Real-World Analysis of the Impact of Radiotherapy on Immunotherapy Efficacy in Non-Small Cell Lung Cancer
Abstract
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Statistics
2.3. Ethics
3. Results
3.1. Patients Characteristics
3.2. XRT Timing Impact on IO-Treated Patients
3.3. XRT Parameters Impact on Outcome of IO-Treated Patients
3.4. Patient and Treatment Characteristics’ Impact on Outcome of IO-Treated Patients
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Parameters | All Patients | No XRT | XRT before IO | XRT after IO | p-Value |
---|---|---|---|---|---|
N (%) | 453 (100) | 167 (100) | 182 (100) | 104 (100) | |
Age (years) median (range) | 67 (34–96) | 69 (38–96) | 67 (43–89) | 66 (34–83) | 0.0369 * |
Sex-male (%) | 296 (65.3) | 107 (64.1) | 116 (63.7) | 73 (70.2) | 0.495 § |
ECOG-PS—N (%) | 0.025 § | ||||
0–1 | 312 (68.7) | 112 (67.1) | 117 (64.3) | 83 (79.8) | |
2–3 | 137 (30.2) | 52 (31.1) | 64 (35.2) | 21 (20.2) | |
4 | 4 (0.9) | 3 (1.8) | 1 (0.5) | 0 | |
XRT site—N (%) | 0.049 § | ||||
None | 167 (36.9) | 167 (100) | |||
Bone | 126 (27.8) | 86 (47.3) | 40 (38.5) | ||
Cranium | 23 (5.1) | 10 (5.5) | 13 (12.5) | ||
Gastro-intestinal | 9 (2.0) | 4 (2.2) | 5 (4.8) | ||
Lung and Mediastinum | 116 (25.6) | 77 (42.3) | 39 (37.5) | ||
Soft tissue | 12 (2.6) | 5 (2.7) | 7 (6.7) | ||
Total XRT dose (Gy)—N (%) | <0.001 § | ||||
None | 167 (36.9) | 167 (100) | |||
1 < dose ≤ 10 | 41 (9.1) | 19 (10.4) | 22 (21.2) | ||
10 < dose ≤ 20 | 75 (16.6) | 47 (25.8) | 28 (26.9) | ||
20 < dose ≤ 30 | 71 (15.7) | 45 (24.7) | 26 (25.0) | ||
30 < dose ≤ 40 | 21 (4.6) | 8 (4.4) | 13 (12.5) | ||
40 < dose ≤ 50 | 29 (6.4) | 18 (9.9) | 11 (10.6) | ||
50 < dose | 49 (10.8) | 45 (24.7) | 4 (3.8) | ||
Fraction size (Gy)—N (%) | <0.001 § | ||||
None | 167 (36.9) | 167 (100) | |||
Fraction ≤ 2 | 54 (11.9) | 49 (26.9) | 5 (4.8) | ||
2 < fraction ≤ 4 | 144 (31.8) | 85 (46.7) | 59 (56.7) | ||
4 < fraction ≤ 8 | 60 (13.2) | 32 (17.6) | 28 (26.9) | ||
8 ≤ Fraction | 28 (6.2) | 16 (8.8) | 12 (11.5) | ||
IO—N (%) | 0.136 § | ||||
Nivolumab | 176 (38.9) | 66 (39.5) | 64 (35.2) | 46 (44.2) | |
Atezolizumab | 32 (7.1) | 8 (4.8) | 19 (10.4) | 5 (4.8) | |
IO plus Chemotherapy | 101 (22.3) | 38 (22.8) | 48 (26.4) | 15 (14.4) | |
IO plus IO | 5 (1.1) | 2 (1.2) | 2 (1.1) | 1 (1.0) | |
Pembrolizumab | 139 (30.7) | 53 (31.7) | 49 (26.9) | 37 (35.6) | |
Treatment line of IO—N (%) | 0.755 *,‡ | ||||
1 | 226 (49.9) | 86 (51.5) | 89 (48.9) | 51 (49.0) | |
≥2 | 227 (50.1) | 81 (48.5) | 93 (51.1) | 53 (51.0) | |
Albumin—gr/dL, mean (95%CI) | 3.54 (3.48–3.60) | 3.46 (3.35–3.57) | 3.51 (3.43–3.59) | 3.72 (3.60–3.84) | 0.005 * |
NLR—mean (95%CI) | 6.77 (6.21–7.34) | 6.01 (5.23–6.78) | 8.02 (7.06–8.99) | 5.52 (4.33–6.71) | <0.001 * |
Histology—N (%) | 0.625 § | ||||
Adenocarcinoma | 309 (68.2) | 118 (70.7) | 123 (67.6) | 68 (65.4) | |
Squamous cell | 92 (20.3) | 31 (18.6) | 35 (19.2) | 26 (25.0) | |
NSCLC-NOS | 52 (11.5) | 18 (10.8) | 24 (13.2) | 10 (9.6) | |
Mutation—N (%) | 0.660 §,# | ||||
None | 349 (77.0) | 125 (74.9) | 144 (79.1) | 80 (76.9) | |
KRAS | 43 (9.5) | 19 (11.4) | 14 (7.7) | 10 (9.6) | |
EGFR | 31 (6.8) | 11 (6.6) | 15 (8.2) | 5 (4.8) | |
ALK | 2 (0.4) | 0 | 1 (0.5) | 1 (1.0) | |
BRAF | 13 (2.9) | 6 (3.6) | 3 (1.6) | 4 (3.8) | |
c-MET | 6 (1.3) | 2 (1.2) | 3 (1.6) | 1 (1.0) | |
ROS1 | 5 (1.1) | 1 (0.6) | 2 (1.1) | 2 (1.9) | |
Other | 4 (0.9) | 3 (1.8) | 0 | 1 (1.0) |
