Skip to main content
Erschienen in: Journal of Neuro-Oncology 1/2019

25.09.2019 | Clinical Study

Efficacy of initial temozolomide for high-risk low grade gliomas in a phase II AINO (Italian Association for Neuro-Oncology) study: a post-hoc analysis within molecular subgroups of WHO 2016

verfasst von: Roberta Rudà, Alessia Pellerino, Andrea Pace, Carmine Maria Carapella, Cristina Dealis, Manuela Caroli, Marina Faedi, Lorenzo Bello, Enrica Migliore, Giulia Marchese, Luca Bertero, Paola Cassoni, Riccardo Soffietti

Erschienen in: Journal of Neuro-Oncology | Ausgabe 1/2019

Einloggen, um Zugang zu erhalten

Abstract

Introduction

The optimal management of high risk WHO grade II gliomas after surgery is debated including the role of initial temozolomide to delay radiotherapy and risk of cognitive defects.

Methods

A post-hoc analysis of a phase II multicenter study on high risk WHO grade II gliomas, receiving initial temozolomide alone, has re-evaluated the long-term results within the molecular subgroups of WHO 2016. The primary endpoint of the study was response according to RANO, being seizure response, PFS and OS secondary endpoints.

Results

Response rate among oligodendrogliomas IDH-mutant and 1p/19q codeleted (76%) was significantly higher than that among diffuse astrocytomas either mutant (55%) or wild-type (36%). A reduction of seizure frequency > 50% was observed in 87% of patients and a seizure freedom in 72%. The probability of seizure reduction > 50% was significantly associated with the presence of an IDH mutation. Median PFS, PFS at 5 and 10 years, median OS and OS at 5 and 10 years were significantly longer in oligodendrogliomas IDH-mutant and 1p/19q codeleted. Sixty-seven percent of patients with oligodendroglioma IDH mutant and 1p/19q codeleted did not recur with a median follow up of 9.3 years, while 59% did not receive radiotherapy at recurrence with a median follow up of 8.2 years.

