102 results on '"Meriel Jenney"'
Search Results
2. Frontline and Relapsed Rhabdomyosarcoma (FAR-RMS) Clinical Trial: A Report from the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG)
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Julia Chisholm, Henry Mandeville, Madeleine Adams, Veronique Minard-Collin, Timothy Rogers, Anna Kelsey, Janet Shipley, Rick R. van Rijn, Isabelle de Vries, Roelof van Ewijk, Bart de Keizer, Susanne A. Gatz, Michela Casanova, Lisa Lyngsie Hjalgrim, Charlotte Firth, Keith Wheatley, Pamela Kearns, Wenyu Liu, Amanda Kirkham, Helen Rees, Gianni Bisogno, Ajla Wasti, Sara Wakeling, Delphine Heenen, Deborah A. Tweddle, Johannes H. M. Merks, and Meriel Jenney
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rhabdomyosarcoma ,clinical trial ,chemotherapy ,radiotherapy ,randomisation ,novel agents ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The Frontline and Relapsed Rhabdomyosarcoma (FaR-RMS) clinical trial is an overarching, multinational study for children and adults with rhabdomyosarcoma (RMS). The trial, developed by the European Soft Tissue Sarcoma Study Group (EpSSG), incorporates multiple different research questions within a multistage design with a focus on (i) novel regimens for poor prognostic subgroups, (ii) optimal duration of maintenance chemotherapy, and (iii) optimal use of radiotherapy for local control and widespread metastatic disease. Additional sub-studies focusing on biological risk stratification, use of imaging modalities, including [18F]FDG PET-CT and diffusion-weighted MRI imaging (DWI) as prognostic markers, and impact of therapy on quality of life are described. This paper forms part of a Special Issue on rhabdomyosarcoma and outlines the study background, rationale for randomisations and sub-studies, design, and plans for utilisation and dissemination of results.
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- 2024
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3. Time to broaden the eligibility criteria in paediatric oncology trials? An analysis of patients with rhabdomyosarcoma non-eligible to the EpSSG RMS2005 trial
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Gianni Bisogno, Gian Luca De Salvo, Veronique Minard-Colin, Raquel Davila Fajardo, Beatrice Coppadoro, Meriel Jenney, Andrea Ferrari, Raquel Hladun Alvaro, Patrizia Dall’Igna, Heidi Glosli, and Johannes H.M. Merks
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Eligibility criteria ,Clinical trial ,Rhabdomyosarcoma ,Non-eligible patients ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Purpose: Clinical trials include a series of eligibility and exclusion criteria that define the study population to reduce inter-patient heterogeneity and increase safety. Little is known about children with oncological diseases excluded from trials because they do not satisfy these criteria. We analysed the eligibility criteria adopted in the European paediatric Soft tissue sarcoma Study Group RMS2005 study and the survival of non-eligible patients. Patients and methods: RMS2005 run from 10/2005–12/2016. Eligibility criteria were age ≤ 25 years; pathologically proven diagnosis of rhabdomyosarcoma (RMS); no evidence of metastases; no pre-treatment; no pre-existing conditions preventing treatment; no previous malignant tumours and an interval between diagnostic surgery and the start of treatment ≤ 8 weeks. Clinical characteristics, 5-year progression-free survival (PFS), and overall survival (OS) were analysed for eligible and non-eligible patients. Results: The 79 non-eligible patients (4.3% of registered patients) were older than eligible patients (p
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- 2023
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4. Biological Role and Clinical Implications of MYOD1L122R Mutation in Rhabdomyosarcoma
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Daniela Di Carlo, Julia Chisholm, Anna Kelsey, Rita Alaggio, Gianni Bisogno, Veronique Minard-Colin, Meriel Jenney, Raquel Dávila Fajardo, Johannes H. M. Merks, Janet M. Shipley, and Joanna L. Selfe
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MYOD1 ,spindle cell ,sclerosing rhabdomyosarcoma ,high-risk ,children ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Major progress in recent decades has furthered our clinical and biological understanding of rhabdomyosarcoma (RMS) with improved stratification for treatment based on risk factors. Clinical risk factors alone were used to stratify patients for treatment in the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) RMS 2005 protocol. The current EpSSG overarching study for children and adults with frontline and relapsed rhabdomyosarcoma (FaR-RMS NCT04625907) includes FOXO1 fusion gene status in place of histology as a risk factor. Additional molecular features of significance have recently been recognized, including the MYOD1L122R gene mutation. Here, we review biological information showing that MYOD1L122R blocks cell differentiation and has a MYC-like activity that enhances tumorigenesis and is linked to an aggressive cellular phenotype. MYOD1L122R mutations can be found together with mutations in other genes, such as PIK3CA, as potentially cooperating events. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, ten publications in the clinical literature involving 72 cases were reviewed. MYOD1L122R mutation in RMS can occur in both adults and children and is frequent in sclerosing/spindle cell histology, although it is also significantly reported in a subset of embryonal RMS. MYOD1L122R mutated tumors most frequently arise in the head and neck and extremities and are associated with poor outcome, raising the issue of how to use MYOD1L122R in risk stratification and how to treat these patients most effectively.
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- 2023
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5. Patient Reported Outcomes and Measures in Children with Rhabdomyosarcoma
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Marloes van Gorp, Martha A. Grootenhuis, Anne-Sophie Darlington, Sara Wakeling, Meriel Jenney, Johannes H. M. Merks, Lisa Lyngsie Hjalgrim, and Madeleine Adams
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childhood cancer ,rhabdomyosarcoma ,patient-reported outcomes ,patient-reported outcome measures ,quality of life ,adverse events ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
In addition to optimising survival of children with rhabdomyosarcoma (RMS), more attention is now focused on improving their quality of life (QOL) and reducing symptoms during treatment, palliative care or into long-term survivorship. QOL and ongoing symptoms related to the disease and its treatment are outcomes that should ideally be patient-reported (patient-reported outcomes, PROs) and can be assessed using patient-reported outcome measures (PROMS). This commentary aims to encourage PRO and PROM use in RMS by informing professionals in the field of available PROMs for utilisation in paediatric RMS and provide considerations for future use in research and clinical practice. Despite the importance of using PROMs in research and practice, PROMs have been reported scarcely in paediatric RMS literature so far. Available literature suggests lower QOL of children with RMS compared to general populations and occurrence of disease-specific symptoms, but a lack of an RMS-specific PROM. Ongoing developments in the field include the development of PROMs targeted at children with RMS specifically and expansion of PROM evaluation within clinical trials.
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- 2023
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6. Local staging and treatment in extremity rhabdomyosarcoma. A report from the EpSSG‐RMS2005 study
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Sheila E. J. Terwisscha van Scheltinga, Marc H. W. A. Wijnen, Hélène Martelli, Timothy Rogers, Henry Mandeville, Mark N. Gaze, Keiran McHugh, Nadege Corradini, Daniel Orbach, Meriel Jenney, Anna Kelsey, Julia Chisholm, Soledad Gallego, Heidi Glosli, Andrea Ferrari, Ilaria Zanetti, Gian Luca De Salvo, Veronique Minard‐Colin, Giani Bisogno, Max M. van Noesel, and Hans H. M. Merks
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local therapy ,lymph node metastases ,radiotherapy ,rhabdomyosarcoma ,staging ,surgery ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Rhabdomyosarcoma of the extremities present with two main challenges: correct evaluation of initial regional nodal involvement and define adequate local treatment. Methods Pediatric patients with localized rhabdomyosarcoma of the extremity included in the EpSSG‐RMS2005 study between 2005 and 2014 were evaluated for staging, treatment, and survival. The outcome was compared to the preceding European SIOP‐MMT studies. Results Of the 162 patients included, histology was unfavorable in 113 (70%), 124 (77%) were younger than 10 years, 128 (79%) were IRS III, and 47 (29%) were node‐positive. A regional node biopsy was performed in 97 patients (60%) and modified the lymph node stage in 15/97 (16%). Primary and delayed surgery was performed in 155 (96%) and radiotherapy delivered in 118 (73%) patients. Relapse occurred in 61 cases (38%), local in 14 (23%), regional in 13 (21%), distant in 22 (36%), and combined relapse in 12 (20%) with five progressive diseases (8%) and four secondary tumors (7%). Five‐year event free (EFS) and overall survival (OS) were 58.4% (95%CI, 50.3‐65.7) and 71.7% (63.6‐78.4), respectively. In the previous studies MMT89 and MMT95, tumor surgery was performed in 32/53 (60%) and 74/82(90%), respectively, and radiotherapy delivered in 13/53 (25%) and 26/82 (30%), respectively. Five‐year EFS and OS were 35.6%, and 50.3% in MMT89 and 54.3% and 68.2% in the MMT95 study. Conclusions Even if the lymph node staging was not always complete according to the RMS2005 protocol, node sampling changed lymph node status in a significant number of patients. Despite the higher rate of patients treated with locoregional radiotherapy, survival in RMS2005 did not improve compared to the previous European SIOP‐MMT95 study.
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- 2020
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7. Shedding a Light on the Challenges of Adolescents and Young Adults with Rhabdomyosarcoma
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Andrea Ferrari, Susanne Andrea Gatz, Veronique Minard-Colin, Rita Alaggio, Shushan Hovsepyan, Daniel Orbach, Patrizia Gasparini, Anne-Sophie Defachelles, Michela Casanova, Giuseppe Maria Milano, Julia C. Chisholm, Meriel Jenney, Gianni Bisogno, Timothy Rogers, Henry C. Mandeville, Janet Shipley, Aisha B. Miah, Johannes H. M. Merks, and Winette T. A. van der Graaf
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rhabdomyosarcoma ,adolescents ,young adults ,AYA ,review ,clinical trial ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Rhabdomyosarcoma (RMS) is a typical tumour of childhood but can occur at any age. Several studies have reported that adolescent and young adult (AYA) patients with RMS have poorer survival than do younger patients. This review discusses the specific challenges in AYA patients with pediatric-type RMS, exploring possible underlying factors which may influence different outcomes. Reasons for AYA survival gap are likely multifactorial, and might be related to differences in tumor biology and intrinsic aggressiveness, or differences in clinical management (that could include patient referral patterns, time to diagnosis, enrolment into clinical trials, the adequacy and intensity of treatment), as well as patient factors (including physiology and comorbidity that may influence treatment tolerability, drug pharmacokinetics and efficacy). However, improved survival has been reported in the most recent studies for AYA patients treated on pediatric RMS protocols. Different strategies may help to further improve outcome, such as supporting trans-age academic societies and national/international collaborations; developing specific clinical trials without upper age limit; defining integrated and comprehensive approach to AYA patients, including the genomic aspects; establishing multidisciplinary tumor boards with involvement of both pediatric and adult oncologists to discuss all pediatric-type RMS patients; developing dedicated projects with specific treatment recommendations and registry/database.
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- 2022
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8. Nonmetastatic Rhabdomyosarcoma in Children and Adolescents: Overall Results of the European Pediatric Soft Tissue Sarcoma Study Group RMS2005 Study
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Gianni Bisogno, Veronique Minard-Colin, Ilaria Zanetti, Andrea Ferrari, Soledad Gallego, Raquel Dávila Fajardo, Henry Mandeville, Anna Kelsey, Rita Alaggio, Daniel Orbach, Sheila Terwisscha van Scheltinga, Gabriela Guillén Burrieza, Myriam Ben-Arush, Heidi Glosli, Peter Mudry, Sima Ferman, Christine Devalck, Anne Sophie Defachelles, Johannes Hendrikus Maria Merks, and Meriel Jenney
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Cancer Research ,Oncology - Abstract
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The RMS2005 study included two phase III randomized trials for high-risk (HR) and observational trials for low (LR), standard (SR), and very high-risk (VHR) patients who have been partially reported. Herein, we present a comprehensive report of results achieved for the complete unselected nonmetastatic cohort and analyze the evolution of treatment in comparison with previous European protocols. After a median follow-up of 73.1 months, the 5-year event-free survival (EFS) and overall survival (OS) of the 1,733 patients enrolled were 70.7% (95% CI, 68.5 to 72.8) and 80.4% (95% CI, 78.4 to 82.3), respectively. The results by subgroup: LR (80 patients) EFS 93.7% (95% CI, 85.5 to 97.3), OS 96.7% (95% CI, 87.2 to 99.2); SR (652 patients) EFS 77.4% (95% CI, 73.9 to 80.5), OS 90.6% (95% CI, 87.9 to 92.7); HR (851 patients) EFS 67.3% (95% CI, 64.0 to 70.4), OS 76.7% (95% CI, 73.6 to 79.4); and VHR (150 patients) EFS 48.8% (95% CI, 40.4 to 56.7), OS 49.7% (95% CI, 40.8 to 57.9). The RMS2005 study demonstrated that 80% of children with localized rhabdomyosarcoma could be long-term survivors. The study has established the standard of care across the European pediatric Soft tissue sarcoma Study Group countries with the confirmation of a 22-week vincristine/actinomycin D regimen for LR patients, the reduction of the cumulative ifosfamide dose in the SR group, and for HR disease, the omission of doxorubicin and the addition of maintenance chemotherapy.
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- 2023
9. Metastatic Rhabdomyosarcoma: Results of the European Paediatric Soft Tissue Sarcoma Study Group MTS 2008 Study and Pooled Analysis With the Concurrent BERNIE Study
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Reineke A. Schoot, Julia C. Chisholm, Michela Casanova, Veronique Minard-Colin, Birgit Geoerger, Alison L. Cameron, Beatrice Coppadoro, Ilaria Zanetti, Daniel Orbach, Anna Kelsey, Timothy Rogers, Cecile Guizani, Markus Elze, Myriam Ben-Arush, Kieran McHugh, Rick R. van Rijn, Sima Ferman, Soledad Gallego, Andrea Ferrari, Meriel Jenney, Gianni Bisogno, Johannes H.M. Merks, Institut Català de la Salut, [Schoot RA] Princess Máxima Centre for Paediatric Oncology, Utrecht, the Netherlands. [Chisholm JC] Children and Young Peoples Unit, Royal Marsden Hospital and Institute of Cancer Research, Sutton, Surrey, United Kingdom. [Casanova M] Paediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Minard-Colin V] Gustave-Roussy Cancer Campus, Department of Paediatric and Adolescent Oncology, Université Paris-Saclay, Villejuif, France. [Geoerger B] Gustave-Roussy Cancer Campus, Department of Paediatric and Adolescent Oncology, Université Paris-Saclay, Villejuif, France. Gustave-Roussy Cancer Campus, INSERM U1015, Université Paris Saclay, Villejuif, France. [Cameron AL] Bristol Haematology and Oncology Centre, University Hospitals Bristol. [Gallego S] Servei d’Oncologia i Hematologia Pediàtriques, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Radiology and Nuclear Medicine, and Other Research
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Cancer Research ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,neoplasias::neoplasias por tipo histológico::neoplasias de tejido conjuntivo y de tejidos blandos::neoplasias de tejido muscular::miosarcoma::rabdomiosarcoma [ENFERMEDADES] ,Otros calificadores::Otros calificadores::/efectos adversos [Otros calificadores] ,Disease-Free Survival ,Tumors de parts toves - Tractament ,Quimioteràpia combinada ,Neoplasms ,Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Antineoplastic Combined Chemotherapy Protocols ,Rhabdomyosarcoma ,Other subheadings::Other subheadings::/adverse effects [Other subheadings] ,Humans ,Sarcoma - Tractament ,Ifosfamide ,Child ,Neoplasms::Neoplasms by Histologic Type::Neoplasms, Connective and Soft Tissue::Neoplasms, Muscle Tissue::Myosarcoma::Rhabdomyosarcoma [DISEASES] ,Cyclophosphamide ,terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Sarcoma ,Second Primary ,Oncology ,Vincristine ,Dactinomycin ,Doxorubicin ,Neoplasms, Second Primary - Abstract
PURPOSE Outcome for patients with metastatic rhabdomyosarcoma (RMS) is poor. This study presents the results of the MTS 2008 study with a pooled analysis including patients from the concurrent BERNIE study. PATIENTS AND METHODS In MTS 2008, patients with metastatic RMS received four cycles of ifosfamide, vincristine, and actinomycin D (IVA) plus doxorubicin, five cycles of IVA, and 12 cycles of maintenance chemotherapy (low-dose cyclophosphamide and vinorelbine). The BERNIE study randomly assigned patients to the addition or not of bevacizumab to the same chemotherapy. Local therapy (surgery/radiotherapy) was given to the primary tumor and all metastatic sites when feasible. RESULTS MTS 2008 included 270 patients (median age, 9.6 years; range, 0.07-20.8 years). With a median follow-up of 50.3 months, 3-year event-free survival (EFS) and overall survival (OS) were 34.9% (95% CI, 29.1 to 40.8) and 47.9% (95% CI, 41.6 to 53.9), respectively. In pooled analyses on 372 patients with a median follow-up of 55.2 months, 3-year EFS and OS were 35.5% (95% CI, 30.4 to 40.6) and 49.3% (95% CI, 43.9 to 54.5), respectively. Patients with ≤ 2 Oberlin risk factors (ORFs) had better outcome than those with ≥ 3 ORFs: 3-year EFS was 46.1% versus 12.5% ( P < .0001) and 3-year OS 60.0% versus 26.0% ( P < .0001). Induction chemotherapy and maintenance appeared tolerable; however, about two third of patients needed dose adjustments during maintenance. CONCLUSION Outcome remains poor for patients with metastatic RMS and multiple ORFs. Because of the design of the studies, it was not possible to determine whether the intensive induction regimen and/or the addition of maintenance treatment resulted in apparent improvement of outcome compared with historical cohorts. Further studies, with novel treatment approaches are urgently needed, to improve outcome for the group of patients with adverse prognostic factors.
