tbuckley/cabot-search huggingface dataset:
A phase I study of amrubicin (AMR) and irinotecan (CPT-11) in relapsed small cell lung cancer
Authors: T. Mio, M. Kawahara, M. Fukushima, K. Yanagihara, T. Daimon, K. Furuse
Journal: Journal of Clinical Oncology (2007)

18181 Background: AMR and CPT-11 have shown excellent activity in extensive small cell lung cancer (SCLC). The aim of this study was to determine the maximum tolerated dose (MTD) of amrubicin in combination with a fixed dose of CPT-11. Methods: Eligibility criteria were patients having pathologically proven SCLC, had relapsed after one or two previous chemotherapies, ECOG performance status (PS) of 0–2 and adequate organ function. Irinotecan was delivered as 50 mg/m 2 on days 1 and 8, every 21 days. AMR was delivered on day 1. Doses of AMR were level 1: 80mg/ m 2 , level 2: 90 mg/m 2 and level 3: 100 mg/ m 2 . Dose elevation was determined using continuous reassessment method (CRM). Tolerability was assessed after the 1 st cycle. Another two cycles were conducted when disease progression or unacceptable toxicities were not observed. Results: Between June 2004 and October 2006, 18 patients were enrolled with the following characteristics: male/female, 15/3; median age, 66.3 years (range 57–61); PS 0/1/2: 4/14/0. Median number of previous treatment cycles was 5. A total of 40 courses were conducted. Grade 3/4 hematological toxicities of 1 st cycle were: leukocytopenia: 67% (G3/4: 8/4); neutropenia: 89% (G3/4: 6/10), thrombocytopenia: 11% (G3/4: 1/1). Grade 3 febrile neutropenia occurred in 1 patient. Other grade 3 or greater non-hematological toxicities were observed in 4 of 40 courses (grade 3 infection in 3 courses and diarrhea in 1). In the first course, DLT was observed in 2 of 6 patients at dose level 2 (prolonged grade 4 neutropenia, febrile neutropenia), in 1 of 6 at dose level 3 (prolonged grade 4 neutropenia), MTD of amrubicin were determined by CRM to be 100 mg/m 2 (level 3). Objective response was obtained in 4 patients (28%). Conclusions: This combination was well tolerated and showed activities in SCLC, though hematological toxicities were rather severe. Phase II trials are being planned in chemo naïve SCLC. No significant financial relationships to disclose.
A new classification of dynamic CT images predictive of malignant characteristics of hepatocellular carcinoma.
Authors: Y. Kawamura, K. Ikeda, M. Hirakawa, T. Hosaka, N. Akuta, M. Kobayashi, S. Saitoh, F. Suzuki, Y. Suzuki, H. Kumada
Journal: Journal of Clinical Oncology (2010)

e14598 Background: The aim of this study was to elucidate whether the histopathological characteristics of hepatocellular carcinoma (HCC) can be predicted from baseline dynamic-CT images. Methods: This retrospective study included 86 consecutive patients with HCC who underwent surgical resection between January 2000 and September 2008. The arterial and portal-phase dynamic-CT images obtained preoperatively were classified into four enhancement patterns: Type-1 and Type-2 are homogeneous enhancement patterns without or with increased arterial blood flow, respectively, Type-3; heterogeneous enhancement pattern with septum-like structure, and Type-4; irregularly-shaped ring structures with enhancement pattern. We also evaluated the predictive factors for poorly-differentiated HCC, specific macroscopic type of HCC (simple nodular type with extranodular growth [SNEG] and confluent multinodular [CMN]) by univariate and multivariate analyses. Results: The percentages of poorly-differentiated HCC according to the enhancement pattern were 3 of 51 nodules (6%) of Type-1 and 2, 3 of 24 (13%) of Type-3, and 8 of 11 (73%) of Type-4. The percentages of SNEG/CMN according to the enhancement pattern were 12 of 51 nodules (24%) of Type-1 and 2, 13 of 24 (54%) of Type-3, and 5 of 11 (45%) of Type-4. Multivariate analysis identified Type-4 pattern as a significant and independent predictor of poorly-differentiated HCC (p < 0.001) while Type-3 pattern was a significant predictor of SNEG/CMN (p = 0.017). Conclusions: Heterogeneity of dynamic-CT images correlates with malignant characteristics of HCC and can be potentially used to predict the malignant potential of HCC before treatment. No significant financial relationships to disclose.
Phase 2 study of the pan-isoform PI3 kinase inhibitor BKM120 in metastatic urothelial carcinoma patients.
Authors: Gopa Iyer, Christopher Michael Tully, Ilana Rebecca Garcia-Grossman, Sasinya N. Scott, Mariel Elena Boyd, Asia S. McCoy, Michael F. Berger, Hikmat Al-Ahmadie, David B. Solit, Jonathan E. Rosenberg, Dean F. Bajorin
Journal: Journal of Clinical Oncology (2015)

