bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic predictors of acute toxicities related to radiation therapy following lumpectomy for breast cancer: a case-series study
Authors: Ambrosone Christine B , Tian Chunqiao , Ahn Jiyoung , Kropp Silke , Helmbold Irmgard , von Fournier Dietrich , Haase Wulf , Sautter-Bihl Marie Luise , Wenz Frederik , Chang-Claude Jenny 
Published: July 2006

Abstract
Introduction
The cytotoxic effects of radiation therapy are mediated primarily through increased formation of hydroxyl radicals and reactive oxygen species, which can damage cells, proteins and DNA; the glutathione S-transferases (GSTs) function to protect against oxidative stress. We hypothesized that polymorphisms encoding reduced or absent activity in the GSTs might result in greater risk for radiation-associated toxicity.

Methods
Women receiving therapy in radiation units in Germany following lumpectomy for breast cancer (1998–2001) provided a blood sample and completed an epidemiological questionnaire (n = 446). Genotypes were determined using Sequonom MALDI-TOF (GSTA1, GSTP1) and Masscode (GSTM1, GSTT1). Biologically effective radiotherapy dose (BED) was calculated, accounting for differences in fractionation and overall treatment time. Side effects considered were grade 2c and above, as classified using the modified Common Toxicity Criteria. Predictors of toxicity were modelled using Cox regression models in relation to BED, with adjustment for treating clinic, photon field, beam energy and boost method, and potential confounding variables.

Results
Low activity GSTP1 genotypes were associated with a greater than twofold increase in risk for acute skin toxicities (adjusted hazard ratio 2.28, 95% confidence interval 1.04–4.99). No associations were noted for the other GST genotypes.

Conclusion
These data indicate that GSTP1 plays an important role in protecting normal cells from damage associated with radiation therapy. Studies examining the effects of GSTP1 polymorphisms on toxicity, recurrence and survival will further inform individualized therapeutics based on genotypes.
Unloading work of breathing during high-frequency oscillatory ventilation: a bench study
Authors: van Heerde Marc , Roubik Karel , Kopelent Vitek , Plötz Frans B , Markhorst Dick G 
Published: July 2006

Abstract
Introduction
With the 3100B high-frequency oscillatory ventilator (SensorMedics, Yorba Linda, CA, USA), patients' spontaneous breathing efforts result in a high level of imposed work of breathing (WOB). Therefore, spontaneous breathing often has to be suppressed during high-frequency oscillatory ventilation (HFOV). A demand-flow system was designed to reduce imposed WOB.

Methods
An external gas flow controller (demand-flow system) accommodates the ventilator fresh gas flow during spontaneous breathing simulation. A control algorithm detects breathing effort and regulates the demand-flow valve. The effectiveness of this system has been evaluated in a bench test. The Campbell diagram and pressure time product (PTP) are used to quantify the imposed workload.

Results
Using the demand-flow system, imposed WOB is considerably reduced. The demand-flow system reduces inspiratory imposed WOB by 30% to 56% and inspiratory imposed PTP by 38% to 59% compared to continuous fresh gas flow. Expiratory imposed WOB was decreased as well by 12% to 49%. In simulations of shallow to normal breathing for an adult, imposed WOB is 0.5 J l-1 at maximum. Fluctuations in mean airway pressure on account of spontaneous breathing are markedly reduced.

Conclusion
The use of the demand-flow system during HFOV results in a reduction of both imposed WOB and fluctuation in mean airway pressure. The level of imposed WOB was reduced to the physiological range of WOB. Potentially, this makes maintenance of spontaneous breathing during HFOV possible and easier in a clinical setting. Early initiation of HFOV seems more possible with this system and the possibility of weaning of patients directly on a high-frequency oscillatory ventilator is not excluded either.
Corticosteroids influence the mortality and morbidity of acute critical illness
Authors: Rady Mohamed Y , Johnson Daniel J , Patel Bhavesh , Larson Joel , Helmers Richard 
Published: July 2006

Abstract
Introduction
Use of corticosteroids for adrenal supplementation and attenuation of the inflammatory and immune response is widespread in acute critical illness. The study hypothesis was that exposure to corticosteroids influences the mortality and morbidity in acute critical illness.

