118 results on '"Devalck C"'
Search Results
2. High yield of surveillance in patients diagnosed with constitutional mismatch repair deficiency
- Author
-
Ghorbanoghli, Z., Kouwen, M.C.A. van, Versluys, B., Bonnet, D., Devalck, C., Tinat, J., Januszkiewicz-Lewandowska, D., Costas, C.C., Cottereau, E., Hardwick, J.C.H., Wimmer, K., Brugieres, L., Colas, C., Vasen, H.F.A., Ghorbanoghli, Z., Kouwen, M.C.A. van, Versluys, B., Bonnet, D., Devalck, C., Tinat, J., Januszkiewicz-Lewandowska, D., Costas, C.C., Cottereau, E., Hardwick, J.C.H., Wimmer, K., Brugieres, L., Colas, C., and Vasen, H.F.A.
- Abstract
Contains fulltext : 294692.pdf (Publisher’s version ) (Closed access), BACKGROUND: Constitutional mismatch repair deficiency (CMMRD) is a rare autosomal recessively inherited syndrome that is caused by biallelic pathogenic variants of the mismatch repair genes. It is characterised by the development of multiple tumours in the first and second decade of life including brain, gastrointestinal and haematological tumours often resulting in early death. In order to improve the prognosis of these patients, the European collaborative group 'care for CMMRD' developed a surveillance programme in 2014 and established a registry of patients with CMMRD in Paris. The aim of the study was to evaluate the outcome of this programme. METHODS: Twenty-two patients with a definitive diagnosis of CMMRD and with at least one follow-up study were selected from the registry. Medical data on the outcome of surveillance were collected from these patients. RESULTS: During a mean follow-up of 4 years, the programme detected eight malignant tumours including three brain tumours, three upper gastrointestinal cancers and two colorectal cancers. Most tumours could successfully be treated. In addition, many adenomas were detected in the duodenum, and colorectum and subsequently removed. Seven patients developed a symptomatic malignancy, including two brain tumours, one small bowel cancer and four haematological malignancies. At the end of the follow-up, 16 out of 22 patients (73%) who participated in the surveillance programme were still alive. CONCLUSION: The study suggests a beneficial effect of surveillance of the digestive tract and brains.
- Published
- 2023
3. Quantitative diffusion-weighted MRI response assessment in rhabdomyosarcoma: an international retrospective study on behalf of the European paediatric Soft tissue sarcoma Study Group Imaging Committee.
- Author
-
Ewijk, R. van, Chatziantoniou, C., Adams, M., Bertolini, P., Bisogno, G., Bouhamama, A., Caro-Dominguez, P., Charon, V., Coma, A., Dandis, R., Devalck, C., Donno, G. De, Ferrari, Andrea, Fiocco, M., Gallego, S., Giraudo, C., Glosli, H., Horst, S.A.J. Ter, Jenney, M., Klein, W.M., Leemans, A., Leseur, J., Mandeville, H.C., McHugh, K., Merks, J.H.M., Minard-Colin, V., Moalla, S., Morosi, C., Orbach, D., Ording Muller, L.S., Pace, E., Paolo, P.L. Di, Perruccio, K., Quaglietta, L., Renard, M., Rijn, R.R. van, Ruggiero, A., Sirvent, S.I., Luca, A. De, Schoot, R.A., Ewijk, R. van, Chatziantoniou, C., Adams, M., Bertolini, P., Bisogno, G., Bouhamama, A., Caro-Dominguez, P., Charon, V., Coma, A., Dandis, R., Devalck, C., Donno, G. De, Ferrari, Andrea, Fiocco, M., Gallego, S., Giraudo, C., Glosli, H., Horst, S.A.J. Ter, Jenney, M., Klein, W.M., Leemans, A., Leseur, J., Mandeville, H.C., McHugh, K., Merks, J.H.M., Minard-Colin, V., Moalla, S., Morosi, C., Orbach, D., Ording Muller, L.S., Pace, E., Paolo, P.L. Di, Perruccio, K., Quaglietta, L., Renard, M., Rijn, R.R. van, Ruggiero, A., Sirvent, S.I., Luca, A. De, and Schoot, R.A.
- Abstract
Contains fulltext : 300161.pdf (Publisher’s version ) (Open Access), OBJECTIVE: To investigate the feasibility of diffusion-weighted magnetic resonance imaging (DW-MRI) as a predictive imaging marker after neoadjuvant chemotherapy in patients with rhabdomyosarcoma. MATERIAL AND METHODS: We performed a multicenter retrospective study including pediatric, adolescent and young adult patients with rhabdomyosarcoma, Intergroup Rhabdomyosarcoma Study group III/IV, treated according to the European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS2005 or MTS2008 studies. DW-MRI was performed according to institutional protocols. We performed two-dimensional single-slice tumor delineation. Areas of necrosis or hemorrhage were delineated to be excluded in the primary analysis. Mean, median and 5th and 95th apparent diffusion coefficient (ADC) were extracted. RESULTS: Of 134 included patients, 82 had measurable tumor at diagnosis and response and DW-MRI scans of adequate quality and were included in the analysis. Technical heterogeneity in scan acquisition protocols and scanners was observed. Mean ADC at diagnosis was 1.1 (95% confidence interval [CI]: 1.1-1.2) (all ADC expressed in * 10(-3) mm(2)/s), versus 1.6 (1.5-1.6) at response assessment. The 5th percentile ADC was 0.8 (0.7-0.9) at diagnosis and 1.1 (1.0-1.2) at response. Absolute change in mean ADC after neoadjuvant chemotherapy was 0.4 (0.3-0.5). Exploratory analyses for association between ADC and clinical parameters showed a significant difference in mean ADC at diagnosis for alveolar versus embryonal histology. Landmark analysis at nine weeks after the date of diagnosis showed no significant association (hazard ratio 1.3 [0.6-3.2]) between the mean ADC change and event-free survival. CONCLUSION: A significant change in the 5th percentile and the mean ADC after chemotherapy was observed. Strong heterogeneity was identified in DW-MRI acquisition protocols between centers and in individual patients., 01 november 2023
- Published
- 2023
4. How DNA methylation profiling can help in the diagnosis of pediatric brain tumors. Case report of central nervous system neuroblastoma FOXR2-activated
- Author
-
Rocq, L, primary, Fricx, C, additional, Lubansu, A, additional, Sadeghi, N, additional, Devalck, C, additional, Absil, L, additional, Racu, M-L, additional, D'Haene, N, additional, Salmon, I, additional, and Lebrun, L, additional
- Published
- 2023
- Full Text
- View/download PDF
5. Spermatogenesis after gonadotoxic childhood treatment: follow-up of 12 patients
- Author
-
Delgouffe, E, primary, Braye, A, additional, Vloeberghs, V, additional, Mateizel, I, additional, Ernst, C, additional, Ferster, A, additional, Devalck, C, additional, Tournaye, H, additional, Gies, I, additional, and Goossens, E, additional
- Published
- 2023
- Full Text
- View/download PDF
6. Hydroxyurea treatment for sickle cell disease: impact on haematopoietic stem cell transplantation's outcome
- Author
-
Brachet, C, Azzi, N, Demulder, A, Devalck, C, Gourdin, A, Gulbis, B, Klein, A, Le, P Q, Loop, M, Sariban, E, and Ferster, A
- Published
- 2004
- Full Text
- View/download PDF
7. Hepatic regenerating nodules: a mimic of recurrent cancer in children
- Author
-
Brisse, H., Servois, V., Bouche, B., Avni, F., Petit, P., Thibault, F., Zucker, J. -M., Devalck, C., and Neuenschwander, S.
- Published
- 2000
- Full Text
- View/download PDF
8. Inflammatory myofibroblastic tumors : case report of gross hematuria in an 8-year-old child
- Author
-
Perchec, A, primary, Ziereisen, F, additional, Ferreiro, C, additional, Devalck, C, additional, De Saint Aubain, N, additional, Robberecht, F, additional, Rebuffat, E, additional, and Goetghebuer, T, additional
- Published
- 2020
- Full Text
- View/download PDF
9. Unusual presentation of an acute common Epstein-Barr virus infection
- Author
-
Goffin, L., Lukusa, B., Maquet, J.-C., Milani, S. Malekzadeh, Fonteyne, C., Devalck, C., and Vergison, A.
- Published
- 2003
10. Transplanted sickle-cell disease patients with autologous bone marrow recovery after graft failure develop increased levels of fetal haemoglobin which corrects disease severity
- Author
-
Ferster, A., Corazza, F., Vertongen, F., Bujan, W., Devalck, C., Fondu, P., Cochaux, P., Lambermont, M., Khaladji, Z., and Sariban, E.
