Table 1.
Study descriptions early stage NSCLC.
| Study (characteristics); location | Beam, energy, technique | Chemotherapy | Fractionation schedule, TTD/n or fr/OTT | Patient selection criteria/risk factors | Stage distribution |
|---|---|---|---|---|---|
| PROTON BEAM ONLY | |||||
| Bush et al. (26) (prospective, n = 37); U.S. Loma Linda | Proton Photon + proton PSc | No | 51 GyE/10 fr/2 weeks PBT Photons 45 Gy/25fr + protons, 28.8 GyE/16 fr/5 weeks | NSCLC stage I–IIIA; medically inoperable/refused surgery | Stage I, 27; Stage II, 2; Stage IIIA, 8 |
| Shioyama et al. (27) (retrospective, n = 51); Japan, Tsukuba | Proton, 250 MeV, PSc (n = 33) Photon + proton (n = 18) | 6 patients prior chemotherapy (all advanced stages) | Median 76 Gy (range 49-93 Gy), median fr dose 3.0 Gy (range 2–6 Gy), median OTT 43 days | NSCLC, medically inoperable/refused surgery | Stage IA/IB, 9/19; Stage IIA/IIB, 3/6; Stage IIIA/IIIB, 8; Stage IV, 1, recurrent disease, 5. |
| Bush et al. (14) (Phase II, n = 68); U.S. Loma Linda | Proton, PSc | No | 51 GyE/10 fr/2 weeks (n = 22); 60 GyE/10 fr/2 weeks (n = 46) | NSCLC stage I, medically inoperable (n = 63)/refused surgery (n = 5) | Stage IA, 29; Stage IB, 39 |
| Nihei et al. (15) (Retrospective, n = 37); Japan, Chiba | Proton, 150 or 190 MeV, PSc | No | 70 GyE/20 fr/4–5 weeks (n = 3); 80 GyE/20 fr/4–5 weeks (n = 17); 88 GyE/20 fr/4–5 weeks (n = 16); 94 GyE/20 fr/4–5 weeks (n = 1) | NSCLC stage I; medically inoperable (n = 23)/refused surgery (n = 14), tumor size ≤ 5 cm, pO2 ≥ 60 torr, Zubrad PS 0-2 | Stage IA, 17; Stage IB, 20 |
| Hata et al. (16) (prospective, n = 21), Japan, Tsukuba | Proton, 155-200 MeV, PSc | No | 50 GyE/10 fr/2 weeks (n = 3); 60 GyE/10 fr/2 weeks (n = 18) | NSCLC stage I, medically inoperable (n = 9)/refused surgery (n = 12), ECOG PS 0–2, no previous RT or chemotherapy for NSCLC | Stage IA, 11; Stage IB 10 |
| Nakayama et al. (17) (retrospective, n = 55) (58 tumors) Japan, Tsukuba | Proton, 155–250 MeV, PSc | No | Peripheral tumors 66 GyE/10 fr/2 weeks (n = 41), central tumors 72.6 GyE/22 fr/4.5 weeks (n = 17) | NSCLC stage I; EORTC PS 0–2, medically inoperable (n = 52)/refused surgery (n = 3), Exclusion: pleural effusion, tumor close to stomach/esophagus | Stage IA, 30; Stage IB, 28 |
| Bush et al. (18) (Phase 2, n = 111); U.S. Loma Linda | Proton, PSc | No | Dose escalation during study, 51 GyE/10 fr/2 weeks (n = 29), 60 GyE/10 fr/2 weeks (n = 56), 70 GyE/10 fr/2 weeks (n = 26) | NSCLC stage I, medically inoperable/refused surgery | Stage IA, 47; Stage IB, 64 |
| Kanemoto et al. (19) (Retrospective, n = 74, 80 tumors), Japan, Tsukuba | Proton, 155–250 MeV, PSc | No | Peripheral tumors 66 GyE/10–12 fr/2–2.5 weeks (n = 59), central tumors 72.6 GyE/22 fr/4.5 weeks (n = 21) | NSCLC stage I | Stage IA, 59; Stage IB, 21 |
| C-ION (COMBINED WITH PROTON BEAM) | |||||
| Iwata et al. (24) (retrospective, n = 80), Japan, Hyogo | Proton 150 MeV, PSc C-ion 320 MeV, PSc | No | Proton: 80 GyE/20 fr/4 weeks (n = 20), 60 GyE/10 fr/2 weeks (n = 37), C-ion: 52.8 GyE/4 fr/1 week (n = 23) | NSCLC stage I, medically inoperable (n = 47)/refused surgery (n = 43), WHO PS 0–2, no history lung cancer or previous chest RT/chemo | Stage IA, 42; Stage IB, 38 |
| Iwata et al. (25) {retrospective [partially subgroup of cohort Iwata (24)], n = 70}, Japan, Hyogo | Proton 150 MeV, PSc C-ion 320 MeV, PSc | No | Proton: 80 GyE/20 fr/4 weeks (n = 14), 60 GyE/10 fr/2 weeks (n = 20), 66 GyE/10 fr/2 weeks (n = 8), 70.2 GyE/26 fr/5.5 weeks (n = 1) C-ion: 52.8 GyE/4 fr/1 week (n = 16), 66 GyE/10 fr/2 weeks (n = 8), 68.4 GyE/9 fr/2 weeks (n = 3) | NSCLC cT2a/T2bN0M0, medically inoperable (n = 40)/refused surgery (n = 30), WHO PS 0–2, no history lung cancer or previous chest RT/chemotherapy | Stage IB, 47; Stage IIA, 23 |
| Miyamoto et al. (20) (phase I/II, n = 81, 82 tumors), Japan, Chiba | C-ion, 290–350–400 MeV, PSc | No | 59.4–95.4 GyE/18 fr/6 weeks (n = 48), 68.4–79.2 GyE/9 fr/3 weeks (n = 34) | Inoperable NSCLC stage I, WHO PS 0–2, no history of RT to target, no prior chemotherapy <4 weeks | Stage IA, 41; Stage IB, 41 |
| Miyamoto et al. (21) (phase II, n = 79), Japan, Chiba | C-ion, 290–350–400 MeV, PSc | No | 52.8 GyE/4 fr/1 week (IA) 60 GyE/4 fr/1 week (IB) | NSCLC stage I, medically inoperable/refused surgery, WHO PS 0-2, no history of RT to target, no prior chemotherapy <4 weeks | Stage IA, 42; Stage IB, 37 |
| Miyamoto et al. (22) (phase II, n = 50, 51 tumors), Japan, Chiba | C-ion, 290–350–400 MeV, PSc | No | 72 GyE/9 fr/3 weeks | Peripheral NSCLC Stage I, WHO PS 0-2, no history of RT to target, no prior chemotherapy <4 weeks | Stage IA, 30; Stage IB, 21 |
| Sugane et al. (23) (phase II, n = 28, 29 tumors), Japan, Chiba | C-ion, 290–350–400 MeV, PSc | No | 72.0 GyE/9 fr/3 weeks (all, 1999–2000,n = 12), 60.0 GyE/4 fr/1 week (IA, n = 11), 52.8 GyE/4 fr/1 week (IB, n = 6) | NSCLC stage I; elderly, aged ≥80 years | Stage IA, 12; Stage IB, 17 |
ECOG, Eastern Cooperative Oncology Group; EORTC, European Organization for Research and Treatment of Cancer; OTT, overall treatment time; PS, performance score; PSc, passive scattering; RT, radiotherapy; TTD, total tumor dose; WHO, World Health Organization.