bluuebunny/crossref_metadata_2025_split huggingface dataset:
Successful Treatment of Childhood High-Risk Hepatoblastoma With Dose-Intensive Multiagent Chemotherapy and Surgery: Final Results of the SIOPEL-3HR Study
Authors: Zsíros József , Maibach Rudolf , Shafford Elizabeth , Brugieres Laurence , Brock Penelope , Czauderna Piotr , Roebuck Derek , Childs Margaret , Zimmermann Arthur , Laithier Veronique , Otte Jean-Bernard , de Camargo Beatriz , MacKinlay Gordon , Scopinaro Marcelo , Aronson Daniel , Plaschkes Jack , Perilongo Giorgio 
Published: April 2010

Purpose The primary objective was to determine the efficacy of a newly designed preoperative chemotherapy regimen in an attempt to improve the cure rate of children with high-risk hepatoblastoma. Patients and Methods High risk was defined as follows: tumor in all liver sections (ie, Pretreatment Extension IV [PRETEXT-IV]), or vascular invasion (portal vein [P+], three hepatic veins [V+]), or intra-abdominal extrahepatic extension (E+), or metastatic disease, or α-fetoprotein less than 100 ng/mL at diagnosis. Patients were treated with alternating cycles of cisplatin and carboplatin plus doxorubicin (preoperatively, n = 7; postoperatively, n = 3) and delayed tumor resection. Results Of the 151 patients (150 evaluable for response) 118 (78.7%) achieved a partial response to chemotherapy. Complete resection of the liver tumor could be achieved in 115 patients (76.2%) either by partial hepatectomy (55.6%) or by liver transplantation (20.6%). In 106 children (70.2%), complete resection of all tumor lesions (including metastases) was achieved. Among the patients with initial lung metastases, 52.2% achieved complete remission of the lung lesions with chemotherapy alone. In half of the patients with initial PRETEXT-IV tumor as the only high-risk feature, the tumor could be completely resected with partial hepatectomy. Event-free (EFS) and overall survival (OS) estimates at 3 years were 65% (95% CI, 57% to 73%) and 69% (95% CI, 62% to 77%) for the whole group. EFS and OS for all patients with PRETEXT-IV tumor were 68% and 69%, respectively, and they were 56% and 62%, respectively, for patients with metastasis. Conclusion The applied treatment rendered a great proportion of tumors resectable, and, in comparison with previously published results, led to an improved survival in patients with high-risk hepatoblastoma.
Conditional Survival and the Choice of Conditioning Set for Patients With Colon Cancer: An Analysis of NSABP Trials C-03 Through C-07
Authors: Zamboni Beth A. , Yothers Greg , Choi Mehee , Fuller Clifton D. , Dignam James J. , Raich Peter C. , Thomas Charles R. , O'Connell Michael J. , Wolmark Norman , Wang Samuel J. 
Published: April 2010

Purpose Colon cancer overall survival (OS) is usually computed from the time of diagnosis. Survival gives the initial prognosis but does not reflect how prognosis changes with changing hazard rates over time. Conditional survival (probability of surviving y additional years given they have survived x years [CS or OS|OS]) is an alternative measure that accounts for elapsed time since diagnosis, providing more relevant prognostic information. We extend the concept of CS to condition on the set of patients alive, recurrence-free, and second primary cancer-free (disease-free survival [OS|DFS]). Patients and Methods Using data from National Surgical Adjuvant Breast and Bowel Project trials C-03 through C-07, 5-year OS|DFS was calculated on patients who were disease free up to 5 years after diagnosis, stratified by age, stage, nodal status, and performance status (PS). Results For stage II, OS|DFS improved from 87% to 92% at 5 years. For stage III, OS|DFS improved from 69% to 88%. Patients younger than 50 years showed OS|DFS improvement from 79% to 95%; those older than 70 years showed no sustained increase in OS|DFS. Node-negative patients with ≥ 12 nodes resected showed little change (89% to 94%); those with more than four positive nodes showed an improvement (57% to 86%). Patients with a PS of 0 or 1 demonstrated a small improvement; those with a PS of 2 did not (64% to 58%). Conclusion Prognosis improves over time for almost all groups of patients with colon cancer, especially those with positive nodes. OS|DFS is a more relevant measure of prognosis for those who have already survived disease free a period of time after diagnosis.
Clinical Utility of Microarray-Based Gene Expression Profiling in the Diagnosis and Subclassification of Leukemia: Report From the International Microarray Innovations in Leukemia Study Group
Authors: Haferlach Torsten , Kohlmann Alexander , Wieczorek Lothar , Basso Giuseppe , Kronnie Geertruy Te , Béné Marie-Christine , De Vos John , Hernández Jesus M. , Hofmann Wolf-Karsten , Mills Ken I. , Gilkes Amanda , Chiaretti Sabina , Shurtleff Sheila A. , Kipps Thomas J. , Rassenti Laura Z. , Yeoh Allen E. , Papenhausen Peter R. , Liu Wei-min , Williams P. Mickey , Foà Robin 
Published: April 2010