- Published
- 1995
11. Survie et toxicité tardive après radiothérapie pour un neuroblastome localisé. Dix ans d’expérience de la Société française de lutte contre les cancers de l’enfant (SFCE)
- Author
-
Ducassou, A., primary, Gambart, M., additional, Munzer, C., additional, Carrie, C., additional, Claude, L., additional, Habrand, J., additional, Bolle, S., additional, Bernier, V., additional, Helfre, S., additional, Leseur, J., additional, Padovani, L., additional, Huchet, A., additional, Bergeron, C., additional, Valteau-Couanet, D., additional, Schleiermacher, G., additional, Coze, C., additional, Defachelles, A., additional, Plouvier, E., additional, Plantaz, D., additional, Perel, Y., additional, Devalck, C., additional, and Laprie, A., additional
- Published
- 2013
- Full Text
- View/download PDF
12. Hydroxyurea for treatment of severe sickle cell anemia: a pediatric clinical trial.
- Author
-
UCL - MD/GYPE - Département de gynécologie, d'obstétrique et de pédiatrie, Ferster, A., Vermylen, Christiane, Cornu, Guy, Buyse, M., Corazza, F, Devalck, C, Fondu, P., Toppet, M, Sariban, E., UCL - MD/GYPE - Département de gynécologie, d'obstétrique et de pédiatrie, Ferster, A., Vermylen, Christiane, Cornu, Guy, Buyse, M., Corazza, F, Devalck, C, Fondu, P., Toppet, M, and Sariban, E.
- Abstract
Hydroxyurea (HU) enhances the synthesis of fetal hemoglobin (HbF) and can improve the clinical course of some adult patients with sickle cell anemia (SCA). In a randomized trial, we studied the biologic effects and the clinical benefit of HU in children and young adults with severe SCA. Twenty-five patients (median age, 9 years) were randomized to receive either HU (at the initial dosage of 20 mg/kg/d) or a placebo for 6 months and were then switched to the other arm for the next 6 months. Among the 22 evaluable patients (median age, 8 years), significant increases in HbF and mean corpuscular volume occurred during the HU treatment period. The white blood cell and reticulocytes counts decreased significantly, but these changes were not clinically relevant. Sixteen of 22 patients (73%) experienced a complete disappearance of events requiring hospitalization. The number of days of hospitalization as well as the number of hospitalizations for patients on HU, as compared with those for the patients receiving placebo, were significantly reduced. We conclude that treatment with HU in children and young adults is feasible, well-tolerated, and improves the clinical course of SCA. The long-term effects of HU require further investigation.
- Published
- 1996
13. Adverse outcome of infants with metastatic neuroblastoma, MYCN amplification and/or bone lesions: results of the French Society of Pediatric Oncology
- Author
-
Minard, V, primary, Hartmann, O, additional, Peyroulet, M C, additional, Michon, J, additional, Coze, C, additional, Defachelle, A S, additional, Lejars, O, additional, Perel, Y, additional, Bergeron, C, additional, Boutard, P, additional, Leverger, G, additional, Stephan, J L, additional, Thyss, A, additional, Chastagner, P, additional, Couillault, G, additional, Devalck, C, additional, Lutz, P, additional, Mechinaud, F, additional, Millot, F, additional, Plantaz, D, additional, Rialland, X, additional, and Rubie, H, additional
- Published
- 2000
- Full Text
- View/download PDF
14. Discrepant flow cytometric expression and function of P-glycoprotein in neuroblastic tumors
- Author
-
De Moerloose, B., primary, Dhooge, C., additional, Laureys, G., additional, Benoit, Y., additional, Demarche, M., additional, Devalck, C., additional, Plantaz, D., additional, Leroy, J., additional, and Philipp�, J., additional
- Published
- 1999
- Full Text
- View/download PDF
15. Comparison between vasoactive intestinal polypeptide and pituitary adenylate cyclase activating polypeptide levels in neuroblastoma tumour tissues
- Author
-
Vertongen, P, primary, De Clerck, P, additional, Fournet, J.-C, additional, Martelli, H, additional, Hélardot, P, additional, Devalck, C, additional, Peeters, T, additional, Sariban, E, additional, and Robberecht, P, additional
- Published
- 1997
- Full Text
- View/download PDF
16. Defective Polymorphonuclear Leukocyte Functions in Children Receiving Chemotherapy for Cancer Are Partially Restored by Recombinant Human Granulocyte Colony-Stimulating Factor In Vitro
- Author
-
Lejeune, M., primary, Sariban, E., additional, Cantinieaux, B., additional, Ferster, A., additional, Devalck, C., additional, and Fondu, P., additional
- Published
- 1996
- Full Text
- View/download PDF
17. Hydroxyurea for treatment of severe sickle cell anemia: a pediatric clinical trial
- Author
-
Ferster, A, primary, Vermylen, C, additional, Cornu, G, additional, Buyse, M, additional, Corazza, F, additional, Devalck, C, additional, Fondu, P, additional, Toppet, M, additional, and Sariban, E, additional
- Published
- 1996
- Full Text
- View/download PDF
18. Lymphome T leucémisé comme première manifestation d'une ataxie-télangiectasie
- Author
-
de Laet, C, primary, Casimir, G, additional, Duchâteau, J, additional, Vamos, E, additional, Devalck, C, additional, Sariban, E, additional, and Ferster, A, additional
- Published
- 1996
- Full Text
- View/download PDF
19. Neurologic complications after bone marrow transplantation for sickle cell anemia [letter; comment]
- Author
-
Ferster, A, primary, Christophe, C, additional, Dan, B, additional, Devalck, C, additional, and Sariban, E, additional
- Published
- 1995
- Full Text
- View/download PDF
20. Bone marrow transplantation corrects the splenic reticuloendothelial dysfunction in sickle cell anemia
- Author
-
Ferster, A, primary, Bujan, W, additional, Corazza, F, additional, Devalck, C, additional, Fondu, P, additional, Toppet, M, additional, Verhas, M, additional, and Sariban, E, additional
- Published
- 1993
- Full Text
- View/download PDF
21. CD30+ Anaplastic Large-Cell Lymphoma in Children: Analysis of 82 Patients Enrolled in Two Consecutive Studies of the French Society of Pediatric Oncology
- Author
-
Brugie`res, L., Deley, M.C. Le, Pacquement, H., Meguerian-Bedoyan, Z., Terrier-Lacombe, M.J., Robert, A., Pondarre´, C., Leverger, G., Devalck, C., Rodary, C., Delsol, G., and Hartmann, O.
- Abstract
The purpose of this study was (1) to investigate the efficacy of chemotherapy regimens designed by the French Society of Pediatric Oncology for childhood anaplastic large-cell lymphoma (ALCL) and (2) to identify prognostic factors in these children. Eighty-two children with newly diagnosed ALCL were enrolled in two consecutive studies, HM89 and HM91. The diagnosis of ALCL was based on immuno-morphological features and all the cases but 2 were investigated using ALK1 antibody directed to the NPM/ALK protein associated with the 2;5 translocation. Treatment consisted of 2 courses of COPADM (methotrexate, cyclophosphamide, doxorubicin, vincristine, and prednisone) and a maintenance treatment of 5 to 7 months. Seventy-eight patients (95%) achieved a complete remission and 21 relapsed. The probability of survival and event-free survival at 3 years was of 83% (72% to 90%) and 66% (54% to 76%), respectively, with a median follow-up of 49 months. In multivariate analysis, visceral involvement, mediastinal involvement, and lacticodeshydrogenase (LDH) level =800 UI/L were shown to be predictive of a higher risk of failure. In conclusion, this type of regimen demonstrated efficacy in childhood ALCL. However, therapeutic results have to be improved for children with adverse prognostic parameters such as visceral or mediastinal involvement or a high LDH level.
- Published
- 1998
- Full Text
- View/download PDF
22. Discrepant flow cytometric expression and function of P-glycoprotein in neuroblastic tumors
- Author
-
Moerloose, B. De, Dhooge, C., Laureys, G., Benoit, Y., Demarche, M., Devalck, C., Plantaz, D., Leroy, J., and Philippé, J.