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- 2022
10. Genomic Classification and Clinical Outcome in Rhabdomyosarcoma: A Report From an International Consortium
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Paola Angelini, Sabri Jamal, Debbie Hughes, Erin R. Rudzinski, Hsien-Chao Chou, Julia C. Chisholm, Marielle E. Yohe, Joanna Selfe, Tammy Lo, Janet Shipley, Meriel Jenney, Javed Khan, Elisa Izquierdo, Mike Hubank, Young K. Song, Stephen X. Skapek, Rajesh Patidar, Xinyu Wen, Douglas S. Hawkins, Rebecca Brown, Donald A. Barkauskas, David Hall, Anna Kelsey, Sally L. George, Jack F. Shern, Susanne A. Gatz, Kristine Jones, Sivasish Sindiri, Belynda Hicks, Jun S. Wei, Louis Chesler, and Corinne M. Linardic
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Male ,0301 basic medicine ,Oncology ,Cancer Research ,Time Factors ,DNA Mutational Analysis ,Outcome (game theory) ,0302 clinical medicine ,INDEL Mutation ,Risk Factors ,Databases, Genetic ,Medicine ,Rhabdomyosarcoma, Embryonal ,Child ,Rhabdomyosarcoma ,Soft tissue sarcoma ,Genomics ,Progression-Free Survival ,Phenotype ,Child, Preschool ,030220 oncology & carcinogenesis ,Disease Progression ,Female ,Adult ,medicine.medical_specialty ,Adolescent ,MEDLINE ,Risk Assessment ,Young Adult ,03 medical and health sciences ,Text mining ,Predictive Value of Tests ,Internal medicine ,Biomarkers, Tumor ,Recurrent disease ,Humans ,Genetic Predisposition to Disease ,Survival rate ,Rhabdomyosarcoma, Alveolar ,business.industry ,Gene Expression Profiling ,Gene Amplification ,Infant, Newborn ,Infant ,medicine.disease ,United Kingdom ,United States ,030104 developmental biology ,Transcriptome ,business ,Gene Deletion - Abstract
PURPOSE Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood. Despite aggressive therapy, the 5-year survival rate for patients with metastatic or recurrent disease remains poor, and beyond PAX-FOXO1 fusion status, no genomic markers are available for risk stratification. We present an international consortium study designed to determine the incidence of driver mutations and their association with clinical outcome. PATIENTS AND METHODS Tumor samples collected from patients enrolled on Children's Oncology Group trials (1998-2017) and UK patients enrolled on malignant mesenchymal tumor and RMS2005 (1995-2016) trials were subjected to custom-capture sequencing. Mutations, indels, gene deletions, and amplifications were identified, and survival analysis was performed. RESULTS DNA from 641 patients was suitable for analyses. A median of one mutation was found per tumor. In FOXO1 fusion-negative cases, mutation of any RAS pathway member was found in > 50% of cases, and 21% had no putative driver mutation identified. BCOR (15%), NF1 (15%), and TP53 (13%) mutations were found at a higher incidence than previously reported and TP53 mutations were associated with worse outcomes in both fusion-negative and FOXO1 fusion-positive cases. Interestingly, mutations in RAS isoforms predominated in infants < 1 year (64% of cases). Mutation of MYOD1 was associated with histologic patterns beyond those previously described, older age, head and neck primary site, and a dismal survival. Finally, we provide a searchable companion database ( ClinOmics ), containing all genomic variants, and clinical annotation including survival data. CONCLUSION This is the largest genomic characterization of clinically annotated rhabdomyosarcoma tumors to date and provides prognostic genetic features that refine risk stratification and will be incorporated into prospective trials.
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- 2021
11. Radiotherapy quality assurance in paediatric clinical trials: first report from six QUARTET-affiliated trials
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Sarah M Kelly, Andrada Turcas, Coreen Corning, Simon Bailey, Adela Cañete, Enrico Clementel, Andrea di Cataldo, Karin Dieckmann, Mark N Gaze, Gail Horan, Meriel Jenney, Ruth Ladenstein, Laetitia Padovani, Dominique Valteau-Couanet, Tom Boterberg, and Henry Mandeville
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Quality Control ,Health Care ,Quality Assurance, Health Care ,Oncology ,Radiation Oncology ,Radiology, Nuclear Medicine and imaging ,Hematology ,Quality Assurance ,Clinical Trial ,Pediatrics ,radiotherapy - Published
- 2023
12. Erratum to ‘Linking EORTC QLQ-C-30 and PedsQL/PEDQOL physical functioning scores in patients with osteosarcoma’ [Eur J Cancer 170 (2022) 209-235]
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Axel Budde, Katja Baust, Leonie Weinhold, Mark Bernstein, Stefan Bielack, Catharina Dhooge, Lars Hjorth, Katherine A. Janeway, Meriel Jenney, Mark D. Krailo, Neyssa Marina, Rajaram Nagarajan, Sigbjørn Smeland, Matthew R. Sydes, Patricia De Vos, Jeremy Whelan, Andreas Wiener, Gabriele Calaminus, and Matthias Schmid
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Cancer Research ,Oncology - Published
- 2022
13. Embryonal rhabdomyosarcoma completely resected at diagnosis: The European paediatric Soft tissue sarcoma Study Group RMS2005 experience
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Christophe Bergeron, Meriel Jenney, Federica De Corti, Soledad Gallego, Hans Merks, Heidi Glosli, Andrea Ferrari, Dominique Ranchère-Vince, Gian Luca De Salvo, Ilaria Zanetti, Julia Chisholm, Véronique Minard-Colin, Timothy Rogers, Gianni Bisogno, Adriana Rose, Christine Devalck, Sima Ferman, Peter Mudry, Myriam Weyl Ben Arush, Daniela Sejnova, Maja Cesen, and J. Hans Merks
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Male ,0301 basic medicine ,Cancer Research ,medicine.medical_treatment ,0302 clinical medicine ,Risk Factors ,Antineoplastic Combined Chemotherapy Protocols ,Rhabdomyosarcoma ,Rhabdomyosarcoma, Embryonal ,Prospective Studies ,Stage (cooking) ,Child ,media_common ,Soft tissue sarcoma ,Ifosfamide ,Prognosis ,Combined Modality Therapy ,Survival Rate ,Oncology ,Vincristine ,Child, Preschool ,030220 oncology & carcinogenesis ,Dactinomycin ,Female ,Childhood cancer ,medicine.drug ,medicine.medical_specialty ,Adolescent ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,media_common.cataloged_instance ,European union ,Cyclophosphamide ,Retrospective Studies ,Chemotherapy ,business.industry ,Infant ,medicine.disease ,030104 developmental biology ,Doxorubicin ,Embryonal rhabdomyosarcoma ,business ,Follow-Up Studies - Abstract
Rhabdomyosarcoma (RMS) is the most common form of soft tissue sarcoma in children. We report the results of the European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS 2005 study, which prospectively evaluated the reduction of chemotherapy in patients with embryonal RMS (ERMS) after initial surgery.Between October 2005 and December 2016, all patients with localised ERMS with an initial microscopically complete resection (IRS group I) with lymph node-negative (N0) were prospectively enrolled in the low-risk (n = 70, subgroup A; age 10 years and tumour size ≤ 5 cm) or standard-risk group (n = 108, subgroup B; age ≥ 10 years or tumour size 5 cm. Subgroup A received 8 courses of vincristine and dactinomycin (VA) for 22 weeks; subgroup B received 4 courses of VA with ifosfamide (IVA) and 5 courses of VA for 25 weeks.The 5-year event-free survival (EFS) and overall survival (OS) were 90.8% (95% confidence interval [CI]: 85.0-94.4) and 95.7% (95% CI: 90.5-98.1), respectively (n = 178). The EFS and OS were 95.5% (95% CI: 86.8-98.5) and 100% (subgroupA), and 87.8% (95% CI: 79.3-93.0) and 93.0% (95% CI: 84.8-96.8)(subgroup B), respectively. Bearman stage 2 veno-occlusive disease (VOD) occurred in 4 very young patients.VA treatment for 8 courses was effective and well tolerated by the subgroup of patients with low-risk ERMS (group A). Four courses of IVA and 5 courses of VA instead of 9 courses of IVA also has very good results. Careful monitoring for liver toxicity is important in very young patients. European union drug regulating authorities clinical trials EUDRACT No. 2005-000217-35.
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- 2021
14. Local staging and treatment in extremity rhabdomyosarcoma. A report from the EpSSG‐RMS2005 study
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Nadège Corradini, Hans H.M. Merks, Keiran McHugh, Max M. van Noesel, Giani Bisogno, Marc H. W. A. Wijnen, Mark N. Gaze, Hélène Martelli, Veronique Minard-Colin, Henry Mandeville, Timothy Rogers, Meriel Jenney, Gian Luca De Salvo, Heidi Glosli, Andrea Ferrari, Anna Kelsey, Daniel Orbach, Ilaria Zanetti, Julia C. Chisholm, Sheila E. J. Terwisscha van Scheltinga, and Soledad Gallego
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Male ,0301 basic medicine ,Cancer Research ,Biopsy ,medicine.medical_treatment ,surgery ,0302 clinical medicine ,Recurrence ,Neoplasm Metastasis ,Stage (cooking) ,Child ,Rhabdomyosarcoma ,Lymph node ,Original Research ,medicine.diagnostic_test ,Disease Management ,Prognosis ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Combined Modality Therapy ,Tumor Burden ,Treatment Outcome ,medicine.anatomical_structure ,Oncology ,Child, Preschool ,030220 oncology & carcinogenesis ,Female ,Radiology ,lymph node metastases ,Diagnostic Imaging ,medicine.medical_specialty ,Adolescent ,Clinical Decision-Making ,lcsh:RC254-282 ,03 medical and health sciences ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,radiotherapy ,Neoplasm Staging ,local therapy ,rhabdomyosarcoma ,staging ,business.industry ,Infant ,Clinical Cancer Research ,Extremities ,Histology ,medicine.disease ,Survival Analysis ,Radiation therapy ,030104 developmental biology ,Secondary tumors ,Tumor surgery ,business - Abstract
Rhabdomyosarcoma of the extremities present with two main challenges: correct evaluation of initial regional nodal involvement and define adequate local treatment. Methods Pediatric patients with localized rhabdomyosarcoma of the extremity included in the EpSSG‐RMS2005 study between 2005 and 2014 were evaluated for staging, treatment, and survival. The outcome was compared to the preceding European SIOP‐MMT studies. Results Of the 162 patients included, histology was unfavorable in 113 (70%), 124 (77%) were younger than 10 years, 128 (79%) were IRS III, and 47 (29%) were node‐positive. A regional node biopsy was performed in 97 patients (60%) and modified the lymph node stage in 15/97 (16%). Primary and delayed surgery was performed in 155 (96%) and radiotherapy delivered in 118 (73%) patients. Relapse occurred in 61 cases (38%), local in 14 (23%), regional in 13 (21%), distant in 22 (36%), and combined relapse in 12 (20%) with five progressive diseases (8%) and four secondary tumors (7%). Five‐year event free (EFS) and overall survival (OS) were 58.4% (95%CI, 50.3‐65.7) and 71.7% (63.6‐78.4), respectively. In the previous studies MMT89 and MMT95, tumor surgery was performed in 32/53 (60%) and 74/82(90%), respectively, and radiotherapy delivered in 13/53 (25%) and 26/82 (30%), respectively. Five‐year EFS and OS were 35.6%, and 50.3% in MMT89 and 54.3% and 68.2% in the MMT95 study. Conclusions Even if the lymph node staging was not always complete according to the RMS2005 protocol, node sampling changed lymph node status in a significant number of patients. Despite the higher rate of patients treated with locoregional radiotherapy, survival in RMS2005 did not improve compared to the previous European SIOP‐MMT95 study., Adequate staging is important for the treatment of extremity RMS. Despite local therapy intensification, survival in RMS2005 did not improve compared to the previous European SIOP‐MMT95 study.
