nach oben

Erschienen in:

03.11.2018 | Clinical Study

Pre-irradiation intensive induction and marrow-ablative consolidation chemotherapy in young children with newly diagnosed high-grade brainstem gliomas: report of the “head-start” I and II clinical trials

verfasst von: Diana S. Osorio, Neha Patel, Lingyun Ji, Richard Sposto, Joseph Stanek, Sharon L. Gardner, Jeffrey C. Allen, Albert Cornelius, Geoffrey B. McCowage, Amanda Termuhlen, Ira J. Dunkel, Melanie Comito, James Garvin, Jonathan L. Finlay

Erschienen in: Journal of Neuro-Oncology | Ausgabe 3/2018

Einloggen, um Zugang zu erhalten

Abstract

Background

The dismal outcome in children with high-grade brainstem gliomas (BSG) accentuates the need for effective therapeutic strategies. We investigated the role of intensive, including marrow-ablative, chemotherapy regimens in the treatment of young children with newly-diagnosed high-grade BSG.

Methods

Between 1991-and-2002, 15 eligible children less than 10 years of age with a diagnosis of high-grade BSG were treated on “Head-Start” I and II protocols (HSI and HSII). Treatment included Induction with 4–5 cycles of one of three intensive chemotherapy regimens followed by Consolidation with one cycle of marrow-ablative chemotherapy (thiotepa, carboplatin and etoposide) with autologous hematopoietic cell rescue (AHCR). Irradiation was required for children over 6 years of age or for those with residual tumor at the end of Consolidation.

Results

We had two long-term survivors who were found retrospectively to harbor low-grade glial tumors and thus were not included in the survival analysis. Of the remaining 13 patients, the 1-year event-free (EFS) and overall (OS) survival for these children were 31% (95% CI 9–55%) and 38% (95% CI 14–63%), respectively. Median EFS and OS were 6.6 (95% CI 2.7, 12.7) and 8.7 months (95% CI 6.9, 20.9), respectively. Eight patients developed progressive disease during study treatment (seven during Induction and one at the end of Consolidation). Ten children received focal irradiation, five for residual tumor (three following Induction and two following Consolidation) and five due to disease progression.

Conclusions

Children with high-grade BSG did not benefit from this intensive chemotherapy strategy administered prior to irradiation.

Walker DA, Punt JA, Sokal M (1999) Clinical management of brain stem glioma. Arch Dis Child 80(6):558–564CrossRefPubMedPubMedCentral

Cartmill M, Punt J (1999) Diffuse brain stem glioma. A review of stereotactic biopsies. Childs Nerv Syst 15(5):235–237CrossRefPubMed

Maria BL, Rehder K, Eskin TA et al (1993) Brainstem glioma: I. Pathology, clinical features, and therapy. J Child Neurol 8(2):112–128CrossRefPubMed

Espinoza JC, Haley K, Patel N et al (2016) Outcome of young children with high-grade glioma treated with irradiation-avoiding intensive chemotherapy regimens: Final report of the Head Start II and III trials. Pediatr Blood Cancer 63(10):1806–1813CrossRefPubMedPubMedCentral

Zimmerman RA (1996) Neuroimaging of primary brainstem gliomas: diagnosis and course. Pediatr Neurosurg 25(1):45–53CrossRefPubMed

Hargrave D, Bartels U, Bouffet E (2006) Diffuse brainstem glioma in children: critical review of clinical trials. Lancet Oncol 7(3):241–248CrossRefPubMed

Jansen MH, van Vuurden DG, Vandertop WP, Kaspers GJ (2012) Diffuse intrinsic pontine gliomas: a systematic update on clinical trials and biology. Cancer Treat Rev 38(1):27–35CrossRefPubMed

Eifel PJ, Cassady JR, Belli JA (1987) Radiation therapy of tumors of the brainstem and midbrain in children: experience of the Joint Center for Radiation Therapy and Children’s Hospital Medical Center (1971–1981). Int J Radiat Oncol Biol Phys 13(6):847–852CrossRefPubMed

Freeman CR, Suissa S (1986) Brain stem tumors in children: results of a survey of 62 patients treated with radiotherapy. Int J Radiat Oncol Biol Phys 12(10):1823–1828CrossRefPubMed

10.

