Background
Materials and methods
Patients
Laboratory and imaging examination
Treatment
Chemotherapy
Arterial chemoembolization
Surgical procedure
Neoadjuvant therapy adverse events and pathological response assessment
Statistical analysis
Results
Patient characteristics
Characteristic | Conventional group (n = 101) | Combined group (n = 102) | P | |
---|---|---|---|---|
Sex | 0.254 | |||
Male | 80 (79.2%) | 73 (71.6%) | ||
Female | 21 (20.8%) | 29 (28.4%) | ||
Age | Median (IQR, years) | 57 (50–65) | 61 (51-67.25) | 0.151 |
< 60 years | 59 (58.4%) | 49 (48%) | 0.16 | |
BMI | Median (IQR, kg/m2) | 21.64 (20.24–24.22) | 22.15 (20.48–24.22) | 0.637 |
Smoking | 59 (58.4%) | 60 (58.8%) | 1 | |
Drinking | 53 (52.5%) | 59 (57.8%) | 0.482 | |
Comorbidity | ||||
Hypertension | 14 (13.9%) | 16 (15.7%) | 0.844 | |
Coronary heart disease | 3 (3%) | 4 (3.9%) | 1 | |
Diabetes | 14 (13.9%) | 8 (7.8%) | 0.183 | |
Other | 15 (14.9%) | 12 (11.8%) | 0.542 | |
Family history | 4 (4%) | 7 (6.9%) | 0.537f | |
ASA | 0.622 | |||
1 | 2 (2%) | 1 (1%) | ||
2 | 63 (62.4%) | 56 (54.9%) | ||
3 | 35 (34.6%) | 44 (43.1%) | ||
4 | 1 (1%) | 1(1%) | ||
Pretreatment Hb (IQR, g/L) | 118 (86–133) | 125 (92–139) | 0.17 | |
Pretreatment neutrophils (IQR, *108) | 3.74 (3.09–4.76) | 3.72 (2.92–4.92) | 0.969 | |
Pretreatment lymphocyte (IQR, *108) | 1.37 (1.06–1.68) | 1.41 (1.13–1.73) | 0.574 | |
Pretreatment platelet (IQR, *108) | 243 (203–351) | 235 (181–307) | 0.235 | |
Pretreatment albumin (IQR, g/L) | 38 (34–41) | 31 (33–40) | 0.567 | |
Pretreatment CEA(>5.2 ng/ml) | 36 (35.6%) | 26 (25.5%) | 0.129 | |
Pretreatment CA19-9 (> 27 U/ml) | 34 (33.7%) | 29 (28.4%) | 0.451 | |
Tumor location | 0.766 | |||
Upper stomach | 35 (34.6%) | 36 (35.3%) | ||
Middle stomach | 22 (21.8%) | 26 (25.5%) | ||
Lower stomach | 44 (43.6%) | 40 (39.2%) | ||
Tumor size (IQR, cm) | 6 (5-7.7) | 5.57 (4.6–6.8) | 0.236 | |
Borrmann typing | 0.49 | |||
I | 26 (25.7%) | 34 (33.3%) | ||
II | 12 (11.9%) | 12 (11.8%) | ||
III | 51 (34.6%) | 49 (48%) | ||
IV | 12 (11.9%) | 7 (6.9%) | ||
Clinical T stage | 0.859 | |||
T3 | 24 (23.8%) | 27 (26.5%) | ||
T4a | 70 (69.3%) | 67 (65.7%) | ||
T4b | 7 (6.9%) | 8 (7.8%) | ||
Clinical N stage | 0.374 | |||
N0 | 11 (10.9%) | 17 (16.7%) | ||
N1 | 29 (28.7%) | 27 (26.5%) | ||
N2 | 42 (41.6%) | 46 (45.1%) | ||
N3 | 19 (18.8%) | 12 (11.8%) | ||
Clinical TNM stage | 0.825 | |||
IIa | 2 (2%) | 3 (2.9%) | ||
IIb | 16 (15.8%) | 22 (21.6%) | ||
IIIa | 31 (30.7%) | 30 (29.4%) | ||
IIIb | 35 (34.7%) | 33 (32.4%) | ||