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- 2020
15. Adolescents and young adults with rhabdomyosarcoma treated in the European paediatric Soft tissue sarcoma Study Group (EpSSG) protocols: a cohort study
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Andrea Ferrari, Julia C Chisholm, Meriel Jenney, Veronique Minard-Colin, Daniel Orbach, Michela Casanova, Gabriela Guillen, Heidi Glosli, Rick R van Rijn, Reineke A Schoot, Alison L Cameron, Timothy Rogers, Rita Alaggio, Myriam Ben-Arush, Henry C Mandeville, Christine Devalck, Anne-Sophie Defachelles, Beatrice Coppadoro, Gianni Bisogno, Johannes H M Merks, and Radiology and nuclear medicine
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Adolescent ,Sarcoma ,Disease-Free Survival ,Cohort Studies ,Observational Studies as Topic ,Young Adult ,Clinical Trials, Phase III as Topic ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Antineoplastic Combined Chemotherapy Protocols ,Rhabdomyosarcoma ,Developmental and Educational Psychology ,Humans ,Prospective Studies ,Neoplasm Recurrence, Local ,Child ,Randomized Controlled Trials as Topic ,Retrospective Studies - Abstract
Background: Adolescent and young adult patients with rhabdomyosarcoma often have poorer outcomes than do children. We aimed to compare the findings of adolescent and young adult patients with children enrolled in two prospective clinical protocols. Methods: This retrospective observational analysis was based on data from the European paediatric Soft tissue sarcoma Study Group (EpSSG) rhabdomyosarcoma 2005 trial (phase 3 randomised trial for localised rhabdomyosarcoma, open from April, 2006, to December, 2016) and the EpSSG MTS 2008 protocol (prospective, observational, single-arm study for metastatic rhabdomyosarcoma, open from June, 2010, to December, 2016), which involved 108 centres from 14 different countries in total. For this analysis, patients were categorised according to their age into children (age 0–14 years) and adolescents and young adults (age 15–21 years). For the analysis of adherence to treatment and toxicity, only patients with high-risk localised rhabdomyosarcoma included in the randomised part of the rhabdomyosarcoma 2005 study were considered. The primary outcome of event-free survival (assessed in all participants) was defined as the time from diagnosis to the first event (eg, tumour progression, relapse) or to the latest follow-up. Secondary outcomes were overall survival, response to chemotherapy, and toxicity. Findings: Our analysis included 1977 patients, 1720 children (median age 4·7 years; IQR 2·6–8·4) and 257 adolescents and young adults (16·6 years; 15·8–18·0). 1719 patients were from the EpSSG rhabdomyosarcoma 2005 study (1523 aged
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- 2022
16. Linking EORTC QLQ-C-30 and PedsQL/PEDQOL physical functioning scores in patients with osteosarcoma
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Axel Budde, Katja Baust, Leonie Weinhold, Mark Bernstein, Stefan Bielack, Catharina Dhooge, Lars Hjorth, Katherine A. Janeway, Meriel Jenney, Mark D. Krailo, Neyssa Marina, Rajaram Nagarajan, Sigbjørn Smeland, Matthew R. Sydes, Patricia De Vos, Jeremy Whelan, Andreas Wiener, Gabriele Calaminus, and Matthias Schmid
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Physical functioning quality-of-life (QoL) ,Adult ,Cancer Research ,Osteosarcoma ,Adolescent ,Patient-reported outcome (PRO) ,Medizin ,EORTC QLQ-C30 ,Bone Neoplasms ,Breast Neoplasms ,humanities ,Score linking ,Paediatric quality of life questionnaire (PEDQOL) ,Oncology ,Paediatric quality of life inventory (PedsQL) ,Surveys and Questionnaires ,Medicine and Health Sciences ,Quality of Life ,Humans ,Female ,Childhood cancer ,Child - Abstract
Purpose: The available questionnaires for quality-of-life (QoL) assessments are age-group specific, limiting comparability and impeding longitudinal analyses. The comparability of measurements, however, is a necessary condition for gaining scientific evidence. To overcome this problem, we assessed the viability of harmonising data from paediatric and adult patient-reported outcome (PRO) measures. Method: To this end, we linked physical functioning scores from the Paediatric Quality of Life Inventory (PedsQL) and the Paediatric Quality of Life Questionnaire (PEDQOL) to the European Organisation for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-C30) for adults. Samples from the EURAMOS-1 QoL sub-study of 75 (PedsQL) and 112 (PEDQOL) adolescent osteosarcoma patients were concurrently administered both paediatric and adult questionnaires on 98 (PedsQL) and 156 (PEDQOL) occasions. We identified corresponding scores using the single-group equipercentile linking method. Results: Linked physical functioning scores showed sufficient concordance to the EORTC QLQ-C30: Lin's r Z 0.74 (PedsQL) and Lin's r Z 0.64 (PEDQOL). Conclusion: Score linking provides clinicians and researchers with a common metric for assessing QoL with PRO measures across the entire lifespan of patients. (C) 2022 The Author(s). Published by Elsevier Ltd.
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- 2022
17. Therapy and prognostic significance of regional lymph node involvement in embryonal rhabdomyosarcoma: a report from the European paediatric Soft tissue sarcoma Study Group
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Myriam Ben-Arush, Veronique Minard-Colin, Giovanni Scarzello, Raquel D. Fajardo, Sheila Terwisscha Van Scheltinga, Valérie Bernier, Meriel Jenney, Soledad Gallego, Ilaria Zanetti, Maja Cesen, Johannes H.M. Merks, and Gianni Bisogno
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Cancer Research ,History ,Polymers and Plastics ,Lymph node involvement ,Infant ,Pediatric oncology ,Prognosis ,Chemotherapy ,Embryonal rhabdomyosarcoma ,Industrial and Manufacturing Engineering ,Disease-Free Survival ,Oncology ,Antineoplastic Combined Chemotherapy Protocols ,Rhabdomyosarcoma ,Humans ,Rhabdomyosarcoma, Embryonal ,Lymph Nodes ,Business and International Management ,Child ,Rhabdomyosarcoma, Alveolar - Abstract
Regional lymph node disease (N1) is a component of the risk-based treatment stratification in rhabdomyosarcoma (RMS). The purpose of this study was to determine the contribution of nodal disease to the prognosis of patients with non-metastatic embryonal RMS (ERMS) and analyse their outcome by treatment received.Between 2005 and 2016, 1294 children with ERMS were enrolled in the European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS 2005 protocol, 143 patients with N1. Treatment comprised 9 cycles of ifosfamide, vincristine and dactinomycin. Some patients also received doxorubicin and/or maintenance if enrolled in the randomised studies. Local treatment was planned after 4 cycles of chemotherapy and included surgery to remove macroscopic residual tumour and/or radiotherapy (primary tumour and involved nodes).N1 patients were older and presented with tumours of unfavourable size, invasiveness, site and resectability. Unlike alveolar RMS, nodal involvement was more frequent in the head and neck area and rare in extremity sites. The 5-year event-free and overall survival were 75.5% and 86.3% for patients with N0, and 65.2% and 70.7% for patients with N1, respectively. The nodal involvement and the result of surgery at diagnosis (Intergroup Rhabdomyosarcoma Study group) were independent prognostic factors on multivariate analysis. Considering only patients with N1 ERMS, we were not able to identify any treatment variables which correlated with the outcome.In the case of nodal involvement, patients with ERMS present different characteristics and a better outcome than alveolar RMS. Regional nodal involvement is an independent prognostic factor in ERMS, therefore it is appropriate to include this population in the high-risk category.
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- 2022
18. Perianal/perineal rhabdomyosarcoma: Results of the SIOP MMT 95, Italian RMS 96, and EpSSG RMS 2005 studies
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Timothy Rogers, Ilaria Zanetti, Beatrice Coppadoro, Hélène Martelli, Meriel Jenney, Veronique Minard‐Colin, Sheila E. J. Terwisscha van Scheltinga, Clare Skerritt, Raquel Dávila Fajardo, Florent Guérin, Anna Kelsey, Johannes H. M. Merks, Henry Mandeville, Gabriela Guillén, Heidi Glosli, Federica De Corti, and Gianni Bisogno
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Male ,Adolescent ,perianal ,Infant ,Hematology ,Young Adult ,pediatric ,Oncology ,perineal ,rhabdomyosarcoma ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Organometallic Compounds ,Humans ,Mesenchymoma ,Female ,Rhabdomyosarcoma, Embryonal ,Neoplasm Recurrence, Local ,Child - Abstract
Rhabdomyosarcoma of the perianal/perineal region (PRMS) is rare, with poor survival and limited understanding of the functional consequences of treatment.International Society of Pediatric Oncology (SIOP) malignant mesenchymal tumor (MMT) 95, Italian RMS 96, and European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS 2005 studies were interrogated to identify factors that impact survival; in RMS 2005, functional outcomes were analyzed.Fifty patients (nonmetastatic) were identified, median age 6.4 years (range: 0.1-19.6): 29 male, 21 female. Tumors were5 cm in 33 patients. Histopathological subtype was alveolar in 35. Lymph nodes were involved in 23 patients. In RMS 2005, 16/21 (76%) tested alveolar tumors had positive FOXO1 fusion status. Diagnostic biopsy was performed in 37. Primary resection (13) was complete (R0) in one. Delayed primary excision (16) was complete in three. Radiotherapy (RT) in 34/50 patients included external beam (28), brachytherapy (3), and both (3). Nodal RT was given in 16/23 N1 patients (70%). Median follow-up of alive patients (29) was 84.1 months (range: 3.6-221.1). Relapse or progression occurred in 24 patients (48%), 87% were fatal and most events (63%) were locoregional. Five-year event-free survival (EFS) was 47.8 (95% CI: 32.8-61.3), and 5-year overall survival (OS) was 52.6 (95% CI: 36.7-66.2), with age ≥10 years and tumor size5 cm impacting 5-year EFS and OS (p .05). Functional outcome data showed bowel, genito-urinary, and psychological issues; fecal incontinence in four of 21 survivors, and urinary symptoms in two of 21.About 60% of patients with nonmetastatic PRMS survive; older patients and those with large tumors have the worst outcomes. Biopsy should be the initial procedure, and definitive local therapy individualized. Quality-of-life and functional studies are needed to better understand the consequences of treatment.
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- 2022
19. Localised rhabdomyosarcoma in infants (<12 months) and young children (12–36 months of age) treated on the EpSSG RMS 2005 study
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Daniel Orbach, Anna Kelsey, Gianni Bisogno, Ilaria Zanetti, Veronique Minard-Colin, Johannes H. M. Merks, Olga Slater, Mette Jorgensen, Meriel Jenney, Heidi Glosli, Mark N. Gaze, Beatrice Coppadoro, Maja Cesen, Federica De Corti, Soledad Gallego, Naima Smeulders, Andrea C. Ferrari, and Jennifer E. Gains
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Male ,Cancer Research ,Pediatrics ,medicine.medical_specialty ,History ,medicine.medical_treatment ,Brachytherapy ,Young children ,Localised disease ,History, 21st Century ,Median follow-up ,Rhabdomyosarcoma ,Medicine ,Humans ,Radical surgery ,Child ,Preschool ,EpSSG ,Infants ,RMS 2005 ,Child, Preschool ,Female ,Infant ,Infant, Newborn ,Chemotherapy ,business.industry ,medicine.disease ,Newborn ,Chemotherapy regimen ,21st Century ,Radiation therapy ,Oncology ,business - Abstract
Infants (12 months) with rhabdomyosarcoma have historically had poorer outcome than the older age groups. We present outcomes for infants and young children aged 12-36 months with localised rhabdomyosarcoma with a particular emphasis on infants.All children less than 36 months of age enrolled on the EpSSG RMS 2005 study for localised disease are included. Treatment comprised chemotherapy, local surgery and/or radiation therapy adapted to risk group and age. Main outcome measures were event free survival (EFS) and overall survival (OS).Outcome data were available for 485/490 patients aged less than 36 months, 110 were infants. Infants received chemotherapy according to the risk group with no toxic deaths. Radiotherapy was delivered to 33.6% of infants and 63.5% of 12-36 months old, with respectively 41.7% and 22.2% receiving brachytherapy. Radical surgery was performed in 62% of infants and 57.1% of 12-36 months old. Median follow up for patients who are alive (n = 393) was 72.7 months (range 6.9-158.2). Five-year OS for infants was 88.4% (95%CI 80.3-93.2), which is significantly better than the OS in 12-36 months old patients of 78.0% (95%CI 73.2-82.0; p = 0.0204). Five-year EFS for infants was 72.5% (95%CI 62.8-80.0) compared with 66.1% (95%CI 61.0-70.7; p = 0.2663) for 12-36 months old.Infants treated on RMS 2005 achieved excellent EFS and OS. The EpSSG RMS 2005 chemotherapy regimen, combined with an increase in the application of adequate local therapy, improvements in imaging and supportive care and potentially favourable patients' characteristics may have contributed to these results.
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- 2022
20. Indeterminate Pulmonary Nodules at Diagnosis in Rhabdomyosarcoma
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Gian Luca De Salvo, Gianni Bisogno, Meriel Jenney, Carlo Morosi, Daniel Orbach, Bas Vaarwerk, Ilaria Zanetti, Hervé Brisse, Andrea Ferrari, Julia C. Chisholm, Johannes H. M. Merks, Kieran McHugh, Nadège Corradini, Rick R. van Rijn, Radiology and Nuclear Medicine, CCA - Cancer Treatment and Quality of Life, and Paediatric Oncology
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Male ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Time Factors ,Adolescent ,Soft Tissue Neoplasms ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Predictive Value of Tests ,Risk Factors ,Rhabdomyosarcoma ,medicine ,Humans ,In patient ,Clinical significance ,Progression-free survival ,Child ,business.industry ,Soft tissue sarcoma ,Infant, Newborn ,Infant ,Solitary Pulmonary Nodule ,Nodule (medicine) ,medicine.disease ,Progression-Free Survival ,Tumor Burden ,Europe ,Oncology ,030220 oncology & carcinogenesis ,Predictive value of tests ,Child, Preschool ,Multiple Pulmonary Nodules ,Female ,Radiology ,medicine.symptom ,Indeterminate ,business ,Tomography, X-Ray Computed - Abstract
Purpose To evaluate the clinical significance of indeterminate pulmonary nodules at diagnosis (defined as ≤ 4 pulmonary nodules < 5 mm or 1 nodule measuring ≥ 5 and < 10 mm) in patients with pediatric rhabdomyosarcoma (RMS). Patients and Methods We selected patients with supposed nonmetastatic RMS treated in large pediatric oncology centers in the United Kingdom, France, Italy, and the Netherlands, who were enrolled in the European Soft Tissue Sarcoma Study Group (E pSSG) RMS 2005 study. Patients included in the current study received a diagnosis between September 2005 and December 2013, and had chest computed tomography scans available for review that were done at time of diagnosis. Local radiologists were asked to review the chest computed tomography scans for the presence of pulmonary nodules and to record their findings on a standardized case report form. In the E pSSG RMS 2005 Study, patients with indeterminate pulmonary nodules were treated identically to patients without pulmonary nodules, enabling us to compare event-free survival and overall survival between groups by log-rank test. Results In total, 316 patients were included; 67 patients (21.2%) had indeterminate pulmonary nodules on imaging and 249 patients (78.8%) had no pulmonary nodules evident at diagnosis. Median follow-up for survivors (n = 258) was 75.1 months; respective 5-year event-free survival and overall survival rates (95% CI) were 77.0% (64.8% to 85.5%) and 82.0% (69.7% to 89.6%) for patients with indeterminate nodules and 73.2% (67.1% to 78.3%) and 80.8% (75.1% to 85.3%) for patients without nodules at diagnosis ( P = .68 and .76, respectively). Conclusion Our study demonstrated that indeterminate pulmonary nodules at diagnosis do not affect outcome in patients with otherwise localized RMS. There is no need to biopsy or upstage patients with RMS who have indeterminate pulmonary nodules at diagnosis.
