Oncologic Outcome and Immune Responses of Radiotherapy with Anti-PD-1 Treatment for Brain Metastases Regarding Timing and Benefiting Subgroups
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients and Treatment
2.2. Outcome Evaluation
2.3. Toxicity Evaluation
2.4. Statistical Analysis
3. Results
3.1. Patient, Lesion, and Treatment Characteristics
3.2. Outcome Evaluation and Treatment Response
3.2.1. Impact on Survival of the Entire RT-ICI Cohort
3.2.2. Timing of RT-ICI Application with Regard to Different Subgroups
3.3. Toxicity Evaluation
4. Discussion
4.1. Impact on Survival, Response Rate, and Oncologic Outcome
4.2. Combination of RT-ICI and Timing
4.3. Subgroup Analyses Regarding Concurrent Application of RT-ICI
4.4. Distinctive Reactions of the Immune System to Concurrent RT-ICI
4.5. Toxicity Analysis
4.6. Limitations
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Appendix A
Patient and Lesion Characteristics | All Patients (n = 93) | Non-Concurrent RT-ICI (n = 30) | Concurrent RT-ICI (n = 63) | p-Value |
---|---|---|---|---|
BMI (kg/m2) | 0.469 | |||
UW (<18.5) | 4 (4.8%) | 0 (0%) | 4 (7.3%) | |
NW (18.5–24.9) | 27 (32.1%) | 10 (34.5%) | 17 (30.9%) | |
OW (25.0–29.9) | 28 (33.3%) | 11 (37.9%) | 17 (30.9%) | |
OB (≥30) | 25 (29.8%) | 8 (27.6%) | 17 (30.9%) | |
PD-L1 status | 0.640 | |||
≥1% (positive) | 20 (51.3%) | 4 (44.4%) | 16 (53.3%) | |
<1% (negative) | 19 (48.7%) | 5 (55.6%) | 14 (46.7%) | |
High tumor burden | 55 (62.5%) | 15 (51.7%) | 40 (67.8%) | 0.143 |
Treatment characteristics | ||||
Prior RT | 41 (45.6%) | 13 (43.3%) | 28 (46.7%) | 0.765 |
ICI type | 0.426 | |||
pembrolizumab | 63 (67.7%) | 22 (73.3%) | 41 (65.1%) | |
nivolumab | 30 (32.3%) | 8 (26.7%) | 22 (34.9%) | |
ICI duration (weeks), mean ± STD | 22.2 ± 22.8 | 15.9 ± 19.2 | 27.0 ± 24.3 | 0.067 |
Prior systemic treatment | 61 (68.5%) | 23 (79.3%) | 38 (63.3%) | 0.128 |
Characteristics for Univariate Cox Regression Analysis | OS HR (95% CI) | p-Value | PFS HR (95% CI) | p-Value |
---|---|---|---|---|
BMI (kg/m2) (reference: OW); overall log rank | 0.127 | <0.001 | ||
UW vs. OW | 3.354 (0.982–11.460) | 0.054 | 12.471 (3.415–45.542) | <0.001 |
NW vs. OW | 1.072 (0.561–2.046) | 0.834 | 1.358 (0.753–2.446) | 0.309 |
OB vs. OW | 1.590 (0.854–2.961) | 0.144 | 1.590 (0.877–2.885) | 0.127 |
PD-L1 status (reference: positive) | ||||
negative vs. positive | 0.678 (0.293–1.57) | 0.364 | 1.421 (0.683–2.958) | 0.348 |
High tumor burden (reference: no) | ||||
yes vs. no | 1.223 (0.733–2.042) | 0.440 | 0.957 (0.6–1.527) | 0.854 |
ICI type (reference: pembrolizumab) | ||||
nivolumab vs. pembrolizumab | 0.994 (0.575–1.719) | 0.982 | 1.282 (0.782–2.1) | 0.325 |
