André O von Bueren1, Carsten Friedrich2, Katja von Hoff3, Robert Kwiecien4, Klaus Müller5, Torsten Pietsch6, Monika Warmuth-Metz7, Peter Hau8, Martin Benesch9, Joachim Kuehl10, Rolf D Kortmann5, Stefan Rutkowski3. 1. Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Germany; Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, University Medical Center Goettingen, Germany. Electronic address: andre.vonbueren@med.uni-goettingen.de. 2. Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Germany; Division of Pediatric Oncology, Hematology and Hemostaseology, Department of Woman's and Children's Health, University Hospital Leipzig, Leipzig, Germany. 3. Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Germany. 4. Institute of Biostatistics and Clinical Research, University of Muenster, Germany. 5. Department of Radiation Oncology, University Medical Center of Leipzig, Germany. 6. Department of Neuropathology, University of Bonn, Germany. 7. Department of Neuroradiology, University of Wuerzburg, Germany. 8. Department of Neurology, University Medical Center Regensburg, Regensburg, Germany. 9. Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Austria. 10. Department of Pediatrics, University of Wuerzburg, Germany.
Abstract
BACKGROUND: Due to the rarity of metastatic medulloblastoma in adults, knowledge about the efficacy and toxicity of intensified chemotherapy and radiotherapy is limited. PATIENTS AND METHODS: Adults with disseminated medulloblastoma registered in the HIT2000 trial as observational patients and treated according to one of two different treatment regimens were analysed. The sandwich strategy MET-HIT2000AB4 consists of postoperative chemotherapy, hyperfractionated craniospinal radiotherapy, and maintenance chemotherapy; while the HIT'91 maintenance strategy consists of postoperative craniospinal radiotherapy, and maintenance chemotherapy. RESULTS: Twenty-three patients (median age: 30.7years), diagnosed from November 2001 to July 2009, and treated in 18 institutions in Germany and Austria, were eligible. The median follow-up of surviving patients was 3.99years. The 4-year event-free survival (EFS) and overall survival (OS)±standard error (SE) were 52%±12% and 91%±6%, respectively. The survival was similar in both treatment groups (HIT'91 maintenance strategy, n=9; MET-HIT2000AB4 sandwich strategy, n=14). Patients with large cell/anaplastic medulloblastoma relapsed and died (n=2; 4-year EFS/OS: 0%) and OS differed compared to patients with classic (n=11; 4-year EFS/OS: 71%/91%) and desmoplastic medulloblastoma (n=10; 4-year EFS/OS: 48%/100%), respectively (p=0.161 for EFS and p=0.033 for OS). Treatment-induced toxicities consisted mainly of neurotoxicity (50% of patients, ⩾ °II), followed by haematotoxicity and nephrotoxicity/ototoxicity. The professional outcome appeared to be negatively affected in the majority of evaluable patients (9/10). CONCLUSIONS: Treatment of adults with metastatic medulloblastoma according to the intensified paediatric HIT2000 protocol was feasible with acceptable toxicities. EFS rates achieved by both chemotherapeutic protocols were favourable and appear to be inferior to those obtained in older children/adolescents with metastatic disease.
BACKGROUND: Due to the rarity of metastatic medulloblastoma in adults, knowledge about the efficacy and toxicity of intensified chemotherapy and radiotherapy is limited. PATIENTS AND METHODS: Adults with disseminated medulloblastoma registered in the HIT2000 trial as observational patients and treated according to one of two different treatment regimens were analysed. The sandwich strategy MET-HIT2000AB4 consists of postoperative chemotherapy, hyperfractionated craniospinal radiotherapy, and maintenance chemotherapy; while the HIT'91 maintenance strategy consists of postoperative craniospinal radiotherapy, and maintenance chemotherapy. RESULTS: Twenty-three patients (median age: 30.7years), diagnosed from November 2001 to July 2009, and treated in 18 institutions in Germany and Austria, were eligible. The median follow-up of surviving patients was 3.99years. The 4-year event-free survival (EFS) and overall survival (OS)±standard error (SE) were 52%±12% and 91%±6%, respectively. The survival was similar in both treatment groups (HIT'91 maintenance strategy, n=9; MET-HIT2000AB4 sandwich strategy, n=14). Patients with large cell/anaplastic medulloblastoma relapsed and died (n=2; 4-year EFS/OS: 0%) and OS differed compared to patients with classic (n=11; 4-year EFS/OS: 71%/91%) and desmoplastic medulloblastoma (n=10; 4-year EFS/OS: 48%/100%), respectively (p=0.161 for EFS and p=0.033 for OS). Treatment-induced toxicities consisted mainly of neurotoxicity (50% of patients, ⩾ °II), followed by haematotoxicity and nephrotoxicity/ototoxicity. The professional outcome appeared to be negatively affected in the majority of evaluable patients (9/10). CONCLUSIONS: Treatment of adults with metastatic medulloblastoma according to the intensified paediatric HIT2000 protocol was feasible with acceptable toxicities. EFS rates achieved by both chemotherapeutic protocols were favourable and appear to be inferior to those obtained in older children/adolescents with metastatic disease.
Authors: Benjamin H Kann; Nataniel H Lester-Coll; Henry S Park; Debra N Yeboa; Jacqueline R Kelly; Joachim M Baehring; Kevin P Becker; James B Yu; Ranjit S Bindra; Kenneth B Roberts Journal: Neuro Oncol Date: 2017-02-01 Impact factor: 12.300
Authors: Dagmar Beier; Martin Proescholdt; Christiane Reinert; Torsten Pietsch; David T W Jones; Stefan M Pfister; Elke Hattingen; Clemens Seidel; Linda Dirven; Ralf Luerding; Jaap Reijneveld; Monika Warmuth-Metz; Matteo Bonsanto; Michael Bremer; Stephanie E Combs; Stefan Rieken; Ulrich Herrlinger; Holger Kuntze; Regine Mayer-Steinacker; Dag Moskopp; Thomas Schneider; Andreas Beringer; Uwe Schlegel; Walter Stummer; Helmut Welker; Astrid Weyerbrock; Frank Paulsen; Stefan Rutkowski; Michael Weller; Wolfgang Wick; Rolf-Dieter Kortmann; Ulrich Bogdahn; Peter Hau Journal: Neuro Oncol Date: 2018-02-19 Impact factor: 12.300
Authors: Didier Frappaz; Marc Barritault; Laure Montané; Florence Laigle-Donadey; Olivier Chinot; Emilie Le Rhun; Alice Bonneville-Levard; Andreas F Hottinger; David Meyronnet; Anne-Sophie Bidaux; Gwenaële Garin; David Pérol Journal: Neuro Oncol Date: 2021-11-02 Impact factor: 13.029
Authors: Linda Dirven; Ralf Luerding; Dagmar Beier; Elisabeth Bumes; Christiane Reinert; Clemens Seidel; Matteo Mario Bonsanto; Michael Bremer; Stefan Rieken; Stephanie E Combs; Ulrich Herrlinger; Corinna Seliger; Holger Kuntze; Regine Mayer-Steinacker; Annette Dieing; Claudius Bartels; Oliver Schnell; Astrid Weyerbrock; Sabine Seidel; Oliver Grauer; Minou Nadji-Ohl; Frank Paulsen; Michael Weller; Wolfgang Wick; Peter Hau Journal: J Neurooncol Date: 2020-05-04 Impact factor: 4.130