Table 1 Baseline characteristics of the eligible studies
First Author | Year | Study design | Phase | Histology | Type of ICIs | Treatment in the Treatment Group | Radiotherapy modalities | Radiotherapy dose and fraction | Sample size | Cough (grades 1–5, n) | Cough (grades 3–5, n) | Pneu-monia (grades 1–5, n) | Pneum-onia (grades 3–5, n) | Upper respiratory tract infection (grades 1–5, n) | Upper respiratory tract infection (grades 3–5, n) | Dyspnoea (grades 1–5, n) | Dyspnoea (grades 3–5, n) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Joe [9] | 2023 | Open-label, RCT | II | Early-Stage Non-Small Cell Lung Cancer | PD-1 | Nivolumab  + RT | SBRT | 50 Gy/4Fx or 70 Gy/10Fx | 66 | NA | NA | 1 | 1 | NA | NA | 1 | 1 |
Zhu [10] | 2023 | Single-arm | II | Locally Advanced Oesophageal Squamous Cell Carcinoma | PD-1 | Toripalimab  + Paclitaxel  + Cisplatin  + RT | IMRT | 50.4 Gy/28Fx | 42 | 29 | 1 | 28 | 2 | NA | NA | NA | NA |
Omuro [11] | 2023 | Open-label, RCT | III | MGMT-unmethylated Glioblastoma | PD-1 | Nivolumab  + RT | Focal RT | 60 Gy/30Fx | 278 | 2 | 0 | 2 | 1 | NA | NA | 1 | 1 |
Wise-Draper [12] | 2022 | Open-label, Nonrandomized, Double-arm | II | Resectable Local–Regionally Advanced Head and Neck Squamous Cell Carcinoma | PD-1 | Pembrolizumab  + Surgery  ± Cisplatin  + RT | IMRT | 60–66 Gy/30-33Fx | 92 | 8 | 0 | 2 | 2 | NA | NA | 2 | 1 |
Li [13] | 2022 | Open-label, Single-arm | II | Unresectable Hepatocellular Carcinoma | PD-1 | Camrelizumab  + RT | SBRT | 30–50 Gy/10Fx | 21 | NA | NA | 1 | 0 | NA | NA | NA | NA |
Kwan [14] | 2022 | Single-arm | II | Metastatic Castration-Resistant Prostate Cancer | PD-L1 | Avelumab  + RT | SBRT | 20 Gy/1Fx | 31 | 1 | 0 | 1 | 1 | NA | NA | NA | NA |
Chao [15] | 2022 | Single-arm | II | Metastatic Gastric, Gastroesophageal Junction, or Esophageal either Squamous Cell or Adenocarcinoma | PD-1 | Pembrolizumab  + RT | NA | 30 Gy/10Fx | 14 | NA | NA | 2 | 0 | NA | NA | NA | NA |
Lim [16] | 2022 | Single-blind, RCT | III | Supratentorial Glioblastoma | PD-1 | Nivolumab  + Temozolomide  + RT | NA | 60 Gy/NA | 354 | 58 | 0 | 17 | 17 | 20 | 0 | 29 | 4 |
Kim [17] | 2022 | Open-label, RCT | II | Unresectable, Recurrent, or Stage IV Merkel Cell Carcinoma | PD-1 + CTLA-4 | Nivolumab  + Ipilimumab  + RT | SBRT | 24 Gy/3Fx | 24 | 6 | 0 | 3 | 1 | 1 | 0 | 5 | 0 |
Zhou [18] | 2022 | Double-blind, RCT | III | Unresectable Stage III Non-Small Cell Lung Cancer | PD-L1 | Sugemalimab(after cCRT/sCRT)  + Platinum-based Chemotherapy  + RT | NA | 54–66 Gy/NA | 255 | NA | NA | 57 | 13 | NA | NA | NA | NA |
Tai [19] | 2021 | Open-label, Single-arm | II | Hepatocellular Carcinoma with Child-Pugh A cirrhosis | PD-1 | Nivolumab  + Y90-radioembolisation | SIRT | - | 36 | 1 | 0 | 1 | 0 | NA | NA | NA | NA |
Peters [20] | 2021 | Single-arm | II | Locally Advanced Stage IIIA-B Non-Small Cell Lung Cancer | PD-1 | Nivolumab  + Cisplatin/Carboplatin  + Vinorelbine/Etoposide/Pemetrexed  + RT | NA | 66 Gy/33Fx | 79 | 31 | 0 | 34 | 9 | 7 | 0 | 26 | 1 |
Ni [21] | 2021 | Open-label, Single-arm | II | Metastatic Non-Small Cell Lung Cancer | PD-1 | Sintilimab  + GM-CSF  + RT | SBRT | 24 Gy/3Fx | 20 | 1 | 0 | NA | NA | NA | NA | NA | NA |
