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©2013 Baishideng Publishing Group Co.
World J Gastroenterol. Dec 28, 2013; 19(48): 9282-9293
Published online Dec 28, 2013. doi: 10.3748/wjg.v19.i48.9282
Published online Dec 28, 2013. doi: 10.3748/wjg.v19.i48.9282
Table 1 Tumour regression scoring according to Mandard et al[14]
Grade | Definition |
TRG 1 | No residual cancer |
TRG 2 | Rare residual cancer cells |
TRG 3 | Fibrosis outgrowing residual cancer |
TRG 4 | Residual cancer outgrowing fibrosis |
TRG 5 | Absence of regressive changes |
Table 2 Clinical and pathological characteristics of the 218 patients operated on for esophageal and gastro-esophageal adenocarcinoma, according to treatment n (%)
Characteristic | Surgery only 82 (37.6) | Neoadjuvant chemotherapy and surgery 136 (62.4) | Pvalue | |
Preoperative status | ||||
Age (range)1 yr | 74.32 (42.08-85.41) | 63.76 (32.77-81.28) | < 0.0001 | |
Sex ratio (M:F)1 | 68 (82.9):14 (17.1) | 118 (86.8):18 (13.2) | 0.439 | |
cT stage | 1 | 17 (20.7) | 0 (0.0) | < 0.0001 |
2 | 30 (36.6) | 16 (16.0) | ||
3 | 34 (41.5) | 114 (84.0) | ||
4 | 1 (1.2) | 6 (4.4) | ||
cN stage | 0 | 36 (43.9) | 19 (14.0) | < 0.0001 |
1 | 46 (56.1) | 117 (86.0) | ||
cM stage | 0 | 80 (97.6) | 134 (98.5) | 0.613 |
1 | 1 (2.4) | 2 (1.4) | ||
Performance status | 0 | 8 (11.6) | 35 (25.7) | 0.001 |
1 | 51 (73.9) | 96 (70.6) | ||
2 | 10 (14.5) | 5 (3.7) | ||
ASA | 1 | 3 (3.7) | 11 (8.1) | 0.005 |
2 | 56 (68.3) | 106 (78.5) | ||
3 | 23 (28) | 18 (13.3) | ||
O-POSSUM | 18 (12-30) | 16 (12-26) | < 0.0001 | |
Tumour site | Middle 1/3 | 1 (1.2) | 1 (0.7) | 0.418 |
Lower 1/3 | 32 (39) | 57 (41.9) | ||
GEJ-S1 | 19 (23.2) | 23 (16.9) | ||
GEJ-S2 | 18 (22.0) | 34 (25.0) | ||
GEJ-S3 | 12 (14.6) | 20 (14.7) | ||
Operative outcomes | ||||
Length of operation (min)1 | 255 (120-480) | 261 (120-471) | 0.409 | |
Blood loss (mL)1 | 300 (0-2200) | 318 (0-3000) | 0.429 | |
Clavien Dindo Max | 0 | 26 (31.7) | 53 (39.3) | 0.59 |
1 | 5 (6.1) | 8 (5.9) | ||
2 | 35 (42.7) | 40 (29.6) | ||
3 | 6 (7.3) | 17 (12.6) | ||
4 | 6 (7.3) | 17 (12.6) | ||
5 | 4 (4.9) | 0 (0) | ||
Anastomotic leaks | 8 (9.8) | 9 (6.7) | 0.413 | |
Pathological outcomes | ||||
pT or ypT | 0 | 3 (3.6) | 8 (5.9) | 0.692 |
1 | 23 (28) | 23 (16.9) | ||
2 | 17 (20.7) | 34 (25) | ||
3 | 34 (41.5) | 66 (48.5) | ||
4 | 5 (6.1) | 5 (3.7) | ||
