Radiotherapy delays malignant transformation and prolongs survival in patients with IDH-mutant gliomas (2024)

Show Author's information Hide Author's Information Yanwei Liu^{¹^,²^,^*},Huiyuan Chen^{²^,³^,^*},Guanzhang Li^{²^,⁴},Jing Zhang^{¹^,²},Kun Yao^⁵,Chenxing Wu^⁶,Shouwei Li^⁶,Xiaoguang Qiu^{¹^,²} ( )

Department of Radiation Oncology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China

National Clinical Research Center for Neurological Diseases, Beijing 100070, China

Department of Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, China

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China

Department of Neuropathology, Sanbo Brain Hospital, Capital Medical University, Beijing 100093, China

Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing 100093, China

^*These authors contributed equally to this work.

Abstract

Objective

IDH-mutant lower-grade gliomas (LGGs, grade 2 or 3) eventually transform into secondary grade 4 astrocytomas (sA_IDHmut/G4). Here, we sought to describe the transformation time, risk factors, and outcomes in malignant transformation of IDH-mutant LGGs.

Methods

We screened data for 108 patients with sA_IDHmut/G4 in the Chinese Glioma Genome Atlas who had initial IDH-mutant LGGs and underwent reoperation during 2005–2021. We evaluated the transformation time from IDH-mutant LGGs to sA_IDHmut/G4, and associated risk factors and outcomes. Malignant transformation was defined as pathological confirmation of grade 4 astrocytoma.

Results

The median age of the 108 patients with IDH-mutant LGGs was 35 years (range, 19–54); the median age at transformation was 40 years (range, 25–62); and the median follow-up time for all patients was 146 months (range, 121–171). The average transformation time was 58.8 months for all patients with LGGs (range, 5.9–208.1); 63.5 and 51.9 months for grade 2 and 3 gliomas, respectively; and 58.4 and 78.1 months for IDH-mutant/1p/19q-non-codeleted astrocytomas and IDH-mutant/1p/19q-codeleted oligodendrogliomas, respectively. Univariate and multivariate analysis indicated that radiotherapy [hazard ratio (HR), 0.29; 95% confidence interval (CI), 0.137–0.595; P = 0.001] and non-A blood type (HR, 0.37; 95% CI, 0.203–0.680; P = 0.001) were protective factors against delayed malignant transformation. Radiotherapy was associated with improved survival after transformation (HR, 0.44; 95% CI, 0.241–0.803; P = 0.008), overall survival (HR, 0.50; 95% CI, 0.265–0.972; P = 0.041), and progression-free survival (HR, 0.25; 95% CI, 0.133–0.479; P < 0.0001) in patients with IDH-mutant gliomas.

Conclusions

Radiotherapy is associated with delayed malignant transformation and improved survival in patients with IDH-mutant gliomas.

Keywords: radiotherapy, survival, malignant transformation, Lower-grade gliomas, IDH mutation

References(30)

Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med. 2009; 360: 765-73.

DOI Google Scholar

Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021; 23: 1231-51.

DOI Google Scholar

Shaw EG, Berkey B, Coons SW, Bullard D, Brachman D, Buckner JC, et al. Recurrence following neurosurgeon-determined gross-total resection of adult supratentorial lowgrade glioma: results of a prospective clinical trial. J Neurosurg. 2008; 109: 835-41.

DOI Google Scholar

Hu H, Mu Q, Bao Z, Chen Y, Liu Y, Chen J, et al. Mutational landscape of secondary glioblastoma guides MET-targeted trial in brain tumor. Cell. 2018; 175: 1665-78.

DOI Google Scholar