Copyright
©The Author(s) 2021.
World J Gastrointest Oncol. Dec 15, 2021; 13(12): 2161-2179
Published online Dec 15, 2021. doi: 10.4251/wjgo.v13.i12.2161
Published online Dec 15, 2021. doi: 10.4251/wjgo.v13.i12.2161
Table 1 Criteria of five tumor regression grading systems
TRG system | Description |
JGCA/JGCA2017-TRG | |
0 | No response |
1a | 67%-99% residual tumor/tumor bed |
1b | 34%-66% residual tumor/tumor bed |
2/2a | 10%-33% residual tumor/tumor bed |
/2b | < 10% residual tumor/tumor bed |
3 | Complete response |
Becker-TRG | |
1a | Complete response |
1b | < 10% residual tumor/tumor bed |
2 | 10%-50% residual tumor/tumor bed |
3 | > 50% residual tumor/tumor bed |
AJCC/CAP-TRG | |
0 | No residual tumor |
1 | Single cells or rare small groups of cancer cells |
2 | More than single cells or rare small groups of cancer cells with evident tumor regression |
3 | Extensive residual tumor or no response |
Mandard-TRG | |
1 | No residual tumor |
2 | Rare residual tumor |
3 | Fibrosis outgrowing residual tumor |
4 | Residual tumor outgrowing fibrosis |
5 | No response |
Table 2 Clinical and demographic characteristics of the study population
Characteristics | n (%) |
No. of patients | 413 |
Age, median (IQR), yr | 61 (54-67) |
BMI, median (IQR), (kg/m2) | 23.04 (20.83-25.10) |
Male | 304 (73.61) |
ASA score | |
1 | 102 (24.70) |
2 | 255 (61.74) |
3 | 56 (13.56) |
ECOG | |
0 | 229 (55.45) |
1 | 168 (40.68) |
2 | 16 (3.87) |
Location | |
Upper | 166 (40.19) |
Middle | 51 (12.35) |
Lower | 170 (41.16) |
Diffuse | 26 (6.30) |
Diameter (cm) | 3.0 (1.5-4.0) |
Differentiation | |
Well | 27 (6.54) |
Moderate | 176 (42.86) |
Poor | 209 (50.61) |
Mucinous or signet cell | 85 (20.58) |
LVI | 132 (31.96) |
Cycles of treatment | 2 (2-3) |
ypT | |
ypT0 | 37 (8.96) |
ypT1 | 25 (6.05) |
ypT2 | 55 (13.32) |
ypT3 | 66 (15.98) |
ypT4 | 230 (55.69) |
ypN | |
N0 | 169 (40.92) |
N1 | 64 (15.50) |
N2 | 70 (16.95) |
N3 | 110 (26.63) |
ypStage | |
pCR | 32 (7.75) |
I | 57 (13.80) |
II | 116 (28.09) |
III | 208 (50.36) |
Total gastrectomy | 180 (43.58) |
Regimen | |
Platin-based | 364 (88.14) |
Taxol-based | 25 (6.05) |
Triplet | 24 (5.81) |
Adjuvant chemotherapy | 308 (74.58) |
Postoperative complications | |
Grade 0-1 | 277 (67.07) |
Grade 2 | 78 (18.89) |
Grade 3-4 | 58 (14.04) |
JGCA2017-TRG | |
Grade 3 (no residual) | 36 (8.72) |
Grade 2b (< 10%) | 39 (9.44) |
Grade 2a (10%-33%) | 29 (7.02) |
Grade 1b (34%-66%) | 78 (18.89) |
Grade 1a (67%-99%) | 205 (49.64) |
Grade 0 (no response) | 26 (6.30) |
JGCA-TRG | |
Grade 3 (no residual) | 36 (8.72) |
Grade 2 (< 33%) | 68 (16.46) |
Grade 1b (34%-66%) | 78 (18.89) |
Grade 1a (67%-99%) | 205 (49.64) |
Grade 0 (no response) | 26 (6.30) |
Becker-TRG | |
1a (no residual) | 36 (8.72) |
1b (< 10%) | 39 (9.44) |
2 (10%-50%) | 65 (15.74) |
