Predictors of Tumor Dynamics Over a 6-Week Course of Concurrent Chemoradiotherapy for Glioblastoma and the Effect on Survival

Wee Loon Ong; James Stewart; Arjun Sahgal; Hany Soliman; Chia-Lin Tseng; Jay Detsky; Hanbo Chen; Ling Ho; Sunit Das; Pejman Maralani; Nir Lipsman; Greg Stanisz; James Perry; Mary Jane Lim-Fat; Eshetu G Atenafu; Angus Lau; Mark Ruschin; Sten Myrehaug

doi:10.1016/j.ijrobp.2024.03.036

Predictors of Tumor Dynamics Over a 6-Week Course of Concurrent Chemoradiotherapy for Glioblastoma and the Effect on Survival

Int J Radiat Oncol Biol Phys. 2024 Mar 30:S0360-3016(24)00453-X. doi: 10.1016/j.ijrobp.2024.03.036. Online ahead of print.

Authors

Wee Loon Ong¹, James Stewart², Arjun Sahgal³, Hany Soliman³, Chia-Lin Tseng³, Jay Detsky³, Hanbo Chen³, Ling Ho², Sunit Das⁴, Pejman Maralani⁵, Nir Lipsman⁶, Greg Stanisz⁷, James Perry⁸, Mary Jane Lim-Fat⁸, Eshetu G Atenafu⁹, Angus Lau¹⁰, Mark Ruschin¹¹, Sten Myrehaug¹²

Affiliations

¹ Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Canada; Alfred Health Radiation Oncology, Central Clinical School, Monash University, Melbourne, Australia.
² Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada.
³ Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Canada.
⁴ Division of Neurosurgery, University of Toronto, Toronto, Canada; Division of Neurosurgery and Centre for Ethics, St Michael's Hospital, Toronto, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, SickKids Hospital, Toronto, Canada.
⁵ Department of Medical Imaging, Sunnybrook Health Sciences Centre, Toronto, Canada.
⁶ Division of Neurosurgery, University of Toronto, Toronto, Canada; Department of Physical Sciences, Sunnybrook Research Institute, Toronto, Canada; Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto Canada.
⁷ Department of Physical Sciences, Sunnybrook Research Institute, Toronto, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Canada; Department of Neurosurgery and Paediatric Neurosurgery, Medical University Lublin, Poland.
⁸ Division of Neurology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
⁹ Department of Biostatistics, University Health Network, University of Toronto, Toronto, Canada.
¹⁰ Department of Physical Sciences, Sunnybrook Research Institute, Toronto, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Canada.
¹¹ Department of Radiation Oncology, University of Toronto, Toronto, Canada; Department of Medical Physics, Sunnybrook Odette Cancer Centre, Toronto, Canada.
¹² Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Canada. Electronic address: Sten.Myrehaug@sunnybrook.ca.

PMID: 38561051
DOI: 10.1016/j.ijrobp.2024.03.036

Abstract

Purpose: We present the final analyses of tumor dynamics and their prognostic significance during a 6-week course of concurrent chemoradiotherapy for glioblastoma in the Glioblastoma Longitudinal Imaging Observational study.

Methods and materials: This is a prospective serial magnetic resonance imaging study in 129 patients with glioblastoma who had magnetic resonance imaging obtained at radiation therapy (RT) planning (F0), fraction 10 (F10), fraction 20 (F20), and 1-month post-RT. Tumor dynamics assessed included gross tumor volume relative to F0 (V_rel) and tumor migration distance (d_migration). Covariables evaluated included: corpus callosum involvement, extent of surgery, O⁶-methylguanine-DNA-methyltransferase methylation, and isocitrate dehydrogenase mutation status.

Results: The median V_rel were 0.85 (range, 0.25-2.29) at F10, 0.79 (range, 0.09-2.22) at F20, and 0.78 (range, 0.13-4.27) at 1 month after completion of RT. The median d_migration were 4.7 mm (range, 1.1-20.4 mm) at F10, 4.7 mm (range, 0.8-20.7 mm) at F20, and 6.1 mm (range, 0.0-45.5 mm) at 1 month after completion of RT. Compared with patients who had corpus callosum involvement (n = 26), those without corpus callosum involvement (n = 103) had significant V_rel reduction at F20 (P = .03) and smaller d_migration at F20 (P = .007). Compared with patients who had biopsy alone (n = 19) and subtotal resection (n = 71), those who had gross total resection (n = 38) had significant V_rel reduction at F10 (P = .001) and F20 (P = .001) and a smaller d_migration at F10 (P = .03) and F20 (P = .002). O⁶-Methylguanine-DNA-methyltransferase methylation and isocitrate dehydrogenase mutation status were not significantly associated with tumor dynamics. The median progression-free survival and overall survival (OS) were 8.5 months (95% CI, 6.9-9.9) and 20.4 months (95% CI, 17.6-25.2). In multivariable analyses, patients with V_rel ≥ 1.33 at F10 had worse OS (hazard ratio [HR], 4.6; 95% CI, 1.8-11.4; P = .001), and patients with d_migration ≥ 5 mm at 1-month post-RT had worse progression-free survival (HR, 1.76; 95% CI, 1.08-2.87) and OS (HR, 2.2; 95% CI, 1.2-4.0; P = .007).

Conclusions: Corpus callosum involvement and extent of surgery are independent predictors of tumor dynamics during RT and can enable patient selection for adaptive RT strategies. Significant tumor enlargement at F10 and tumor migration 1-month post-RT were associated with poorer OS.