There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

Offering a unifying theoretical perspective not readily available in any other text, this innovative guide to econometrics uses simple geometrical arguments to develop students' intuitive understanding of basic and advanced topics, emphasizing throughout the practical applications of modern theory and nonlinear techniques of estimation. One theme of the text is the use of artificial regressions for estimation, reference, and specification testing of nonlinear models, including diagnostic tests for parameter constancy, serial correlation, heteroscedasticity, and other types of mis-specification. Explaining how estimates can be obtained and tests can be carried out, the authors go beyond a mere algebraic description to one that can be easily translated into the commands of a standard econometric software package. Covering an unprecedented range of problems with a consistent emphasis on those that arise in applied work, this accessible and coherent guide to the most vital topics in econometrics today is indispensable for advanced students of econometrics and students of statistics interested in regression and related topics. It will also suit practising econometricians who want to update their skills. Flexibly designed to accommodate a variety of course levels, it offers both complete coverage of the basic material and separate chapters on areas of specialized interest.

Estimation and Inference in Econometrics

We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer.

The somatic genomic landscape of glioblastoma

It is important that the medical profession plays a significant role in critically evaluating the use of diagnostic procedures and therapies as they are introduced and tested in the detection, management, or prevention of disease states. Rigorous and expert analysis of the available data documenting absolute and relative benefits and risks of those procedures and therapies can produce helpful guidelines that improve the effectiveness of care, optimize patient outcomes, and favorably affect the overall cost of care by focusing resources on the most effective strategies.

The American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) have jointly engaged in the production of such guidelines in the area of cardiovascular disease since 1980. The ACC/AHA Task Force on Practice Guidelines, whose charge is to develop, update, or revise practice guidelines for important cardiovascular diseases and procedures, directs this effort. The Task Force is pleased to have this guideline developed in conjunction with the European Society of Cardiology (ESC). Writing committees are charged with the task of performing an assessment of the evidence and acting as an independent group of authors to develop or update written recommendations for clinical practice.

Experts in the subject under consideration have been selected from all 3 organizations to examine subject-specific data and write guidelines. The process includes additional representatives from other medical practitioner and specialty groups when appropriate. Writing committees are specifically charged to perform a formal literature review, weigh the strength of evidence for or against a particular treatment or procedure, and include estimates of expected health outcomes where data exist. Patient-specific modifiers, comorbidities, and issues of patient preference that might influence the choice of particular tests or therapies are considered as well as frequency of follow-up and cost effectiveness. When available, information from studies on cost will be considered; however, review …

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ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines

Purpose
Chemotherapy-induced nausea and vomiting (CINV) is a side effect related to administration of the adjuvant temozolomide (TMZ) in patients affected by glioblastoma. After chemoradiotherapy, adjuvant TMZ is administered as an oral multiple-day regimen, and TMZ-associated CINV may interfere with the continuation of chemotherapy, with potentially negative consequences on clinical efficacy. The aim of the present study was to investigate the efficacy of palonosetron for prevention of CINV-induced by adjuvant TMZ.

Palonosetron for the prevention of chemotherapy-induced nausea and vomiting in glioblastoma patients treated with temozolomide: a phase II study

Until the recent approval of vinflunine, no standard second-line chemotherapy existed for advanced transitional cell carcinoma (TCC). Few data exist about third-line chemotherapy for metastatic disease. Although administered in up-front regimens, anthracyclines were never evaluated beyond second-line treatment. This study assessed the activity of pegylated liposomal doxorubicin (PLD) in patients with advanced TCC previously treated with two chemotherapy regimens. From May 2005 to June 2009, 23 patients with metastatic TCC were recruited: median age was 62 years (49–76 years) with a median ECOG PS of 1. Patients received PLD 35 mg/m2 every 21 days. All patients were evaluable for efficacy and toxicity. No patient showed complete response. Three patients (13 %) had partial response; seven patients (30 %) showed stable disease for a disease control rate of 43 %. The median time to progression (TTP) was 4.1 months with a median survival time (MST) of 6.3 months. Treatment was well tolerated: no patient developed grade 4 toxicities. This is the first study which evaluated the role of anthracyclines as third-line chemotherapy in metastatic TCC. Despite its manageable profile of toxicity, PLD showed modest activity. Beyond second-line chemotherapy, supportive care still represents the best therapeutic option for patients with metastatic TCC.

