Table 1.
pLGG treated with radiation therapy in the literature.
| Author/Year | Mean age at RT (year; range) | Pathology | RT modality | Median RT dose (range) Gy | Patients who received chemotherapy prior to RT |
Prior surgical resection/biopsy |
Outcome | Toxicity reported |
|---|---|---|---|---|---|---|---|---|
| Rodrigues et al., 2021 (21) | 9.22 years | Astrocytoma NOS (n=249, 68%) Pilocytic astrocytoma (n=64, 17.5%) Diffuse astrocytoma (n=22, 6%) Oligodendroglioma (n=5, 1.4%) Glioma NOS (n=18, 4.9%) Mixed glioma (n=8, 2.2%) |
EBRT | 34/366 (9.3%) | Surgery (n=248, 67.8%) | No survival assessment in study | Secondary neoplasm 7.4% in RT treated group | |
| Indelicato et al., 2019 (20) | 10.2 (2–21) years 48.6% (n=36) of the patients were <30 years old |
WHO grade I: (n=122, 70%) WHO grade II: (n=52, 30%) |
Proton | 129 treated with 54Gy and 45 treated with <54 Gy | 74/174 (43%) 1 prior regimen (n=29, 17%), 2 prior regimens (n=23, 13%). 3+ prior regimen (n=22, 13%) |
No prior surgery (n=22, 13%) STR/biopsy (n=147, 84%) GTR (n=5, 3%) |
5-year PFS and OS 84% and 92%, respectively | Reduced local control in brainstem/spinal cord tumor (62% vs 90% other locations) and in those that received dose <54 Gy (67% in <54Gy vs 91%) Nausea or vomiting (12.6%) New central hormone deficiency (22%) Pseudo progression (32%) Significant toxicity in 4% of patients; brainstem necrosis requiring corticosteroids (n=2), symptomatic vasculopathy (n=2), radiation retinopathy (n = 1), epilepsy (n = 1), and death from radiation-induced high-grade glioma (n = 1). |
| Ludmir et al., 2019 (22) | 10 (1–17.6) years | WHO grade I (n=62, 75%) WHO grade II (n=21, 25%) |
IMRT (n=32, 39%) Proton (n=51, 61%) |
50.4 (45–59.4) Gy | 32/83 (39%) | Biopsy (n=42, 51%) STR (n=37, 45%) GTR (n=4, 5%) |
Improved local control with proton RT (HR 0.34, 95% CI: 0.10–1.18, p=0.099) | Pseudo progression (n=31, 37%); 8/32 (25%) IMRT patients and 23/51 (45%) proton (p=0.048). Higher doses of RT (>50.4Gy) were more likely to have pseudo progression (p=0.016) |
| Cherlow et al., 2019 (23) | 13.6 (3–21) years (median) | Pilocytic astrocytoma (n=66; 78%) Diffuse astrocytoma (n=12, 14%) LGG NOS (n=2, 2%) LGG oligodendroglioma (n=1, 1%) |
IMRT (n=60, 71%) 3D-CRT (n=25; 29%) |
54 Gy | 36/85 (42%) | PFS (5-year) 71% OS (5-year) 93% | Tumor necrosis (n=1) Acute visual loss reversed with steroids (n=1) Acute diplopia reversed with steroids (n=1) |
|
| Mannina et al., 2016 (24) | 10.9 (4–20) years | WHO grade I (n=15, 100%) | Proton | 54 (50.4–59.4) Gy | 9/15 (60%) | Biopsy only: (n=5, 33%) ≥ 1 subtotal resection: (n=10, 67%) 2 STR (n=3, 30%) |
5-year OS and intervention free survival 93% and 73%, respectively | Pseudo progression (20%) Secondary malignancy, ALL (n=1), radio necrosis (n=1) |
| Raikar et al., 2014 (25) | 9.4 years | WHO grade I (n=10, 59%) WHO grade II (n=7, 41%) |
Conformal RT (n=13, 76%) CyberKnife (n=2, 12%) Gamma Knife (n=2, 12%) |
50–54 Gy (CRT) 14–16Gy (GammaKnife) 21–26Gy (CyberKnife) |
13/17 (76%) 1 prior regimen (n=7, 54%), 2 prior regimens (n=4, 31%), 3 prior regimens (n=1, 8%), 4 prior regimens (n=1, 8%) |