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- 2019
21. Non-parameningeal head and neck rhabdomyosarcoma in children, adolescents, and young adults: Experience of the European paediatric Soft tissue sarcoma Study Group (EpSSG) - RMS2005 study
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Soledad Gallego, Meriel Jenney, Heidi Glosli, Gianni Bisogno, Daniel Orbach, Anna Kelsey, Gian L. De Salvo, Mark N. Gaze, Janet Shipley, Johannes H. M. Merks, Julia C. Chisholm, Kieran McHugh, Henry Mandeville, Veronique Minard-Colin, Ilaria Zanetti, Nadège Corradini, EpSSG members, Ludi E. Smeele, Frédéric Kolb, Andrea C. Ferrari, Oral and Maxillofacial Surgery, and CCA - Cancer Treatment and Quality of Life
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0301 basic medicine ,Male ,Cancer Research ,Time Factors ,medicine.medical_treatment ,RMS2005 ,0302 clinical medicine ,Risk Factors ,Rhabdomyosarcoma ,Prospective Studies ,Young adult ,Israel ,Child ,Children ,Soft tissue sarcoma ,Age Factors ,Chin ,Progression-Free Survival ,Europe ,medicine.anatomical_structure ,Oncology ,Head and Neck Neoplasms ,030220 oncology & carcinogenesis ,Child, Preschool ,Lymphatic Metastasis ,Disease Progression ,Female ,EpSSG ,Brazil ,Adult ,medicine.medical_specialty ,Adolescent ,Argentina ,Context (language use) ,Risk Assessment ,03 medical and health sciences ,Young Adult ,Internal medicine ,Head and neck non-parameningeal primary ,medicine ,Humans ,business.industry ,Infant ,Cheek ,medicine.disease ,Nasolabial fold ,Adolescents and young adults ,Radiation therapy ,030104 developmental biology ,Neoplasm Recurrence, Local ,business - Abstract
Background/objectives The primary aim of this study was to analyse and evaluate the impact of different local treatments on the pattern of relapse in children with primary head and neck non-parameningeal (HNnPM) rhabdomyosarcoma (RMS), treated in the European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS2005 study. The secondary aim was to assess whether current risk stratification is valid for this specific site. Design/methods This study includes all patients with localised HNnPM RMS enrolled in the RMS2005 study between 2005 and 2016. Treatment comprised chemotherapy adapted to risk group, with local surgery and/or radiation therapy. The main outcome measures were event-free survival (EFS) and overall survival (OS). Results A total of 165 patients were identified; the median age was 6.4 years (range, 0.1–25). The most common tumour sites were cheek/chin (22%) and nasal ala/nasolabial fold (20%). Histology was unfavourable for 40%, and regional nodal involvement present in 26%. Local therapy included surgery (58%) and/or radiotherapy (72%) to primary tumour and/or regional lymph nodes. After a median follow-up of 66 months (range, 6–158), 42 patients experienced an event, and 17 are still alive. Tumour events were frequent in oral primary (36%), parotid site (26%), cheek/chin (24%), and nasal ala/nasolabial fold (24%) and included locoregional failure in 84% of cases. The 5-year EFS and OS were 75% (95% confidence interval [CI]: 67.3–81.2) and 84.9% (95% CI: 77.5–89.7), respectively. Favourable histology was associated with a better EFS (82.3% versus 64.6%; p = 0.02) and nodal spread with a worse OS (88.6% versus 76.1%; p = 0.04). Different sublocations within the HNnPM primary did not have significant impact on outcome. Conclusion Locoregional relapse/progression is the main tumour failure event in this site. Despite frequent unfavourable risk factors, HNnPM RMS remains a favourable location in the context of a risk-adapted strategy.
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- 2021
22. Severe toxicity free survival: physician-derived definitions of unacceptable long-term toxicities following acute lymphocytic leukaemia
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Liv Andrés-Jensen, Andishe Attarbaschi, Edit Bardi, Shlomit Barzilai-Birenboim, Deepa Bhojwani, Melanie M Hagleitner, Christina Halsey, Arja Harila-Saari, Raphaele R L van Litsenburg, Melissa M Hudson, Sima Jeha, Motohiro Kato, Leontien Kremer, Wojciech Mlynarski, Anja Möricke, Rob Pieters, Caroline Piette, Elizabeth Raetz, Leila Ronceray, Claudia Toro, Maria Grazia Valsecchi, Lynda M Vrooman, Sigal Weinreb, Naomi Winick, Kjeld Schmiegelow, Madeline R Adams, Liv Andres-Jensen, Katja Baust, Tineke Boesten, Gabriele Calaminus, Rachel Conyers, Anne-Sophie Darlington, Maëlle de Ville, Gabriele Escherich, Melanie Hagleitner, Jen-Yin Hou, Ting-Huan Huang, Melissa Hudson, Meriel Jenney, Maryna Krawczuk-Rybak, Leontine Kremer, Melchior Lautem, Hse-Che Liu, Elixabet Lopez Lopez, Marion Mateos, Katarzyna Muszynska-Roslan, Riitta Niinimaki, Toby Trahair, Inge van der Sluis, Raphaële van Litsenburg, Lynda Vrooman, Andreas Wiener, Michihiro Yano, Ting-Chi Yeh, Ester Zapotocka, Andres-Jensen, L, Attarbaschi, A, Bardi, E, Barzilai-Birenboim, S, Bhojwani, D, Hagleitner, M, Halsey, C, Harila-Saari, A, van Litsenburg, R, Hudson, M, Jeha, S, Kato, M, Kremer, L, Mlynarski, W, Moricke, A, Pieters, R, Piette, C, Raetz, E, Ronceray, L, Toro, C, Valsecchi, M, Vrooman, L, Weinreb, S, Winick, N, and Schmiegelow, K
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medicine.medical_specialty ,Activities of daily living ,MEDLINE ,Antineoplastic Agents ,Blindness ,Antineoplastic Agent ,03 medical and health sciences ,0302 clinical medicine ,Refractory ,Physicians ,Medicine ,Humans ,Acute lymphocytic leukaemia ,Renal Insufficiency ,Intensive care medicine ,Child ,Hearing Loss ,Hearing Lo ,Severe toxicity ,MED/01 - STATISTICA MEDICA ,business.industry ,Cancer ,Hematology ,Hematologic Disease ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,medicine.disease ,Hematologic Diseases ,Progression-Free Survival ,Blindne ,Clinical trial ,Transplantation ,Physician ,030220 oncology & carcinogenesis ,business ,Human ,030215 immunology - Abstract
5-year overall survival rates have surpassed 90% for childhood acute lymphocytic leukaemia, but survivors are at risk for permanent health sequelae. Although event-free survival appropriately represents the outcome for cancers with poor overall survival, this metric is inadequate when cure rates are high but challenged by serious, persistent complications. Accordingly, a group of experts in paediatric haematology-oncology, representative of 17 international acute lymphocytic leukaemia study groups, launched an initiative to construct a measure, designated severe toxicity-free survival (STFS), to quantify the occurrence of physician-prioritised toxicities to be integrated with standard cancer outcome reporting. Five generic inclusion criteria (not present before cancer diagnosis, symptomatic, objectifiable, of unacceptable severity, permanent, or requiring unacceptable treatments) were used to assess 855 health conditions, which resulted in inclusion of 21 severe toxicities. Consensus definitions were reached through a modified Delphi process supplemented by two additional plenary meetings. The 21 severe toxicities include severe adverse health conditions that substantially affect activities of daily living and are refractory to therapy (eg, refractory seizures), are without therapeutic options (eg, blindness), or require substantially invasive treatment (eg, cardiac transplantation). Incorporation of STFS assessment into clinical trials has the potential to improve and diversify treatment strategies, focusing not only on traditional outcome events and overall survival but also the frequencies of the most severe toxicities. The two major aims of this Review were to: prioritise and define unacceptable long-term toxicity for patients with childhood acute lymphocytic leukaemia, and define how these toxicities should be combined into a composite quantity to be integrated with other reported outcomes. Although STFS quantifies the clinically unacceptable health tradeoff for cure using childhood acute lymphocytic leukaemia as a model disease, the prioritised severe toxicities are based on generic considerations of relevance to any other cancer diagnosis and age group.
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- 2021
23. Combined resistance and aerobic exercise intervention improves fitness, insulin resistance and quality of life in survivors of childhood haemopoietic stem cell transplantation with total body irradiation
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Ruth Elson, Keith Tolfrey, Jacqueline Cornish, Meriel Jenney, Nikki L Davis, Michael C. Stevens, Andrew D. Moss, Elizabeth Crowne, and Claire E. Stewart
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,RJ101 ,RC1200 ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,Cancer Survivors ,Quality of life ,Internal medicine ,medicine ,Humans ,Aerobic exercise ,Longitudinal Studies ,Child ,Exercise ,business.industry ,Hematopoietic Stem Cell Transplantation ,Resistance Training ,Cardiorespiratory fitness ,Hematology ,Total body irradiation ,Prognosis ,medicine.disease ,Combined Modality Therapy ,Transplantation ,Cardiorespiratory Fitness ,Oncology ,Hematologic Neoplasms ,030220 oncology & carcinogenesis ,Pediatrics, Perinatology and Child Health ,Body Composition ,Quality of Life ,Homeostatic model assessment ,Lean body mass ,Female ,Insulin Resistance ,business ,Whole-Body Irradiation ,Follow-Up Studies ,030215 immunology - Abstract
Purpose: To investigate the effects of a supervised combined resistance and aerobic training programme on cardiorespiratory fitness, body composition, insulin resistance and quality of life (QoL) in survivors of childhood haematopoietic stem cell transplantation (HSCT) with total body irradiation (TBI).\ud Participants: HSCT/TBI survivors (n = 20; 8 females). Mean (range) for age at study and time since HSCT/TBI was 16.7 (10.9‐24.5) and 8.4 (2.3‐16.0) years, respectively.\ud Methods: After a 6‐month run‐in, participants undertook supervised 45‐ to 60‐minute resistance and aerobic training twice weekly for 6 months, with a 6‐month follow‐up. The following assessments were made at 0, 6 (start of exercise programme), 12 (end of exercise programme) and 18 months: Body composition via dual energy X‐ray absorptiometry, homeostatic model assessment of insulin resistance (HOMA‐IR), cardiorespiratory fitness (treadmill‐based peak rate of oxygen uptake (VO2 peak) test), QoL questionnaires (36‐Item Short Form Health Survey (SF‐36) and Minneapolis‐Manchester Quality of Life Instrument (MMQL).\ud Results: Results expressed as mean (standard deviation) or geometric mean (range). There were significant improvements in VO2 peak (35.7 (8.9) vs 41.7 (16.1) mL/min/kg, P = 0.05), fasted plasma insulin (16.56 (1.48‐72.8) vs 12.62 (1.04‐54.97) mIU/L, P = 0.03) and HOMA‐IR (3.65 (0.30‐17.26) vs 2.72 (0.22‐12.89), P = 0.02) after the exercise intervention. There were also significant improvements in the SF‐36 QoL general health domain (69.7 (14.3) vs 72.7 (16.0), P = 0.001) and the MMQL school domain (69.1 (25.2) vs (79.3 (21.6), P = 0.03) during the exercise intervention. No significant changes were observed in percentage body fat, fat mass or lean mass.\ud Conclusion: The supervised 6‐month combined resistance and aerobic exercise programme significantly improved cardiorespiratory fitness, insulin resistance and QoL in childhood HSCT/TBI survivors, with no change in body composition, suggesting a metabolic training effect on muscle. These data support a role for targeted physical rehabilitation services in this group at high risk of diabetes and cardiovascular disease.
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- 2020
24. Alveolar rhabdomyosarcoma with regional nodal involvement: Results of a combined analysis from two cooperative groups
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Sheila Terwisscha van Scheltinga, Gianni Bisogno, Meriel Jenney, David M. Parham, Daniel Orbach, Leo Mascarenhas, Ilaria Zanetti, Yueh Yun Chi, Johannes H. M. Merks, Lynn Million, Minjie Li, Gian Luca De Salvo, Douglas S. Hawkins, Veronique Minard-Colin, Soledad Gallego, Rajkumar Venkatramani, Suzanne L. Wolden, David A. Rodeberg, and Henry Mandeville
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Male ,medicine.medical_specialty ,Vincristine ,alveolar rhabdomyosarcoma ,medicine.medical_treatment ,Vinorelbine ,chemotherapy ,nodal involvement ,prognostic factors ,rhabdomyosarcoma ,Gastroenterology ,Article ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,Humans ,Rhabdomyosarcoma ,Child ,Rhabdomyosarcoma, Alveolar ,Retrospective Studies ,Chemotherapy ,Ifosfamide ,business.industry ,Soft tissue sarcoma ,Infant, Newborn ,Infant ,Hematology ,medicine.disease ,Prognosis ,Irinotecan ,Survival Rate ,Oncology ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Alveolar rhabdomyosarcoma ,Female ,Lymph Nodes ,business ,medicine.drug ,Follow-Up Studies - Abstract
Background Treatment of children and adolescents with alveolar rhabdomyosarcoma (ARMS) and regional nodal involvement (N1) have been approached differently by North American and European cooperative groups. In order to define a better therapeutic strategy, we analyzed two studies conducted between 2005 and 2016 by the European paediatric Soft tissue sarcoma Study Group (EpSSG) and Children's Oncology Group (COG). Methods We retrospectively identified patients with ARMS N1 enrolled in either EpSSG RMS2005 or in COG ARST0531. Chemotherapy in RMS2005 comprised ifosfamide + vincristine + dactinomycin + doxorubicin (IVADo), IVA and maintenance (vinorelbine, cyclophosphamide); in ARST0531, it consisted of either vincristine + dactinomycin + cyclophosphamide (VAC) or VAC alternating with vincristine + irinotecan (VI). Local treatment was similar in both protocols. Results The analysis of the clinical characteristics of 239 patients showed some differences between study groups: in RMS2005, advanced Intergroup Rhabdomyosarcoma Study Group (IRS) and large tumors predominated. There were no differences in outcomes between the two groups: 5-year event-free survival (EFS), 49% (95% confidence interval [CI]: 39-59) and 44% (95% CI: 30-58), and overall survival (OS), 51% (95% CI: 41-61) and 53.6% (95% CI: 40-68) in RMS2005 and ARST0531, respectively. In RMS2005, EFS of patients with FOXO1-positive tumors was significantly inferior to those with FOXO1-negative (49.3% vs 73%, P = .034). In contrast, in ARST0531, EFS of patients with FOXO1-positive tumors was 45% compared with 43.8% for those with FOXO1-negative. Conclusions The outcome of patients with ARMS N1 was similar in both protocols. However, patients with FOXO1 fusion-negative tumors enrolled in RMS2005 showed a significantly better outcome, suggesting that different strategies of chemotherapy may have an impact in the outcome of this subgroup of patients.