- Abstract
Patients suffering from neuroblastic tumors are currently being classified into prognostic subsets based on different clinical and biologic features. In this study, a triple-color flow cytometric assay and a functional test were applied to neuroblastoma cell lines and patients with a neuroblastic tumor, and the value of P-glycoprotein expression and function as potential prognostic characteristics, was determined. Twenty-two single-cell suspensions prepared from tumors, and neuroblasts from four bone marrow samples were analyzed by triple-color flow cytometry. Neuroblasts were identified by NB84-positivity and absence of CD45. P-glycoprotein expression was evaluated using 4E3 and MRK16 antibodies. Eighteen samples were tested with a functional assay, based on accumulation and retention of rhodamine-123 with and without the inhibitor verapamil. Six neuroblastoma cell lines were also evaluated. P-glycoprotein expression was seen in 18 of 26 patient samples and in three of six cell lines. The highest expression levels were found in low stage neuroblastoma and well-differentiated tumors; whereas the highest activities were found in stage 4 neuroblastoma and the lowest in ganglioneuroblastoma and ganglioneuroma patients. In 10 of 17 samples, concordant results were found between the flow cytometric immunological test and immunocytochemistry. The described flow cytometric technique is a new, alternative approach to detect P-glycoprotein expression and function in neural crest tumors. Based on the expression level and the activity value, patients can be segregated into different phenotypic groups. In particular, those patients with high P-glycoprotein activity might benefit from treatment regimens containing reversal agents. Cytometry 37:125132, 1999. © 1999 Wiley-Liss, Inc.
- Published
- 1999
- Full Text
- View/download PDF
23. CD30+ Anaplastic Large-Cell Lymphoma in Children: Analysis of 82 Patients Enrolled in Two Consecutive Studies of the French Society of Pediatric Oncology
- Author
-
Brugières, L., Deley, M.C. Le, Pacquement, H., Meguerian-Bedoyan, Z., Terrier-Lacombe, M.J., Robert, A., Pondarré, C., Leverger, G., Devalck, C., Rodary, C., Delsol, G., and Hartmann, O.
- Published
- 1998
- Full Text
- View/download PDF
24. Acute ifosfamide-induced proximal tubular toxic reaction
- Author
-
DEVALCK, C
- Published
- 1991
- Full Text
- View/download PDF
25. Translocation (9;22) (q34;q12–13) in a case of childhood rhabdoid tumor
- Author
-
Heimann, P., Devalck, C., Debusscher, C., Sariban, E., Deroy, G., and Vamos, E.
- Published
- 1994
- Full Text
- View/download PDF
26. Multiple, complex clonal chromosome aberrations in a case of childhood hepatic angiosarcoma
- Author
-
Heimann, P, Ogur, G., Debusscher, C., Devalck, C., Sariban, E., and Vamos, E.
- Published
- 1992
- Full Text
- View/download PDF
27. Comprehensive analysis of constitutional mismatch repair deficiency-associated non-Hodgkin lymphomas in a global cohort.
- Author
-
Rigaud C, Forster VJ, Al-Tarrah H, Attarbaschi A, Bianchi V, Burke A, Burkhardt B, Colas C, Devalck C, Edwards M, Elitzur S, Garthe AK, Goldberg Y, Guerrini-Rousseau L, Horpaopan S, Januszkiewicz-Lewandowska D, Kabíčková E, Kratz CP, Loeffen J, Pérez-Alonso V, Pineda M, Minard-Colin V, Rueda D, Ruiz-Ponte C, Trinquand A, Uyttebroeck A, Wimmer K, Auperin A, Tabori U, and Brugieres L
- Abstract
Background: Constitutional mismatch repair deficiency syndrome (CMMRD) is a rare childhood cancer predisposition syndrome associated with a broad spectrum of malignancies, including non-Hodgkin lymphomas (NHL). Most patients die due to cancer before the age of 20 years. Limited data exist on CMMRD-associated lymphomas and their outcome., Methods: We conducted a retrospective study including all CMMRD-associated NHL patients registered before 2020 in the European and North American databases or reported by members of the European Intergroup for Childhood Non-Hodgkin Lymphoma (EICNHL). Events considered to define event-free survival included relapse/progression, second malignancy (SML), or death, whichever occurred first., Findings: The analysis included 74 patients, with 20 having multiple metachronous NHL. The median age at diagnosis was 9.4 years. Previous malignancies were reported in 36% of the patients, café au lait spots in 96%, and consanguinity in 54%. The initial lymphoma subtypes were 53 T-cell lymphoblastic lymphomas (T-LBL), four B-lymphoblastic lymphomas, and 17 mature B-cell non-Hodgkin lymphoma (B-NHL). All patients were treated with curative intent, with current chemotherapy regimens adapted to their subtype. The median follow-up was 8.7 years. After the first lymphoma, the 5-year event-free and overall survival rates were, respectively, 23.5% [95% confidence interval (CI): 14.9-35.1] and 61.5% [95% CI: 49.6-72.1]. The 5-year cumulative risk of progression/relapse, SML or death as a first event was 20.8%, 52.9%, and 2.7%., Interpretation: Standard treatments for sporadic NHL are effective in most CMMRD-associated NHL cases, but multiple malignancies, including lymphomas, impair prognosis. Future strategies should evaluate the potential of less genotoxic therapies, including immunotherapy, in preventing SMLs while maintaining effective control of NHL., (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)
- Published
- 2024
- Full Text
- View/download PDF
28. Localized incompletely resected standard risk rhabdomyosarcoma in children and adolescents: Results from the European Paediatric Soft Tissue Sarcoma Study Group RMS 2005 trial.
- Author
-
Mandeville HC, Bisogno G, Minard-Colin V, Alaggio R, Ben-Arush M, Chargari C, Coppadoro B, Craigie R, Devalck C, Ferman S, Ferrari A, Glosli H, Alvaro RH, Hol M, Mudry P, Orbach D, Albiac MR, Merks JHM, and Jenney MEM
- Abstract
Background: The authors report the prospective evaluation of reduced dose alkylator chemotherapy combined with radiotherapy for European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) standard risk nonalveolar rhabdomyosarcoma (NA-RMS)., Patients and Methods: Localized node negative Intergroup Rhabdomyosarcoma Study (IRS) II/III NA-RMS at favorable sites (subgroup C), <25 years old, received five cycles of ifosfamide, vincristine, and dactinomycin (IVA) chemotherapy (30 g/m
2 ifosfamide) and four cycles of vincristine and dactinomycin (if receiving radiotherapy), or nine cycles of IVA (54 g/m2 ifosfamide) ± radiotherapy. Delayed primary tumor excision was considered for IRS III tumors. The primary end points were event-free survival (EFS) and overall survival (OS)., Results: From October 2005 to December 2016, 359 evaluable patients were recruited: orbit, 164 (45.7%); head and neck nonparameningeal, 77 (21.4%); and genitourinary non-bladder/prostate, 118 (32.9%). EFS and OS were 77.4% (95% confidence interval [CI], 72.5-81.6) and 93.5% (95% CI, 90.1-95.8), respectively. Lower dose alkylator chemotherapy and radiotherapy achieved 5-year OS of 93.7% but the difference with higher dose alkylator chemotherapy +/- radiotherapy was not significant (p = 0.8003). Adjuvant radiotherapy improved EFS with 5-year estimates of 84.7% versus 65.2% for nonirradiated (p < .0001), but not OS (p = .9298). Omitting radiotherapy for orbital tumors reduced OS (5-year was 87.1% vs. 97.3% for irradiated, p = .0257). Following R0 resection (n = 60), radiotherapy did not significantly improve EFS or OS., Conclusions: Radiotherapy for local tumor control allows for reduction of cumulative dose of alkylators in EpSSG standard risk subgroup C RMS patients. The omission of radiotherapy did not affect OS in all patients except those with orbital RMS and was associated with inferior EFS., (© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)- Published
- 2024
- Full Text
- View/download PDF
29. Reappraisal of prognostic factors used in the European Pediatric Soft Tissue Sarcoma Study Group RMS 2005 study for localized rhabdomyosarcoma to optimize risk stratification and generate a prognostic nomogram.