Conclusions

The beneficial effects of initial temozolomide prevail in oligodendrogliomas IDH-mutant and 1p/19q codeleted: thus, these tumors, when incompletely resected or progressive after surgery alone, or with intractable seizures, should receive temozolomide as initial treatment with salvage radiotherapy and/o reoperation and/or second-line chemotherapy at recurrence.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat van den Bent MJ, Afra D, de Witte O et al (2005) Long-term efficacy of early versus delayed radiotherapy for low-grade astrocytoma and oligodendroglioma in adults: the EORTC 22845 randomised trial. Lancet 366(9490):985–990CrossRef van den Bent MJ, Afra D, de Witte O et al (2005) Long-term efficacy of early versus delayed radiotherapy for low-grade astrocytoma and oligodendroglioma in adults: the EORTC 22845 randomised trial. Lancet 366(9490):985–990CrossRef
2.
Zurück zum Zitat Buckner JC, Shaw EG, Pugh SL et al (2016) Radiation plus procarbazine, CCNU, and vincristine in low-grade glioma. N Engl J Med 374(14):1344–1355CrossRef Buckner JC, Shaw EG, Pugh SL et al (2016) Radiation plus procarbazine, CCNU, and vincristine in low-grade glioma. N Engl J Med 374(14):1344–1355CrossRef
3.
Zurück zum Zitat Douw L, Klein M, Fagel SS et al (2009) Cognitive and radiological effects of radiotherapy in patients with low-grade glioma: long-term follow-up. Lancet Neurol 8(9):810–818CrossRef Douw L, Klein M, Fagel SS et al (2009) Cognitive and radiological effects of radiotherapy in patients with low-grade glioma: long-term follow-up. Lancet Neurol 8(9):810–818CrossRef
4.
Zurück zum Zitat Brada M, Viviers L, Abson C et al (2003) Phase II study of primary temozolomide chemotherapy in patients with WHO grade II gliomas. Ann Oncol 14(12):1715–1721CrossRef Brada M, Viviers L, Abson C et al (2003) Phase II study of primary temozolomide chemotherapy in patients with WHO grade II gliomas. Ann Oncol 14(12):1715–1721CrossRef
5.
Zurück zum Zitat Wahl M, Phillips JJ, Molinaro AM et al (2017) Chemotherapy for adult low-grade gliomas: clinical outcomes by molecular subtype in a phase II study of adjuvant temozolomide. Neuro-Oncology 19(2):242–251PubMed Wahl M, Phillips JJ, Molinaro AM et al (2017) Chemotherapy for adult low-grade gliomas: clinical outcomes by molecular subtype in a phase II study of adjuvant temozolomide. Neuro-Oncology 19(2):242–251PubMed
6.
Zurück zum Zitat Pouratian N, Gasco J, Sherman JH et al (2007) Toxicity and efficacy of protracted low dose temozolomide for the treatment of low grade gliomas. J Neurooncol 82(3):281–288CrossRef Pouratian N, Gasco J, Sherman JH et al (2007) Toxicity and efficacy of protracted low dose temozolomide for the treatment of low grade gliomas. J Neurooncol 82(3):281–288CrossRef
7.
Zurück zum Zitat Kesari S, Schiff D, Drappatz J et al (2009) Phase II study of protracted daily temozolomide for low-grade gliomas in adults. Clin Cancer Res 15(1):330–337CrossRef Kesari S, Schiff D, Drappatz J et al (2009) Phase II study of protracted daily temozolomide for low-grade gliomas in adults. Clin Cancer Res 15(1):330–337CrossRef
8.
Zurück zum Zitat Baumert BG, Hegi ME, van den Bent MJ et al (2016) Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033–26033): a randomised, open-label, phase 3 intergroup study. Lancet Oncol 17(11):1521–1532CrossRef Baumert BG, Hegi ME, van den Bent MJ et al (2016) Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033–26033): a randomised, open-label, phase 3 intergroup study. Lancet Oncol 17(11):1521–1532CrossRef
9.
Zurück zum Zitat Pellerino A, Franchino F, Pace A et al. (2017) Temozolomide (TMZ) 1 week on/1 week off as initial treatment for high risk low grade oligodendroglial tumors: a phase II AINO (Italian Association for Neuro-Oncology) study. Neuro Oncol 19(suppl_3):iii21CrossRef Pellerino A, Franchino F, Pace A et al. (2017) Temozolomide (TMZ) 1 week on/1 week off as initial treatment for high risk low grade oligodendroglial tumors: a phase II AINO (Italian Association for Neuro-Oncology) study. Neuro Oncol 19(suppl_3):iii21CrossRef
10.
Zurück zum Zitat Louis DN, Perry A, Reifenberger G et al (2016) The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 131(6):803–820CrossRef Louis DN, Perry A, Reifenberger G et al (2016) The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 131(6):803–820CrossRef
11.
Zurück zum Zitat van den Bent MJ, Wefel JS, Schiff D et al (2011) Response assessment in neuro-oncology (a report of the RANO group): assessment of outcome in trials of diffuse low-grade gliomas. Lancet Oncol 12(6):583–593CrossRef van den Bent MJ, Wefel JS, Schiff D et al (2011) Response assessment in neuro-oncology (a report of the RANO group): assessment of outcome in trials of diffuse low-grade gliomas. Lancet Oncol 12(6):583–593CrossRef
12.
Zurück zum Zitat Hoang-Xuan K, Capelle L, Kujas M et al (2004) Temozolomide as initial treatment for adults with low-grade oligodendrogliomas or oligoastrocytomas and correlation with chromosome 1p deletions. J Clin Oncol 22(15):3133–3138CrossRef Hoang-Xuan K, Capelle L, Kujas M et al (2004) Temozolomide as initial treatment for adults with low-grade oligodendrogliomas or oligoastrocytomas and correlation with chromosome 1p deletions. J Clin Oncol 22(15):3133–3138CrossRef
13.
