Table 2.
Summary of results of tumour related outcomes studies on PBT in children and young adults with CNS tumours
| Study details Author, year [ref] |
Tumour type |
N | Overall Survival | Progression-Free Survival | Time to Progression | Response Rates | Local Failure Rate | Distant Failure Rate |
|---|---|---|---|---|---|---|---|---|
|
Eaton (2016)[23]a Shared PBT cohort with Yock 2016[31] |
MB |
88 PBT: 45 XRT: 43 |
6 yrs:- PBT: 82.0% (95% CI: 65.4–91.1) XRT: 87.6% (95% CI: 72.7–94.7) (p = 0.285) |
6 yr RFS:- PBT: 78.8% (95% CI: 63–89) XRT: 76.5% (95% CI: 60.6–86.6) (p = 0.948) 10 pts in each cohort experienced a recurrence (p = 0.908) |
NR | NR | NR | NR |
| Grewal (2019)[24] | MB | 14 |
OS: 1 yr 93% (KM) OS: 5 yr 84% (95% CI 48 0 96%) |
RFS: 1 yr 86% RFS: 5 yrs 70% (95% CI 48–96%) |
Median time to relapse post RT: 0.9 yr | NR | NR | Progression outside posterior fossa = 3pts (42%) |
|
Jimenez (2013)[43]b |
MB /sPNET |
15 |
3.25 yrs: 85.6% (95% CI: 68.6–100) |
NR | NR | NR | Local failure rate = 1 pts at 12 months | No distant failure reported |
| Sethi (2014)[29]d | MB | 109 | 3.2 yrs: 89% | NR |
Median: 1.55 yrs (0.23–3.24) |
NR | 3.2 yrs: 5% | 3.2 yrs: 10% |
| Yock (2016)[31]b | MB | 59 |
All pts:- 5.0 yrs: 83% (95% CI: 70–90) 7.0 yrs: 81% (95% CI: 67–89); Standard-risk pts (n = 39; 66%):- 5.0 yrs: 86% (95% CI: 70–94) 7.0 yrs: 86% (95% CI: 70–94); Intermediate-high risk pts (n = 20; 34%):- 5.0 yrs: 75% (95% CI: 50–89) 7.0 yrs: 68% (95% CI: 42–84) |
All pts: 5.0 yrs: 80% (95% CI: 67–88) 7.0yrs: 75% (95% CI: 61–84) Standard-risk pts (n = 39; 66%):- 5.0 yrs: 85% (95% CI: 69–93) 7.0 yrs: 81% (95% CI: 64–91) Intermediate-high risk pts (n = 20; 34%):- 5.0 yrs: 70% (95% CI: 45–85) 7.0 yrs: 63% (95% CI: 37–81) |
Standard-risk pts (n = 39; 66%):- median 2.5 yrs (1.3–4.4) Intermediate-high risk pts (n = 24; 34%):- median 1.3 yrs (0.8–2.3) |
NR | NR | NR |
| Ares (2016)[32]b | Epend | 50 |
5.0 yrs: 84% (SD ± 6.8%); Five pts (10%) died of progressive disease due to local or distant failure at a median time of 2.75 yrs (range 2–4) |
NR | NR |
Of 17 pts who achieved an STR: CR: n = 13 (76%) PR/SD: n = 3 (18%) PD: n = 1 (6%) All 17 pts progressed at a mean interval of 19 mths (range 9–16 mths) |
5.0 yrs: 22% | 2/ 50 4% (no time given) |
| Eaton (2015)[33]c | Epend | 20 |
3.0 yrs: 76% (95% CI: 67.6–89.6) |
Median: 1.6 yrs (95% CI: 1.0–2.2) 1.0 yrs: 66.5% (95% CI: 55.2–77.8) 3.0 yrs: 28.1% (95% CI: 15.6–40.6) |
NR | NR |
3.0 yrs: 5/11 (45%) pts with a first local failure Failure rates directly related to pattern of first failure |
3.0 yrs: 6/9 (67%) pts first distant failure Failure rates directly related to pattern of first failure |
| Indelicato (2017)[34]d | Epend | 179 | 3.0 yrs: 90.4% | 3.0 yrs 75.9% | NR | NR |
3 yrs: 14.6% (95% CI: 9.6–21.7) Median time to local failure was 1.4 yrs (range, 0.2–2.5) |
3 years: 15.4% (95% CI: 10.4–22.2) Median time to distant failure was 1.0 yrs (range, 0.2–6.1) |
| MacDonald (2013)[35]b | Epend | 70 |
3.0 yrs: 95% (95% CI: NR) |
3.0 yrs: 76% (95% CI: NR) |
NR | NR |
3.0 yrs: 17% 5.0 yrs: 23% |
3.0 yrs: 14% 5.0 yrs: 17% |
| Sato (2017)[36]a | Epend |
79 PBT: 41 XRT: 38 |
3.0 yrs: PBT: 97% (95% CI: 83–99) XRT: 81% (95% CI: 63–90) (P = 0.08) |
3.0 yrs PFSe: PBT: 82% (95% CI: 64–92) XRT: 60% (95% CI: 42%-74%) (P = 0.031) 3.0 yrs local RFSe:- PBT: 88% XRT: 65% |
NR | NR |
PBT: n = 6 (15%) at 2.6 yrs median follow-up XRT: n = 18 (47%) at 4.9 yrs median follow-up |
PBT: n = 1 (2%) at 2.6 yrs median follow-up XRT: n = 3 (8%) at 4.9 yrs median follow-up |
