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Titolo:
Postoperative neoadjuvant chemotherapy before radiotherapy as compared to immediate radiotherapy followed by maintenance chemotherapy in the treatment of medulloblastoma in childhood: Results of the German prospective randomized trial HIT '91
Autore:
Kortmann, RD; Kuhl, J; Timmermann, B; Mittler, U; Urban, C; Budach, V; Richter, E; Willich, N; Flentje, M; Berthold, F; Slavc, I; Wolff, J; Meisner, C; Wiestler, O; Sorensen, N; Warmuth-Metz, M; Bamberg, M;
Indirizzi:
Univ Tubingen, Dept Radiotherapy, D-72076 Tubingen, Germany Univ TubingenTubingen Germany D-72076 herapy, D-72076 Tubingen, Germany Univ Tubingen, Inst Med Informat Proc, D-72076 Tubingen, Germany Univ Tubingen Tubingen Germany D-72076 t Proc, D-72076 Tubingen, Germany Univ Wuerzburg, Childrens Hosp, Wuerzburg, Germany Univ Wuerzburg Wuerzburg Germany rg, Childrens Hosp, Wuerzburg, Germany Univ Wuerzburg, Dept Radiotherapy, Wuerzburg, Germany Univ Wuerzburg Wuerzburg Germany Dept Radiotherapy, Wuerzburg, Germany Univ Wuerzburg, Dept Neurosurg, Wuerzburg, Germany Univ Wuerzburg Wuerzburg Germany rg, Dept Neurosurg, Wuerzburg, Germany Univ Wuerzburg, Dept Neuroradiol, Wuerzburg, Germany Univ Wuerzburg Wuerzburg Germany , Dept Neuroradiol, Wuerzburg, Germany Univ Magdeburg, Childrens Hosp, D-39106 Magdeburg, Germany Univ MagdeburgMagdeburg Germany D-39106 osp, D-39106 Magdeburg, Germany Graz Univ, Childrens Hosp, Graz, Austria Graz Univ Graz AustriaGraz Univ, Childrens Hosp, Graz, Austria Univ Berlin, Charite, Dept Radiotherapy, Berlin, Germany Univ Berlin Berlin Germany Charite, Dept Radiotherapy, Berlin, Germany Univ Luebeck, Dept Radiotherapy, Luebeck, Germany Univ Luebeck Luebeck Germany ebeck, Dept Radiotherapy, Luebeck, Germany Univ Muenster, Dept Radiotherapy, Muenster, Germany Univ Muenster Muenster Germany er, Dept Radiotherapy, Muenster, Germany Univ Cologne, Childrens Hosp, Cologne, Germany Univ Cologne Cologne Germany Cologne, Childrens Hosp, Cologne, Germany Univ Vienna, Childrens Hosp, Vienna, Austria Univ Vienna Vienna AustriaUniv Vienna, Childrens Hosp, Vienna, Austria Univ Calgary, Childrens Hosp, Calgary, AB, Canada Univ Calgary Calgary ABCanada gary, Childrens Hosp, Calgary, AB, Canada Univ Bonn, Dept Neuropathol, D-5300 Bonn, Germany Univ Bonn Bonn GermanyD-5300 nn, Dept Neuropathol, D-5300 Bonn, Germany Univ Bonn, Brain Tumor Reference Ctr, D-5300 Bonn, Germany Univ Bonn Bonn Germany D-5300 Tumor Reference Ctr, D-5300 Bonn, Germany
Titolo Testata:
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
fascicolo: 2, volume: 46, anno: 2000,
pagine: 269 - 279
SICI:
0360-3016(20000115)46:2<269:PNCBRA>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
PEDIATRIC-ONCOLOGY SIOP; PRERADIATION CHEMOTHERAPY; BRAIN-TUMORS; INTERNATIONAL-SOCIETY; ADJUVANT CHEMOTHERAPY; RADIATION TREATMENT; CHILDREN; CLASSIFICATION; METHOTREXATE; IRRADIATION;
Keywords:
medulloblastoma; radiotherapy; chemotherapy; quality assurance;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Kortmann, RD Univ Tubingen, Dept Radiotherapy, Hoppe Seyler Str 3, D-72076Tubingen, Germany Univ Tubingen Hoppe Seyler Str 3 Tubingen Germany D-72076 ny
Citazione:
R.D. Kortmann et al., "Postoperative neoadjuvant chemotherapy before radiotherapy as compared to immediate radiotherapy followed by maintenance chemotherapy in the treatment of medulloblastoma in childhood: Results of the German prospective randomized trial HIT '91", INT J RAD O, 46(2), 2000, pp. 269-279