IIIc | 17 (16.8%) | 14 (13.7%) | ||
Chemotherapy regimen | 0.152 | |||
NPOS | 56 (55.4%) | 67 (65.7%) | ||
DOS | 45 (44.6%) | 35 (34.3%) | ||
Number of neoadjuvant therapy cycles | 0.175 | |||
2 | 49 (48.5%) | 57 (55.9%) | ||
3 | 40 (39.6%) | 40 (39.2%) | ||
4 | 12 (11.9%) | 5(4.9%) | ||
Number of chemoembolization | ||||
1 | 91 (89.2%) | |||
2 | 11(10.8%) |
Neoadjuvant therapy adverse events
Grade (CTCAE v 4.0) | Conventional group (n = 101) | Combined group (n = 102) | |||||||
---|---|---|---|---|---|---|---|---|---|
Grade 1–2 | Grade 3 | Grade 4 | ≥Grade 3 | Grade 1–2 | Grade 3 | Grade 4 | ≥Grade 3 | ||
All adverse events | 60 (59.4%) | 16 (15.8%) | 3 (3%) | 17 (16.8%) * | 66 (64.7%) | 25 (24.5%) | 5 (4.9%) | 26(25.5%) * | |
Leukopenia | 26 (25.7%) | 1 (1%) | 1 (1%) | 2 (2%) | 25 (24.5%) | 4 (3.9%) | 4 (3.9%) | 8 (7.8%) | |
Neutropenia | 31 (30.7%) | 3 (3%) | 1 (1%) | 4 (4%) | 22 (21.6%) | 8 (7.8%) | 4 (3.9%) | 12 (11.8%) | |
Thrombocytopenia | 7 (6.9%) | 1 (1%) | 0 | 1 (1%) | 7 (6.86%) | 2 (2%) | 0 | 2 (2%) | |
Febrile neutropenia | 0 | 2 (2%) | 0 | 2 (2%) | 0 | 2 (2%) | 1 (1%) | 3 (2.9%) | |
Anemia | 13 (12.9%) | 9 (8.9%) | 0 | 9 (8.9%) | 19 (18.6%) | 6 (7.8%) | 1 (1%) | 7 (6.86%) | |
Nausea and vomiting | 16 (15.8%) | 4 (4%) | 0 | 4 (4%) | 29 (28.4%) | 3 (2.9%) | 0 | 3 (2.9%) | |
Anorexia | 11 (10.9%) | 0 | 0 | 0 | 19 (18.6%) | 1 (1%) | 0 | 1 (1%) | |
ALT or AST increased | 18 (17.8%) | 2 (2%) | 0 | 2 (2%) | 13 (12.7%) | 5 (4.9%) | 0 | 5 (4.9%) | |
Serum creatinine increased | 3 (3%) | 0 | 0 | 0 | 1 (1%) | 0 | 0 | 0 | |
Infection | 1 (1%) | 0 | 0 | 0 | 0 | 3 (2.9%) | 0 | 3 (2.9%) | |
Diarrhea | 3 (3%) | 3 (3%) | 0 | 3 (3%) | 1 (1%) | 0 | 0 | 0 | |
Other | 2 (2%) | 0 | 1 (1%) | 1 (1%) | 2 (2%) | 2 (2%) | 0 | 2 (2%) |
Details of surgery and postoperative clinical outcomes
Conventional group (n = 101) | Combined group (n = 102) | P | ||
---|---|---|---|---|
Surgical approach | 0.291 | |||
Laparoscopy | 93 (92.1%) | 99 (97.1%) | ||
Open | 3 (3%) | 1 (1%) | ||
Conversion to open | 5 (4.9%) | 2 (2%) | ||
Gastrectomy type | 0.261 | |||
Total gastrectomy | 51 (50.5%) | 60 (58.8%) | ||
Distal gastrectomy | 50 (49.5%) | 42 (41.2%) | ||
Combined resection | 8 (7.9%) | 5 (4.9%) | 0.407 | |
Residual tumor status | 1 | |||
R0 | 98 (97%) | 99 (97.1%) | ||
R1 | 3 (3%) | 3 (2.9%) | ||
Operation time (IQR, min) | 222 (175-267.5) | 200 (160–245) | 0.029 | |
Blood loss (IQR, ml) | 100 (50–200) | 75 (50-175.25) | 0.011 | |
Blood transfusion | 17 (16.8%) | 18 (17.6%) | 1 | |
Intraoperative complications | 3 (3%) | 3 (2.9%) | 1 | |