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- 2020
25. Paratesticular rhabdomyosarcoma-Impact of locoregional approach on patient outcome: A report from the European paediatric Soft tissue sarcoma Study Group (EpSSG)
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Gianni Bisogno, Ross J. Craigie, Anna Kelsey, Gabriela Guillén Burrieza, Gian Luca De Salvo, Timothy Rogers, Hélène Martelli, Beatrice Coppadoro, Florent Guérin, Naima Smeulders, Meriel Jenney, Federica De Corti, Ilaria Zanetti, and Sheila Terwisscha van Scheltinga
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,paratesticular ,Malignancy ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Testicular Neoplasms ,Median follow-up ,Rhabdomyosarcoma ,medicine ,Humans ,In patient ,Child ,Chemotherapy ,business.industry ,Soft tissue sarcoma ,Significant difference ,Infant ,Hematology ,medicine.disease ,Surgery ,Survival Rate ,pediatric ,Oncology ,030220 oncology & carcinogenesis ,Paratesticular rhabdomyosarcoma ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Guideline Adherence ,business ,rhabdomyosarcoma ,030215 immunology ,Follow-Up Studies - Abstract
BACKGROUND Paratesticular rhabdomyosarcoma (PT RMS) is rare compared to benign scrotal pathology. Inappropriate first surgery (InFS) required supplementary treatment to maintain excellent outcomes. Initial staging of regional lymph nodes is important. The aim of this study was to determine to what extent the quality of locoregional approach impacted on patient morbidity and survival. DESIGN/METHODS Analysis was performed on all nonmetastatic PT RMS patients enrolled in the European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS 2005 protocol. Aspects assessed were adherence to surgical guidelines and impact of protocol violations, relapse analysis, and survival outcomes. RESULTS Analysis was performed on 237 patients, with median follow up of 67.1 months. Median age was 9.0 years. InFS occurred in 75 of 237 (32%) patients. InFS required intensified chemotherapy (10) and local therapy. After InFS, 61 required primary reexcision and five delayed surgery. Of 26 recurrences, the risk of relapse was higher in patients ≥10 years (21/26) and was mainly locoregional in 16 of 26 recurrences (± metastatic). Sixteen of 26 died with 14 of 16 patients ≥10 years. Nodal relapse neither occurred when N1 nodes were identified at diagnosis, nor after surgical staging. Five-year overall survival (OS) at age
- Published
- 2020
26. A new standard of care for patients with high-risk rhabdomyosarcoma? – Authors' reply
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Soledad Gallego Melcon, Gianni Bisogno, Gian Luca De Salvo, Andrea C. Ferrari, Meriel Jenney, and Christophe Bergeron
- Subjects
Pediatrics ,medicine.medical_specialty ,Standard of care ,Cyclophosphamide ,business.industry ,Humans ,Standard of Care ,Vinorelbine ,Maintenance Chemotherapy ,Rhabdomyosarcoma ,medicine.disease ,Oncology ,medicine ,business ,Maintenance chemotherapy ,medicine.drug - Published
- 2020
27. Vinorelbine and continuous low-dose cyclophosphamide as maintenance chemotherapy in patients with high-risk rhabdomyosarcoma (RMS 2005): a multicentre, open-label, randomised, phase 3 trial
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Julia C. Chisholm, Sima Ferman, Soledad Gallego Melcon, Hélène Martelli, Meriel Jenney, Anna Kelsey, Gianni Bisogno, Myriam Weyl Ben‐Arush, Gian Luca De Salvo, Christophe Bergeron, Peter Múdry, Andrea Ferrari, Johannes H. M. Merks, Daniel Orbach, Ilaria Zanetti, Christine Devalck, Veronique Minard-Colin, Heidi Glosli, Michela Casanova, Paediatric Oncology, and CCA - Cancer Treatment and Quality of Life
- Subjects
0301 basic medicine ,education.field_of_study ,medicine.medical_specialty ,Ifosfamide ,business.industry ,Standard treatment ,Population ,Hazard ratio ,medicine.disease ,Vinorelbine ,Cancérologie ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Alveolar rhabdomyosarcoma ,Embryonal rhabdomyosarcoma ,education ,Rhabdomyosarcoma ,business ,medicine.drug - Abstract
Background: For more than three decades, standard treatment for rhabdomyosarcoma in Europe has included 6 months of chemotherapy. The European paediatric Soft tissue sarcoma Study Group (EpSSG) aimed to investigate whether prolonging treatment with maintenance chemotherapy would improve survival in patients with high-risk rhabdomyosarcoma. Methods: RMS 2005 was a multicentre, open-label, randomised, controlled, phase 3 trial done at 102 hospitals in 14 countries. We included patients aged 6 months to 21 years with rhabdomyosarcoma who were considered to be at high risk of relapse: those with non-metastatic incompletely resected embryonal rhabdomyosarcoma occurring at unfavourable sites with unfavourable age (≥10 years) or tumour size (>5 cm), or both; those with any non-metastatic rhabdomyosarcoma with nodal involvement; and those with non-metastatic alveolar rhabdomyosarcoma but without nodal involvement. Patients in remission after standard treatment (nine cycles of ifosfamide, vincristine, dactinomycin with or without doxorubicin, and surgery or radiotherapy, or both) were randomly assigned (1:1) to stop treatment or continue maintenance chemotherapy (six cycles of intravenous vinorelbine 25 mg/m2 on days 1, 8, and 15, and daily oral cyclophosphamide 25 mg/m2, on days 1–28). Randomisation was done by use of a web-based system and was stratified (block size of four) by enrolling country and risk subgroup. Neither investigators nor patients were masked to treatment allocation. The primary outcome was disease-free survival in the intention-to-treat population. Secondary outcomes were overall survival and toxicity. This trial is registered with EudraCT, number 2005-000217-35, and ClinicalTrials.gov, number NCT00339118, and follow-up is ongoing. Findings: Between April 20, 2006, and Dec 21, 2016, 371 patients were enrolled and randomly assigned to the two groups: 186 to stop treatment and 185 to receive maintenance chemotherapy. Median follow-up was 60·3 months (IQR 32·4–89·4). In the intention-to-treat population, 5-year disease-free survival was 77·6% (95% CI 70·6–83·2) with maintenance chemotherapy versus 69·8% (62·2–76·2) without maintenance chemotherapy (hazard ratio [HR] 0·68 [95% CI 0·45–1·02]; p=0·061), and 5-year overall survival was 86·5% (95% CI 80·2–90·9) with maintenance chemotherapy versus 73·7% (65·8–80·1) without (HR 0·52 [95% CI 0·32–0·86]; p=0·0097). Toxicity was manageable in patients who received maintenance chemotherapy: 136 (75%) of 181 patients had grade 3–4 leucopenia, 148 (82%) had grade 3–4 neutropenia, 19 (10%) had anaemia, two (1%) had thrombocytopenia, and 56 (31%) had an infection. One (1%) patient had a grade 4 non-haematological toxicity (neurotoxicity). Two treatment-related serious adverse events occurred: one case of inappropriate antidiuretic hormone secretion and one of a severe steppage gait with limb pain, both of which resolved. Interpretation: Adding maintenance chemotherapy seems to improve survival for patients with high-risk rhabdomyosarcoma. This approach will be the new standard of care for patients with high-risk rhabdomyosarcoma in future EpSSG trials. Funding: Fondazione Città della Speranza, Association Léon Berard Enfant Cancéreux, Clinical Research Hospital Program (French Ministry of Health), and Cancer Research UK., SCOPUS: ar.j, info:eu-repo/semantics/published
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- 2019
28. Germ cell tumours in children and adolescents
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Anthony Penn, Meriel Jenney, and James C. Nicholson
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Pediatrics, Perinatology and Child Health - Published
- 2018
29. Prognostic relevance of early radiologic response to induction chemotherapy in pediatric rhabdomyosarcoma: A report from the International Society of Pediatric Oncology Malignant Mesenchymal Tumor 95 study
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Daniel Orbach, Soledad Gallego, Meriel Jenney, Nathalie Cozic, Johanna H. van der Lee, Bas Vaarwerk, Christine Devalck, Johannes H. M. Merks, Willemijn B. Breunis, Anna Kelsey, Michael C. Stevens, Kieran McHugh, Odile Oberlin, Rick R. van Rijn, Mark N. Gaze, Julia C. Chisholm, Christophe Bergeron, Heidi Glosli, and Veronique Minard-Colin
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Chemotherapy ,business.industry ,Proportional hazards model ,medicine.medical_treatment ,Hazard ratio ,Induction chemotherapy ,Cancer ,medicine.disease ,Pediatric cancer ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Rhabdomyosarcoma ,business ,Progressive disease - Abstract
BACKGROUND: Early response to induction chemotherapy is used in current European guidelines to evaluate the efficacy of chemotherapy and subsequently to adapt treatment in pediatric patients with rhabdomyosarcoma (RMS). However, existing literature on the prognostic value of early radiologic response on survival is contradictory; here the prognostic value is analyzed with data from the International Society of Pediatric Oncology (SIOP) Malignant Mesenchymal Tumor 95 (MMT-95) study. METHODS: This study examined 432 Intergroup Rhabdomyosarcoma Study Grouping III (macroscopic residue) patients enrolled in the SIOP MMT-95 study with a response assessment after 3 courses of chemotherapy (a 2-dimensional assessment). Patients with progressive disease (PD) after 3 courses of chemotherapy were excluded (n57). Failure-free survival (FFS) and overall survival (OS), calculated with the Kaplan-Meier method, were compared for 3 groups (complete response [CR]/partial response [PR], objective response [OR], and no response [NR]). The prognostic impact of early response was assessed through the calculation of Cox proportional hazards. RESULTS: After 3 courses of chemotherapy, 85.2% of the patients had CR/PR, 8.6% had OR, and 6.3% had NR. For all patients, the 5-year FFS and OS rates were 60% (95% confidence interval [CI], 56%-65%) and 74% (95% CI, 70%-78%), respectively. However, a Cox proportional hazards regression analysis revealed no significant difference in FFS or OS between the response groups. The adjusted hazard ratios for an OR and NR were 1.09 (95% CI, 0.63-1.88) and 0.81 (95% CI, 0.39-1.67), respectively, for FFS and 0.91 (95% CI, 0.47-1.76) and 1.27 (95% CI, 0.61-2.64), respectively, for OS. CONCLUSIONS: No evidence was found for the idea that early radiologic response to chemotherapy is prognostic for survival for patients with RMS. Treatment adaptation based on early response (except for patients with PD) should, therefore, no longer be incorporated into future studies. (C) 2017 American Cancer Society.
- Published
- 2017
30. Quality of Life of Patients With Osteosarcoma in the European American Osteosarcoma Study-1 (EURAMOS-1): Development and Implementation of a Questionnaire Substudy
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Mark L. Bernstein, Andreas Wiener, Neyssa Marina, Jeremy Whelan, Katja Baust, Lars Hjorth, Gordana Jovic, Meriel Jenney, Patricia de Vos, Babasola O Popoola, Stefan S. Bielack, Mark Krailo, Gabriele Calaminus, Pancras C.W. Hogendoorn, Cristina Sauerland, Sigbjørn Smeland, Carmen Teske, Rajaram Nagarajan, Clara V Schweinitz, Matthew R. Sydes, and Kiana Kreitz
- Subjects
medicine.medical_specialty ,sarcoma ,Medizin ,Psychological intervention ,Disease ,INTERNATIONAL COLLABORATION ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,Quality of life ,law ,osteosarcoma ,ADOLESCENTS ,medicine ,Medicine and Health Sciences ,HISTOLOGIC RESPONSE ,cancer ,Young adult ,GENERIC CORE SCALES ,030304 developmental biology ,0303 health sciences ,Original Paper ,child ,business.industry ,MURAMYL TRIPEPTIDE ,survivors of childhood cancer ,General Medicine ,RANDOMIZED PHASE-III ,CHEMOTHERAPY ,CANCER ,humanities ,3. Good health ,Group Affiliation ,quality of life ,030220 oncology & carcinogenesis ,adolescent ,Cohort ,Physical therapy ,SURVIVAL ,young adult ,Observational study ,observational study ,business ,HIGH-GRADE OSTEOSARCOMA - Abstract
Background The quality of life (QoL) of patients with osteosarcoma (OS) may be adversely affected by the disease or its treatment. Therefore, it is important to understand the QoL of patients undergoing treatment for OS to improve the QoL. We report on the first prospective international QoL study that was embedded within a large randomized clinical trial from 4 national study groups. Objective This paper aimed to describe the QoL study development, methodology, accrual details, and characteristics of the QoL cohort. Methods A total of 2260 patients registered in the EURopean AMerican Osteosarcoma Study-1 (EURAMOS-1), of whom 97.92% (2213/2260) were eligible for the optional QoL assessment and could participate in terms of questionnaire availability. Overall, 61.86% (1369/2213) of patients and/or proxies completed the QoL evaluation at the first assessment time point (E1) after the start of preoperative treatment. The QoL measures used (self- and/or proxy reports) depending on the patient’s age and national study group. Participants and nonparticipants in the ancillary QoL study were compared regarding relevant demographic and disease-related characteristics at registration in the trial. Results The participation rate at time point E1 did not differ with regard to age, gender, the occurrence of pathological fracture, or the presence of any metastases at diagnosis. No differences were found regarding the primary tumor site. Only the national study group affiliation had an influence on participation. Participation decreased linearly with trial progress up to 20% at the final time point of QoL assessment. Conclusions This study demonstrates the feasibility of international cooperation for the purpose of assessing and understanding the QoL of pediatric and adolescent/young adult patients with cancer. Future outcomes of this QoL substudy will help to adapt interventions to improve QoL.
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- 2019
31. Nonparameningeal head and neck rhabdomyosarcoma in children and adolescents: Lessons from the consecutive International Society of Pediatric Oncology Malignant Mesenchymal Tumor studies
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Michael C. Stevens, Johannes H. M. Merks, Christine Devalck, Max M. van Noesel, Meriel Jenney, Christophe Bergeron, Véronique Mosseri, Anna Kelsey, Daniel Orbach, Bernadette Brenann, Veronique Minard-Colin, Catherine Rechnitzer, and Soledad Gallego
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Retrospective cohort study ,medicine.disease ,Surgery ,Radiation therapy ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Otorhinolaryngology ,030220 oncology & carcinogenesis ,Internal medicine ,Relative risk ,Malignant mesenchymal tumor ,Pediatric oncology ,Medicine ,Combined Modality Therapy ,business ,Rhabdomyosarcoma ,Survival rate - Abstract
Background This article reports risk factors and long-term outcome in localized nonparameningeal head and neck rhabdomyosarcomas in children and adolescents from a combined dataset from 3 consecutive international trials. Methods Data from 140 children (9.3% of total) prospectively enrolled in the International Society of Pediatric Oncology Malignant Mesenchymal Tumor (SIOP-MMT)-84/89/95 studies were analyzed. Results Primary site was: superficial face in 46%; oral cavity (21%); neck (19%); and salivary glands (14%). Local control was achieved in 96%, but 49% relapsed (locoregionally 91%). At median follow-up of 10 years, 5-year overall survival (OS) was 74.7% (67.4% to 81.9%) and event-free survival 48.9% (40.6% to 57.2%), although this improved with successive studies. Radiotherapy (RT) as first-line treatment was independently prognostic for event-free survival (relative risk [RR] = 0.4 [range, 0.2–0.7]; p
- Published
- 2016
32. Conservative strategy in infantile fibrosarcoma is possible: The European paediatric Soft tissue sarcoma Study Group experience
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Bernadette Brennan, Gianni Bisogno, Michaela Casanova, Daniel Orbach, Gian Luca De Salvo, Nadine Francotte, Michael C. Stevens, Angela De Paoli, Max M. van Noesel, Christophe Bergeron, Johannes H. M. Merks, Peter Múdry, Rito Alaggio, Dominique Ranchère, Andrea Ferrari, Meriel Jenney, Anna Kelsey, Soledad Gallego, CCA -Cancer Center Amsterdam, and Paediatric Oncology
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Male ,Reoperation ,ETV6-NTRK3 transcript ,medicine.medical_specialty ,Cancer Research ,Fibrosarcoma ,medicine.medical_treatment ,Antineoplastic Agents ,Soft Tissue Neoplasms ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Cost of Illness ,030225 pediatrics ,Infantile fibrosarcoma ,medicine ,Humans ,Combined Modality Therapy ,Chemotherapy ,Prospective Studies ,Watchful Waiting ,Prospective cohort study ,Neoplasm Staging ,Cancer ,business.industry ,Soft tissue sarcoma ,Infant ,medicine.disease ,Newborn ,Surgery ,Oncology ,Regimen ,Treatment Outcome ,Chemotherapy, Adjuvant ,Vincristine ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,Dactinomycin ,Feasibility Studies ,Female ,Infantile Fibrosarcoma ,business ,Watchful waiting ,Follow-Up Studies ,Rare disease - Abstract
Background Infantile fibrosarcoma (IFS) is a very rare disease occurring in young infants characterised by a high local aggressiveness but overall with a favourable survival. To try to reduce the total burden of therapy, the European pediatric Soft tissue sarcoma Study Group has developed conservative therapeutic recommendations according to initial resectability. Material and methods Between 2005 and 2012, children with localised IFS were prospectively registered. Initial surgery was suggested only if possible without mutilation. Patients with initial complete (IRS-group I/R0) or microscopic incomplete (group II/R1) resection had no further therapy. Patients with initial inoperable tumour (group III/R2) received first-line vincristine-actinomycin-D chemotherapy (VA). Delayed conservative surgery was planned after tumour reduction. Aggressive local therapy (mutilating surgery or external radiotherapy) was discouraged. Results A total of 50 infants (median age 1.4 months), were included in the study. ETV6-NTRK3 transcript was present in 87.2% of patients where investigation was performed. According to initial surgery, 11 patients were classified as group I, 8 as group II and 31 as group III. VA chemotherapy was first delivered to 25 children with IRS-III/R2 and one with IRS-II/R1 disease. Response rate to VA was 68.0%. Mutilating surgery was only performed in three cases. After a median follow-up of 4.7 years (range 1.9–9.0), 3-year event-free survival and overall survival were respectively 84.0% (95% confidence interval [CI] 70.5–91.7) and 94.0% (95% CI 82.5–98.0). Conclusions Conservative therapy is possible in IFS as only three children required mutilating surgery, and alkylating or anthracycline based chemotherapy was avoided in 71.0% of patients needing chemotherapy. VA regimen should be first line therapy in order to reduce long term effects.
