Conformal radiotherapy after surgery for paediatric ependymoma: a prospective study
Thomas E. Merchant,Chenghong Li,Xiaoping Xiong,Larry E. Kun,Frederic A. Boop,Robert A. Sanford +5 more
TL;DR: This treatment approach to include children under the age of 3 years with the aim of improving tumour control was extended and tumour grade, tumour location, ethnic origin, sex, age when undergoing conformal radiotherapy, total radiotherapy dose, number of surgical procedures, surgery extent, and preradiotherapy chemotherapy were considered.
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Abstract: Summary Background Therapy for ependymoma includes aggressive surgical intervention and radiotherapy administered by use of methods that keep the risk of side-effects to a minimum. We extended this treatment approach to include children under the age of 3 years with the aim of improving tumour control. Methods Between July 11, 1997, and Nov 18, 2007, 153 paediatric patients (median age 2·9 years [range 0·9–22·9 months]) with localised ependymoma were treated. 85 patients had anaplastic ependymoma; the tumours of 122 were located in the infratentorial region, and 35 had received previous chemotherapy. Patients received conformal radiotherapy after definitive surgery (125 patients had undergone gross total, 17 near total, and 11 subtotal resection). Doses of 59·4 Gy (n=131) or 54·0 Gy (n=22) were prescribed to a 10 mm margin around the target volume. Disease control, patterns of failure, and complications were recorded for patients followed over 10 years. Overall survival, event-free survival (EFS), cumulative incidence of local recurrences, and cumulative incidence of distant recurrences were assessed. Variables considered included tumour grade, tumour location, ethnic origin, sex, age when undergoing conformal radiotherapy, total radiotherapy dose, number of surgical procedures, surgery extent, and preradiotherapy chemotherapy. Findings After a median follow-up of 5·3 years (range 0·4–10·4), 23 patients had died and tumour progression noted in 36, including local (n=14), distant (n=15), and combined failure (n=7). 7-year local control, EFS, and overall survival were 87·3% (95% CI 77·5–97·1), 69·1% (56·9–81·3), and 81·0% (71·0–91·0), respectively. The cumulative incidences of local and distant failure were 16·3% (9·6–23·0) and 11·5% (5·9–17·1), respectively. In the 107 patients treated with immediate postoperative conformal radiotherapy (without delay or chemotherapy), 7-year local control, EFS, and overall survival were 88·7% (77·9–99·5), 76·9% (63·4–90·4), and 85·0% (74·2–95·8), respectively; the cumulative incidence of local and distant failure were 12·6% (5·1–20·1), and 8·6% (2·8–14·3), respectively. The incidence of secondary malignant brain tumour at 7 years was 2·3% (0–5·6) and brainstem necrosis 1·6% (0–4·0). Overall survival was affected by tumour grade (anaplastic vs differentiated: HR 3·98 [95% CI 1·51–10·48]; p=0·0052), extent of resection (gross total vs near total or subtotal: 0·16 [0·07–0·37]; p vs white: 3·0 [1·21–7·44]; p=0·018). EFS was affected by tumour grade (anaplastic vs differentiated: 2·52 [1·27–5·01]; p=0·008), extent of resection (gross total vs near total or subtotal: 0·20 [0·11–0·39]; p vs female: 2·19 [1·03–4·66]; p=0·042). Local failure was affected by extent of resection (gross total vs near total or subtotal: 0·16 [0·067–0·38]; p vs female: 3·85 [1·10–13·52]; p=0·035), and age ( vs ≥3 years: 3·25 [1·30–8·16]; p=0·012). Distant recurrence was only affected by tumour grade (anaplastic vs differentiated: 4·1 [1·2–14·0]; p=0·017). Interpretation Treatment of ependymoma should include surgery with the aim of gross-total resection and conformal, high-dose, postoperative irradiation. Future trials might consider treatment stratification based on sex and age. Funding American Cancer Society and American Lebanese Syrian Associated Charities (ALSAC).
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Phase II study of intravenous etoposide in patients with relapsed ependymoma (CNS 2001 04)
John R. Apps,Shanna Maycock,J. Ellison,Tim Jaspan,Timothy A Ritzmann,Donald Macarthur,Conor Mallucci,Keith Wheatley,Gareth J. Veal,Richard Grundy,Susan Picton +10 more
TL;DR: Results confirm the dismal prognosis of this disease, provide a rationale to include etoposide within drug combinations, and highlight the need to develop novel treatments for recurrent ependymoma.
Treatment and outcome of pediatric intracranial ependymoma after first relapse
Zhiming Liu,Zhe Han,Junmei Wang,Tao Sun,Wei Fang Liu,Bo Li,Jian Gong,Chunde Li,Fuyan Zhao,Yong-ji Tian +9 more
TL;DR: A retrospective analysis of 159 children who underwent initial treatment for intracranial ependymoma at Beijing Tiantan Hospital from 2013 to 2017 showed that both tumor resection and radiotherapy at first relapse had independent prognostic significance for survival.
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Epen-02. optimising biomarkers for accurate ependymoma diagnosis, prognostication and stratification within international clinical trials: a biomeca study
Rebecca Chapman,David R Ghasemi,Felipe Andreiuolo,Valentina Zschernack,Arnault Tauziede Espariat,Francesca R. Buttarelli,Felice Giangaspero,Jacques Grill,Christine Haberler,Simon M. L. Paine,Ian Scott,Thomas S. Jacques,Martin Sill,Stefan M. Pfister,John-Paul Kilday,Pierre Leblond,Maura Massimino,Hendrik Witt,Piergiorgio Modena,Pascale Varlet,Torsten Pietsch,Richard Grundy,Kristian W. Pajtler,Timothy A Ritzmann +23 more
TL;DR: In this paper , the most accurate and reproducible ependymoma subgroup biomarker detection techniques, across 147 cases from International Society of Pediatric Oncology (SIOP) EpEndymoma II trial participants, enrolled in the pan-European 'Biomarkers of Ependymomas in Children and Adolescents (BIOMECA)' study, were established across six European BIOMECA laboratories.