- Author
-
De Salvo GL, Del Bianco P, Minard-Colin V, Chisholm J, Jenney M, Guillen G, Devalck C, Van Rijn R, Shipley J, Orbach D, Kelsey A, Rogers T, Guerin F, Scarzello G, Ferrari A, Cesen Mazic M, Merks JHM, and Bisogno G
- Subjects
- Humans, Male, Female, Child, Preschool, Child, Prognosis, Infant, Risk Assessment, Adolescent, Europe epidemiology, Forkhead Box Protein O1 genetics, Forkhead Box Protein O1 metabolism, Oncogene Proteins, Fusion genetics, Rhabdomyosarcoma mortality, Rhabdomyosarcoma pathology, Rhabdomyosarcoma therapy, Nomograms
- Abstract
Background: The objective of this study was to investigate the role of clinical factors together with FOXO1 fusion status in patients with nonmetastatic rhabdomyosarcoma (RMS) to develop a predictive model for event-free survival and provide a rationale for risk stratification in future trials., Methods: The authors used data from patients enrolled in the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) RMS 2005 study (EpSSG RMS 2005; EudraCT number 2005-000217-35). The following baseline variables were considered for the multivariable model: age at diagnosis, sex, histology, primary tumor site, Intergroup Rhabdomyosarcoma Studies group, tumor size, nodal status, and FOXO1 fusion status. Main effects and significant second-order interactions of candidate predictors were included in a multiple Cox proportional hazards regression model. A nomogram was generated for predicting 5-year event-free survival (EFS) probabilities., Results: The EFS and overall survival rates at 5 years were 70.9% (95% confidence interval, 68.6%-73.1%) and 81.0% (95% confidence interval, 78.9%-82.8%), respectively. The multivariable model retained five prognostic factors, including age at diagnosis interacting with tumor size, tumor primary site, Intergroup Rhabdomyosarcoma Studies clinical group, and FOXO1 fusion status. Based on each patient's total score in the nomogram, patients were stratified into four groups. The 5-year EFS rates were 94.1%, 78.4%, 65.2%, and 52.1% in the low-risk, intermediate-risk, high-risk, and very-high-risk groups, respectively, and the corresponding 5-year overall survival rates were 97.2%, 91.5%, 74.3%, and 60.8%, respectively., Conclusions: The results presented here provide the rationale to modify the EpSSG stratification, with the most significant change represented by the replacement of histology with fusion status. This classification was adopted in the new international trial launched by the EpSSG., (© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)
- Published
- 2024
- Full Text
- View/download PDF
30. Quantitative diffusion-weighted MRI response assessment in rhabdomyosarcoma: an international retrospective study on behalf of the European paediatric Soft tissue sarcoma Study Group Imaging Committee.
- Author
-
van Ewijk R, Chatziantoniou C, Adams M, Bertolini P, Bisogno G, Bouhamama A, Caro-Dominguez P, Charon V, Coma A, Dandis R, Devalck C, De Donno G, Ferrari A, Fiocco M, Gallego S, Giraudo C, Glosli H, Ter Horst SAJ, Jenney M, Klein WM, Leemans A, Leseur J, Mandeville HC, McHugh K, Merks JHM, Minard-Colin V, Moalla S, Morosi C, Orbach D, Ording Muller LS, Pace E, Di Paolo PL, Perruccio K, Quaglietta L, Renard M, van Rijn RR, Ruggiero A, Sirvent SI, De Luca A, and Schoot RA
- Subjects
- Adolescent, Young Adult, Humans, Child, Diffusion Magnetic Resonance Imaging methods, Retrospective Studies, Sarcoma, Rhabdomyosarcoma diagnostic imaging
- Abstract
Objective: To investigate the feasibility of diffusion-weighted magnetic resonance imaging (DW-MRI) as a predictive imaging marker after neoadjuvant chemotherapy in patients with rhabdomyosarcoma., Material and Methods: We performed a multicenter retrospective study including pediatric, adolescent and young adult patients with rhabdomyosarcoma, Intergroup Rhabdomyosarcoma Study group III/IV, treated according to the European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS2005 or MTS2008 studies. DW-MRI was performed according to institutional protocols. We performed two-dimensional single-slice tumor delineation. Areas of necrosis or hemorrhage were delineated to be excluded in the primary analysis. Mean, median and 5th and 95th apparent diffusion coefficient (ADC) were extracted., Results: Of 134 included patients, 82 had measurable tumor at diagnosis and response and DW-MRI scans of adequate quality and were included in the analysis. Technical heterogeneity in scan acquisition protocols and scanners was observed. Mean ADC at diagnosis was 1.1 (95% confidence interval [CI]: 1.1-1.2) (all ADC expressed in * 10
-3 mm2 /s), versus 1.6 (1.5-1.6) at response assessment. The 5th percentile ADC was 0.8 (0.7-0.9) at diagnosis and 1.1 (1.0-1.2) at response. Absolute change in mean ADC after neoadjuvant chemotherapy was 0.4 (0.3-0.5). Exploratory analyses for association between ADC and clinical parameters showed a significant difference in mean ADC at diagnosis for alveolar versus embryonal histology. Landmark analysis at nine weeks after the date of diagnosis showed no significant association (hazard ratio 1.3 [0.6-3.2]) between the mean ADC change and event-free survival., Conclusion: A significant change in the 5th percentile and the mean ADC after chemotherapy was observed. Strong heterogeneity was identified in DW-MRI acquisition protocols between centers and in individual patients., (© 2023. The Author(s).)- Published
- 2023
- Full Text
- View/download PDF
31. Pediatric Patient with a Diagnosis of Pelvic Extraosseous Ewing's Sarcoma: A Case Report.
- Author
-
Amaouche S, Devalck C, and Damry N
- Abstract
Ewing's sarcoma (ES) is a malignant tumor that arises mainly from bone tissue. Primary extraosseous Ewing sarcoma (EES) is a rare form of the Ewing's sarcoma family of tumor, and pelvic localization is even more unusual, considered to be one of the rarest localizations [1]. We present the case of a seven-year-old boy with persistent abdominal pain. Ultrasound (US), contrast-enhanced computed tomography (CECT), and magnetic resonance imaging (MRI) revealed the presence of a large, solid, and heterogeneous mass in the pelvis. The histological and immunohistochemistry were compatible with pelvic EES. Teaching point: Extraosseous Ewing's sarcoma is a rare pediatric tumoral entity that requires clinician and radiological vigilance and detection., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2023 The Author(s).)
- Published
- 2023
- Full Text
- View/download PDF
32. HLA haplotype frequencies and diversity in patients with hemoglobinopathies.
- Author
-
Scigliuolo GM, Boukouaci W, Cappelli B, Volt F, Rivera Franco MM, Dhédin N, de Latour RP, Devalck C, Dalle JH, Castelle M, Hermine O, Chardin MO, Poiré X, Brichard B, Paillard C, Rafii H, Kenzey C, Wu CL, Bouassida J, Robin M, Raus N, Rocha V, Ruggeri A, Gluckman E, and Tamouza R
- Abstract
The genetic diversity of the human leukocyte antigen (HLA) system was shaped by evolutionary constraints exerted by environmental factors. Analyzing HLA diversity may allow understanding of the underlying pathways and offer useful tools in transplant setting. The aim of this study was to investigate the HLA haplotype diversity in patients with sickle cell disease (SCD, N = 282) or β-thalassemia (β-Thal, N = 60), who received hematopoietic cell transplantation (HCT) reported to Eurocord and the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC). We identified 405 different HLA-A-B-DRB1 haplotypes in SCD and 108 in β-Thal patients. Using data from African and European populations of the "1000 Genomes Project" for comparison with SCD and β-Thal, respectively, we found that the haplotypes HLA-A*30-B*14-DRB1*15 (OR 7.87, 95% CI: 1.66-37.3, p
b = 0.035), HLA-A*23-B*08 (OR 6.59, 95% CI: 1.8-24.13, pb = 0.023), and HLA-B*14-DRB1*15 (OR 10.74, 95% CI: 3.66-31.57, pb = 0.000) were associated with SCD, and the partial haplotypes HLA-A*30-B*13 and HLA-A*68-B*53 were associated with β-Thal (OR 4.810, 95% CI: 1.55-14.91, pb = 0.033, and OR 17.52, 95% CI: 2.81-184.95, pb = 0.011). Our results confirm the extreme HLA genetic diversity in SCD patients likely due to their African ancestry. This diversity seems less accentuated in patients with β-Thal. Our findings emphasize the need to expand inclusion of donors of African descent in HCT donor registries and cord blood banks., Competing Interests: The authors declare they have no conflicts of interest., (© 2023 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)- Published
- 2023
- Full Text
- View/download PDF
33. High yield of surveillance in patients diagnosed with constitutional mismatch repair deficiency.
- Author
-
Ghorbanoghli Z, van Kouwen M, Versluys B, Bonnet D, Devalck C, Tinat J, Januszkiewicz-Lewandowska D, Costas CC, Cottereau E, Hardwick JCH, Wimmer K, Brugieres L, Colas C, and Vasen HFA
- Subjects
- Humans, Follow-Up Studies, DNA Mismatch Repair, Mismatch Repair Endonuclease PMS2 genetics, Neoplastic Syndromes, Hereditary diagnosis, Neoplastic Syndromes, Hereditary epidemiology, Neoplastic Syndromes, Hereditary genetics, Colorectal Neoplasms diagnosis, Colorectal Neoplasms epidemiology, Colorectal Neoplasms genetics, Brain Neoplasms diagnosis, Brain Neoplasms genetics
- Abstract
Background: Constitutional mismatch repair deficiency (CMMRD) is a rare autosomal recessively inherited syndrome that is caused by biallelic pathogenic variants of the mismatch repair genes. It is characterised by the development of multiple tumours in the first and second decade of life including brain, gastrointestinal and haematological tumours often resulting in early death. In order to improve the prognosis of these patients, the European collaborative group 'care for CMMRD' developed a surveillance programme in 2014 and established a registry of patients with CMMRD in Paris. The aim of the study was to evaluate the outcome of this programme., Methods: Twenty-two patients with a definitive diagnosis of CMMRD and with at least one follow-up study were selected from the registry. Medical data on the outcome of surveillance were collected from these patients., Results: During a mean follow-up of 4 years, the programme detected eight malignant tumours including three brain tumours, three upper gastrointestinal cancers and two colorectal cancers. Most tumours could successfully be treated. In addition, many adenomas were detected in the duodenum, and colorectum and subsequently removed. Seven patients developed a symptomatic malignancy, including two brain tumours, one small bowel cancer and four haematological malignancies. At the end of the follow-up, 16 out of 22 patients (73%) who participated in the surveillance programme were still alive., Conclusion: The study suggests a beneficial effect of surveillance of the digestive tract and brains., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2023
- Full Text
- View/download PDF
34. Nonmetastatic Rhabdomyosarcoma in Children and Adolescents: Overall Results of the European Pediatric Soft Tissue Sarcoma Study Group RMS2005 Study.
