Introduction
Materials and methods
Results
Author (year) | Treatment planning study assessment | Number of PBT pediatric patients | PBT results |
---|---|---|---|
Retinoblastoma | |||
Krengli (2005) [17] | PBT with different beam arrangements/tumor locations; Isodose comparison, DVH analysis (for target and OARs) | – | Homogeneous target coverage, effective OARs-sparing. Potential reduction of SMNs and side effects. |
Lee (2005) [18] | PBT vs 3D-CRT, electrons and IMRT; Isodose comparison, DVH analysis (target coverage and mean orbital volume receiving ≥5Gy) | 3/8 | Superior target coverage and orbital bone dose-sparing |
Hodgkin lymphoma | |||
Andolino (2011) [19] | BS-PT vs 3D-CRT; DVH analysis (breast parameters); paired t-test | 10 | Significant reduction of dosimetric breast parameters |
Hoppe (2012) [20] | INPT vs 3D-CRT and IMRT; Mean heart doses, mean doses to cardiac subunits; Wilcoxon paired t-test | 2/13 total INPT patients (including adults) | Reduction of mean heart dose and mean doses to all major cardiac subunits (p < 0.05) (entire cohort) |
Hoppe (2012) [21] | INPT vs 3D-CRT and IMRT; 50% reduction in the body V4; mean doses to OARs; paired t-tests | 1/10 total INPT patients (including adults) | Reduced body V4 (p < 0.01) and mean doses to OARs (entire cohort) |
Hoppe (2014) [4]a | INPT vs 3D-CRT and IMRT; integral body dose; mean doses to OARs | 5/15 total INPT patients (including adults) | Reduced integral dose and mean doses to OARs (entire cohort) |
Knäusl (2013) [22] | Treatment planning comparison (dosimetric parameters and DVHs for target and breast, thyroid, lungs, heart, bones) and SMNs assessment between PET-based RT with 3D-CRT, IMRT and PBT | 10 | The PET-based treatment planning ensures dosimetric advantages for OARs. PBT can further improve these results in terms of toxicity risk reduction |
Soft tissue sarcoma | |||
Weber (2004) [23] | IMPT vs IMRT, dose-escalated IMPT; DVH analysis (for target and OARs), inhomogeneity coefficient, conformity index | 5 | Similar level of tumor conformation, improved homogeneity with mini-beam IMPT, substantial reduction of OARs integral doses, dose-escalation always possible |
Rhabdomyosarcoma | |||
Miralbell (2002) [24] | PBT, IMPT vs conventional RT and IMRT; model-based SMNs risk assessment | 1/2 | Reduction of SMNs risk by a factor of ≥2 |
Ladra (2014) [25] | PBT vs IMRT; dosimetric parameters for target and OARs; paired t-tests, Fisher’s exact test | 54 | Comparable target coverage (p = 0.82). Reduced mean integral dose. Significant sparing for 26 of 30 OARs (p < 0.05) |
Kozak (2009) [26] | PBT vs IMRT; dosimetric parameters for target (target covarage and dose-conformity) and OARs two-tailed, Wilcoxon signed-rank test | 10 | Acceptable and comparable target coverage. Significant superior OARs-sparing, except for ipsilateral cochlea and mastoid / borderline significance for ipsilateral parotid (p = 0.05) |
