OS06.5.A CLINICAL AND LOCATION-SPECIFIC DETERMINANTS TO DISTINGUISH TUMOR PROGRESSION FROM TREATMENT-INDUCED EFFECTS IN HIGH GRADE GLIOMA
Authors: van der Boog A T J , Tetteroo R , David S , Flies C M , Brouwer M , Cialdella F , Dankbaar J , Snijders T J , Robe P A , Verhoeff J J C 
Published: September 2023

Abstract

BACKGROUND
Treatment response is an important early prognostic factor in high grade glioma, but distinguishing tumor progression from treatment-induced effects (TIEs) remains a difficult challenge in follow-up. The aim of this study was to explore tumor locations that might be associated with either tumor progression or TIEs. In addition, we investigated the role of clinical characteristics as covariates in classifying new or increasing contrast enhancements (CEs).

MATERIAL AND METHODS
We retrospectively included patients with histologically confirmed supratentorial WHO grade III or IV gliomas treated between 2011 and 2017. All patients who received first-time radiation therapy (RT), had at least 6 months of follow-up after RT and had new or increasing CE within the radiation field on follow-up MRI were included. Besides histological confirmation, new CEs were either defined, as TIEs when the lesions stabilized/decreased on subsequent imaging follow-up, or as tumor progression when the lesion grew or when anti-tumor treatment was started, in concordance with the RANO guidelines. Gross tumor volume (GTV) was investigated after non-linear registration to MNI stereotaxic space. Voxel-based analysis (VBA) was performed with family-wise error correction for multiple comparisons in order to identify voxels associated with either tumor progression or TIEs. Next, patient, tumor and treatment characteristics were multivariably analyzed as potential etiologic factors and confounders with regard to tumor progression or TIEs with binary logistic regression. Characteristics that showed a significant association were subsequently investigated with VBA.

RESULTS
The inclusion criteria were met by 407 patients. VBA showed a cluster of GTV voxels that was significantly associated with TIEs in the right temporal lobe, predominantly in the inferior longitudinal fasciculus (ILF). In multivariable analysis, clinical deterioration at time of new CE was associated with tumor progression (OR: 2.601; 95% CI: 1.649-4.102; P&lt;0.001). An RT dose &gt;58Gy EQD2 was significantly associated with TIEs (odds ratio (OR): 2.959; 95% confidence interval (CI): 1.043-8.403; P=0.041). No GTV voxels were significantly associated with clinical deterioration at time of new CE or with an RT dose &gt;58Gy EQD2.

CONCLUSION
Our study identified a specific location in the right ILF that was associated with TIEs. Additionally, lower RT doses and clinical deterioration at time of new CE were more likely to be associated with tumor progression than TIEs in high grade glioma. However, these characteristics were not associated with any location, suggesting an independent relation between TIEs and the right ILF. These findings may help clinicians in distinguishing between tumor progression and TIEs in follow-up imaging, leading to more accurate diagnoses and appropriate treatment decisions.