Skip to main content

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

From: Proton therapy in the most common pediatric non-central nervous system malignancies: an overview of clinical and dosimetric outcomes

Author (year)MethodNumber of PBT pediatric patientsMed FU #
mo or y (range)
Med Total Dose #
CGE or Gy (RBE) (range)
Combined treatmentsOutcomes #
Retinoblastoma
 Sethi (2014) [12]R/C (protons vs photons)55/866.9 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]R49 (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]P5/15 (mix A-P patients)37 mo (26–55)15–25.5 CGEVariable ** (chemotherapy)3y RFS: 93% (1 relapse among pediatrics)
3y EFS 87%
No acute or late grade ≥ 3 toxicities
 Wray (2016) [31]R2236 mo21 Gy (RBE; range, 15–36) including 9 patients treated with a sequential boost due to an incomplete responseVariable ** (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]R13/29 (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]R3026.5 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]R3/26 (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]R1036 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]R64 (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]R3/40 (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]R2646 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]R16 (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]P543.9 yVariable 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]R8355.4 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]R175 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]R727 mo (10–90)36–50.4 CGEVariable ** (surgery, chemotherapy)71% of patients with no evidence of disease
Good treatment tolerance
No SMNs
 Yock (2005) [28]R76.3 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]R39Mean 41 mo (9–106 mo)54 Gy (RBE) (50.4–55.8)Neoadjuvant and concomitant chemotherapy10 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]R661.5 y50.4 Gy (RBE)Chemotherapy2-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]R5524.5 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]R3038.4 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
  1. # If not specifically reported, results are referred to entire cohort when mixed population is considered
  2. RBE: relative biological effectiveness, CGE: cobalt Gray equivalent;
  3. FU Follow-up, A-P Adult-pediatric
  4. R Retrospective, C Comparative, P Prospective
  5. **variable: different surgery/chemotherapy/RT approaches performed in the patient population
  6. LC Local control, OS Overall survival, PFS Progression free survival, RFS Relapse-free survival
  7. EFS Event-free survival, FFS Failure-free survival, DSS Disease specific survival, DFS Disease free survival
  8. SS Surgical stabilization
  9. * actuarial rate
  10. CI Confidence interval
  11. aStudies by Sethi et al. and Mouw et al. based on the same patients cohort treated with PBT at Massachusetts General Hospital between 1986 and 2012 [46]