pN or ypN | 0 | 40 (48.8) | 73 (53.7) | 0.758 |
1 | 20 (24.4) | 21 (15.4) | ||
2 | 11 (13.4) | 25 (18.4) | ||
3 | 11 (13.4) | 17 (12.5) | ||
pM or ypM | 0 | 82 (100) | 136 (100) | 1.00 |
Tumour regression grade | 1 | - | 8 (5.8) | n/a |
2 | - | 28 (20.6) | ||
3 | - | 20 (14.7) | ||
4 | - | 45 (33.1) | ||
5 | - | 35 (25.7) | ||
Nodal downstaged (cN1 to p or ypN1) | 13 (15.9) | 60 (44.1) | < 0.0001 | |
Positive nodes1 | 1 (0-21) | 0 (0-24) | 0.789 | |
Nodal yield1 | 18 (4-49) | 18 (3-53) | 0.242 | |
Resection clearance | R0 | 65 (79.3) | 110 (80.9) | 0.772 |
Vascular invasion | 24 (29.3) | 41 (30.1) | 0.891 | |
Lymphatic invasion | 9 (11) | 22 (16.2) | 0.28 | |
Perineural invasion | 8 (9.8) | 20 (14.7) | 0.291 | |
Maximum tumour diameter (mm)1 | 25 (0-90) | 25 (0-155) | 0.998 | |
Morphology | Ulcer | 48 (60) | 96 (74.4) | 0.029 |
Polypoid | 22 (27.5) | 23 (17.8) | ||
Fungating | 2 (2.5) | 3 (2.3) | ||
Diffuse infiltrating | 8 (10) | 7 (5.4) | ||
Grade | G1 | 6 (7.3) | 16 (11.8) | 0.669 |
G2 | 30 (36.6) | 37 (27.2) | ||
G3 | 46 (56.1) | 82 (60.3) | ||
G4 | 0 (0) | 1 (0.7) | ||
Sites of recurrence | Local | 3 (3.7) | 8 (5.9) | 0.461 |
Nodal | 5 (6.1) | 14 (10.4) | 0.281 | |
Distant | 18 (22.0) | 44 (32.6) | 0.093 |
Table 3 Clinical and pathological characteristics of the 136 patients treated with neoadjuvant chemotherapy for esophageal and gastro-esophageal adenocarcinoma, classified as responders Tumour regression grade 1-2 or non-reponders tumour regression grade 3-5 n (%)
TRG 1-2 36 (26.5) | TRG 3-5 100 (73.5) | Pvalue | ||
Preoperative status | ||||
Age (range) yr1 | 65.27 (26.99-76.04) | 63.51 (32.77-81.28) | 0.410 | |
Sex ratio (M:F)1 | 32 (88.9):4 (11.1) | 86 (86):14 (14) | 0.662 | |
cT stage | 1 | 0 (0) | 0 (0) | 0.396 |
2 | 2 (5.6) | 14 (14) | ||
3 | 33 (91.7) | 81 (81) | ||
4 | 1 (2.8) | 5 (5) | ||
cN stage | 0 | 5 (13.9) | 14 (14) | 0.987 |
1 | 31 (86.1) | 86 (86) | ||
cM stage | 0 | 35 (97.1) | 99 (99) | 0.456 |
1 | 1 (2.8) | 1 (1) | ||
Performance status | 0 | 12 (33.3) | 23 (23) | 0.225 |
1 | 23 (63.9) | 73 (73) | ||
2 | 1 (2.8) | 4 (4.0) | ||
ASA | 1 | 2 (5.6) | 9 (9.1) | 0.408 |
2 | 32 (88.9) | 74 (74.7) | ||
3 | 2 (5.6) | 16 (16.2) | ||
O-POSSUM | 15 (12-23) | 16 (12-26) | 0.476 | |
Tumour site | Middle 1/3 | 1 (2.8) | 0 (0) | 0.738 |
Lower 1/3 | 15 (41.7) | 42 (42) | ||
GEJ-S1 | 7 (19.4) | 16 (16) | ||
GEJ-S2 | 9 (25) | 25 (25) | ||