Purpose The Microarray Innovations in Leukemia study assessed the clinical utility of gene expression profiling as a single test to subtype leukemias into conventional categories of myeloid and lymphoid malignancies. Methods The investigation was performed in 11 laboratories across three continents and included 3,334 patients. An exploratory retrospective stage I study was designed for biomarker discovery and generated whole-genome expression profiles from 2,143 patients with leukemias and myelodysplastic syndromes. The gene expression profiling–based diagnostic accuracy was further validated in a prospective second study stage of an independent cohort of 1,191 patients. Results On the basis of 2,096 samples, the stage I study achieved 92.2% classification accuracy for all 18 distinct classes investigated (median specificity of 99.7%). In a second cohort of 1,152 prospectively collected patients, a classification scheme reached 95.6% median sensitivity and 99.8% median specificity for 14 standard subtypes of acute leukemia (eight acute lymphoblastic leukemia and six acute myeloid leukemia classes, n = 693). In 29 (57%) of 51 discrepant cases, the microarray results had outperformed routine diagnostic methods. Conclusion Gene expression profiling is a robust technology for the diagnosis of hematologic malignancies with high accuracy. It may complement current diagnostic algorithms and could offer a reliable platform for patients who lack access to today's state-of-the-art diagnostic work-up. Our comprehensive gene expression data set will be submitted to the public domain to foster research focusing on the molecular understanding of leukemias.
Surgery and Adjuvant Chemotherapy Use Among Veterans With Colon Cancer: Insights From a California Study
Authors: Hynes Denise M. , Tarlov Elizabeth , Durazo-Arvizu Ramon , Perrin Ruth , Zhang Qiuying , Weichle Thomas , Ferreira M. Rosario , Lee Todd , Benson Al B. , Bhoopalam Nirmala , Bennett Charles L. 
Published: April 2010

Purpose US veterans have been shown to be a vulnerable population with high cancer rates, and cancer care quality in Veterans Affairs (VA) hospitals is the focus of a congressionally mandated review. We examined rates of surgery and chemotherapy use among veterans with colon cancer at VA and non-VA facilities in California to gain insight into factors associated with quality of cancer care. Methods A retrospective cohort of incident colon cancer patients from the California Cancer Registry, who were ≥ 66 years old and eligible to use VA and Medicare between 1999 and 2001, were observed for 6 months after diagnosis. Results Among 601 veterans with colon cancer, 72% were initially diagnosed and treated in non-VA facilities. Among veterans with stage I to III cancer, those diagnosed and initially treated in VA facilities experienced similar colectomy rates as those at non-VA facilities. Stage III patients diagnosed and initially treated in VA versus non-VA facilities had similar odds of receiving adjuvant chemotherapy. In both settings, older patients had lower odds of receiving chemotherapy than their younger counterparts even when race and comorbidity were considered (age 76 to 85 years: odds ratio [OR] = 0.18; 95% CI, 0.07 to 0.46; age ≥ 86 years: OR = 0.17; 95% CI, 0.04 to 0.73). Conclusion In California, older veterans with colon cancer used both VA and non-VA facilities for cancer treatment, and odds of receiving cancer-directed surgery and chemotherapy were similar in both systems. Among stage III patients, older age lowered odds of receiving adjuvant chemotherapy in both systems. Further studies should continue to explore potential health system effects on quality of colon cancer care across the United States.
Clinical Relevance of Conditional Survival of Cancer Patients in Europe: Age-Specific Analyses of 13 Cancers
Authors: Janssen-Heijnen Maryska L.G. , Gondos Adam , Bray Freddie , Hakulinen Timo , Brewster David H. , Brenner Hermann , Coebergh Jan-Willem W. 
Published: April 2010