- Author
-
Bisogno G, Minard-Colin V, Zanetti I, Ferrari A, Gallego S, Dávila Fajardo R, Mandeville H, Kelsey A, Alaggio R, Orbach D, Terwisscha van Scheltinga S, Guillén Burrieza G, Ben-Arush M, Glosli H, Mudry P, Ferman S, Devalck C, Defachelles AS, Merks JHM, and Jenney M
- Subjects
- Adolescent, Child, Humans, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Dactinomycin, Disease-Free Survival, Rhabdomyosarcoma drug therapy, Sarcoma pathology
- 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.
- Published
- 2023
- Full Text
- View/download PDF
35. [Nodular lymphocyte predominant Hodgkin lymphoma (paragranuloma of Poppema) in children: Case report, review of the literature and treatment].
- Author
-
Wilgenhof K, Théate I, Devalck C, Forsyth R, and Dehou MF
- Subjects
- Male, Humans, Child, Prognosis, Lymphocytes pathology, Hodgkin Disease diagnosis, Hodgkin Disease therapy, Hodgkin Disease pathology
- Abstract
We present the case of a 12 year old child with a limp. The diagnostic work-up reveals splenomegaly, multifocal bone involvement and abdominal adenopathies. A biopsy of an intra-abdominal lesion shows a lymphoid mass with a nodular architecture composed of poorly defined nodules. We identify large cells with irregular, sometimes poly-lobulated nuclei with a particular immunohistochemical profile. Those "pop-corn" cells are positive for CD20, CD79a, pax-5 and bcl-6 and are negative for CD15, CD30, bcl-2, TdT, CD56 and EMA. There is a diffuse follicular helper T cell population that is located in between the tumour cells. The overall picture is indicative of a nodular lymphocyte predominant Hodgkin lymphoma. Advanced stage of this disease is rare in children and there is currently little data to guide optimal treatment. Because of a stage IV disease, the patient is treated with chemotherapy after which complete metabolic remission is observed. 3.5 years after the initial diagnosis, our patient relapses. He is treated with chemotherapy and an autologous peripheral blood stem cell transplantation. He remains in complete remission since then. This case illustrates the favorable prognosis of the disease even after relapse., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
36. Adolescents and young adults with rhabdomyosarcoma treated in the European paediatric Soft tissue sarcoma Study Group (EpSSG) protocols: a cohort study.
- Author
-
Ferrari A, Chisholm JC, Jenney M, Minard-Colin V, Orbach D, Casanova M, Guillen G, Glosli H, van Rijn RR, Schoot RA, Cameron AL, Rogers T, Alaggio R, Ben-Arush M, Mandeville HC, Devalck C, Defachelles AS, Coppadoro B, Bisogno G, and Merks JHM
- Subjects
- Adolescent, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Child, Child, Preschool, Clinical Trials, Phase III as Topic, Cohort Studies, Disease-Free Survival, Humans, Neoplasm Recurrence, Local pathology, Observational Studies as Topic, Prospective Studies, Randomized Controlled Trials as Topic, Retrospective Studies, Young Adult, Rhabdomyosarcoma therapy, Sarcoma
- 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 <15 years and 196 aged 15-21 years) and 258 patients were from the EPSSG MTS 2008 study (197 aged <15 years and 61 aged 15-21 years). Adolescent and young adult patients were more likely than were children to have metastatic tumours (61 [23·7%] of 257 vs 197 [11·5%] of 1720; p<0·0001), unfavourable histological subtypes (119 [46·3%] vs 451 [26·2%]; p<0·0001), tumours larger than 5 cm (177 [68·9%] vs 891 [51·8%]; p<0·0001), and regional lymph node involvement (109 [42·4%] vs 339 [19·7%]; p<0·0001). Adolescent and young adult patients had lower 5-year event-free survival (52·6% [95% CI 46·3-58·6] vs 67·8% [65·5-70·0]; p<0·0001) and lower 5-year overall survival (57·1% [50·4-63·1] vs 77·9% [75·8-79·8]; p<0·0001) than did children. The multivariable analysis confirmed the inferior prognosis of patients aged 15-21 years (hazard ratios 1·48 [95% CI 1·20-1·83; p=0·0002] for poorer event-free survival and 1·73 [1·37-2·19; p<0·0001] for poorer overall survival). Modifications of administered chemotherapy occurred in 13 (15·3%) of 85 adolescents and young adults, and in 161 (21·4%) of 754 children. Grade 3-4 haematological toxicity and infection were observed more frequently in children than in adolescent and young adult patients., Interpretation: This study found better outcomes for adolescent and young adult patients than those reported in epidemiological studies (eg, the EUROCARE-5 study reported 5-year overall survival of 39·6% for patients aged 15-19 years in the 2000-07 study period), suggesting that adolescent and young adult patients, at least up to age 21 years, can be treated with intensive paediatric therapies with no major tolerability issues and should be included in paediatric rhabdomyosarcoma trials. However, the inferior outcomes in adolescent and young adult patients compared with those in children, despite receiving similar therapy, suggest that a tailored and intensive treatment strategy might be warranted for these patients., Funding: Fondazione Città della Speranza., Competing Interests: Declaration of interests JCC has acted as a consultant and advisor for Bayer. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
37. Brachytherapy for Pediatric Patients at Gustave Roussy Cancer Campus: A Model of International Cooperation for Highly Specialized Treatments.
- Author
-
Chargari C, Haie-Meder C, Espenel S, Garcia MA, Ben-Arush M, Bolle S, Borjesson A, Cesen M, Lago RC, Defachelles AS, De Moerloose B, Devalck C, Edslev P, Farinha NJ, Francotte N, Glosli H, Gouy S, Burrieza GG, Helfre S, Irtan S, Kattamis A, Lacerda A, Levy A, Hjalgrim LL, Mansuy L, Mascard E, Moalla S, Orbach D, Owens C, Philippe-Chomette P, Pizer B, Pluchart C, Renard M, Rognlien AGW, Rome A, Sarnacki S, Safwat A, Schiavetti A, Serre J, Verite C, Weid NV, Wysocki M, Valteay-Couanet D, Deutsch E, Minard-Colin V, Martelli H, and Guérin F
- Subjects
- Child, Female, Humans, International Cooperation, Male, Neoplasm Recurrence, Local radiotherapy, Retrospective Studies, Brachytherapy methods, Prostatic Neoplasms radiotherapy, Rhabdomyosarcoma radiotherapy, Urinary Bladder Neoplasms radiotherapy
- Abstract
Purpose: Childhood cancer is rare, and treatment is frequently associated with long-term morbidity. Disparities in survival and long-term side effects encourage the establishment of networks to increase access to complex organ-conservative strategies, such as brachytherapy. We report our experience of an international cooperation model in childhood cancers., Methods and Materials: We examined the outcome of all children referred to our center from national or international networks to be treated according to a multimodal organ-conservative approach, including brachytherapy., Results: We identified 305 patients whose median age at diagnosis was 2.2 years (range, 1.4 months to 17.2 years). Among these patients, 99 (32.4%) were treated between 2015 and 2020; 172 (56.4%) were referred from national centers; and 133 (43.6%) were international patients from 31 countries (mainly Europe). Also, 263 patients were referred for primary treatment and 42 patients were referred for salvage treatment. Genitourinary tumors were the most frequent sites, with 56.4% bladder/prostate rhabdomyosarcoma and 28.5% gynecologic tumors. In addition to brachytherapy, local treatment consisted of partial tumor resection in 207 patients (67.9%), and 39 patients (13%) had additional external radiation therapy. Median follow-up was 58 months (range, 1 month to 48 years), 93 months for national patients, and 37 months for international patients (P < .0001). Five-year local control, disease-free survival, and overall survival rates were 90.8% (95% confidence interval [CI], 87.3%-94.4%), 84.4% (95% CI, 80.1%-89.0%), and 93.3% (95% CI, 90.1%-96.5%), respectively. Patients referred for salvage treatment had poorer disease-free survival (P < .01). Implementation of image guided pulse-dose-rate brachytherapy was associated with better local control among patients with rhabdomyosarcoma referred for primary treatment (hazard ratio, 9.72; 95% CI, 1.24-71.0). At last follow-up, 16.7% patients had long-term severe treatment-related complications, and 2 patients (0.7%) had developed second malignancy., Conclusions: This retrospective series shows the feasibility of a multinational referral network for brachytherapy allowing high patient numbers in rare pediatric cancers. High local control probability and acceptable late severe complication probability could be achieved despite very challenging situations. This cooperation model could serve as a basis for generating international reference networks for high-tech radiation such as brachytherapy to increase treatment care opportunities and cure probability., (Copyright © 2022 Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
38. 15-Year-Old Patient with an Unusual Alpha-Fetoprotein-Producing Sertoli-Leydig Cell Tumor of Ovary.
