| 【Background】Currently,the fourth most common malignant tumour in China is primary liver cancer,of which,90% of cases are hepatocellular carcinoma,and it is also the second most common cause of death from tumours in China,posing a great threat to the health of our people.Unlike Western countries,most of the patients suffering from primary liver cancer in China are infected with the hepatitis B virus and have further developed into cirrhosis.Most of the patients have already developed into middle to late stage liver cancer by the time they are diagnosed with the disease,which is more serious and has a poor prognosis,while the five-year survival rate for large liver cancer,or even giant liver cancer(tumour diameter >10cm),is even below 10%.Large liver cancers have a high recurrence rate after surgery,which affects the overall survival of patients.At present,in addition to sorafenib,the first-line drug recommended by national guidelines,the combination of other molecularly targeted drugs and immune checkpoint inhibitors,such as lenvatinib in combination with the PD1 monoclonal antibody Keytruda,has also made progress in the treatment of advanced hepatocellular carcinoma,but the treatment related to the prevention of recurrence of liver cancer after surgery is less effective,and the treatment with immune checkpoint inhibitors is expensive.In contrast,the effectiveness and safety of the FOLFOX4 regimen of chemotherapy in the treatment of hepatocellular carcinoma has been proven.While sorafenib is the first-line drug for the treatment of liver cancer,targeted drug therapy is not effective in controlling tumours and needs to be combined with other methods and drugs to achieve satisfactory results.To this end,this study investigated the efficacy of FOLFOX4 chemotherapy combined with sorafenib in patients with hepatocellular carcinoma(CNLC stage IIa,tumour maximal diameter >5cm)after surgery,chemotherapy with FOLFOX4 alone,and no chemotherapy or targeted therapy in patients with hepatocellular carcinoma(CNLC stage IIa,tumour maximal diameter >5cm)by collecting data and following up according to inclusion and exclusion criteria.This study was conducted to investigate the efficacy of FOLFOX4 chemotherapy in combination with sorafenib in patients with hepatocellular carcinoma(CNLC stage IIa,tumour maximum diameter >5cm)in the post-operative period.【Objective】To analysis the postoperative efficacy of FOLFOX4 case chemotherapy in combination with sorafenib in patients with hepatocellular carcinoma(CNLC stage IIa,tumour maximal diameter >5cm).【Methods】In this study,clinical data including gender,age,preoperative AFP,preoperative AST,MVI and tumour size were collected from patients with hepatocellular carcinoma and patients who met the inclusion criteria were divided into the following three groups:(1)FOLFOX4 + sorafenib treatment group(n=33 cases),radical hepatectomy followed by FOLFOX4 chemotherapy combined with sorafenib targeted therapy(2)FOLFOX4 chemotherapy alone group(n=31 cases),radical hepatectomy followed by FOLFOX4 chemotherapy(3)Control group(n=28 cases),radical hepatectomy followed by no chemotherapy and targeted therapy.Patients were followed up by telephone contact or outpatient clinics,and detailed records of recurrence and survival were kept,such as the time of recurrence,treatment modality and postoperative pathological results.Using SPSS 23.0 statistical software,a one-way analysis of relevant risk factors was performed using the Kaplan-Meier(Log-rank)method,and the statistically significant factors analysed were further analysed using a Cox regression model.Statistical tumour-free survival and overall survival,tumour-free survival and overall survival were analysed using Kaplan-Meier(Log-rank)analysis.【Results】1.Age,gender,HBs Ag,AST,AFP,surgical bleeding and the presence of microvascular invasion were tested by chi-square test in the three different postoperative treatment groups,and the differences were not statistically significant(P > 0.05).2.The one-way Kaplan-Meier(Log-rank)method and multi-factor Cox regression model analysis suggested that the risk factors affecting the postoperative survival time and tumour-free survival time of patients with hepatocellular carcinoma were microvascular invasion and different treatment groups.3.The median tumour-free survival time in the surgery alone group was 21.0months(95% CI: 13.1-28.9 months);the median tumour-free survival time in the FOLFOX4 group was 28.0 months(95% CI: 22.0-34.0 months);and the median tumour-free survival time in the FOLFOX4+sorafenib group was 30.0 months(95%CI: 25.8-34.2 months);the difference in median tumour-free survival time between the three subgroups mentioned above was statistically different(c~2 = 10.554,P<0.05).There was no statistically significant difference between the surgery-only group and the FOLFOX4 group(P>0.05),a statistically significant difference between the surgery-only group and the FOLFOX4+sorafenib group(P<0.05),and no statistically significant difference between the FOLFOX4 group and the FOLFOX4+sorafenib group(P>0.05).4.Survival rates at 1,3 and 5 years after surgery alone: 74.3%,36.0% and 7.9%,with a median survival