bluuebunny/crossref_metadata_2025_split huggingface dataset:
Central nervous system relapse in patients with breast cancer is associated with advanced stages, with the presence of circulating occult tumor cells and with the HER2/neu status
Authors: Souglakos John , Vamvakas Lambros , Apostolaki Stella , Perraki Maria , Saridaki Zacharenia , Kazakou Irine , Pallis Athanasios , Kouroussis Charalambos , Androulakis Nikos , Kalbakis Kostas , Millaki Georgia , Mavroudis Dimitris , Georgoulias Vassilis 
Published: July 2006

Abstract
Introduction
To evaluate the incidence of central nervous system (CNS) involvement in patients with breast cancer treated with a taxane-based chemotherapy regimen and to determine predictive factors for CNS relapse.

Methods
The medical files of patients with early breast cancer (n = 253) or advanced stage breast cancer (n = 239) as well of those with other solid tumors (n = 336) treated with or without a taxane-based chemotherapy regimen during a 42-month period were reviewed. HER2/neu overexpression was identified by immunohistochemistry, whereas cytokeratin 19 (CK-19) mRNA-positive circulating tumor cells (CTCs) in the peripheral blood were identified by real-time PCR.

Results
The incidence of CNS relapse was similar in patients suffering from breast cancer or other solid tumors (10.4% and 11.4%, respectively; P = 0.517). The incidence of CNS relapse was significantly higher in breast cancer patients with advanced disease (P = 0.041), visceral disease and bone disease (P = 0.036), in those who were treated with a taxane-containing regimen (P = 0.024), in those with HER2/neu-overexpressing tumors (P = 0.022) and, finally, in those with detectable CK-19 mRNA-positive CTCs (P = 0.008). Multivariate analysis revealed that the stage of disease (odds ratio, 0.23; 95% confidence interval, 0.007–0.23; P = 0.0001), the HER2/neu status (odds ratio, 29.4; 95% confidence interval, 7.51–101.21; P = 0.0001) and the presence of CK-19 mRNA-positive CTCs (odds ratio, 8.31; 95% confidence interval, 3.97–12.84; P = 0.001) were independent predictive factors for CNS relapse.

Conclusion
CNS relapses are common among breast cancer patients treated with a taxane-based chemotherapy regimen, patients with HER2/neu-positive tumor and patients with CK-19 mRNA-positive CTCs.
Epigenetic silencing and deletion of the BRCA1gene in sporadic breast cancer
Authors: Birgisdottir Valgerdur , Stefansson Olafur A , Bodvarsdottir Sigridur K , Hilmarsdottir Holmfridur , Jonasson Jon G , Eyfjord Jorunn E 
Published: July 2006

Abstract
Introduction
BRCA1 or BRCA2 germline mutations increase the risk of developing breast cancer. Tumour cells from germline mutation carriers have frequently lost the wild-type allele. This is predicted to result in genomic instability where cell survival depends upon dysfunctional checkpoint mechanisms. Tumorigenic potential could then be acquired through further genomic alterations. Surprisingly, somatic BRCA mutations are not found in sporadic breast tumours. BRCA1 methylation has been shown to occur in sporadic breast tumours and to be associated with reduced gene expression. We examined the frequency of BRCA1 methylation in 143 primary sporadic breast tumours along with BRCA1 copy number alterations and tumour phenotype.

Methods
Primary sporadic breast tumours were analysed for BRCA1α promoter methylation by methylation specific PCR and for allelic imbalance (AI) at BRCA1 and BRCA2 loci by microsatellite analysis and TP53 (also known as p53) mutations by constant denaturing gel electrophoresis. The BRCA1 methylated tumours were analysed for BRCA1 copy alterations by fluorescence in situ hybridisation and BRCA1 expression by immunostaining.

Results
BRCA1 methylation was found in 13/143 (9.1%) sporadic breast tumours. The BRCA1 methylated tumours were significantly associated with estrogen receptor (ER) negativity (P = 0.0475) and displayed a trend for BRCA1 AI (P = 0.0731) as well as young-age at diagnosis (≤ 55; P = 0.0898). BRCA1 methylation was not associated with BRCA2 AI (P = 0.5420), although a significant association was found between BRCA1 AI and BRCA2 AI (P < 0.0001).
Absent/markedly reduced BRCA1 expression was observed in 9/13 BRCA1 methylated tumours, most of which had BRCA1 deletion. An elevated TP53 mutation frequency was found among BRCA1 methylated tumours (38.5%) compared with non-methylated tumours (17.2%). The BRCA1 methylated tumours were mainly of tumour grade 3 (7/13) and infiltrating ductal type (12/13). Only one methylated tumour was of grade 1.