Time of liquid diet (IQR, day) | 7 (5–10) | 6 (5–8) | 0.006 | |
Postoperative hospital stays (IQR, day) | 11 (8–17) | 10 (8–13) | 0.012 | |
Reoperation | 4 (4%) | 5 (4.9%) | 1 | |
Readmission | 2 (2%) | 1 (1%) | 0.621 | |
Mortality | 1 (1%) | 1 (1%) | 1 |
Clavien–Dindo classification | Conventional group (n = 101) | Combined group (n = 102) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Grade I-II | Grade III | Grade IV | Grade V | ≥III grade | Grade I-II | Grade III | Grade IV | Grade V | ≥III grade | ||
Anastomotic leakage | 8 (7.9%) | 4 (4%) | 1 (1%) | 1 (1%) | 6 (5.9%) | 8 (7.8%) | 5 (4.9%) | 2 (2%) | 1 (1%) | 8 (7.9%) | |
Abdominal infection | 26 (25.7%) | 2 (2%) | 2 (2%) | 0 | 4 (4%) | 18 (17.6%) | 4 (3.9%) | 3 (2.9%) | 0 | 7 (6.9%) | |
Intestinal obstruction | 15 (14.9%) | 0 | 0 | 0 | 0 | 3 (2.9%) | 2 (2%) | 1 (1%) | 0 | 3 (2.9%) | |
Hemorrhage | 1 (1%) | 0 | 2 (2%) | 0 | 2 (2%) | 1 (1%) | 1 (1%) | 2 (2%) | 0 | 3 (2.9%) | |
Wound infection | 3 (3%) | 2 (2%) | 0 | 0 | 2 (2%) | 0 | 3 (2.9%) | 0 | 0 | 3 (2.9%) | |
Pulmonary infection | 23 (22.8%) | 2 (2%) | 0 | 0 | 2 (2%) | 21 (20.6%) | 3 (2.9%) | 1 (1%) | 0 | 4 (3.9%) | |
Cardiovascular events | 0 | 1 (1%) | 0 | 0 | 1 (2%) | 4 (3.9%) | 0 | 0 | 0 | 0 | |
Thrombotic events | 1 (1%) | 0 | 0 | 0 | 0 | 3 (2.9%) | 0 | 0 | 0 | 0 | |
Urinary tract infection | 3 (3%) | 0 | 0 | 0 | 0 | 4 (3.9%) | 0 | 0 | 0 | 0 | |
Any complication events | 44 (43.6%) | 9 (8.9%) | 3 (3%) | 1 (1%) | 10 (9.9%) | 38 (37.3%) | 11 (10.8%) | 4 (3.9%) | 1 (1%) | 13 (12.7%) |
Pathological characteristics
Conventional group (n = 101) | Combined group (n = 102) | P | ||
---|---|---|---|---|
Pathological Type | 0.314 | |||
Adenocarcinoma | 94 (93.1%) | 92 (90.2%) | ||
Mucinous | 7 (6.9%) | 10 (9.8%) | ||
Degree of differentiation | 0.661 | |||
Poorly/Mucinous | 49 (48.5%) | 54 (52.9%) | ||
Moderate | 51 (50.5%) | 46 (45.1%) | ||
Well | 1 (1%) | 2 (2%) | ||
T Stage | 0.03 | |||
ypT0 | 5 (5%) | 17 (16.7%) | ||
ypT1 | 7 (6.9%) | 9 (8.8%) | ||
ypT2 | 23 (12.9%) | 17 (16.7%) | ||
ypT3 | 54 (53.5%) | 42 (41.2%) | ||
ypT4 | 12 (11.9%) | 18 (17.6%) | ||
N Stage | 0.055 | |||
ypN0 | 38 (37.6%) | 57 (55.9%) | ||
ypN1 | 17 (16.8%) | 15 (14.7%) | ||
ypN2 | 26 (25.7%) | 15 (14.7%) | ||
ypN3 | 20 (19.8%) | 15 (14.7%) | ||
M Stage | 0.748 | |||
ypM0 | 97 (96%) | 96 (94.1%) | ||
ypM1 | 4 (4%) | 6 (5.9%) | ||
TRG | 0.028 | |||
Grade 0 | 5 (5%) | 17 (16.7%) | ||
Grade 1 | 18 (17.8%) | 23 (22.5%) | ||
Grade 2 | 56 (55.4%) | 46 (45.1%) | ||
Grade 3 | 22 (21.8%) | 16 (15.7%) | ||
