Intraoperative Hyperthermic Intraperitoneal Chemotherapy After Cytoreductive Surgery In Ovarian Cancer:a Meta-analysis

Background and purposeEpithelial ovarian cancer(EOC)is the most common ovarian malignancy,and it is also the leading cause of death from gynecological cancer.Due to the lack of clinical signs and the absence of effective early diagnostic tests that can be applied in the population,nearly 70–80% of patients are diagnosed in advanced stages,when peritoneal carcinomatosis or distance metastasis are established.The standard first-line treatment for advanced ovarian cancer includes optimal cytoreductive surgery(CRS)and systemic chemotherapy based on platinums.However in patients with complete cytoreduction the recurrence rate is high,which leads to a very low survival rate in patients with ovarian cancer,especially for patients who have been associated with peritoneal cancer at the time of initial diagnosis.Delaying the progression of the disease,extending the overall survival period,and determining the best treatment plan while maintaining the patient’s quality of life are the main goals of gynecologic oncologists.The natural history of ovarian cancer is mostly confined to the abdominal cavity,this feature provides the possibility and basis for local drug usein the abdominal cavity.In the past decades a new treatment method has become increasingly popular in the treatment of malignant tumors associated with peritoneal dissemination,namely intraoperative hyperthermic intraperitoneal chemotherapy after cytoreductive surgery.This combination therapy has both The surgical advantage of resection of visible foci,but also through the cooperation of a large number of perfusive mechanical flushing,hyperthermia,thermal effects and chemotherapeutic co-regional thermochemotherapy to effectively eliminate and remove residual cancer cells and micrometastases in the abdominal cavity and pelvic cavity.This study intends to combine the effects of CRS and HIPEC on the survival time of advanced stages and recurrent EOC and the incidence of related adverse events,and analyze the effectiveness and safety of the results,to provide a feasible reference for the treatment and later large-scale clinical trials.Materials and methodsFirstly,study inclusion and exclusion criteria were established.Patients in the trial group were treated with CRS combined with intraoperative HIPEC and supplemented with systemic intravenous chemotherapy.The control group was treated with cytoreductive surgery and intravenous chemotherapy alone.The type of study was a clinical controlled trial.PubMed,EMbase,The Cochrane Library,MEDLINE online database,China Biomedical Document Service System(CBM),Wanfang Database,and journals of related disciplines were searched,aiming to retrieve all clinical controlled trials about intraoperative HIPEC versus conventional CRS and intravenous chemotherapy.The languages were limited to Chinese and English(The final search was current to January 2018).We read and select relevant studies according to inclusion and exclusion criteria.The data information were extracted and collected basing on the use of data extraction tables.We used the Cochrane systematic review manual bias risk assessment tool and the NOS scale to evaluate the quality of RCTs and case-control trials retrospectivly.Outcomes were survival,OS,PFS,and SAE.The RevMan 5.3 software was used to select the corresponding effect model to calculate the HR or OR value based on theheterogeneity among the selected studies.ResultsA total of 10 studies including 849 patients were recruited into this Meta-analysis,all of which were high quality literature.Among them,5 studies included patients with stage III epithelial ovarian cancer,4 5 studies included patients with recurrent ovarian cancer,1 had both.The combined effect of meta-analysis was as follows:1.Survival rate in each year: In contrast to conventional cytoreductive surgery and postoperative intravenous chemotherapy,the HIPEC group improved the 1-year survival rate of patients with ovarian cancer(OR=2.52,95%CI 1.59~4.00),and this survival The benefits lasted for 2,3,4,and 5 years(OR=1.94,95%CI 1.40 ~2.70;OR=3.35,95%CI 1.93 ~6.53;OR=2.00,95%CI 1.39 ~2.89;OR=2.29,95 %CI 1.35 ~3.89),the differences were statistically significant(P <0.05).2.Overall survival: The HIPEC group can prolong the overall survival of patients with ovarian cancer.(HR=0.63,95%CI 0.50 ~0.79),subgroup analysis showed that CRS combined with intraoperative HIPEC can prolong the overall survival of patients with stage III ovarian cancer(HR=0.70,95%CI 0.55 ~ 0.90)and recurrent ovarian cancer The overall survival period was(HR=0.44,95%CI 0.23 ~0.86).(P<0.05).3.Progression-free survival: The HIPEC group can prolong the progression-free survival of patients with ovarian cancer(HR=0.62,95% CI 0.49~0.78)(P<0.05).4.Serious adverse events: There was no significant difference in the incidence of intestinal perforation,intestinal obstruction,and sepsis between the hyperthermic intraperitoneal chemotherapy group and the control group(P>0.05).Conclusions1.Intraoperative hyperthermic intraperitoneal chemotherapy improve the long-term survival of patients with epithelial ovarian cancer compared to traditionaltreatment.2.Intraoperative hyperthermic intraperitoneal chemotherapy can reduce the risk of progression and recurrence of of epithelial ovarian cancer compared with traditional standard therapy.3.Intraoperative hyperthermic intraperitoneal chemotherapy did not increase the incidence of intestinal perforation,intestinal obstruction,and sepsis and seems have relatively high security.