Prior systemic treatment (reference: no) | ||||
yes vs. no | 0.983 (0.581–1.663) | 0.950 | 1.194 (0.724–1.968) | 0.488 |
Patient and Lesion Characteristics | All Patients (n = 92) | Other Cancer Types (n = 27) | Malignant Melanoma (n = 65) | p-Value |
---|---|---|---|---|
Gender (female) | 38 (41.3%) | 7 (25.9%) | 31 (47.7%) | 0.054 |
Age (years), mean ± STD | 62.1 ± 13.2 | 58.5 ± 9.1 | 63.6 ± 14.4 | 0.049 |
ECOG-PS | 0.049 | |||
0 | 28 (31.5%) | 8 (30.8%) | 20 (31.7%) | |
1 | 41 (46.1%) | 8 (30.8%) | 33 (52.4%) | |
>1 | 20 (22.5%) | 10 (38.5%) | 10 (15.9%) | |
NLR | 0.180 | |||
<3 (low) | 35 (44.9%) | 6 (31.6%) | 29 (49.2%) | |
≥3 (high) | 43 (55.1%) | 13 (68.4%) | 30 (50.8%) | |
LDH | 0.651 | |||
≤ULN (245 U/L) | 38 (55.9%) | 6 (50.0%) | 32 (57.1%) | |
>ULN (245 U/L) | 30 (44.1%) | 6 (50.0%) | 24 (42.9%) | |
Extracranial disease | 41 (47.1%) | 14 (53.8%) | 27 (44.3%) | 0.412 |
Number of BMs | 0.272 | |||
≤2 | 55 (61.1%) | 13 (52%) | 42 (64.6%) | |
>2 | 35 (38.9%) | 12 (48%) | 23 (35.4%) | |
Total PTV (cm3) | 0.036 | |||
≤3 | 37 (43.0%) | 6 (25%) | 31 (50%) | |
>3 | 49 (57.0%) | 18 (75%) | 31 (50%) | |
Neurological symptoms | 38 (43.2%) | 14 (56.0%) | 24 (38.1%) | 0.126 |
Treatment characteristics | ||||
RT concept | 0.057 | |||
SRS | 64 (69.6%) | 14 (51.9%) | 50 (76.9%) | |
WBRT | 21 (22.8%) | 10 (37.0%) | 11 (16.9%) | |
other | 7 (7.6%) | 3 (11.1%) | 4 (6.2%) | |
BED (Gy) | 0.004 | |||
<60 | 31 (34.8%) | 15 (57.7%) | 16 (25.4%) | |
≥60 | 58 (65.2%) | 11 (42.3%) | 47 (74.6%) | |
RT courses | 0.808 | |||
1 | 32 (35.2%) | 10 (37.0%) | 22 (34.4%) | |
>1 | 59 (64.8%) | 17 (63.0%) | 42 (65.6%) | |
RT timing | 0.811 | |||
concurrently | 62 (67.4%) | 17 (63.0%) | 45 (69.2%) | |
before ICI | 19 (20.7%) | 6 (22.2%) | 13 (20.0%) | |
after ICI | 11 (12.0%) | 4 (14.8%) | 7 (10.8%) | |
Dexamethasone | 0.097 | |||
no | 10 (11.6%) | 4 (16.0%) | 6 (9.8%) | |
prophylactical ≤4 mg | 59 (68.6%) | 13 (52.0%) | 46 (75.4%) | |
therapeutical >4 mg | 17 (19.8%) | 8 (32.0%) | 9 (14.8%) | |
ICI duration (weeks), mean ± STD | 22.2 ± 22.8 | 19.7 ± 23.3 | 22.9 ± 22.8 | 0.352 |
Prior systemic treatment | 61 (68.5%) | 25 (96.2%) | 36 (57.1%) | <0.001 |
Prior anti-CTLA4 | 22 (24.4%) | 0 (0%) | 22 (34.9%) | <0.001 |
Characteristics for Selected OS Rates | 6-Month OS Rate | 12-Month OS Rate | 24-Month OS Rate | 36-Month OS Rate | p-Value (Log Rank) |
---|---|---|---|---|---|
All patients (n = 93) | 70.8% | 50.7% | 40.0% | 32.1% | |
ECOG-PS | 0.031 | ||||
0 | 88.7% | 69.4% | 61.3% | 52.4% | |
1 | 68.3% | 48.8% | 36.6% | 26.6% | |
>1 | 50.0% | 27.8% | 16.7% | 0% | |
Cancer type | 0.003 | ||||