Zurück zum Zitat Avila EK, Chamberlain M, Schiff D et al (2017) Seizure control as a new metric in assessing efficacy of tumor treatment in low-grade glioma trials. Neuro-Oncology 19(1):12–21CrossRef Avila EK, Chamberlain M, Schiff D et al (2017) Seizure control as a new metric in assessing efficacy of tumor treatment in low-grade glioma trials. Neuro-Oncology 19(1):12–21CrossRef
14.
Zurück zum Zitat Kaloshi G, Benouaich-Amiel A, Diakite F et al (2007) Temozolomide for low-grade gliomas: predictive impact of 1p/19q loss on response and outcome. Neurology 68(21):1831–1836CrossRef Kaloshi G, Benouaich-Amiel A, Diakite F et al (2007) Temozolomide for low-grade gliomas: predictive impact of 1p/19q loss on response and outcome. Neurology 68(21):1831–1836CrossRef
15.
Zurück zum Zitat Sherman JH, Moldovan K, Yeoh HK et al (2011) Impact of temozolomide chemotherapy on seizure frequency in patients with low-grade gliomas. J Neurosurg 114(6):1617–1621CrossRef Sherman JH, Moldovan K, Yeoh HK et al (2011) Impact of temozolomide chemotherapy on seizure frequency in patients with low-grade gliomas. J Neurosurg 114(6):1617–1621CrossRef
16.
Zurück zum Zitat Koekkoek JA, Dirven L, Heimans JJ et al (2015) Seizure reduction in a low-grade glioma: more than a beneficial side effect of temozolomide. J Neurol Neurosurg Psychiatry 86(4):366–373CrossRef Koekkoek JA, Dirven L, Heimans JJ et al (2015) Seizure reduction in a low-grade glioma: more than a beneficial side effect of temozolomide. J Neurol Neurosurg Psychiatry 86(4):366–373CrossRef
17.
Zurück zum Zitat Rudà R, Magliola U, Bertero L et al (2013) Seizure control following radiotherapy in patients with diffuse gliomas: a retrospective study. Neuro-Oncology 15(12):1739–1749CrossRef Rudà R, Magliola U, Bertero L et al (2013) Seizure control following radiotherapy in patients with diffuse gliomas: a retrospective study. Neuro-Oncology 15(12):1739–1749CrossRef
18.
Zurück zum Zitat Stockhammer F, Misch M, Helms HJ et al (2012) IDH1/2 mutations in WHO grade II astrocytomas associated with localization and seizure as the initial symptom. Seizure 21(3):194–197CrossRef Stockhammer F, Misch M, Helms HJ et al (2012) IDH1/2 mutations in WHO grade II astrocytomas associated with localization and seizure as the initial symptom. Seizure 21(3):194–197CrossRef
19.
Zurück zum Zitat Liubinas SV, D'Abaco GM, Moffat BM et al (2014) IDH1 mutation is associated with seizures and protoplasmic subtype in patients with low-grade gliomas. Epilepsia 55(9):1438–1443CrossRef Liubinas SV, D'Abaco GM, Moffat BM et al (2014) IDH1 mutation is associated with seizures and protoplasmic subtype in patients with low-grade gliomas. Epilepsia 55(9):1438–1443CrossRef
20.
Zurück zum Zitat Donovan LE, Lassman AB (2019) Chemotherapy Treatment and Trials in Low-Grade Gliomas. Neurosurg Clin N Am 30(1):103–109CrossRef Donovan LE, Lassman AB (2019) Chemotherapy Treatment and Trials in Low-Grade Gliomas. Neurosurg Clin N Am 30(1):103–109CrossRef
21.
Zurück zum Zitat Jhaveri J, Liu Y, Chowdhary M et al (2018) Is less more? Comparing chemotherapy alone with chemotherapy and radiation for high-risk grade 2 glioma: an analysis of the National Cancer Data Base. Cancer 124(6):1169–1178CrossRef Jhaveri J, Liu Y, Chowdhary M et al (2018) Is less more? Comparing chemotherapy alone with chemotherapy and radiation for high-risk grade 2 glioma: an analysis of the National Cancer Data Base. Cancer 124(6):1169–1178CrossRef
22.
Zurück zum Zitat Houillier C, Wang X, Kaloshi G et al (2010) IDH 1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas. Neurology 75(17):1560–1566CrossRef Houillier C, Wang X, Kaloshi G et al (2010) IDH 1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas. Neurology 75(17):1560–1566CrossRef
23.
Zurück zum Zitat Leu S, von Felten S, Frank S et al (2013) IDH/MGMT-driven molecular classification of low-grade glioma is a strong predictor for long-term survival. Neuro-Oncology 15(4):469–479CrossRef Leu S, von Felten S, Frank S et al (2013) IDH/MGMT-driven molecular classification of low-grade glioma is a strong predictor for long-term survival. Neuro-Oncology 15(4):469–479CrossRef
24.
Zurück zum Zitat Bell EH, Zhang P, Fisher BJ et al (2018) Association of MGMT promoter methylation status with survival Outcomes in Patients With High-Risk Glioma Treated With Radiotherapy and Temozolomide: An Analysis From the NRG Oncology/RTOG 0424 Trial. JAMA Oncol 4(10):1405–1409CrossRef Bell EH, Zhang P, Fisher BJ et al (2018) Association of MGMT promoter methylation status with survival Outcomes in Patients With High-Risk Glioma Treated With Radiotherapy and Temozolomide: An Analysis From the NRG Oncology/RTOG 0424 Trial. JAMA Oncol 4(10):1405–1409CrossRef
25.
Zurück zum Zitat Johnson BE, Mazor T, Hong C et al (2014) Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma. Science 343(6167):189–193CrossRef Johnson BE, Mazor T, Hong C et al (2014) Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma. Science 343(6167):189–193CrossRef
Metadaten
Titel
Efficacy of initial temozolomide for high-risk low grade gliomas in a phase II AINO (Italian Association for Neuro-Oncology) study: a post-hoc analysis within molecular subgroups of WHO 2016
verfasst von
Roberta Rudà
Alessia Pellerino
Andrea Pace
Carmine Maria Carapella
Cristina Dealis
Manuela Caroli
Marina Faedi
Lorenzo Bello
Enrica Migliore
Giulia Marchese
Luca Bertero
Paola Cassoni
Riccardo Soffietti
Publikationsdatum
25.09.2019
Verlag
Springer US
Erschienen in
Journal of Neuro-Oncology / Ausgabe 1/2019
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-019-03277-x

