Tumor response and prognosis after chemotherapy
Based on the RECIST, 24 and 69 patients had PD and non-PD, respectively. Accordingly, the disease control rate was 74.2% (69/93), while the median survival times of patients with PD and non-PD were 163 and 562 days, respectively (Fig. 1), the difference therein being statistically significant (p < 0.0001).
Conversion Surgery And Pathological Findings
Among the 93 patients included herein, 19 (20.4%) underwent gastrectomy with lymphadenectomy as conversion surgery after chemotherapy. Surgical and pathological findings are summarized in Table 2. Distal gastrectomy and total gastrectomy were performed in 3 and 16 patients, while D1+, D2, and D2 + lymphadenectomy was performed in 5, 12, and 2 patients, respectively. Although 18 patients achieved R0 resection, one developed occult metastasis identified during pathological examinations of the greater omentum. Moreover, nine, three, one, and six patients had a pathological nodal status of N0, N1, N2, and N3, respectively. Histological assessment revealed 15, 2, and 2 patients with grade 1a, 1b, and 2 tumor response, respectively, with no patient exhibiting grade 3 response.
Table 2
Surgical and pathological findings of patients undergoing conversion surgery (n = 19)
Factor | | n (%) |
Operative procedure | | |
Total gastrectomy | | 16 (84.2) |
Distal gastrectomy | | 3 (15.8) |
Lymph node dissection | | |
D1+ | | 5 (26.3) |
D2 | | 12 (63.2) |
D2+ | | 2 (10.5) |
Depth of tumor invasion | | |
pT1 | | |
pT2 | | 2 (10.5) |
pT3 | | 10 (52.6) |
pT4 | | 7 (36.8) |
Lymph node metastasis | | |
pN0 | | 9 (47.4) |
pN1 | | 3 (15.8) |
pN2 | | 1 (5.3) |
pN3 | | 6 (31.6) |
Residual tumor status | | |
R0 | | 18 (94.7) |
R1 | | 1 (5.3) |
R2 | | 0 (0.0) |
Histological response | | |
Grade 1a | | 15 (78.9) |
Grade 1b | | 2 (10.5) |
Grade 2 | | 2 (10.5) |
Grade 3 | | 0 |
Relationship Between Conversion Surgery And Clinicopathological Findings
The mean age (± standard deviation) of the 19 and 74 patients who underwent conversion surgery and chemotherapy alone was 57.6 ± 12.2 and 65.9 ± 11.5 years, respectively (Table 3). Accordingly, we determined that the presence or absence of conversion surgery was significantly correlated with age (p = 0.0134). Among the 37 patients receiving taxane-based chemotherapy, 12 (32.4%) underwent conversion surgery. On the other hand, among 56 patients receiving platinum-based chemotherapy, 7 (12.5%) underwent conversion surgery. Accordingly, we determined that conversion surgery was significantly associated with the first-line regimen (p = 0.0337) (Table 3). Furthermore, among the 69 patients with non-PD, 19 (27.5%) underwent conversion surgery. None of the patients who underwent conversion surgery had PD. Accordingly, we determined that conversion surgery was significantly correlated with tumor response (p = 0.0024) (Table 3).
