tbuckley/cabot-search huggingface dataset:
Clinical significance of epidermal growth factor receptor gene mutations on treatment outcome after cytotoxic chemotherapy in Japanese patients with non-small cell lung cancer (NSCLC)
Authors: K. Hotta, K. Kiura, S. Toyooka, N. Takigawa, J. Soh, Y. Fujiwara, M. Tabata, M. Uno, H. Date, M. Tanimoto
Journal: Journal of Clinical Oncology (2007)

7670 Background: The relationship between EGFR mutation status and clinical outcome has not fully been assessed in NSCLC patients receiving cytotoxic agents. The aim of this study was to clarify its association. We also examined if this association could be affected by the prior gefitinib treatment or not. Methods: Patients with advanced or postoperative recurrent NSCLC who received both cytotoxic chemotherapy and gefitinib monotherapy through their treatment course and whose tumors were assessable for EGFR mutation analysis were included in this study. EGFR mutation was determined in exons 19 and 21 by direct sequencing. Results: Sixty patients were included in the study, including 6 (10%) patients who received the first-line gefitinib monotherapy followed by cytotoxic chemotherapy in the second-line or later settings. Of the 54 (90%) patients, 22 also underwent subsequent cytotoxic chemotherapy after the relapse to gefitinib monotherapy. EGFR mutations were detected in 17 (28%) patients. In the first-line cytotoxic chemotherapy setting (n=54), EGFR mutations significantly affected progression-free survival (PFS) with 6-month PFS rates of 45.8 vs. 21.9% (p=0.05). This was also observed in the multivariate analysis (HR=0.42, p=0.04). EGFR mutation was also significantly correlated with overall survival (OS) in the multivariate analysis (HR=0.26, p &lt;0.01). Contrary, in the 28 (47%) of 60 patients who received cytotoxic chemotherapy after gefitinib monotherapy, there were no differences in PFS stratified by EGFR mutation status. The sensitivity to gefitinib was, however, correlated with EGFR mutation status and its sensitivity was retained even in the second-line setting in patients with EGFR mutations. Conclusion: EGFR mutation was significantly associated with better PFS in the first-line cytotoxic chemotherapy regimens. However, its association was not observed in the cytotoxic regimens administered after the relapse to gefitinib monotherapy, while the sensitivity to gefitinib was associated with EGFR mutation even in the second-line or later setting. No significant financial relationships to disclose.
Abstract #2313: Induced oxidative stress and cell death in the A549 lung adenocarcinoma cell line by ionizing radiation is enhanced by supplementation with docosahexaenoic acid
Authors: Keith Kikawa, Joseph Herrick, Rachael Tateo, Jonathan Tay, Ronald Pardini
Journal: Cancer Research (2009)

Both ionizing radiation and docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid (PUFA), have been shown to inhibit tumor cell growth at least in part by increasing oxidative stress. In the current study, the effects of ionizing radiation, DHA, or a combination of the two on lipid peroxidation (TBARS), cell proliferation, apoptosis (Annexin V-FITC) and anchorage-independent cell growth (soft agar) in A549 lung adenocarcinoma cells were examined. While one previous report using a breast cancer xenograft did not show a significant enhancement to radiation therapy with DHA supplementation (Hardman  et al ., 2005), most other studies have shown DHA is capable of improving tumor cell response to ionizing radiation. Significant decreases in cell proliferation and colony formation in soft agar were noted for ionizing radiation or DHA treatments, while a combination of the two showed significant reductions over either treatment alone. Conversely, lipid peroxidation and early and late stage apoptosis showed significant increases with ionizing radiation and DHA treatments, while cells receiving both treatments demonstrated further significant increases. These findings confirm the potential of DHA supplementation to enhance cancer treatments using ionizing radiation by increasing oxidative stress and enhancing tumor cell death.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2313.
Using health-related quality of life (QL) parameters as primary endpoints in a multinational prospective NSCLC chemotherapy (chemo) trial: The Asia-Pacific QL trial
Authors: R. J. Gralla, P. J. Hollen, S. Thongprassert, H. Kim, S. Yuankai, T. Hsia, C. Wu, K. Park, T. Liu
Journal: Journal of Clinical Oncology (2009)