MM | 77.8% | 57.1% | 44.3% | 37.6% | |
other | 51.8% | 33.0% | 28.3% | 17.7% | |
NLR | 0.009 | ||||
<3 (low) | 85.3% | 61.8% | 55.9% | 46.6% | |
≥3 (high) | 58.5% | 39.0% | 26.8% | 20.1% | |
LDH | 0.028 | ||||
≤ULN (245 U/L) | 89.5% | 68.4% | 47.4% | 39.5% | |
>ULN (245 U/L) | 50.0% | 30.0% | 30.0% | 26.3% | |
PTV | 0.002 | ||||
≤3 cm3 | 89.2% | 62.2% | 53.8% | 44.8% | |
>3 cm3 | 53.9% | 38.1% | 26.9% | 22.4% | |
Neurological symptoms | 0.003 | ||||
yes | 50.0% | 34.2% | 26.3% | 21.1% | |
no | 87.0% | 65.3% | 52.1% | 42.5% | |
RT concept | 0.016 | ||||
SRS | 80.2% | 55.1% | 43.3% | 34.2% | |
WBRT | 36.8% | 26.3% | 21.1% | 21.1% | |
BED | 0.011 | ||||
<60 | 41.4% | 31.0% | 24.1% | 24.1% | |
≥60 | 85.8% | 60.8% | 48.2% | 35.7% | |
RT-ICI application | 0.173 | ||||
concurrently | 77.4% | 58.1% | 44.0% | 34.2% | |
non-concurrently | 57.1% | 35.7% | 32.1% | 28.1% | |
RT timing | <0.001 | ||||
concurrently | 77.4% | 58.1% | 44.0% | 34.2% | |
before ICI | 76.5% | 47.1% | 47.1% | 41.2% | |
after ICI | 27.3% | 18.2% | 9.1% | 9.1% | |
Dexamethasone application | 0.075 | ||||
>4 mg | 41.2% | 29.4% | 29.4% | 23.5% | |
≤4 mg | 77.1% | 55.5% | 43.1% | 34.8% | |
Prior anti-CTLA4 treatment | 0.022 | ||||
yes | 90.9% | 68.2% | 50.0% | 50.0% | |
no | 63.8% | 44.7% | 36.6% | 25.3% | |
Abscopal effects | 0.752 | ||||
yes | 100% | 80.0% | 40.0% | 40.0% | |
no | 64.0% | 46.0% | 34.0% | 26.0% | |
Pseudoprogression | 0.332 | ||||
yes | 100% | 76.9% | 53.8% | 46.2% | |
no | 78.0% | 53.8% | 42.6% | 32.0% | |
Immune-related adverse events | 0.147 | ||||
yes | 79.1% | 62.8% | 46.2% | 35.6% | |
no | 62.5% | 37.5% | 31.3% | 28.1% |
Adverse Events (AEs) | All Patients (n = 93) | Non-Concurrent RT-ICI (n = 30) | Concurrent RT-ICI (n = 63) | p-Value |
---|---|---|---|---|
All AEs | 60 (74.1%) | 19 (70.4%) | 41 (75.9%) | 0.591 |
CTCAE Grade 1 | 10 (16.7%) | 3 (15.8%) | 7 (17.1%) | 0.746 |
CTCAE Grade 2 | 33 (55%) | 9 (47.4%) | 24 (58.5%) | |
CTCAE Grade 3 | 12 (20%) | 5 (26.3%) | 7 (17.1%) | |
CTCAE Grade 4 | 1 (1.7%) | 0 (0%) | 1 (2.4%) | |
Immune-related AEs | 44 (56.4%) | 12 (46.2%) | 32 (61.5%) | 0.196 |
CTCAE Grade 1 | 11 (25%) | 3 (25%) | 8 (25%) | 0.071 |
CTCAE Grade 2 | 24 (54.5%) | 4 (33.3%) | 20 (62.5%) | |
CTCAE Grade 3 | 6 (13.6) | 3 (25%) | 3 (9.4%) | |
CTCAE Grade 4 | 1 (2.3%) | 0 (0%) | 1 (3.1%) | |
Acute CNS toxicity | 27 (35.1%) | 6 (22.2%) | 21 (42%) | 0.083 |
CTCAE Grade 1 | 4 (14.8%) | 1 (16.7%) | 3 (14.3%) | 0.884 |
CTCAE Grade 2 | 17 (63%) | 3 (50%) | 14 (66.7%) | |
CTCAE Grade 3 | 3 (11.1%) | 1 (16.7%) | 2 (9.5%) | |
Fatigue | 25 (32.1%) | 8 (29.6%) | 17 (33.3%) | 0.739 |