GEJ-S3 | 4 (11.1) | 16 (16) | ||
Operative outcomes | ||||
Length of operation (min)1 | 262 (163-427) | 260 (120-471) | 0.513 | |
Blood loss (mL)1 | 300 (0-3000) | 325 (0-1700) | 0.673 | |
Clavien Dindo Max | 0 | 14 (38.9) | 39 (39.4) | 0.531 |
1 | 2 (5.6) | 6 (6.1) | ||
2 | 14 (38.9) | 26 (26.3) | ||
3 | 4 (11.1) | 13 (13.1) | ||
4 | 2 (5.6) | 15 (15.2) | ||
5 | 0 (0) | 0 (0) | ||
Anastomotic leaks | 1 (2.8) | 8 (8.1) | 0.276 | |
Pathological outcomes | ||||
yPT | 0 | 8 (22.2) | 0 (0) | < 0.0001 |
1 | 11 (30.6) | 12 (12) | ||
2 | 9 (25) | 25 (25) | ||
3 | 8 (22.2) | 58 (58) | ||
4 | 0 (0) | 5 (5) | ||
yPN | 0 | 34 (94.4) | 39 (39) | < 0.0001 |
1 | 0 (0) | 21 (21) | ||
2 | 2 (5.6) | 23 (23) | ||
3 | 0 (0) | 17 (17) | ||
yPM | 0 | 36 (100) | 100 (100) | 0.579 |
Nodal downstaged (cN1 to ypN0) | 30 (83.3) | 30 (30) | < 0.0001 | |
Positive nodes1 | 0 (0-5) | 1 (0-24) | < 0.0001 | |
Nodal yield1 | 18 (4-25) | 18 (3-53) | 0.984 | |
Resection clearance | R0 | 35 (97.2) | 75 (75) | 0.004 |
Vascular invasion | 4 (11.1) | 37 (37) | 0.004 | |
Lymphatic invasion | 4 (11.1) | 18 (18) | 0.338 | |
Perineural invasion | 2 (5.6) | 18 (18) | 0.072 | |
Maximum tumour diameter1 | (mm) | 15 (0-110) | 30 (0-155) | < 0.0001 |
Morphology | Ulcer | 30 (93.8) | 66 (68) | 0.003 |
Polypoid | 2 (6.3) | 21 (21.6) | ||
Fungating | 0 (0) | 3 (3.1) | ||
Diffuse infiltrating | 0 (0) | 7 (7.2) | ||
Grade | G1 | 8 (22.2) | 8 (8) | 0.104 |
G2 | 9 (25) | 28 (28) | ||
G3 | 19 (52.8) | 63 (63) | ||
G4 | 0 (0) | 1 (1) | ||
Sites of recurrence | Local | 0 (0) | 8 (8.1) | 0.080 |
Nodal | 1 (2.8) | 13 (13.1) | 0.082 | |
Distant | 2 (5.6) | 42 (42.4) | < 0.0001 |
Table 4 Univariate and multivariate Cox regression analyses of patient and tumour factors with disease free survival for patients undergoing neoadjuvant chemotherapy (n = 136)
Univariate | Multivariate | ||||||
HR | 95%CI | Pvalue | HR | 95%CI | Pvalue | ||
Patient factors | |||||||
Age | 0.972 | (0.944-1.00) | 0.054 | ||||
Sex | Female | 1.000 | Ref | ||||
Male | 0.953 | (0.453-2.005) | 0.899 | ||||
ASA | 1 | 1.000 | Ref | ||||
2 | 0.696 | (0.313-1.548) | 0.374 | ||||
3 | 0.947 | (0.352-2.546) | 0.914 | ||||
Performance status | 0 | 1.000 | Ref | ||||
1 | 1.016 | (0.578-1.789) | 0.955 | ||||
2 | 0.950 | (0.218-4.129) | 0.945 | ||||
O-POSSUM | |||||||
Tumour response | |||||||
TRG | 1 | 1.000 | Ref | ||||
