Table 5.
Recent proton therapy studies for pediatric brain tumors
| Author [ref] | year | Tumor type | # pts | Median Age [years] |
Median Dose [GyRBE] (range) |
Median FU [months] (range) |
Outcome | Late Toxicity |
|---|---|---|---|---|---|---|---|---|
| De Amorim Bernstein et al.96 | 2013 | AT/RT | 10 | 2.3 | 50.4 (50.4–55.8); three pts CSI (18–23.4) |
27.3 (11.3–99.4) |
LC 100%, DC 80%, OS 90% | Endocrine G2 (2pts hypothyroidism, 3pts GH deficiency) |
| Mc Govern et al.84 | 2014 | AT/RT | 31 | 1.6 | 50.4 (9–54); 14 pts CSI (23.4–36) |
24 (3-53) |
Median OS 34.3mo, PFS 20.8mo | five pts imaging changes interpreted as RN |
| Weber et al.95 | 2015 | AT/RT | 15 | 1.4 | 54 all patients, no CSI | 33.4 (9.7–69.2) |
LF 20%, DBF 27%, SF 2%. 2y OS 64.6%, 2y PFS 66% | 2y tox free survival 90%. No decrease of QoL after PT |
| Bishop et al.91 | 2014 | Craniopharyngioma | 52 (21 PT) |
8.9 | 50.4 (50.4–54) | 59.6 (PT 33mo) |
3y OS 96%, nodular FFS 96%, cystic FFS 76%. Same outcome for PT and IMRT | Endocrine G2 77%. No difference between PT and IMRT |
| MacDonald et al.97 | 2013 | Ependymoma | 70 | 3.2 | 55.8 (50.4–60) | 46 (12–140.4) |
3y LC 83%, PFS 76%, OS 95% 5y LC 77%, DC 83% |
one pt hypothyroidism, two pts GH deficit, two pts hearing loss, two pts cavernoma. No drop in MI and OAS scores |
| Mizumoto et al.98 | 2015 | Ependymoma | 6 | 5 | 56.7 (50.4–61.2) | 24.5 (13-44) |
OS 100%, PFS 80% | one pt one-time seizure, one pt alopecia, no difficulty in daily life |
| Ares et al.92 | 2016 | Ependymoma | 50 | 2.6 | 59.4 (54–60) | 43.4 (8.5–113.7) |
5y LC 78%, OS 84% | 38% G1/2, two pts G3 deafness, one pt G5 brainstem necrosis |
| Sato et al.99 | 2017 | Ependymoma | 79 (41 PT) |
3.7 | 55.8 (50.4–59.4) | PT 31.2 (7.2–86.4) IMRT 58.8 (13.2–140.4) |
3y OS 81% IMRT vs 97% PT (p = .08), PFS 60% IMRT vs 82% PT (p = .0307), Recurrence 55% IMRT vs 17% PT (p = .005) | Vascular disorder G2 + 10% (6 RN, one stroke, one cavernoma) |
| MacDonald et al.93 | 2011 | Germ cell tumors | 22 | 11 | Total 44 (30.6–57.6) 1pt IF only seven pts WVRT 19.5–23.4 1pt WBRT 25.5 13 pts CSI 18.3–27 |
28 (13-97) |
LC 100%, PFS 95%, OS 100% | two pts hypothyroidism, 2pts GH deficit. No new NC or auditory deficit |
| Hug et al.94 | 2002 | Low grade glioma | 27 | 8.7 | 55.2 (50.4–63) | 39.6 (7.2–81.6) |
LF 22%, OS 85% | Moya-Moya one pt |
| Greenberger et al.78 | 2014 | Low grade glioma | 32 (nine mix PT and photons) |
11 | 52.2 (48.6–54) | 91.2 (38.4–218.4) |
6y PFS 89.7%, 8y PFS 82.8%, 8y OS 100% | Endocrine G2 > 80% at 10y (>40 GFy to pituitary and hypothalamus is RF), two pts G3 vasculopathy (Moya-Moya), age > 7y and hippocampus dose RF for NC decline, VA/VF decline four events, other visual tox nine events |
| Jimenez et al.100 | 2013 | Medulloblastoma / supratentorial PNET | 15 | 2.9 | Total 54 (39.6–54) CSI 21.6 (18–30.6) |
39 (3-102) |
3y LF 7.7%, OS 85.6% | Ototoxicity nine pts (2 G3), Endocrine G2 three pts, significant height loss, NS if GH deficiency pts excluded, no loss from baseline IQ |
| Eaton et al.101 | 2016 | Medulloblastoma | 88 (45 PT) | 6 | Total 54–55.8 CSI 23.4 (18–27) |
74.4 PT pts 84 photon pts |
6y RFS 78.8% PT vs 76.5% photon (p = .948). 6y OS 82% PT vs 87.6% photon (p = .285) | NR |
| Yock et al.102 | 2016 | Medulloblastoma | 59 | 6.6 | Total 54 CSI 23.4 (23.4–36) |
84 (62.4–98.4) |
3y PFS 83% 5y PFS 80%, OS 83% 7y PFS 75%, OS 81% |
Ototoxicity G3 + 12% at 3y and 16% at 5y and 7y, FSIQ decline by 1.5 point/y, Endocrine deficit 27%, 55 and 63% at 3, 5 and 7y, Cataract two pts, BS injury one pt, Stroke two pt |
NS, not statistically significative. WBRT, whole brain radiotherapy; AT/RT, atypical teratoid/rhabdoid tumor; CSI, craniospinal irradiation ; DBF, distant brain failure; DC, distant control; FFS, failure free survival;FSIQ, full scale intelligence quotient; FU, follow-up; G, toxicity grade;GH, growth hormone; GyRBE, Gray in relative biological effectiveness; IF, involved field;LC, local control; LF, local failure;MI, mean intelligence; NC, neurocognitive; NR, not reported; OAS, overall adaptive skills; OS, overall survival;PFS, progression free survival;RF, risk factor; RFS, recurrence free survival;RN, radiation necrosis; SF, spinal failure, PT: proton therapy;VA, visual acuity; VF, visual field; WVRT, whole ventricle radiotherapy; mo, months;pts, patients.