Table 3
Relationship between conversion surgery and clinicopathological findings (n = 93)
| | Treatments (%) | | |
Factor | | Conversion surgery (n = 19) | | Chemotherapy alone (n = 74) | | p value |
Gender | | | | | | 0.7965 |
Male | | 12 (21.8) | | 43 (78.2) | | |
Female | | 7 (18.4) | | 31 (81.6) | | |
Age (years) | | 57.6 ± 12.2 | | 65.9 ± 11.5 | | 0.0134 |
Tumor location | | | | | | 0.7951 |
Whole/Upper | | 12 (22.2) | | 42 (77.8) | | |
Middle/Lower | | 7 (18.0) | | 32 (82.1) | | |
Macroscopic type | | | | | | 0.6083 |
Type non-T4 | | 11 (23.4) | | 36 (76.6) | | |
Type 4 | | 8 (17.4) | | 38 (82.6) | | |
Depth of tumor invasion | | | | | | 1.0000 |
cT3 | | 1 (20.0) | | 4 (80.0) | | |
cT4 | | 18 (20.5) | | 70 (79.6) | | |
Lymph node metastasis | | | | | | 0.0734 |
cN0-1 | | 12 (29.3) | | 29 (70.7) | | |
cN2-3 | | 7 (13.5) | | 45 (86.5) | | |
Number of distant metastatic sites | | | | | | 0.1799 |
1 (peritoneal dissemination alone) | | 18 (23.7) | | 58 (76.3) | | |
≥2 | | 1 (5.9) | | 16 (94.1) | | |
Histological type | | | | | | 1.0000 |
Differentiated | | 3 (20.0) | | 12 (80.0) | | |
Undifferentiated | | 16 (20.5) | | 62 (79.5) | | |
First-line chemotherapy regimen | | | | | | 0.0337 |
Platinum-based chemotherapy | | 7 (12.5) | | 49 (87.5) | | |
Taxane-based chemotherapy | | 12 (32.4) | | 25 (67.6) | | |
Tumor response to chemotherapy | | | | | | 0.0024 |
PD | | 0 (0.0) | | 24 (100.0) | | |
Non-PD | | 19 (27.5) | | 50 (72.5) | | |
PD progressive disease | | | | | | |
Prognostic Analysis In Both The Non-pd And Pd Groups
Among all included patients (n = 93), those who underwent conversion surgery and chemotherapy alone had a 3-year OS rate of 55.6% and 4.2%, respectively (p < 0.0001) (Fig. 2).
Univariate analysis indicated that lymph node metastasis status (N0-1 vs. N2-3), number of distant metastatic sites (1 vs. ≥2), tumor response, and conversion surgery were significantly correlated with survival among patients with non-PD and PD (p = 0.0156, p = 0.0081, p < 0.0001, and p < 0.0001, respectively) (Table 4). Multivariate analysis further identified the number of distant metastatic sites (1 vs. ≥2), tumor response, and conversion surgery as independent prognostic factors (p = 0.0092, p < 0.0001, and p < 0.0001, respectively) (Table 4).
Table 4
Univariate and multivariate analyses of survival in both the progressive and non-progressive disease groups (n = 93)
| | Univariate analysis | | Multivariate analysis |
Independent factor | | Hazard ratio | | 95% CI | | p value | | Hazard ratio | | 95% CI | | p value |
Gender | | | | | | 0.1585 | | | | | | |
Female | | 1.000 | | reference | | | | | | | | |
Male | | 1.384 | | 0.881–2.191 | | | | | | | | |
Age (years) | | | | | | 0.1306 | | | | | | |
<60 | | 1.000 | | reference | | | | | | | | |
≥60 | | 1.446 | | 0.899–2.395 | | | | | | | | |
Tumor location | | | | | | 0.3623 | | | | | | |
Whole/Upper | | 1.000 | | reference | | | | | | | | |
Middle/Lower | | 1.239 | | 0.777–1.954 | | | | | | | | |
Macroscopic type | | | | | | 0.3696 | | | | | | |
Type non-T4 | | 1.000 | | reference | | | | | | | | |
Type 4 | | 0.812 | | 0.516–1.284 | | | | | | | | |
Depth of tumor invasion | | | | | | 0.6592 | | | | | | |
cT3 | | 1.000 | | reference | | | | | | | | |
cT4 | | 1.248 | | 0.513–4.121 | | | | | | | | |
Lymph node metastasis | | | | | | 0.0156 | | | | | | 0.6698 |
cN0-1 | | 1.000 | | reference | | | | 1.000 | | reference | | |
cN2-3 | | 1.757 | | 1.112–2.811 | | | | 1.113 | | 0.681–1.836 | | |
Number of distant metastatic sites | | | | | | 0.0081 | | | | | | 0.0092 |
1 (peritoneal dissemination alone) | | 1.000 | | reference | | | | 1.000 | | reference | | |
≥2 | | 2.382 | | 1.269–4.238 | | | | 2.410 | | 1.258–4.403 | | |
Histological type | | | | | | 0.4435 | | | | | | |
Differentiated | | 1.000 | | reference | | | | | | | | |
Undifferentiated | | 1.291 | | 0.690–2.693 | | | | | | | | |
First-line chemotherapy regimen | | | | | | 0.8917 | | | | | | |
Platinum-based chemotherapy | | 1.000 | | reference | | | | | | | | |
Taxane-based chemotherapy | | 0.969 | | 0.610–1.528 | | | | | | | | |
Tumor response to chemotherapy | | | | | | < 0.0001 | | | | | | < 0.0001 |
Non-PD | | 1.000 | | reference | | | | 1.000 | | reference | | |
PD | | 5.793 | | 3.330–9.922 | | | | 4.559 | | 2.530–8.176 | | |
Conversion surgery | | | | | | < 0.0001 | | | | | | < 0.0001 |
Absence | | 1.000 | | reference | | | | 1.000 | | reference | | |
Presence | | 0.177 | | 0.082–0.347 | | | | 0.234 | | 0.105–0.482 | | |
CI confidence interval, PD progressive disease | | | | | | | | | | |
Prognostic Analysis In The Non-pd Group Alone
Among patients in the non-PD group (n = 69), those who underwent conversion surgery and chemotherapy alone had a 3-year OS rate of 55.6% and 6.6%, respectively (p < 0.0001) (Fig. 3).