2 | 1.099 | (0.099-12.148) | 0.939 | ||||
3 | 8.404 | (1.071-65.929) | 0.043 | ||||
4 | 7.829 | (1.054-58.163) | 0.044 | ||||
5 | 15.422 | (2.083-114.189) | 0.007 | ||||
TRG grouped | 1-2 | 1.000 | Ref | 1.000 | Ref | ||
3-5 | 9.504 | (2.973-30.380) | < 0.0001 | 6.315 | (1.261-31.616) | 0.025 | |
Lymph node response | |||||||
Lymph nodes downstaged | Yes | 1.000 | Ref | 1.000 | Ref | ||
No | 5.784 | (3.064-10.919) | < 0.0001 | 6.161 | (1.683-22.554) | 0.006 | |
Tumour factors | |||||||
ypT stage | 0 | 1.000 | Ref | 1.000 | Ref | ||
1 | 2.085 | (0.232-18.711) | 0.512 | 0.281 | (0.020-3.928) | 0.345 | |
2 | 5.214 | (0.687-39.549) | 0.110 | 0.286 | (0.022-3.705) | 0.338 | |
3 | 9.490 | (1.293-69.635) | 0.027 | 0.469 | (0.034-6.460) | 0.571 | |
4 | 52.907 | (6.008-465.873) | < 0.0001 | 1.519 | (0.087-26.389) | 0.774 | |
ypN stage | 0 | 1.000 | Ref | 1.000 | Ref | ||
1 | 4.791 | (2.434-9.431) | < 0.0001 | 0.476 | (0.133-1.700) | 0.253 | |
2 | 4.102 | (2.005-8.392) | < 0.0001 | 0.254 | 0.070-0.927) | 0.038 | |
3 | 7.449 | (3.522-15.756) | < 0.0001 | 0.476 | (0.129-1.755) | 0.265 | |
ypM stage | 0 | 1.000 | Ref | 1.000 | Ref | ||
1 | 3.172 | (1.253-8.031) | 0.015 | 2.693 | (0.924-7.847) | 0.069 | |
Vascular invasion | No | 1.000 | Ref | 1.000 | Ref | ||
Yes | 3.444 | (2.080-5.702) | < 0.0001 | 1.929 | (1.034-3.600) | 0.039 | |
Lymphatic invasion | No | 1.000 | Ref | 1.000 | Ref | ||
Yes | 2.201 | (1.268-3.821) | 0.005 | 1.253 | (0.637-2.462) | 0.514 | |
Perineural invasion | No | 1.000 | Ref | 1.000 | Ref | ||
Yes | 5.073 | (2.896-8.886) | < 0.0001 | 2.766 | (1.444-5.300) | 0.002 | |
Resection clearance | R0 | 1.000 | Ref | 1.000 | Ref | ||
R1 | 3.869 | (2.272-6.588) | < 0.0001 | 1.805 | (0.940-3.468) | 0.076 |
Table 5 Clinical and pathological characteristics of the 113 patients with pathological N0 stage, according to treatment n (%)
pN0 Surgery alone 40 (35.4) | ypN0 Neoadjuvant chemotherapy and surgery 73 (64.6) | Pvalue | ||
Preoperative status | ||||
Age (range) yr1 | 73.62 (56.73-85.41) | 65.59 (32.77-78.43) | < 0.0001 | |
Sex ratio (M:F)1 | 31 (77.5):9 (22.5) | 66 (90.4):7 (9.8) | 0.061 | |
cT stage | 1 | 13 (32.5) | 0 (0) | < 0.0001 |
2 | 17 (42.5) | 9 (12.3) | ||
3 | 10 (25) | 61 (83.6) | ||
4 | 0 (0) | 3 (4.1) | ||
cN stage | 0 | 27 (67.5) | 13 (17.8) | < 0.0001 |
1 | 13 (32.5) | 60 (82.2) | ||