Purpose When cancer survivors wish to receive accurate information on their current prognosis during follow-up, conditional 5-year relative survival may be most suitable. We have estimated conditional 5-year relative survival for 13 cancers using a large European database—European Network for Indicators on Cancer (EUNICE)—of 10 dedicated long-standing cancer registries across Europe. Patients and Methods Patients age 15 years and older diagnosed between 1985 and 2004 were included. Conditional 5-year relative survival for each age group was computed for every additional year survived up to 10 years. Period analysis with follow-up period 2000 to 2004 was used. Results All patients with cutaneous melanoma or colorectal, endometrial, or testis cancer and younger patients with stomach, glottis, cervix, ovary, or thyroid cancer or non-Hodgkin's lymphoma exhibited hardly any excess mortality (conditional 5-year relative survival > 95%) given that they were alive at a defined time point within 10 years of initial diagnosis. However, patients with supraglottis, lung, breast, and kidney cancer, as well as older patients with most cancers exhibited substantial excess mortality (conditional 5-year relative survival < 90%). Initial differences in relative survival at diagnosis between age groups largely disappeared with time since initial diagnosis for melanoma, or stomach, colorectal, corpus uteri, or testicular cancer but persisted for patients diagnosed with other tumors. Differences between stage groups became smaller over time or disappeared. Conclusion Conditional relative survival shows clinically relevant variations according to time since diagnosis, type of cancer, and age, and can help serve as a guide for cancer survivors in planning for their future and for doctors in planning schedules for surveillance.
Associations Among Cancer Survivorship Discussions, Patient and Physician Expectations, and Receipt of Follow-Up Care
Authors: Cheung Winson Y. , Neville Bridget A. , Earle Craig C. 
Published: April 2010

Purpose To explore the associations among cancer survivorship discussions, patient-physician expectations, and receipt of follow-up care in cancer survivors. Patients and Methods We surveyed cancer survivors about various aspects of their care, including expectations of their providers' roles, whether discussions with a physician had occurred, and self-reported patterns of follow-up. Primary care providers (PCPs) and oncologists were also surveyed for their own perceived roles. We developed a scoring system to evaluate the level of agreement in expectations between patients and physicians and between PCPs and oncologists (where 0 = most discordant and 4 = most concordant). Regression and stratified analyses were conducted to examine the relationships among expectations, discussions, and follow-up. Results In total, 535 patients (54%) and 378 physicians (62%) responded. Survivorship care expectations were most discrepant between PCPs and oncologists (mean score, 1.78), moderate between patients and oncologists (mean score, 1.97), and most similar between patients and PCPs (mean score, 2.82). Having a conversation specifically about cancer follow-up was associated with better concordance between patients and oncologists, but not for patients and their PCPs or between physicians. Better concordance in patient-oncologist expectations also correlated with greater odds of receiving certain aspects of follow-up care, such as influenza vaccinations and physical examinations, but only if a discussion about cancer follow-up had occurred. Conclusion A discussion about cancer follow-up may affect survivorship care through its primary influence on patient-oncologist expectations. Further work is required to clarify the aspects of survivorship discussions that are important for optimal cancer survivorship care planning.
Poly(ADP)-Ribose Polymerase Inhibition: Frequent Durable Responses in BRCA Carrier Ovarian Cancer Correlating With Platinum-Free Interval
Authors: Fong Peter C. , Yap Timothy A. , Boss David S. , Carden Craig P. , Mergui-Roelvink Marja , Gourley Charlie , De Greve Jacques , Lubinski Jan , Shanley Susan , Messiou Christina , A'Hern Roger , Tutt Andrew , Ashworth Alan , Stone John , Carmichael James , Schellens Jan H.M. , de Bono Johann S. , Kaye Stan B. 
Published: April 2010