CTCAE Grade 1 | 10 (40%) | 1 (12.5%) | 9 (52.9%) | 0.104 |
CTCAE Grade 2 | 9 (36%) | 3 (37.5%) | 6 (3.3%) | |
CTCAE Grade 3 | 5 (20%) | 3 (37.5%) | 2 (11.8%) | |
Other AEs | 10 (13%) | 4 (14.8%) | 6 (12%) | 0.726 |
CTCAE Grade 1 | 4 (40%) | 1 (25%) | 3 (50%) | 0.251 |
CTCAE Grade 2 | 2 (20%) | 0 (0%) | 2 (33.3%) | |
CTCAE Grade 3 | 3 (30%) | 2 (50%) | 1 (16.7%) | |
Radionecrosis | 8 (9%) | 1 (3.4%) | 7 (11.7%) | 0.204 |
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Patient and Lesion Characteristics | All Patients (n = 93) |
---|---|
Gender (female) | |
female | 38 (40.9%) |
male | 55 (59.1%) |
Age (years), mean ± STD | 62.1 ± 13.2 |
ECOG-PS | |
0 | 28 (31.5%) |
1 | 41 (46.1%) |
>1 | 20 (22.5%) |
Cancer type | |
MM | 65 (70.7%) |
NSCLC | 21 (22.8%) |
other | 6 (6.5%) |
NLR | |
<3 (low) | 35 (44.9%) |
≥3 (high) | 43 (55.1%) |
LDH | |
≤ULN (245 U/L) | 38 (55.9%) |
>ULN (245 U/L) | 30 (44.1%) |
Extracranial disease | 41 (47.1%) |
Number of BMs, mean ± STD | 3.4 ± 3.4 |
Total PTV (cm3), mean ± STD | 277.5 ± 452.9 |
Neurological symptoms | 38 (43.2%) |
Treatment characteristics | |
RT concept | |
SRS | 65 (69.9%) |
WBRT | 21 (22.6%) |
other | 7 (7.5%) |
BED (Gy), mean ± STD | 55.7 ± 10.1 |
RT courses | |
1 | 32 (35.2%) |
>1 | 59 (64.8%) |
RT timing | |
concurrently | 63 (67.7%) |
before ICI | 19 (20.4%) |
after ICI | 11 (11.8%) |
Dexamethasone | |
no | 10 (11.6%) |
prophylactic dose ≤4 mg | 59 (68.6%) |
therapeutic dose >4 mg | 17 (19.8%) |
ICI duration (weeks), mean ± STD | 22.2 ± 22.8 |
Prior systemic treatment | 61 (68.5%) |
Prior anti-CTLA4 treatment | 22 (24.2%) |
Patient and Lesion Characteristics | Non-Concurrent RT-ICI (n = 30) | Concurrent RT-ICI (n = 63) | p-Value |
---|---|---|---|
Gender (female) | 12 (40%) | 26 (41.3%) | 0.907 |
Age (years), mean ± STD | 61 ± 12.7 | 62,7 ± 13.5 | 0.495 |
ECOG-PS | 0.457 | ||
0 | 7 (24.1%) | 21 (35%) | |
1 | 16 (55.2%) | 25 (41.7%) | |
>1 | 6 (20.7%) | 14 (23.3%) | |
Cancer type | 0.823 | ||
MM | 20 (66.7%) | 45 (72.6%) | |
NSCLC | 8 (26.7%) | 13 (21%) | |
other | 2 (6.7%) | 4 (6.5%) | |
NLR | 0.421 | ||
<3 (low) | 10 (38.5%) | 25 (48.1%) | |
≥3 (high) | 16 (61.5%) | 27 (51.9%) | |
LDH | 0.006 | ||
≤ULN (245 U/L) | 8 (33.3%) | 30 (68.2%) | |
>ULN (245 U/L) | 16 (66.7%) | 14 (31.8%) | |
Extracranial disease | 11 (37.9%) | 30 (51.7%) | 0.224 |
Number of BMs | 0.145 | ||
≤2 | 21 (72.4%) | 35 (56.5%) | |
>2 | 8 (27.6%) | 27 (43.5%) | |
Total PTV (cm3), mean ± STD | 192.1 ± 388.5 | 318.7 ± 478.6 | 0.046 |
Total PTV (cm3) | 0.170 | ||
≤3 | 15 (53.6%) | 22 (37.9%) | |
>3 | 13 (46.4%) | 36 (62.1%) | |
Neurological symptoms | 10 (35.7%) | 28 (46.7%) | 0.334 |
