tbuckley/cabot-search huggingface dataset:
Comparative evaluation of two methods of chemotherapy dose calculation according to body surface area and body mass index in obese females with breast cancer.
Authors: T. Refaat, S. Abdelmoneim, Y. Rostom
Journal: Journal of Clinical Oncology (2010)

678 Background: Obese patients experience planned or unplanned reduction in chemotherapy dose. There seems to be a consistent tendency to underdose obese patients. Methods: In Alexandria Clinical Oncology Department, from October 2004 to June 2005, 120 obese female breast cancer patients were prospectively recruited, signed IRB approved informed consent and randomized. A woman was classified as obese if her body surface area (BSA) > 2 and/or body mass index >/= 27.3 kg/m2. They received adjuvant FAC chemotherapy calculated according to either the actual (group I) or ideal (group II) BSA. Ideal BSA was calculated according to ideal body weight. The patients were followed prospectively during chemotherapy and for 60 months. Results: Both groups were comparable regarding age (mean 47.5 years), weight (mean 85.5 kg), height (mean 157 cm), menopausal status, hormonal receptors' status, PS, grade, and stage without any statistical difference. The most common acute lab toxicity was the hematological toxicity that was statistically significant on comparing the hemoglobin level (HB) between the first cycle and sixth cycle (p > 0.002) in group I but of no significance in group II. There was an overall statistical significant difference between group I and II as regard the HB level (p < 0.0001), WBCs counts (p > 0.002) and liver function test -ALT level- (p < 0.0001). The same pattern was also noted between the 2 groups as regards renal toxicity, gastrointestinal toxicity, nail discoloration, and hair loss. After 60 months of follow up, there was no statistical significant difference as regards the disease-free survival (mean 46.48 months in group I versus 49.3 months in group II) or treatment failure (19 patients -31.7%- in group I versus 18 patients -30%- in group II with p > 0.843). Conclusions: There was a trend towards a higher toxicity profile in the obese females who received FAC chemotherapy for early stage breast cancer dosed according to the actual BSA. However, no significant differences as regard the treatment failure or disease free survival after 60 months of follow up. We believe that this innovative method used in calculating the chemotherapy dose is less toxic, safer and relatively effective. No significant financial relationships to disclose.
The household dust bio-environment and lung function in adult asthma
Authors: Paul D. Blanc, Stephen Van Dyken, Steve Vesper, Patricia Quinlan, Laura Trupin, Carlos Iribarren, Patricia P. Katz, Edward H. Yelin, Miriam Cisternas, John R. Balmes
Journal: European Respiratory Journal (2011)

Background: The household bio-environment includes molds, bacteria, and animal antigens that may affect lung function, especially in asthma.

Methods: Dust from adult asthmatics' homes was quantified for: Environmental Relative Moldiness Index (ERMI, a DNA-based assay reflecting indoor mold); chitin (found in mold cell walls and invertebrate exoskeletons, assayed by blot densitometry); endotoxin (LPS; limulus assay); beta-1,3-glucans (BG), dust mite (DM), and cockroach (CKR) (ELISAs). We analyzed Spearman correlations among the exposures. Linear regression tested ERMI, chitin, LPS, and BG as predictors of FEV1, with stratification by greater than/less than a detectable level (>DL) of both DM and CKR.

Results: Data from 72 dwellings were available for all variables. Chitin was significantly correlated with BG (r=0.29; p=0.01) and DM (r=0.33; p 0.3). Among 37 subjects with DM or CKR >DL, results were similar, but among 35 subjects <DL for DM/CKR, FEV1% predicted was positively related to both chitin (+7.3%; p<0.01) and ERMI (+2.1% per unit; p<0.01).

Discussion: Chitin and ERMI levels may be associated with better FEV1; the ERMI effect may depend on absent DM/CKR co-exposure.

Clinical: In adult asthma, DM and CKR control interventions should consider other potential co-exposures in the complex home bio-environment.