3 (> 50%) | 273 (66.10) |
AJCC-TRG | |
0 (complete response) | 36 (8.72) |
1 (moderate response) | 48 (11.62) |
2 (minimal response) | 89 (21.55) |
3 (poor response) | 240 (58.11) |
Mandard-TRG | |
1 (complete response) | 36 (8.72) |
2 (Fibrosis + scattered tumor cells) | 48 (11.62) |
3 (Fibrosis predominance + tumor cells) | 89 (21.55) |
4 (Tumor cells preponderance + fibrosis) | 214 (51.82) |
5 (No response) | 26 (6.30) |
Table 3 Univariate analyses for overall survival and progression-free survival using a Cox proportional hazards model
Variables | OS | DFS | ||
HR (95%CI) | P value | HR (95%CI) | P value | |
Age | ||||
≤ 65 | ||||
> 65 | 1.12 (0.84-1.51) | 0.439 | 1.12 (0.84-1.49) | 0.4351 |
BMI | ||||
≤ 23.9 | 1.39 (1.04-1.87) | 0.027 | 1.31 (0.98-1.74) | 0.065 |
> 23.9 | ||||
Gender | ||||
Male | ||||
Female | 1.14 (0.84-1.56) | 0.393 | 1.06 (0.78-1.45) | 0.690 |
ASA score | ||||
1-2 | ||||
3 | 1.00 (0.67-1.49) | 0.993 | 0.97 (0.65-1.43) | 0.874 |
ECOG | ||||
0 | ||||
1-2 | 1.29 (0.98-1.70) | 0.073 | 1.30 (0.99-1.71) | 0.056 |
Location | ||||
Diffuse vs Upper | 3.32 (2.07-5.31) | < 0.001 | 2.97 (1.86-4.73) | < 0.001 |
Diffuse vs Middle | 2.63 (1.51-4.56) | < 0.001 | 2.28 (1.32-3.94) | 0.003 |
Diffuse vs Lower | 3.94 (2.45-6.35) | < 0.001 | 3.52 (2.19-5.65) | < 0.001 |
Diffuse | 1.00 | 1.00 | ||
Diameter (cm) | ||||
≤ 5 | ||||
> 5 | 2.79 (2.00-3.88) | < 0.001 | 2.99 (2.17-4.13) | < 0.001 |
Differentiation | ||||
Well-Moderate | ||||
Poor | 1.43 (1.08-1.90) | 0.012 | 1.51 (1.15-1.99) | 0.003 |
Histology | ||||
Non-mucinous | ||||
Mucinous or signet cell | 1.86 (1.39-2.53) | < 0.001 | 1.77 (1.31-2.40) | < 0.001 |
Lymphovascular invasion | ||||
No | ||||
Yes | 2.75 (2.08-3.64) | < 0.001 | 2.91 (2.21-3.83) | < 0.001 |
ypT | ||||
ypT0-2 | ||||
ypT3-4 | 3.54 (2.35-5.36) | < 0.001 | 3.66 (2.44-5.49) | < 0.001 |
ypN | ||||
ypN0 | ||||
ypN+ | 3.50 (2.50-4.90) | < 0.001 | 3.59 (2.58-4.98) | < 0.001 |
Resection type | ||||
Subtotal | ||||
Total | 1.79 (1.35-2.36) | < 0.001 | 1.74 (1.32-2.28) | < 0.001 |
Cycle of NACT | ||||
≤ 2 | ||||
> 2 | 1.18 (0.89-1.56) | 0.247 | 1.18 (0.90-1.55) | 0.233 |
NACT regimen | ||||
Platin-based | 1.00 | 1.00 | ||
Paclitaxel-based | 1.10 (0.62-1.92) | 0.752 | 1.27 (0.75-2.15) | 0.373 |
Triplet drug | 1.05 (0.59-1.89) | 0.862 | 1.03 (0.57-1.84) | 0.930 |
Adjuvant chemotherapy | ||||
Received | ||||
Not received | 1.36 (1.00-1.85) | 0.050 | 1.18 (0.87-1.60) | 0.286 |
Complications | ||||
Clavien-dindo 0-2 | ||||
Clavien-dindo 3-4 | 1.15 (0.78-1.69) | 0.491 | 1.11 (0.76-1.63) | 0.585 |
JGCA2017-TRG | ||||
Grade 3 (no residual) | 1.00 | 1.00 | ||
Grade 2b (< 10%) | 8.97 (2.06-39.02) | 0.003 | 8.75 (2.01-38.09) | 0.004 |
Grade 2a (10%-33%) | 13.55 (3.11-58.93) | 0.001 | 14.03 (3.23-61.06) | < 0.001 |
Grade 1b (34%-66%) | 12.83 (3.10-53.18) | < 0.001 | 14.05 (3.40-58.09) | < 0.001 |