8086 Background: Survival and QL improvements are major goals in treating advanced NSCLC. Enhancing survival for all treated patients (pts) with advanced NSCLC beyond that achieved with 3 rd generation chemo regimens is difficult in this highly symptomatic cancer; questions remain as to the impact of chemo on QL and symptoms (“PROs” or patient reported outcomes). This study was designed to: 1) evaluate the impact of chemo on QL and symptoms for all pts, 2) evaluate QL by response category (CR+PR = MR or major response, stable disease = SD, and progression); and 3) test whether barriers in QL evaluation are overcome by using a computer-assisted validated instrument (LCSS-QL). Methods: All pts received initial docetaxel-based chemo (83% with cisplatin or carboplatin) based on known response and survival results (Fossella JCO 2003) and were assessed every 3 weeks with the LCSS-QL. Results: 300 pts are entered and 243 evaluated; 91% have repeated QL measures through 3 cycles of chemo in this ongoing trial. Demographics: 77% Stage IV; 72% men; 67% adenocarcinoma; median age 58; KPS 90–100 = 66%, 70–80 = 34%. A 37% MR rate was achieved. QL feasibility: high patient and staff acceptability found (at 43 sites, 8 countries). For the whole group (using 5% as a minimally important difference), after 3 chemo cycles all 9 LCSS parameters were stable, except overall QL and cough (&gt; 5% and 7% improvements). Evaluating PROs by chemo response: in all parameters after completion of only 2 chemo cycles, pts with MR had better symptom control than pts with progression (p&lt;0.05 in 4 of the 6 major symptoms after cycle 3). Total LCSS-QL score was better for pts with MR (p=.007) or SD (p=.03) compared with progressive NSCLC. Conclusions: For docetaxel-based chemo: 1) MR is associated with better symptom control and total QL than SD or progression; 2) even with only a minority (37%) having a major response, QL and PRO parameters are stable or better for the whole group by key decision points of 2 and 3 chemo cycles; 3) with 91% compliance with the computer-assisted LCSS-QL, evaluation of QL in multiple centers is achievable during chemo trials. This study demonstrates that QL and PRO evaluation is feasible and should influence chemotherapy treatment decisions. [Table: see text]
Teresa Krystyna Szulęcka
Authors: Karel de Pauw
Journal: BMJ (2015)

<h3>Objective.</h3> It has been reported that there is an association between rheumatoid arthritis (RA) and increased susceptibility to sexual dysfunction (SD). This systematic review and metaanalysis aimed to investigate whether RA was a risk factor for SD. <h3>Methods.</h3> MEDLINE (PubMed), EMBASE, and the Cochrane Library were systematically searched for all studies assessing sexual function in patients with RA. The association between RA and risk of SD was summarized using relative risk (RR) with 95% CI. <h3>Results.</h3> Overall, 44,745 participants (mean age 43.2 yrs) were included from 7 studies (4 cross-sectional and 3 case-control studies). Of these, 6642 were patients with RA, with the mean disease duration from 5.7 years to 12.17 years. The methodological qualities of the included studies were judged as moderate to high. Synthesis of results demonstrated that RA was significantly associated with an increased risk of SD in females (RR 1.73, 95% CI 1.36–2.22, p &lt; 0.001; heterogeneity: I<sup>2</sup> 60.3%, p = 0.028) as well as in males (RR 1.99, 95% CI 1.64–2.43, p &lt; 0.001). The outcomes related to the Grading of Recommendations Assessment, Development, and Evaluation approach showed that the absolute effect of RA on SD was 10 more per 1000 (6–15 more); the overall quality of evidence was rated as low. <h3>Conclusion.</h3> Evidence from included studies indicates that patients with RA have a significantly increased risk of SD, which suggests that both patients and clinicians should be aware of the potential role of RA in the development of SD.
Analysis of the role of Y1494 in α6β4 integrin-mediated breast carcinoma progression.
Authors: Udayan Dutta, Leslie Shaw
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