NIH/NIEHS R01 ES 10906.
Abstract 87: Sestrin2 Promotes LKB1-Mediated AMPK Activation in the Ischemic Heart
Authors: Ji Li, Alex Morrison, Yina Ma, Jinli Wang, Zhenling Liu, Andrei Budanov, Jun-Hee Lee, Michael Karin
Journal: Circulation Research (2014)

AMP-activated protein kinase (AMPK) has emerged as a pertinent stress-activated protein kinase shown to have substantial cardioprotective capabilities against myocardial ischemia/reperfusion injury. When activated during ischemia, AMPK produces effects that have been demonstrated to be beneficial to the myocardium by means of increasing GLUT4 translocation and glucose uptake, activating eNOS, decreasing apoptosis, and increasing autophagic flux. However, the molecular basis behind the regulation of AMPK activity in the ischemic and reperfused heart remains incompletely understood. Recent evidence implicates the role of Sestrin2 in the AMPK signaling pathway and it is hypothesized that Sestrin2 plays an influential role during myocardial ischemia in order to promote AMPK activation. Sestrin2 protein was found to be expressed in adult cardiomyocytes and accumulated in the heart during ischemic conditions. Sesn2 KO mice were used to determine the importance of Sestrin2 during I/R injury. Sesn2 KO cardiac phenotype analysis indicated no significant difference in left ventricular function as measured by a pressure-volume loop catheter. When wild type (WT) and Sesn2 KO mice were subjected to in vivo I/R, myocardial infarct size was significantly greater in Sesn2 KO compared to WT hearts. Similarly, Langendorff perfused hearts indicated exacerbated post-ischemic contractile function in Sesn2 KO hearts when compared to WT. Ischemic AMPK activation was found to be impaired in the Sesn2 KO hearts. Immunoprecipitation of Sestrin2 demonstrated an association with AMPK. Moreover, LKB1, a major AMPK upstream kinase was associated with the Sestrin2-AMPK complex in a time-dependent manner during ischemia while this interaction was nearly abolished in Sesn2 KO hearts. Thus, Sestrin2 plays an important role in cardioprotection against I/R injury by acting as an LKB1-AMPK scaffold to initiate AMPK activation during ischemic insults.
A factorial phase III randomized trial of rofecoxib and prolonged constant infusion of gemcitabine at 10mg/m<sup>2</sup>/min (PCI-G) in first-line treatment of adult patients (pts) with advanced non-small cell lung cancer (NSCLC): The GECO study
Authors: C. Gridelli, A. Ceribelli, V. Gebbia, T. Gamucci, F. Ciardiello, F. Carrozza, A. Favaretto, B. Daniele, D. Galetta, A. Morabito
Journal: Journal of Clinical Oncology (2006)

7069 Background: Preclinical and clinical evidence suggest that rofecoxib and PCI-G might improve efficacy of treatment of advanced NSCLC. Methods: Advanced (stage IV or IIIb with supraclavear nodes or pleural effusion) NSCLC pts, aged &lt;70, PS 0–1, were eligible. A 2x2 factorial design was applied to test if addition of rofecoxib (50 mg daily) or PCI-G could improve overall survival (OAS) compared with standard first-line treatment [cisplatin (80 mg/m 2 d 1) and gemcitabine (1200 mg/m 2 dd 1&amp;8) every 21 days]. To have 80% power of detecting a 0.67 HR of death, with bilateral alpha = 0.05, 400 pts were planned and 200 deaths were required for each comparison. Response was assessed with RECIST, quality of life (QoL) by EORTC questionnaires. Results: From Jan ’03 to May ’05, 400 pts were enrolled. Rofecoxib arms were closed (Oct 1st,’04) due to manufacturer decision of drug withdrawing for safety issues. As of Dec ’05, analyses include 400 pts (246 deaths) for PCI-G and 240 pts (enrolled as of Jul 1st,’04 to have a 3-month chance of treatment) for rofecoxib comparison (168 deaths). Median age was 60. PCI-G did not improve OAS (median 47.3 vs 42.9 weeks with standard infusion, HR 0.97, 95% CI 0.75–1.25), nor any other secondary end-point. Rofecoxib did not prolong OAS (median 43.6 vs 44.1 weeks without rofecoxib, HR 1.01, 95% CI 0.74–1.38), but improved response rate (41.2% vs 26.4%, p = 0.02), global QoL, physical and role functioning, fatigue, pain and analgesic consumption. In both comparisons, there was no clinically relevant difference in toxicity. Conclusions: Neither PCI-G nor rofecoxib prolonged OAS. Rofecoxib improved response rate and several QoL items, including pain-related and global QoL. Partially supported by AIRC; rofecoxib freely supplied by MS&amp;D Italy. No significant financial relationships to disclose.
Senator questions pain panel’s ties to industry
Authors: Michael McCarthy
Journal: BMJ (2016)

A US senator has begun an inquiry into possible conflicts of interests among members of an expert committee that advises the US government on policy on pain treatment.