Methods
This case–control retrospective study was performed in a single multidisciplinary intensive care unit at a tertiary care institution and consisted of 10,285 critically ill patients admitted between 1 January 1999 and 31 December 2004. Demographics, comorbidities, acute illness characteristics including severity measured by Sequential Organ Failure Assessment, concurrent medications, therapeutic interventions and incidence of infections were obtained from electronic medical records, were examined with multiple regression analysis and were adjusted for propensity of corticosteroid exposure. The primary outcome was hospital death, and the secondary outcome was transfer to a care facility at hospital discharge.

Results
Corticosteroid exposure in 2,632 (26%) patients was characterized by younger age, more females, higher Charlson comorbidity and maximal daily Sequential Organ Failure Assessment scores compared with control patients. Corticosteroids potentiated metabolic and neuromuscular sequels of critical illness with increased requirements for diuretics, insulin, protracted weaning from mechanical ventilation, need for tracheostomy and discharge to a care facility. Early exposure to corticosteroids predisposed to recurrent and late onset of polymicrobial and fungal hospital-acquired infections. Corticosteroids increased the risk for death or disability after adjustments for comorbidities and acute illness characteristics.

Conclusion
Corticosteroids increased the risk for death or disability in critical illness. Hospital-acquired infections and metabolic and neuromuscular sequels of critical illness were exacerbated by corticosteroids. Careful appraisal of the indications for use of corticosteroids is necessary to balance the benefits and risks from exposure in acute critical illness.
Pooled Analysis of Phase II Window Studies in Children With Contemporary High-Risk Metastatic Rhabdomyosarcoma: A Report From the Soft Tissue Sarcoma Committee of the Children's Oncology Group
Authors: Lager Joanne J. , Lyden Elizabeth R. , Anderson James R. , Pappo Alberto S. , Meyer William H. , Breitfeld Philip P. 
Published: July 2006

Purpose The Soft Tissue Sarcoma Committee of the Children's Oncology Group has conducted five upfront window trials in patients with newly diagnosed metastatic rhabdomyosarcoma to identify promising new treatment agents. Patients and Methods This pooled analysis identified a total of 420 patients (115 from Intergroup Rhabdomyosarcoma Study III [IRS-III] and 305 from the five window trials). We assessed window therapy response rate, failure-free survival (FFS), and overall survival (OS). Results Response rates (complete + partial response) assessed at week 6 of window therapy ranged from 41% to 55% and did not predict FFS (P = .073) or OS (P = .31). FFS was influenced by trial (P = .048); patients enrolled onto IRS-III and the ifosfamide/etoposide and ifosfamide/doxorubicin trials fared best. When grouped and compared with topoisomerase I poison trials, ifosfamide/topoisomerase II inhibitor trials had superior FFS (P = .013). However, there was no difference in survival. Conclusion Upfront phase II window trials can efficiently provide robust estimates of activity for new agents and combinations in newly diagnosed patients with high-risk rhabdomyosarcoma. Our data indicate that, for some phase II window trials, the risk of treatment failure may be increased but that the trend towards lower survival for some of the window trials compared with IRS-III is not statistically significant. Window nonresponders did not suffer worse FFS or OS than patients who responded to window therapy. Finally, these results provide a rationale for incorporating ifosfamide, etoposide, doxorubicin, and topoisomerase I poisons in future trials of high-risk metastatic rhabdomyosarcoma.
Phase II Study of Pemetrexed for Second-Line Treatment of Transitional Cell Cancer of the Urothelium
Authors: Sweeney Christopher J. , Roth Bruce J. , Kabbinavar Fairooz F. , Vaughn David J. , Arning Michael , Curiel Rafael E. , Obasaju Coleman K. , Wang Yanping , Nicol Steven J. , Kaufman Donald S. 
Published: July 2006