Segal [22] | 2021 | Single-arm | II | Metastatic Colorectal Cancer | PD-L1 + CTLA-4 | Nivolumab  + Tremelimumab  + RT | EBRT | 20–70 Gy/3-30Fx | 24 | 1 | 0 | NA | NA | NA | NA | 1 | 0 |
Mayadev [23] | 2020 | Double-blind, RCT | III | Locally Advanced Cervical Cancer | PD-L1 | Durvalumab  + Cisplatin/Carboplatin  + RT | EBRT + BCRT | 45 Gy/25Fx +  27.5–30 Gy or 35–40 Gy/NA | 385 | NA | NA | 2 | 2 | 24 | 0 | 1 | 1 |
Jabbour [24] | 2020 | Nonrandomized Controlled Trial | I | Unresectable Stage IIIA or IIIB Non-Small Cell Lung Cancer | PD-1 | Pembrolizumab(before, after and whole CRT)  + Carboplatin  + Paclitaxel  + RT | IMRT/VMAT/Proton | 60 Gy/30Fx | 21 | 16 | 0 | 7 | 2 | NA | NA | 16 | 2 |
Elbers [25] | 2020 | Single-arm, Feasibility Trial | I | Advanced-Stage Head and Neck Squamous Cell Carcinoma of the Oral Cavity, Oropharynx, Hypopharynx or Larynx | PD-L1 | Aavelumab  + Cetuximab  + RT | VMAT | Elective irradiation 46 Gy/23Fx then sequential boost 24 Gy/12Fx to primary tumor or 54.25 Gy/35Fx with SIB 70 Gy to primary tumor | 10 | NA | NA | 3 | 2 | NA | NA | NA | NA |
Barroso-Sousa [26] | 2020 | Single-arm | II | Hormone Receptor-Positive Metastatic Breast Cancer | PD-1 | Pembrolizumab  + RT | NA | 20 Gy/5Fx | 8 | 1 | 0 | NA | NA | 1 | 0 | 2 | 0 |
Xie [27] | 2020 | Open-label, Nonrandomized, Two-cohort, Four-arm | I | Metastatic Pancreatic Ductal Adenocarcinoma | Cohort A: PD-L1 Cohort B: PD-L1 + CTLA-4 | Cohort A: Durvalumab + RT Cohort B: Durvalumab + Tremelimumab + RT | SBRT | Cohort A1: 8 Gy/1Fx, Cohort A2: 5 Gy/5Fx, Cohort B1: 8 Gy/1Fx, Cohort B2: 5 Gy/5Fx | 14, 11, 19, 21 | 1, 1, 3, 3 | 0, 0, 0, 0 | 0, 1, 2, 0 | 0, 1, 0, 0 | 1, 0, 0, 1 | 0, 0, 0, 0 | 4.2.6.7 | 1.0.1.1 |
Yu [28] | 2019 | Double-blind, RCT | III | Locoregionally Advanced Head and Neck Squamous Cell Carcinoma | PD-L1 | Avelumab  + Cisplatin  + RT | IMRT | 70 Gy/35Fx | 345 | 74 | 0 | 61 | 25 | NA | NA | 40 | 7 |
Gerber [29] | 2017 | Double-blind, RCT | III | Locally Advanced Non-Small Cell Lung Cancer | PD-1 | Nivolumab  + Cisplatin  + Etoposide  + Thoracic RT | 3DCRT/IMRT | 60 Gy/30Fx | 3 | 3 | 0 | 2 | 1 | NA | NA | 1 | 0 |
NCT(03102242) [30] | NA | Single-arm | II | Unresectable Stage III Non-Small Cell Lung Cancer | PD-L1 | Atezolizumab  + Carboplatin  + Paclitaxel  + RT | NA | 60 Gy/NA | 64 | 29 | 0 | 15 | 5 | 11 | 1 | 34 | 1 |
NCT(04081688) [31] | NA | Single-arm | I | Metastatic Non-Small Cell Lung Cancer | PD-L1 + CD27 | Atezolizumab  + Varlilumab  + RT | SBRT | NA/NA | 15 | 2 | 0 | 3 | 3 | NA | NA | 6 | 4 |
NCT(03421652) [32] | NA | Single-arm | II | Urothelial Bladder Cancer | PD-1 | Nivolumab  + RT | NA | 64 Gy/32-35fX | 20 | 3 | 0 | NA | NA | NA | NA | 3 | NA |
NCT(03040999) [33] | NA | Double-blind, RCT | III | Locally Advanced Head and Neck Squamous Cell Carcinoma | PD-1 | Pembrolizumab  + Cisplatin  + RT | AFX/SFX | 70 Gy/35Fx | 398 | 65 | 0 | 66 | 43 | NA | NA | 22 | 2 |
NCT(02659540) [34] | NA | Open-label, Double-arm | I | Unresectable Stage IV Melanoma | PD-1 + CTLA-4 | Divolumab  + Ipilimumab  + RT | Arm1: Conventional, Arm2: Hypofractionated | 30 Gy/10Fx, 27 Gy/3Fx | 10, 10 | 2, 4 | 0, 1 | 1, 2 | 0, 0 | 2, NA | 1, NA | 4.3 | 2.2 |