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Comparative Study
. 2019 May 6;21(5):686-695.
doi: 10.1093/neuonc/noz042.

Increased risk of pseudoprogression among pediatric low-grade glioma patients treated with proton versus photon radiotherapy

Ethan B Ludmir  1 , Anita Mahajan  1   2 , Arnold C Paulino  1   3 , Jeremy Y Jones  3   4 , Leena M Ketonen  1 , Jack M Su  3 , David R Grosshans  1 , Mary Frances McAleer  1 , Susan L McGovern  1 , Yasmin A Lassen-Ramshad  5 , Adekunle M Adesina  3 , Robert C Dauser  1 , Jeffrey S Weinberg  1 , Murali M Chintagumpala  3
Affiliations
Comparative Study

Increased risk of pseudoprogression among pediatric low-grade glioma patients treated with proton versus photon radiotherapy

Ethan B Ludmir et al. Neuro Oncol. .

Abstract

Background: Pseudoprogression (PsP) is a recognized phenomenon after radiotherapy (RT) for high-grade glioma but is poorly characterized for low-grade glioma (LGG). We sought to characterize PsP for pediatric LGG patients treated with RT, with particular focus on the role of RT modality using photon-based intensity-modulated RT (IMRT) or proton beam therapy (PBT).

Methods: Serial MRI scans from 83 pediatric LGG patients managed at 2 institutions between 1998 and 2017 were evaluated. PsP was scored when a progressive lesion subsequently decreased or stabilized for at least a year without therapy.

Results: Thirty-two patients (39%) were treated with IMRT, and 51 (61%) were treated with PBT. Median RT dose for the cohort was 50.4 Gy(RBE) (range, 45-59.4 Gy[RBE]). PsP was identified in 31 patients (37%), including 8/32 IMRT patients (25%) and 23/51 PBT patients (45%). PBT patients were significantly more likely to have post-RT enlargement (hazard ratio [HR] 2.15, 95% CI: 1.06-4.38, P = 0.048). RT dose >50.4 Gy(RBE) similarly predicted higher rates of PsP (HR 2.61, 95% CI: 1.20-5.68, P = 0.016). Multivariable analysis confirmed the independent effects of RT modality (P = 0.03) and RT dose (P = 0.01) on PsP incidence. Local progression occurred in 10 patients: 7 IMRT patients (22%) and 3 PBT patients (6%), with a trend toward improved local control for PBT patients (HR 0.34, 95% CI: 0.10-1.18, P = 0.099).

Conclusions: These data highlight substantial rates of PsP among pediatric LGG patients, particularly those treated with PBT. PsP should be considered when assessing response to RT in LGG patients within the first year after RT.

Keywords: low-grade glioma; pediatric malignancy; proton beam therapy; pseudoprogression; radiotherapy.

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Figures

Fig. 1
Fig. 1
RT modality predicts for PsP. Cumulative PsP incidence over time by RT modality; significantly increased PsP risk with PBT (gray) versus IMRT (black; HR 2.15, 95% CI: 1.06–4.38, P = 0.048).
Fig. 2
Fig. 2
Case of severe PsP toxicity. A 3.9-year-old female patient presenting with cervicomedullary WHO grade II fibrillary astrocytoma treated with 50.4 Gy(RBE) PBT with subsequent symptomatic PsP requiring ventricular shunt and permanent tracheostomy. T2 mid-sagittal MRI images shown. (A) Pre-PBT baseline scan demonstrates infiltrative cervicomedullary tumor. (B) Four-month post-PBT scan demonstrates increased size of infiltrating tumor (ventricular shunt placed prior to this scan). (C) Twelve-month post-PBT scan demonstrates spontaneous decreased size of tumor; ventricular shunt remains in place.
Fig. 3
Fig. 3
Disease-related outcomes. (A) Kaplan–Meier survival curves for overall survival (OS, black) and local control (LC, gray) for the full cohort. (B) Kaplan–Meier survival curves for LC by RT modality; trend toward improved LC for patients treated with PBT (gray) versus IMRT (black; HR 0.34, 95% CI: 0.10–1.18, P = 0.099).
See this image and copyright information in PMC

Comment in

  • Pseudoprogression in low-grade glioma.
    Slater JM, Shih HA. Slater JM, et al. Transl Cancer Res. 2019 Dec;8(Suppl 6):S580-S584. doi: 10.21037/tcr.2019.11.16. Transl Cancer Res. 2019. PMID: 35117135 Free PMC article. No abstract available.

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