The Interagency Pain Research Coordinating Committee (IPRCC) is being consulted by the Department of Health and Human Services about changes to opioid prescribing guidelines that have been suggested by the US Centers for Disease Control and Prevention (CDC).

A draft of those guidelines,1 released last December, focused on the use of opioids for the treatment of chronic non-cancer pain. The draft guidelines recommended that opioids should be used as a last resort for these patients and that treatment with non-opioid drugs and physical, …
Computed Tomography and Ventral Hernia Recurrence—Reply
Authors: Julie L. Holihan, Lillian S. Kao, Mike K. Liang
Journal: JAMA Surgery (2016)

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Oxaliplatin (OXA) plus folinic acid (FA) and 5-fluorouracil (FU) i.v. bolus (OXAFAFU) versus irinotecan (IRI) plus FA and FU i.v. bolus (IRIFAFU) in advanced colorectal carcinoma (ACC): Activity and toxicity results of the SICOG 0103 randomized trial
Authors: P. Comella, B. Massidda, G. Filippelli, F. De Vita, D. Natale, A. Farris, F. Buzzi, L. Maiorino, S. Tafuto, S. Mancarella
Journal: Journal of Clinical Oncology (2004)

4143 Background: IRIFAFU regimen showed activity and toxicity similar to other IRI+FU based combinations in ACC (Comella et al, Ann Oncol 2002). Primary end-point of SICOG trial 0103 was to compare response rate (RR) of OXAFAFU with that of IRIFAFU in ACC. Methods: ACC patients (pts) with measurable disease randomly received: IRI 200 mg/m2 i.v. (90-min) on day 1, and l-FA 250 mg/m2 i.v. (2-hour) + FU 850 mg/m2 i.v. (bolus) on day 2 (IRIFAFU); or OXA 100 mg/m2 i.v. (2-hour) on day 1, and l-FA 250 mg/m2 i.v. (2-hour) + FU 1,050 mg/m2 i.v. (bolus) on day 2 (OXAFAFU high dose [HD]); both regimens were given every 2 weeks. After a planned interim analysis on the first 145 treated pts, OXA was reduced to 85 mg/m2, and FU to 850 mg/m2 (OXAFAFU low dose[LD]). Results: From January 2001 to June 2003, 274 (135 IRIFAFU, 71 OXAFAFUHD, 68 OXAFAFULD) pts were treated. Pre-treatment characteristics according to arms: PS=1–2: 54/38/26; adjuvant FAFU: 34/19/15; two or more disease sites: 63/40/31; liver mets: 99/56/52. WHO toxicity (% pts) according to arms: febrile neutropenia= 4/10/1.5; Grade 4 neutropenia=14/35/19; Grade 3 or more diarrhea=25/10/10. Sixty-day mortality rate=4.4/4.2/4.3. Lévi Grade 3 neuropathy occurred in 11%/3% of pts treated with OXAFAFUHD/OXAFAFULD. RR according to arms: IRIFAFU=31%, OXAFAFUHD=41%, OXAFAFULD=44%. After a median follow-up of 19 months, 166 (60%) pts showed progression, and 118 (43%) pts died: overall median progression-free and survival times were 7.7 and 17.3 months. Numbers of events are still few for comparative analysis. Conclusions: OXAFAFULD regimen produced a significantly greater RR (Fisher's test, p=0.0478), and a lower toxicity than IRIFAFU. Updated results on progression-free and overall survival according to arm of treatment will be presented at the time of the meeting. No significant financial relationships to disclose.
Successful changes in the diagnosis of earlier stages in invasive cervical cancer following a cancer detection program in Tucuman, Argentina
Authors: J. J. Zarba, S. V. Holgado, M. Sanchez Segura, A. Gonzalez, V. Audi, A. Elias
Journal: Journal of Clinical Oncology (2007)