3037 

The α6β4 integrin is a cell surface adhesion receptor for the laminin family of extracellular matrix proteins and has been implicated in promoting tumor progression and metastasis. Although some progress has been made in understanding how the α6β4 integrin contributes to carcinoma progression, we still know relatively little about the mechanisms by which this integrin receptor regulates tumor cell invasion and survival. We previously identified a tyrosine residue, Y1494, in the β4 cytoplasmic domain that is required for the ability of the α6β4 integrin to promote breast carcinoma cell invasion and survival. To examine further the contribution of Y1494 to tumor progression, we examined MDA-MB-435 breast carcinoma cells expressing either wildtype-β4 or Y1494F mutant-β4 for their ability to form colonies in both soft agar and Matrigel. Cells expressing the wildtype-β4 subunit formed colonies of a similar size and number in soft agar when compared with MDA-MB-435 cells that had been transfected with vector alone. In contrast, cells expressing the mutant Y1494F-β4 subunit were significantly impaired in their ability to grow in soft agar assays. Although all of the cell lines grew as colonies in Matrigel, only cells expressing the wildtype-β4 subunit were invasive. Taken together, these results suggest a vital role for Y1494 in α6β4-mediated anchorage independent growth and invasion. To assess the impact of Y1494 on tumor growth and metastasis, cells expressing wildtype and Y1494F mutant β4 were injected orthotopically into the mammary fat pad of immuno-compromised mice. All of the mice injected with cells expressing either vector or wildtype-β4 developed tumors. However, only 10% of the mice injected with cells expressing the Y1494F mutant-β4 subunit developed tumors. We are currently investigating the mechanism by which Y1494 positively contributes to the function of the α6β4 integrin. Our preliminary results reveal a role for Y1494 in the α6β4-dependent activation of the Erk1/2 MAPKs. (Supported by Susan G. Komen Foundation and the American Cancer Society)
A population-based study examining the impact of a multidisciplinary rapid access clinic on utilization of initial treatment options for patients with localized prostate cancer.
Authors: Clement K. Ho, Joseph D. Ruether, Bryan J Donnelly, Marc Kerba
Journal: Journal of Clinical Oncology (2013)

15 Background: Treatment decisions in localized prostate cancer (LPCa) are complicated by the variety of available options. A rapid access cancer clinic (RAC) has been unique to Calgary, Alberta (AB) since 2007. RAC offers multidisciplinary prostate cancer care by a urologist, medical oncologist, and radiation oncologist. It is hypothesized that treatment utilization data from decisions taken at RAC may serve to benchmark the appropriateness of treatment decisions on a population level. Objectives: To compare utilization rates for initial treatment of LPCa between AB and RAC. Methods: Records of patients with clinically LPCa in AB between 2007-9 were reviewed with ethics approval. Records were linked to the AB cancer registry database. Clinical, treatment and health services characteristics pertaining to patients attending RAC were compared to those managed elsewhere in AB. The primary endpoints were utilization rates by initial treatment; prostatectomy (P), radiotherapy (RT), hormone therapy (H), active surveillance (A). A logistics regression model was constructed to examine the influence of RAC on initial treatment decisions, while controlling for interactions and factors of interest. Results: 2,660 patients were diagnosed with LPCa. 375 presented to RAC. Utilization rates among RAC patients: P-60.3% (95%CI: 55.3-65.2), A-16%(12.3-19.7), RT-11.7%(8.5-15.0) and H-8.0%(CI:5.2-10.8). This compares to AB rates of P-47.2%(45.9-48.3), A-6.1%(15.2-17.0), RT-18.8%(17.9-19.7), and H-14.5%(13.6-15.4). On multivariate analysis, RAC was associated with a trend towards receiving RT (OR 1.6, p=0.097). Conclusions: A specialized clinic for LPCa may be associated with a higher likelihood of receiving radiotherapy as initial treatment compared to the prostate cancer population in Alberta.
Use of oblique supine magnetic resonance imaging in breast-conserving surgery following neoadjuvant chemotherapy
Authors: R. Nakamura, M. Sakakibara, T. Nagashima, H. Fujimoto, M. Arai, H. Hashimoto, K. Kaneoya, T. Ueda, M. Miyazaki
Journal: Journal of Clinical Oncology (2007)

