Impact of PD-L1 Scores and Changes on Clinical Outcome in Rectal Cancer Patients Undergoing Neoadjuvant Chemoradiotherapy
Abstract
:1. Introduction
2. Experimental Section
2.1. Patients
2.2. Immunohistochemistry
2.3. Microsatellite Status
2.4. Tumor Regression Grade
2.5. Statistical Analysis
3. Results
3.1. Patient and Treatment Characteristics
3.2. PD-L1 Expression Prior to Neoadjuvant CRT and PD-L1 Changes after Completion of CRT
3.3. PD-L1 Expression Prior to Neoadjuvant CRT and Association with Surrogate Endpoints
3.4. PD-L1 Expression and Clinical Outcome
3.4.1. PD-L1 Expression Prior to Neoadjuvant CRT
3.4.2. PD-L1 Changes after Completion of CRT
3.5. Univariate and Multivariate Analysis for DFS and OS
4. Discussion
Author Contributions
Funding
Conflicts of Interest
Appendix A
DFS | OS | |||
---|---|---|---|---|
PD-L1 Expression Prior to CRT (n) | Median (months) | p-Value (log-rank) | Median (months) | p-Value (log-rank) |
TPS | ||||
<1% (4) ≥1% (61) | 24.5 NR | 0.04 | 56.7 NR | 0.21 |
≤5% (39) >5% (26) | NR NR | 0.83 | NR NR | 0.16 |
≤10% (48) >10% (17) | NR NR | 0.27 | NR NR | 0.11 |
≤20% (56) >20% (9) | NR NR | 0.20 | NR NR | 0.27 |
≤50% (61) >50% (4) | NR NR | 0.41 | NR NR | 0.23 |
CPS | ||||
<1 (2) ≥1 (63) | 24.5 NR | 0.17 | 44.7 NR | 0.32 |
≤10 (15) >10 (50) | NR NR | 0.34 | NR NR | 0.58 |
≤20 (34) >20 (31) | NR NR | 0.85 | 134.2 NR | 0.05 |
≤50 (52) >50 (13) | NR NR | 0.97 | NR NR | 0.24 |
IC | ||||
<1% (2) ≥1% (63) | 24.5 NR | 0.17 | 44.7 NR | 0.32 |
≤5% (11) >5% (54) | NR NR | 0.60 | 132.9 NR | 0.47 |
≤10% (23) >10% (42) | NR NR | 0.87 | NR NR | 0.66 |
≤20% (46) >20% (19) | NR NR | 0.64 | NR NR | 0.18 |
≤50% (59) >50% (6) | NR NR | 0.88 | NR NR | 0.43 |
Parameter | PD-L1 TPS ≤1% N = 17 (%) | PD-L1 TPS >1% N = 48 (%) | p-Value |
---|---|---|---|
Age | 0.755 | ||
≤65 years | 11 (65) | 29 (60) | |
>65 years | 6 (35) | 19 (40) | |
Sex | 0.368 | ||
female | 4 (23) | 17 (35) | |
male | 13 (77) | 31 (65) | |
cTNM stage | 0.559 | ||
I | 0 (0) | 1 (2) | |
II | 9 (53) | 19 (40) | |
III | 8 (47) | 28 (58) | |
cT stage | 0.662 | ||
T2 | 1 (6) | 1 (2) | |
T3 | 14 (82) | 43 (90) | |
T4 | 2 (12) | 4 (8) | |
cN stage | 0.422 | ||
N- | 9 (53) | 20 (42) | |
N+ | 8 (47) | 28 (58) | |
Histologic grade | 0.230 | ||
I | 1 (6) | 0 (0) | |
II | 14 (82) | 42 (91) | |
III | 2 (12) | 4 (9) | |
NA | 0 | 2 | |
Lymphovascular invasion | 0.657 | ||
no | 11 (85) | 30 (79) | |
yes | 2 (15) | 8 (21) | |
NA | 4 | 10 | |
Venous invasion | 0.069 | ||
no | 10 (83) | 38 (97) | |
yes | 2 (17) | 1 (3) | |
NA | 5 | 9 |
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Parameter | N = 72 (%) |
---|---|
Age | |
≤65 years | 44 (61) |
>65 years | 28 (39) |
Sex | |
female | 23 (32) |
male | 49 (68) |
ypN stage | |
N- | 48 (67) |
N+ | 24 (33) |
cTNM stage | |
I | 1 (1) |
II | 29 (40) |
III | 37 (52) |
IV | 5 (7) |
Histologic grade | |
I | 1 (1) |
II | 61 (87) |
III | 8 (12) |
NA | 2 |
Dworak tumor regression grade | |
0 | 3 (4) |