time of 29.0 months(95% CI: 18.5 to 39.5 months);survival rates at 1,3 and 5 years after surgery in the FOLFOX4 group: 86.7%,45.8% and22.0%,with a median survival time of 37.0 months(95% CI: 21.4 to 52.6 months);survival rates at 1,3 and 5 years after surgery in the FOLFOX4 + sorafenib group:90.8 %,67.7% and 33.7%,with a median survival time of 21.4 to 52.6 months.In the FOLFOX4+sorafenib group,survival rates at 1,3 and 5 years were 90.8 %,67.7 %and 33.7 %,with a median survival time of 44.0 months(95 % CI: 35.9-52.1 months);the overall postoperative survival times of the three groups were statistically different(c~2= 7.631,P < 0.05).There was no statistically significant difference between the surgery-only group and the FOLFOX4 group(P>0.05),a statistically significant difference between the surgery-only group and the FOLFOX4+sorafenib group(P<0.05),and no statistically significant difference between the FOLFOX4 group and the FOLFOX4+sorafenib group(P>0.05).5.Among MVI-positive patients,the median tumour-free survival time was 13.0months(95% CI: 6.6-19.3 months)in the surgery alone group,19.0 months(95% CI:17.3-20.6 months)in the FOLFOX4 group and 24.0 months(95% CI: 3.6-44.3months)in the FOLFOX4+sorafenib group.: 3.6 to 44.3 months);the difference in median tumour-free survival time between the three subgroups mentioned above was statistically different(c~2 = 9.830,p < 0.05).Among them,there was a statistically significant difference between the surgery alone group and the FOLFOX4 group(P<0.05),a statistically significant difference between the surgery alone group and the FOLFOX4+sorafenib group(P<0.05),and no statistically significant difference between the FOLFOX4 group and the FOLFOX4+sorafenib group(P>0.05).Survival rates at 1,3 and 5 years in the surgery alone group: 60.0%,13.3% and 0.0%,with a median overall survival time of 22.0 months(95% CI: 9.4 to 34.6 months);survival rates at 1,3 and 5 years in the FOLFOX4 group: 81.3%,38.6% and 14.5%,with a median overall survival time of 28.0 months(95% CI: 0.0 to 56.9 months);in the FOLFOX4+sorafenib group,the 1-,3-and 5-year survival rates were 83.0%,48.0%and 24.0%,with a median overall survival time of 37.0 months(95% CI: 9.9-64.0months);the difference in median tumour-free survival time between the above three subgroups was statistically significant(c~2=7.734.P < 0.05).There was a statistically significant difference between the surgery alone group and the FOLFOX4 group(P<0.05),between the surgery alone group and the FOLFOX4+sorafenib group(P<0.05),and no statistically significant difference between the FOLFOX4 group and the FOLFOX4+sorafenib group(P>0.05).6.Among MVI-negative patients,the median tumour-free survival time was27.0 months(95% CI: 6.8 to 47.2 months)in the surgery alone group;30.0 months(95% CI: 26.9 to 33.1 months)in the FOLFOX4 group;and 33.0 months(95% CI:29.5 to 36.5 months)in the FOLFOX4 + sorafenib group.29.5 to 36.5 months);the difference in median tumour-free survival time between the above three subgroups was not statistically different(c~2=1.888,p>0.05).The 1-,3-and 5-year survival rates in the surgery alone group were 83.9%,45.0% and 15.0%,with a median overall survival time of 39.0 months(95% CI: 32.0 to 46.0 months);the 1-,3-and 5-year survival rates in the FOLFOX4 group were 85.7%,43.7% and 29.1%,with a median overall survival time of 37.0 months(95% CI: 30.5 to 43.5 months);in the FOLFOX4+sorafenib group,the 1-,3-and 5-year survival rates were 86.7%,80.0%and 32.0%,with a median overall survival time of 44.0 months(95% CI: 33.8-54.1months);the difference in median overall survival time between the three subgroups mentioned above was not statistically different(c~2=1.071.P>0.05).7.The incidence of abdominal pain and diarrhea,skin rash and skin reactions on hands and feet were significantly higher in the FOLFOX4+Sorafenib group than in the control group,and the difference was statistically significant(P﹤0.05),while the difference was not statistically significant(P﹥0.05)when comparing the incidence of nausea and vomiting,fatigue and poor circulation,fever and leukopenia in the two groups.The adverse effects in both groups resolved after symptomatic treatment.【Conclusions】1.Prophylactic postoperative treatment with FOLFOX4 combined with sorafenib in patients with hepatocellular carcinoma(CNLC stage IIa,tumour maximal diameter >5cm)improved patients’ tumour-free survival time and overall survival time after surgery.2、Patients with MVI-positive hepatocellular carcinoma(CNLC stage IIa,maximum tumour diameter >5cm)treated prophylactically with FOLFOX4 combined with sorafenib or FOLFOX4 after surgery can improve patients’ tumour-free survival time and overall survival time after surgery.3.Both the FOLFOX4+Sorafenib regimen and the FOLFOX4 regimen have a higher safety profile,and the FOLFOX4+Sorafenib regimen has more severe adverse effects compared to the FOLFOX4 regimen,which can resolve with symptomatic treatment.4.Microvascular invasion was an independent risk factor affecting tumour-free survival time and overall survival time after surgery in patients with hepatocellular carcinoma. |
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