tbuckley/cabot-search huggingface dataset:
The addition of taxanes to adjuvant chemotherapy for lymph node positive (N+) early breast cancer (BC): Institutional practice variation in the National Comprehensive Cancer Network (NCCN)
Authors: E. J. Sherman, E. M. Lepisto, J. C. Niland, N. Nicotera, R. A. Ottesen, R. L. Theriault, S. B. Edge, J. Wilson, M. A. Bookman, J. C. Weeks
Journal: Journal of Clinical Oncology (2005)

654 Background: The addition of adjuvant (ADJ) paclitaxel to N+ BC has been evaluated in 2 large randomized studies. NSABP B28 was first presented in NOV-2000. No survival benefit was reported. In MAY-1998 CALGB 9344 was reported and showed a significant survival advantage associated with the addition of paclitaxel; but no significant survival advantage on reanalysis in NOV-2000. Ultimately, a significant survival advantage re-emerged on analysis in MAY-2002. We evaluated variations in ADJ taxane (TAX) at multiple academic centers associated with these dates. Methods: Using the NCCN BC Outcomes Database, we analyzed rates and determinants of ADJ TAX use for N+ stage 2 BC at 8 NCCN institutions between JUL-1997 and MAY-2003. The analysis was restricted to patients (pts) who received non-protocol treatment, and to those institutions contributing >10 eligible pts during each time period. Variables significant at p≤0.2 in univariable analysis were examined in a multivariable (MV) logistic regression model. The primary outcome was the initiation of ADJ TAX within 150 days of the start of chemotherapy. The analysis was done for 4 time periods (see table). Historical TAX utilization was recorded for the period 7/97–5/98, prior to the release of phase III TAX data. Results: Significant results on MV analysis (p<0.05) for incorporation of ADJ TAX were: NCCN institution, number of N+, hormone receptor status, insurance type, date of TAX use, age, tumor size, and Her-2/neu status. Variables analyzed, but not significant, included: comorbidity score, diabetes, chronic obstructive pulmonary disease, income, education, and performance status. Conclusions: We observed significant practice variation in the use of ADJ TAX over time, and across the NCCN institutions for each time interval, even after controlling for clinical and sociodemographic characteristics. Author Disclosure By institution, % of pts receiving ADJ TAX over time and Odds Ratio on MV analysis Institution 7/97–5/98 (n=131) 6/98–11/00 (n=846) 12/00–5/02 (n=611) 6/02–5/03 (n=383) 7/97–5/03 (n=1,971) A (reference institution) 10.00% 48.19% 1.00 43.68% 1.00 71.79% 1.00 47.16% 1.00 B 6.90% 59.93% 1.46 25.69% 0.32 28.00% 0.13 39.49% 0.54 C 9.09% 54.29% 1.13 22.22% 0.30 53.3% 0.36 43.09% 0.65 D 9.09% 61.96% 2.35 63.27% 2.04 76.47% 1.05 58.88% 1.79 E 18.37% 81.87% 9.34 68.70% 2.63 88.29% 2.71 73.35% 4.12 F Insufficient Data 47.92% 0.80 37.84% 0.71 78.95% 2.96 50.00% 0.94 G Insufficient Data 71.95% 1.96 28.70% 0.37 21.92% 0.09 40.00% 0.52 H Insufficient Data 76.32% 4.38 71.43% 3.28 73.81% 0.99 74.53% 2.82 All Sites 12.21% 65.84% 45.83% 61.62% 55.25% No significant financial relationships to disclose.
Parental criminality and medical histories of delinquent children
Authors: D O Lewis, S S Shanok, D A Balla
Journal: American Journal of Psychiatry (1979)

In clinical practice the authors observed that many of the delinquent children of psychiatrically impaired and/or criminal parents had remarkably adverse health histories. To test their clinical impression they systematically compared the medical histories of 20 delinquent children with criminal parents and 85 delinquent children with less obviously maladapted parents. They found a strong association between paternal criminality and serious medical problems in these delinquent children. On the basis of this finding the authors suggest that the behavioral manifestations resulting from such physical illness or neglect, although they appear genetic in nature, may reflect the physical and psychological consequences of parental neglect and/or battering.
Time to review utility of multidisciplinary team meetings
Authors: Sarah Thornton
Journal: BMJ (2015)

Eigenmann is right to question the efficacy of multidisciplinary teams (MDTs),1 which have become the accepted mode of working despite the flimsy evidence base.2

The consensus that MDTs are a good thing is rooted in several presumed benefits, such as standardisation and continuity of care, effective use of resources, improved trial recruitment, and safeguarding of patients (from maverick doctors).

