tbuckley/cabot-search huggingface dataset:
Early predictive value of 18F-FDG-PET assessment in advanced esophagogastric junction and gastric cancer patients treated with cetuximab-containing therapy
Authors: F. Di Fabio, C. Pinto, F. Rojas Llimpe, P. Castellucci, S. Fanti, V. Mutri, S. Giaquinta, P. Di Tullio, S. Pini, G. Compagnone, A. Martoni
Journal: Journal of Clinical Oncology (2009)

e15601 Background: 18F-FDG-PET/CT (PET) was reported to predict the pathological response during preoperative chemotherapy in esophagogastric junction (GEJ) or gastric (G) cancer pts. The aim of this study is to evaluate the usefulness of an early change in PET at several time-points in predicting response to cetuximab-containing therapy in pts with advanced GEJ or G cancer. Methods: We evaluated 51 pts with locally advanced/metastatic GEJ or G adenocarcinoma who underwent a first line cetuximab- treatment in two Italian phase II studies. Twenty nine pts (GEJ/G = 5/24; locally advanced/metastatic = 2/27) received cetuximab in combination with cisplatin/docetaxel (DOCETUX study) and 22 pts (GEJ/G = 2/20; locally advanced/metastatic = 3/19) received cetuximab in combination with FOLFIRI (FOLCETUX Study). PET scans were performed at baseline, and in FDG-avid pts, again on day 21 in the DOCETUX study and on day 42 in the FOLCETUX study. Metabolic response was defined as a decrease in maximum standard uptake value (SUV) ≥35% on the basis of our previous study (Di Fabio et al., Gastric Cancer 10:221–227, 2007).Objective response, according to RECIST criteria, was assessed by CT scan at baseline and every 6 weeks. Results: Five pts (10.2%) had FDG non- avid tumor (all pts with signet cell carcinoma). In the 46 FDG-avid tumor pts, the median SUV at baseline was 10.3 (range 5.0 - 36.4). The response rate (RR) was significantly higher in pts with a drop ≥35% in SUV from baseline to day 42: 83% (10/12 pts) in metabolic responders vs. 25% (2/8 pts) in non-metabolic responders (p= 0.019). In contrast, the SUV change at day 21 did not correlate with objective response: RR 57.1% (8/14 pts) in metabolic responders vs. 41.7% (5/12 pts) in non-metabolic responders (p= 0.695). The RR in non-avid tumor pts was 20% (1/5 pts). Conclusions.Our study suggests that in advanced gastric cancer pts with FDG-avid tumor the PET predicts objective response at day 42, but not at day 21. A PET response assessment can provide an opportunity to change the treatment in non-responder pts. Prospective trials defining the role of PET in gastric cancer are warranted. No significant financial relationships to disclose.
Evaluation of responsiveness to change to psychosocial group therapy (PGT) and to the process of dying of psychosocial and quality of life (QOL) measures
Authors: J. Lemieux, D. Beaton, L. Bordeleau, S. Hogg-Johnson, P. Goodwin
Journal: Journal of Clinical Oncology (2005)

8035 Background: Responsiveness, the ability of a measure to accurately detect change when it has occurred, is essential for questionnaires used in intervention trials. Good responsiveness minimizes false negative trials and lowers the sample size (SS) needed to detect an effect. Methods: Using data from the “Breast Expressive-Supportive Therapy” study in metastatic breast cancer (Goodwin PJ NEJM 2001), we assessed group responsiveness to two types of change: the PGT (between group difference of within person changes) and the process of dying (within person changes). Questionnaires are: Profile of Mood States (POMS), Impact of Events Scale (IES), Psychosocial Adjustment to Illness Scale (PAIS), EORTC QLQ-C30, Mental Adjustment to Cancer (MAC) and a pain visual analog scale (PAIN-VAS). The effect size (ES) is the difference in scores divided by the baseline standard deviation (SD) (positive reflecting improvement, negative reflecting deterioration). Results were similar when ES was calculated using SD of change. Results: POMS was the most responsive to PGT (ES 0.30). The MAC, IES and the EORTC emotional subscale were not responsive (ES 0.09, 0.02, -0.01 respectively). The PAIS was intermediate (ES 0.24). For the process of dying, responsiveness was high for the EORTC (ES functional scales -0.71, global QOL -0.70 and symptoms -0.57), PAIN-VAS (ES -0.79) and PAIS (ES -0.65). It was low for POMS (ES -0.22), MAC (-0.21) and IES (0.11). Based on the relative efficiency (square of T-statistic ratio), SS needed to detect what was observed to be an ES of 0.3 for PGT using POMS as the standard are: 348 pts using POMS, 621 using PAIS and > 1000 for the other questionnaires. For the process of dying, SS needed to detect what was observed to be an ES of -0.7 in global QOL using EORTC as the standard are: 16 pts using the EORTC, 27 using the PAIS and 107 using the POMS. Conclusions: This study shows that POMS is the most responsive questionnaire to the effect of PGT,whereas the EORTC and PAIS (addressing symptoms and function) are the most responsive to end of life deterioration. Most responsive questionnaires require the smallest SS. Thus, choice of questionnaire is dependent on the research question. No significant financial relationships to disclose.
Efficacy of GM-CSF vs G-CSF in reducing chemotherapy-induced complications (CIC): A systematic review of literature
Authors: E. Badamgarav, G. H. Lyman, L. Pinto, M. Bernal, R. W. Dubois
Journal: Journal of Clinical Oncology (2004)