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Children with Brain Tumors: Role of the Neurosurgeon
Peter F. Morgenstern,Mark M. Souweidane +1 more
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TL;DR: The surgical management of children with brain tumors has evolved considerably over the years and continues to be the first line of therapy for most tumors of the central nervous system.
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The Statistical Analysis of Failure Time Data.
Abstract: Preface.1. Introduction.1.1 Failure Time Data.1.2 Failure Time Distributions.1.3 Time Origins, Censoring, and Truncation.1.4 Estimation of the Survivor Function.1.5 Comparison of Survival Curves.1.6 Generalizations to Accommodate Delayed Entry.1.7 Counting Process Notation.Bibliographic Notes.Exercises and Complements.2. Failure Time Models.2.1 Introduction.2.2 Some Continuous Parametric Failure Time Models.2.3 Regression Models.2.4 Discrete Failure Time Models.Bibliographic Notes.Exercises and Complements.3. Inference in Parametric Models and Related Topics.3.1 Introduction.3.2 Censoring Mechanisms.3.3 Censored Samples from an Exponential Distribution.3.4 Large-Sample Likelihood Theory.3.5 Exponential Regression.3.6 Estimation in Log-Linear Regression Models.3.7 Illustrations in More Complex Data Sets.3.8 Discrimination Among Parametric Models.3.9 Inference with Interval Censoring.3.10 Discussion.Bibliographic Notes.Exercises and Complements.4. Relative Risk (Cox) Regression Models.4.1 Introduction.4.2 Estimation of beta.4.3 Estimation of the Baseline Hazard or Survivor Function.4.4 Inclusion of Strata.4.5 Illustrations.4.6 Counting Process Formulas. 4.7 Related Topics on the Cox Model.4.8 Sampling from Discrete Models.Bibliographic Notes.Exercises and Complements.5. Counting Processes and Asymptotic Theory.5.1 Introduction.5.2 Counting Processes and Intensity Functions.5.3 Martingales.5.4 Vector-Valued Martingales.5.5 Martingale Central Limit Theorem.5.6 Asymptotics Associated with Chapter 1.5.7 Asymptotic Results for the Cox Model.5.8 Asymptotic Results for Parametric Models.5.9 Efficiency of the Cox Model Estimator.5.10 Partial Likelihood Filtration.Bibliographic Notes.Exercises and Complements.6. Likelihood Construction and Further Results.6.1 Introduction.6.2 Likelihood Construction in Parametric Models.6.3 Time-Dependent Covariates and Further Remarks on Likelihood Construction.6.4 Time Dependence in the Relative Risk Model.6.5 Nonnested Conditioning Events.6.6 Residuals and Model Checking for the Cox Model.Bibliographic Notes.Exercises and Complements.7. Rank Regression and the Accelerated Failure Time Model.7.1 Introduction.7.2 Linear Rank Tests.7.3 Development and Properties of Linear Rank Tests.7.4 Estimation in the Accelerated Failure Time Model.7.5 Some Related Regression Models.Bibliographic Notes.Exercises and Complements.8. Competing Risks and Multistate Models.8.1 Introduction.8.2 Competing Risks.8.3 Life-History Processes.Bibliographic Notes.Exercises and Complements.9. Modeling and Analysis of Recurrent Event Data.9.1 Introduction.9.2 Intensity Processes for Recurrent Events.9.3 Overall Intensity Process Modeling and Estimation.9.4 Mean Process Modeling and Estimation.9.5 Conditioning on Aspects of the Counting Process History.Bibliographic Notes.Exercises and Complements.10. Analysis of Correlated Failure Time Data.10.1 Introduction.10.2 Regression Models for Correlated Failure Time Data.10.3 Representation and Estimation of the Bivariate Survivor Function.10.4 Pairwise Dependency Estimation.10.5 Illustration: Australian Twin Data.10.6 Approaches to Nonparametric Estimation of the Bivariate Survivor Function.10.7 Survivor Function Estimation in Higher Dimensions.Bibliographic Notes.Exercises and Complements.11. Additional Failure Time Data Topics.11.1 Introduction.11.2 Stratified Bivariate Failure Time Analysis.11.3 Fixed Study Period Survival Studies.11.4 Cohort Sampling and Case-Control Studies.11.5 Missing Covariate Data.11.6 Mismeasured Covariate Data.11.7 Sequential Testing with Failure Time Endpoints.11.8 Bayesian Analysis of the Proportional Hazards Model.11.9 Some Analyses of a Particular Data Set.Bibliographic Notes.Exercises and Complements.Glossary of Notation.Appendix A: Some Sets of Data.Appendix B: Supporting Technical Material.Bibliography.Author Index.Subject Index.
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Regression models and life tables (with discussion
David Cox
- 01 Jan 1972
TL;DR: The drum mallets disclosed in this article are adjustable, by the percussion player, as to balance, overall weight, head characteristics and tone production of the mallet, whereby the adjustment can be readily obtained.
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Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples.
Richard Peto,M.C. Pike,P. Armitage,N. E. Breslow,David Cox,S V Howard,N Mantel,Klim McPherson,Julian Peto,Pete Smith +9 more
TL;DR: Efficient methods of analysis of randomized clinical trials in which the authors wish to compare the duration of survival among different groups of patients are described.
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