Cotter (2011) [27] | PBT vs IMRT; dosimetric parameters for target and OARs Wilcoxon signed-rank test | 7 | Comparable target coverage. Significant reduction in mean OARs dose (p < 0.05) and bone volume receiving > 35 Gy |
Lee (2005) [18] | PBT vs 3D-CRT and IMRT; Isodose and dose-volume comparison for target and OARs | 3/8 | Superior target coverage and OARs dose-sparing (0% of mean ovarian volume received ≥2 Gy) |
Yock (2005) [28] | PBT vs 3D-CRT; DVH analysis for OARs (orbital and CNS structures) | 7 | Superior OARs dose-sparing |
Wilms tumor | |||
Hillbrand (2008) [29] | Passively scattered/scanned beams PBT vs conventional RT and IMRT; DVH analysis (liver and kidney dosimetric parameters); model-based SMNs risk assessment | 4/9 | Superior dose-sparing for liver and kidney (mean liver and kidney dose reduced by 40–60%). Reduced SMNs risk with scanned beams PBT |
Author (year) | Method | Number of PBT pediatric patients | Med FU # mo or y (range) | Med Total Dose # CGE or Gy (RBE) (range) | Combined treatments | Outcomes # |
---|---|---|---|---|---|---|
Retinoblastoma | ||||||
Sethi (2014) [12] | R/C (protons vs photons) | 55/86 | 6.9 y (1–24.4) | 44.16 Gy (RBE) (40.0–50.0) | Variable ** (chemotherapy) | 10y cumulative incidence of in-field SMNs: 0% (vs 14% with photons, p = 0.015) |
Mouw (2014)a [30] | R | 49 (60 eyes) | 8 y (1–24) | 44.0 Gy (RBE) (40–46.8) | Variable ** (chemotherapy, cryotherapy/laser) | Enucleation-free survival: 81.6% No in-field SMNs |
Hodgkin lymphoma | ||||||
Hoppe (2014) [4] | P | 5/15 (mix A-P patients) | 37 mo (26–55) | 15–25.5 CGE | Variable ** (chemotherapy) | 3y RFS: 93% (1 relapse among pediatrics) 3y EFS 87% No acute or late grade ≥ 3 toxicities |
Wray (2016) [31] | R | 22 | 36 mo | 21 Gy (RBE; range, 15–36) including 9 patients treated with a sequential boost due to an incomplete response | Variable ** (chemotherapy) | 2-year and 3-year OS rates: 94%, 2-year and 3-year PFS rates were both 86%. 3 high-risk patients recurred. No acute or late grade ≥ 3 toxicities |
Chordoma/Chondrosarcoma | ||||||
Hug (2002) [32] | R | 13/29 (mix benign-malignant) | 40 mo (13–92) | CH: 73.7 CGE (70–78.6) CS: 70.0 CGE (69.6–70.2) | Variable ** (surgery; protons-photons) | 5y LC*: 60% CH, 100% CS 5y OS*: 60% CH, 100% CS 2% severe late effects |
Habrand (2008) [33] | R | 30 | 26.5 mo (mean) | 68.4 CGE (54.6–71) (Mean total dose for CS/CH) | Variable ** (surgery; protons-photons) | 5y OS: 81% CH, 100% CS 5y PFS: 77% CH and 100% CS Grade 2 late toxicity: 7 patients; grade 3: 1 patient |
Rutz (2007) [34] | R | 3/26 (mix A-P patients) | 35 mo (13–73) | CH: 72 CGE (59.4–74.4) | Variable ** (surgery; photon RT) | 3y OS*: 84% 3y PFS*: 77% Late toxicity: 4 patients |
Rutz (2008) [35] | R | 10 | 36 mo (8–77) | CH: 74 CGE CS: 66 CGE (63.2–68) | Variable ** (surgery; chemotherapy) | LC, OS and FFS: 100% Late toxicity: grade 1 (2 patients), grade 2 (1 patient) |
Ares (2009) [36] | R | 64 (mix A-P patients) | 38 mo (mean) (14–92) | CH: 73.5 RBE CS: 68.4 RBE | Variable ** | 5y LC*: 81% CH and 94% CS 5y DSS*: 81% CH and 100% CS 5y OS*: 62% CH and 91% CS high-grade toxicity: 4 patients |