6140 Background: While GM-CSF, a multilineage factor, activates neutrophils, eosinophils and monocyte/macrophages, G-CSF, a lineage-specific factor, regulates neutrophil production. GM-CSF is not approved for reducing CIC such as febrile neutropenia (FN); however, a number of studies have been published in this setting. We conducted a systematic literature review to evaluate the efficacy of GM-CSF vs G-CSF.Methods: MEDLINE databases were systematically reviewed for articles published between 01/87–02/03 containing search terms GM-CSF, neutropenia, and G-CSF among others. Two reviewers conducted the review and inter-rater reliability was calculated. Results: Nine solid tumor/lymphoma studies were accepted (inter-rater reliability 0.7). GM-CSF was compared with placebo in 6 RCTs and with G-CSF in 3 studies (see table). Conclusions: Head-to-head comparative trials of G-CSF and GM-CSF in reducing CIC are lacking. Identified GM-CSF studies did not show significant reduction in FN and fever. GM-CSF's multilineage nature limits its role in this clinical setting. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Inc. Amgen, Inc. Amgen, Inc.
Which symptoms are prevalent in patients with recurrent ovarian cancer?
Authors: P. W. Walker
Journal: Journal of Clinical Oncology (2008)

20689 Background: Improved characterization of the symptoms of recurrent ovarian cancer pts is needed to facilitate better treatment and palliation. Methods: Single center study involving platinum-resistant advanced ovarian cancer patients. After informed consent, pts were interviewed and asked to complete the Memorial Symptom Assessment Scale [MSAS] with additional added symptom questions from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-OV28 [EORTC QLQ-OV 28] as well as the complete Functional Assessment of Cancer Therapy for pts with ovarian cancer [FACT-O]. Pts were asked to rate the frequency from 0–4 (0=not at all, 4=very frequent), severity from 0–4 (0=not at all, 4=very severe) and distress level from 0–4 (0=not at all, 4=very severe) of each symptom. Results: Fifty pts were interviewed. The median age of the study group was 56 (range 35–77), predominately white (86%), and education beyond high school (92%). 42 pts had ECOG performance status < 1 (84%). Among symptoms with scores > 2 on each of the dimensions of frequency (F), severity (S) and distress (D): “lack of energy” (n = S28, D23, F35), “worrying” (S26, D21, F30) and “pain” (S23, D20, F29) ranked 1,2 and 3 for each of the dimensions. The top seven ranked symptoms with scores >2 on each of the dimensions were identical and in addition to “lack of energy”, “worrying” and “pain” included: “muscle aches and pain” (S23, D17, F25), “feeling bloated” (S19, D18, F20), “difficulty sleeping” (S18, D18, F24) and “feeling nervous” (S19, D17, F23). For the 18 symptoms studied: correlations between frequency and severity ranged from 0.81–0.97, correlations between frequency and distress ranged from 0.69–0.96, and correlations between distress and severity ranged from 0.71–0.92. Conclusions: Specific and not frequently assessed psychological as well as somatic symptoms were prevalent among platinum resistant ovarian cancer pts studied and these correlated with quality of life. Close correlation between severity, distress and frequency as dimensions of symptoms suggest that these may be collapsed to a single dimension for each symptom. No significant financial relationships to disclose.
Risk of cardiac (CD) and pulmonary (PD) death after post-operative radiotherapy (PORT) for non-small cell lung cancer (NSCLC): Analysis of the Surveillance, Epidemiology, and End-Results (SEER) program
Authors: B. E. Lally, F. C. Detterbeck, C. R. Thomas, M. Machtay, A. A. Miller, T. E. Oaks, W. J. Petty, M. E. Robbins, A. W. Blackstock
Journal: Journal of Clinical Oncology (2006)