Treatment characteristics | |||
RT concept | 0.306 | ||
SRS | 24 (80%) | 41 (65.1%) | |
WBRT | 5 (16.7%) | 16 (25.4%) | |
other | 1 (3.3%) | 6 (9.5%) | |
BED (Gy), mean ± STD | 58 ± 11.1 | 54.6 ± 9.5 | 0.143 |
BED (Gy) | 0.319 | ||
<60 | 8 (27.6%) | 23 (38.3%) | |
≥60 | 21 (72.4%) | 37 (61.7%) | |
RT courses | 0.107 | ||
1 | 14 (46.7%) | 18 (29.5%) | |
>1 | 16 (53.3%) | 43 (70.5%) | |
RT timing | <0.001 | ||
concurrently | 0 (0%) | 63 (100%) | |
before ICI | 19 (63.3%) | 0 (0%) | |
after ICI | 11 (36.7%) | 0 (0%) | |
Dexamethasone | 0.055 | ||
no | 1 (3.6%) | 9 (15.5%) | |
prophylactic dose ≤4 mg | 24 (85.7%) | 35 (60.3%) | |
therapeutic dose >4 mg | 3 (10.7%) | 14 (24.1%) | |
ICI duration (weeks), mean ± STD | 15.9 ± 19.2 | 27.0 ± 24.3 | 0.067 |
Prior systemic treatment | 23 (79.3%) | 38 (63.3%) | 0.128 |
Prior anti-CTLA4 treatment | 11 (36.7%) | 11 (18%) | 0.051 |
Follow-Up/Outcome | All Patients (n = 93) |
---|---|
Follow-up (months), mean ± STD | 23.8 ± 24.3 |
OS (months), median (95% CI) | 12.19 (4.36–20.02) |
OS status | |
alive | 23 (25.8%) |
dead | 66 (74.2%) |
PFS (months), median (95% CI) | 4.70 (2.53–6.86) |
LC | |
3 months | 52 (69.3%) |
6 months | 50 (89.3%) |
Overall response rate | |
CR | 7 (7.6%) |
PR | 15 (16.3%) |
SD | 15 (16.3%) |
PD | 55 (59.8%) |
Clinical benefit (CR + PR + SD) | 37 (40.2%) |
Progression rate | |
cerebral progression | 13 (14.3%) |
systemic progression | 13 (14.3%) |
overall progression | 39 (42.9%) |
no progression | 26 (28.6%) |
cerebral response rate | 39 (42.9%) |
abscopal effects | 5 (9.1%) |
pseudoprogression | 13 (17.8%) |
Characteristics for Univariate Cox Regression Analysis | OS HR (95% CI) | p-Value | PFS HR (95% CI) | p-Value |
---|---|---|---|---|
Gender (reference: male) | ||||
female vs. male | 1.256 (0.765–2.062) | 0.368 | 1.267 (0.798–2.011) | 0.316 |
Age (years) (reference: ≤65) | ||||
>65 vs. ≤65 years | 1.149 (0.701–1.883) | 0.581 | 0.83 (0.523–1.317) | 0.429 |
ECOG-PS (reference: ECOG 0); overall log rank | 0.031 | 0.255 | ||
1 vs. 0 | 1.823 (0.991–3.354) | 0.053 | 1.523 (0.896–2.590) | 0.120 |
≥2 vs. 0 | 2.532 (1.228–5.222) | 0.012 | 1.515 (0.784–2.929) | 0.217 |
Cancer type (reference: other) | ||||
MM vs. other | 0.457 (0.267–0.782) | 0.004 | 0.628 (0.382–1.033) | 0.067 |
NLR (reference: low (<3)) | ||||
≥3 (high) vs. <3 (low) | 2.037 (1.184–3.506) | 0.010 | 1.318 (0.81–2.143) | 0.266 |
LDH (reference: normal, ≤ULN) | ||||
>ULN (245 U/L) vs. ≤ULN (245 U/L) | 1.853 (1.059–3.241) | 0.031 | 1.066 (0.630–1.803) | 0.812 |
Extracranial disease (reference: no) | ||||
yes vs. no | 1.132 (0.684–1.875) | 0.629 | 0.767 (0.484–1.214) | 0.257 |