1544 Background: The PDCCUT provides annually free cancer screening to many low-income, underinsured women. Effective control of cervical cancer depends primarily on early detection of precancerous lesions and also on the diagnosis of earlier stages of invasive lesions through use of the Papanicolaou test, followed by timely evaluation and treatment. The goal of this study is to determine the impact of the PDCCUT on the stage at initial diagnosis of invasive cervical cancer. Methods:This is a retrospective, cross-sectional and exploratory study of data registered in CRRCGMT from 376 women with cervical cancer diagnosis. UICC/FIGO is the staging system used. Every 3 years -from 1985 to 2005- rates were calculated; also trend of stages I-IIa and IIb-IV were estimated. Patients-stages were analyzed, before and after 2001 (beginning of the program). Changes in cervical cancer rates before and after the introduction of organized screening were compared. Conclusion: The results showed a progressive increase in the diagnosis of earlier stages of cervical cancer indicating the impact of PDCCUT. The last trienium rate is coincident with the increase of citological diagnosis (Papanicolaou). A lower rate in the diagnosis of EIIb-IV stages is expected in the next trienium. Evaluation of clinical practice in a Cancer Program allows to improve asistencial quality. [Table: see text] [Table: see text] No significant financial relationships to disclose.
Quality Improvement in Breast Cancer Project: Compliance With Antiresorptive Agents and Changing Patterns of Drug Use
Authors: Charles P Borden, Charles L Shapiro, Maria Teresa Ramirez, Linda Kotur, William Farrar
Journal: Journal of the National Comprehensive Cancer Network (2014)

The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute participated in NCCN's Quality Improvement in Breast Cancer initiative. The Opportunities for Improvement (OFI) team elected to improve concordance with the NCCN Clinical Practice Guidelines in Oncology for Breast Cancer recommendation that all patients diagnosed with skeletal metastases receive bisphosphonates. Assembling a multidisciplinary team of clinicians, researchers, and administrative stakeholders, the OFI team followed Six Sigma's approach to problem-solving known as DMAIC (define, measure, analyze, improve, and control). Baseline concordance was 79%, which was below the recommended target range. Initial analysis quickly revealed that 5 cases were concordant, resulting in a new baseline of 89%. The key root cause identified for the remaining gap was lack of documentation. The solution included education regarding documentation for existing staff, in addition to hard-wiring the material into new physician orientation, discussion of all patients with bone disease at tumor board meetings, and improved consistency with use of the new electronic medical record system. After implementation, the reported concordance was 92%, and the lack of documentation problem decreased from 11% in the baseline study to 6%. The team concluded that use of the NCCN Oncology Outcomes Database as an opportunity for clinical quality improvement initiatives not only is possible but also should be an essential element of any clinical program looking to continuously improve.
Expert consensus statement to guide the evidence-based classification of Paralympic athletes with vision impairment: a Delphi study
Authors: H J C (Rianne) Ravensbergen, D L Mann, S J Kamper
Journal: British Journal of Sports Medicine (2016)

Background Paralympic sports are required to develop evidence-based systems that allocate athletes into ‘classes’ on the basis of the impact of their impairment on sport performance. However, sports for athletes with vision impairment (VI) classify athletes solely based on the WHO criteria for low vision and blindness. One key barrier to evidence-based classification is the absence of guidance on how to address classification issues unique to VI sport. The aim of this study was to reach expert consensus on how issues specific to VI sport should be addressed in evidence-based classification. Method A four-round Delphi study was conducted with 25 participants who had expertise as a coach, athlete, classifier and/or administrator in Paralympic sport for VI athletes. Results The experts agreed that the current method of classification does not fulfil the requirements of Paralympic classification, and that the system should be different for each sport to account for the sports’ unique visual demands. Instead of relying only on tests of visual acuity and visual field, the panel agreed that additional tests are required to better account for the impact of impairment on sport performance. There was strong agreement that all athletes should not be required to wear a blindfold as a means of equalising the impairment during competition. Conclusions There is strong support within the Paralympic movement to change the way that VI athletes are classified. This consensus statement provides clear guidance on how the most important issues specific to VI should be addressed, removing key barriers to the development of evidence-based classification.
Estrogen-independent cell proliferation occurs in the majority of estrogen receptor positive (ER+)/HER2 gene-amplified primary breast cancers: Evidence from a combined analysis of two independent neoadjuvant letrozole studies
Authors: M. J. Ellis, Y. Tao, O. Young, S. White, A. Proia, J. Jackson, L. Renshaw, A. Krause, D. B. Evans, W. R. Miller, M. J. Dixon
Journal: Journal of Clinical Oncology (2005)