Weitere Artikel der Ausgabe 1/2019

Journal of Neuro-Oncology 1/2019 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Schützt Olivenöl vor dem Tod durch Demenz?

10.05.2024 Morbus Alzheimer Nachrichten

Konsumieren Menschen täglich 7 Gramm Olivenöl, ist ihr Risiko, an einer Demenz zu sterben, um mehr als ein Viertel reduziert – und dies weitgehend unabhängig von ihrer sonstigen Ernährung. Dafür sprechen Auswertungen zweier großer US-Studien.

Bluttest erkennt Parkinson schon zehn Jahre vor der Diagnose

10.05.2024 Parkinson-Krankheit Nachrichten

Ein Bluttest kann abnorm aggregiertes Alpha-Synuclein bei einigen Menschen schon zehn Jahre vor Beginn der motorischen Parkinsonsymptome nachweisen. Mit einem solchen Test lassen sich möglicherweise Prodromalstadien erfassen und die Betroffenen früher behandeln.

Darf man die Behandlung eines Neonazis ablehnen?

08.05.2024 Gesellschaft Nachrichten

In einer Leseranfrage in der Zeitschrift Journal of the American Academy of Dermatology möchte ein anonymer Dermatologe bzw. eine anonyme Dermatologin wissen, ob er oder sie einen Patienten behandeln muss, der eine rassistische Tätowierung trägt.

Wartezeit nicht kürzer, aber Arbeit flexibler

Psychotherapie Medizin aktuell

Fünf Jahren nach der Neugestaltung der Psychotherapie-Richtlinie wurden jetzt die Effekte der vorgenommenen Änderungen ausgewertet. Das Hauptziel der Novellierung war eine kürzere Wartezeit auf Therapieplätze. Dieses Ziel wurde nicht erreicht, es gab jedoch positive Auswirkungen auf andere Bereiche.

Update Neurologie

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