Conclusion
BRCA1 methylation is frequent in primary sporadic breast tumours. We found an indication for BRCA1 methylation to be associated with AI at the BRCA1 locus. Almost all BRCA1 methylated tumours with absent/markedly reduced BRCA1 expression (8/9) displayed BRCA1 deletion. Thus, epigenetic silencing and deletion of the BRCA1 gene might serve as Knudson's two 'hits' in sporadic breast tumorigenesis. We observed phenotypic similarities between BRCA1 methylated and familial BRCA1 tumours, based on BRCA1 deletion, TP53 mutations, ER status, young age at diagnosis and tumour grade.
How can the response to volume expansion in patients with spontaneous respiratory movements be predicted?
Authors: Heenen Sarah , De Backer Daniel , Vincent Jean-Louis 
Published: July 2006

Abstract
Introduction
The aim of the study was to evaluate the ability of different static and dynamic measurements of preload to predict fluid responsiveness in patients with spontaneous respiratory movements.

Methods
The subjects were 21 critically ill patients with spontaneous breathing movements receiving mechanical ventilation with pressure support mode (n = 9) or breathing through a face mask (n = 12), and who required a fluid challenge. Complete hemodynamic measurements, including pulmonary artery occluded pressure (PAOP), right atrial pressure (RAP), pulse pressure variation (ΔPP) and inspiratory variation in RAP were obtained before and after fluid challenge. Fluid challenge consisted of boluses of either crystalloid or colloid until cardiac output reached a plateau. Receiver operating characteristics (ROC) curve analysis was used to evaluate the predictive value of the indices to the response to fluids, as defined by an increase in cardiac index of 15% or more.

Results
Cardiac index increased from 3.0 (2.3 to 3.5) to 3.5 (3.0 to 3.9) l minute-1 m-2 (medians and 25th and 75th centiles), p < 0.05. At baseline, ΔPP varied between 0% and 49%. There were no significant differences in ΔPP, PAOP, RAP and inspiratory variation in RAP between fluid responders and non-responders. Fluid responsiveness was predicted better with static indices (ROC curve area ± SD: 0.73 ± 0.13 for PAOP, p < 0.05 vs ΔPP and 0.69 ± 0.12 for RAP, p = 0.054 compared with ΔPP) than with dynamic indices of preload (0.40 ± 0.13 for ΔPP and 0.53 ± 0.13 for inspiratory changes in RAP, p not significant compared with ΔPP).

Conclusion
In patients with spontaneous respiratory movements, ΔPP and inspiratory changes in RAP failed to predict the response to volume expansion.
Why Do Patients Choose Chemotherapy Near the End of Life? A Review of the Perspective of Those Facing Death From Cancer
Authors: Matsuyama Robin , Reddy Sashidhar , Smith Thomas J. 
Published: July 2006

Purpose The number of patients receiving chemotherapy near the end of life is increasing, as are concerns about goals of treatment, toxicity, and costs. We sought to determine the available sources of knowledge, the choices, and concerns of actual patients, and how patients balanced competing issues. Methods We used a literature search from 1980 to present. Results Available patient sources provide little information about prognosis, choices, alternatives, consequences, or how to choose. Many patients would choose chemotherapy for a small benefit in health outcomes, and for a smaller benefit than perceived by their health care providers for their own treatment. Adverse effects are less a concern for patients than for their well health care providers. There are no decision aids to assist patients with metastatic disease in making their choices, such as there are for adjuvant breast therapy. Conclusion The perspective of the patient is different from that of a well person. Patients are willing to undergo treatments that have small benefits with major toxicity. Receiving realistic information about the different options of care and the likelihood of successful treatment or adverse effects is difficult. These factors may explain some of the increased use of chemotherapy near the end of life. Decision aids and honest, unbiased sources to inform patients of their prognosis, choices, consequences, typical outcomes, and ways to make decisions are needed. More prospective information about how patients make their choices, and what they would consider a good choice, would assist informed decision making.
Phase I Trial of Oral Fenretinide in Children With High-Risk Solid Tumors: A Report From the Children's Oncology Group (CCG 09709)
Authors: Villablanca Judith G. , Krailo Mark D. , Ames Matthew M. , Reid Joel M. , Reaman Gregory H. , Reynolds C. Patrick 
Published: July 2006