- Author
-
Serife K, Karampelas S, Hottat N, Devalck C, and Vanden Houte K
- Abstract
Ovarian Sertoli-Leydig cell tumors (SLCTs) are extremely rare ovarian sex-cord stromal tumors. Alpha-fetoprotein (AFP) production by SLCTs is a rare event generally linked to the presence of hepatocytes or intestinal mucinous epithelium as heterologous elements. We report here a case of a 15-year-old female complaining about abdominal pain, constipation, and spaniomenorrhea with high level of serum AFP leading to a clinical suspicion of malignant germ cell tumor. Final histopathological diagnosis was a moderately differentiated Sertoli-Leydig cell tumor of the ovary with alpha-fetoprotein-producing cells without hepatocytic or intestinal epithelium differentiation. NGS analysis showed mutation in DICER1 gene. SLCTs occur in patients at any age with a mean age of 25 years. The presence of alpha-fetoprotein-producing cells is an important tool in the differential diagnosis of germ cell tumors and challenging in this case of SLCT because of its rarity in this context. An adequate sampling and exhaustive immunohistochemical analyses are mandatory to make the correct differential diagnosis and confirm the presence of alpha-fetoprotein-producing cells and also define the differentiation because of therapeutic strategies between conservative surgery and/or chemotherapy., Competing Interests: The authors declare that they have no conflict of interest regarding the publication of this article., (Copyright © 2022 Kaçar Serife et al.)
- Published
- 2022
- Full Text
- View/download PDF
39. The feasibility of using liquid biopsies as a complementary assay for copy number aberration profiling in routinely collected paediatric cancer patient samples.
- Author
-
Van Paemel R, Vandeputte C, Raman L, Van Thorre J, Willems L, Van Dorpe J, Van Der Linden M, De Wilde J, De Koker A, Menten B, Devalck C, Vicha A, Grega M, Schleiermacher G, Iddir Y, Chicard M, van Zogchel L, Stutterheim J, Lak NSM, Tytgat GAM, Laureys G, Speleman F, De Wilde B, Lammens T, De Preter K, and Van Roy N
- Subjects
- Adolescent, Child, Child, Preschool, Feasibility Studies, Female, Humans, Male, Prospective Studies, Retrospective Studies, Biomarkers, Tumor genetics, Cell-Free Nucleic Acids genetics, DNA Copy Number Variations genetics, Liquid Biopsy methods
- Abstract
Background: Paediatric tumours are often characterised by the presence of recurrent DNA copy number alterations (CNAs). These DNA copy number profiles, obtained from a tissue biopsy, can aid in the correct prognostic classification and therapeutic stratification of several paediatric cancer entities (e.g. MYCN amplification in neuroblastoma) and are part of the routine diagnostic practice. Liquid biopsies (LQBs) offer a potentially safer alternative for such invasive tumour tissue biopsies and can provide deeper insight into tumour heterogeneity., Procedure: The robustness and reliability of LQB CNA analyses was evaluated. We performed retrospective CNA profiling using shallow whole-genome sequencing (sWGS) on paired plasma circulating cell-free DNA (cfDNA) and tissue DNA samples from routinely collected samples from paediatric patients (n = 128) representing different tumour entities, including osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, Wilms tumour, brain tumours and neuroblastoma., Results: Overall, we observed a good concordance between CNAs in tissue DNA and cfDNA. The main cause of CNA discordance was found to be low cfDNA sample quality (i.e. the ratio of cfDNA (<700 bp) and high molecular weight DNA (>700 bp)). Furthermore, CNAs were observed that were present in cfDNA and not in tissue DNA, or vice-versa. In neuroblastoma samples, no false-positives or false-negatives were identified for the detection of the prognostic marker MYCN amplification., Conclusion: In future prospective studies, CNA analysis on LQBs that are of sufficient quality can serve as a complementary assay for CNA analysis on tissue biopsies, as either cfDNA or tissue DNA can contain CNAs that cannot be identified in the other biomaterial., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
40. Defective Sec61α1 underlies a novel cause of autosomal dominant severe congenital neutropenia.
- Author
-
Van Nieuwenhove E, Barber JS, Neumann J, Smeets E, Willemsen M, Pasciuto E, Prezzemolo T, Lagou V, Seldeslachts L, Malengier-Devlies B, Metzemaekers M, Haßdenteufel S, Kerstens A, van der Kant R, Rousseau F, Schymkowitz J, Di Marino D, Lang S, Zimmermann R, Schlenner S, Munck S, Proost P, Matthys P, Devalck C, Boeckx N, Claessens F, Wouters C, Humblet-Baron S, Meyts I, and Liston A
- Subjects
- Antigens, CD34 metabolism, Chromosome Disorders, Female, Genes, Dominant, HL-60 Cells, Humans, Neutropenia genetics, Pedigree, Single-Cell Analysis, Unfolded Protein Response genetics, Exome Sequencing, Young Adult, Congenital Bone Marrow Failure Syndromes genetics, Mutation genetics, Neutropenia congenital, Neutrophils physiology, SEC Translocation Channels genetics
- Abstract
Background: The molecular cause of severe congenital neutropenia (SCN) is unknown in 30% to 50% of patients. SEC61A1 encodes the α-subunit of the Sec61 complex, which governs endoplasmic reticulum protein transport and passive calcium leakage. Recently, mutations in SEC61A1 were reported to be pathogenic in common variable immunodeficiency and glomerulocystic kidney disease., Objective: Our aim was to expand the spectrum of SEC61A1-mediated disease to include autosomal dominant SCN., Methods: Whole exome sequencing findings were validated, and reported mutations were compared by Western blotting, Ca2
+ flux assays, differentiation of transduced HL-60 cells, in vitro differentiation of primary CD34 cells, quantitative PCR for unfolded protein response (UPR) genes, and single-cell RNA sequencing on whole bone marrow., Results: We identified a novel de novo missense mutation in SEC61A1 (c.A275G;p.Q92R) in a patient with SCN who was born to nonconsanguineous Belgian parents. The mutation results in diminished protein expression, disturbed protein translocation, and an increase in calcium leakage from the endoplasmic reticulum. In vitro differentiation of CD34+ cells recapitulated the patient's clinical arrest in granulopoiesis. The impact of Q92R-Sec61α1 on neutrophil maturation was validated by using HL-60 cells, in which transduction reduced differentiation into CD11b+ CD16+ cells. A potential mechanism for this defect is the uncontrolled initiation of the unfolded protein stress response, with single-cell analysis of primary bone marrow revealing perturbed UPR in myeloid precursors and in vitro differentiation of primary CD34+ cells revealing upregulation of CCAAT/enhancer-binding protein homologous protein and immunoglobulin heavy chain binding protein UPR-response genes., Conclusion: Specific mutations in SEC61A1 cause SCN through dysregulation of the UPR., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2020