Few …
Involvement of Fas-Mediated Apoptosis in the Hematopoietic Progenitor Cells of Graft-Versus-Host Reaction-Associated Myelosuppression
Authors: Takehiko Mori, Takashi Nishimura, Yasuo Ikeda, Tomomitsu Hotta, Hideo Yagita, Kiyoshi Ando
Journal: Blood (1998)
Phase I and Pharmacokinetic Study of LU79553, a DNA Intercalating Bisnaphthalimide, in Patients With Solid Malignancies
Authors: Miguel A. Villalona-Calero, Joseph P. Eder, Deborah L. Toppmeyer, Lee F. Allen, Robert Fram, Raja Velagapudi, Michael Myers, Anthony Amato, Kathleen Kagen-Hallet, Betty Razvillas, Donald W. Kufe, Daniel D. Von Hoff, Eric K. Rowinsky
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To determine the maximum-tolerated dose and characterize the pharmacokinetic behavior of LU79553, a novel bisnaphthalimide antineoplastic agent, when administered as a daily intravenous infusion for 5 days every 3 weeks. PATIENTS AND METHODS: Patients with advanced solid malignancies received escalating doses of LU79553. Plasma sampling and urine collections were performed on both days 1 and 5 of the first course. RESULTS: Thirty patients received 105 courses of LU79553 at doses ranging from 2 to 24 mg/m 2 /d. Proximal myopathy, erectile dysfunction, and myelosuppression precluded the administration of multiple courses at doses above 18 mg/m 2 /d. These toxicities were intolerable in two of six patients after receiving three courses at the 24-mg/m 2 /d dose level. At the 18-mg/m 2 /d dose, one of six patients developed febrile neutropenia and grade 2 proximal myopathy after three courses of LU79553. The results of electrophysiologic, histopathologic, and ultrastructural studies supported a drug-induced primary myopathic process. A patient with a platinum- and taxane-resistant papillary serous carcinoma of the peritoneum experienced a partial response lasting 22 months. Pharmacokinetics were dose-independent, optimally described by a three-compartment model, and there was modest drug accumulation over the 5 days of treatment. CONCLUSION: Although no dose-limiting events were noted in the first two courses of LU79553, cumulative muscular toxicity precluded repetitive treatment with LU79553 at doses above 18 mg/m 2 /d, which is the recommended dose for subsequent disease-directed evaluations. The preliminary antitumor activity noted is encouraging, but the qualitative and cumulative nature of the principal toxicities, as well as the relatively small number of patients treated repetitively, mandate that rigorous and long-term toxicologic monitoring be performed in subsequent evaluations of this unique agent.
Triphenylethylenes: A New Class of Protein Kinase C Inhibitors
Authors: C A O'Brian, R M Liskamp, D H Solomon, I B Weinstein
Journal: JNCI Journal of the National Cancer Institute (1986)

The Ca2+- and phospholipid-dependent phosphotransferase activity of protein kinase C was inhibited by the triphenylethylene compounds clomiphene [drug concentration causing 50% inhibition (IC50) = 25 microM], 4-hydroxytamoxifen (IC50 = 25 microM), and N-desmethyltamoxifen (IC50 = 8 microM). The Ca2+- and phospholipid-independent phosphorylation of protamine sulfate, which is catalyzed by protein kinase C, was not inhibited by the triphenylethylenes, suggesting that they do not interact directly with the active site of protein kinase C. The inhibitory potency of each triphenylethylene was reduced when the phospholipid concentration was increased, providing evidence that these drugs inhibited protein kinase C by interacting with phospholipids. The potencies of the effects of the triphenylethylenes on protein kinase C in the lipid environment of intact cells were evaluated by determining their efficacies in the inhibition of [3H]phorbol 12,13-dibutyrate (PDBu) binding to mouse embryo C3H/10T1/2 cells. Micromolar concentrations of each drug inhibited [3H]PDBu binding in these cells. N-Desmethyltamoxifen, 4-hydroxytamoxifen, and tamoxifen inhibited protein kinase C with the same order of potency as that which has been reported for their inhibition of MCF-7 cell growth by Reddel et al. (1983). N-Desmethyltamoxifen and 4-hydroxytamoxifen were also more potent than tamoxifen in the inhibition of the growth of mouse embryo fibroblast C3H/10T1/2 cells. These correlations suggest that the mechanism of growth inhibition by tamoxifen and its metabolites includes interactions with protein kinase C.
Scintigraphic evaluation of mandibular bone turnover inhibition by bisphosphonates in patients with solid tumors
Authors: T. Van den Wyngaert, M. T. Huizing, E. Fossion, J. B. Vermorken
Journal: Journal of Clinical Oncology (2009)