Pegylated liposomal doxorubicin as third-line chemotherapy in patients with metastatic transitional cell carcinoma of urothelial tract: results of a phase II study

Current treatment of glioblastoma in the elderly includes surgery, radiotherapy and chemotherapy, but the prognosis remains extremely poor, and its optimal management is still debated. Longer survival after extensive resection compared with biopsy only has been reported, although the survival advantage remains modest. Radiation in the form of standard (60 Gy in 30 fractions over 6 weeks) and abbreviated courses of radiotherapy (30-50 Gy in 6-20 fractions over 2-4 weeks) has been employed in elderly patients with glioblastoma, showing survival benefits compared with supportive care alone. Temozolomide is an alkylating agent recently employed in older patients with newly diagnosed glioblastoma. The addition of concomitant and/or adjuvant chemotherapy with temozolomide to radiotherapy, which is currently the standard treatment in adults with glioblastoma, is emerging as an effective therapeutic option for older patients with favorable prognostic factors. The potential benefits on survival, improvement in quality of life and toxicity of different schedules of radiotherapy plus temozolomide need to be addressed in future randomized studies.

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Treatment of glioblastoma in elderly patients: an overview of current treatments and future perspective

Chapter 16 – Radiotherapy

Combination of procarbazine, lomustine and vincristine (PCV) with radiation therapy (RT) has been associated with longer survival in patients with anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA), especially in those with chromosome 1p/19q codeletion. We report a multicenter retrospective study of 84 consecutive adult patients with AO and AOA treated with RT plus concomitant and adjuvant temozolomide (TMZ) between February 2004 and January 2011. Correlations between chromosome 1p/19q codeletion, isocitrate dehydrogenase1 (IDH1) mutation, and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation with survival outcomes have been analyzed. For all 84 patients the median overall survival (OS) and progression-free survival rates were 55.6 and 45.2 months, respectively. Grade 3 or 4 hematological toxicity occurred in 17 % of patients. Chromosome 1p/19q codeletion was detected in 57 %, IDH1 mutation in 63 %, and MGMT promoter methylation in 74 % of evaluable patients. In multivariate analysis the presence of chromosome 1p/19q codeletion was associated with significant survival benefit (median OS 34 months in noncodeleted tumors and not reached in codeleted tumors; HR 0.16, 95 % CI 0.03-0.45; P = 0.005). IDH1 mutation was also of prognostic significance for longer survival (P = 0.001; HR 0.20, 95 % 0.06-0.41), whereas MGMT promoter methylation was only of borderline significance. The study indicates that RT with concomitant and adjuvant TMZ is a relatively safe treatment associated with longer survival in patients with 1p/19q codeleted and IDH1 mutated tumors. Results from ongoing randomized studies will be essential to clarify if RT plus TMZ may provide survival as good as or better than RT combined with PCV for patients with AO and AOA.

Giuseppe Minniti

Papers

Palonosetron for the prevention of chemotherapy-induced nausea and vomiting in glioblastoma patients treated with temozolomide: a phase II study

Pegylated liposomal doxorubicin as third-line chemotherapy in patients with metastatic transitional cell carcinoma of urothelial tract: results of a phase II study

Treatment of glioblastoma in elderly patients: an overview of current treatments and future perspective

Chapter 16 – Radiotherapy

Chemoradiation for anaplastic oligodendrogliomas: clinical outcomes and prognostic value of molecular markers