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. 2024 Aug 30;6(1):vdae151.
doi: 10.1093/noajnl/vdae151. eCollection 2024 Jan-Dec.

Tumor volume features predict survival outcomes for patients diagnosed with diffuse intrinsic pontine glioma

Affiliations

Tumor volume features predict survival outcomes for patients diagnosed with diffuse intrinsic pontine glioma

D'Andre Spencer et al. Neurooncol Adv. .

Abstract

Background: Diffuse intrinsic pontine glioma (DIPG) is a fatal childhood central nervous system tumor. Diagnosis and monitoring of tumor response to therapy is based on magnetic resonance imaging (MRI). MRI-based analyses of tumor volume and appearance may aid in the prediction of patient overall survival (OS).

Methods: Contrast-enhanced T1- and FLAIR/T2-weighted MR images were retrospectively collected from children with classical DIPG diagnosed by imaging (n = 43 patients). MRI features were evaluated at diagnosis (n = 43 patients) and post-radiation (n = 40 patients) to determine OS outcome predictors. Features included 3D tumor volume (Twv), contrast-enhancing tumor core volume (Tc), Tc relative to Twv (TC/Twv), and Twv relative to whole brain volume. Support vector machine (SVM) learning was used to identify feature combinations that predicted OS outcome (defined as OS shorter or longer than 12 months from diagnosis).

Results: Features associated with poor OS outcome included the presence of contrast-enhancing tumor at diagnosis, >15% Tc/Twv post-radiation therapy (RT), and >20% ∆Tc/Twv post-RT. Consistently, SVM learning identified Tc/Twv at diagnosis (prediction accuracy of 74%) and ∆Tc/Twv at <2 months post-RT (accuracy = 75%) as primary features of poor survival.

Conclusions: This study demonstrates that tumor imaging features at diagnosis and within 4 months of RT can predict differential OS outcomes in DIPG. These findings provide a framework for incorporating tumor volume-based predictive analyses into the clinical setting, with the potential for treatment customization based on tumor risk characteristics and future applications of machine-learning-based analysis.

Keywords: MRI; SVM learning; diffuse intrinsic pontine glioma; survival outcomes; tumor volume.

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Conflict of interest statement

None of the authors have a conflict to declare related to the work in this manuscript.

Figures

Figure 1.
Figure 1.
Diagnostic tumor MRI volume is predictive of survival outcomes (A) Representative axial MRI from one patient showing overlaying Twv and Tc tumor volume segmentations. (B) Twv relative to whole brain volume (WBV) between shorter (n = 22) versus longer (n = 21 with available WBV data) survivors. Mann–Whitney test, P = .622. (C) Left: Survival comparison of patients with contrast-enhancing tumor on T1 imaging (Tc+) (n = 23) versus those without contrast-enhancing tumor on T1 imaging (Tc−) (n = 20), Log-rank test, P = .010. Right: Survival comparison of patients with Tc/Twv > 25% (n = 3) vs. those with Tc/Twv < 25% (n = 40) at diagnosis, Log-rank test, P = .009. (D) Comparison of Tc/Twv (%) between shorter (OS < 12 months, n = 22) versus longer survivors (OS ≥ 12 months, n = 21), Mann–Whitney test, P = .0255.
Figure 2.
Figure 2.
Tc/Twv following radiation therapy predicts survival outcomes. (A) Comparison of Tc/Twv at initial diagnosis (‘Pre-RT’; n = 43) and following RT at <2 months (n = 37; Wilcoxon signed rank, corrected P = .0007) and 2–4 months post-RT (n = 37; Wilcoxon signed rank, corrected P = .0001). There was no significant difference in the Tc/Twv ratios between the <2 months and 2–4 months MRI timepoints (P = .475) (B) Difference in Tc/Twv at < 2 mo post-RT between shorter (n = 19) and longer (n = 18) survivors, Mann–Whitney test, P = .0242. (C) Survival comparison between patients with ≥15% Tc/Twv (n = 19) and those with <15% Tc/Twv (n = 18) at <2 months post-RT, Log-rank test, P = .03. (D) Difference in ∆Tc/Twv from diagnosis to <2 mo post-RT between shorter (n = 19) and longer (n = 18) survivors, Mann–Whitney test, P = .0132. (E) Survival comparison at the <2 months post-RT timepoint between patients with a large ∆Tc/Twv increase (n = 9; ∆ Tc/Twv > 19%, top 25% of all patients) and patients within the bottom 25% (n = 9; ∆ Tc/Twv between −1.6% and 0.15%), Log-rank test, P = .023.
Figure 3.
Figure 3.
Whole tumor volume changes post-radiation provide limited insight into patient survival outcomes. (A) Change in Twv from baseline to <2 months RT and baseline to 2–4 months post-RT (n = 37 patients for each timepoint). There was no difference in Twv volume change between the 2 timepoints (Wilcoxon matched-pairs signed rank test, P = .598). (B) Twv percent change at <2 months post-RT between shorter and longer survivors. Mann–Whitney test, P = .105. (C) Survival comparison between patients who experienced a decrease (n = 21) versus an increase (n = 16) in Twv volume from diagnosis to <2 months post-RT, Log-rank test, P = .025. (D) OS outcome of patients who experienced a Twv percent increase greater than 25% of the initial diagnosis volume (“non-responders”) (n = 10), decrease greater than 25% (‘responders’) (n = 13), or a Twv percent change less than 25% (“stable”) (n = 14). Log-rank test, P = .5. (E) OS outcome of patients who experienced a Twv percent increase greater than 50% of the initial diagnosis volume (extreme “non-responders”) (n = 9), decrease greater than 50% (extreme ‘responders’) (n = 4), or a Twv percent change less than 50% (“stable”)(n = 24). Log-rank test, P = .2. (F) Summary of MRI volume features at each timepoint that are independently predictive of OS.

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