2742

Qualitative and Quantitative Imaging Phenotypes can Predict CDKN2A/B Homozygous Deletion Status in IDH-mutant Astrocytomas
Yae Won Park1, Ki Sung Park2, Sung Soo Ahn1, Inho Park1, and Se Hoon Kim1
1Yonsei University College of Medicine, Seoul, Korea, Republic of, 2Pohang University of Science and Technology, Seoul, Korea, Republic of

Synopsis

CDKN2A/B homozygous deletion is a key molecular marker in the 2021 WHO classification of IDH-mutant astrocytomas; presence of CDKN2A/B homozygous deletion results in a grade of 4. On multivariable analysis, infiltrative pattern, larger tumor volume, and higher 95th percentile of nCBV were independent predictors of CDKN2A/B homozygous deletion. The infiltrative pattern and larger volume may be reflected from the increased tumor cell proliferation, whereas the higher 95th percentile of nCBV may reflect the increased angiogenesis due to CDKN2A/B homozygous deletion.

Objectives

Cyclin-dependent kinase inhibitor (CDKN)2A/B homozygous deletion is a key molecular marker in the 2021 World Health Organization (WHO) classification of isocitrate dehydrogenase (IDH)-mutant astrocytomas; the presence CDKN2A/B homozygous deletion in IDH-mutant histological grade 2 or 3 astrocytomas lead to designation to grade 4, even in the absence of microvascular proliferation or necrosis. The purpose of this study was to assess whether qualitative and quantitative imaging parameters can noninvasively predict the CDKN2A/B homozygous deletion status of IDH-mutant astrocytomas.

Methods

Preoperative MRI data of 34 patients with IDH-mutant astrocytomas (29 without and 5 with CDKN2A/B homozygous deletion, respectively) from our institution were included. Qualitative imaging assessment was performed. The mean ADC, 5th percentile of ADC, mean normalized cerebral blood volume (nCBV), and 95th percentile of nCBV were also assessed via automatic tumor segmentation. Univariate and multivariate logistic regression models were constructed.

Results

On univariable analysis, corpus callosum involvement (Odds ratio [OR] = 20.25, P = 0.010), ependymal extension (OR = 15.33, P = 0.024), proportion of necrosis > 5% (OR = 13.00, P = 0.019), infiltrative pattern (OR = 54.00, P = 0.003), and 95th percentile of nCBV (OR = 2.32, P = 0.28) were predictors of CDKN2A/B homozygous deletion. On multivariable analysis, tumor volume (OR = 1.01, P = 0.027), infiltrative pattern (OR = 38.02, P = 0.028), the volume (OR = 1.01, P = 0.027), and 95th percentile of nCBV (OR = 2.83, P = 0.043) were independent predictors of CDKN2A/B homozygous deletion. The area under the curve, accuracy, sensitivity, and specificity of the multivariable model were 0.94 (95% confidence interval 0.80-0.99), 94.1%, 80.0, and 96.6%, respectively.

Conclusion

Presence of infiltrative pattern, larger tumor volume, and higher 95th percentile of nCBV may be useful imaging biomarkers for CDKN2A/B homozygous deletion in IDH-mutant astrocytomas.

Acknowledgements

None.

References

Louis DN, Perry A, Wesseling P et al (2021) The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 10.1093/neuonc/noab106

Louis DN, Wesseling P, Aldape K et al (2020) cIMPACT-NOW update 6: new entity and diagnostic principle recommendations of the cIMPACT-Utrecht meeting on future CNS tumor classification and grading. Brain Pathol 30:844-856

Shirahata M, Ono T, Stichel D et al (2018) Novel, improved grading system(s) for IDH-mutant astrocytic gliomas. Acta Neuropathol 136:153-16


Figures

Figure 1. Representative case of histological grade 3 IDH-mutant astrocytoma without CDKN2A/B homozygous deletion on. On conventional imaging the right frontal lobe T2 hyperintense tumor shows a total volume of 17.96 cm3. The proportion of enhancing tumor is less than 5% with minimal/mild enhancement quality. The tumor shows an expansive pattern (size of precontrast T1 abnormality approximates size of FLAIR abnormality). (d) The nCBV map shows a mean and 95th rCBV of 0.32 and 2.30, respectively. (e) Copy number variation profile shows absence of CDKN2A/B homozygous deletion.

Figure 2. Representative case of a histological grade 3 IDH-mutant astrocytoma with CDKN2A/B homozygous deletion. On conventional imaging the right frontal lobe T2 hyperintense tumor shows a proportion of enhancing tumor more than 5% with marked/avid enhancement quality. The tumor shows an infiltrative pattern (size of precontrast T1 abnormality much smaller than size of FLAIR abnormality) with a total volume of 102.04 cm3. (d) The nCBV map shows a mean and 95th rCBV of 2.42 and 7.79, respectively. (e) The copy number variation profile shows presence of CDKN2A/B homozygous deletion.

Figure 3. Receiver operating characteristic (ROC) curves of the multivariable model to predict the CDKN 2A/B homozygous deletion status in IDH-mutant astrocytoma

Proc. Intl. Soc. Mag. Reson. Med. 30 (2022)
2742
DOI: https://doi.org/10.58530/2022/2742