Low Grade Chiasmatic-Hypothalamic Glioma - Carboplatin and Vincristin Chemotherapy Effectively Defers Radiotherapy within a Comprehensive Treatment Strategy

Abstract

Background: Low grade gliomas arise in all CNS-locations and age groups, chiasmatic-hypothalamic tumors occur especially in young children. Early radiotherapy (RT) shall be deferred by chemotherapy (CT) within the concept of the HIT-LGG 1996 study, offering a comprehensive treatment strategy for all age groups. Patients: 198 of 905 protocol patients (21.9 %) had a chiasmatic (34), chiasmatic-hypothalamic (144) or hypothalamic (20) primary tumor, median age at diagnosis 3.6 years (0.2-16.3 y.), 54 had neurofibromatosis (27.3 %), 108 female (54.5 %). 98 children had severe visual impairment as their first symptom. The initial neurosurgical intervention resulted in 5 complete, 26 subtotal, 45 partial resections, 67 biopsies; 55 children had a diagnosis on the basis of neuroradiologic findings. Histology showed 132 pilocytic astrocytoma I°, 6 astrocytoma II°/nos and 2 DIGG/DIA I° (3 not known). Results: 82 children were treated at diagnosis, 68 upon clinical or radiological progression following observation times of 3.0 to 115.0 months. RT: 27 children received conventional (18) or interstitial (8) RT (1 not documented) at a median age of 7.3 years; 7 tumors went into further progression. At a median observation time of 50.1 months 21 tumors are stable, 3 regressive (2 not evaluable, 1 death). CT: 123 children received vincristin/carboplatin at a median age of 3.7 years. 105/123 achieved CR/PR/SD. 44/123 tumors were progressive after median 22.5 months, 37 with a chiasmatic-hypothalamic primary, 16/44 were irradiated. At a median observation time of 44.7 months 2 children are in complete remission, 92 tumors are stable, 8 regressive, 9 progressive. 4 children died, 8 are not evaluable. At 60 months overall survival of the cohort is 0.93; PFS of the CT-group is 0.61, the RT-free survival 0.83. Within the CT-group children with an age at diagnosis < 1 year and non-pilocytic histology are at increased risk for early progression. Causative factors cannot be defined, yet. Conclusion: Within the comprehensive treatment strategy for low grade glioma HIT-LGG 1996 chemotherapy is effective to delay the need for early radiotherapy in chiasmatic-hypothalamic glioma. More effective reduction of the risk for progression has to be sought for young children < 1 year.

Zusammenfassung

Hintergrund: Niedrig-maligne Gliome kommen in allen Altersgruppen und ZNS-Lokalisationen vor, besonders bei jungen Kindern häufen sich chiasmatisch-hypothalamische Tumoren. Entsprechend der HIT-LGG 1996 Studienstrategie, die Therapieempfehlungen für alle Altersgruppen beinhaltet, soll bei ihnen eine frühe Radiotherapie (RT) durch eine Chemotherapie (CT) vermieden werden. Patienten: 198 von 905 Protokollpatienten (21,9 %) hatten einen chiasmatischen (34), chiasmatisch-hypothalamischen (144) oder hypothalamischen (20) Primärtumor, medianes Diagnosealter 3,6 Jahre (0,2-16,3 J.), 54 mit Neurofibromatose (27,3 %), 108 weiblich (54,5 %). 98 Kinder hatten gravierende Seheinschränkungen als Erstsymptom. Der neurochirurgische Primäreingriff führte zu 5 kompletten, 26 subtotalen, 45 partiellen Resektionen, 67 Kinder hatten eine Biopsie; bei 55 Kindern erfolgte eine neuroradiologische Diagnosestellung. Neben 132 pilozytischen Astrozytomen I° wurden 6 Astrozytome II°/nicht näher bezeichnet und 2 DIGG/DIA I° histologisch diagnostiziert (3 nicht bekannt). Ergebnisse: 82 Kinder wurden bei Diagnosestellung behandelt, 68 bei klinischer oder radiologischer Progression nach Beobachtungszeiten von 3,0 bis 115,0 Monaten. RT: 27 Kinder erhielten eine konventionelle (18) oder interstitielle (8) RT (1nicht bekannt) bei einem medianen Alter von 7,3 Jahren. 7 Tumoren waren nachfolgend progredient. Nach median 50,1 Monaten sind 21 Tumoren stabilisiert, 3 regredient (2 nicht auswertbar, 1 Kind verstarb). CT: 123 Kinder erhielten Vincristin/Carboplatin bei einem medianen Alter von 3,7 Jahren. 105/123 erreichten eine CR/PR/SD, 44/123 Tumoren waren nach median 22,5 Monaten progredient, davon 37 mit chiasmatisch-hypothalamischem Sitz. 16/44 Kinder wurden nachfolgend bestrahlt. Bei einer Beobachtungsdauer von median 44,7 Monaten sind 2 Kinder in kompletter Remission, 92 Tumoren stabilisiert, 8 regredient, 9 progredient. 4 Kinder verstarben, 8 sind nicht auswertbar. Nach 60 Monaten liegt das Überleben (OS) der Gesamtgruppe bei 0,93; das progressionsfreie Überleben (PFS) der CT-Gruppe ist 0,61, das RT-freie Überleben 0,83. In der CT-Kohorte neigen aber Kinder mit einem Diagnosealter < 1 Jahr oder nicht-pilozytischer Histologie zu früher Progression. Die ursächlichen prognostischen Faktoren sind zu definieren. Schlussfolgerung: Im Rahmen der HIT-LGG-1996-Studie kann die Chemotherapie für Kinder mit chiasmatisch-hypothalamischen Tumoren den Strahlentherapiebeginn effektiv hinauszögern. Strategien für eine effektivere Reduktion des Progressionsrisikos für junge Kinder sind zu suchen.

Key words

Chiasmatic-hypothalamic glioma - children - chemotherapy - radiotherapy

Schlüsselwörter

Chiasmatisch-hypothalamische Gliome - Kinder - Chemotherapie - Radiotherapie

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