I | 16 (22) |
II | 25 (35) |
III | 20 (28) |
IV | 8 (11) |
Microsatellite status | |
MSS | 56 (98) |
MSI | 1 (2) |
NA | 15 |
CRT backbone | |
5-FU or capecitabine | 29 (40) |
5-FU + oxaliplatin or capecitabine + oxaliplatin | 43 (60) |
NAR score | |
low | 11 (15) |
intermediate | 36 (50) |
high | 25 (35) |
Adjuvant chemotherapy | |
yes | 36 (52) |
no | 33 (48) |
NA | 3 |
UVA | MVA | |||
---|---|---|---|---|
HR (95% CI) | p-Value | HR (95% CI) | p-Value | |
Sex male (n = 45) female (n = 22) | 1.86 (0.39–8.95) | 0.44 | − | − |
Age >65 (n = 25) ≤65 (n = 42) | 0.56 (0.12–2.69) | 0.47 | − | − |
ypN stage N+ (n = 20) N− (n = 47) | 1.21 (0.30–4.84) | 0.79 | − | − |
Dworak TRG 3–4 (n = 28) 0–2 (n = 39) | 0.74 (0.18–2.95) | 0.67 | − | − |
Histologic grade 3 (n = 7) 1 + 2 (n = 58) | 0.20 (0.002–17.98) | 0.49 | − | − |
Adjuvant chemotherapy yes (n = 35) no (n = 30) | 0.88 (0.22–3.52) | 0.86 | − | − |
PD-L1 TPS pre-CRT >1% (n = 48) ≤1% (n = 17) | 0.40 (0.11–1.50) | 0.18 | − | − |
NAR score intermediate/high (n = 56) low (n = 11) | 27.20 (0.02–43,658.20) | 0.38 | − | − |
UVA | MVA | |||
---|---|---|---|---|
HR (95% CI) | p-Value | HR (95% CI) | p-Value | |
Sex male (n = 45) female (n = 22) | 2.24 (0.74–6.76) | 0.15 | - | - |
Age >65 (n = 25) ≤65 (n = 42) | 3.12 (1.25–7.82) | 0.02 | 4.09 (1.54–10.86) | 0.005 |
ypN stage N+ (n = 20) N− (n = 47) | 1.11 (0.42–2.91) | 0.84 | - | - |
Dworak TRG 3–4 (n = 28) 0–2 (n = 39) | 1.10 (0.44–2.75) | 0.84 | - | - |
Histologic grade 3 (n = 7) 1 + 2 (n = 58) | 0.67 (0.25–1.84) | 0.44 | - | - |
Adjuvant chemotherapy yes (n = 35) no (n = 30) | 0.72 (0.28–1.83) | 0.49 | - | - |
PD-L1 TPS pre-CRT >1% (n = 48) ≤1% (n = 17) | 0.36 (0.14–0.91) | 0.03 | 0.29 (0.11–0.76) | 0.01 |
NAR score intermediate/high (n = 56) low (n = 11) | 1.89 (0.44–8.17) | 0.40 | − | − |
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Huemer, F.; Klieser, E.; Neureiter, D.; Schlintl, V.; Rinnerthaler, G.; Pagès, F.; Kirilovsky, A.; El Sissy, C.; Iglseder, W.; Singhartinger, F.; et al. Impact of PD-L1 Scores and Changes on Clinical Outcome in Rectal Cancer Patients Undergoing Neoadjuvant Chemoradiotherapy. J. Clin. Med. 2020, 9, 2775. https://doi.org/10.3390/jcm9092775
Huemer F, Klieser E, Neureiter D, Schlintl V, Rinnerthaler G, Pagès F, Kirilovsky A, El Sissy C, Iglseder W, Singhartinger F, et al. Impact of PD-L1 Scores and Changes on Clinical Outcome in Rectal Cancer Patients Undergoing Neoadjuvant Chemoradiotherapy. Journal of Clinical Medicine. 2020; 9(9):2775. https://doi.org/10.3390/jcm9092775
Chicago/Turabian StyleHuemer, Florian, Eckhard Klieser, Daniel Neureiter, Verena Schlintl, Gabriel Rinnerthaler, Franck Pagès, Amos Kirilovsky, Carine El Sissy, Wolfgang Iglseder, Franz Singhartinger, and et al. 2020. "Impact of PD-L1 Scores and Changes on Clinical Outcome in Rectal Cancer Patients Undergoing Neoadjuvant Chemoradiotherapy" Journal of Clinical Medicine 9, no. 9: 2775. https://doi.org/10.3390/jcm9092775