6122 Background: Since radiation treatment planning and delivery techniques have evolved over time, we investigated if the risk of CD and PD after PORT for NSCLC has decreased. Methods: We selected postoperative patients with non-metastatic NSCLC diagnosed in 1980–1995 from the SEER data. To account for peri-operative mortality, patients with survival less than 6 months were excluded. Variables analyzed included age, gender, laterality, disease stage, SEER geographic region, ethnicity/race, and histology. CD and PD were calculated at 10 years and compared for patients diagnosed during 1980–83, 1984–88, 1989–91, and 1992–95. Cox proportional hazards models (CPHM) were used to calculate the hazard of CD and PD. Results: This analysis included 29,093 patients treated with observation (OB) and 8334 patients who received PORT. For the patients treated with OB, the 10 yr mortality rates for CD/PD were 17%/2%, 15%/3%, 15%/3%, and 14%/&lt;0.1% for years of diagnosis of 1980–83, 1984–88, 1989–91, and 1992–95, respectively. For the patients who were treated with PORT, the 10 yr mortality rates for CD/PD were 21%/3%, 21%/4%, 15%/4%, and 14%/&lt;0.1% for years of diagnosis of 1980–83, 1984–88, 1989–91, and 1992–95, respectively. CPHM showed the hazard of CD for patients treated with OB to be significantly decreasing; 1980–83 (HR=1.412; CI=1.257–1.585; p&lt;0.0001), 1984–88 (HR=1.260; CI=1.124–1.413; p&lt;0.0001), 1989–91 (HR=1.180; CI=1.054–1.321; p=0.0042), and 1992–95 (HR=1.00; Ref.). CPHM showed the hazard of CD for patients who received PORT to be significantly decreasing; 1980–83 (HR=1.568; CI=1.222–2.011; p=0.0004), 1984–88 (HR=1.435; CI=1.125–1.830; p=0.0036), 1989–91 (HR=0.992; CI=0.767–1.282; p=0.9504), and 1992–95 (HR=1.00; Ref.). Although PD showed a similar decreasing trend relative to year of diagnosis, CPHM did not demonstrate this to be statistically significant. Conclusions: There was a greater reduction in the CD rate in the PORT group compared to the OB group. While there appeared to be a trend in the reduction of PD, the results were not significant which may be secondary to too few events occurring. No significant financial relationships to disclose.
Gene therapy for pretreated ovarian cancer via a novel fiber modified mdr1 targeting conditionally replicating adenovirus
Authors: I. Beyer, G. J. Bauerschmitz, M. Breidenbach, A. Dragoi, D. Niederacher, W. Janni, D. T. Rein
Journal: Journal of Clinical Oncology (2009)

e16513 Background: Ovarian cancer (OC) is a leading cause of death from gynecologic malignancies. Oncolytic adenoviruses (CRAd) are a new approach for cancer treatment. In this study, we constructed a fiber-modified CRAd containing the multi drug resistance gene (mdr) 1 promoter to control viral replication (Ad5/3MDR1). Antineoplastic agents induce mdr1-gene expression triggering chemoresistance. Methods: RT-PCR was performed for expression of mdr1 in cell lines and primary patient samples. We constructed Ad5/3MDR1luc1 to determine relative activity in a variety of cell lines, patient samples, and normal control cells. Replication and oncolysis of Ad5/3MDR1 were assessed in naïve and pretreated OC cell lines. The specificity of viral replication was analyzed in co-culture of pretreated OC cell lines and human fibroid cells. A mouse model of peritoneal carcinomatosis was used to evaluate the efficacy of a combined chemo- and gene therapy for OC. Results: RT-PCR reveals a significantly (p &lt; 0.05) increased expression of the mdr1 gene in OC cell lines and patient samples. Compared to the ubiquitous cmv promoter, mdr1 showed a high level of activity in chemoresistant OC cell lines (7.3%-11.5 %) and OC patient samples (8.8%-12.4%), whereas activity in normal fibroblasts (&lt;1%) was low. Ad5/3MDR1 shows highly selective replication in chemoresistant OC cells in a co-culture with fibroblast cells. Cell killing of Ad5/3MDR1 was comparable to Ad5/3Δ24, a CRAD that replicates in cancer cells inactive in the Rb/p16 pathway, in chemotherapy naïve OC cells but displayed significantly (1.5 log; p &lt; 0.05) higher oncolytic potency in pretreated OC cell lines and primary cells from pretreated OC patients. Moreover, in a therapeutic orthotopic mouse model of peritoneal carcinomatosis, dramatically enhanced survival was noted with Ad5/3MDR1. Conclusions: Ad5/3MDR1 is a promising candidate for gene therapy of metastatic chemoresistant OC with great potential for clinical testing. No significant financial relationships to disclose.
The antioxidant effect of lovastatin and vitamin E on phagocyte-induced DNA damage
Authors: A. B. Weitberg
Journal: Journal of Clinical Oncology (2008)

