TY - JOUR
T1 - Long-term survivors of glioblastoma
T2 - Tumor molecular, clinical, and imaging findings
AU - Briceno, Nicole
AU - Vera, Elizabeth
AU - Komlodi-Pasztor, Edina
AU - Abdullaev, Zied
AU - Choi, Anna
AU - Grajkowska, Ewa
AU - Kunst, Tricia
AU - Levine, Jason
AU - Lindsley, Matthew
AU - Fernandez, Kelly
AU - Reyes, Jennifer
AU - Boris, Lisa
AU - Burton, Eric
AU - Panzer, Marissa
AU - Polskin, Lily
AU - Penas-Prado, Marta
AU - Pillai, Tina
AU - Theeler, Brett J
AU - Wu, Jing
AU - Wall, Kathleen
AU - Papanicolau-Sengos, Antonios
AU - Quezado, Martha
AU - Smirniotopoulos, James
AU - Aldape, Kenneth
AU - Armstrong, Terri S
AU - Gilbert, Mark R
N1 - Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.
PY - 2024
Y1 - 2024
N2 - BACKGROUND: Glioblastoma (GBM) is the most aggressive primary brain malignancy with <45% living a year beyond diagnosis. Previously published investigations of long-term survivors (LTS) provided clinical data but rarely incorporated a comprehensive clinical and molecular analysis. Herein, we identify clinical, imaging, molecular, and outcome features for 23 GBM-LTS patients and compare them with a matched cohort of short-term survivors (STS).METHODS: Molecularly confirmed Isocitrate Dehydrogenase (IDH) wildtype GBM patients living ≥3 years post-diagnosis (NLTS = 23) or <3 years (NSTS = 75) were identified from our Natural History study. Clinical and demographic characteristics were compared. Tumor tissue was analyzed with targeted next generation sequencing (NGS) (NLTS = 23; NSTS = 74) and methylation analysis (NLTS = 18; NSTS = 28). Pre-surgical MRI scans for a subset of LTS (N = 14) and STS control (N = 28) matched on sex, age, and extent of resection were analyzed.RESULTS: LTS tended to be younger. Diagnostic MRIs showed more LTS with T1 tumor hypointensity. LTS tumors were enriched for MGMTp methylation and tumor protein 53 (TP53) mutation. Three patients with classic GBM histology were reclassified based on NGS and methylation testing. Additionally, there were LTS with typical poor prognostic molecular markers.CONCLUSIONS: Our findings emphasize that generalized predictions of prognosis are inaccurate for individual patients and underscore the need for complete clinical evaluation including molecular work-up to confirm the diagnosis. Continued accrual of patients to LTS registries that containcomprehensive clinical, imaging, tumor molecular data, and outcomes measures may pro\vide important insights about individual patient prognosis.
AB - BACKGROUND: Glioblastoma (GBM) is the most aggressive primary brain malignancy with <45% living a year beyond diagnosis. Previously published investigations of long-term survivors (LTS) provided clinical data but rarely incorporated a comprehensive clinical and molecular analysis. Herein, we identify clinical, imaging, molecular, and outcome features for 23 GBM-LTS patients and compare them with a matched cohort of short-term survivors (STS).METHODS: Molecularly confirmed Isocitrate Dehydrogenase (IDH) wildtype GBM patients living ≥3 years post-diagnosis (NLTS = 23) or <3 years (NSTS = 75) were identified from our Natural History study. Clinical and demographic characteristics were compared. Tumor tissue was analyzed with targeted next generation sequencing (NGS) (NLTS = 23; NSTS = 74) and methylation analysis (NLTS = 18; NSTS = 28). Pre-surgical MRI scans for a subset of LTS (N = 14) and STS control (N = 28) matched on sex, age, and extent of resection were analyzed.RESULTS: LTS tended to be younger. Diagnostic MRIs showed more LTS with T1 tumor hypointensity. LTS tumors were enriched for MGMTp methylation and tumor protein 53 (TP53) mutation. Three patients with classic GBM histology were reclassified based on NGS and methylation testing. Additionally, there were LTS with typical poor prognostic molecular markers.CONCLUSIONS: Our findings emphasize that generalized predictions of prognosis are inaccurate for individual patients and underscore the need for complete clinical evaluation including molecular work-up to confirm the diagnosis. Continued accrual of patients to LTS registries that containcomprehensive clinical, imaging, tumor molecular data, and outcomes measures may pro\vide important insights about individual patient prognosis.
U2 - 10.1093/noajnl/vdae019
DO - 10.1093/noajnl/vdae019
M3 - Article
C2 - 38420614
SN - 2632-2498
VL - 6
SP - vdae019
JO - Neuro-Oncology Advances
JF - Neuro-Oncology Advances
IS - 1
ER -