324 Background: PI3 kinase (PI3K) pathway alterations are found in 39% of urothelial carcinoma (UC) (TCGA). Prior reports have shown significant responses in metastatic UC patients (pts) whose tumors harbor PI3K pathway alterations treated with mTOR inhibitors, providing a rationale to investigate BKM120 in mUC. Methods: This phase II study enrolled mUC pts progressing on platinum-based chemotherapy (up to 4 prior agents). The primary and secondary endpoints were proportion of pts progression-free at 2 months and response rate (RR) by Response Criteria in Solid Tumors (RECIST) v1.1, respectively. A Simon 2-stage design was used to discriminate between a 2 month PFS rate of &lt;60% (at which point the trial would be halted) vs. &gt;80%. Pts received 100 mg drug once daily. To identify predictors of response/resistance to BKM120, targeted exon capture sequencing was performed to define the mutation status of PIK3CA, PTEN, AKT1, TSC1, and additional genes within tumors from all treated pts. Results: 13 of 15 enrolled pts were eligible for the primary endpoint. Median age was 65 (53-82). Pts had received an average of 3 agents (2-4) before enrollment. The median progression-free survival (PFS) was 2.77 months (95% CI: 1.83-3.71) with 6 pts displaying stable disease (SD) and 1 partial response (PR) at 2 months (PFS rate 54%). Sequencing identified 2 pts with PIK3CA mutations (E542K, H1047R) who experienced progression as best RECIST response. Tumor from the pt with a 16 month PR harbored a TSC1 R500* nonsense mutation. 1 pt with SD lasting 3.7 months had a TSC1 L330fs truncation. Conclusions: While BKM120 therapy did not display a significant improvement in 2-month PFS rate compared to standard chemotherapy in the second-line setting, 2 pts, one with a durable PR and one with SD, had tumors with inactivating mutations in TSC1. Based upon these results, an expansion cohort is accruing in which select mUC pts whose tumors harbor PI3K pathway alterations receive BKM120. Clinical trial information: NCT01551030.
Abstract 14979: Proprotein Convertase Subtilisin / Kexin Type 9 (PCSK9) is a Novel Risk Predictor in Statin-Treated Coronary Artery Disease Patients
Authors: Christian Werner, Michael M Hoffmann, Michael Böhm, Ulrich Laufs
Journal: Circulation (2014)

Objective:  Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an essential regulator of hepatic LDL receptor turnover and serum LDL-C concentrations. PCSK9 inhibitors currently emerge as a new option to lower LDL-C and as therapeutic tools in the prevention of cardiovascular (CV) disease. The association of PCSK9 and event-free survival has not been clarified prospectively in high-risk patients. This prospective cohort study analyzes risk prediction with PCSK9 serum concentrations in patients with stable coronary artery disease (CAD) on statin treatment.   Methods & Results:  PCSK9 concentrations were measured by ELISA in 504 consecutive patients with clinically stable CAD confirmed by angiography (median age 68 years, 83% male, 95% treated with statins, median LDL-C 100mg/dl). PCSK9 correlated strongly with fasting triglycerides (R=0.33, p  The primary outcome was the composite endpoint of cardiovascular death and cardiovascular hospitalization for acute coronary syndrome or hospitalization for unplanned, symptom-induced coronary angiography and revascularization (including bypass surgery) within 48 months follow-up. Comparison of event-free-survival between PCSK9 tertiles showed that serum concentrations of PCSK9 predicted CV outcomes (PCSK9 >622ng/ml vs.    Summary & Conclusion:  PCSK9 serum concentrations predict cardiovascular events in patients with stable coronary artery disease on statin treatment. Fasting triglycerides, but not LDL-cholesterol, are correlated with PCSK9 and modify risk prediction by PCSK9.
Treatment of recurrent malignant glioma with G207, a genetically engineered herpes simplex virus-1, followed by irradiation: Phase I study results
Authors: M. Karrasch, G. Y. Gillespie, E. Braz, P. G. Liechty, L. B. Nabors, A. D. Lakeman, C. A. Palmer, J. N. Parker, R. J. Whitley, J. M. Markert
Journal: Journal of Clinical Oncology (2009)

