How can clinicians distinguish true progression from pseudoprogression in MGMT-methylated glioblastoma? Dr Jigisha Thakkar discusses the clinical implications of time to true progression in MGMT-methylated glioblastoma and approaches to distinguishing pseudoprogression from treatment failure.
Interpreting MRI changes after chemoradiotherapy remains challenging in glioblastoma, particularly when pseudoprogression mimics tumour progression. In this interview, Dr Jigisha P Thakkar (Loyola University Medical Center, Maywood, IL, USA) discusses a retrospective analysis of time to first true progression in MGMT-methylated glioblastoma and how these findings may inform surveillance imaging and clinical decision-making.
Please summarize the rationale behind conducting your retrospective analysis and the main aims
Glioblastoma was redefined in the 2021 WHO Classification of Tumours of the Central Nervous System, with glioblastoma now restricted to IDH-wildtype tumours. However, the time to first true progression in patients with MGMT-methylated glioblastoma under this revised definition has not been well established. Our aim was to define the expected timeframe for true progression and explore whether this, alongside advanced imaging techniques and knowledge of treatment-specific pseudoprogression risk, could improve diagnostic accuracy and help distinguish true progression from pseudoprogression.
Your findings suggest that most patients with MGMT-methylated glioblastoma do not develop true progression within the first 18 months after surgery. When MRI changes suggest progression during this period, how should clinicians approach distinguishing suspected pseudoprogression from true progression, and what practical steps would you recommend before moving to second-line treatment?
Most patients with MGMT-methylated glioblastoma in our study did not develop true progression within the first 18 months after surgery. Therefore, MRI changes during this period should be interpreted carefully. If progression is suspected, a short-interval MRI, for example in 6 weeks, can help assess the evolution of the changes. In symptomatic patients with suspected pseudoprogression, a short course of corticosteroids or bevacizumab may be considered, followed by repeat imaging. If the MRI changes continue to progress, tissue diagnosis with biopsy or re-resection should be considered before proceeding to second-line tumour-directed treatment.
MGMT methylation is associated with a greater likelihood of pseudoprogression, but it is also an important predictive biomarker for temozolomide benefit. How should clinicians integrate MGMT status with radiological and clinical findings when deciding whether apparent progression represents treatment failure?
Pseudoprogression can occur during chemoradiotherapy and may persist beyond completion of treatment, particularly in MGMT-methylated glioblastoma. Therefore, MGMT status, the timing of the MRI changes, the patient’s clinical status and serial imaging findings should all be considered when assessing whether apparent progression represents treatment failure. Advanced radiographic imaging may provide additional information, while corticosteroids or bevacizumab can be considered in selected patients with symptomatic suspected pseudoprogression. The time to true progression identified in our study may also provide an additional reference point when interpreting these changes.
Your analysis focuses on the time to first ‘true’ progression rather than simply radiographic progression. Do you think current response-assessment criteria adequately capture the clinical reality of glioblastoma, and where are the greatest opportunities to improve the way progression is defined?
Current response-assessment criteria do not fully capture the clinical reality of glioblastoma, particularly because treatment-related changes can mimic tumour progression. Progression assessment could be improved by incorporating advanced imaging, such as perfusion imaging, alongside conventional MRI. It may also be helpful to consider the expected timeframe for progression according to tumour biology and treatment, as well as the treatment-specific risk of pseudoprogression in MGMT-methylated and MGMT-unmethylated glioblastoma.
What conclusions can you draw from the results, and what questions remain unanswered?
Most patients with MGMT-methylated glioblastoma in our study did not develop true progression within the first 18 months after surgery. Therefore, MRI changes during this period should be interpreted carefully. Considering the expected timeframe for true progression alongside advanced imaging techniques and treatment-specific pseudoprogression risk may improve diagnostic accuracy. Further research is needed to identify biomarkers that can predict treatment response and pseudoprogression, as well as to determine whether particular anatomical tumour locations are associated with a higher risk of pseudoprogression.
Looking ahead, what do you see as the most promising approaches for distinguishing true progression from pseudoprogression earlier – whether through advanced imaging, molecular biomarkers or other techniques – and what evidence would be needed before these approaches could meaningfully change routine clinical practice?
A combination of advanced imaging, including perfusion imaging and metabolic imaging such as PET or SPECT, together with molecular biomarkers could help distinguish true progression from pseudoprogression. However, these approaches would need to be validated in larger, prospective studies before they could be incorporated into routine clinical practice. The goal would be to develop a reliable, non-invasive approach that can distinguish treatment-related changes from genuine tumour progression earlier and with greater confidence.
This content has been developed independently by Touch Medical Media for touchONCOLOGY in collaboration with Dr Jigisha Thakkar. Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.
Disclosure: Dr Jigisha Thakkar has no financial or non-financial conflicts of interest to declare in relation to this interview.
Cite: Distinguishing true progression from pseudoprogression in MGMT-methylated glioblastoma. touchONCOLOGY. 6th October 2026.
Editor: Sophie Nickelson, Editorial Director