1523 Background: Lovastatin is an HMG-CoA reductase inhibitor used in the treatment of hypercholesterolemia. Since chronic inflammation may be important in the process of carcinogenesis, novel anti-inflammatory therapies may be useful in cancer prevention. We investigated the antioxidant properties of lovastatin in the presence and absence of D-L-alpha-tocopherol (vitamin E) as evidenced by their effect on phagocyte-induced genotoxicity in mammalian cells. Methods: MRC5 fetal human lung fibroblasts were obtained at passage 18 and not used beyond passage 24. In some experiments, 106 MRC5 cells were exposed to 106 human phagocytes stimulated with 100nM 12-O-tetradecanoylphorbol-13-acetate (TPA) for 30 min. In others, MRC5 cells were incubated with 10 uM lovastatin for 30 min or 10-5M vitamin E for 24 hrs or both prior to the addition of the stimulated phagocytes. After treatment, single-strand breaks were measured by the fluorometric analysis of DNA unwinding. Superoxide anion was measured by following the superoxide dismutase inhibitable reduction of ferricytochrome C at 550 nm. Hydrogen peroxide formation was measured using the method of Pick and Keisari as modified by Frenkel and Chrzan. Results: Lovastatin in its naturally occurring lactone form had no effect on superoxide anion production by stimulated phagocytes. When converted to its acid form, however, superoxide anion formation was inhibited by 36%. Similarly, in its acid form, lovastatin completely inhibited hydrogen peroxide formation by stimulated phagocytes. DNA single-strand breakage was assayed in human lung cells exposed to stimulated phagocytes with and without lovastatin and/or vitamin E. Stimulated phagocytes induced a decrease in double-stranded DNA to 48% of control values which, after pretreatment with lovastatin reverted to 91% of control values. In cells preincubated with lovastatin and vitamin E, double-stranded DNA reverted to 100% of control values. Conclusions: Lovastatin acts as an antioxidant by decreasing oxygen radical production by human phagocytes and may be important in abrogating the carcinogenic effect of chronic inflammation. Since vitamin E protects cell membranes from oxidant stress, the combination with lovastatin has the potential to be effective as an anticarcinogenic strategy. No significant financial relationships to disclose.
Arming the oncolytic virus enadenotucirev (EnAd) to generate enhanced locally-acting immunotherapies for cancer
Authors: Brian R Champion, Nalini Rasiah, Sam Illingworth, Hugo Calderon, Matthieu Besneux, Rochelle Lear, Darren Plumb, Prithvi Kodialbail, Alice Brown
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts EnAd is a potent, chimeric Ad11p/Ad3 adenovirus with selective oncolytic activity against a range of epithelial cancer cells. Ongoing clinical studies have shown that i.v. dosed EnAd infects and selectively replicates in tumor cells, producing detectable levels of viral protein,
Abstract 14965: Cardiac MRI Derived T1 Times in Cardiomyopathy Associated with Duchenne Muscular Dystrophy are Abnormal
Authors: Jonathan H Soslow, Bruce M Damon, David A Parra, W B Burnette, Wenli Wang, Larry W Markham
Journal: Circulation (2012)

Introduction: Patients with Duchenne muscular dystrophy (DMD) have variable severity and age of onset of cardiomyopathy (CM). The ability to predict early CM could alter therapeutic approaches and ...
Texas state breast cancer plan: 18-year report card
Authors: D. Vugrin
Journal: Journal of Clinical Oncology (2004)