Abstract

Purpose: The German Society of Pediatric Hematology and Oncology (GPOH) conducted a randomized, prospective, multicenter trial (HIT '91) in order to improve the survival of children with medulloblastoma by using postoperative neoadjuvant chemotherapy before radiation therapy as opposed to maintenance chemotherapy after immediate postoperative radiotherapy. Methods and Materials: Between 1991 and 1997, 158 patients were enrolled and 137 patients randomized. Seventy-two patients were allocated to receive neoadjuvant chemotherapy before radiotherapy (arm I, investigational). Chemotherapy consisted of ifosfamide, etoposide, intravenous high-dose methotrexate, cisplatin, and cytarabine given in two cycles. In arm II (standard arm), 65 patients were assigned to receive immediate postoperative radiotherapy, with concomitant vincristine followed by 8 cycles of maintenance chemotherapy consisting of cisplatin, CCNU, and vincristine ("Philadelphia protocol"). All patients received radiotherapy to the craniospinal axis (35.2 Gy total dose, 1.6 Gy fractionated dose/5 times per week followed by a boost to posterior fossa with 20 Gy, 2.0 Gy fractionated dose). Results: During chemotherapy Grade III/IV infections were predominant in arm I (40%). Peripheral neuropathy and ototoxicity were prevailing in arm II(37% and 34%, respectively). Dose modification was necessary in particularin arm II (63%). During radiotherapy acute toxicity was mild in the majority of patients and equally distributed in both arms, Myelosuppression led to a mean prolongation of treatment time of 11.5 days in arm I and 7.5 days in arm II, and interruptions in 35% of patients in arm I. Quality control of radiotherapy revealed correct treatment in more than 88% for dose prescription, more than 88% for coverage of target volume, and 98% for field matching. At a median follow-up of 30 months (range 1.4-62 months), the Kaplan-Meier estimates for relapse-free survival at 3 years for all randomized patients were 0.70 +/- 0.08; for patients with residual disease: 0.72 +/- 0.06;without residual disease: 0.68 +/- 0.09; M0: 0.72 +/- 0.04; M1: 0.65 +/- 0.12; and M2/3: 0.30 +/- 0,15, For all randomized patients without M2/3 disease: 0.65 +/- 0.05 (arm I) and 0.78 +/- 0.06 (arm II) (p < 0.03); patients between 3 and 5.9 years: 0.60 +/- 0.13 and 0.64 +/- 0,14, respectively, butpatients between 6 and 18 years: 0.62 +/- 0.09 and 0.84 +/- 0.08, respectively (p < 0.03). In a univariate analysis the only negative prognostic factors were M2/3 disease (p < 0.002) and an age of less than 8 years (p < 0,03). Conclusions: Maintenance chemotherapy would seem to be more effective in low-risk medulloblastoma, especially in patients older than 6 years of age. Neoadjuvant chemotherapy was accompanied by increased myelotoxicity of the subsequent radiotherapy, causing a higher rate of interruptions and an extended overall treatment time, Delayed and/or protracted radiotherapy may therefore have a negative impact on outcome, M2/3 disease was associated with a poor survival in both arms, suggesting the need for a more intensive treatment. Young age and M2/3 stage were negative prognostic factors in medulloblastoma, but residual or M1 disease was not, suggesting a new stratification system for risk subgroups. High quality of radiotherapy may be a major contributing factor for the overall outcome, (C) 2000 Elsevier Science Inc.

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Documento generato il 05/07/20 alle ore 02:44:19