Table 1.
Main study characteristics.
| Author | Year | Nation | N | Study Type | RT dose/fraction | ICIs Sequencing |
ICIs Type |
Intervention Period | Toxicity ≥ Grade 3 (%) |
Grade 5 Toxicity (%) | All Grade Pneumonitis (%) |
Pneumonitis≥ Grade 3 (%) |
Grade 5 Pneumonitis (%) |
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Shukla | 2021 | USA | 92 | Prospective | 5940-6660c Gy | Sequential | Pemb (PD-1) |
12 months | NR | NR | 18.5% | 4.3% | 1.1% | |
| Shaverdian | 2017 | USA | 24 | Prospective | NR | Sequential | Pemb (PD-1) |
NR | NR | NR | 8.4% | 4.2% | 0% | |
| Finn | 2020 | UK | 475 | Prospective | <6000cGy (8%) 6000-6600c Gy (86%) >6600cGy (6%) |
Sequential | Dura (PD-L1) |
12 months | 37.1% | 4.4% | 33.9% | 4.6% | 1.1% | |
| LeClair | 2022 | USA | 83 | Retrospective | <6000cGy (4%) 6000cGy (48%) >6000cGy (34%) NR (16%) |
Sequential | Dura (PD-L1) |
average of 13.9 (range 1-47) doses | NR | NR | 25.3% | 7.2% | 1.2% | |
| Landman | 2021 | Israel | 39 | Retrospective | Mean dose 6990cGy |
Sequential | Dura (PD-L1) |
average of 21 (range 1-26) doses | NR | NR | 15% | 15% | 3% | |
| Aredo | 2021 | USA | 13 | Retrospective | 5000cGy (7.7%) 6000cGy (46.2%) 6600cGy (46.2%) |
Sequential | Dura (PD-L1) |
average of 6 (range 4-14) doses | 41.7% | 0% | 23% | 15.4% | 0% | |
| Hassanzadeh | 2020 | USA | 34 | Retrospective | 6000-7000cGy/30-35f | Sequential | Dura (PD-L1) |
average of 8.5 (range 1-26) doses | NR | NR | 26.5% | 5.9% | 0% | |
| Miura | 2020 | Japan | 41 | Retrospective | 6000Gy/30f (98%) 5400Gy/25f (2%) |
Sequential | Dura (PD-L1) |
NR | 7.3% | 0% | 61.0% | 2.4% | 0% | |
| Jung | 2020 | Korea | 21 | Retrospective | 5400-6600c Gy | Sequential | Dura (PD-L1) |
NR | NR | NR | 81% | 14.3% | 0% | |
| Inoue | 2020 | Japan | 30 | Retrospective | NR | Sequential | Dura (PD-L1) |
NR | NR | NR | 73.3% | 0% | 0% | |
| Chu | 2020 | China | 29 | Retrospective | <6000cGy (63.9%) 6000-6600c Gy (25.8%) >6600cGy (9.7%) |
Sequential | Dura (PD-L1) |
2.8 (1.8–3.7) months | 13.8% | 0% | 17.2% | 6.9% | 0% | |
| Lin | 2020 | USA | 40 | Prospective | 6000-6600cGy | Sequential (25%)/Concurrent and Sequential (75%) |
Atez (PD-L1) |
12 months | 80% | 10% | 25% | 2.5% | 0% | |
| Yamaguchi | 2019 | Japan | 40 | Retrospective | 5000-6000cGy (60%) 800-3000cGy (40%) |
Sequential | Nivo (PD-1) |
NR | NR | NR | 20% | NR | NR | |
| Tamiya | 2017 | Japan | 50 | Retrospective | NR | Sequential | Nivo (PD-1) |
NR | NR | NR | 22% | NR | NR | |
| Jang | 2021 | Korea | 51 | Retrospective | 4600–7300Gy | Sequential | Dura (PD-L1) (68.6%) Pemb (PD-1) (11.8%) Nivo (PD-1) (9.8%) Atez (PD-L1) (9.8%) |
average of 9 (range 2-24) doses | NR | NR | 52.9% | 5.9% | 0% | |
| Barrón | 2020 | Colombia | 40 | Retrospective | <6000cGy (52.5%) ≥6000cGy (47.5%) |
Sequential | Pemb (PD-1) or Nivo (PD-1) |
NR | NR | NR | 40% | 10% | 0% | |
| Amino | 2020 | Japan | 20 | Retrospective | 5400-6600cGy | Sequential | Pemb (PD-1) (5%) Nivo (PD-1) (95%) |
NR | 5% | 0% | 5% | 0% | 0% | |
| Boyer | 2016 | USA | 16 | Prospective | 3600-7400cGy | Before | Ipi (CTLA4) |
2 doses | 0% | 0% | 0% | 0% | 0% | |
| Bruni | 2021 | Italy | 155 | Retrospective | <6000cGy (7.7%) 6000-6600c Gy (82.0%) >6600cGy (10.3%) |
Concurrent (58.7%) Sequential (41.3%) |
Dura (PD-L1) |
NR | NR | NR | 17.4% | 2.5% | 0% | |
| Peters | 2021 | Switzerland | 77 | Prospective | 6600Gy/33f | Concurrent and Sequential |
Nivo (PD-1) |
12 months | NR | NR | 44.2% | 11.7% | 1.3% | |
| Jabbou | 2020 | Canada | 21 | Prospective | 6000Gy/30f (95%) 4000cGy/20f (5%) |
Concurrent and Sequential |
Pemb (PD-1) |
12 months | NR | 4.8% | 33% | 10% | 4.7% | |
| SBRT | ||||||||||||||
| Bestvina | 2021 | USA | 37 | Prospective | 4500cGy/3f | Concurrent/Sequential | Pemb (PD-1) Nivo (PD-1) |
2 years | 56.8% | 8.1% | `24.3% | 24.3% | 0% | |
| Chen | 2020 | USA | 33 | Retrospective | 5000cGy/4f 6000cGy/10f |
Concurrent/Sequential | CTLA-4+PD-1/PD-1 | 4 doses/NR | NR | 0% | 12,1% | 12.1% | 0% | |
| RT & SBRT | ||||||||||||||
| Voong | 2019 | USA | 100 | Retrospective | NR | NR | PD-1 PD-L1 |
NR | NR | NR | 19% | NR | NR | |
| Welsh | 2020 | USA | 80 | Prospective | 5000cGy/4f/4500cGy/30f | Concurrent | Pemb (PD-1) |
32 doses | NR | NR | 5% | 3.75% | 0% | |
N, Number of patients; ICIs, Immune checkpoint inhibitors; Nivo, Nivolumab; Ipi, Ipilimumab; PD-1, Programmed death-1; CTLA-4, Cytotoxic T lymphocyte-associated antigen-4; USA, United States of America; Pemb, Pembrolizumab; NR, Not reported; UK, United Kingdom; Dura, Durvalumab; PD-L1, Programmed death ligand-1; Atez, Atezolizumab.