6156 Background: In the 1980s, the Texas State Health Department projected that between 1986 and 2000 the number of new cancer cases in Texas would increase by more than 85%. In 1986 the Legislature responded by creating the Texas Cancer Council (TCC) to implement and administer the statewide cancer incidence and mortality reduction program. Funding came from tax dollars. Existing agencies and organizations served as the building blocks to implement the programs through competitive grants. The objective of this study is to evaluate results of the breast cancer action plans. Methods: TCC databases, funded projects and publications were researched and analyzed. Incidence and mortality data were obtained from the Texas Cancer Registry. Results: Between 1986 and 2003, TCC funded over 150 project years for breast cancer related programs (alone or in combination with other cancers) focusing on public, professional education, screening, resource development and data collection. It produced the State Breast Cancer Action Plan in 1993 and 2003, funded development and operations of Cancer Registry, Texas Cancer Data Center, Physician, Nursing and Medical Student Oncology Education Programs (POEP, NOEP, CATCHUM), Texas Cancer Gateway, mammographic units etc. Large population has been reached. Major beneficiaries of education and screening programs were non- and under insured, minorities and rural population (groups traditionally bypassed by preventive care) in all regions of the state. Age-adjusted breast cancer mortality between 1992–2001 (EAPC) decreased by 2.2 but varied between different races. Racial (White, Hispanic, African American) incidence, morality and regional differences have been documented. Conclusion: This seems to be an effective model for coordinated and cooperative public, private and volunteer organizations efforts toward reducing the cancer burden. No significant financial relationships to disclose.
Multiple inter-strut Hollow;SES,PESおよびBMS留置後の光干渉断層による特異な知見
Authors: Hosogi Shingo, Shimizu Hayato, Yoshino Mitsuru, Miyake Koshi, Eguchi Haruki, Tsujimoto Yuki, Shibayama Kentaro, Saitoh Naoki, Ohtsuru Suguru, Okamoto Yoji, Kusunose Mana, Imai Masao, Tasaka Hiroshi, Kosedo Ippei, Hasegawa Daiji, Shigemoto Yoshikazu, Habara Seiji, Tanaka Hiroyuki, Maruo Takeshi, Hirono Akitoshi, Nishibori Yoshiharu, Fuku Yasushi, Oka Naoki, Kato Harumi, Yamamoto Hiroyuki, Fujii Satoki, Goto Tsuyoshi, Inoue Katsumi, Kadota Kazushige, Mitsudo Kazuaki
Journal: Circulation (2010)
Randomized, dose-defined, phase 1B study of recombinant human mannose-binding lectin (rhMBL, EZN-2232) in patients with multiple myeloma undergoing high-dose chemotherapy
Authors: E. J. Anaissie, M. Pineda-Roman, F. Van Rhee, S. Waheed, E. Kiwan, Y. Alsayed, S. Kalambakas, A. Buchbinder, B. Barlogie
Journal: Journal of Clinical Oncology (2008)

20579 Background: Mannose-binding lectin (MBL) is an important component of the innate humoral immune defense. MBL recognizes a variety of microorganisms including bacteria, fungi, and viruses. Low MBL levels are associated with increased susceptibility to infections, especially in immunocompromised patients. rhMBL replacement therapy may decrease the incidence of serious infectious complications observed in MBL-deficient patients who are undergoing chemotherapy. Methods: Patients with multiple myelomareceiving melphalan-based high-dose chemotherapy followed by autologous hematopoietic stem cell transplant whose MBL was <300 ng/mL were eligible for enrollment. Patients were randomized to 1 of 3 groups: no rhMBL, 0.5 mg/kg rhMBL, or 1.0 mg/kg rhMBL. rhMBL was administered as 4 weekly intravenous infusions. All patients received anti-infectious prophylactic supportive therapy per institutional standards. rhMBL concentration was assessed using an ELISA colorimetric assay. Results: Eighteen patients (14 males; median age = 57.4 years) were treated at rhMBL doses of 0 (n=4), 0.5 (n=6), or 1.0 mg/kg (n=8). No drug-related serious adverse events or grade 4 or 5 adverse events (AEs) were reported. All grade 3 AEs were considered unlikely related to rhMBL. The most frequently reported grade 3 AEs were: neutropenia (n=8); bacteremia (n=3); and increased C reactive protein, dehydration, and thrombocytopenia (n=2 each). No rhMBL antibodies were detected. Normalization of in vitro C4b complement deposition tracked the rhMBL concentration. Mean PK results are summarized in the table below. Conclusions: rhMBL was safe and well tolerated in this population. Normalization of in vitro complement activity was achieved with weekly administration of rhMBL. The activity of rhMBL with respect to the prevention of infectious complications is being assessed. Dose (mg/kg) AUC0- ∞ (h·ng/mL)×103 Terminal t½ (h) Cmax (ng/mL) Week 1 Week 3 Week 1 Week 3 Week 1 Week 3 0.5 321 239 38 35 8204 7655 1.0 496 421 42 35 13967 12168 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Enzon Pharmaceuticals Enzon Pharmaceuticals Enzon Pharmaceuticals