Table 2.
Proton therapy studies for early stage non-small cell lung cancer.
| First author | Year published | No. patients | Stage | Fractionation regimen | Median follow up | Overall survival | Local control | Toxicity |
|---|---|---|---|---|---|---|---|---|
| Bush and colleagues44 | 1999 | 37 | I (n = 27), II (n = 2), IIIA (n = 8) | 51 CGEs in 10 fractions or 45 Gy in 25 fractions + 28.8 CGEs in 16 fractions = 73.8 CGEs to GTV | 14 months | 2 years 31% (39% stage I) | 2 years 87% | 6% grade 2 pneumonitis (0% for protons alone) |
| Shioyama and colleagues45 | 2003 | 51 | IA (n = 9), IB (n = 19), II (n = 9), III (n = 8), IV (n = 1), recurrent (n = 5) | Median 76 CGEs in median 3.0 CGEs fractions with protons alone (n = 33) or protons + photons (n = 18) | 30 months | 5 years 29% (70% IA, 16% IB) | 5 years 57% (89% IA, 39% IB) | 8% grade ⩾2 lung |
| Bush and colleagues46 | 2004 | 68 | IA (n = 29), IB (n = 39) | 51 CGEs in 10 fractions (n = 22) or 60 CGEs in 10 fraction (n = 46) | 30 months | 3 years 44% (27% for 51 CGEs, 55% for 60 CGEs) | 3 years 74% (87% IA 49% IB) | 0% symptomatic pneumonitis |
| Nihei and colleagues47 | 2006 | 37 | IA (n = 17), IB (n = 20) | 70 CGEs in 20 fractions (n = 3), 80 CGEs in 20 fractions (n = 17), 88 CGEs in 20 fractions (n = 16), 94 CGEs in 20 fractions (n = 1) | 24 months | 2 years 84% | 2 years 80% | 16% grade ⩾2 pneumonitis/pleural effusion |
| Hata and colleagues48 | 2007 | 21 | IA (n = 11), IB (n = 10) | 50 CGEs in 10 fractions (n = 3) or 60 CGEs in 10 fractions (n = 18) | 25 months | 2 years 74% (100% IA, 47% IB) | 2 years 95% (100% IA, 90% IB) | 5% grade 2 pneumonitis, 10% late grade 2 subcutaneous induration/myositis |
| Nakayama and colleagues49 | 2010 | 55 (58 tumors) | IA (n = 30), IB (n = 28) | 66 CGEs in 10 fractions (peripheral, n = 41) or 72.6 CGEs in 22 fractions (central, n = 17) | 17.7 months | 2 years 97.8% | 2 years 97% | 7% grade ⩾2 pneumonitis, 2% rib fracture |
| Iwata and colleagues50 | 2010 | 80 | IA (n = 42), IB (n = 38) | Proton: 80 CGEs in 20 fractions (n = 20) or 60 CGEs in 10 fractions (n = 37); carbon ion: 52.8 CGEs in 4 fractions (n = 23) | 30.5 months | 3 years 75% (74% IA, 76% IB) | 3 years 82% (87% IA, 77% IB) | 12% grade ⩾2 lung, 16% grade ⩾2 skin, 23% rib fracture |
| Busch and colleagues | 2013 | 111 | IA (n = 47), IB (n = 64) | 51 CGEs in 10 fractions (n = 29), 60 CGEs in 10 fractions (n = 56), or 70 CGEs in 10 fractions (n = 26) | 30.5 months | 4 years 18% for 51 CGEs, 32% for 60 CGEs, 51% for 70 CGEs | 4 years 45% for 60 CGEs, 74% for 70 CGEs | 0% grade ⩾2 pneumonitis, 4% rib fractures |
| Iwata and colleagues52 | 2013 | 70 | IA (n = 47), IB (n = 23) | Proton: 80 CGEs in 20 fractions (n = 14), 60 CGEs in 10 fractions (n = 20), 66 CGEs in 10 fractions (n = 8), or 70.2 CGEs in 26 fractions (n = 1); carbon ion: 52.8 CGEs in 4 fractions (n = 16), 66 CGEs in 10 fractions (n = 8), or 68.4 CGEs in 9 fractions (n = 3) | 51 months | 4 years 58% (72% for operable patient, n = 30) | 4 years 75% | 3% grade ⩾2 pneumonitis, 7% grade ⩾2 skin, 27% rib fracture |
| Kanemoto and colleagues53 | 2014 | 74 (80 lesions) | IA (n = 59), IB (n = 21) | 66 CGEs in 10–12 fractions (peripheral, n = 59) or 72.6 CGEs in 22 fractions (central, n = 21) | 31 months | 5 years 65.8% | 5 years 81.8% | 3% grade 2 skin, 1% grade 2 esophagitis, 1% grade 3 pneumonitis, 14% rib fracture |
| Makita and colleagues54 | 2015 | 56 | IA (n = 43), IB (n = 13) | 66 CGEs in 10 fractions (peripheral, n = 32) or 80 CGEs in 25 fractions (central, n = 24) | 33.7 months | 3 years 81.3% | 3 years 96% | 16.1% grade 2, 1.8% grade 3 pneumonitis, 17.9% grade 1 and 2 rib fractures |
| Chang and colleagues55 | 2017 | 35 | IA (n = 12), IB (n = 16), IIA (n = 4), IIB (n = 3) | 87.5 Gy at 2.5 Gy/fraction | 83.1 months | 5 years 28.1 % |
5 years 85% | 51.4% grade 2, 2.9% grade 3 dermatitis, 2.9% grade 3 pneumonitis |
CGE, cobalt gray equivalents; GTV, gross tumor volume.