Number of BM (reference: ≤2 BM) | ||||
>2 vs. ≤2 | 1.154 (0.691–1.926) | 0.585 | 1.616 (1.004–2.599) | 0.048 |
PTV (cm3) (reference: ≤3) | ||||
>3 vs. ≤3 | 2.213 (1.305–3.754) | 0.003 | 1.819 (1.124–2.943) | 0.015 |
Neurological symptoms (reference: no) | ||||
yes vs. no | 2.114 (1.285–3.478) | 0.003 | 1.424 (0.897–2.262) | 0.134 |
RT concept (reference: SRS) | ||||
WBRT vs. SRS | 1.985 (1.112–3.543) | 0.019 | 1.828 (1.053–3.174) | 0.032 |
BED (Gy) (reference: <60) | ||||
≥60 vs. <60 | 0.519 (0.309–0.871) | 0.013 | 0.599 (0.370–0.969) | 0.037 |
RT courses (reference: 1) | ||||
>1 vs. 1 | 0.725 (0.433–1.213) | 0.221 | 0.620 (0.386–0.995) | 0.048 |
RT timing, 12 months (reference: non-concurrent) | ||||
concurrent vs. non-concurrent | 0.527 (2.86–0.973) | 0.041 | 0.883 (0.526–1.485) | 0.640 |
RT timing (reference: concurrent); overall log rank | <0.001 | 0.067 | ||
RT after ICI vs. concurrent | 3.971 (1.839–7.814) | <0.001 | 2.104 (1.079–4.099) | 0.029 |
RT before ICI vs. concurrent | 0.955 (0.504–1.809) | 0.887 | 0.964 (0.546–1.703) | 0.900 |
Dexamethasone application >4 mg (reference: no) | ||||
yes vs. no | 1.698 (0.941–3.063) | 0.079 | 1.477 (0.833–2.617) | 0.182 |
Prior systemic treatment (reference: no) | ||||
yes vs. no | 0.983 (0.581–1.663) | 0.950 | 1.194 (0.724–1.968) | 0.488 |
Prior anti-CTLA4 treatment (reference: no) | ||||
yes vs. no | 0.498 (0.271–0.914) | 0.024 | 0.586 (0.338–1.014) | 0.056 |
Abscopal effects (reference: no) | ||||
yes vs. no | 0.847 (0.301–2.379) | 0.752 | 2.036 (0.786–5.271) | 0.143 |
Pseudoprogression (reference: no) | ||||
yes vs. no | 0.687 (0.32–1.474) | 0.335 | 0.646 (0.316–1.319) | 0.230 |
Immune-related adverse events (reference: no) | ||||
yes vs. no | 0.677 (0.399–1.15) | 0.149 | 0.637 (0.388–1.046) | 0.075 |
Radionecrosis (reference: no) | ||||
yes vs. no | 1.152 (0.523–2.54) | 0.725 | 0.795 (0.364–1.734) | 0.564 |
Characteristics for Multivariate Cox Regression Analysis | OS HR (95% CI) | p-Value |
---|---|---|
ECOG-PS (reference: ECOG 0) | ||
1 vs. 0 | 1.694 (0.873–3.289) | 0.119 |
≥2 vs. 0 | 2.756 (1.253–6.061) | 0.012 |
Cancer type (reference: other) | ||
MM vs. other | 0.516 (0.288–0.926) | 0.026 |
RT timing (reference: non-concurrent) | ||
concurrent vs. non-concurrent | 0.539 (0.299–0.971) | 0.040 |
RT concept (reference: SRS) | ||
WBRT vs. SRS | 0.763 (0.280–2.077) | 0.596 |
other vs. SRS | 0.117 (0.014–1.006) | 0.051 |
BED (Gy) (reference: <60) | ||
≥60 vs. <60 | 0.494 (0.195–1.252) | 0.137 |
PTV (cm3) (reference: ≤3) | ||
>3 vs. ≤3 | 1.947 (1.007–3.763) | 0.048 |
Follow-Up/Outcome | Non-Concurrent RT-ICI (n = 30) | Concurrent RT-ICI (n = 63) | p-Value |