Packer RJ, Boyett JM, Zimmerman RA et al (1994) Outcome of children with brain stem gliomas after treatment with 7800 cGy of hyperfractionated radiotherapy. A Childrens Cancer Group Phase I/II Trial. Cancer 74(6):1827–1834CrossRefPubMed

11.

Packer RJ, Prados M, Phillips P et al (1996) Treatment of children with newly diagnosed brain stem gliomas with intravenous recombinant beta-interferon and hyperfractionated radiation therapy: a childrens cancer group phase I/II study. Cancer 77(10):2150–2156CrossRefPubMed

12.

Jakacki RI, Siffert J, Jamison C, Velasquez L, Allen JC (1999) Dose-intensive, time-compressed procarbazine, CCNU, vincristine (PCV) with peripheral blood stem cell support and concurrent radiation in patients with newly diagnosed high-grade gliomas. J Neurooncol 44(1):77–83CrossRefPubMed

13.

Broniscer A, Leite CC, Lanchote VL, Machado TM, Cristofani LM (2000) Radiation therapy and high-dose tamoxifen in the treatment of patients with diffuse brainstem gliomas: results of a Brazilian cooperative study. Brainstem Glioma Cooperative Group. J Clin Oncol 18(6):1246–1253CrossRefPubMed

14.

Bernier-Chastagner V, Grill J, Doz F et al (2005) Topotecan as a radiosensitizer in the treatment of children with malignant diffuse brainstem gliomas: results of a French Society of Paediatric Oncology Phase II Study. Cancer 104(12):2792–2797CrossRefPubMed

15.

Estlin EJ, Lashford L, Ablett S et al (1998) Phase I study of temozolomide in paediatric patients with advanced cancer. United Kingdom Children’s Cancer Study Group. Br J Cancer 78(5):652–661CrossRefPubMedPubMedCentral

16.

Broniscer A, Iacono L, Chintagumpala M et al (2005) Role of temozolomide after radiotherapy for newly diagnosed diffuse brainstem glioma in children: results of a multiinstitutional study (SJHG-98). Cancer 103(1):133–139CrossRefPubMed

17.

Sharp JR, Bouffet E, Stempak D et al (2010) A multi-centre Canadian pilot study of metronomic temozolomide combined with radiotherapy for newly diagnosed paediatric brainstem glioma. Eur J Cancer 46(18):3271–3279CrossRefPubMed

18.

Cohen KJ, Heideman RL, Zhou T et al (2011) Temozolomide in the treatment of children with newly diagnosed diffuse intrinsic pontine gliomas: a report from the Children’s Oncology Group. Neuro-oncology 13(4):410–416CrossRefPubMedPubMedCentral

19.

Calvert AH, Newell DR, Gumbrell LA et al (1989) Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol 7(11):1748–1756CrossRefPubMed

20.

Mason WP, Grovas A, Halpern S et al (1998) Intensive chemotherapy and bone marrow rescue for young children with newly diagnosed malignant brain tumors. J Clin Oncol 16(1):210–221CrossRefPubMed

21.

Fouladi M, Nicholson HS, Zhou T et al (2007) A phase II study of the farnesyl transferase inhibitor, tipifarnib, in children with recurrent or progressive high-grade glioma, medulloblastoma/primitive neuroectodermal tumor, or brainstem glioma: a Children’s Oncology Group study. Cancer 110(11):2535–2541CrossRefPubMed

22.

Jennings MT, Sposto R, Boyett JM et al (2002) Preradiation chemotherapy in primary high-risk brainstem tumors: phase II study CCG-9941 of the Children’s Cancer Group. J Clin Oncol 20(16):3431–3437CrossRefPubMed

23.

Jenkin RDT, Boesel C, Boesel C, Fau - Ertel I, Ertel I, Fau - Evans A et al. (1987) Brain-stem tumors in childhood: a prospective randomized trial of irradiation with and without adjuvant CCNU, VCR, and prednisone. A report of the Childrens Cancer Study Group. 66(2):227-233

24.

Jones C, Karajannis MA, Jones DT et al. (2016) Pediatric high-grade glioma: biologically and clinically in need of new thinking. Neuro-oncology. 19(2):153-161PubMedCentral

25.

Duffner PK, Horowitz ME, Krischer JP et al (1993) Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors. N Engl J Med 328(24):1725–1731CrossRefPubMed

26.