Staab (2011) [37] | R | 3/40 (mix A-P patients) | 43 mo (24–91) | CH: 72.5 Gy (RBE) (mean total dose) (59.4–75.2) | Variable ** (surgery; protons-photons) | 5y LC*: 62% 5y DFS*: 57% 5y OS*: 80% (rates were 100% without SS) |
Rombi (2013) [38] | R | 26 | 46 mo (mean) (4.5–126.5) | CH: 74 RBE (73.8–75.6) CS: 66 RBE (54.72) | Variable ** (surgery) | 5y LC*: 81% CH and 80% CS 5y OS*: 89% CH and 75% CS No high-grade late toxicities |
Soft tissue sarcoma | ||||||
Timmerman (2007) [39] | R | 16 (various histologies) | 18.6 mo (4.3–70.8) | 50 CGE (46–61.2) | Variable ** (surgery, chemotherapy) | LC: 75% 1y PFS: 81.8% 2y PFS:71.6% 1y OS: 90.9% 2y OS: 69.3% Mild acute toxicity (G3-G4 in bone marrow with concurrent chemotherapy) |
Rhabdomyosarcoma | ||||||
Ladra (2014) [25] | P | 54 | 3.9 y | Variable according to tumor site 45–50.4 Gy (RBE) | Variable ** | 3y EFS: 69%; 5y EFS: 65% 3y OS: 80%; 5y OS 77% 3y LC: 78%; 5y LC: 78% Late grade 3 toxicity: 3 patients / No SMNs |
Leiser (2016) [40] | R | 83 | 55.4 mo (0.9–126.3) | 54 Gy (RBE) (41.4–64.8) | Variable ** (chemotherapy) | 5y LC: 78.5% (95% CI, 69.5–88.5%) 5y OS: 80% (95% CI, 71.8–90.0%) 5y grade 3 toxicity: 3.6% No grade 4–5 toxicity SMNs: 1.2% (1/83) Quality of life significantly increased |
Childs (2012) [41] | R | 17 | 5 y (2–10.8) | 50.4 Gy (RBE) (50.4–56.0) | Variable ** (chemotherapy, photon RT, surgery) | 5y-FFS: 59% (95% CI, 33–79%), 5y-OS: 64% (95% CI, 37–82%). 5y-Late effects in 10 patients (58.8%) |
Cotter (2011) [27] | R | 7 | 27 mo (10–90) | 36–50.4 CGE | Variable ** (surgery, chemotherapy) | 71% of patients with no evidence of disease Good treatment tolerance No SMNs |
Yock (2005) [28] | R | 7 | 6.3 y (3.5–9.7) | 46.6 CGE (40–55) | Variable ** (photon RT, chemotherapy) | DFS: 100%, LC: 6/7 patients (85%) Excellent orbital functional outcome |
Weber (2016) [42] | R | 39 | Mean 41 mo (9–106 mo) | 54 Gy (RBE) (50.4–55.8) | Neoadjuvant and concomitant chemotherapy | 10 patients failed. PFS*: 72% (95% CI, 67–94%), 5-year OS: 73% (95% CI, 69–96%). A delay in the initiation of PT (> 13 weeks) was a significant detrimental factor for PFS. 3 (8%) patients had grade 3 toxicity (eye/ear). 5-year grade 3 toxicity free survival*: 95% (95% CI, 94–96%) |
Vern-Gross (2016) [43] | R | 66 | 1.5 y | 50.4 Gy (RBE) | Chemotherapy | 2-year LC* and OS*: 88 and 89%. Permanent toxicity affected only 9 pts. (eye, ear, ormonal). Median survival after initial recurrence was 6 months (range:1–25) |
Mizumoto (2018) [44] | R | 55 | 24.5 mo (1.5–320) | 50.4 GyE (36.0–60.0) | Variable ** (surgery, chemotherapy) | 1- and 2-year OS rates were 91.9 and 84.8% 1- and 2-year PFS rates were 81.6 and 72.4% 1- and 2-year LCRs were 95.6 and 93.0% 13 patients recurred Grade > 3 late toxicities were not occurred |
Ewing sarcoma | ||||||
Rombi (2012) [45] | R | 30 | 38.4 mo (17.4 mo - 7.4 years) | 54 Gy (RBE) (45–59.4) | Variable ** (surgery; chemotherapy) | 3y EFS*, 60% 3y LC*: 86% 3y OS*: 89% Mild/moderate acute skin toxicity 4 hematological SMNs with combined chemotherapy |