9519 Background: Bisphosphonates (BP) have been associated with the occurrence of osteonecrosis of the jaw (ONJ), possibly by causing an excessive inhibition of local bone turnover. However, little in vivo evidence currently exists to support this theory. Methods: Whole-body scintigrams acquired after administration of 99mTc labeled medronate of 120 patients were studied. Patients with skeletal metastases from a solid tumor (n=40) were individually matched with cancer patients without BP exposure (n=40) and controls with neither a malignancy nor BP use (n=40). Controls were matched for age, gender, malignancy, steroid and hormonal therapy use, where appropriate. Patients with established ONJ or intense focal abnormalities in the studied regions were excluded. Mandibular bone turnover (MBT) was quantified relative to the femurs by defining regions-of-interest on the scintigrams with correction for background activity. The study had a power of 90% to detect a 10% reduction in MBT after BP use. Results were analyzed using a repeated-measures ANOVA with a two-sided significance level of p&lt;0.05. Results: The patients with BP exposure (34 female, 6 male) had a median age of 62 years (range 25–80) and received a median number of 11 zoledronic acid administrations (range 1–48). Malignancies included: breast (n=30), prostate (n=4), colon (n=2) and bladder cancer (n=2); and neuroendocrine carcinoma (n=2). The mean MBT was significantly lower in BP using cancer patients (2.59) compared with matched controls from oncological patients without BP use 3.01 (difference 0.42; 95% CI 0.13 - 0.72; p=0.006), or patients without cancer or BP exposure 3.09 (difference 0.50; 95% CI 0.21 - 0.78; p=0.001). In contrast, there was no significant difference in MBT between non-BP users (difference 0.08; 95% CI -0.31 - 0.46; p=0.7). Likewise, no correlation between MBT and the number of BP administrations could be demonstrated (r 2 =0.01; p=0.4), suggesting a stochastic rather than a deterministic effect. Conclusions: This in vivo data suggests that BP cause a higher inhibition of bone turnover in the mandible relative to the femur, which strengthens the hypothesis that the inhibition of bone turnover may be important in the pathophysiology of ONJ. [Table: see text]
Expression of Virus-Like Particles in Feline Preimplantation Embryos&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: R A Bowen
Journal: JNCI Journal of the National Cancer Institute (1980)

Embryos recovered from random-source domestic cats between 1 and 7 days after ovulation and unfertilized oocytes recovered within 6 hours of ovulation were examined ultrastructurally for the presence of types A and C viruses. Intracisternal type A particles were found consistently within cells of the inner cell mass in blastocysts but not within trophoblast cells or cells from earlier stages of development. Mature type C viruses were not observed. Novel virus-like particles were found within cytoplasmic cisternae in many of the embryos; these particles did not appear to be associated with a particular stage of embryonic development.
Bronchoscopy and endobronchial biopsies in children: Useful or not?
Authors: Fardou Heida, Marielle Pijnenburg, Leonie Vanlaeken, Wim Timens, Bart Rottier
Journal: European Respiratory Journal (2012)

INTRODUCTION:

Bronchoscopy and endobronchial biopsies are diagnostic tools in the evaluation of difficult asthma and other paediatric airway diseases. The yield of these procedures in clinical practice is uncertain. Therefore our aim was to evaluate if bronchoscopy and endobronchial biopsies change management.

METHODS:

Retrospectively we collected data on diagnosis and treatment before and after bronchoscopy in all children undergoing bronchoscopy with endobronchial biopsies between 0 and 18 yrs. Difficult asthma was defined as uncontrolled asthma despite high dose ICS dose and LABA. In endobronchial biopsies reticular basement membrane (RBM) thickness was measured.

RESULTS:

Of the 74 children (37 male, mean age 7.8 yrs), 26 had asthma and 13 had difficult asthma. The diagnosis of children undergoing bronchoscopy changed in 31.3 % of the cases: 10 children got a second diagnosis, which could explain the persistent symptoms, 8 children were misdiagnosed. In these 18 children airwaymalacia (n=10) and anatomic abnormalities (n=7) were the most common. In 9.5 % of the cases biopsies changed the diagnosis; in 3 of them ciliary dyskinesia was suspected. In 25 % medication was changed after bronchoscopy.

Children without asthma had a RBM of 5,6 μm \[SD +/- 1,4]; in children with asthma RBM thickness was 5,11 μm [SD +/- 1,05] and in those with difficult asthma 6,0 μm [SD +/- 1,34\] (p=0.49).