Biopsy (n=7, 41%) STR (n=10, 59%) GTR (n=0) |
PFS (3-year) OS (3 and 10-year) 100% |
|
| Greenberger et al., 2014 (18) | 11.0 (2.7–21.5) years | WHO grade I: (n=19, 59.4%) WHO grade II: (n=6, 18.8%) low grade (not specified) (n=2, 6.3%), no pathology: (n=5, 15.6%) |
Proton | 52.2 (48.6–54) Gy | 16/32 (50%) One prior regimen (n=6, 18.8%) 2 prior (n=7, 21.9%) 3 prior (n=3, 9.4%) none (n=16,50%) |
No prior surgery: (n=5, 15.6%) Biopsy only: (n=6, 18.7%) 1 prior resection: (n=17, 53.1%) 2 or more resections: (n=4, 12.5%) |
6-year PFS 89.7%, 8-year PFS 82.8%; OS (8-year) 100% | Decline in neurocognitive outcome in children < 7 years in age and those with higher doses to left temporal lobe/hippocampus. Higher risk of endocrinopathy in patients with mean dose of ≥40 Gy to hypothalamus, pituitary, or optic chiasm Moya moya (n=2) |
| Paulino et al., 2013 (26) | 10 (1–17) years (median) |
WHO grade I (n=32, 82%) WHO grade II (n=7; 18%) |
IMRT | 50.4 Gy (45–54Gy) | 10/39 (25.6%) | STR (n=19; 48.7%) | PFS (8-year) 78.2%, OS (8-year) 93.7% | Age at time of RT was significant for PFS, with more disease progression observed in patients ≤5 years of age at time of IMRT. Moya moya (n=1) Children with centrally located tumor more likely to develop endocrine abnormalities compared to hemispheric or posterior fossa tumors, hormone deficiency (n=10) |
| Merchant et al., 2009 (27) | 9.7 (2.2–19.8) years | WHO grade I (n=67, 86%) WHO grade II (n=11, 14%) |
IMRT (n=3, 4%) 3D-CRT (n=75, 96%) |
50.4 (one patient with OPG), otherwise 54Gy in all others | 25/78 (32%) | Biopsy (n=30, 38%) STR (n=35, 45%) No prior surgery (n=13, 17%) |
EFS 87.4% (5-year), 74.3% (10-year) OS 98.5% (5-year), 95.8% (10-year) |
Vasculopathy (n=5); younger children <5yo were at greatest risk Second malignancy (n=1) Younger age associated with more marked decline in cognitive scores with most marked decline in <5yo Thyroid hormone and GH deficiencies (10-year cumulative incidence), 64% and 48.9%, respectively |
| Marcus et al., 2005 (28) | 9 (2–26) years | WHO grade I (n=35, 70%) WHO grade II (n=15, 30%) |
SRT | Mean 52.2 (50.4–58) Gy | 12/50 | STR (n=38, 76%) | PFS (5-year) 82.5% (8-year) 65% OS 97.8% at 5-years, 82% at 8 years |
Transformation to higher grade tumor, anaplastic astrocytoma (n=2) RT induced PNET (n=1) Moya-moya (n=4) No significant acute toxicity attributable to SRT |
| Hug et al., 2002 (29) | 8.7 (2–18) years | Diffuse low grade astrocytoma (n=9, 33%) JPA (n=14, 52%), no path (n=4, 19%) |
Proton | Mean 55.2 (50.4–63) | No comment on prior therapy | STR/biopsy (n=25, 92%) GTR, but residual enhancement (n=1, 4%) GTR (complete radiographic resection) (n=1, 4%) |
At mean follow up 3.3 years 6/27 patients local failure, 4/27 died | Transformation to high grade GBM (n=1) New onset hypopituitarism (n=4) Moya moya (n=1) |
EBRT, external beam radiation therapy; IMRT, Intensity-modulated radiation therapy; SRT, Stereotactic radiotherapy; WHO, World Health Organization; GTR, Gross total resection; STR, Sub total resection; RT, radiation; PFS, Progression free survival; OS, Overall survival.