PurposeTo determine the maximal tolerated dosage (MTD) of oral fenretinide given as intact capsules for 7 days, repeated every 21 days, in children with high-risk solid tumors.MethodsChildren 21 years of age or younger received daily doses from 350 mg/m2to 3,300 mg/m2(divided into two or three doses), with pharmacokinetics during course one. The MTD was defined as zero to one of six patients with dose-limiting toxicity (DLT), with at least two of three or two of six DLT at next higher dose.ResultsFifty-four patients, age 2 years to 20 years (median, 9 years), were treated: neuroblastoma (n = 39), Ewing sarcoma (n = 5), and other (n = 10). Prior therapy included autologous stem cell transplantation (n = 42), 13-cis-RA (n = 35), and 9-cis-RA (n = 1). One of four patients at 1,050 mg/m2with prior liver transplant had grade 3 ALT/abdominal pain/nausea/dehydration and grade 4 AST/emesis. At 1,860 mg/m2, one of seven patients had grade 3 hypoalbuminemia/hypophosphatemia. At 2,475 mg/m2, one of eight patients had grade 3 alkaline phosphatase; three of five patients had DLT at 3,300 mg/m2: grade 3 AST/ALT (n = 1), grade 4 bilirubin/grade 3 AST/ALT (n = 1), pseudotumor cerebri (n = 1). Pseudotumor cerebri also occurred at 600 mg/m2and 800 mg/m2. There was one complete response and 13 patients with stable disease (SD) for 8 or more courses in 30 assessable neuroblastoma patients. SD for 8 or more courses was seen in one of five Ewing sarcoma patients and one melanoma patient. Mean N-4-hydroxyphenyl retinamide plasma level (day 7, steady-state concentration) was 9.9 μmol/L at MTD.ConclusionThe pediatric MTD of oral capsular fenretinide was 2,475 mg/m2per day, which achieved levels active against neuroblastoma in vitro with minimal toxicity. Response data support a phase II trial in neuroblastoma.
Trastuzumab in Combination With Heregulin-Activated Her-2 (erbB-2) Triggers a Receptor-Enhanced Chemosensitivity Effect in the Absence of Her-2 Overexpression
Authors: Menendez Javier A. , Mehmi Inderjit , Lupu Ruth 
Published: July 2006

Purpose The decision for treating breast cancer patients with trastuzumab is based on HER-2 amplification and/or overexpression. Methods Using MCF-7 cells (Her-2 ±) engineered to overexpress heregulin (MCF-7/HRG), a ligand for the Her-2/3/4 network, we investigated whether HRG-induced transactivation of Her-2 affected breast cancer cell sensitivity to chemotherapy and whether trastuzumab trigger receptor-enhanced chemosensitivity (REC) when combined with chemotherapy without Her-2 overexpression. Results MCF-7/HRG cells were more than 10-fold resistant to the alkylating agent cisplatin (CDDP), while trastuzumab coexposure completely reversed HRG-promoted CDDP resistance. A synergistic interaction between trastuzumab in combination with CDDP (paclitaxel or vincristine) was obtained in MCF-7/HRG cells. Trastuzumab prevented activation of the antiapoptotic and proliferative cascades and inhibited HRG-induced Her-2/3 phosphorylation. CDDP efficacy was enhanced by trastuzumab in cells expressing endogenously high levels of HRG. Conversely, trastuzumab coexposure was ineffective in enhancing chemotherapy efficacy in cells that did not secrete HRG, such as MCF-7 cells overexpressing a structural mutated HRG isoform. Therefore, trastuzumab-induced REC, in the absence of Her-2 overexpression, occurs through the kinase activity of Her-2/3. Interestingly, HRG expression in tumor biopsies from invasive breast carcinomas (n = 189) revealed that, whereas the minority (12%) of Her-2 positive tumors (n = 60; 32%) demonstrated Her-2 phosphorylation, the majority (67%) of HRG-overexpressing and Her-2 tumors (n = 57; 30%) were in active Her-2 status. Conclusion We demonstrate that assessment of HRG expression and Her-2 activation define a particular breast cancer patient population for which trastuzumab plus CDDP or taxol are extremely efficient without Her-2 overexpression.
5-Hydroxytryptamine-3 Receptor Antagonist With or Without Short-Course Dexamethasone in the Prophylaxis of Radiation Induced Emesis: A Placebo-Controlled Randomized Trial of the National Cancer Institute of Canada Clinical Trials Group (SC19)
Authors: Wong Rebecca K.S. , Paul Nancy , Ding Keyue , Whitehead Marlo , Brundage Michael , Fyles Anthony , Wilke Derek , Nabid Abdenour , Fortin Andre , Wilson Don , McKenzie Michael , Ackerman Ida , Souhami Luis , Chabot Pierre , Pater Joseph 
Published: July 2006