Purpose To assess the antitumor activity and toxicity of pemetrexed as second-line chemotherapy in patients with locally advanced or metastatic transitional cell carcinoma (TCC) of the urothelium. Patients and Methods Eligible patients had a performance status of 0 or 1, adequate organ function, previous treatment with one prior chemotherapy regimen for locally advanced or metastatic TCC of the urothelium or relapsed within 1 year of adjuvant or neoadjuvant treatment. Patients received pemetrexed 500 mg/m2 intravenously on day 1 every 21 days, with vitamin B12, folic acid, and dexamethasone prophylaxis. Results Forty-seven patients were enrolled and included in the intent-to-treat efficacy analysis. Responses: 3 (6.4%) complete responses and 10 (21.3%) partial responses produced an overall response rate of 27.7%. Ten patients (21.3%) had stable disease and 22 patients (46.8%) progressed. The median time to progressive disease was 2.9 months (95% CI, 1.7 months to 4.6 months) and median overall survival was 9.6 months (95% CI, 5.1 months to 14.6 months). Median duration of response was 5.0 months (95% CI, 3.9 months to 13.8 months). Of the 47 patients assessable for safety, grade 3 or 4 hematologic events were thrombocytopenia (8.5%; 0.0%), neutropenia (4.3%; 4.3%) and anemia (2.1%; 2.1%), respectively. Nonlaboratory toxicities included grade 4 stomatitis/pharyngitis, sepsis syndrome (one patient each), and grade 3 fatigue (three patients) and diarrhea (two patients). Conclusion Single-agent pemetrexed is safe and active as second-line treatment of patients with advanced TCC of the urothelium. Additional evaluation in the first- or second-line setting in TCC of the urothelium is warranted.
Prognostic Factors for Local Control and Survival After Radiotherapy of Metastatic Spinal Cord Compression
Authors: Rades Dirk , Fehlauer Fabian , Schulte Rainer , Veninga Theo , Stalpers Lukas J.A. , Basic Hiba , Bajrovic Amira , Hoskin Peter J. , Tribius Silke , Wildfang Ingeborg , Rudat Volker , Engenhart-Cabilic Rita , Karstens Johann H. , Alberti Winfried , Dunst Juergen , Schild Steven E. 
Published: July 2006

Purpose To evaluate potential prognostic factors for local control and survival after radiotherapy of metastatic spinal cord compression (MSCC). Patients and Methods The following potential prognostic factors were investigated retrospectively in 1,852 patients irradiated for MSCC: age, sex, performance status, primary tumor, interval between tumor diagnosis and MSCC (≤ 15 v > 15 months), number of involved vertebrae (one to two v ≥ three), other bone metastases, visceral metastases, pretreatment ambulatory status, time of developing motor deficits before radiotherapy (faster, 1 to 14 v slower, > 14 days), and radiation schedule (short-course v long-course radiotherapy). Results On univariate analysis, improved local control of MSCC was associated significantly with favorable histology (breast cancer, prostate cancer, lymphoma/myeloma), no visceral metastases, and long-course radiotherapy. On multivariate analysis, absence of visceral metastases and radiation schedule maintained significance. On univariate analysis, improved survival was associated significantly with female sex, favorable histology, no visceral or other bone metastases, good performance status, being ambulatory before radiotherapy, longer interval between tumor diagnosis and MSCC, and slower development of motor deficits before radiotherapy. Long-course radiotherapy showed a trend. On multivariate analysis, histology, visceral metastases, other bone metastases, ambulatory status before radiotherapy, interval between tumor diagnosis and MSCC, and time of developing motor deficits maintained significance. Conclusion Poorer local control after radiotherapy for MSCC is associated with visceral metastases and short-course radiotherapy. Long-course radiotherapy seems preferable for patients with more favorable prognoses, given that these patients may live long enough to develop MSCC recurrences. Long-term survival after radiotherapy for MSCC may be predicted if several prognostic factors are considered.
Phase II Multicenter Trial of Bevacizumab Plus Fluorouracil and Leucovorin in Patients With Advanced Refractory Colorectal Cancer: An NCI Treatment Referral Center Trial TRC-0301
Authors: Chen Helen X. , Mooney Margaret , Boron Matthew , Vena Don , Mosby Kimberly , Grochow Louise , Jaffe Carl , Rubinstein Lawrence , Zwiebel James , Kaplan Richard S. 
Published: July 2006

Purpose To provide bevacizumab (BV) -based therapy to patients with advanced colorectal cancers (CRC) who had exhausted standard chemotherapy options, and to evaluate the response to BV combined with fluorouracil (FU) and leucovorin (LV) in this patient population. Patients and Methods This was a multicenter, single-arm treatment trial conducted under the National Cancer Institute Treatment Referral Center network nationwide. Patients were treated with BV 5 mg/kg every 2 weeks combined with FU/LV; FU was administered by bolus or continuous infusion. Eligibility criteria included advanced CRC that had progressed after irinotecan- and oxaliplatin-based chemotherapy, Eastern Cooperative Oncology Group performance status 0 to 2, and absence of thromboembolism. The primary end point was objective response rate (RR) in the first 100 assessable patients. All patients received follow-up for toxicity and survival. Results Due to rapid accrual, a total of 350 patients were enrolled at 32 participating sites nationwide by October 2003. In the initially planned cohort of 100 assessable patients, the objective RR was 4% (95% CI, 1.1% to 9.9%) by investigators' assessment and 1% (95% CI, 0% to 5.5%) based on independent review; median progression-free survival was 3.5 months and median overall survival was 9.0 months. The safety profile was similar to prior BV trials in CRC. Grade 3 to 4 hemorrhage occurred in 5% of patients, including 3.8% with bleeding in the GI tract. Other adverse events such as hypertension, thrombosis, and bowel perforation were also observed at rates consistent with other studies. Conclusion For patients with advanced CRC that had progressed after both irinotecan-based and oxaliplatin-based chemotherapy regimens, the combination of BV and FU/LV was associated with rare objective responses.
Differential Impact of Combination Antiretroviral Therapy in Preventing Kaposi's Sarcoma With and Without Visceral Involvement
Authors: Grabar Sophie , Abraham Bruno , Mahamat Aba , Del Giudice Pascal , Rosenthal Eric , Costagliola Dominique 
Published: July 2006