Parameters | HR (95% CI) | p-Value |
---|---|---|
Age | 1.0 (0.99–1.0) | 0.196 |
Sex (men—reference) | 0.81 (0.63–1.04) | 0.110 |
ECOG-PS | ||
0 | Reference | |
1 | 1.77 (1.29–2.42) | <0.001 |
2 | 3.03 (2.15–4.27) | <0.001 |
3 | 6.37 (4.19–9.68) | <0.001 |
4 | 31.81 (11.15–90.79) | <0.001 |
XRT site | ||
None | Reference | |
Bone | 1.36 (1.01–1.83) | 0.040 |
Cranium | 0.99 (0.57–1.75) | 0.988 |
Gastro-intestine | 0.71 (0.31–1.62) | 0.417 |
Lung and Mediastinum | 1.00 (0.74–1.36) | 0.988 |
Soft Tissue | 0.90 (0.45–1.79) | 0.765 |
Total XRT dose (Gray) | ||
None | Reference | |
1< dose ≤ 10 | 1.66 (1.13–2.46) | 0.010 |
10 < dose ≤ 20 | 1.33 (0.95–1.86) | 0.099 |
20 < dose ≤ 30 | 1.18 (0.82–1.69) | 0.376 |
30 < dose ≤ 40 | 0.50 (0.25–0.99) | 0.048 |
40 < dose ≤ 50 | 0.97 (0.59–1.58) | 0.891 |
50 < dose | 0.85 (0.55–1.31) | 0.470 |
Fraction size (Gray) | ||
None | Reference | |
Fraction ≤ 2 | 0.87 (0.57–1.32) | 0.513 |
2 < Fraction ≤ 4 | 1.14 (0.85–1.52) | 0.370 |
4 < Fraction ≤ 8 | 1.48 (1.04–2.10) | 0.027 |
8 < Fraction | 0.82 (0.49–1.37) | 0.452 |
XRT Timing | ||
No XRT | Reference | |
XRT after IO | 1.20 (0.91–1.58) | 0.188 |
XRT before IO | 1.00 (0.74–1.36) | 0.990 |
Timing Cohorts—time window: * | ||
XRT after IO | Reference | |
One month | 0.72 (0.44–1.16) | 0.179 |
Three months | 0.76 (0.50–1.14) | 0.188 |
Six months | 0.77 (0.54–1.09) | 0.139 |
Treatment-line of IO | 1.32 (1.15–1.52) | <0.001 |
Albumin | ||
< lower limit of Normal | Reference | |
≥ lower limit of Normal | 0.34 (0.26–0.45) | <0.001 |
NLR | 1.06 (1.04–1.07) | <0.001 |
Histology | ||
Adenocarcinoma | Reference | |
Squamous cell | 1.01 (0.75–1.36) | 0.940 |
NSCLC NOS | 1.20 (0.85–1.72) | 0.290 |
Mutation | ||
None | Reference | |
KRAS | 9.20 (0.60–1.41) | 0.706 |
EGFR | 1.15 (0.73–1.82) | 0.552 |
ALK | 2.34 (0.58–9.44) | 0.231 |
BRAF | 8.71 (0.43–1.76) | 0.701 |
c-MET | 7.31 (0.27–1.97) | 0.536 |
ROS1 | 1.06 (0-Inf) | 0.990 |
Others | 5.25 (0.13–2.11) | 0.364 |
IO type: | ||
Nivolumab | Reference | |
Pembrolizumab | 0.71 (0.54–0.92) | 0.011 |
IO plus Chemotherapy | 0.36 (0.24–0.54) | <0.001 |
Atezolizumab | 0.79 (0.47–1.34) | 0.386 |
IO plus IO | 0.56 (0.178–1.75) | 0.315 |
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Onn, A.; Gottfried, T.; Stemmer, A.; Appel, S.; Lawrence, Y.R.; Urban, D.; Beller, T.; Daher, S.; Bar, J. Real-World Analysis of the Impact of Radiotherapy on Immunotherapy Efficacy in Non-Small Cell Lung Cancer. Cancers 2021, 13, 2800. https://doi.org/10.3390/cancers13112800
Onn A, Gottfried T, Stemmer A, Appel S, Lawrence YR, Urban D, Beller T, Daher S, Bar J. Real-World Analysis of the Impact of Radiotherapy on Immunotherapy Efficacy in Non-Small Cell Lung Cancer. Cancers. 2021; 13(11):2800. https://doi.org/10.3390/cancers13112800
Chicago/Turabian StyleOnn, Amir, Teodor Gottfried, Amos Stemmer, Sarit Appel, Yaacov R. Lawrence, Damien Urban, Tamar Beller, Sameh Daher, and Jair Bar. 2021. "Real-World Analysis of the Impact of Radiotherapy on Immunotherapy Efficacy in Non-Small Cell Lung Cancer" Cancers 13, no. 11: 2800. https://doi.org/10.3390/cancers13112800
APA StyleOnn, A., Gottfried, T., Stemmer, A., Appel, S., Lawrence, Y. R., Urban, D., Beller, T., Daher, S., & Bar, J. (2021). Real-World Analysis of the Impact of Radiotherapy on Immunotherapy Efficacy in Non-Small Cell Lung Cancer. Cancers, 13(11), 2800. https://doi.org/10.3390/cancers13112800