- Published
- 2016
33. Quality of life Evaluation in patients receiving Steroids (the QuESt tool): initial development in children and young people with acute lymphoblastic leukaemia
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Michael Robling, J Tomlins, A Johnson, Meriel Jenney, John D. Grainger, M Adams, M Velangi, and Stephen Morris
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Adult ,medicine.medical_specialty ,Adolescent ,Psychometrics ,Validity ,Dexamethasone ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Surveys and Questionnaires ,medicine ,Humans ,030212 general & internal medicine ,Cognitive interview ,Young adult ,Child ,Psychiatry ,Glucocorticoids ,Face validity ,Interpretative phenomenological analysis ,business.industry ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,United Kingdom ,Mood ,030220 oncology & carcinogenesis ,Pediatrics, Perinatology and Child Health ,Quality of Life ,business ,Adolescent health ,Clinical psychology - Abstract
BackgroundThe powerful cytotoxic and immunomodulatory effects of corticosteroids are an important element of the success that has been achieved in the treatment of acute lymphoblastic leukaemia (ALL). In addition to physical side effects, corticosteroids can adversely influence behaviour, cognitive function and mood leading to significantly impaired quality of life (QoL). A number of tools exist for assessing QoL, but none of these specifically examines changes attributable to steroids.MethodsChildren and young adults aged 8–24 years and parents of children receiving maintenance therapy for ALL from four UK centres were invited to participate. The study comprised three stages carried out over 2 years: (1) focus groups and interviews where participants were asked to describe their experiences of dexamethasone; (2) analysis of questionnaires sent to healthcare professionals and patients to evaluate the importance and relevance of the questions; and (3) cognitive interviewing.ResultsInterpretative phenomenological analysis of focus group and interview transcripts identified that dexamethasone adversely influenced behaviour, appetite, body image, mood and family relationships. 157 electronic survey responses were analysed leading to further item development. Cognitive interviewing confirmed face validity and internal consistency. QuESt comprises 28 questions within four domains and has three age-specific versions.ConclusionsQuESt is the first treatment-specific QoL measure for children and young adults receiving corticosteroids. It can be completed in 10–15 min by children aged ≥8 years. Further validity and reliability testing will be undertaken. Although the initial application is for ALL, QuESt may also be a valuable tool for understanding the impact of corticosteroids in other paediatric conditions.
- Published
- 2015
34. Abstract B15: Genomic classification and prognosis in rhabdomyosarcoma: A report from the Children’s Oncology Group, the Institute of Cancer Research, and the National Cancer Institute
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Jack F. Shern, Janet Shipley, Susanne A. Gatz, Xinyu Wen, Anna Kelsey, Donald A. Barkauskas, David G. Hall, Joanna Selfe, Rebecca Brown, Julia C. Chisholm, Javed Khan, Douglas S. Hawkins, Meriel Jenney, Rajesh Patidar, Marielle E. Yohe, Corinne M. Linardic, Young Min Song, Jun Wei, Erin Rudinski, and Stephen X. Skapek
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Oncology ,Neuroblastoma RAS viral oncogene homolog ,Cancer Research ,medicine.medical_specialty ,education.field_of_study ,business.industry ,Population ,Cancer ,medicine.disease ,Pediatric cancer ,Internal medicine ,Cancer research ,medicine ,Sarcoma ,HRAS ,business ,Rhabdomyosarcoma ,education ,Survival rate - Abstract
Purpose: Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of childhood. Despite aggressive therapy, the 5-year survival rate for patients with metastatic or recurrent disease remains poor and beyond PAX-FOXO1 fusion status, no genomic markers are available for risk stratification. We therefore performed a large-scale study through an international consortium to more accurately determine the incidence of driver mutations and their association with clinical outcome. Patients and Method: Formalin-fixed, paraffin-embedded material was collected from patients enrolled on Children’s Oncology Group trials and UK patients enrolled on MMT trials. Pathology was reviewed centrally and extracted DNA was subjected to targeted capture sequencing using a panel of 39 genes previously associated with RMS. Mutations, indels, deletions, gene amplifications, and copy number variation was called using analysis pipelines developed at the NCI. Results: DNA from six hundred and forty-one patients was suitable for analyses. A median of 1 variant call was found per tumor. Mutation of a RAS isoform was found in 29% of all fusion negative cases, mutation of a RAS pathway member was seen in greater than 50% of cases, and 24% had no putative driver mutation identified. BCOR (15%), NF1 (11%), and TP53 (12%) mutations were found at a higher incidence than previously reported. Interestingly, mutations in HRAS were notable in the infant population whereas those in NRAS were enriched in adolescents. Among infants < 1 year, 71% of cases harbored a mutation in HRAS or KRAS. In contrast, mutation of MYOD1 was associated with an older age and a head and neck primary site. Finally, 29% of the evaluated tumors harbored multiple driver mutations consistent with subclonal variation and tumor heterogeneity in fusion-negative RMS. Conclusion: This is the largest genomic characterization of clinically annotated RMS tumors to date and provides genetic features that refine risk stratification and can be incorporated into prospective trials. Citation Format: Jack Shern, Joanna Selfe, Rajesh Patidar, Young Song, Marielle Yohe, Jun Wei, Xinyu Wen, Erin Rudinski, Donald Barkauskas, David Hall, Corinne Linardic, Meriel Jenney, Julia Chisholm, Rebecca Brown, Anna Kelsey, Susanne Gatz, Stephen Skapek, Douglas Hawkins, Janet Shipley, Javed Khan. Genomic classification and prognosis in rhabdomyosarcoma: A report from the Children’s Oncology Group, the Institute of Cancer Research, and the National Cancer Institute [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr B15.
- Published
- 2020
35. Addition of dose-intensified doxorubicin to standard chemotherapy for rhabdomyosarcoma (EpSSG RMS 2005): a multicentre, open-label, randomised controlled, phase 3 trial
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Angela De Paoli, Johannes H. M. Merks, Kieran McHugh, Sima Ferman, Giovanni Cecchetto, Angelo Rosolen, Valérie Bernier, Mark N. Gaze, Christophe Bergeron, Florent Guérin, Julia C. Chisholm, Felix Niggli, Michael C. Stevens, Janet Shipley, Adriana Rose, Giovanni Scarzello, H. Mandeville, Modesto Carli, Myriam Weyl Ben‐Arush, Timothy Rogers, Paola Dal Bianco, Gian Luca De Salvo, Federica De Corti, Sheila Terwisscha, Rita Alaggio, Daniela Sejnová, Odile Oberlin, Anna Kelsey, Christine Devalck, Maja Cesen, Andrea Ferrari, Daniel Orbach, Gianni Bisogno, Peter Múdry, Ilaria Zanetti, Meriel Jenney, Soledad Gallego Melcon, Hélène Martelli, Dominique Ranchère, Heidi Glosli, Veronique Minard-Colin, Paediatric Oncology, and CCA - Cancer Treatment and Quality of Life
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Population ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Rhabdomyosarcoma ,medicine ,Humans ,Ifosfamide ,education ,Child ,education.field_of_study ,Chemotherapy ,Dose-Response Relationship, Drug ,business.industry ,Infant ,medicine.disease ,Chemotherapy regimen ,Regimen ,030104 developmental biology ,Oncology ,Doxorubicin ,Vincristine ,030220 oncology & carcinogenesis ,Child, Preschool ,Alveolar rhabdomyosarcoma ,Dactinomycin ,Female ,Embryonal rhabdomyosarcoma ,sense organs ,business ,medicine.drug - Abstract
Background: Rhabdomyosarcoma is an aggressive tumour that can develop in almost any part of the body. Doxorubicin is an effective drug against rhabdomyosarcoma, but its role in combination with an established multidrug regimen remains controversial. Therefore, we aimed to evaluate the possible benefit of early dose intensification with doxorubicin in patients with non-metastatic rhabdomyosarcoma. Methods: We did a multicentre, open-label, randomised controlled, phase 3 trial involving 108 hospitals from 14 countries. We included patients older than 6 months but younger than 21 years with a pathologically proven diagnosis of rhabdomyosarcoma. We assigned each patient to a specific subgroup according to the EpSSG stratification system. Those with embryonal rhabdomyosarcoma incompletely resected and localised at unfavourable sites with or without nodal involvement, or those with alveolar rhabdomyosarcoma without nodal involvement were considered at high risk of relapse. These high-risk patients were randomly assigned (1:1) to receive either nine cycles of IVA (ifosfamide 3 g/m2 given as a 3-h intravenous infusion on days 1 and 2, vincristine 1·5 mg/m2 weekly during the first 7 weeks then only on day 1 of each cycle [given as a single intravenous injection], and dactinomycin 1·5 mg/m2 on day 1 given as a single intravenous injection) or four cycles of IVA with doxorubicin 30 mg/m2 given as a 4-h intravenous infusion on days 1 and 2 followed by five cycles of IVA. The interval between cycles was 3 weeks. Randomisation was done using a web-based system and was stratified (block sizes of four) by enrolling country and risk subgroup. Neither investigators nor patients were masked to treatment allocation. The primary endpoint was 3-year event-free survival assessed by the investigator at each centre in the intention-to-treat population. Patients who received at least one dose of study treatment were considered in the safety analysis. In agreement with the independent data monitoring committee, the study was closed to patient entry on Dec 16, 2013, after futility analysis. This trial is registered with EudraCT, number 2005-000217-35, and is currently in follow-up. Findings: Between Oct 1, 2005, and Dec 16, 2013, 484 patients were randomly assigned to receive each chemotherapy regimen (242 in the IVA group and 242 in the IVA plus doxorubicin group). Median follow-up was 63·9 months (IQR 44·6–78·9). The 3-year event-free survival was 67·5% (95% CI 61·2–73·1) in the IVA plus doxorubicin group and 63·3% (56·8–69·0) in the IVA group (hazard ratio 0·87, 95% CI 0·65–1·16; p=0·33). Grade 3–4 leucopenia (232 [93%] of 249 patients in the IVA plus doxorubicin group vs 194 [85%] of 227 in the IVA group; p=0·0061), anaemia (195 [78%] vs 111 [49%]; p
- Published
- 2018
36. Long-term survivors of childhood cancer: cure and care—the Erice Statement (2006) revised after 10 years (2016)
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Roderick Skinner, Riccardo Haupt, Gisela Michel, Katie Rizvi, Andrea Biondi, Monica Terenziani, Helena J.H. van der Pal, Gabriele Calaminus, participants in PanCare, Michael M. Hawkins, Julianne Byrne, J. D. Beck, Stanislaw Garwicz, Martin Schrappe, Lars Hjorth, Meriel Jenney, Gregory H. Reaman, John J. Spinetta, Edit Bardi, Kevin C. Oeffinger, Eva Frey, Herwig Lackner, Leontien C. M. Kremer, Gerlind Bode, Jaap den Hartogh, Melissa M. Hudson, Claudia E. Kuehni, Momcilo Jankovic, Florent de Vathaire, Gill Levitt, Maria Grazia Valsecchi, Desiree Grabow, Jankovic, M, Haupt, R, Spinetta, J, Beck, J, Byrne, J, Calaminus, G, Lackner, H, Biondi, A, Oeffinger, K, Hudson, M, Skinner, R, Reaman, G, van der Pal, H, Kremer, L, Den Hartogh, J, Michel, G, Frey, E, Bardi, E, Hawkins, M, Rizvi, K, Terenziani, M, Valsecchi, M, Bode, G, Jenney, M, de Vathaire, F, Garwicz, S, Levitt, G, Grabow, D, Kuehni, C, Schrappe, M, Hjorth, L, APH - Quality of Care, Paediatric Oncology, ARD - Amsterdam Reproduction and Development, and CCA - Cancer Treatment and Quality of Life
- Subjects
Adult ,Male ,0301 basic medicine ,Quality of life ,medicine.medical_specialty ,Adolescent ,Statement (logic) ,education ,Childhood cancer ,Declaration ,Childhood cure ,Health informatics ,03 medical and health sciences ,0302 clinical medicine ,Quality of life (healthcare) ,Cancer Survivors ,Neoplasms ,medicine ,Humans ,Childhood care ,Survivors ,Child ,business.industry ,Oncology (nursing) ,Public health ,Cancer ,medicine.disease ,Oncology nursing ,030104 developmental biology ,Oncology ,Health ,030220 oncology & carcinogenesis ,Family medicine ,Female ,business - Abstract
Purpose: The number of persons who have successfully completed treatment for a cancer diagnosed during childhood and who have entered adulthood is increasing over time, and former patients will become aging citizens. Methods: Ten years ago, an expert panel met in Erice, Italy, to produce a set of principles concerning the cure and care of survivors of childhood and adolescent cancer. The result was the Erice Statement (Haupt et al. Eur J Cancer 43(12):1778–80, 2007) that was translated into nine languages. Ten years on, it was timely to review, and possibly revise, the Erice Statement in view of the changes in paediatric oncology and the number and results of international follow-up studies conducted during the intervening years. Results: The long-term goal of the cure and care of a child with cancer is that he/she becomes a resilient and autonomous adult with optimal health-related quality of life, accepted in society at the same level as his/her age peers. “Cure” refers to cure from the original cancer, regardless of any potential for, or presence of, remaining disabilities or side effects of treatment. The care of a child with cancer should include complete and honest information for parents and the child. Conclusions and implication for cancer survivors: Some members of the previous expert panel, as well as new invited experts, met again in Erice to review the Erice Statement, producing a revised version including update and integration of each of the ten points. In addition, a declaration has been prepared, by the Childhood Cancer International Survivors Network in Dublin on October 2016 (see Annex 1).
