Table 1. Proton therapy studies for early-stage non-small cell lung cancer.
| Reference | Sample size | Stage | Dose [Gy (RBE)] | Technique | Median follow-up | Outcomes | Grade ≥3 toxicities | Correlations |
|---|---|---|---|---|---|---|---|---|
| Shioyama et al. (48) [2003] | 51 | IA (n=9), IB (n=19), II (n=9), III (n=8), IV (n=1), recurrent (n=5) | 76.0 Gy (RBE) in 3.0 Gy fractions | PSPT | 30 months | 5 yr: OS 29% (70% IA, 16% IB), CSS 47% (88% IA, 23% IB), DFS 37% (89% IA, 17% IB) | 2% grade 3 lung | Clinical substage (stage I) and OS, CSS, DFS, LC |
| Bush et al. (49) [2004] | 68 | IA (n=29), IB (n=39) | 51 CGE in 10 fractions (n=22), 60 CGE in 10 fractions (n=46) | PBT | 30 months | 3 yr: LC 74%, OS 44%, CSS 72%, DMFS 59% | 0% pneumonitis 0% esophageal | Higher performance status, female gender, and tumor size and OS |
| Nihei et al. (50) [2006] | 37 | IA (n=17), IB (n=20) | 70 Gy (RBE) in 20 fractions (n=3), 80 Gy (RBE) in 20 fractions (n=17), 88 Gy (RBE) in 20 fractions (n=16), or 94 Gy (RBE) in 20 fractions (n=1) | PSPT | 24 months | 2 yr: OS 84%, local PFS 80%, disease PFS 58% | 8% grade 3 pneumonitis | Clinical substage and locoregional recurrence |
| Hata et al. (51) [2007] | 21 | IA (n=11), IB (n=10) | 50 Gy in 10 fractions (n=3) or 60 Gy in 10 fractions (n=18) | PBT | 25 months | 2 yr: OS 74% (100% IA, 47% IB), CSS 86% (100% IA, 70% IB), local PFS 95% (100% IA, 90% IB), DFS 79% (89% IA, 70% IB) | 0% grade ≥3 toxicities | N/A |
| Iwata et al. (52) [2010] | 80 | IA (n=42), IB (n=38) | PBT: 60 Gy (RBE) in 10 fractions (n=37) or 80 Gy (RBE) in 20 fractions (n=20); CIT: 52.8 Gy (RBE) in 4 fractions (n=23) | PBT (n=57), CIT (n=23) | 30.5 months | 3 yr: OS 75% (74% IA, 76% IB), CSS 86% (84% IA, 88% IB), LC 82% (87% IA, 77% IB), DFS 54% (67% IA, 46% IB) | 1% grade 3 pneumonitis, 4% grade 3 dermatitis | None between technique and OS and LC |
| Nakayama et al. (53) [2010] | 55 | IA (n=30), IB (n=28) | 66 Gy (RBE) in 10 fractions (peripheral, n=41) or 72.6 Gy (RBE) in 22 fractions (central, n=17) | PSPT | 17.7 months | 2 yr OS 97.8%, 3 yr PFS 78.9% | 4% grade 3 pneumonitis, 2% rib fracture | None between clinical substage and OS |
| Iwata et al. (54) [2013] | 70 | IIA (n=47), IIB (n=23) | PBT: 60 Gy (RBE) in 10 fractions (n=20), 66 Gy (RBE) in 10 fractions (n=8), 70.2 Gy (RBE) in 26 fractions (n=1), or 80 Gy (RBE) in 20 fractions (n=14); CIT: 52.8 Gy (RBE) in 4 fractions (n=16), 66 Gy (RBE) in 10 fractions (n=8), or 68.4 Gy (RBE) in 9 fractions (n=3) | PBT (n=43), CIT (n=27) | 51 months | 4 yr: OS 58% (53% IIA, 67% IIB), LC 75% (70% IIA, 84% IIB), PFS 46% (43% IIA, 52% IIB) | %3 grade 3 pulmonary | None between clinical substage and OS, LC, and PFS |
| Bush et al. (55) [2013] | 111 | IA (n=47), IB (n=64) | 51 Gy (RBE) in 10 fractions (n=29), 60 Gy (RBE) in 10 fractions (n=56), or 70 Gy in 10 fractions (n=26) | PBT | 48 months | 4 yr: OS and CSS 51% and 74% with 70 Gy; LC 45% with 60 Gy, 74% with 70 Gy | 0% pneumonitis | Tumor size and OS, CSS, LC, and DF; increasing dose and OS |
| Kanemoto et al. (56) [2014] | 74 (80 lesions) | IA (n=59), IB (n=21) | 66 Gy (RBE) in 10–12 fractions (peripheral, n=59) or 72.6 Gy (RBE) in 22 fractions (central, n=21) | PSPT | 31 months | 5 y OS 65.8%, 5 y CSS 73.8%, 5 y PFS 52.5% | 1% pneumonitis, 1% skin ulcer, 14% rib fracture | Radiation dose and local recurrence; tumor location and LC; none between tumor diameter and LC |
| Makita et al. (57) [2015] | 56 | IA (n=43), IB (n=13) | 66 Gy (RBE) in 10 fractions (peripheral, n=32) or 80 Gy (RBE) in 25 fractions (central, n=24) | PSPT | 33.7 months | 3 y OS, PFS, and LC 81.3%, 73.4%, and 96.0% | 2% grade 3 dermatitis, 36% rib fracture (17% asymptomatic), 2% grade 3 pneumonitis | SUVmax and OS and PFS; none between dose and LC, PFS, and OS; none between sex, age, performance status, T-stage, pathology, and OS and PFS. |
| Chang et al. (32) [2017] | 35 | IA (n=12), IB (n-16), IIA (n=4), IIB (n=3) | 87.5 Gy (RBE) in 2.5 Gy (RBE) fractions | PSPT | 83.1 months | 5 yr: OS 28.1%, PFS 53.6%, | 2.9% grade 3 dermatitis, 2.9% grade 3 pneumonitis, | T-stage and distant metastasis; none between T-stage and local and regional recurrence |
| Nantavithya et al. (58) [2018] | 19 | IA (n=11), IB (n=3), IIB (n=1), recurrent (n=4) | 50 Gy (RBE) in 4 fractions | SBRT (n=9), SBPT (n=10) | 32 months | 3 yr: OS and LC 27.8% and 87.5% (SBRT), OS and LC 90.0% and 90% (SBPT) | 10% (n=1) grade 3 skin fibrosis (SBPT) | N/A |
Gy (RBE), Gray (relative biological effectiveness); CGE, cobalt Gray equivalent; PSPT, passive scattering proton therapy; PBT, proton beam therapy; CIT, carbon ion therapy; SBRT, stereotactic body radiotherapy; SBPT, stereotactic body proton therapy; OS, overall survival; CSS, cause-specific survival; DFS, disease-free survival; LC, local control; DMFS, distant-metastasis free survival; PFS, progression-free survival; SUVmax, maximum standardized uptake value; DF, distant failure.