Purpose To study the impact of different potent combined antiretroviral treatment (cART) on the incidence of HIV-associated Kaposi's sarcoma (KS) with and without visceral involvement. Patients and Methods Patients were selected from the French Hospital Database on HIV, a large hospital cohort. The risk of KS was estimated by using Cox proportional hazards models adjusting for age, the CD4 cell nadir, the HIV exposure category, prior AIDS, cART, and the type of cART regimen. cART regimens were distinguished according to whether they contained protease inhibitor (PI), non-nucleoside analog (NNRTI), both, or only nucleoside analog (NRTI). Separate analyzes were conducted according to the initial visceral involvement of KS. Results Among the 54,999 patients included in this study (182,756 person-years of follow-up), 1,634 patients were diagnosed with KS during follow-up, of whom 421 had visceral involvement at diagnosis. The KS incidence rate fell from 32 per 1,000 person-years in 1993 to 1994 to 3 per 1,000 person-years after 1999. PI-containing and NNRTI-containing cART regimens were associated with similar reductions in the risk of KS (hazard ratio, 0.68; 95%CI, 0.61 to 0.75; HR, 0.62; 95% CI, 0.54 to 0.71, respectively). The risk of visceral KS fell more strongly than the risk of cutaneous KS (> 50% and < 30%, respectively). Conclusion The incidence of KS, and especially visceral KS, has fallen sharply since the advent of cART. This effect is likely due to immune restoration rather than to a specific effect on the tumoral process, as PI-containing and NNRTI-containing regimens had similar preventive efficacy.
Association of T-Cell Regulatory Gene Polymorphisms With Susceptibility to Gastric Mucosa-Associated Lymphoid Tissue Lymphoma
Authors: Cheng Tsu-Yao , Lin Jaw-Town , Chen Li-Tzong , Shun Chia-Tung , Wang Hsiu-Po , Lin Ming-Tsang , Wang Tsang-En , Cheng Ann-Lii , Wu Ming-Shiang 
Published: July 2006

Purpose Helicobacter pylori infection and host susceptibility interact to develop gastric mucosa-associated lymphoid tissue (MALT) lymphoma, and activation of specific T cells might play a crucial role in this process. Recent investigations show that the CTLA4, CD28, and ICOS genes are located on chromosome 2q33 and their polymorphisms confer susceptibility to infectious and immune diseases through deregulation of T-cell stimulation. We aimed to determine the role of CTLA4, CD28, and ICOS polymorphisms in gastric MALT lymphoma. Patients and Methods Genotyping for CTLA4 (49 A/G, −318 C/T, and CT60 A/G), CD28 (IVS3+ 17T/C), and ICOS (c.602 A/C and c.1624C/T) was performed for 62 patients with gastric MALT lymphoma and compared with 250 unrelated healthy controls. Results H pylori infection was significantly higher in patients with gastric MALT lymphoma (90.3%) compared with controls (66.4%; P < .001). The CTLA4 −318 C/T genotype was associated with a lower risk of developing gastric MALT lymphoma (odds ratio [OR] = 0.3; P = .022), whereas CTLA4 49 G/G genotype was linked to a higher risk (OR = 4.1; P = .044). In patients with H pylori infection, CTLA4 49 G/G genotype was associated with an even higher risk (OR = 6.4; P = .047). Carriage of the tightly linked −318C –49G haplotype conferred a four-fold higher susceptibility to MALT lymphoma (OR = 4.2; P = .042). Complete remission after H pylori eradication was related to tumor stage but not to genotypes or haplotypes. Conclusion These results indicate a genetic link of CTLA4 gene polymorphisms to development of gastric MALT lymphoma and indirectly support the crucial role of host activated T cells in the MALT lymphomagenesis.
Prospective Comparative Study of Integrated Positron Emission Tomography-Computed Tomography Scan Compared With Remediastinoscopy in the Assessment of Residual Mediastinal Lymph Node Disease After Induction Chemotherapy for Mediastinoscopy-Proven Stage IIIA-N2 Non–Small-Cell Lung Cancer: A Leuven Lung Cancer Group Study
Authors: De Leyn Paul , Stroobants Sigrid , De Wever Walter , Lerut Toni , Coosemans Willy , Decker Georges , Nafteux Philippe , Van Raemdonck Dirk , Mortelmans Luc , Nackaerts Kristiaan , Vansteenkiste Johan 
Published: July 2006