- Published
- 2018
37. Prognostic relevance of early radiologic response to induction chemotherapy in pediatric rhabdomyosarcoma: A report from the International Society of Pediatric Oncology Malignant Mesenchymal Tumor 95 study
- Author
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Bas, Vaarwerk, Johanna H, van der Lee, Willemijn B, Breunis, Daniel, Orbach, Julia C, Chisholm, Nathalie, Cozic, Meriel, Jenney, Rick R, van Rijn, Kieran, McHugh, Soledad, Gallego, Heidi, Glosli, Christine, Devalck, Mark N, Gaze, Anna, Kelsey, Christophe, Bergeron, Michael C G, Stevens, Odile, Oberlin, Veronique, Minard-Colin, and Johannes H M, Merks
- Subjects
Male ,Adolescent ,International Cooperation ,Infant ,Chemoradiotherapy ,Induction Chemotherapy ,Medical Oncology ,Pediatrics ,Disease-Free Survival ,Child, Preschool ,Antineoplastic Combined Chemotherapy Protocols ,Outcome Assessment, Health Care ,Rhabdomyosarcoma ,Humans ,Mesenchymoma ,Female ,Child ,Societies, Medical ,Retrospective Studies - Abstract
Early response to induction chemotherapy is used in current European guidelines to evaluate the efficacy of chemotherapy and subsequently to adapt treatment in pediatric patients with rhabdomyosarcoma (RMS). However, existing literature on the prognostic value of early radiologic response on survival is contradictory; here the prognostic value is analyzed with data from the International Society of Pediatric Oncology (SIOP) Malignant Mesenchymal Tumor 95 (MMT-95) study.This study examined 432 Intergroup Rhabdomyosarcoma Study Grouping III (macroscopic residue) patients enrolled in the SIOP MMT-95 study with a response assessment after 3 courses of chemotherapy (a 2-dimensional assessment). Patients with progressive disease (PD) after 3 courses of chemotherapy were excluded (n = 7). Failure-free survival (FFS) and overall survival (OS), calculated with the Kaplan-Meier method, were compared for 3 groups (complete response [CR]/partial response [PR], objective response [OR], and no response [NR]). The prognostic impact of early response was assessed through the calculation of Cox proportional hazards.After 3 courses of chemotherapy, 85.2% of the patients had CR/PR, 8.6% had OR, and 6.3% had NR. For all patients, the 5-year FFS and OS rates were 60% (95% confidence interval [CI], 56%-65%) and 74% (95% CI, 70%-78%), respectively. However, a Cox proportional hazards regression analysis revealed no significant difference in FFS or OS between the response groups. The adjusted hazard ratios for an OR and NR were 1.09 (95% CI, 0.63-1.88) and 0.81 (95% CI, 0.39-1.67), respectively, for FFS and 0.91 (95% CI, 0.47-1.76) and 1.27 (95% CI, 0.61-2.64), respectively, for OS.No evidence was found for the idea that early radiologic response to chemotherapy is prognostic for survival for patients with RMS. Treatment adaptation based on early response (except for patients with PD) should, therefore, no longer be incorporated into future studies. Cancer 2018;124:1016-24. © 2017 American Cancer Society.
- Published
- 2017
38. Respiratory mortality of childhood, adolescent and young adult cancer survivors
- Author
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Miranda M, Fidler, Raoul C, Reulen, Chloe J, Bright, Katherine E, Henson, Julie S, Kelly, Meriel, Jenney, Antony, Ng, Jeremy, Whelan, David L, Winter, Clare, Frobisher, Michael M, Hawkins, and Hamish, Wallace
- Subjects
Adult ,Male ,Adolescent ,paediatric interstitial lung disease ,Respiratory Tract Diseases ,Respiratory Epidemiology ,clinical epidemiology ,United Kingdom ,Young Adult ,Cancer Survivors ,Risk Factors ,Cause of Death ,Neoplasms ,Humans ,pneumonia ,Female ,Registries ,copd epidemiology ,Child ,Follow-Up Studies - Abstract
Background Exposure to radiation and/or chemotherapy during cancer treatment can compromise respiratory function. We investigated the risk of long-term respiratory mortality among 5-year cancer survivors diagnosed before age 40 years using the British Childhood Cancer Survivor Study (BCCSS) and Teenage and Young Adult Cancer Survivor Study (TYACSS). Methods The BCCSS comprises 34 489 cancer survivors diagnosed before 15 years from 1940 to 2006 in Great Britain. The TYACSS includes 200 945 cancer survivors diagnosed between 15 years and 39 years from 1971 to 2006 in England and Wales. Standardised mortality ratios and absolute excess risks were used. Findings Overall, 164 and 1079 respiratory deaths were observed in the BCCSS and TYACSS cohorts respectively, which was 6.8 (95% CI 5.8 to 7.9) and 1.7 (95% CI 1.6 to 1.8) times that expected, but the risks varied substantially by type of respiratory death. Greatest excess numbers of deaths were experienced after central nervous system (CNS) tumours in the BCCSS and after lung cancer, leukaemia, head and neck cancer and CNS tumours in the TYACSS. The excess number of respiratory deaths increased with increasing attained age, with seven (95% CI 2.4 to 11.3) excess deaths observed among those aged 50+ years in the BCCSS and three (95% CI 1.4 to 4.2) excess deaths observed among those aged 60+ years in the TYACSS. It was reassuring to see a decline in the excess number of respiratory deaths among those diagnosed more recently in both cohorts. Conclusions Prior to this study, there was almost nothing known about the risks of respiratory death after cancer diagnosed in young adulthood, and this study addresses this gap. These new findings will be useful for both survivors and those involved in their clinical management and follow-up.
- Published
- 2017
39. Access to clinical trials for adolescents with soft tissue sarcomas: Enrollment in European pediatric Soft tissue sarcoma Study Group (EpSSG) protocols
- Author
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Daniel Orbach, Gianni Bisogno, Annalisa Trama, Laura Botta, Heidi Glosli, Julia C. Chisholm, Angela De Paoli, Andrea Ferrari, Johannes H. M. Merks, Gemma Gatta, Meriel Jenney, Christophe Bergeron, Gian Luca De Salvo, Soledad Gallego, CCA - Cancer Treatment and Quality of Life, CCA -Cancer Center Amsterdam, and Paediatric Oncology
- Subjects
0301 basic medicine ,Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Population ,Access to care ,Adolescents ,Health Services Accessibility ,03 medical and health sciences ,0302 clinical medicine ,Clinical trials ,Enrollment ,Rhabdomyosarcoma ,medicine ,Humans ,education ,Child ,Retrospective Studies ,education.field_of_study ,Pediatric protocols ,Soft tissue sarcomas ,Pediatrics, Perinatology and Child Health ,Hematology ,Oncology ,Clinical Trials as Topic ,business.industry ,Soft tissue sarcoma ,Age Factors ,Infant, Newborn ,Cancer ,Soft tissue ,Infant ,Retrospective cohort study ,Perinatology and Child Health ,medicine.disease ,Cancer registry ,Clinical trial ,Europe ,030104 developmental biology ,030220 oncology & carcinogenesis ,Child, Preschool ,Female ,business - Abstract
Background Adolescents with cancer are enrolled in clinical trials at far lower rates than children. This report compares the number of adolescents (15–19-year-olds) and children (0–14-year-olds) enrolled in the protocols of the European pediatric Soft tissue sarcoma Study Group (EpSSG) with the number of cases expected to occur. Methods The observed-to-expected (O/E) ratio was detected in the EpSSG countries contributing most of the cases, that is, Italy, France, Spain, the Netherlands, United Kingdom, and Ireland. The observed cases included patients enrolled in any of the EpSSG protocols from October 2008 to October 2015, when all EpSSG protocols were open in these countries. The number of expected cases was calculated from the incidence rates estimated throughout the RARECAREnet database in the countries’ population-based cancer registries. Results In the countries considered, 2,118 cases aged 0–19 years were enrolled in the EpSSG trials from 2008 to 2015: 82.8% were children and 17.2% were adolescents. The O/E ratio was 0.30 among patients 15–19 years old, as opposed to 0.64 for those 0–14 years old. The O/E ratio differed for the different subtypes: in adolescents, it was 0.64 and 0.18 for rhabdomyosarcoma (RMS) and non-rhabdomyosarcoma soft tissue sarcomas (NRSTS), respectively; in children, it was 0.77 and 0.50, respectively. The O/E ratios differed across the countries considered. Conclusions Adolescents were less well represented than children on the EpSSG protocols, with better enrolment for RMS than for NRSTS for all age groups.
- Published
- 2017
40. Germ cell tumours in children and adolescents
- Author
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James C. Nicholson, Meriel Jenney, and Anthony Penn
- Subjects
endocrine system ,Pathology ,medicine.medical_specialty ,Chemotherapy ,Extragonadal ,medicine.medical_treatment ,Biology ,Totipotent Primordial Germ Cell ,Radiation therapy ,medicine.anatomical_structure ,Pediatrics, Perinatology and Child Health ,medicine ,Differential diagnosis ,Young adult ,Stage (cooking) ,Germ cell - Abstract
Germ cell tumours (GCTs) comprise a heterogeneous group of tumours believed to arise from the totipotent primordial germ cell. While uncommon, they may present at any age from in-utero to young adulthood. Prognosis is generally good and considering them in the differential diagnosis of midline as well as gonadal masses may prevent diagnostic delay and/or escalation of potentially harmful treatment. In childhood, approximately 50% are gonadal and 50% extragonadal (20% intracranial/30% extracranial). Clinical presentation relates to mass effect at tumour site. Teratomas account for 50% of paediatric GCTs and, whilst considered benign, may recur if not completely excised. Malignant GCTs often secrete the tumour markers alpha-fetoprotein and human chorionic gonadotrophin, which may help in diagnosis and follow-up. Outcomes are generally good with >90% five-year overall survival. Management involves complete surgical resection for teratomas and non-metastatic gonadal tumours. In the UK, chemotherapy is reserved for stage 2–4 extracranial malignant GCTs. Intracranial tumours typically occur in the midline in the pineal and/or suprasellar regions. Intracranial germinomas are cured in >90% cases with radiotherapy or combined chemo-radiotherapy. About two-thirds of non-germinomatous intracranial tumours are cured with combined chemo-radiotherapy. Current issues relating to the diagnosis and management of teenagers and young adults with GCTs are highlighted.
- Published
- 2014
41. Conservative approach in localised rhabdomyosarcoma of the bladder and prostate: Results from International Society of Paediatric Oncology (SIOP) studies: Malignant mesenchymal tumour (MMT) 84, 89 and 95
- Author
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Soledad Gallego, Odile Oberlin, Anna Kelsey, Meriel Jenney, Annie Rey, Georges Audry, Johannes H. M. Merks, Christine Haie-Meder, Hélène Martelli, and Michael C. Stevens
- Subjects
Oncology ,medicine.medical_specialty ,Multivariate analysis ,business.industry ,Paediatric oncology ,medicine.medical_treatment ,Complete remission ,Hematology ,medicine.disease ,Surgery ,Radiation therapy ,medicine.anatomical_structure ,Prostate ,Internal medicine ,Pediatrics, Perinatology and Child Health ,Cohort ,Medicine ,Radical surgery ,business ,Rhabdomyosarcoma - Abstract
Background The three sequential SIOP MMT studies provide the largest dataset available to date, to define the patient and tumour characteristics, treatment modalities and event-free and overall survival for children with non metastatic rhabdomyosarcoma (RMS) of the bladder and/or prostate (BP). Procedure The combined dataset of 172 patients with BP RMS treated on the SIOP MMT 84, 89 and 95 studies was reviewed to determine tumour characteristics, details of treatment and outcome. Results Median age at diagnosis was 2.5 years (range 2 months–17.8 years) and 138 (79%) were males. Median follow-up was 11.4 years (range 3 months–22 years). The 5-year overall survival of the combined cohort was 77% (CI 70–83%). The 5-year event-free survival was 63% and included 7 patients (4%) who did not achieve complete remission (CR), and 57 (33%) who relapsed. Age ≥ 10 years (RR 3.7) and alveolar pathology (RR 3.3) were identified as independent prognostic factors on multivariate analysis. Fifty-nine (50%) of the 119 survivors were cured without significant local therapy, improving from 31% in MMT84 study to 61% in MMT95 study. Conclusion The clinical strategy of the MMT studies aims to minimise the burden of therapy whilst maintaining survival rates. Overall survival is comparable to that of other international groups, despite the lower use of radiotherapy and or radical surgery, although number of events experienced is higher. Further assessment of the late effects of therapy is required to confirm whether this approach results in lower morbidity in the long-term. Pediatr Blood Cancer 2014;61:217–222. © 2013 Wiley Periodicals, Inc.
- Published
- 2013
42. The use of the SF-36 questionnaire in adult survivors of childhood cancer: evaluation of data quality, score reliability, and scaling assumptions
- Author
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Maurice P. Zeegers, Crispin Jenkinson, Meriel Jenney, David L. Winter, Michael M. Hawkins, Emma R Lancashire, and Raoul C. Reulen
- Subjects
Adult ,Male ,Self-Assessment ,Psychometrics ,Adolescent ,Physical fitness ,Population ,Emotions ,Validity ,lcsh:Computer applications to medicine. Medical informatics ,Cronbach's alpha ,Neoplasms ,Sickness Impact Profile ,Surveys and Questionnaires ,Health care ,Medicine ,Humans ,Registries ,Survivors ,education ,Child ,Social Behavior ,education.field_of_study ,business.industry ,Research ,Public Health, Environmental and Occupational Health ,General Medicine ,United Kingdom ,Logistic Models ,Physical Fitness ,Research Design ,Test score ,Quality of Life ,Ceiling effect ,lcsh:R858-859.7 ,Female ,business ,Clinical psychology - Abstract
Background The SF-36 has been used in a number of previous studies that have investigated the health status of childhood cancer survivors, but it never has been evaluated regarding data quality, scaling assumptions, and reliability in this population. As health status among childhood cancer survivors is being increasingly investigated, it is important that the measurement instruments are reliable, validated and appropriate for use in this population. The aim of this paper was to determine whether the SF-36 questionnaire is a valid and reliable instrument in assessing self-perceived health status of adult survivors of childhood cancer. Methods We examined the SF-36 to see how it performed with respect to (1) data completeness, (2) distribution of the scale scores, (3) item-internal consistency, (4) item-discriminant validity, (5) internal consistency, and (6) scaling assumptions. For this investigation we used SF-36 data from a population-based study of 10,189 adult survivors of childhood cancer. Results Overall, missing values ranged per item from 0.5 to 2.9 percent. Ceiling effects were found to be highest in the role limitation-physical (76.7%) and role limitation-emotional (76.5%) scales. All correlations between items and their hypothesised scales exceeded the suggested standard of 0.40 for satisfactory item-consistency. Across all scales, the Cronbach's alpha coefficient of reliability was found to be higher than the suggested value of 0.70. Consistent across all cancer groups, the physical health related scale scores correlated strongly with the Physical Component Summary (PCS) scale scores and weakly with the Mental Component Summary (MCS) scale scores. Also, the mental health and role limitation-emotional scales correlated strongly with the MCS scale score and weakly with the PCS scale score. Moderate to strong correlations with both summary scores were found for the general health perception, energy/vitality, and social functioning scales. Conclusion The findings presented in this paper provide support for the validity and reliability of the SF-36 when used in long-term survivors of childhood cancer. These findings should encourage other researchers and health care practitioners to use the SF-36 when assessing health status in this population, although it should be recognised that ceiling effects can occur.