Purpose Selective tumor cell cytotoxicity can be achieved through a synthetic lethal strategy using poly(ADP)-ribose polymerase (PARP) inhibitor therapy in BRCA1/2 mutation carriers in whom tumor cells have defective homologous recombination (HR) DNA repair. Platinum-based chemotherapy responses correlate with HR DNA repair capacity. Olaparib is a potent, oral PARP inhibitor that is well tolerated, with antitumor activity in BRCA1/2 mutation carriers. Patients and Methods Patients with BRCA1/2-mutated ovarian cancer were treated with olaparib within a dose-escalation and single-stage expansion of a phase I trial. Antitumor activity was subsequently correlated with platinum sensitivity. Results Fifty patients were treated: 48 had germline BRCA1/2 mutations; one had a BRCA2 germline sequence change of unknown significance, and another had a strong family history of BRCA1/2-associated cancers who declined mutation testing. Of the 50 patients, 13 had platinum-sensitive disease, 24 had platinum-resistant disease, and 13 had platinum-refractory disease (according to platinum-free interval). Twenty (40%; 95% CI, 26% to 55%) achieved Response Evaluation Criteria in Solid Tumors (RECIST) complete or partial responses and/or tumor marker (CA125) responses, and three (6.0%) maintained RECIST disease stabilization for more than 4 months, giving an overall clinical benefit rate of 46% (95% CI, 32% to 61%). Median response duration was 28 weeks. There was a significant association between the clinical benefit rate and platinum-free interval across the platinum-sensitive, resistant, and refractory subgroups (69%, 45%, and 23%, respectively). Post hoc analyses indicated associations between platinum sensitivity and extent of olaparib response (radiologic change, P = .001; CA125 change, P = .002). Conclusion Olaparib has antitumor activity in BRCA1/2 mutation ovarian cancer, which is associated with platinum sensitivity.
Phase II Study of Asparagine-Glycine-Arginine–Human Tumor Necrosis Factor α, a Selective Vascular Targeting Agent, in Previously Treated Patients With Malignant Pleural Mesothelioma
Authors: Gregorc Vanesa , Zucali Paolo A. , Santoro Armando , Ceresoli Giovanni L. , Citterio Giovanni , De Pas Tommaso M. , Zilembo Nicoletta , De Vincenzo Fabio , Simonelli Matteo , Rossoni Gilda , Spreafico Anna , Grazia Viganò Maria , Fontana Floriana , De Braud Filippo G. , Bajetta Emilio , Caligaris-Cappio Federico , Bruzzi Paolo , Lambiase Antonio , Bordignon Claudio 
Published: April 2010

PurposeNGR-hTNF consists of human tumor necrosis factor α (hTNF-α) fused to the tumor-homing peptide asparagine-glycine-arginine (NGR) able to selectively bind an aminopeptidase N isoform overexpressed on tumor blood vessels. Hypervascularity is a prominent and poor-prognosis feature of malignant pleural mesothelioma (MPM). Currently, there are no standard options for patients with MPM who are failing a front-line pemetrexed-based regimen. We explored safety and efficacy of NGR-hTNF in this setting.Patients and MethodsEligible patients had radiologically documented tumor progression and performance status ≤ 2. Primary study aim was progression-free survival (PFS). NGR-hTNF 0.8 μg/m2was given intravenously every 3 weeks. A subsequent cohort of patients received 0.8 μg/m2on a weekly basis.ResultsIn the triweekly cohort (n = 43), only one grade 3 drug-related toxicity was noted, and the most common grades 1 to 2 were short-lived chills (71%). The median PFS was 2.8 months (95% CI, 2.3 to 3.3 months). Nineteen patients (44%) had disease control (one had partial response, and 18 had stable diseases) and experienced a median progression-free time of 4.4 months. In the weekly cohort (n = 14), there was no higher toxicity, and median PFS was 3.0 months (95% CI, 1.9 to 4.1 months). Seven patients (50%) had disease control (all stable diseases) and had a median progression-free interval of 9.1 months. In the overall study population (N = 57), median PFS was 2.8 months. Median progression-free time was 4.7 months in twenty-six patients (46%) who achieved disease control. Median survival was 12.1 months.ConclusionThe tolerability and disease control of NGR-hTNF 0.8 μg/m2weekly warrant additional evaluation in patients with advanced MPM.
Serum testosterone levels measured by isotope dilution-liquid chromatography–tandem mass spectrometry in postmenopausal women versus those in women who underwent bilateral oophorectomy
Authors: Bui Hong N , Struys Eduard A , Martens Frans , de Ronde Willem , Thienpont Linda M , Kenemans Peter , Verhoeven Marieke O , Jakobs Cornelis , Dijstelbloem Hilde M , Blankenstein Marinus A 
Published: April 2010