11064 Background: The success of breast-conserving surgery (BCS) after neoadjuvant chemotherapy (NAC) is dependent on accurate assessment of the extent of surgical excision of the original tumor bed (OTB). However the difficulty in locating microscopic residual disease often leads to a high re-excision rate (RER) and large excision specimen area (ESA). Methods: Magnetic resonance imaging (MRI) scans in the oblique supine position are performed with the patient in the same posture as that adopted during surgery. Maximum intensity projection (MIP) images of MR coronary section images of OTB are generated and used for surgery. OTB images are copied onto transparent sheets overlaid on the MIP images. These images are projected onto the breast before surgery, and used to determine the lines for surgical excision. In the conventional method (CM), OTB is determined by ultrasonography (US) and CT images. The oblique supine MRI method (SMM) has been used at our hospital since 2005. In this study, 14 patients treated prospectively with SMM (12/05- 12/06) were compared with a series of 19 consecutive patients treated with CM (04/03–11/05). ESA and RER were analyzed. Re-excision was performed in cases with a calcified lesion or tumor within 1 cm of the excised margin by X-ray or US during surgery, or invasive cancer was detected within 1 mm by pathological examination. ESA was analyzed using NIH Image. All patients received anthracycline/taxane-based chemotherapy. Results: There were no significant differences in characteristics of patients in the initial stages (T1, 2) or pathological chemotherapy responses between SMM and CM groups. There were four T3.4 cases in the SMM group, but none in the CM group. Clinical responses in CM and SMM were as follows (cases): CR 6, 7; PR 12, 7; SD 1, 0, respectively. RER was significantly greater in CM (36.8%, n=7) than in SMM (7.1%, n=1) (P&lt;0.05). Average ESA in SMM were 19.0 cm 2 (n=2) in T1, 33.6 cm 2 (7) in T2, and 59.3 cm 2 (5) in T3.4, while corresponding values in CM were 49.4 cm 2 (4) and 65.5 cm 2 (15), respectively; ESA was significantly improved in SMM. Conclusions: SMM, which has the benefits of decreased ESA and RER with superior cosmetic results, is a reliable technique for BCS following NAC. No significant financial relationships to disclose.
Increased Dead Space Ventilation Mediates Reduced Exercise Capacity in Systolic Heart Failure
Authors: Kirk Kee, Christopher Stuart-Andrews, Matthew J. Ellis, Jeremy P. Wrobel, Kris Nilsen, Meenal Sharma, Bruce R. Thompson, Matthew T. Naughton
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Patients with chronic heart failure have limited exercise capacity, which cannot be completely explained by markers of cardiac dysfunction. Reduced pulmonary diffusing capacity at rest and excessively high ventilation during exercise are common in heart failure. We hypothesized that the reduced pulmonary diffusing capacity in patients with heart failure would predict greater dead space ventilation during exercise and that this would lead to impairment in exercise capacity.Objectives: To determine the relationship between pulmonary diffusing capacity at rest and dead space ventilation during exercise, and to examine the influence of dead space ventilation on exercise in heart failure.Methods: We analyzed detailed cardiac and pulmonary data at rest and during maximal incremental cardiopulmonary exercise testing from 87 consecutive heart transplant assessment patients and 18 healthy control subjects. Dead space ventilation was calculated using the Bohr equation.Measurements and Main Results: Pulmonary diffusing capacity at rest was a significant predictor of dead space ventilation at maximal exercise (r = −0.524, P < 0.001) in heart failure but not in control subjects. Dead space at maximal exercise also correlated inversely with peak oxygen consumption (r = −0.598, P < 0.001), peak oxygen consumption per kilogram (r = −0.474, P < 0.001), and 6-minute-walk distance (r = −0.317, P = 0.021) in the heart failure group but not in control subjects.Conclusions: Low resting pulmonary diffusing capacity in heart failure is indicative of high dead space ventilation during exercise, leading to excessive and inefficient ventilation. These findings would support the concept of pulmonary vasculopathy leading to altered ventilation perfusion matching (increased dead space) and resultant dyspnea, independent of markers of cardiac function.
A Brazilian analysis in the private payer perspective of the use of health resources in lung cancer patients
Authors: S. D. Stefani, P. A. Brandalise
Journal: Journal of Clinical Oncology (2008)

17565 Background: The health resources utilization (HRU) in lung cancer treatment is variable according to several items: the country where the treatment is performed, hospitalization, administration and drug costs. The objective of this study was to evaluate the HRU in a supplementary medicine environment in Brazil comparing intravenous (IV) treatments often used in clinical practice. Methods: 344 lung cancer patients were selected within the records of a private hospital in Brazil. 143 patients (42%) didn’t receive any chemotherapy and 201 (58%) actually received chemotherapy. Of those, 69 (34%) patients that received pemetrexed (Pem) or docetaxel (Doc). The chemotherapy were: Pem 500 mg/m2 every three weeks, Doc 75 mg/m2 every three weeks, Doc 35 mg/m2 weekly (3 times per cycle) and Doc 40 mg/m2 weekly (3 times per cycle). HRU frequency (hospitalization, clinical visits, complementary examinations, medication, transfusions) related to lung cancer treatment was reviewed retrospectively from clinical records. The costs were calculated in dolars (US$) following the original records for each cycle. The values for neutropenia and febrile neutropenia were also calculated. Results: The study included 69 patients treated with Pem or Doc. Pem 500 mg/m2 every three weeks was used by 20.5%; Doc 75 mg/m2 every three weeks by 17.1%; Doc 35mg/m2 weekly (3 times per cycle) by 8,1% and Doc 40mg/m2 weekly (3 times per cycle) by 1.1%. Mean duration treatment was (SD) 71.62 (112.02) days (D) for Pem 500mg/ m2; 40.76 (27.97) D for Doc 75 mg/m2; 31.67(20.8) D for Doc 35mg/ m2 and 55 (N/A)D for Doc 40 mg/m2. The cost of each cycle was US$ 6,897.00 for Pem 500 mg/m2; US$ 3,041.00 for Doc 75 mg/m2; US$ 5,919.00 for Doc 35 mg/m2 and US$ 6,669.00 for Doc 40 mg/m2. The costs of neutropenia and febrile neutropenia episodes were respectively US$ 1,310.00 and US$ 6,000.00. Conclusions: Besides the cost of the drug is a mean point in HRU we have to consider other variables to have a clear picture of each chemotherapy scheme costs and were the resources have been used. Since the chance of toxicity is different for every kind of treatment, pharmacoeconomic analysis has to include all the inputs to reach the total cost of treatment. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly AstraZeneca Oncology, Bristol-Myers Squibb, Eli Lilly, Novartis, sanofi-aventis, Schering-Plough Libbs, Schering-Plough PUC Campinas, UNIMED
Rapid increases in HIV rates – Orel Oblast, Russian Federation, 1999-2001
Authors: Molotilov, R Safronova, N Gusseynova, N Laricheva, SL Hader, Richard S Garfein, L Paxton
Journal: MMWR Morbidity and Mortality Weekly Report (2003)

