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

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. AQ2 Key Points 1. Pseudoprogression is common following radiotherapy (RT) among pediatric patients with low-grade glioma. 2. Pseudoprogression rates were higher among those treated with proton RT (compared with photon RT), and among those treated with higher doses of RT. 3. Local control is excellent among pediatric low-grade glioma patients treated with RT, irrespective of RT modality. Pediatric low-grade glioma (LGG), comprising World Health Organization (WHO) grades I and II primary glial neoplasms, can be treated using a variety of therapeutic strategies, including surgery, systemic therapy, and radiotherapy (RT). 1,2 Due to concerns regarding long-term sequelae, RT is generally included in the treatment of pediatric LGG 687 Ludmir et al. Pseudoprogression risk for pediatric LGG patients Neuro-Oncology

Pseudoprogression after radiation therapies for low grade glioma in children and adults: A systematic review and meta-analysis

“…After the removal of 214 duplicate articles, the title and abstract of the remaining 300 articles were evaluated against the selection criteria. Full-text analysis was performed for 18 articles, in which 9 retrospective observational cohort studies were assessed to satisfy all selection criteria for quantitative analysis, 5 studies [26][27][28][29][30] describing outcomes of pediatric LGG, and another 4 studies [15,[31][32][33] describing outcomes of adult LGG ( Table 1). Definitions of PsP by each study are included in Table 2.…”

“…The 5 pediatric LGG studies [26][27][28][29][30] described the PsP outcomes of 517 subjects, where 277 (54%) were treated with IMRT, and 240 (46%) were treated with PBT (Table 1). Median age ranged from 8.7 to 13 years old with proportion of female subjects ranging from 40% to 50% and median follow-up ranging from 4.4 to 12.2 years.…”

“…In pediatric LGGs treated by any type of radiation therapy, the incidence of PsP was 33% (95% CI, 26-40%; I 2 = 59%; Pheterogeneity = 0.03). In those treated by IMRT (3 cohort studies [27,28,30]; n = 277 subjects), the incidence of PsP was estimated to be 33% (95% CI, 20-47%; I 2 = NA) by RE modelling (Fig. 2).…”

“…2). In those treated by PBT (3 cohort studies [26,27,29]; n = 240 subjects), the incidence of PsP was estimated to be 34% (95% CI, 23-45%; I 2 = NA) by RE modelling. There was no statistically significant difference in PsP incidence rate between modalities (Pheterogeneity = 0.96).…”

Assembling the brain trust: the multidisciplinary imperative in neuro-oncology

“…Radiotherapy confers survival advantages to patients with glioblastoma 4,5 , medulloblastoma 2,3 , germ cell tumours 6,7 , ependymoma 8 and others 9 . This cost-effective and accessible treatment modality has proven efficacy in the adjuvant setting [2][3][4][5]8 , as well as in the definitive setting 6,7 , as a first-line treatment [2][3][4][5][6][7][8] or after prior lines of therapy 10 . Neuro-radiation oncology has witnessed a burgeoning of new techniques, technologies and strategies that will better optimize the therapeutic ratio.…”