- Published
- 2016
43. Nonparameningeal head and neck rhabdomyosarcoma in children and adolescents: Lessons from the consecutive International Society of Pediatric Oncology Malignant Mesenchymal Tumor studies
- Author
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Daniel, Orbach, Veronique, Mosseri, Soledad, Gallego, Anna, Kelsey, Christine, Devalck, Bernadette, Brenann, Max M, van Noesel, Christophe, Bergeron, Johannes H M, Merks, Catherine, Rechnitzer, Meriel, Jenney, Veronique, Minard-Colin, and Michael, Stevens
- Subjects
Male ,Adolescent ,Infant, Newborn ,Infant ,Combined Modality Therapy ,Disease-Free Survival ,Survival Rate ,Treatment Outcome ,Head and Neck Neoplasms ,Risk Factors ,Child, Preschool ,Rhabdomyosarcoma ,Humans ,Mesenchymoma ,Female ,Neoplasm Recurrence, Local ,Child ,Retrospective Studies - Abstract
This article reports risk factors and long-term outcome in localized nonparameningeal head and neck rhabdomyosarcomas in children and adolescents from a combined dataset from 3 consecutive international trials.Data from 140 children (9.3% of total) prospectively enrolled in the International Society of Pediatric Oncology Malignant Mesenchymal Tumor (SIOP-MMT)-84/89/95 studies were analyzed.Primary site was: superficial face in 46%; oral cavity (21%); neck (19%); and salivary glands (14%). Local control was achieved in 96%, but 49% relapsed (locoregionally 91%). At median follow-up of 10 years, 5-year overall survival (OS) was 74.7% (67.4% to 81.9%) and event-free survival 48.9% (40.6% to 57.2%), although this improved with successive studies. Radiotherapy (RT) as first-line treatment was independently prognostic for event-free survival (relative risk [RR] = 0.4 [range, 0.2-0.7]; p .01) even if it did not impact OS (RR = 1 [range, 0.5-2]).High rates of locoregional relapse were seen in head and neck rhabdomyosarcoma that should be prevented by more frequent use of RT in this primary. © 2016 Wiley Periodicals, Inc. Head Neck 39: 24-31, 2017.
- Published
- 2016
44. Survivorship in Childhood Cancer
- Author
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Meriel Jenney, Monique Peretz Nahum, Amita Mahajan, and Elena Krivoy
- Subjects
business.industry ,Survivorship curve ,Childhood cancer ,Medicine ,business ,Developmental psychology - Published
- 2012
45. Clinical outcomes and health-related quality of life (HRQOL) following haemopoietic stem cell transplantation (HSCT) for paediatric leukaemia
- Author
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Roderick Skinner, Meriel Jenney, P. Darbyshire, Tanya Urquhart, Ajay Vora, Sally-Ann Clarke, J. Cooper, J. Guest, Christine Eiser, and J. Powell
- Subjects
education.field_of_study ,Pediatrics ,medicine.medical_specialty ,business.industry ,Medical record ,medicine.medical_treatment ,Population ,Public Health, Environmental and Occupational Health ,Case-control study ,MEDLINE ,Disease ,Hematopoietic stem cell transplantation ,humanities ,Transplantation ,surgical procedures, operative ,Quality of life ,Pediatrics, Perinatology and Child Health ,Developmental and Educational Psychology ,Medicine ,education ,business - Abstract
Background Haemopoietic stem cell transplantation (HSCT) is a life-saving but intensive procedure associated with potentially severe adverse late effects. We aimed to determine morbidity and health-related quality of life (HRQOL) in a sample of survivors aged 8–18 years at least 1 year post HSCT for paediatric acute leukaemia, compared with a non-transplanted group of survivors matched for age, gender, initial disease and time since treatment. Methods Families (N = 54; HSCT n= 29) recruited from four UK centres completed measures of child behaviour and school attendance, HRQOL and finances. Mothers completed measures of their own well-being. Clinical outcome data were extracted from medical records. Results Children in the HSCT group had significantly more late effects and had received more tests for vision, bone, dental and skin health, and thyroid, lung, and gonadal function than the non-transplanted group. HRQOL scores for the HSCT group were significantly lower in all domains compared with the non-transplanted group and population norms, but were not significantly related to clinical indices. Mothers in the HSCT group had significantly poorer mental well-being than population norms. Conclusion Significant morbidity and compromised HRQOL was found in survivors of HSCT. The burden of caring for a child after HSCT has a continuing toll on mothers' well-being.The importance of counselling families about possible long-term consequences is emphasized.
- Published
- 2010
46. Maintenance low-dose chemotherapy in patients with high-risk (HR) rhabdomyosarcoma (RMS): A report from the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG)
- Author
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Gianni Bisogno, Andrea Ferrari, Heidi Glosli, Michela Casanova, Meriel Jenney, Johannes H. M. Merks, Daniel Orbach, Soledad Gallego Melcon, Christophe Bergeron, Gian Luca De Salvo, Julia C. Chisholm, and Veronique Minard-Colin
- Subjects
0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Vincristine ,Chemotherapy ,Ifosfamide ,business.industry ,medicine.medical_treatment ,Soft tissue sarcoma ,Urology ,medicine.disease ,Vinorelbine ,Metronomic Chemotherapy ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,Low-dose chemotherapy ,030220 oncology & carcinogenesis ,medicine ,business ,Rhabdomyosarcoma ,medicine.drug - Abstract
LBA2 Background: Most patients with localized RMS achieve complete remission during standard (std) treatment but approximately 20-30% of them relapse and chance of salvage is poor. We tested whether adding maintenance metronomic chemotherapy after std chemotherapy would improve survival for patients with non metastatic RMS defined as HR according to EpSSG stratification. Methods: Patients (pts) age >6 months 2 on day 1,8,15 of each cycle and continuous daily oral cyclophosphamide 25 mg/m2 . The study was initially designed with 80% power (5% 2-sided alpha level) to detect an increase in 3 yr Event Free Survival (EFS) from 55% to 67%, a Hazard Ratio of 0.67, but was successively amended to allow a detection of a relative reduction in the relapse rate of 50% in the M-arm, with 80% power, testing at the 5% significance level (2-sided). Results: 670 pts were entered between 4/2006-12/2016, with 371 confirmed eligible and 186 assigned to the std-arm and 185 to M-arm. Clinical features were well balanced in the two arms and included ERMS 67%, ARMS 33%, age 10+ years 21%; IRS Group III 86%; N1 16%. Most common primary tumor sites were parameningeal (32%) and “other” sites (23%). With median follow up of 5 years in surviving pts, 3 yr EFS and overall survival (OS) in M-arm vs Std-arm were respectively: EFS 78.4% (95% IC -71.5-83.8) vs 72.3% (95% IC -65.0-78.3) (p 0.061) and OS 87.3% (95% IC 81.2-91.6) vs 77.4 (95% IC 70.1-83.1) (p = 0.011). Toxicity in the M-arm was manageable: grade 3/4 febrile neutropenia in 25% of pts, grade 4 neurotoxicity in 1.1%. Conclusions: The addition of maintenance after std treatment significantly improves OS in HR RMS patients and support its inclusion in future EpSSG trials. Clinical trial information: 2005-000217-35.
- Published
- 2018
47. Targeted resequencing of pediatric rhabdomyosarcoma: report from the Children’s Oncology Group, the Children’s Cancer and Leukaemia Group, The Institute of Cancer Research UK, and the National Cancer Institute
- Author
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Javed Khan, Douglas S. Hawkins, David Hall, Rebecca Brown, John F. Shern, Corrine M Linardic, Meriel Jenney, Donald A. Barkauskas, Young K. Song, Xinyu Wen, Rajesh Patidar, Ashley Walton, Susanne A. Gatz, Jun S. Wei, Joanna Selfe, Erin R. Rudzinski, Julia C. Chisholm, Stephen X. Skapek, Janet Shipley, and Anna Kelsey
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Formalin fixed paraffin embedded ,business.industry ,Incidence (epidemiology) ,Soft tissue sarcoma ,Cancer ,030204 cardiovascular system & hematology ,Pediatric Rhabdomyosarcoma ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Copy-number variation ,business ,Rhabdomyosarcoma ,Survival rate - Abstract
10515Background: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. Despite aggressive therapy, the 5-year survival rate for patients with metastatic or recurrent disease remains poor. Genomic studies by our group and others have identified 39 genes as known or potential somatic driver mutations in RMS. We therefore performed a large-scale validation study through an international consortium to more accurately determine the incidence of driver mutations and their association with clinical outcome. Methods: Formalin fixed paraffin embedded material was collected from patients enrolled on Children’s Oncology Group trials and UK patients enrolled on MMT trials. Pathology was reviewed centrally and extracted DNA subjected to targeted capture sequencing. Mutations, indels, deletions, gene amplifications and genome-wide copy number variation was called using analysis pipelines developed at the NCI. Results: DNA from six hundred and thirty-one patients was suitable for analyses. A median...
- Published
- 2018
48. Comparison of outcomes based on treatment algorithms for rhabdomyosarcoma of the bladder/prostate: Combined results from the Children's Oncology Group, German Cooperative Soft Tissue Sarcoma Study, Italian Cooperative Group, and International Society of Pediatric Oncology Malignant Mesenchymal Tumors Committee
- Author
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R. B. Raney, Odile Oberlin, Carola A.S. Arndt, Gianni Bisogno, Fernando A. Ferrer, Fred Ullrich, David A. Rodeberg, James R. Anderson, Michael C. Stevens, Ewa Koscielniak, Ines B. Brecht, Modesto Carli, Meriel Jenney, Annie Rey, and William H. Meyer
- Subjects
Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,genetic structures ,Urinary system ,medicine.medical_treatment ,Prostate Rhabdomyosarcoma ,Prostate ,Internal medicine ,Rhabdomyosarcoma ,Humans ,Medicine ,Neoplasm Metastasis ,Child ,health care economics and organizations ,Urinary bladder ,business.industry ,Soft tissue sarcoma ,Prostatic Neoplasms ,Cancer ,medicine.disease ,Radiation therapy ,Treatment Outcome ,medicine.anatomical_structure ,Urinary Bladder Neoplasms ,Child, Preschool ,Female ,business ,Algorithm ,Algorithms - Abstract
The purpose of this study was to determine patient characteristics and outcomes for bladder/prostate (BP) rhabdomyosarcoma (RMS) using an international cohort of prospectively treated patients comparing different treatment algorithms. Data were collected from 379 patients (1979-1998) treated on protocol; Intergroup Rhabdomyosarcoma Study, IRS-IV (n = 239 patients), International Society of Pediatric Oncology Malignant Mesenchymal Tumors (MMT) Committee MMT-84 and -89 (n = 74), Italian Cooperative Group, RMS-79 and RMS-88 Studies (n = 37) or German Cooperative Soft Tissue Sarcoma Study CWS-91 protocols (n = 29). A total of 322 (85%) patients had localized embryonal RMS (ERMS) and 27 had metastatic disease. Thirty patients (21 local disease; 9 metastatic) had nonembryonal BP RMS. Patients with localized ERMS had large tumors (64% >5 cm) that were invasive (54%) with uninvolved regional lymph nodes (N0, 93%). The 5-year failure-free survival (FFS) was 75% and the overall survival (OS) was 84%, with 89% of deaths attributed to disease. Treatment failures were usually local disease recurrence (60%). Predictors of FFS included T-stage (invasiveness), size, and histology. FFS was decreased for patients not receiving initial radiotherapy but this did not translate into a decreased OS. The 21 patients with localized nonembryonal BP RMS had a FFS and OS of 47%. The 36 patients with metastatic disease were more likely to be older and had large tumors that were invasive with alveolar histology and regional lymph node involvement. The 5-year FFS and OS were 41 and 44%, respectively. In conclusion, the majority of BP RMS patients had localized ERMS with a resultant good prognosis using current treatment algorithms. There were differences in FFS between treatment protocols but this did not result in an altered OS.
- Published
- 2010
49. Genetic lesions in a preleukemic aplasia phase in a child with acute lymphoblastic leukemia
- Author
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Mark McKinley, Tracy Chaplin, Sharon W. Horsley, Meriel Jenney, Lyndal Kearney, Bryan D. Young, Mel Greaves, Susan M. Colman, and Caroline M. Bateman
- Subjects
Male ,Cancer Research ,Genotype ,Oncogene Proteins, Fusion ,Anemia ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Bone Marrow ,hemic and lymphatic diseases ,Genetics ,medicine ,Humans ,Preleukemia ,Aplastic anemia ,Childhood Acute Lymphoblastic Leukemia ,In Situ Hybridization, Fluorescence ,Oligonucleotide Array Sequence Analysis ,Retrospective Studies ,Anemia, Aplastic ,Aplasia ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Microarray Analysis ,medicine.disease ,Leukemia ,medicine.anatomical_structure ,Child, Preschool ,Core Binding Factor Alpha 2 Subunit ,Immunology ,Bone marrow - Abstract
In a small fraction ( approximately 2%) of cases of childhood acute lymphoblastic leukemia (ALL) clinical presentation of leukemia is preceded, some 2-9 months earlier, by a transient, remitting phase of nonclassical aplastic anemia, usually in connection with infection. The potential "preleukemic" nature of this prodromal phase has not been fully explored. We have retrospectively analyzed the blood and bone marrow of a child who presented with aplastic anemia 9 months before the development of ETV6-RUNX1 fusion gene positive ALL. High resolution SNP genotyping arrays identified 11 regions of loss of heterozygosity, with and without concurrent copy number changes, at the presentation of ALL. In all cases of copy number change, the deletion or gain identified by single nucleotide polymorphism (SNP) analysis was confirmed in the ALL blasts by FISH. Retrospective analysis of aplastic phase bone marrow showed that the ETV6-RUNX1 fusion was present along with all of the additional genetic changes assessed, albeit subclonal to ETV6-RUNX1. These data identify for the first time the leukemic genotype of an aplasia preceding clinical ALL and indicate that multiple secondary genetic abnormalities can contribute to a dominant subclone several months before a diagnosis of ALL. These data have implications for the biology of ALL and for management of similar patients.
- Published
- 2008
50. Efficacy of carboplatin given in a phase II window study to children and adolescents with newly diagnosed metastatic soft tissue sarcoma
- Author
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Julia C. Chisholm, Meriel Jenney, Kieran McHugh, David Machin, Heather P. McDowell, A.B.M. Foot, and C. Ellershaw
- Subjects
Cancer Research ,medicine.medical_specialty ,Adolescent ,Nausea ,Antineoplastic Agents ,Soft Tissue Neoplasms ,Gastroenterology ,Carboplatin ,Metastasis ,chemistry.chemical_compound ,Risk Factors ,Internal medicine ,Rhabdomyosarcoma ,medicine ,Humans ,Child ,Infusions, Intravenous ,Retrospective Studies ,business.industry ,Soft tissue sarcoma ,Infant ,Soft tissue ,medicine.disease ,Survival Analysis ,Surgery ,Treatment Outcome ,medicine.anatomical_structure ,Oncology ,chemistry ,Child, Preschool ,Vomiting ,Bone marrow ,medicine.symptom ,Bone Marrow Neoplasms ,business - Abstract
Aim The activity of carboplatin was evaluated in a phase II window study in previously untreated children with metastatic soft tissue sarcoma. Methods Children with poor-risk metastatic disease (over 10 years and/or with bone/bone marrow involvement) treated in the SIOP MMT 98 study were scheduled to receive two courses of intravenous carboplatin (area under curve [AUC] of 10), 21 days apart. Results Sixteen eligible patients were entered into the rhabdomyosarcoma (RMS) group. Response (complete remission or partial remission) was seen in five children (31%, 95% confidence interval (CI) 14–56%). Ten eligible patients with other soft tissue sarcomas were recruited into the non-RMS group. Two responses (20%, 95% CI 6–51%) were seen. Toxicity in both groups was predictable nausea, vomiting and marrow suppression and there were no toxic deaths. Conclusion Single-agent carboplatin at AUC of 10 has an acceptable toxicity profile but only moderate efficacy in poor-risk metastatic soft tissue sarcoma.
- Published
- 2007
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