Univariate analysis showed that lymph node metastasis status (N0-1 vs. N2-3), number of distant metastatic sites (1 vs. ≥2), histological type, and conversion surgery were significantly associated survival in the non-PD group (p = 0.0224, p = 0.0092, p = 0.0338, and p < 0.0001, respectively) (Table 5). Multivariate analysis further identified conversion surgery alone as a significant independent predictor of a favorable survival (p < 0.0001) (Table 5).
Table 5
Univariate and multivariate analyses of survival in the non-progressive disease group alone (n = 69)
| | Univariate analysis | | Multivariate analysis |
Independent factor | | Hazard ratio | | 95% CI | | p value | | Hazard ratio | | 95% CI | | p value |
Gender | | | | | | 0.5799 | | | | | | |
Female | | 1.000 | | reference | | | | | | | | |
Male | | 1.166 | | 0.674–2.006 | | | | | | | | |
Age (years) | | | | | | 0.7465 | | | | | | |
<60 | | 1.000 | | reference | | | | | | | | |
≥60 | | 1.095 | | 0.633–1.926 | | | | | | | | |
Tumor location | | | | | | 0.2725 | | | | | | |
Whole/Upper | | 1.000 | | reference | | | | | | | | |
Middle/Lower | | 1.366 | | 0.778–2.358 | | | | | | | | |
Macroscopic type | | | | | | 0.3455 | | | | | | |
Type non-T4 | | 1.000 | | reference | | | | | | | | |
Type 4 | | 0.768 | | 0.444–1.335 | | | | | | | | |
Depth of tumor invasion | | | | | | 0.3063 | | | | | | |
cT3 | | 1.000 | | reference | | | | | | | | |
cT4 | | 1.954 | | 0.599–12.023 | | | | | | | | |
Lymph node metastasis | | | | | | 0.0224 | | | | | | 0.0859 |
cN0-1 | | 1.000 | | reference | | | | 1.000 | | reference | | |
cN2-3 | | 1.888 | | 1.095–3.300 | | | | 1.637 | | 0.933–2.903 | | |
Number of distant metastatic sites | | | | | | 0.0092 | | | | | | 0.1086 |
1 (peritoneal dissemination alone) | | 1.000 | | reference | | | | 1.000 | | reference | | |
≥2 | | 2.953 | | 1.332–6.095 | | | | 1.932 | | 0.856–4.073 | | |
Histological type | | | | | | 0.0338 | | | | | | 0.0581 |
Differentiated | | 1.000 | | reference | | | | 1.000 | | reference | | |
Undifferentiated | | 2.656 | | 1.069–8.873 | | | | 2.454 | | 0.973–8.266 | | |
First-line chemotherapy regimen | | | | | | 0.3648 | | | | | | |
Platinum-based chemotherapy | | 1.000 | | reference | | | | | | | | |
Taxane-based chemotherapy | | 0.774 | | 0.440–1.345 | | | | | | | | |
Conversion surgery | | | | | | < 0.0001 | | | | | | < 0.0001 |
Absence | | 1.000 | | reference | | | | 1.000 | | reference | | |
Presence | | 0.212 | | 0.096–0.429 | | | | 0.243 | | 0.109–0.503 | | |
CI confidence interval, PD progressive disease | | | | | | | | | | |