Grade 1a (67%-99%) | 15.15 (3.74-61.42) | < 0.001 | 15.55 (3.84-62.97) | < 0.001 |
Grade 0 (no response) | 20.24 (4.67-87.68) | < 0.001 | 21.15 (4.88-91.67) | < 0.001 |
JGCA-TRG | ||||
Grade 3 (no residual) | 1.00 | 1.00 | ||
Grade 2 (< 33%) | 10.79 (2.59-45.05) | 0.001 | 10.79 (2.58-45.05) | 0.001 |
Grade 1b (34%-66%) | 12.83 (3.10-53.18) | < 0.001 | 14.04 (3.40-58.05) | < 0.001 |
Grade 1a (67%-99%) | 15.15 (3.74-61.42) | < 0.001 | 15.54 (3.84-62.93) | < 0.001 |
Grade 0 (no response) | 20.24 (4.67-87.66) | < 0.001 | 21.18 (4.89-91.78) | < 0.001 |
Becker-TRG | ||||
1a (no residual) | 1.00 | 1.00 | ||
1b (< 10%) | 8.98 (2.06-39.06) | 0.003 | 8.74 (2.01-38.05) | 0.004 |
2 (10%-50%) | 12.19 (2.92-50.87) | 0.001 | 12.72 (3.05-53.06) | < 0.001 |
3 (> 50%) | 15.50 (3.84-62.62) | < 0.001 | 16.15 (4.00-65.22) | < 0.001 |
AJCC-TRG | ||||
0 (complete response) | 1.00 | 1.00 | ||
1 (moderate response) | 10.46 (2.46-44.48) | 0.001 | 10.31 (2.42-43.90) | 0.002 |
2 (minimal response) | 11.21 (2.71-46.34) | 0.001 | 11.67 (2.83-48.22) | 0.001 |
3 (poor response) | 16.31 (4.03-65.97) | < 0.001 | 16.94 (4.19-68.49) | < 0.001 |
Mandard-TRG | ||||
1 (complete response) | 1.00 | 1.00 | ||
2 (Fibrosis + scattered tumor cells) | 10.46 (2.46-44.48) | 0.001 | 10.33 (2.43-43.95) | 0.002 |
3 (Fibrosis predominance + tumor cells) | 11.20 (2.71-46.30) | 0.001 | 11.66 (2.82-48.16) | 0.001 |
4 (Tumor cells preponderance + fibrosis) | 15.85 (3.91-64.19) | < 0.001 | 16.48 (4.07-66.71) | < 0.001 |
5 (No response) | 20.27 (4.68-87.81) | < 0.001 | 21.22 (4.90-91.96) | < 0.001 |
Table 4 Multivariate Cox hazards regression model for the predictable risk of overall survival and disease-free survival in different covariate inclusion in whole patients
Whole patients (n = 413) | ||||
Covariates | OS | DFS | ||
HR | P value | HR | P value | |
BMI ≤ 23.9 | 1.37 (1.01-1.87) | 0.045 | 1.28 (0.95-1.72) | 0.109 |
ECOG > 0 | 1.19 (0.87-1.61) | 0.271 | 1.18 (0.88-1.60) | 0.272 |
Linitis plastica | 1.74 (0.97-3.13) | 0.063 | 1.30 (0.74-2.30) | 0.362 |
Diameter > 5 cm | 1.20 (0.77-1.88) | 0.426 | 1.43 (0.93-2.19) | 0.102 |
Poorly differentiated | 1.16 (0.85-1.57) | 0.345 | 1.24 (0.92-1.66) | 0.160 |
Mucinous or signet cell | 1.45 (1.03-2.05) | 0.036 | 1.32 (0.94-1.84) | 0.111 |
Lymphovascular invasion | 1.53 (1.12-2.10) | 0.008 | 1.61 (1.18-2.19) | 0.002 |
ypT3-4 | 1.45 (0.92-2.28) | 0.113 | 1.52 (0.97-2.37) | 0.065 |
ypN+ | 1.96 (1.35-2.85) | < 0.001 | 1.94 (1.34-2.82) | < 0.001 |
Total gastrectomy | 1.30 (0.94-1.79) | 0.118 | 1.23 (0.90-1.69) | 0.202 |
Without AC | 1.35 (0.98-1.87) | 0.066 | Not included | NA |
JGCA2017-TRG (Model 1) | ||||
Grade 3 (no residual) | 1.00 | 1.00 | ||
Grade 2b (< 10%) | 4.69 (1.04-21.08) | 0.044 | 4.50 (1.00-20.27) | 0.050 |
