Table 1 Summary of literature describing dosimetric results achieved by PBT and comparison of PBT vs photons

 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

 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

 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

 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

 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