Y Gao1, B Weenink1, M J van den Bent2, L Erdem-Eraslan1, J M Kros3, Pae Sillevis Smitt1, K Hoang-Xuan4, A A Brandes5, M Vos6, F Dhermain7, R Enting8, G F Ryan9, O Chinot10, M Ben Hassel11, M E van Linde12, W P Mason13, J M M Gijtenbeek14, C Balana15, A von Deimling16, Th Gorlia17, R Stupp18, M E Hegi19, B G Baumert20, P J French21. 1. Department of Neurology, Erasmus University Medical Center, 3000CA, Rotterdam, The Netherlands. 2. Department of Neurology, Daniel Den Hoed Cancer Center, 3075 EA, Rotterdam, The Netherlands. 3. Department of Pathology, Erasmus University Medical Center, 3000CA, Rotterdam. 4. APHP Pitié-Salpêtrière, Sorbonne Universités, UPMC, ICM, UMRS, 1127, Paris, France. 5. Ospedale Bellaria, Bologna, Italy. 6. Med Ctr Haaglanden, The Netherlands. 7. I. Gustave Roussy, Villejuif, France. 8. UMCG and University of Groningen, Groningen, The Netherlands. 9. Peter MacCallum Cancer Center, Melbourne, Australia. 10. Aix Marseille, Université, APHM La Timone, Marseille, France. 11. Centre Eugène Marquis, Rennes, France. 12. VU University Medical Center, Academic Medical Center, Amsterdam, The Netherlands. 13. Princess Margaret Hospital, University of Toronto, Toronto, ON, Canada. 14. Radboud University Medical Center Nijmegen, The Netherlands. 15. ICO Badalona Hospital, Germans Trias I Pujol, Barcelona, Spain. 16. German Cancer Consortium (DKTK), CCU Neuropathology German Cancer Research Center (DKFZ), Department Neuropathology, Institute of Pathology, University of Heidelberg, Heidelberg, Germany. 17. European Organisation for Research and Treatment of Cancer Headquarters, Brussels, Belgium. 18. Neuroscience Research Centre, CHUV, Lausanne, Switzerland. 19. Department of Clinical Neurosciences, Lausanne University Hospital, Lausanne, Switzerland. 20. Dept. of Radiation-Oncology, Paracelsus Clinic Osnabrueck, University of Muenster, Germany; Maastricht University Medical Centre, GROW (School for Oncology), Maastricht, The Netherlands. 21. Department of Neurology, Erasmus University Medical Center, 3000CA, Rotterdam, The Netherlands. Electronic address: p.french@erasmusmc.nl.
Abstract
INTRODUCTION: The European Organisation for Research and Treatment of Cancer (EORTC) 22033-26033 clinical trial (NCT00182819) investigated whether initial temozolomide (TMZ) chemotherapy confers survival advantage compared with radiotherapy (RT) in low-grade glioma (LGG) patients. In this study, we performed gene expression profiling on tissues from this trial to identify markers associated with progression-free survival (PFS) and treatment response. METHODS: Gene expression profiling, performed on 195 samples, was used to assign tumours to one of six intrinsic glioma subtypes (IGSs; molecularly similar tumours as previously defined using unsupervised expression analysis) and to determine the composition of immune infiltrate. DNA copy number changes were determined using OncoScan arrays. RESULTS: We confirm that IGSs are prognostic in the EORTC22033-26033 clinical trial. Specific genetic changes segregate in distinct IGSs: most samples assigned to IGS-9 have IDH-mutations and 1p19q codeletion, samples assigned to IGS-17 have IDH-mutations without 1p19q codeletion and samples assigned to other intrinsic subtypes often are IDH-wildtype. A trend towards benefit from RT was observed for samples assigned to IGS-9 (hazard ratio [HR] for TMZ is 1.90, P = 0.065) but not for samples assigned to IGS-17 (HR 0.87, P = 0.62). We did not identify genes significantly associated with PFS within intrinsic subtypes, although follow-up time is limited. We also show that LGGs and glioblastomas differ in their immune infiltrate, which suggests that LGGs are less amenable to checkpoint inhibitor-type immune therapies. Gene expression analysis also allows identification of relatively rare subtypes. Indeed, one patient with a pilocytic astrocytoma was identified. CONCLUSION: IGSs are prognostic for PFS in EORTC22033-26033 clinical trial samples.
RCT Entities:
INTRODUCTION: The European Organisation for Research and Treatment of Cancer (EORTC) 22033-26033 clinical trial (NCT00182819) investigated whether initial temozolomide (TMZ) chemotherapy confers survival advantage compared with radiotherapy (RT) in low-grade glioma (LGG) patients. In this study, we performed gene expression profiling on tissues from this trial to identify markers associated with progression-free survival (PFS) and treatment response. METHODS: Gene expression profiling, performed on 195 samples, was used to assign tumours to one of six intrinsic glioma subtypes (IGSs; molecularly similar tumours as previously defined using unsupervised expression analysis) and to determine the composition of immune infiltrate. DNA copy number changes were determined using OncoScan arrays. RESULTS: We confirm that IGSs are prognostic in the EORTC22033-26033 clinical trial. Specific genetic changes segregate in distinct IGSs: most samples assigned to IGS-9 have IDH-mutations and 1p19q codeletion, samples assigned to IGS-17 have IDH-mutations without 1p19q codeletion and samples assigned to other intrinsic subtypes often are IDH-wildtype. A trend towards benefit from RT was observed for samples assigned to IGS-9 (hazard ratio [HR] for TMZ is 1.90, P = 0.065) but not for samples assigned to IGS-17 (HR 0.87, P = 0.62). We did not identify genes significantly associated with PFS within intrinsic subtypes, although follow-up time is limited. We also show that LGGs and glioblastomas differ in their immune infiltrate, which suggests that LGGs are less amenable to checkpoint inhibitor-type immune therapies. Gene expression analysis also allows identification of relatively rare subtypes. Indeed, one patient with a pilocytic astrocytoma was identified. CONCLUSION: IGSs are prognostic for PFS in EORTC22033-26033 clinical trial samples.
Authors: John P Lynes; Anthony K Nwankwo; Hannah P Sur; Victoria E Sanchez; Kwadwo A Sarpong; Oluwatobi I Ariyo; Gifty A Dominah; Edjah K Nduom Journal: J Immunother Cancer Date: 2020-05 Impact factor: 13.751
Authors: Ainhoa Hernandez; Ana Maria Muñoz-Mármol; Anna Esteve-Codina; Francesc Alameda; Cristina Carrato; Estela Pineda; Oriol Arpí-Lluciá; Maria Martinez-García; Mar Mallo; Marta Gut; Sonia Del Barco; Oscar Gallego; Marc Dabad; Carlos Mesia; Beatriz Bellosillo; Marta Domenech; Noemí Vidal; Iban Aldecoa; Nuria de la Iglesia; Carmen Balana Journal: Sci Rep Date: 2022-08-24 Impact factor: 4.996