T Downstage | 79 (78.2%) | 75 (73.5%) | 0.512 | |
N Downstage | 47 (46.5%) | 54 (52.9%) | 0.401 | |
Pathological Complete Response | 5 (5%) | 17 (16.7%) | 0.012 | |
Angiolymphatic invasion | 12 (11.9%) | 18 (17.6%) | 0.323 | |
Tumor deposit | 6 (5.9%) | 11 (10.8%) | 0.311 | |
HER2 positive | 13 (12.9%) | 9 (8.8%) | 0.376 |
Predictors of pCR to Neoadjuvant Therapy
Patient characteristics | Univariate Analysis | Multivariate Analysis | |||||
---|---|---|---|---|---|---|---|
OR | 95% CI | P | OR | 95% CI | P | ||
Gender | |||||||
Female | ref | ||||||
Male | 3.609 | 0.813–16.022 | 0.091 | 2.199 | 0.438–11.049 | 0.339 | |
Age | |||||||
<60 years | ref | ||||||
≥ 60 years | 1.744 | 0.71–4.284 | 0.225 | ||||
BMI | |||||||
<25 kg/m2 | ref | ||||||
≥ 25 kg/m2 | 1.966 | 0.71–5.445 | 0.194 | ||||
Tumor location | 0.988 | ||||||
Upper stomach | ref | ||||||
Middle stomach | 0.916 | 0.281–2.988 | 0.844 | ||||
Lower stomach | 0.945 | 0.344–2.593 | 0.913 | ||||
Tumor size | |||||||
<5.8 cm | ref | ||||||
≥5.8 cm | 0.824 | 0.339–2.004 | 0.67 | ||||
Pre-treatment NLR | |||||||
<2.86 | ref | ||||||
≥ 2.86 | 0.355 | 0.133–0.948 | 0.039 | 0.193 | 0.016–0.611 | 0.005 | |
Pre-treatment PLR | |||||||
<182 | ref | ||||||
≥ 182 | 0.137 | 0.039–0.478 | 0.002 | 0.077 | 0.018–0.333 | 0.001 | |
CEA | |||||||
<5.2ng/ml | ref | ||||||
≥ 5.2ng/ml | 1.628 | 0.657–4.035 | 0.292 | ||||
CA19-9 | |||||||
<27U/ml | ref | ||||||
≥ 27U/ml | 0.624 | 0.219–1.773 | 0.376 | ||||
Degree of differentiation | |||||||
poor/mucinous | ref | ||||||
moderate/well | 0.994 | 0.409–2.417 | 0.989 | ||||
HER-2 | |||||||
negative | ref | ||||||
positive | 2.756 | 0.352–21.561 | 0.334 | ||||
Clinical T stage | 0.907 | ||||||
T3 | ref | ||||||
T4a | 0.854 | 0.309–2.357 | 0.76 | ||||
T4b | 1.154 | 0.208–6.413 | 0.87 | ||||
Clinical N stage | 0.062 | 0.064 | |||||
N0 | ref | ref | |||||
N1 | 0.208 | 0.048–0.905 | 0.036 | 0.445 | 0.069–2.875 | 0.395 | |
N2 | 0.317 | 0.097–1.039 | 0.058 | 1.044 | 0.063–17.217 | 0.976 | |
N3 | 0.88 | 0.248–3.128 | 0.843 | 5.391 | 0.303–95.933 | 0.251 | |
Clinical TNM stage | |||||||
II | ref | ||||||
III | 0.42 | 0.163–1.078 | 0.071 | 0.306 | 0.025–3.74 | 0.354 | |
Chemotherapy regimen | |||||||
DOS | ref | ||||||
NPOS | 1.156 | 0.461–2.896 | 0.757 | ||||
Arterial chemoembolization | |||||||
No | ref | ||||||
Yes | 3.84 | 1.359–10.853 | 0.011 | 3.766 | 1.177–12.054 | 0.025 | |
Number of chemotherapy cycles | 0.531 | ||||||
2 | ref | ||||||
3 | 0.541 | 0.186–1.579 | 0.261 | ||||
4 | 0.806 | 0.215–3.024 | 0.749 |