During 1999--2001 the estimated number of cases of human immunodeficiency virus (HIV) reported officially in the Russian Federation increased approximately 16-fold from 11000 to 177000. In 2001 of 49434 HIV-infected persons for whom a risk factor was identified 46274 (94%) were injection-drug users (IDUs). However the actual number of HIV-infected persons in Russia is estimated to be four to 10 times higher than reported. Rapid increases in HIV have been reported in urban areas (e.g. Kaliningrad Moscow and St. Petersburg) and also might be occurring in rural areas. During 1997--2000 HIV seroprevalence reportedly increased 33-fold in Orel Oblast a predominantly rural agricultural province (1999 population: 900000) in central European Russia. To confirm and describe this increase and evaluate the risk for continued rapid increase of HIV CDC collaborated with the Orel Oblast AIDS and Infectious Diseases Prevention Center (AIDS Center) to assess recent HIV trends and the prevalence of risk behaviors among IDUs in Orel Oblast. This report summarizes the results of that assessment which indicate continued increases in HIV rates and underscore the need for interventions directed at IDUs and their sex partners to limit further spread of HIV.  (excerpt)
Comparison of RECIST and WHO response criteria in metastatic colorectal carcinoma
Authors: J. H. Choi, M. J. Ahn, H. Rhim, J. W. Kim, K. H. Lee, H. S. Oh, Y. Y. Lee, I. Y. Choi, I. S. Kim
Journal: Journal of Clinical Oncology (2005)

3721 Background: WHO response criteria were adopted as the standard method for evaluation of tumor response. However, some problems have developed with the use of these criteria and required new methodology. Recently, RECIST (Response Evaluation Criteria in Solid Tumors) proposed new guidelines using unidimensional instead of bidimensional measurements, a reduced number of measured lesions, withdrawal of the progression criteria based on isolated increase of a single lesion, and different shrinkage threshold for definitions of tumor response and progression. To clarify the significance of these new guidelines, we have compared the WHO with the RECIST criteria in the same patients with metastatic colorectal cancer. Methods: Between 2002 and 2004, a total of 41 patients with measurable lesions receiving chemotherapy (28 FOLFIRI, 9 XELOX, 4 FOLFOX) for metastatic colorectal carcinoma had been enrolled. One medical oncologist and one radiologist separately reviewed all CT images without any information of patients. The results were compared using the kappa test. Results: The overall response and progression rates according to WHO criteria were 31.7% (1 CR, 12 PR) and 29.3%, respectively. Using RECIST criteria, two patients were reclassified in a more favorable group and the overall response rate was 36.5% (1 CR, 14 PR). The kappa test for concordance of overall response was 0.93 (concordance may be considered as satisfactory for value ≥ 0.75). Concordance level between two investigators using WHO and RECIST were 0.90 and 0.88, respectively. Conclusions: These results suggest that the RECIST criteria are comparable to the WHO criteria in evaluating response in colorectal carcinoma and simple and reproducible guidelines. The use of RECIST criteria is recommended for evaluation of treatment efficacy in clinical trials and practice. No significant financial relationships to disclose.
Abstract 9529: Effects of Sevelamer Carbonate on Arterial Stiffness and Left Ventricular Mass in Patients with Stage 3 Chronic Kidney Disease: Results of a Randomized Controlled Trial
Authors: Colin D Chue, Jonathan N Townend, William E Moody, Nicola C Edwards, Richard P Steeds, Charles J Ferro
Journal: Circulation (2012)

Colin D Chue, 2012 Finalist and Presenting Author