1. Selected studies combining RT with ICI in BM.
| Authors | Tumor type | N | Study design | ICI target | Type of RT | Arms | Median survival (months) | Intracranial control |
| RT, radiotherapy; ICI, immune checkpoint inhibitor; BM, brain metastases; NSCLC, non-small cell lung cancer; RCC, renal cell carcinoma; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; PD-1, programmed cell death protein 1; SRS, stereotactic radiosurgery; WBRT, whole brain radiation therapy; irRC, immune-related response criteria. ICI→RT indicates ICI was administered prior to RT; RT=ICI indicates that ICI was administered concurrently with RT; RT→ICI indicates that ICI was administered after RT; RT≠ICI indicates that RT was not administered concurrently with SRS; RT+ICI indicates ICI was administered with RT but the relative timing of each treatment was not provided. NR indicates that the results were not reported. | ||||||||
| Williams
et al. (35) |
Melanoma | 16 | Prospective | CTLA-4 | SRS/WBRT | RT (WBRT)
+ ICI |
10.6 | 40% at
6 months |
| RT (SRS) + ICI | 18% at 6 months | |||||||
| Skrepnik
et al. (36) |
Melanoma | 25 | Retrospective | CTLA-4 | SRS | RT→ICI | 35.8 | 94.8% |
| RT=ICI | ||||||||
| ICI→RT | ||||||||
| Murphy
et al. (79) |
Melanoma | 26 | Retrospective | CTLA-4/PD-1 | SRS | RT=ICI
(±30 days) |
26.1 | NR |
| RT≠ICI | ||||||||
| Acharya
et al. (80) |
Melanoma | 56 | Retrospective | CTLA-4 and/or PD-1 | SRS | RT + ICI | 58% OS at
1 year |
85% at
1 year |
| RT | 31% OS at
1 year |
66% at
1 year |
||||||
| Mathew
et al. (81) |
Melanoma | 58 | Retrospective | CTLA-4 | SRS | RT + ICI | 56% OS at
6 months |
63% at
6 months |
| RT | 45% OS at 6 months | 65% at 6 months | ||||||
| Anderson
et al. (82) |
Melanoma | 21 | Retrospective | PD-1 | SRS/WBRT | NR | NR | SRS=ICI 32% |
| SRS≠ICI 22% | ||||||||
| An
et al. (83) |
Melanoma | 99 | Retrospective | CTLA-4 | SRS | ICI→RT
(early SRS) |
13.4 | 51% at
1 year |
| ICI→RT
(late SRS) |
11.5 | 25% at
1 year |
||||||
| Qian
et al. (84) |
Melanoma | 75 | Retrospective | CTLA-4/PD-1 | SRS | RT=ICI
(±4 weeks) |
19.1 | NR |
| RT≠ICI | 9.0 | |||||||
| Liniker
et al. (85) |
Melanoma | 53 | Retrospective | PD-1 | Extracranial RT and / or SRS, WBRT | NR | NR | NR |
| Ahmed
et al. (86) |
Melanoma | 55 | Retrospective | CTLA-4/PD-1 | SRS | RT+ICI
(anti-PD-1) |
48% OS at
12 months |
NR |
| RT+ICI
(anti-CTLA-4) |
41% OS at
12 months |
|||||||
| Gerber
et al. (87) |
Melanoma | 13 | Retrospective | CTLA-4 | WBRT | RT=ICI
(±30 days) |
4 | 56% by irRC criteria |
| Silk
et al. (88) |
Melanoma | 70 | Retrospective | CTLA-4 | SRS /WBRT | RT + ICI | 18.3 | NR |
| RT | 5.3 | |||||||
| Chen
et al. (89) |
NSCLC, Melanoma, RCC | 260 | Retrospective | CTLA-4/PD-1 | SRS | RT | 12.9 | NR |
| RT≠ICI | 14.5 | NR | ||||||
| RT=ICI
(±2 weeks) |
24.7 | 88.0% at 1 year | ||||||
| Yusuf
et al. (90) |
Melanoma | 51 | Retrospective | CTLA-4/PD-1 | SRS | RT | 7.1 | NR |
| RT=ICI
(±4 weeks) |
7.4 | |||||||
| RT≠ICI | ||||||||
| Kiess
et al. (91) |
Melanoma | 46 | Retrospective | CTLA-4 | SRS | RT=ICI | 56% OS at
1 year |
100% at
1 year |
| RT→ICI | 65% OS at
1 year |
87% at
1 year |
||||||
| ICI→RT | 50% OS at
1 year |
89% at
1 year |
||||||
| Choong
et al. (92) |
Melanoma | 39 | Retrospective | CTLA-4 /PD-1 | SRS | NR | 54.9% OS at
1 year |
NR |
| Cohen-Inbar
et al. (93) |
Melanoma | 46 | Retrospective | CTLA-4 | SRS | RT→ICI,
RT=ICI |
59% OS at
1 year |
54.4% at
1 year |
| ICI→RT | 33% OS at
1 year |
16.5% at
1 year |
||||||
| Amaral
et al. (94) |
Melanoma | 290 | Retrospective | CTLA-4 and PD-1 | SRS/WBRT | NR | 24.0 | NR |
| Patel
et al. (95) |
Melanoma | 54 | Retrospective | CTLA-4 | SRS | RT | 38.5% OS at
1 year |
71.4% at
1year |
| RT + ICI
(±4 months) |
37.1% OS at
1 year |
92.3% at
1 year |
||||||
| Rahman
et al. (96) |
Melanoma | 74 | Retrospective | CTLA-4/PD-1 | SRS | RT=ICI
(±30 days) |
13.9 | 23.1% at
1 year |
| RT≠ICI | 18.8% at
1 year |
|||||||
| Schmidberger
et al. (97) |
Melanoma | 41 | Retrospective | CTLA-4 | SRS/WBRT | RT→ICI | 11.0 | NR |
| ICI→RT | 3.0 | |||||||
| Diao
et al. (98) |
Melanoma | 72 | Retrospective | CTLA-4 | SRS | RT | NR | NR |
| RT=ICI | ||||||||
| RT≠ICI | ||||||||
| Fang
et al. (99) |
Melanoma | 137 | Retrospective | CTLA-4/PD-1 | SRS | NR | 16.9 | NR |
| Kaidar-Person
et al. (100) |
Melanoma | 58 | Retrospective | CTLA-4/PD-1 | SRS | RT+ICI | 15.0 | NR |
| RT | 5.5 | |||||||
| Martins
et al. (101) |
Melanoma | 84 | Retrospective | CTLA-4/PD-1 | SRS | NR | 12.0 | NR |
| Singh
et al. (102) |
NSCLC | 39 | Retrospective | PD-1 | SRS | RT + ICI | 10.0 | NR |
| Hubbeling
et al. (103) |
NSCLC | 50 | Retrospective | PD-1 | WBRT/SR/partial brain irradiation | RT→ICI
(>4 Weeks) |
NR | NR |
| RT=ICI
(±4 weeks) | ||||||||
| ICI→RT
(>4 weeks) | ||||||||
| Lanier
et al. (104) |
NSCLC, Melanoma | 271 | Retrospective | CTLA-4 and/or PD-1 | SRS | RT + ICI | 15.9 | NR |
| RT | 6.1 | |||||||