2042 Background: G207 is a doubly mutated (deletion of both γ134.5 loci, insertional inactivation of UL39) herpes simplex virus (HSV)-1. Safety and efficacy of intracerebral inoculations of G207 to patients suffering from recurrent malignant gliomas have been demonstrated in previous clinical trials. Methods: In this phase I clinical trial, a total of 1 x 10 9 plaque forming units (pfu) G207 were administered by five stereotactic injections of 0.2 mL each into regions of recurrent malignant glioma defined by MRI, followed by focal radiation therapy 24 hours post injection. Included patients suffered from inoperable pathologically proven recurrent glioblastoma multiforme (GBM) or anaplastic astrocytoma (AA) which was progressive despite radiotherapy or chemotherapy and failed external beam radiotherapy &gt; 5 Gray prior to study enrolment. Results: 9 patients were treated in this phase I study. 5 patients were suffering from relapsed GBM, 4 patients were suffering from relapsed AA. 1 month after treatment, 3 patients (3xGBM) showed SD, 2 patients (1xGBM, 1xAA) PR, and 4 patients (1xGBM, 3xAA) PD. The 2 patients with initial PR (1xGBM, 1xAA) were re-treated with G207/Irradiation at time point of tumor recurrence, showing PR one month after re-treatment again. Median overall survival time for all 9 patients was 229 days (7.6 months), with one patient still alive at time of abstract submission. In patients suffering from relapsed GBM, mOS was 7.4 months, in patients suffering from relapsed AA, mOS was 9.25 months. 20 serious adverse events occurred in this study, only 3 were possible/probable related to G207/irradiation. Within persistent areas of tumor, HSV staining was present by using a polyclonal antibody for HSV, indicating intratumoral G207 replication (proof of concept). Conclusions: In 9 patients suffering from relapsed GBM or AA, stereotactic intracerebral G207 inoculation followed by radiation therapy was feasible, safe, and induced clinically relevant responses. G207/Irradiation re-treatment was possible and induced anew clinical responses. Median overall survival is superior to published data in this patient population. Therefore, further clinical development of G207 in GBM is medically reasonable. [Table: see text]
Abstract 13452: Serum Apolipoprotein B-48 levels Are Significantly Correlated with Plaque Score of Carotid Arteries
Authors: Daisaku Masuda, Manabu Okubo, Hiroyuki Hanada, Masahiro Matsui, Yoh Hidaka, Yasushi Sakata, Shizuya Yamashita
Journal: Circulation (2014)

Introduction: Fasting hypertriglyceridemia is a “residual risk” factor for atherosclerotic cardiovascular diseases and related to postprandial hypertriglyceridemia (PHTG). Intestine-derived lipoproteins such as chylomicrons and chylomicron remnants (CM-Rs), which contain one apolipoprotein(apo) B-48 molecule per one particle, are accumulated in patients with PHTG. Basic studies showed that CM-R had an atherogenic nature and apoB-48 molecule was observed in atherosclerotic plaque twice as many as apoB-100 molecule histologically. We established a CLEIA for measuring serum apoB-48 concentrations and reported that high apoB-48 concentrations correlated with the prevalence of dyslipidemia, diabetes mellitus, metabolic syndrome, chronic kidney disease and coronary heart disease. Hypothesis: We investigated whether serum apoB-48 concentration correlated with subclinical carotid atherosclerosis. Methods: A total of 163 subjects who received ultrasonography of carotid arteries in Osaka University were enrolled. Blood pressure (BP) at the supine position and serum concentrations of apoB-48, plasma glucose, HbA1c, TC, TG HDL-C and LDL-C were measured. Intima-media thickness (IMT) of carotid arteries was measured and plaque score (PS) were calculated in all subjects. Results: All subjects were classified into 4 groups by apoB-48 concentration quartiles: 1st (0-2.2 μg/mL, n=41), 2nd (2.3-3.5 μg/mL, n=39), 3rd (3.6-6.7 μg/mL, n=42) and 4th quartile (≧6.8 μg/mL, n=41), respectively. TG concentrations, prevalence of high BMI (≧25), max-IMT and PS were increased as apoB-48 concentrations were increased. Max-IMT and PS had significant correlations with age, eGFR, systolic BP, log-TG and log-apoB-48 levels and a multiple regression analysis indicated that the age, eGFR, and log-apoB-48 concentrations (p&lt;0.05) were a significant determinant of an increased max-IMT and PS. In subjects whose TG concentrations were &lt;150 mg/dL, max-IMT and PS were significantly higher in subjects of the 4th quartile than those of other quartiles. Conclusions: High serum apoB-48 concentrations strongly correlated with increased max-IMT and PS, indicating that the accumulated CM-Rs might be one of the increased risk for subclinical carotid atherosclerosis.
Elevated multidrug resistance-associated protein 4 (MRP4) expression in localized prostate cancer—A potential androgen regulated protein
Authors: L. G. Horvah, L. Ho, J. G. Kench, J. A. Allen, G. L. Scheffer, P. D. Stricker, J. J. Grygiel, R. L. Sutherland, S. M. Henshall
Journal: Journal of Clinical Oncology (2006)

