Materials and Methods
Patients
Methods
Histopathology Assessment
Follow-Up
Statistics
Results
Patient and Tumor Characteristics
Surgery-Alone Group
Pathological characteristics | Total [N = 81] (100%) | EMVI-positive [N = 19] (23.5%) | EMVI-negative [N = 62] (76.5%) | p value |
---|---|---|---|---|
Localization | ||||
Middle | 14 (17.3) | 8 (42.1) | 6 (9.7) |
0.003
|
Distal | 67 (82.7) | 11 (57.9) | 56 (90.3) | |
Histologic type | ||||
AC | 60 (74.0) | 10 (52.6) | 50 (80.6) |
0.033
|
SCC | 21 (26.0) | 9 (47.4) | 12 (19.4) | |
T stage | ||||
T3 | 74 (91.3) | 19 (100) | 55 (88.7) | 0.190 |
T4 | 7 (8.6) | 0 (0) | 7 (11.3) | |
N stage | ||||
Present | 59 (72.8) | 13 (68.4) | 46 (74.2) | 0.769 |
Absent | 22 (27.2) | 6 (31.6) | 16 (25.8) | |
Differentiation grade | ||||
Well/moderated | 51 (63.0) | 15 (78.9) | 36 (58.1) | 0.113 |
Poor signet/mucinous | 30 (37.0) | 4 (21.0) | 26 (41.9) | |
Tumor length, cma | ||||
> 3 | 64 (81) | 18 (94.7) | 46 (76.7) | 0.154 |
≤ 3 | 15 (19) | 1 (5.3) | 14 (23.3) | |
Perineural invasion | ||||
Present | 51 (63.0) | 14 (73.7) | 37 (59.7) | 0.537 |
Absent | 30 (37.0) | 5 (26.3) | 25 (40.3) | |
Lymphovascular invasion | ||||
Present | 29 (35.8) | 12 (63.2) | 17 (27.4) |
0.006
|
Absent | 52 (64.2) | 7 (36.8) | 45 (72.6) | |
CRM | ||||
Positive, ≤ 1 mm | 39 (48.1) | 7 (36.8) | 32 (51.6) | 0.302 |
Negative, > 1 mm | 42 (51.9) | 12 (63.2) | 30 (48.4) |
Neoadjuvant Treatment Group
Factor | DFS | OS | ||
---|---|---|---|---|
HR (95% CI) | p value | HR (95% CI) | p value | |
Sex (male/female) | 0.6 (0.2–1.2) |
0.155
| 0.6 (0.3–1.3) | 0.227 |
Age | 0.7 (0.3–1.8) | 0.548 | 0.9 (0.4–2.0) | 0.805 |
Tumor length (≤ 3/> 3 cm) | 0.9 (0.9–1.0) | 0.291 | 1.0 (0.9–1.0) | 0.264 |
Localization (mid/distal) | 0.9 (0.6–1.3) | 0.721 | 0.9 (0.4–1.9) | 0.884 |
Histology (SCC/AC) | 0.7 (0.4–1.5) | 0.450 | 0.6 (0.7–1.3) | 0.238 |
pT stage (T3/T4) | 2.9 (1.0–8.3) |
0.047
| 4.0 (1.6–9.8) |
0.002
|
pN1-3 | 1.7 (1.2–2.4) |
0.002
| 1.5 (1.1–2.1) |
0.004
|
Differentiation grade (good/moderate vs. poor/signet cell/mucinous) | 0.8 (0.4–1.5) | 0.641 | 0.7 (0.4–1.4) | 0.367 |
Perineural growth (present/absent) | 1.3 (0.7–2.3) | 0.411 | 1.0 (0.6–1.8) | 0.937 |