Grade 2a (10%-33%) | 5.48 (1.19-25.23) | 0.029 | 5.50 (1.20-25.26) | 0.028 |
Grade 1b (34%-66%) | 5.32 (1.22-23.30) | 0.026 | 5.73 (1.32-24.88) | 0.020 |
Grade 1a (67%-99%) | 6.69 (1.55-28.96) | 0.011 | 6.22 (1.44-26.81) | 0.014 |
Grade 0 (no response) | 8.60 (1.87-39.58) | 0.006 | 8.44 (1.84-38.76) | 0.006 |
JGCA-TRG (Model 2) | ||||
Grade 3 (no residual) | 1.00 | |||
Grade 2 (< 33%) | 5.00 (1.15-21.78) | 0.032 | 4.90 (1.13-21.30) | 0.034 |
Grade 1b (34%-66%) | 5.27 (1.21-23.05) | 0.027 | 5.67 (1.30-24.61) | 0.021 |
Grade 1a (67%-99%) | 6.63 (1.53-28.66) | 0.011 | 6.16 (1.43-26.52) | 0.015 |
Grade 0 (no response) | 8.48 (1.84-39.00) | 0.006 | 8.31 (1.81-38.15) | 0.006 |
Becker-TRG (Model 3) | ||||
1a (no residual) | 1.00 | 1.00 | ||
1b (< 10%) | 4.74 (1.05-21.30) | 0.043 | 4.57 (1.02-20.57) | 0.047 |
2 (10%-50%) | 5.11 (1.16-22.51) | 0.031 | 5.13 (1.17-22.49) | 0.030 |
3 (> 50%) | 6.77 (1.57-29.14) | 0.010 | 6.64 (1.55-28.46) | 0.011 |
AJCC-TRG (Model 4) | ||||
0 (complete response) | 1.00 | 1.00 | ||
1 (moderate response) | 5.39 (1.22-23.78) | 0.026 | 5.34 (1.21-23.50) | 0.027 |
2 (minimal response) | 5.01 (1.15-21.85) | 0.032 | 5.05 (1.16-21.93) | 0.031 |
3 (poor response) | 6.72 (1.56-28.97) | 0.011 | 6.53 (1.52-28.05) | 0.012 |
Mandard-TRG (Model 5) | ||||
1 (complete response) | 1.00 | 1.00 | ||
2 (Fibrosis + scattered tumor cells) | 5.37 (1.22-23.68) | 0.026 | 5.31 (1.21-23.39) | 0.027 |
3 (Fibrosis predominance + tumor cells) | 4.95 (1.14-21.60) | 0.033 | 4.98 (1.15-21.62) | 0.032 |
4 (Tumor cells preponderance + fibrosis) | 6.44 (1.49-27.87) | 0.013 | 6.26 (1.45-26.93) | 0.014 |
5 (No response) | 8.44 (1.83-38.86) | 0.006 | 8.41 (1.83-38.60) | 0.006 |
Table 5 The pairwise comparison of C-indexes between different tumor regression grade based on Cox regression for overall survival
JGCA2017 | JGCA | Becker | AJCC/CAP | Mandard | Modified | |
Overall survival | ||||||
JGCA2017 | 1.000 | 0.308 | 0.006 | 0.018 | 0.053 | < 0.001 |
JGCA | 1.000 | 0.007 | 0.021 | 0.063 | < 0.001 | |
Becker | 1.000 | 0.397 | 0.148 | 0.073 | ||
AJCC/CAP | 1.000 | 0.039 | 0.062 | |||
Mandard | 1.000 | 0.005 | ||||
Modified | 1.000 | |||||
Disease-free survival | ||||||
JGCA2017 | 1.000 | 0.320 | 0.002 | 0.021 | 0.033 | < 0.001 |
JGCA | 1.000 | 0.003 | 0.025 | 0.040 | < 0.001 | |
Becker | 1.000 | 0.273 | 0.136 | 0.046 | ||
AJCC/CAP | 1.000 | 0.112 | 0.024 | |||
Mandard | 1.000 | 0.002 | ||||
Modified | 1.000 |
- Citation: Liu ZN, Wang YK, Zhang L, Jia YN, Fei S, Ying XJ, Zhang Y, Li SX, Sun Y, Li ZY, Ji JF. Comparison of tumor regression grading systems for locally advanced gastric adenocarcinoma after neoadjuvant chemotherapy. World J Gastrointest Oncol 2021; 13(12): 2161-2179
- URL: https://www.wjgnet.com/1948-5204/full/v13/i12/2161.htm
- DOI: https://dx.doi.org/10.4251/wjgo.v13.i12.2161