20022 Background: MRP4 is an ATP-binding cassette transporter and amphipathic anion efflux pump which transports prostaglandins, nucleoside analogues, glutamate and phosphate analogues. High MRP4 expression is prognostic of poor outcome in neuroblastoma and also correlates with MYCN amplification, suggesting regulation by this oncogene. Although MRP4 is known to be expressed in normal prostate epithelium, its expression in prostate cancer (PC) is undefined. This study aimed to define the pattern of expression of MRP4 in normal and malignant prostate tissue and assess the association with androgen exposure. Methods: 84 radical prostatectomy specimens from patients with clinically localized PC (22 neoadjuvant androgen ablation therapy, 62 no neoadjuvant treatment), 42 specimens of hyperplasia adjacent to PC and 16 cases of advanced PC were assessed for MRP4 expression using in situ hybridisation and immunohistochemistry. PC cell lines were assessed by immunoblotting. Results: There were significantly higher levels of MRP4 mRNA and protein expression in localized PC compared to hyperplasia (p=0.006). Conversely, MRP4 protein levels were significantly decreased in PCs treated with neoadjuvant androgen ablation therapy compared to cancers exposed to normal testosterone levels (p &lt; 0.0001). There was also a trend towards decreased MRP4 expression in advanced PCs. Furthermore, immunoblotting revealed that MRP4 protein was more highly expressed in androgen-dependent (LNCaP) compared to androgen-independent (PC3/DU145) cell lines. In addition, in a panel of 14 normal human tissues only kidney and prostate tissue expressed MRP4 protein suggesting limited expression of MRP4 in human tissues. Discussion: Elevated MRP4 expression is found in malignant compared to benign prostate tissue while lower MRP4 expression is seen after androgen ablation suggesting that MRP4 may be an androgen-regulated gene. In addition, there is relatively little expression of MRP4 in normal tissues. These data suggest that MRP4 is important in the progression to PC and that it may be a potential therapeutic target. No significant financial relationships to disclose.
Pemetrexed in second-line therapy in patients with malignant pleural mesothelioma
Authors: M. Serke, T. Bauer
Journal: Journal of Clinical Oncology (2007)

18198 Introduction: Based on the study of Vogelzang (2003) standard treatment in patients with malignant pleural mesothelioma (MPM) is pemetrexed cisplatin with a medium survival of 12 months compared to 9 months with cisplatin therapy. As this treatment prolongs survival, but is not a curative treatment, many patients will relapse during the course of their disease. In sensitive relapses (within more than 3 months) our policy was to reintroduce pemetrexed therapy in unselected consecutive patients. Methods: Retrospective analysis of 17 consecutive patients treated in our hospital. Patient characteristics: 17 patients (pat), 14 males, 3 females, with MPM were included between April 2004 and November 2006 with an age between 45 and 82 years, with a median age of 65 years. Histologic subtypes were: 16 epithelial, 1 biphasic MPM. Pretreatment: 8 pat. had undergone palliative debulcing surgery (pleurectomy) 1 pat. underwent EPP. All patients were pretreated with platinum /pemetrexed, 5 pat. were pretreated with platinum/Gemcitabine before the availability of pemetrexed. 2nd line chemotherapy: 9 pat. were treated with carboplatin AUC5 / pemetrexed 500 mg/m 2 , 1 patient had cisplatinum 75 mg/m 2 /Pemetrexed 500 mg/m 2 and 7 patients had pemetrexed single agent therapy (500 mg/m 2 d1, WH d21), repeated on day 22 respectively. Results: Response: 6% (n=1) PR, MR: 12% (n=2 )., NC: 47% (n=8)., PD: 35% (n= 6), clinical benefit (PR, MR, NC) was seen in 65% of ou pat. Toxicity: Pemetrexed/Carboplatin or pemetrexed therapy were well tolerated, toxicity was mild: one patient developed mild sensory neurotoxicity (peripheral sensory neuropathy) (WHO II) under 6 cycles pemetrexed, 35% developed mild fatigue (Who I and II), one patient had mild renal impairment, no alopecia was seen. Survival: Only 3 patients had still died, median survival from start of second-line pemetrexed-therapy was not reached, time to progression was between 25 and 630 days, 4 pat. had not progressed until now. Conclusion: Second line therapy in MPM is not yet standard of care. Nevertheless patients with progressive disease following pemetrexed/platinum therapy may benefit from second line pemetrexed reintroduction therapy. Clinical benefit was seen in 65% with low toxicity. No significant financial relationships to disclose.
A SOCIOPSYCHIATRIC STUDY OF TWENTY-FIVE YOUNG OFFENDERS
Authors: EDWARD T. ADELSON, CARL SUGAR, S. BERNARD WORTIS
Journal: American Journal of Psychiatry (1949)