Lymphovascular invasion (present/absent) | 1.1 (0.6–2.1) | 0.649 | 1.2 (0.7–2.1) | 0.491 |
CRM (positive/negative) | 2.4 (1.4–4.3) |
0.002
| 2.0 (1.2–3.4) |
0.012
|
EMVI (present/absent) | 1.4 (0.7–2.7) | 0.305 | 1.5 (0.8–2.7) | 0.236 |
EMVI/N (nodal status) | 1.8 (1.3–2.6) |
0.001
| 1.8 (1.3–2.6) |
< 0.001
|
EMVI −/N − | Ref. | Ref. | ||
EMVI +/N − | 1.8 (0.4–7.7) | 0.413 | 1.9 (0.4–8.0) | 0.377 |
EMVI −/N + | 3.6 (1.4–9.3) |
0.008
| 3.9 (1.5–9.9) |
0.005
|
EMVI +/N + | 6.1 (2.0–18.6) |
0.002
| 6.3 (2.1–18.3) |
0.001
|
Factor | DFS | OS | ||
---|---|---|---|---|
HR (95% CI) | p value | HR (95% CI) | p value | |
Sex | 1.0 (10.0–1.0) | 0.983 |
–
| |
pT stage (T3 vs. T4) | 2.1 (0.7–6.2) | 0.183 | 3.7 (1.5–9.2) |
0.006
|
pN1-3 | 0.9 (0.5–1.7) | 0.793 | 0.7 (0.4–1.3) | 0.210 |
CRM [positive/negative] | 2.4 (1.3–4.6) |
0.005
| 1.5 (0.9–2.7) | 0.156 |
EMVI/N (nodal status) | 1.8 (1.3–2.7) |
0.001
| 1.8 (1.3–2.6) |
< 0.001
|
EMVI −/N − | Ref. | Ref. | ||
EMVI +/N − | 2.5 (0.6–11.1) | 0.214 | 1.9 (0.5–8.2) | 0.364 |
EMVI −/N + | 3.0 (1.1–7.8) |
0.024
| 3.5 (1.3–9.1) |
0.010
|
EMVI +/N + | 7.0 (2.3–21.8) |
0.001
| 6.5 (2.2–19.1) |
0.001
|
Pathological characteristics | Total [N = 37] (100%) | EMVI-positive [N =8] (21.6%) | EMVI-negative [N = 29] (78.4%) | p value |
---|---|---|---|---|
Localization | ||||
Middle | 1 (2.7) | 0 (0) | 1 (3.4) | 0.784 |
Distal | 36 (97.3) | 8 (100) | 28 (96.6) | |
Histologic type | ||||
AC | 35 (94.6) | 7 (87.5) | 28 (96.6) | 0.390 |
SCC | 2 (5.4) | 1 (12.5) | 1 (3.4) | |
T stage | ||||
T3 | 37 (100) | 8 (100) | 29 (100) | – |
N stage | ||||
Present | 17 (45.9) | 4 (50) | 13 (44.8) | 0.553 |
Absent | 20 (54.1) | 4 (50) | 16 (55.2) | |
Differentiation grade | ||||
Well/moderated | 23 (62.2) | 5 (62.5) | 18 (62.1) | 0.657 |
Poor signet/mucinous | 14 (37.8) | 3 (37.5) | 11 (37.9) | |
Tumor length, cm | ||||
> 3 | 31 (83.8) | 7 (87.5) | 24 (82.8) | 0.613 |
≤ 3 | 6 (16.2) | 1 (3.5) | 5 (17.2) | |
Perineural invasion | ||||
Present | 15 (40.5) | 6 (75.0) | 9 (31.0) |
0.034
|
Absent | 22 (59.5) | 2 (25.0) | 20 (68.9) | |
Lymphovascular invasion | ||||
Present | 15 (40.5) | 6 (75.0) | 9 (31.0) |
0.034
|
Absent | 22 (59.5) | 2 (25.0) | 20 (68.9) | |