Purpose To evaluate the effectiveness of prophylactic dexamethasone for the control of radiation induced emesis (RIE) when added to ondansetron during days 1 to 5 of fractionated radiotherapy. The study had two hypotheses: ondansetron and dexamethasone could provide superior control of RIE over ondansetron alone during the prophylactic period and; the combination could provide sustained control of RIE during subsequent fractions of radiotherapy. Patients and Methods Between May 2001 to Jan 2004, 211 patients receiving radiotherapy (≥ 15 fractions) to the upper abdomen were randomly assigned to receive ondanstron 8 mg bid with either dexamethasone 4 mg daily or placebo during fractions 1 to 5. Rescue antiemetics were provided. Results During the prophylactic period there was a trend for improved complete control of nausea in the dexamethasone arm (50% v 38%; P = .06) while complete and partial control of emesis, average nausea score, and use of rescue medications were similar in the two groups. During the overall study period patients receiving dexamethasone had better complete control of emesis (23% v 12%; P = .02) and a lower average nausea score (0.28 v 0.39; P = .03); there was a trend towards less use of rescue medications with dexamethasone (70% v 80%; P = .09); other outcomes were similar on the two arms. Quality of life analysis showed a significant difference in appetite. Conclusion The addition of dexamethasone to ondansetron as prophylaxis provides a modest improvement in protection against RIE during moderately emetogenic fractionated radiotherapy. It is a potentially useful addition to 5-hydroxytryptamine-3 receptor antagonists in this setting.
Double-Blind, Placebo-Controlled, Randomized Study of Eicosapentaenoic Acid Diester in Patients With Cancer Cachexia
Authors: Fearon Kenneth C.H. , Barber Matthew D. , Moses Alastair G. , Ahmedzai Sam H. , Taylor Gillian S. , Tisdale Michael J. , Murray Gordon D. 
Published: July 2006

Purpose Eicosapentaenoic acid (EPA) has been proposed to have specific anticachectic effects. This trial compared EPA diethyl ester with placebo in cachectic cancer patients for effects on weight and lean body mass. Patients and Methods Five hundred eighteen weight-losing patients with advanced gastrointestinal or lung cancer were studied in a multicenter, double-blind, placebo controlled trial. Patients were randomly assigned to receive a novel preparation of pure EPA at a dose of 2 g or 4 g daily or placebo (2g EPA, n = 175; 4 g EPA, n = 172; placebo, n = 171). Patients were assessed at 4 weeks and 8 weeks. Results The groups were well balanced at baseline. Mean weight loss at baseline was 18% (n = 518). Over the 8-week treatment period, both intention-to-treat analysis and per protocol analysis revealed no statistically significant improvements in survival, weight, or other nutritional variables. There was, however, a trend in favor of EPA with analysis of the primary end point, weight, at 8 weeks showing a borderline, nonsignificant treatment effect (P = .066). Relative to placebo, mean weight increased by 1.2 kg with 2 g EPA (95% CI, 0 kg to 2.3 kg) and by 0.3 kg with 4g EPA (−0.9 kg to 1.5 kg). Conclusion The results indicate no statistically significant benefit from single agent EPA in the treatment of cancer cachexia. Future studies should concentrate on other agents or combination regimens.
Multicentric Breast Cancer: A New Indication for Sentinel Node Biopsy—A Multi-Institutional Validation Study
Authors: Knauer Michael , Konstantiniuk Peter , Haid Anton , Wenzl Etienne , Riegler-Keil Michaela , Pöstlberger Sabine , Reitsamer Roland , Schrenk Peter 
Published: July 2006