A review of the case material points up 4 significant findings: 1. The short period of residence in New York City of a large number of offenders, i.e., less than 6 months at the time of arrest. As is to be expected, the greatest metropolis in the world attracts the unstable, unrooted, impulsive adolescent who seeks his fortune and anonymity because life in his home town offers little adventure. They seem to take jobs of short duration, with little compensation in terms of monetary reward or satisfaction, and thus, frustrated and disappointed again, are apt to choose an easy way of survival. 2. The loss of parents by death, desertion, and broken homes was found in the life history of almost half of the offenders. In this respect this group is similar to younger and adolescent offenders, as reported by others studying delinquency. It is fair to assume, therefore, that separation from parents at the early age cited, before the tenth year, is a serious predisposing factor toward antisocial and delinquent behavior. 3. The inability of these boys to sustain efforts in terms of educational and vocational achievement is striking. Despite their "affect-hunger" they did not sublimate by learning a skill, or trade, or schooling for some of their unfilled needs. The lack of libidinal development and subsequent weak ego growth seems to result in a total inability to achieve satisfaction in a socially acceptable sense, in terms of schooling and work. 4. The high incidence of neurotic traits indicates that for the most part behavior in this group fell between two poles—antisocial character and neurotic acting out. The majority of the subjects showed a combination of both. In addition, our psychiatric findings would place these offenders in three major groups, as follows: (A.) The antisocial character, (B.) The antisocial character associated with neurotic conflicts, (C.) Primarily neurotic personalities with minimal antisocial character formation.
Documenting the impact of alopecia in breast cancer: Assessing the performance of the alopecia patient assessment (APA) questionnaire.
Authors: Elisabeth Piault-Louis, Jennifer Petersen, Jonathon Gable, Stacie Hudgens
Journal: Journal of Clinical Oncology (2015)

84 Background: The APA questionnaire was developed to document the emotional and social burden of alopecia experienced by breast cancer patients undergoing therapy. Content, clarity, and relevance of the measure were assessed by patients undergoing chemotherapy; the instructions, recall and APA items were found to be clear and relevant (Mathias et al., 2013). The next phase consists of documenting the performance of the APA measure as an evaluative tool for use in clinical research. Methods: The APA was implemented in a US observational multicentre, prospective, longitudinal cohort of 497 patients with HER2+ metastatic breast cancer (SystHERs) with a mixed modality for data collection (first paper and then transition to ePRO). The APA was collected at baseline and every 90 (± 15) days. The psychometric analysis was adapted based on the study design and on the manifestation of alopecia (onset, duration) in this population. The select set of psychometric tests included quality and pattern of completion, construct validity and reliability. Results: Quality of completion as measured by correct scale use was 85.2% (compliance was 95.6%). Discrimination indices were above the 0.3 threshold for each item on the APA and ranged from 0.59 to 0.82 at baseline. The scale demonstrated good internal consistency as assessed by 0.88 Cronbach alpha. Weighted kappa agreement of 0.49 was observed between the APA and the ‘I am bothered by hair loss’ item (B5) of the Functional Assessment of Cancer Therapy-Breast (FACT-B) measure. Conclusions: The APA is a valid and reliable measure able to discriminate change in patients’ daily functioning resulting from an alopecia event related to treatment for breast cancer. Results support the use of the APA in clinical research to better characterize the impact of alopecia on patients’ lives.
Reduced Toxicity Conditioning With Fludarabine, BCNU, Melphalan and Anti-Thymocyte Globulin Followed By Allogeneic Stem Cell Transplant For Patients With Primary and Post ET/PV Myelofibrosis: Single Center Experience At Mayo Clinic Arizona
Authors: Veena Fauble, Ruben A. Mesa, Pierre Noel, Roberta Adams, Yu-hui Chang, Jose F Leis, Nandita Khera, Lisa Sproat, Craig Reeder, Jared Klein, Jeffrey A Betcher, Meagan Higgins, Lori DeCook, Jane Palmer, Susan Gerber, Kimberly Henderson, Kristen Beebe, Rochelle Chiffelle, Jane Olsen, Angela Toro, James L Slack
Journal: Blood (2013)