cM stage | 0 | 40 (100) | 71 (97.3) | 0.293 |
1 | 0 (0) | 2 (2.8) | ||
Performance status | 0 | 3 (9.4) | 16 (21.9) | 0.045 |
1 | 25 (78.1) | 54 (74) | ||
2 | 4 (12.5) | 3 (4.1) | ||
ASA | 1 | 2 (5) | 6 (8.2) | 0.268 |
2 | 31 (77.5) | 59 (80.8) | ||
3 | 7 (17.5) | 8 (11) | ||
O-POSSUM1 | 17 (14-29) | 16 (12-26) | 0.015 | |
Tumour site | Middle 1/3 | 0 (0) | 1 (1.4) | 0.190 |
Lower 1/3 | 15 (37.5) | 35 (47.9) | ||
OGJ-S1 | 11 (27.5) | 12 (16.4) | ||
OGJ-S2 | 8 (20) | 16 (21.9) | ||
OGJ-S3 | 6 (15) | 9 (12.3) | ||
Operative outcomes | ||||
Length of operation (min)1 | 240 (120-360) | 278 (120-471) | 0.082 | |
Blood loss (mL)1 | 200 (0-2200) | 350 (0-3000) | 0.167 | |
Clavien Dindo Max | 0 | 14 (35) | 24 (32.9) | 0.709 |
1 | 1 (2.5) | 3 (4.1) | ||
2 | 17 (42.5) | 27 (37) | ||
3 | 4 (10) | 10 (13.7) | ||
4 | 2 (5) | 9 (12.3) | ||
5 | 2 (5) | 0 (0) | ||
Anastomotic leaks | 4 (10) | 7 (9.6) | 0.944 | |
Pathological outcomes | ||||
TRG 1-2 | - | 34 (46.6) | NA | |
TRG 3-5 | - | 39 (53.4) | ||
pT or ypT | 0 | 2 (5) | 11 (15.1) | 0.224 |
1 | 22 (55) | 20 (27.4) | ||
2 | 5 (12.5) | 20 (27.4) | ||
3 | 10 (25) | 24 (32.9) | ||
4 | 0 (0) | 1 (1.4) | ||
Nodal Downstaged (cN1 to p or ypN0) | 15 (37.5) | 61 (83.6) | < 0.0001 | |
Nodal yield1 | 16 (4-49) | 18 (3-52) | 0.150 | |
Resection clearance | R0 | 35 (87.5) | 69 (94.5) | 0.189 |
Vascular invasion | 7 (17.5) | 10 (13.7) | 0.590 | |
Lymphatic invasion | 2 (5) | 6 (8.2) | 0.525 | |
Perineural invasion | 2 (5) | 5 (6.8) | 0.698 | |
Maximum tumour diameter (mm)1 | 24 (0-50) | 24 (0-110) | 0.324 | |
Morphology | Ulcer | 25 (65.8) | 53 (79.1) | 0.135 |
Polypoid | 10 (26.3) | 11 (16.4) | ||
Fungating | 1 (2.6) | 1 (1.5) | ||
Diffuse infiltrating | 2 (5.3) | 2 (3) | ||
Grade | G1 | 4 (10) | 13 (17.8) | 0.811 |
G2 | 17 (42.5) | 20 (27.4) | ||
G3 | 19 (47.5) | 40 (54.8) | ||
G4 | 0 (0) | 0 (0) | ||
Site of recurrence | Local | 0 (0) | 2 (2.7) | 0.293 |
Nodal | 1 (2.5) | 4 (5.5) | 0.463 | |
Distant | 3 (7.5) | 12 (16.4) | 0.182 |
- Citation: Noble F, Nolan L, Bateman AC, Byrne JP, Kelly JJ, Bailey IS, Sharland DM, Rees CN, Iveson TJ, Underwood TJ, Bateman AR. Refining pathological evaluation of neoadjuvant therapy for adenocarcinoma of the esophagus. World J Gastroenterol 2013; 19(48): 9282-9293
- URL: https://www.wjgnet.com/1007-9327/full/v19/i48/9282.htm
- DOI: https://dx.doi.org/10.3748/wjg.v19.i48.9282