Purpose Multicentric breast cancer has been considered to be a contraindication for sentinel node (SN) biopsy (SNB). In this prospective multi-institutional trial, SNB-feasibility and accuracy was evaluated in 142 patients with multicentric cancer from the Austrian Sentinel Node Study Group (ASNSG) and compared with data from 3,216 patients with unicentric cancer. Patients and Methods Between 1996 and 2004, 3,730 patients underwent SNB at 15 ASNSG-affiliated hospitals. Patient data were entered in a multicenter database. One hundred forty-two patients presented with multicentric invasive breast cancer and underwent SNB. Results Intraoperatively, a mean number of 1.67 SNs were excised (identification-rate, 91.5%). The incidence of SN metastases was 60.8% (79 of 130). This was confirmed by axillary lymph node dissection (ALND) in 125 patients. Of patients with positive SNs, 60.8% (48 of 79) showed involvement of nonsentinel nodes (NSNs), as did three patients with negative SNs (false-negative rate, 4.0). Sensitivity, negative predictive value, and overall accuracy were 96.0%, 93.3%, and 97.3%, respectively. Ninety-one percent of the patients underwent mastectomy, and 9% were treated with breast conserving surgery. None of the patients have shown axillary recurrence so far (mean follow-up, 28.8 months). Compared with 3,216 patients with unicentric cancer, there was a significantly higher rate of SN metastases as well as in NSNs, whereas there was no difference in detection and false-negative rates. Conclusion Multicentric breast cancer is a new indication for SNB without routine ALND in controlled trials. Given adequate quality control and an interdisciplinary teamwork of surgical, nuclear medicine, and pathology units, SNB is both feasible and accurate in this disease entity.
Aggressiveness of Familial Prostate Cancer
Authors: Kupelian Patrick A. , Reddy Chandana A. , Reuther Alwyn M. , Mahadevan Arul , Ciezki Jay P. , Klein Eric A. 
Published: July 2006

Purpose To report on the aggressiveness of sporadic versus familial prostate cancer. Patients and Methods The study sample consisted of 4,112 stage T1-3 prostate cancer patients. The outcome of interest was biochemical relapse-free survival (bRFS). The analysis was performed for two distinct time periods, 1986 to 1992 (year ≤ 1992) and 1993 to 2002 (year ≥ 1993), to encompass both the early and late prostate-specific antigen (PSA) eras. Results A positive family history (FH positive) was reported in 16%. The 10-year bRFS rates for patients with negative family history (FH negative) versus FH positive were 59% and 63%, respectively (P = .90). However, in the year ≤ 1992 period, the 10-year bRFS rates for FH negative versus FH positive were 45% and 34%, respectively (P = .015). In the year ≥ 1993 period, the 10-year bRFS rates for FH negative versus FH positive were 61% and 67%, respectively (P = .54). Multivariate analysis failed to reveal family history as an independent predictor of relapse (P = .42). However, in the subset of patients in each era, family history was an independent predictor of relapse only for those treated in the year ≤ 1992 period (P = .038). Conclusion Family history was an independent predictor of biochemical failure only early in the PSA era, and men with an FH positive presented with more favorable disease later in the PSA era. This suggests that with stage migration and improved therapy, the impact of family history on prognosis has become minimal. However, underlying genetic factors affecting prostate cancer behavior in individuals with familial prostate cancer may still be important in determining individual prognosis.
High Survival and Organ Function Rates After Primary Chemoradiotherapy for Intermediate-Stage Squamous Cell Carcinoma of the Head and Neck Treated in a Multicenter Phase II Trial
Authors: Cohen Ezra E.W. , Haraf Daniel J. , List Marcy A. , Kocherginsky Masha , Mittal Bharat B. , Rosen Fred , Brockstein Bruce , Williams Rosalyn , Witt Mary Ellyn , Stenson Kerstin M. , Kies Merrill S. , Vokes Everett E. 
Published: July 2006

Purpose Patients with intermediate-stage squamous cell carcinoma of the head and neck traditionally have been treated with initial surgical resection followed by radiotherapy (RT) alone or chemoradiotherapy. A previous study in this patient population reported a 91% locoregional control rate and 65% overall survival (OS) rate at 5 years, with chemoradiotherapy used as primary treatment. This study was undertaken to assess whether shortening treatment duration with hyperfractionated RT would be feasible and improve locoregional control, organ preservation, and progression-free survival. Methods Eligible patients with stage II or III disease received fluorouracil, hydroxyurea, and RT given twice daily on a week-on/week-off schedule. Quality-of-life scores were measured using three validated indexes. Results All 53 patients enrolled are included in the analysis, with a median follow-up of 42 months (range, 5 to 98 months). Grade 3 or 4 in-field mucositis was observed in 77% and 9%, respectively. No patients required surgical salvage at the primary tumor site (pathological complete response rate, 100%). The 3-year progression-free and OS rates are 67% and 78%, respectively. The 3-year disease-specific mortality rate is 7%. At the time of analysis, 87% of surviving patients do not require enteral feeding support. Quality-of-life and performance assessment indicated that, although acute treatment toxicities were severe, most patients returned to pretreatment function by 12 months. Conclusion Concurrent chemoradiotherapy with hyperfractionated RT is feasible in this patient population and yields high local control and cure rates. Compared with our historical control using once-daily fractionation, hyperfractionation is accompanied by increased acute in-field toxicity.