Background Differentiation between subtle changes in low serum testosterone concentrations, common in women and children, is not possible with current commercially available assays. The objectives of the study were to develop a method based on stable isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) with adequate sensitivity and specificity and to investigate the applicability of this assay in serum samples from pre- and postmenopausal women. Methods For 16 women, testosterone levels were measured in blood samples drawn two years before and after physiological menopause, and for eight women in samples drawn before and after bilateral oophorectomy. Testosterone was extracted from serum, derivatized and analysed on an LC-MS/MS. Results The developed ID-LC-MS/MS method allowed for specific and reproducible measurement of testosterone. Comparison with stable isotope dilution-gas chromatography coupled to mass spectrometry detection by Deming regression analysis gave a slope of 1.025 and an intercept of 0.055 nmol/L ( r = 0.9998). A significant decrease was found in testosterone concentrations before and after bilateral oophorectomy ( P = 0.02), whereas no significant difference was found before and after natural menopause ( P = 0.4). Conclusions The ID-LC-MS/MS assay measures serum testosterone with acceptable accuracy and is useful in female samples, supporting the conclusion that the postmenopausal ovary contributes to circulating testosterone. To our knowledge, our analytical method compares favourably to similar published methods in terms of sensitivity. The sensitivity and specificity of this method comply with the reference method for measurement of testosterone in serum samples of women, children and men suffering from hypogonadism and can also be used for men with testosterone in the reference range.
Falsely elevated troponin I results due to outliers indicate a lack of analytical robustness
Authors: Ungerer Jacobus P J , Pretorius Carel J , Dimeski Goce , O'Rourke Peter K , Tyack Shirley A 
Published: April 2010

Aims Troponin (Tn) is the preferred biochemical marker for the diagnosis of acute coronary syndrome. Spurious false Tn results (outliers) may cause significant problems with clinical management. We investigated the occurrence of outliers and whether this phenomenon could be explained by analytical imprecision. Methods and results Troponin I (TnI) was measured in duplicate with Beckman AccuTnI reagent if the first TnI result was ≥0.04 μg/L ( n = 5265). All TnI requests were performed in duplicate in a subset of samples for one calendar month ( n = 881). A total of 13,178 TnI requests were received during the study period. Variables were sample type, centrifugation speed and analyser. Results were identified as outliers when the difference between two results exceeded a critical difference (CD) limit defined by CD = z × √2 × SDAnalytical. Outliers at the 0.0005 probability level were detected in 102 of 5265 duplicate observations (1.94 ± 0.37%). This translated into an outlier rate of 0.55 ± 0.13% for all TnI results and 1.37 ± 0.31% for results above 0.04 μg/L. Outliers resulted only in falsely elevated TnI values and were not dependent on the analyser, centrifugation speed or sample type. Conclusion TnI outliers occurred more frequently than anticipated, could not be explained by analytical imprecision and indicated a lack of robustness in the assay. The high rate and the magnitude of the errors will complicate clinical management and carry a risk of detrimental patient outcome. The outlier rate is a useful parameter to define the robustness of assays.
Clinical accuracy of midnight salivary cortisol measured by automated electrochemiluminescence immunoassay method in Cushing's syndrome
Authors: Carrozza Cinzia , Corsello Salvatore Maria , Paragliola Rosa Maria , Ingraudo Francesca , Palumbo Sara , Locantore Pietro , Sferrazza Antonella , Pontecorvi Alfredo , Zuppi Cecilia 
Published: April 2010

Background The diagnosis of Cushing's syndrome (CS) represents a challenge for endocrinologists. Several screening tests are used, but none of them seems to be the gold standard for the diagnosis. The aim of this study was to confirm the diagnostic value of salivary cortisol (SC) as a first-level screening test and to evaluate the clinical performance of a electrochemiluminescence immunoassay (ECLIA) method. Methods In 33 patients with a strong clinical suspicion of CS, we evaluated urinary free cortisol, circadian rhythm plasma cortisol (PC) and morning PC after low-dose dexamethasone suppression test (LDDST). At the same sampling times, we evaluated SC analysed by the same automated method. Correlation studies were evaluated by Spearman index (significance P < 0.05). Results On the basis of biochemical results CS was confirmed in 21/33. SC was significantly correlated to PC at 12:00 and 23:00. Thus, we chose 8.3 nmol/L as midnight SC cut-off value with 100% sensitivity and 97.4% specificity. The cut-off chosen after LDDST was 1.7 nmol/L (100% sensitivity and 72% specificity). Conclusion SC assay showed a good clinical accuracy and the ECLIA method can be used in clinical routine to obtain fast results easily.