Doz F, Neuenschwander S, Bouffet E et al (2002) Carboplatin before and during radiation therapy for the treatment of malignant brain stem tumours: a study by the Societe Francaise d’Oncologie Pediatrique. Eur J Cancer 38(6):815–819CrossRefPubMed

27.

Kretschmar CS, Tarbell NJ, Barnes PD, Krischer JP, Burger PC, Kun L (1993) Pre-irradiation chemotherapy and hyperfractionated radiation therapy 66 Gy for children with brain stem tumors. A phase II study of the Pediatric Oncology Group, Protocol 8833. Cancer 72(4):1404–1413CrossRefPubMed

28.

Frappaz D, Schell M, Thiesse P et al (2008) Preradiation chemotherapy may improve survival in pediatric diffuse intrinsic brainstem gliomas: final results of BSG 98 prospective trial. Neuro-oncology 10(4):599–607CrossRefPubMedPubMedCentral

29.

Gokce-Samar Z, Beuriat PA, Faure-Conter C et al (2016) Pre-radiation chemotherapy improves survival in pediatric diffuse intrinsic pontine gliomas. Childs Nerv Syst 32(8):1415–1423CrossRefPubMed

30.

Donelli MG, Zucchetti M, D’Incalci M (1992) Do anticancer agents reach the tumor target in the human brain? Cancer Chemother Pharmacol 30(4):251–260CrossRefPubMed

31.

Postmus PE, Holthuis JJ, Haaxma-Reiche H et al (1984) Penetration of VP 16–213 into cerebrospinal fluid after high-dose intravenous administration. J Clin Oncol 2(3):215–220CrossRefPubMed

32.

Hochberg FH, Parker LM, Takvorian T, Canellos GP, Zervas NT (1981) High-dose BCNU with autologous bone marrow rescue for recurrent glioblastoma multiforme. J Neurosurg 54(4):455–460CrossRefPubMed

33.

Mbidde EK, Selby PJ, Perren TJ et al (1988) High dose BCNU chemotherapy with autologous bone marrow transplantation and full dose radiotherapy for grade IV astrocytoma. Br J Cancer 58(6):779–782CrossRefPubMedPubMedCentral

34.

Johnson DB, Thompson JM, Corwin JA et al (1987) Prolongation of survival for high-grade malignant gliomas with adjuvant high-dose BCNU and autologous bone marrow transplantation. J Clin Oncol 5(5):783–789CrossRefPubMed

35.

Papadakis V, Dunkel IJ, Cramer LD et al (2000) High-dose carmustine, thiotepa and etoposide followed by autologous bone marrow rescue for the treatment of high risk central nervous system tumors. Bone Marrow Transplant 26(2):153–160CrossRefPubMed

36.

Edwards MS, Levin VA, Seager ML, Pischer TL, Wilson CB (1979) Phase II evaluation of thioTEPA for treatment of central nervous system tumors. Cancer Treat Rep 63(8):1419–1421PubMed

37.

Heideman RL, Cole DE, Balis F et al (1989) Phase I and pharmacokinetic evaluation of thiotepa in the cerebrospinal fluid and plasma of pediatric patients: evidence for dose-dependent plasma clearance of thiotepa. Cancer Res 49(3):736–741PubMed

38.

Tartaglia RLCD, Heideman R, Balis F (1989) Chemosensitivity of central nervous tumors to thiotepa and tepa. Proc Am Assoc Cancer Res 30:1833

39.

Ascendo JAT, Feldman (1989) High dose thiotepa with autologous bone marrow transplantation and localized radiotherapy for patients with astrocytoma grade III-IV. Proc Am Assoc Cancer Res 9:90

40.

Heideman RL, Packer RJ, Reaman GH et al (1993) A phase II evaluation of thiotepa in pediatric central nervous system malignancies. Cancer 72(1):271–275CrossRefPubMed

41.

Heideman RL, Douglass EC, Krance RA et al (1993) High-dose chemotherapy and autologous bone marrow rescue followed by interstitial and external-beam radiotherapy in newly diagnosed pediatric malignant gliomas. J Clin Oncol 11(8):1458–1465CrossRefPubMed

42.

Kalifa C, Hartmann O, Demeocq F et al (1992) High-dose busulfan and thiotepa with autologous bone marrow transplantation in childhood malignant brain tumors: a phase II study. Bone Marrow Transplant 9(4):227–233PubMed

43.