Purpose Mediastinal restaging after induction therapy for non–small-cell lung cancer remains a difficult and controversial issue. The goal of this prospective study was to compare the performance of integrated positron emission tomography (PET) –computed tomography (CT) and remediastinoscopy in the evaluation of mediastinal lymph node metastasis after induction chemotherapy. Patients and Methods Thirty consecutive stage IIIA-N2 non–small-cell lung cancer patients surgically treated at our institution were entered onto this prospective study. N2 disease was proven by cervical mediastinoscopy, at which a mean number of 3.8 lymph node levels were biopsied. After completion of induction chemotherapy, the mediastinum was reassessed by integrated PET-CT and remediastinoscopy. All patients underwent thoracotomy with attempted complete resection and systematic nodal dissection. Results PET-CT showed no evidence of nodal disease (N0) in 13 patients, Hilar nodal disease (N1) disease in three patients, and residual mediastinal disease (N2) in 14 patients. Remediastinoscopy was positive in only five patients. The preinduction involved lymph node level could be accurately re-evaluated in 18 patients. This was not the case in the other 12 because of extensive fibrosis and adhesions. In 17 patients, persistent N2 disease was found at thoracotomy. The sensitivity, specificity, and accuracy of PET-CT were 77%, 92%, and 83%, respectively. These parameters for remediastinoscopy were 29%, 100%, and 60%, respectively. Sensitivity (P < .0001) and accuracy (P = .012) were significantly better for PET-CT. Conclusion After a thorough staging mediastinoscopy, postinduction remediastinoscopy had a disappointing sensitivity because of adhesions and fibrosis. Integrated PET-CT yielded a better result than that obtained in previous studies with side-by-side PET and CT images.
O6-Methylguanine-DNA Methyltransferase Expression Strongly Correlates With Outcome in Childhood Malignant Gliomas: Results From the CCG-945 Cohort
Authors: Pollack Ian F. , Hamilton Ronald L. , Sobol Robert W. , Burnham Judith , Yates Allan J. , Holmes Emiko J. , Zhou Tianni , Finlay Jonathan L. 
Published: July 2006

Purpose O6-Methylguanine-DNA methyltransferase (MGMT) functions to counteract the cytotoxic effects of alkylating agents, such as nitrosoureas, which play a central role in the treatment of childhood malignant gliomas. Epigenetic silencing of MGMT has been associated with prolonged survival in adults with malignant gliomas, although the association between MGMT expression status and outcome in pediatric malignant gliomas has not been defined. Methods We examined the association between MGMT expression and survival duration using tumor samples from the Children's Cancer Group 945 study, the largest randomized trial for childhood malignant gliomas completed to date. All patients received alkylator-based chemotherapy as a component of adjuvant therapy. Archival histopathologic material yielded tissue of sufficient quality for immunohistochemical assessment of MGMT expression status in 109 specimens. Results Twelve of the 109 samples demonstrated overexpression of MGMT compared with normal brain. Five-year progression-free survival was 42.1% ± 5% in the 97 patients whose tumors had low levels of MGMT expression versus 8.3% ± 8% in the 12 patients whose tumors overexpressed MGMT (P = .017, exact log-rank test). The association between MGMT overexpression and adverse outcome remained significant after stratifying for institutional histologic diagnosis (eg, anaplastic astrocytoma or glioblastoma multiforme), as well as age, amount of residual tumor, and tumor location. Conclusion Overexpression of MGMT in childhood malignant gliomas is strongly associated with an adverse outcome in children treated with alkylator-based chemotherapy, independently of a variety of clinical prognostic factors.