Table 2 Summary of literature describing clinical outcomes of PBT in the most common pediatric non-CNS malignancies
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 |