2005 PRETEXT: a revised staging system for primary malignant liver tumours of childhood developed by the SIOPEL group

Over the last 15 years, various oncology groups throughout the world have used the PRETEXT system for staging malignant primary liver tumours of childhood. This paper, written by members of the radiology and surgery committees of the International Childhood Liver Tumor Strategy Group (SIOPEL), presents various clarifications and revisions to the original PRETEXT system

CYP2D6 Genotype and Tamoxifen Response in Postmenopausal Women with Endocrine-Responsive Breast Cancer: The Breast International Group 1-98 Trial

Background Adjuvant tamoxifen therapy is effective for postmenopausal women with endocrine-responsive breast cancer. Cytochrome P450 2D6 (CYP2D6) enzyme metabolizes tamoxifen to clinically active metabolites, and CYP2D6 polymorphisms may adversely affect tamoxifen efficacy. In this study, we investigated the clinical relevance of CYP2D6 polymorphisms. Methods We obtained tumor tissues and isolated DNA from 4861 of 8010 postmenopausal women with hormone receptor-positive breast cancer who enrolled in the randomized, phase III double-blind Breast International Group (BIG) 1-98 trial between March 1998 and May 2003 and received tamoxifen and/or letrozole treatment. Extracted DNA was used for genotyping nine CYP2D6 single-nucleotide polymorphisms using polymerase chain reaction-based methods. Genotype combinations were used to categorize CYP2D6 metabolism phenotypes as poor, intermediate, and extensive metabolizers (PM, IM, and EM, respectively; n = 4393 patients). Associations of CYP2D6 metabolism phenotypes with breast cancer-free interval (referred to as recurrence) and treatment-induced hot flushes according to randomized endocrine treatment and previous chemotherapy were assessed. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. Results No association between CYP2D6 metabolism phenotypes and breast cancer-free interval was observed among patients who received tamoxifen monotherapy without previous chemotherapy (P = .35). PM or IM phenotype had a non-statistically significantly reduced risk of breast cancer recurrence compared with EM phenotype (PM or IM vs EM, HR of recurrence = 0.86, 95% CI = 0.60 to 1.24). CYP2D6 metabolism phenotype was associated with tamoxifen-induced hot flushes (P = .020). Both PM and IM phenotypes had an increased risk of tamoxifen-induced hot flushes compared with EM phenotype (PM vs EM, HR of hot flushes = 1.24, 95% CI = 0.96 to 1.59; IM vs EM, HR of hot flushes = 1.23, 95% CI = 1.05 to 1.43). Conclusions CYP2D6 phenotypes of reduced enzyme activity were not associated with worse disease control but were associated with increased hot flushes, contrary to the hypothesis. The results of this study do not support using the presence or absence of hot flushes or the pharmacogenetic testing of CYP2D6 to determine whether to treat postmenopausal breast cancer patients with tamoxife

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

The influence of the surgeon's and the hospital's caseload on survival and local recurrence after colorectal cancer surgery

BACKGROUND: Past studies have identified surgeon- and institution- related characteristics as prognostic factors in colorectal cancer surgery. The present work assesses the influence of the surgeon's and the hospital's caseload on long-term results of colorectal cancer surgery. METHODS: The data on 2706 patients from 2, randomized, colorectal cancer trials (Swiss Group for Clinical Cancer Research [SAKK] 40/81, SAKK 40/87) investigating adjuvant intraportal and systemic chemotherapy and 1 concurrent registration study (SAKK 40/88) were reviewed. A first analysis included 1809 eligible, nonmetastatic patients from all 3 studies. A subsequent subgroup analysis included 915 eligible patients from both randomized trials. Overall survival (OS), disease-free survival (DFS), and local recurrence (LR) were analyzed in multivariate models taking into account the possible effect of clustering. The main potential covariates were surgeon's annual caseload (>5 operations/year vs 26 operations/year vs < or =26 operations/year), tumor site, T stage, and nodal status. RESULTS: Primary analysis of all 3 studies combined found a high surgeon's caseload to be positively associated with OS (P = .025) and marginally with DFS (P = .058). Separate analysis for each trial, however, showed that a high surgeon's caseload was beneficial for outcome in both randomized trials but not in the registration study. A subgroup analysis of 915 patients with 376 rectal and 539 colonic primaries from both randomized trials, therefore, was performed. Neither age, gender, year of operation, adjuvant chemotherapy (intraportal vs systemic vs operation alone), hospital academic status (university vs non-university), training status of the surgeon (certified surgeon vs surgeon-in-training), nor inclusion in 1 of the 2 randomized trials (SAKK 40/81 vs SAKK 40/87) was a significant predictor of outcome. However, both high surgeon's and high hospital's annual caseloads were independent, beneficial prognostic factors for OS (P = .0003, P = .044) and DFS (P = .0008, P = .020), and marginally significant factors for LR (P = .057, P = .055). CONCLUSIONS: High surgeon's and hospital's annual caseloads are strong, independent prognostic factors for extending overall and disease-free survival and reducing the rate of local recurrence in 2 randomized colorectal cancer trials

Prostate specific antigen doubling time as auxiliary end point in hormone refractory prostatic carcinoma

In hormone refractory prostatic carcinoma (HRPCa), the majority of patients have bone metastases only, which are by definition non-measurable. This makes objective evaluation of chemotherapeutic agents difficult. Prostate specific antigen (PSA) as a dynamic model was analyzed as potential auxiliary end point in HRPCa

The treatment of hepatoblastoma: Its evolution and the current status as per the SIOPEL trials

Aim of the Review: To describe the significant improvement in the diagnosis, treatment and outcome of children diagnosed with hepatoblastoma (HB) that has occurred in the past four decades. Recent findings are mainly focused on lessons learned from the experiences of the Childhood Liver Tumors Strategy Group (SIOPEL). Important milestones were the risk stratification of HB that allowed to tailor down therapy for standard-risk HB and intensify treatment for high-risk HB. The multi-institutional international cooperative SIOPEL trials are reviewed and current treatment guidelines are given. Intensified cooperation between the SIOPEL and the Children′s Oncology Group (COG) and the national study groups from Germany (GPOH) and Japan (JPLT) led to the acceptance and use of one staging system (PRETEXT) and the formation of a single robust database containing data of 1605 HB patients. This will allow analysis with enough statistical power of treatment directing factors that will form one of the bases of the next-generation clinical trial that is currently designed by all four collaborating study groups. Summary: Successive SIOPEL trials and increasing international collaboration have improved survival rates of patients with HB through risk stratification, advances in chemotherapy and increased complete resection rates including liver transplantation as a surgical option