9538 Background: Relationships between HER2 status and the efficacy of aromatase inhibitor (AI) therapy for early stage breast cancer require further study. The LET 024 neoadjuvant trial reported that ER+ and HER1+ and/or HER2+ positive (immunohistochemistry - IHC) primary tumors were more responsive to letrozole (LET) than tamoxifen. To further investigate the impact of HER2 status on the efficacy of endocrine treatment, HER2 gene amplification status was determined on 198 LET 024 trial samples, supplemented with 128 tumor samples from Edinburgh. Methods: Samples were screened by HER2 IHC, with FISH on tumors with 2+ or 3+ staining. Sample 1+ and 0+ tumors were never HER2 AMP+. Clinical and Ki67 biomarker outcomes were compared in HER2 AMP+ tumors versus HER2 AMP- tumors. All tumors were ER by central IHC testing. Results: There were too few AMP+ cases in the LET 024 trial for adequate analysis. To overcome the problem of small sample size the LET arm of the LET 024 trial and the Edinburgh LET experience were pooled. 20 LET treated HER2 AMP+ tumors exhibited a 65% clinical RR versus 70% for HER2 AMP- tumors. Mammogram data and ultrasound measurements supported the conclusion that the RR to LET was not impaired by HER2 AMP+. In contrast, LET-induced Ki67 decreases were significantly less in the HER2 AMP+ versus AMP- tumors (M-W P=0.0001) and Ki67 fell to ≤1% in only 13% of the LET-treated HER2 AMP+ tumors versus 60% of the LET-treated HER2 AMP- tumors (Fisher P=0.0001). Conclusions: Tumor regression with neoadjuvant LET was unaffected by HER2 AMP+ status. In contrast suppression of Ki67 after 3 to 4 months of treatment was greatly impeded in HER2 AMP+ tumors versus HER2 AMP- tumors. These data suggest that cell cycle regulation is partially or completely estrogen-independent in the majority of HER2 AMP+ primary tumors which may portend the development of long-term resistance to adjuvant aromatase inhibitor therapy in this patient cohort. Furthermore Ki67 analysis may prove to be an effective tool to identify other genetic events that promote estrogen independent growth and endocrine therapy resistance. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis Novartis
Pharmacokinetics (PK) and pharmacodynamics (PD) of E7820-an oral sulfonamide with novel, alpha-2 integrin mediated antiangiogenic properties: Results of a phase I study
Authors: M. M. Mita, A. C. Mita, M. Goldston, Q. S. Chu, A. W. Tolcher, A. Ricart, P. Desai, C. S. Okereke, E. K. Rowinsky, C. Takimoto
Journal: Journal of Clinical Oncology (2005)

3082 Background: : E7820 is a first in class orally administered antiangiogenic sulfonamide that inhibits alpha-2 integrin. E7820 is a potent inhibitor of endothelial cell proliferation and vascular tube formation in vitro, and it effectively inhibits the growth of human breast and pancreatic cancer xenografts. Methods: This open-label, non-randomized phase I study of E7820 in patients (pts) with metastatic and/or recurrent solid tumors utilizes a standard dose escalation design to evaluate the safety and to determine the maximum tolerated dose of daily oral administration of E7820. Secondary objectives include characterization of the PK profile, assessment of PD markers (DCE-MRI, VEGF and bFGF levels in plasma and serum, and changes in alpha-2 integrin expression in circulating platelets), and preliminary exploration of antitumor activity. Results: To date, 18 pts (13 male/5 female; median age 68 [range 40–80]), have been treated with E7820 at doses ranging from 10 to 100 mg/day. No dose-limiting toxicity or E7820-related serious adverse events have been observed. Pts received a median of 3 cycles (range 1–8). Side effects include: grade 1 or 2 fatigue, anorexia, constipation, diarrhea, nausea, vomiting, dizziness, maculopapular rash, mucositis, liver enzymes elevation, paresthesia, and fever. No objective responses have been observed to date. Five pts had stable disease lasting from 3 to 7+ months, and 4 pts continued therapy for 4+ cycles. PK data up to 70 mg demonstrate a Tmax at 2 hr, a dose-dependent increase in both Cmax and AUC, an accumulation factor ranged from 1.08 to 1.82 with higher values seen at the 70 mg dose level and a half-life of 5.7 to 11.9 hr. The Cmax at doses above 70 mg/d approaches the concentrations active in vivo in preclinical models. Conclusions: E7820 at doses up to 100 mg/day has an excellent safety profile in pts with solid malignancies. Enrollment to higher dose levels and analysis of PD endpoints are ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eisai Global Clinical Eisai Eisai