Finlay JL, Goldman S, Wong MC et al (1996) Pilot study of high-dose thiotepa and etoposide with autologous bone marrow rescue in children and young adults with recurrent CNS tumors. The Children’s Cancer Group. J Clin Oncol 14(9):2495–2503CrossRefPubMed

44.

Finlay JL, August C, Packer R et al (1990) High-dose multi-agent chemotherapy followed by bone marrow ‘rescue’ for malignant astrocytomas of childhood and adolescence. J Neurooncol 9(3):239–248CrossRefPubMed

45.

Bouffet E, Mottolese C, Jouvet A et al (1997) Etoposide and thiotepa followed by ABMT (autologous bone marrow transplantation) in children and young adults with high-grade gliomas. Eur J Cancer 33(1):91–95CrossRefPubMed

46.

Fagioli F, Biasin E, Mastrodicasa L et al (2004) High-dose thiotepa and etoposide in children with poor-prognosis brain tumors. Cancer 100(10):2215–2221CrossRefPubMed

47.

Guruangan S, Dunkel IJ, Goldman S et al (1998) Myeloablative chemotherapy with autologous bone marrow rescue in young children with recurrent malignant brain tumors. J Clin Oncol 16(7):2486–2493CrossRefPubMed

48.

Kedar A, Maria BL, Graham-Pole J et al (1994) High-dose chemotherapy with marrow reinfusion and hyperfractionated irradiation for children with high-risk brain tumors. Med Pediatr Oncol 23(5):428–436CrossRefPubMed

49.

Dunkel IJ, Garvin JH Jr, Goldman S et al (1998) High dose chemotherapy with autologous bone marrow rescue for children with diffuse pontine brain stem tumors. Children’s Cancer Group. J Neurooncol 37(1):67–73CrossRefPubMed

50.

Bouffet E, Raquin M, Doz F et al (2000) Radiotherapy followed by high dose busulfan and thiotepa: a prospective assessment of high dose chemotherapy in children with diffuse pontine gliomas. Cancer 88(3):685–692CrossRefPubMed

Titel: Pre-irradiation intensive induction and marrow-ablative consolidation chemotherapy in young children with newly diagnosed high-grade brainstem gliomas: report of the “head-start” I and II clinical trials
verfasst von: Diana S. Osorio
Neha Patel
Lingyun Ji
Richard Sposto
Joseph Stanek
Sharon L. Gardner
Jeffrey C. Allen
Albert Cornelius
Geoffrey B. McCowage
Amanda Termuhlen
Ira J. Dunkel
Melanie Comito
James Garvin
Jonathan L. Finlay
Publikationsdatum: 03.11.2018
Verlag: Springer US
Erschienen in: Journal of Neuro-Oncology / Ausgabe 3/2018
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-018-03003-z

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Frühe Alzheimertherapie lohnt sich

25.04.2024 AAN-Jahrestagung 2024 Nachrichten

Ist die Tau-Last noch gering, scheint der Vorteil von Lecanemab besonders groß zu sein. Und beginnen Erkrankte verzögert mit der Behandlung, erreichen sie nicht mehr die kognitive Leistung wie bei einem früheren Start. Darauf deuten neue Analysen der Phase-3-Studie Clarity AD.

Viel Bewegung in der Parkinsonforschung

25.04.2024 Parkinson-Krankheit Nachrichten

Neue arznei- und zellbasierte Ansätze, Frühdiagnose mit Bewegungssensoren, Rückenmarkstimulation gegen Gehblockaden – in der Parkinsonforschung tut sich einiges. Auf dem Deutschen Parkinsonkongress ging es auch viel um technische Innovationen.

Demenzkranke durch Antipsychotika vielfach gefährdet

23.04.2024 Demenz Nachrichten

Wenn Demenzkranke aufgrund von Symptomen wie Agitation oder Aggressivität mit Antipsychotika behandelt werden, sind damit offenbar noch mehr Risiken verbunden als bislang angenommen.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Background

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2018

Diagnostic accuracy of MRI texture analysis for grading gliomas

Clinical and prognostic features of spinal meningioma: a thorough analysis from a single neurosurgical center

Reirradiation and PD-1 inhibition with nivolumab for the treatment of recurrent diffuse intrinsic pontine glioma: a single-institution experience

Stereotactic radiosurgery for hypervascular intracranial tumors

Clinical factors associated with mortality within three months after radiosurgery of asymptomatic brain metastases from non-small cell lung cancer