CONCLUSION:

Bronchoscopy showed an important role to reveal underlying causes of persistent symptoms such as airwaymalacia and anatomic abnormalities. In 25% of patients bronchoscopy led to a change in treatment. We found no significant difference in RBM thickness between nonasthmatic, asthmatic children and children with difficult asthma.
사례보고 : 급성 신부전을 동반한 전격성 간염으로 발현하여 간이식을 시행한 A형간염 4예
Authors: 오세훈 ( Se Hoon Oh ), 이준혁 ( Joon Hyoek Lee ), 황지원 ( Ji Won Hwang ), 김혜영 ( Hye Young Kim ), 이창훈 ( Chang Hoon Lee ), 곽금연 ( Geum Youn Gwak ), 최문석 ( Moon Seok Choi ), 고광철 ( Kwang Chul Koh ), 백승운 ( Seung Woon Paik ), 유병철 ( Byung Chul Yoo )
Journal: Clinical and Molecular Hepatology (2009)

A형간염은 대부분의 경우 가벼운 임상경과를 거치게 되나 드물게 전격성 간염으로 발전하여 사망에 이르거나 간이식을 시행하게 된다. 저자들은 비교적 높은 연령의 환자에서 급성 신부전을 동반한 전격성 간염으로 발현되어 간이식까지 시행했던 A형간염 4예를 경험하였기에 보고하고자 한다. 본 증례들은 공통적으로 1) 30대 후반 이상의 상대적 고령에 발생, 2) 급성 신부전을 동반, 3) 간종대를 동반, 4) 조직 소견에서 아광범성 간괴사 소견의 특징을 보였다.
Comorbidity and choice of adjuvant endocrine therapy in breast cancer patients (pts) older than 70 years
Authors: S. Monfardini, A. Brunello, A. Molino, C. Sacco, E. Simoncini, G. Gasparini, M. A. Bella, D. Crivellari, L. Vamvakas, U. Basso
Journal: Journal of Clinical Oncology (2006)

8546 Background: Tamoxifen (Tam) and aromatase inhibitors (AI) have different profiles of toxicity which may influence the therapeutic choice in the presence of associated diseases, but few data are available concerning the prevalence of such comorbidities. Methods: A retrospective analysis on 434 consecutive pts (≥70 years) radically operated for breast cancer was conducted in 26 italian centers to determine how comorbidity influenced the choice of endocrine therapy during the year 2004. Results: Out of 434 pts, 367 with estrogen receptor positivity (median age 75, range 70–93) were treated with endocrine therapy alone (330 pts) or combined with chemotherapy (37 pts). The mean number of comorbidities was 1.8; 99 pts (26.2%) had ≥3 associated diseases. Tam was given to 194 pts (52,8%), AI to 173 pts (47,2%): Anastrozole (149 pts) Letrozole (22 pts) or Exemestane (2 pts). In 126/367 pts (34%) AI were prescribed instead of Tam because of the contraindications listed in the table below. AI were the preferred choice in 46/367 (12,5 %) pts in the absence of contraindications to Tam. Whereas the prevalence of osteoporosis is more than 30% in women after 70 years in Italy, a reduction of bone density had been instrumentally documented only in 10 pts (2.7%) of this survey, and AI were prescribed in 6 of them. Conclusions: Tam was still the preferred option in elderly women with early breast cancer, but was contraindicated in more than one third of pts. These data suggest that osteoporosis is being probably underdiagnosed in patients over 70 years. In view of a possible treatment with bisphosphonates, screening bone mineralometry should become standard before starting therapy with AI. [Table: see text] No significant financial relationships to disclose.
Predictive value of EGFR and KRAS mutations detected in plasma from non-small cell lung cancer (NSCLC) patients treated with docetaxel and intermittent erlotinib
Authors: P. C. Mack, W. S. Holland, R. A. Burich, Y. Li, L. Beckett, P. N. Lara, A. M. Davies, D. R. Gandara
Journal: Journal of Clinical Oncology (2008)

