Based on the inclusion and exclusion criteria, 598 patients were included in our study. Our study included 170 recurrent GC patients and 428 metastatic GC patients. The general characteristics including the kinds of chemotherapy regimen of all enrolled patients are listed in Table 1. The age and gender proportions and surgical and pathological factors of the patient population were similar to those observed in other studies .
There were 312 patients treated with the first line chemotherapy regimens, yet the GC in 188 patients remained in a development condition, and then those patients were treated with the second or/and third line chemotherapy regimens including FOLFIRI and docetaxel single agent. The cycles of chemotherapy used for our GC patients was 4.4±3.705(1-20). 286 patients (47.8%) failed to receive further chemotherapy after 1-2 cycles of chemotherapy treatment.
Follow-up and survival
Of the 598 GC patients, the median follow-up time was 11.60 months (range 0-76), and the median OS after chemotherapy was 12 months (95 % CI 11.221–12.779), with 1-, 3-, and 5-year OS rates of 45.40%, 3.80%, and 0.90 %, respectively.
The 598 patients were divided into the HBini≤ 80 g/L cohort and the HBini level > 80 g/L cohort. Our study included 40 patients in the HBini≤ 80 g/L cohort and 558 patients in the HBini level > 80 g/L cohort. The clinical features which have potential effects on GC patient OS and PFS were well matched between our two groups (Table 2).
For the HBini≤ 80 g/L cohort, the median OS was 10 months with 1-, 3-, and 5-year survival rates of 35.40%, 0%, and 0%, respectively, while in the HBini level > 80 g/L cohort, the median OS was 12 months with 1-, 3-, and 5-year survival rates of 46.10%, 4.10%, and 3.00%, respectively. The OS of the HBini≤ 80 g/L cohort was significantly worse than that of the HBini level > 80 g/L cohort (p=0.009, Figure 1A, Table 3).
Then, we compared the OS and PFS between the HBini≤ 80 g/L cohort and the cohort with HBini between 80 g/L and 110 g/L. Our results revealed that the HBini≤ 80 g/L cohort did not have a trend of worse OS and PFS than the mild anaemia cohort (Supplementary Table 1).
Kaplan-Meier analysis was also used to analyse the correlation between HBini level and PFS. Our results revealed that patients with HBini levels ≤ 80 g/L also had a trend toward a shortened median PFS (p=0.049, Figure 1B, Table 3). Interestingly, we also found that HBdec ≥30 g/L was associated with a significantly shortened median OS (p=0.039, Figure 1C), and a similar relationship was found with decreased median PFS (p=0.001, Figure 1D, Table 3).
Red blood cell (RBC) transfusion is an important treatment modality, while chemotherapy is beneficial for improving the prognosis of recurrent and metastatic GC patients. We analysed the different treatment modalities and clinicopathological parameters for the OS and PFS in our patients.
Using univariate analysis, we found that RBC transfusion was associated with neither median OS nor median PFS. The factors that significantly influenced OS were HBini level, HBini ≤80 g/L, metastatic sites ≥3, liver metastases, paclitaxel-based combination of three regimens, the number of chemotherapy cycles, treatment response, and HBdec ≥30 g/L (p<0.05). Additionally, HBini level, the lowest haemoglobin level, metastatic sites ≥3, liver metastases, bone metastases, number of chemotherapy cycles, chemotherapy including paclitaxel, treatment response and HBdec ≥30 g/L were significantly associated with PFS (p<0.05) (Table 4).
Multivariate analysis showed that HBini level ≤80 g/L (HR=1.879, 95% CI=1.301-2.767, p=0.001), liver metastases (HR=1.234, 95% CI=1.022-1.490, p=0.029), chemotherapy including paclitaxel (HR=1.225, 95% CI=1.013-1.481, p=0.036), treatment response (HR=1.457, 95% CI=1.173-1.808, p=0.001), and HBdec ≥30 g/L (HR=1.536, 95% CI=1.206 -1.957, p=0.001) were significant adverse prognosis factors of OS. More importantly, the number of chemotherapy cycles was also significantly correlated with improved OS (HR=0.879, 95% CI=0.855-0.904, p <0.001) (Table 5).
For PFS, HBini level ≤80 g/L (HR=1.516, 95% CI=1.082-2.126, p=0.016), chemotherapy including paclitaxel (HR=1.273, 95% CI=1.068-1.517, p=0.007), treatment response (HR=2.235, 95% CI=1.818-2.747, p<0.001), the number of chemotherapy cycles (HR=0.922, 95% CI=0.899-0.945, p<0.001), and HBdec ≥30 g/L (HR=1.543, 95% CI=1.233-1.932, p<0.001) were independent prognostic factors (Table 5).
To further determined the reason why chemotherapy including paclitaxel could influence the prognosis in our cohort patients, we analyzed the difference of clinical characteristics between patients who received chemotherapy including paclitaxel and and those who did not. Our results revealed that the the patients who received chemotherapy including paclitaxel were older than those who did not receive paclitaxel including chemotherapy in our cohort (Figure 2) .
Relationship between the degree of decrease in haemoglobin levels and the clinicopathological parameters of our patients
We then investigated whether we could identify correlations between the degree of decrease in haemoglobin levels and the clinicopathological parameters of our GC patients. Our results suggested that bone metastases, chemotherapy including platinum, the number of chemotherapy cycles, and treatment response were associated with the degree of haemoglobin decrease (p<0.05) (Table 6). Multivariate analyses revealed that the degree of HBdec were significantly correlated with the number of chemotherapy cycles and chemotherapy including platinum (p<0.001 and p=0.019, respectively), and was not relevant with chemotherapy included paclitaxel (Table 7).
Chemotherapy drugs can not only kill cancer cells, but also damage healthy cells, which causes side effects. Our results revealed that the most common side effects of chemotherapy were myelosuppression, diarrhea and vomiting, yet which could not influence the OS and PFS in our cohort (Table 8).