- Full Text
- View/download PDF
41. Constitutional mismatch repair deficiency-associated brain tumors: report from the European C4CMMRD consortium.
- Author
-
Guerrini-Rousseau L, Varlet P, Colas C, Andreiuolo F, Bourdeaut F, Dahan K, Devalck C, Faure-Conter C, Genuardi M, Goldberg Y, Kuhlen M, Moalla S, Opocher E, Perez-Alonso V, Sehested A, Slavc I, Unger S, Wimmer K, Grill J, and Brugières L
- Abstract
Background: Malignant brain tumors (BT) are among the cancers most frequently associated with constitutional mismatch repair deficiency (CMMRD), a rare childhood cancer predisposition syndrome resulting from biallelic germline mutations in mismatch repair genes. This study analyzed data from the European "Care for CMMRD" (C4CMMRD) database to describe their clinical characteristics, treatments, and outcome with the aim of improving its diagnosis/treatment., Methods: Retrospective analysis of data on patients with CMMRD and malignant BT from the C4CMMRD database up to July 2017., Results: Among the 87 registered patients, 49 developed 56 malignant BTs: 50 high-grade gliomas (HGG) (with giant multinucleated cells in 16/21 histologically reviewed tumors) and 6 embryonal tumors. The median age at first BT was 9.2 years [1.1-40.6], with nine patients older than 18. Twenty-seven patients developed multiple malignancies (including16 before the BT). Most patients received standard treatment, and eight patients immunotherapy for relapsed HGG. The 3- and 5-year overall survival (OS) rates were 30% (95% CI: 19-45) and 22% (95% CI: 12-37) after the first BT, with worse prognosis for HGG (3-year OS = 20.5%). Six patients were alive (median follow-up 2.5 years) and 43 dead (38 deaths, 88%, were BT-related). Other CMMRD-specific features were café-au-lait macules (40/41), multiple BTs (5/15), developmental brain anomalies (11/15), and consanguinity (20/38 families)., Conclusions: Several characteristics could help suspecting CMMRD in pediatric malignant BTs: giant cells on histology, previous malignancies, parental consanguinity, café-au-lait macules, multiple BTs, and developmental brain anomalies. The prognosis of CMMRD-associated BT treated with standard therapies is poor requiring new therapeutic up-front approaches., (© The Author(s) 2019. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)
- Published
- 2019
- Full Text
- View/download PDF
42. 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.
- Author
-
Bisogno G, De Salvo GL, Bergeron C, Gallego Melcón S, Merks JH, Kelsey A, Martelli H, Minard-Colin V, Orbach D, Glosli H, Chisholm J, Casanova M, Zanetti I, Devalck C, Ben-Arush M, Mudry P, Ferman S, Jenney M, and Ferrari A
- Subjects
- Adolescent, Antineoplastic Combined Chemotherapy Protocols adverse effects, Argentina, Brazil, Child, Cyclophosphamide adverse effects, Disease Progression, Disease-Free Survival, Europe, Female, Humans, Israel, Male, Remission Induction, Rhabdomyosarcoma, Alveolar mortality, Rhabdomyosarcoma, Alveolar pathology, Rhabdomyosarcoma, Embryonal mortality, Rhabdomyosarcoma, Embryonal pathology, Risk Assessment, Risk Factors, Time Factors, Vinorelbine adverse effects, Young Adult, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Cyclophosphamide administration & dosage, Maintenance Chemotherapy adverse effects, Maintenance Chemotherapy mortality, Rhabdomyosarcoma, Alveolar drug therapy, Rhabdomyosarcoma, Embryonal drug therapy, Vinorelbine administration & dosage
- 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/m
2 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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)- Published
- 2019
- Full Text
- View/download PDF
43. Mutations in MAGT1 lead to a glycosylation disorder with a variable phenotype.
- Author
-
Blommaert E, Péanne R, Cherepanova NA, Rymen D, Staels F, Jaeken J, Race V, Keldermans L, Souche E, Corveleyn A, Sparkes R, Bhattacharya K, Devalck C, Schrijvers R, Foulquier F, Gilmore R, and Matthijs G
- Subjects
- Adolescent, Child, Congenital Disorders of Glycosylation metabolism, DNA Mutational Analysis, Hexosyltransferases metabolism, Humans, Male, Membrane Proteins metabolism, Tumor Suppressor Proteins metabolism, Cation Transport Proteins genetics, Congenital Disorders of Glycosylation genetics
- Abstract
Congenital disorders of glycosylation (CDG) are a group of rare metabolic diseases, due to impaired protein and lipid glycosylation. We identified two patients with defective serum transferrin glycosylation and mutations in the MAGT1 gene. These patients present with a phenotype that is mainly characterized by intellectual and developmental disability. MAGT1 has been described to be a subunit of the oligosaccharyltransferase (OST) complex and more specifically of the STT3B complex. However, it was also claimed that MAGT1 is a magnesium (Mg
2+ ) transporter. So far, patients with mutations in MAGT1 were linked to a primary immunodeficiency, characterized by chronic EBV infections attributed to a Mg2+ homeostasis defect (XMEN). We compared the clinical and cellular phenotype of our two patients to that of an XMEN patient that we recently identified. All three patients have an N -glycosylation defect, as was shown by the study of different substrates, such as GLUT1 and SHBG, demonstrating that the posttranslational glycosylation carried out by the STT3B complex is dysfunctional in all three patients. Moreover, MAGT1 deficiency is associated with an enhanced expression of TUSC3, the homolog protein of MAGT1, pointing toward a compensatory mechanism. Hence, we delineate MAGT1-CDG as a disorder associated with two different clinical phenotypes caused by defects in glycosylation., Competing Interests: The authors declare no conflict of interest.- Published
- 2019
- Full Text
- View/download PDF
44. Addition of dose-intensified doxorubicin to standard chemotherapy for rhabdomyosarcoma (EpSSG RMS 2005): a multicentre, open-label, randomised controlled, phase 3 trial.
- Author
-
Bisogno G, Jenney M, Bergeron C, Gallego Melcón S, Ferrari A, Oberlin O, Carli M, Stevens M, Kelsey A, De Paoli A, Gaze MN, Martelli H, Devalck C, Merks JH, Ben-Arush M, Glosli H, Chisholm J, Orbach D, Minard-Colin V, and De Salvo GL
- Subjects
- Adolescent, Child, Child, Preschool, Dactinomycin administration & dosage, Disease-Free Survival, Dose-Response Relationship, Drug, Female, Humans, Ifosfamide administration & dosage, Infant, Male, Vincristine administration & dosage, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Doxorubicin administration & dosage, Rhabdomyosarcoma drug therapy
- 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/m
2 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<0·0001), thrombocytopenia (168 [67%] vs 59 [26%]; p<0.0001), and gastrointestinal adverse events (78 [31%] vs 19 [8%]; p<0·0001) were significantly more common in the IVA plus doxorubicin group than in the IVA group. Grade 3-5 infections (198 [79%] vs 128 [56%]; p<0·0001) were also significantly more common in the IVA plus doxorubicin group than in the IVA group, in which one patient had grade 5 infection. Two treatment-related deaths were reported (one patient developed septic shock and one affected by Goldenhar syndrome developed intractable seizures) in the IVA plus doxorubicin group, both occurring after the first cycle of treatment, and none were reported in the IVA group., Interpretations: The addition of dose-intensified doxorubicin to standard IVA chemotherapy did not show a significant improvement in the outcome of patients with high-risk non-metastatic rhabdomyosarcoma. Therefore, the IVA chemotherapy regimen should remain the standard of care for patients with localised rhabdomyosarcoma in Europe., Funding: Fondazione Città della Speranza, Italy, and the Association Léon Berard Enfant Cancéreux, France., (Copyright © 2018 Elsevier Ltd. All rights reserved.)- Published
- 2018
- Full Text
- View/download PDF
45. Neonatal screening improves sickle cell disease clinical outcome in Belgium.
- Author
-
Lê PQ, Ferster A, Dedeken L, Vermylen C, Vanderfaeillie A, Rozen L, Heijmans C, Huybrechts S, Devalck C, Cotton F, Ketelslegers O, Dresse MF, Fils JF, and Gulbis B
- Subjects
- Adolescent, Adult, Anemia, Sickle Cell diagnosis, Anemia, Sickle Cell ethnology, Belgium epidemiology, Child, Child, Preschool, Ethnicity, Female, Hospitalization statistics & numerical data, Humans, Infant, Infant, Newborn, Male, Propensity Score, Survival Analysis, Young Adult, Anemia, Sickle Cell mortality, Neonatal Screening, Outcome Assessment, Health Care
- Abstract
Objectives To compare the outcomes of sickle cell disease patients diagnosed through neonatal screening with those who were not. Methods In an observational multicenter study in Belgium, 167 screened and 93 unscreened sickle cell disease patients were analyzed for a total of 1116 and 958 patient-years of follow-up, respectively. Both groups were compared with propensity score analysis, with patients matched on three covariates (gender, genotype, and central Africa origin). Bonferroni correction was applied for all comparisons. Results Kaplan-Meier estimates of survival without bacteremia were significantly higher in the screened group than the unscreened group (94.47%; [95% CI, 88.64-97.36%] versus 83.78% [95% CI, 72.27-90.42%]), p = 0.032. Non-significant differences between both groups were reported for survival without acute chest syndrome, acute anemia, cerebral complication, severe infection, and vaso-occlusive crisis. Significantly lower hospitalization rate and days per 100 patient-years were observed in the screened compared with the unscreened group (0.27 vs. 0.63 and 1.25 vs. 2.82, p = 0.0006 and <0.0001). Conclusion These data confirm the benefit of a neonatal screening programme in reducing bacteremia and hospitalization.