| De Amorim Bernstein (2013)[37]b | AT/RT | 10 | 2.3 yrs – last fu: 90% | NR | NR |
CCR: n = 6 (70%) CR: n = 2 (20%) SD: n = 1 (10%) |
2.3 yrs: 0% | 2.3 yrs: n = 2 (20%) |
| Haskins (2015)[38]c | AT/RT | 16 |
Mean: 5.6 years (95% CI: 4.4–6.9) 3.2 yrs: 81% (95% CI: NR) |
1.4 yrs: 75% (95% CI: NR) |
NR |
1.4 yrs:- NED: n = 6 (38%) SD: n = 7 (44%) DOD: n = 3 (18%) PD: 6% (Secondary malignancy) |
3.2 yrs: n = 2 (13%) | 2.3 yrs: n = 4 (26%) |
| McGovern (2014)[39]a,c | AT/RT | 31 |
Median OS from diag: 2.9 yrs; 2.0 yrs from diag: 68.3% (95% CI: 53.9–8.1); 2.0 yrs from end of PBT: 52.9% (95% CI: 36.0–77.8) |
Median PFS from diag: 1.7 yrs; 2.0 yrs from diag: 47.6% (95% CI: 32.2–70.5); 2.0 yrs from end of PBT: 45.9% (95% CI: 29.4–71.4) |
NR | NR | NR | NR |
| Weber (2015)[40]a | AT/RT | 15 |
2.0 yrs: 64.6% (95% CI: 39–90) |
2.0 yrs: 66% (95% CI: 42–90) |
NR |
N = 7 (residual disease prior to PBT): CR: n = 2 (29%) SD: n = 3 (42%) PD: n = 2 (29%) |
2.8 yrs: n = 3 (20%) | 2.8 yrs: n = 4 (27%) |
| Bishop (2014)[42]c | Cranio | 52 |
3.0 yrs (whole cohort): 96% 3.0 yrs (PBT vs XRT): 94.1% vs 96.8% (p = 0.74) |
NR | NR | NR | NR | NR |
| Luu (2006)[45]d | Cranio | 16 |
5.0 yrs (1 resection): 100%; 5.0 yrs (> 1 resection): 60% |
NR | NR | NR | 5.0 yrs: n = 1 (6%) | NR |
| Jimenez (2021)[43]b | Cranio | 77 | 5.0 yrs: 97.7% (95%CI 84.6 – 99.7%) | NR | NR | NR |
5.0 yrs: 9.9% (95% CI 3.5 – 20.2%) Median fu: 4.8yrs (range 0.8 – 15.6) 6 pts had LF Median time to failure 3.6yrs (range 1.8 – 8.4) from RT end |
NR |
| Winkfield (2009)[46] | Cranio | 24 | NR | NR | NR | NR | 3.4 yrs: 0% | NR |
| Greenberger (2014)[47]b | LGG | 32 |
8 yrs: 100% (95% CI: NR)f |
6.0 yrs: 90% (95% CI:NR) 8.0 yrs: 83% (95% CI:NR) |
NR | NR | NR | NR |
| Hug (2002)[48]c | LGG | 27 |
3.3 yrs: 85% (95% CI: NR) |
NR | NR | NR | 3.3 yrs: 22% | 3.3 yrs: 0% |
| Indelicato (2019)[49]d | LGG | 174 | 5.0 yrs: 92% (95% CI, 85%-95%) | 5.0 yrs: 84% (95% CI, 77%-89%) | Median time to LF: 1.0 yr (0.3–4.4) | NR | 5.0 yrs: 15% | NR |
| MacDonald (2011)[50]d | GCT | 22 | 2.3 yrs: 100% |
2.3 yrs: 95% (95% CI: NR) |
NR | NR |
2.3 yrs: Germinoma: 0% NGGCT: 0% |
2.3 yrs: Germinoma: 0% NGGCT: n = 1 (11%) |
| Farnia (2014)[51]a | Pineo | 22 |
3.2 yrsg: 90%h PBT: 88% (2 deaths) PHOT: 45% (6 deaths) |
NR | NR | NR | 1.7 yrs: 10% | 1.4 yrs: 10% |
Key:- a: survival outcomes measured from the time of diag; b: survival outcomes measured from the start of PBT; c: survival outcomes measured from completion of PBT; d: time survival outcomes measured from not reported; e: PFS and RFS values approximate as not reported directly in study but extrapolated from Kaplan Meier curves by reviewer; f: patients required to have at least 3-year follow-up to be eligible for study; g: study also included 21 adult patients but survival outcomes and adverse event data not reported separately for children; h: not calculated according to Kaplan–Meier method but rather 9/10 patients alive at time of analysis.
CCR continuing complete response, CR complete response, Cranio Craniopharyngioma, DOD died of disease, Epend Ependymoma, GCT Germ Cell Tumour, LGG Low Grade Gliomas, MB Medulloblastoma, NED no evidence of disease, NGGCT Non-Germinomatous Germ Cell Tumour, NR not reported, PBT proton beam therapy, PD progressive disease, PIN Pineoblastoma, Photon RT photon radiotherapy, PR partial response, Pineo pineoblastoma, pts patients, RFS recurrence-free survival, RR response rate, SD Stable disease, (s)PNET (supratentorial) Primitive Neuroectodermal Tumour