8062 Background: Activating epidermal growth factor receptor (EGFR) mutations in NSCLC are associated with enhanced response to EGFR tyrosine kinase inhibitors; whereas KRAS mutations are associated with poor response. Determining the presence of EGFR/KRAS mutations in tumor DNA shed into plasma could have considerable clinical utility. We used an allele-specific PCR assay to detect EGFR & KRAS mutations in plasma DNA from NSCLC patients (pts) treated with docetaxel and intermittent erlotinib (Davies, ASCO 2007). Methods: Plasma from 49 NSCLC pts on this phase I/II trial was obtained. Mutations were detected using an allele-specific, real-time PCR assay with Scorpion primers (DxS, UK). This assay detects mutations comprising as little as 0.1% of total DNA (Holland ASCO 2007). Statistics: Cox Proportional Hazard Model; 2-sided Fisher’s Exact Test. Results: EGFR mutations (exons 19, 21 and/or 20) were detected in 12/49 pts. KRAS mutations were detected in 2/49. Pts were dichotomized into two groups: those with activating mutations (exon 19del or exon 21 L858R) and those with wt EGFR or harboring a T790M resistance mutation. The 7 pts with activating mutations had significantly improved progression-free survival (PFS), with a median of 11.8 months vs. 4.2 months for all others. A non-significant trend was observed for overall survival (OS) with a median of 40.2 months vs. 25.5 months (p=.12; HR 0.38 [95%CI: 0.11–1.31]), respectively. A significant relationship was also observed between EGFR mutational status and best response (45 evaluable): for pts with favorable mutations, 6 had PR/CR vs. 1 with SD; for all others, 8 had PR vs. 30 with SD/PD (p=0.0021). Both CR pts had exon 19 deletions, and all 13 PD pts were EGFR wt. Two pts with mutant KRAS rapidly progressed after 35 and 48 days, with survival of 103 and 48 days. Conclusions: 1) Allele-specific Scorpion technology can detect EGFR/KRAS mutations in shed tumor DNA in plasma. 2) OS was enhanced in this study (>2 year median); pts with activating EGFR mutations had a non-significant trend towards improved survival. 3) The presence of activating EGFR mutations (absent a T790M) significantly correlated with a favorable PFS and response rate in advanced NSCLC pts. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration OSI Oncology Genentech™ BioOncology
Association of chronic co-morbidities with long term survival with metastatic renal cell carcinoma (mRCC).
Authors: Matthew T. Campbell, Amishi Yogesh Shah, Kirtan Das Nautiyal, Neda Hashemi, Paul Gettys Corn, Lance C. Pagliaro, Eric Jonasch, Nizar M. Tannir
Journal: Journal of Clinical Oncology (2015)

472 Background: Since the introduction of targeted therapy, patients (pts) with mRCC are living longer. Cumulative toxicities of sequential targeted therapies remain an area largely unexplored. Methods: A retrospective review of consecutive mRCC pts evaluated at MDACC from 1/1/2001 to 12/31/2008 was conducted. We characterized pts who lived &gt;4 yrs with metastatic disease. In the table below, de novo hypertension (HTN) refers to new onset HTN on VEGF or mTOR targeted therapy (TT), HTN exacerbation refers to HTN in pts with already documented HTN on TT, HTN exacerbation after de novo HTN refers to pts who had exacerbations during subsequent TT after de novo HTN on TT. Descriptive statistics were used. Results: 205 pts with evaluable initial data were characterized for baseline co-morbidities listed in the table below; 37 pts did not have adequate follow up. Of the remaining 168 pts, 12 were managed with surgical resections only and did not receive any systemic therapy, 12 pts received systemic therapy (Tx), but not TT, and 144 received TT: 142 pts (84.5%) received at least 1 VEGF-directed agent, 115 pts (68.5%) received multiple VEGF-directed agents, 75 pts (44.6%) received mTOR inhibitors. Conclusions: Development of HTN and HTN exacerbations are markers of treatment efficacy. The long-term survivors identified in our series had high rates of HTN, hyperlipidemia, hypothyroidism, and VTE. Toxicity cost is an important aspect of long-term survivorship and warrants continued study. [Table: see text]
Experimental Production of Labial and Lingual Carcinoma by Local Application of 4-Nitroquinoline &lt;italic&gt;N&lt;/italic&gt;-Oxide&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Hiroshi Fujino, Takehiro Chino, Tamaki Imai
Journal: JNCI Journal of the National Cancer Institute (1965)

A 0.25 percent solution of 4-nitroquinoline N-oxide in propylene glycol, when applied by repeated painting of the mucosa of the lower lip in mice, gave rise to labial and/or lingual carcinoma of the squamous cell pattern in 16 (47.0%) of the 34 animals surviving 180 days or more of the experiment. This application of 4-nitroquinoline N-oxide, when accompanied by mechanical injury to the lower lip with a metal wire, gave rise to oral carcinoma of the same pattern in 61 (77.21%) of the 79 animals surviving the same experimental period. The carcinoma so produced metastasized to the regional lymph nodes in 8 of 61 animals and to the lung in 1 mouse. A sarcoma of the spindle cell type developed in the lower lip and/or the gingiva in 4 of the 113 survivors.