pts) receiving &gt; 80% planned dose for each component. Secondary outcomes are safety, activity and QOL. Methods: Pts with previously untreated inoperable LAPC, M0, measurable disease, ECOG 0–2 were given Gem (1000mg/m 2 d1 + d15 q28), Ox (100mg/m 2 d2 + d16 q28) in both ind (1 cycle) &amp; con (3 cycles), &amp; 5FU 200mg/m 2 /d over 6 weeks during RT of 54Gy in 30 fractions of 1.8Gy. Results: 48 pts were enrolled, median age 61y (44–81y), PS 0/1=96%, regional lymph nodes=44%, T4=46%. Worst grade (G) for anaemia (10%); fatigue, nausea (8%); diarrhoea, vomiting, neutropenia, infection (4%); stomatitis, anorexia (2%) was G3. Thrombocytopenia was G3=2% G4=2%; liver function was G3=23% G4=6%; late radiation toxicity was G3=2% G4=2% (both gastric bleeding). Half of all pts completed all planned cycles (24 pts); 29% of pts received &gt;80% of all treatment (14 pts); 70% of pts received &gt;80% of all chemoradiation (33 pts). Pts ceased treatment for toxicity (16%), PD (21%) or doctor/pt preference (4/2%). Global QOL did not significantly change from baseline. Median duration of LC, PFS, OS were 15.8, 9.9, 15.4m at median follow up of 29.7m. Exploratory analysis of age, disease stage, PS, CA19–9 or WCC found no univariate predictors of PFS or treatment completion. 8/48 pts survived &gt;24m. Conclusions: Compared to our previous study using the same radiation schedule, addition of oxaliplatin was associated with improved LC, PFS &amp; OS (prev. 11.9, 7.1 &amp; 11.7m) without significant offset by toxicity. The extended duration of LC and a subset who had a very prolonged benefit may be due to patient selection but equally may suggest an incremental benefit from more intensive systemic therapy requiring further study in controlled trials. [Table: see text]