---|---|---|---|
Follow-up (months), mean ± STD | 25.7 ± 34.5 | 22.9 ± 17.6 | 0.591 |
OS (months), median (95% CI) | 6.83 (2.15–11.52) | 17.61 (6.02–29.20) | 0.173 |
RT before ICI | 10.15 (0.00–33.48) | - | |
RT after ICI | 2.20 (0.00–5.25) | - | |
OS status | 0.071 | ||
alive | 4 (13.8%) | 19 (31.7%) | |
dead | 25 (86.2%) | 41 (68.3%) | |
PFS (months), median (95% CI) | 4.70 (1.18–7.01) | 5.49 (1.80–9.18) | 0.383 |
RT before ICI | 5.29 (3.79–6.79) | - | |
RT after ICI | 2.14 (1.43–2.84) | - | |
LC | |||
3 months | 18 (81.8%) | 34 (64.2%) | 0.131 |
6 months | 9 (69.2%) | 41 (95.3%) | 0.008 |
Lesion response at 3 months | 0.552 | ||
smaller/stable | 17 (65.4%) | 30 (51.7%) | |
larger/new bm | 3 (11.5%) | 11 (19%) | |
mixed response | 1 (3.8%) | 8 (13.8%) | |
Lesion response at 6 months | 0.107 | ||
smaller/stable | 8 (61.5%) | 37 (75.5%) | |
larger/new bm | 2 (15.4%) | 0 (0%) | |
mixed response | 1 (7.7%) | 2 (4.1%) | |
Overall response rate | 0.151 | ||
CR | 1 (3.3%) | 6 (9.7%) | |
PR | 7 (23.3%) | 8 (12.9%) | |
SD | 2 (6.7%) | 13 (21%) | |
PD | 20 (66.7%) | 35 (56.5%) | |
Clinical benefit (CR + PR + SD) | 10 (33.3%) | 27 (43.5%) | |
Progression rate | 0.015 | ||
cerebral progression | 3 (10%) | 10 (16.4%) | |
systemic progression | 7 (23.3%) | 6 (9.8%) | |
overall progression | 17 (56.7%) | 22 (36.1%) | |
no progression | 3 (10%) | 23 (37.7%) | |
cerebral response rate | 10 (33.3%) | 29 (47.5%) | 0.198 |
abscopal effects | 0 (0%) | 5 (16.1%) | 0.039 |
pseudoprogression | 1 (5%) | 12 (22.6%) | 0.079 |
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Trommer, M.; Adams, A.; Celik, E.; Fan, J.; Funken, D.; Herter, J.M.; Linde, P.; Morgenthaler, J.; Wegen, S.; Mauch, C.; et al. Oncologic Outcome and Immune Responses of Radiotherapy with Anti-PD-1 Treatment for Brain Metastases Regarding Timing and Benefiting Subgroups. Cancers 2022, 14, 1240. https://doi.org/10.3390/cancers14051240
Trommer M, Adams A, Celik E, Fan J, Funken D, Herter JM, Linde P, Morgenthaler J, Wegen S, Mauch C, et al. Oncologic Outcome and Immune Responses of Radiotherapy with Anti-PD-1 Treatment for Brain Metastases Regarding Timing and Benefiting Subgroups. Cancers. 2022; 14(5):1240. https://doi.org/10.3390/cancers14051240
Chicago/Turabian StyleTrommer, Maike, Anne Adams, Eren Celik, Jiaqi Fan, Dominik Funken, Jan M. Herter, Philipp Linde, Janis Morgenthaler, Simone Wegen, Cornelia Mauch, and et al. 2022. "Oncologic Outcome and Immune Responses of Radiotherapy with Anti-PD-1 Treatment for Brain Metastases Regarding Timing and Benefiting Subgroups" Cancers 14, no. 5: 1240. https://doi.org/10.3390/cancers14051240