CRM | ||||
Positive ≤ 1 mm | 4 (10.8) | 1 (12.5) | 3 (10.3) | 0.640 |
Negative > 1 mm | 33 (89.2) | 7 (87.5) | 26 (89.6) | |
Mandard classification | ||||
TRG2/3 | 24 (64.9) | 4 (50) | 20 (68.9) | 0.278 |
TRG4/5 | 13 (35.1) | 4 (50) | 9 (31.0) |
Survival Analysis
Surgery-Alone Group
Neoadjuvant Treatment Group
Factor | DFS | OS | ||
---|---|---|---|---|
HR (95% CI) | p value | HR (95% CI) | p value | |
Sex (male/female) | 0.7 (0.2–3.1) | 0.653 | 0.8 (0.2–3.4) | 0.732 |
Age | 0.2 (0.0–1.5) |
0.120
| 0.4 (0.1–1.9) | 0.267 |
Tumor length (≤ 3/> 3 cm) | 1.1 (0.3–4.0) | 0.942 | 1.4 (0.4–4.9) | 0.568 |
Localization (mid/distal) | 0.5 (0.1–4.1) | 0.557 | 0.4 (0.0–2.8) | 0.327 |
Histology (SCC/AC) | 0.5 (0.1–4.0) | 0.544 | 0.6 (0.0–4.2) | 0.327 |
pN1-3 | 1.9 (0.8–4.6) |
0.157
| 2.0 (0.8–5.0) |
0.129
|
Differentiation grade (good/moderate vs. poor/signet cell/mucinous) | 1.0 (0.4–2.3) | 0.942 | 1.0 (0.4–2.5) | 0.966 |
Perineural growth (present/absent) | 1.1 (0.5–2.6) | 0.840 | 1.2 (0.5–3.0) | 0.656 |
Lymphovascular invasion (present/absent) | 1.1 (0.4–2.5) | 0.885 | 0.9 (0.4–2.3) | 0.879 |
CRM (positive/negative) | 2.3 (0.7–7.3) |
0.155
| 3.7 (1.1–12.4) |
0.034
|
EMVI (present/absent) | 1.1 (0.4–3.1) | 0.829 | 0.9 (0.3–2.9) | 0.955 |
EMVI/N (nodal status) | 1.3 (0.9–19) |
0.173
| 1.3 (0.9–2.0) |
0.174
|
EMVI −/N − | Ref. | Ref. | ||
EMVI +/N − | 0.9 (0.2–4.2) | 0.997 | 1.0 (0.2–4.9) | 0.961 |
EMVI −/N + | 1.8 (0.7–4.9) | 0.236 | 2.1 (0.8–5.7) |
0.148
|
EMVI +/N + | 2.1 (0.5–8.3) | 0.287 | 1.8 (0.4–9.1) | 0.463 |
Mandard classification TRG2/3/TRG4/5 | 1.4 (0.6–3.4) | 0.401 | 1.2 (0.5–3.0) | 0.667 |
Factor | DFS | OS | ||
---|---|---|---|---|
HR (95% CI) | p value | HR (95% CI) | p value | |
Age | 0.2 (0.0–1.5) | 0.120 | – | |
pN1-3 | 1.3 (0.9–2.0) | 0.174 | 1.6 (1.1–2.5) |
0.020
|
CRM (positive/negative) | 1.4 (0.4–5.3) | 0.572 | 2.1 (0.6–7.9) | 0.272 |
EMVI/N (nodal status) | 0.7 (0.3–1.9) | 0.524 | 0.7 (0.3–1.6) | 0.460 |
EMVI −/N − | Ref. | Ref. | ||
EMVI +/N − | 1.1 (0.2–5.4) | 0.888 | 1.0 (0.2–4.9) | 0.967 |
EMVI −/N + | 0.5 (0.1–3.9) | 0.512 | 0.3 (0.0–3.5) | 0.366 |
EMVI +/N + | 0.6 (0.1–5.4) | 0.692 | 0.3 (0.0–3.9) | 0.382 |