- Published
- 2018
- Full Text
- View/download PDF
46. Automated RBC exchange compared to manual exchange transfusion for children with sickle cell disease is cost-effective and reduces iron overload.
- Author
-
Dedeken L, Lê PQ, Rozen L, El Kenz H, Huybrechts S, Devalck C, Diallo S, Heijmans C, and Ferster A
- Subjects
- Automation, Child, Cost-Benefit Analysis, Erythrocyte Transfusion economics, Erythrocyte Transfusion standards, Ferritins blood, Hemoglobin, Sickle metabolism, Humans, Anemia, Sickle Cell therapy, Erythrocyte Transfusion methods, Iron Overload prevention & control
- Abstract
Background: Chronic transfusion in sickle cell disease (SCD) remains the gold standard therapy for stroke prevention and for patients with severe disease despite adequate hydroxyurea treatment. The aim of our study was to assess the safety and efficacy of automated red blood cell exchange (aRBX) in patients with SCD previously treated with manual exchange transfusion (MET). Costs related to transfusion and chelation overtime were evaluated., Study Design and Methods: Beginning in January 2012, children with SCD who weighed 30 kg or more on MET could switch to aRBX. Clinical, biological, and procedures' data, including costs, were recorded for the last 6 months on MET and compared to those after the first and the second year on aRBX., Results: Ten patients switched from MET to aRBX at a median age of 11.8 years. After the switch, median hemoglobin S (HbS) increased significantly (33.5% on MET compared to 45% on aRBX; p < 0.001) but remained in the target values for all patients. Median ferritin decreased significantly (663.3 µg/L on MET compared to 126.8 µg/L on aRBX; p < 0.001) and intervals between procedures were significantly longer. The requirements of red blood cells (RBCs)/kg/year were not different on MET (0.88 unit/kg/year) than during the second year on aRBX (1.07 unit/kg/year; p = NS). MET costs were similar compared to aRBX since chelation was stopped in previously treated patients., Conclusion: Erythrocytapheresis reduces iron overload and allows a longer interval between procedures without a higher RBC requirement from the second year on aRBX. The cost did not increase as estimated in our Belgian Health Care System., (© 2018 AABB.)
- Published
- 2018
- Full Text
- View/download PDF
47. Children and adolescents with marginal zone lymphoma have an excellent prognosis with limited chemotherapy or a watch-and-wait strategy after complete resection.
- Author
-
Ronceray L, Abla O, Barzilai-Birenboim S, Bomken S, Chiang AK, Jazbec J, Kabickova E, Lazic J, Beishuizen A, Mellgren K, Tanaka F, Pillon M, Devalck C, Gouttenoire M, Makarova O, Burkhardt B, and Attarbaschi A
- Subjects
- Adolescent, Child, Child, Preschool, Disease-Free Survival, Female, Follow-Up Studies, Humans, Male, Retrospective Studies, Survival Rate, Lymphoma, B-Cell, Marginal Zone mortality, Lymphoma, B-Cell, Marginal Zone physiopathology, Lymphoma, B-Cell, Marginal Zone therapy
- Abstract
Data on management of pediatric marginal zone lymphoma (MZL) are scarce. This retrospective study assessed characteristics and outcome in 66 patients who were <18 years old. Forty-four (67%) had an extranodal MZL (EMZL), 21 (32%) a nodal MZL (NMZL), and one patient a splenic MZL. Thirty-three patients (50%) received a variable combination of adjuvant chemotherapy/immunotherapy/radiotherapy, while the remainder, including 20 of 21 with NMZL, entered an active observation period. Overall survival was excellent (98 ± 2%), although 11 patients relapsed (17%; NMZL, n = 1; EMZL, n = 10), seven after any therapy and four after complete resection only. In conclusion, outcome of NZML, in particular, seems to be excellent after (in)complete resection and observation only., (© 2017 Wiley Periodicals, Inc.)
- Published
- 2018
- Full Text
- View/download PDF
48. 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
-
Vaarwerk B, van der Lee JH, Breunis WB, Orbach D, Chisholm JC, Cozic N, Jenney M, van Rijn RR, McHugh K, Gallego S, Glosli H, Devalck C, Gaze MN, Kelsey A, Bergeron C, Stevens MCG, Oberlin O, Minard-Colin V, and Merks JHM
- Subjects
- Adolescent, Chemoradiotherapy methods, Child, Child, Preschool, Disease-Free Survival, Female, Humans, Induction Chemotherapy, Infant, International Cooperation, Male, Mesenchymoma surgery, Outcome Assessment, Health Care methods, Outcome Assessment, Health Care statistics & numerical data, Retrospective Studies, Rhabdomyosarcoma surgery, Societies, Medical, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Medical Oncology methods, Mesenchymoma therapy, Pediatrics methods, Rhabdomyosarcoma therapy
- 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 (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., 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. Cancer 2018;124:1016-24. © 2017 American Cancer Society., (© 2017 American Cancer Society.)
- Published
- 2018
- Full Text
- View/download PDF
49. Paratesticular rhabdomyosarcoma in children and adolescents-Outcome and patterns of relapse when utilizing a nonsurgical strategy for lymph node staging: Report from the International Society of Paediatric Oncology (SIOP) Malignant Mesenchymal Tumour 89 and 95 studies.
- Author
-
Rogers T, Minard-Colin V, Cozic N, Jenney M, Merks JHM, Gallego S, Devalck C, Gaze MN, Kelsey A, Oberlin O, Stevens M, Spicer RD, Bergeron C, and Martelli H
- Subjects
- Adolescent, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Child, Child, Preschool, Combined Modality Therapy, Disease-Free Survival, Humans, Infant, Kaplan-Meier Estimate, Lymphatic Metastasis diagnosis, Male, Orchiectomy methods, Retroperitoneal Neoplasms mortality, Retroperitoneal Neoplasms therapy, Rhabdomyosarcoma mortality, Rhabdomyosarcoma therapy, Scrotum surgery, Young Adult, Neoplasm Staging methods, Retroperitoneal Neoplasms pathology, Rhabdomyosarcoma pathology
- Abstract
Purpose: To report the results from International Society of Pediatric Oncology (SIOP) Malignant Mesenchymal Tumors studies (MMT 89 and 95) of males with nonmetastatic paratesticular rhabdomyosarcoma., Methods: From 1989 to 2003, 159 patients were included. Radical inguinal orchidectomy was recommended, but retroperitoneal lymph node (LN) assessment was based on imaging alone. The treatment was stratified by stage (SIOP tumor-node-metastasis staging system) and histology., Results: Median age at presentation was 5.6 years (range 0.3-17.6) and 120 patients were of <10 years (75%). Patients ≥10 years had tumors of >5 cm more frequently compared to patients of <10 years (54% vs. 22%, P = 0.0004). The 5- year overall and progression-free survivals were 94% and 83%, respectively. Seventy-eight percent of relapses occurred in the retroperitoneal LN. Thirty-one percent of stage N0 patients of age ≥10 years developed node relapse, compared with 8% of N0 patients aged <10 years (P = 0.0005)., Conclusions: Older patients with paratesticular rhabdomyosarcoma have a significant risk of LN relapse. These results support a surgical approach to LN staging in this subgroup of patients., (© 2017 Wiley Periodicals, Inc.)
- Published
- 2017
- Full Text
- View/download PDF
50. Nonparameningeal head and neck rhabdomyosarcoma in children and adolescents: Lessons from the consecutive International Society of Pediatric Oncology Malignant Mesenchymal Tumor studies.
- Author
-
Orbach D, Mosseri V, Gallego S, Kelsey A, Devalck C, Brenann B, van Noesel MM, Bergeron C, Merks JH, Rechnitzer C, Jenney M, Minard-Colin V, and Stevens M
- Subjects
- Adolescent, Child, Child, Preschool, Combined Modality Therapy, Disease-Free Survival, Female, Head and Neck Neoplasms mortality, Head and Neck Neoplasms pathology, Humans, Infant, Infant, Newborn, Male, Mesenchymoma mortality, Mesenchymoma pathology, Retrospective Studies, Rhabdomyosarcoma mortality, Rhabdomyosarcoma pathology, Risk Factors, Survival Rate, Treatment Outcome, Head and Neck Neoplasms therapy, Mesenchymoma therapy, Neoplasm Recurrence, Local epidemiology, Rhabdomyosarcoma therapy
- 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 < .01) even if it did not impact OS (RR = 1 [range, 0.5-2])., Conclusion: 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., (© 2016 Wiley Periodicals, Inc.)
- Published
- 2017
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.