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Blockbuster! Chemotherapeutic peritoneal heat perfusion can prolong the life of patients with advanced ovarian cancer by one yea

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  Based on the secondary analysis of GOG172 and GOG172 trials in the United States gynecological tumor group(GOG),the researchers found that the survival benefits of intraperitoneal chemotherapy for advanced ovarian cancer patients could last for at least 10 years.With each additional dose of intraperitoneal chemotherapy,the risk of death from ovarian cancer was reduced by 12 percent,especially in patients undergoing satisfactory cellulectomy.
  Based on the results of this study,the guidelines of NCCN,FIGO and ESMO have all considered abdominal chemotherapy as one of the first-line treatment options for patients with advanced ovarian cancer who have received satisfactory tumor cell inactivation.
  Ovarian cancer cell inactivation(CDS):surgical treatment of advanced ovarian cancer,the removal of tumor tissue as far as possible,so that the maximum residual lesion diameter does not exceed 2cm,in order to facilitate the postoperative chemotherapy to achieve long-term remission or even radical treatment.
  The scope of surgery includes total hysterectomy,bilateral adnexa,appendix,greater omentum and other resectable metastatic lesions,and even partial resection of the bladder and intestine.
  Heat peritoneal perfusion chemotherapy(HIPEC):by in vivo implantation chemotherapy pump in advance or abdominal puncture methods will constant temperature 45℃~42 liquid rapidly into the abdominal cavity chemotherapy and then charged changes position make chemotherapy liquid evenly distributed,the essence of HIPEC is perfusion in precision constant temperature,cycle,on the basis of full abdomen intraperitoneal chemotherapy.
  HIPEC realizes accurate temperature control of intraperitoneal heat chemotherapy through a set of precise intraperitoneal perfusion treatment system,so as to prevent and treat implantation metastasis of abdominal malignant tumors.HIPEC has unique advantages in the treatment of gastric cancer,colorectal cancer,peritoneal pseudomyxoma and other tumor peritoneal metastasis and the control of malignant peritoneal effusion.
  HIPEC's main mechanism of action is as follows:
  The physical action of heat itself can directly kill tumor cells;
  Peritoneal heat perfusion can increase the permeability of tumor cells to chemotherapy drugs.
  Peritoneal heat perfusion chemotherapy can inhibit the repair and proliferation of tumor cell injury.
  A large number of small sample clinical trials have proved that peritoneal thermal perfusion chemotherapy can improve the overall survival rate of patients with initial and recurrent ovarian cancer compared with intravenous chemotherapy.For recurrent ovarian cancer,the median survival and three-year survival rates of patients receiving intravenous chemotherapy after peritoneal thermal perfusion were higher than those of patients receiving intravenous chemotherapy alone,and the difference was statistically significant(figure 1 and figure 2).
  Figure 1 comparison of the median survival of peritoneal heat perfusion chemotherapy and intravenous chemotherapy for ovarian cancer
  Figure 2 comparison of progression-free survival between intravenous chemotherapy and peritoneal heat perfusion chemotherapy for ovarian cancer
  Although these studies confirm that patients with advanced ovarian cancer can benefit from HIPEC treatment,the quality of these evidences is not high,and most of them are single-center studies with small samples or retrospective studies.Therefore,higher evidence should be verified from HIPEC treatment of advanced ovarian cancer in a large sample,multi-center,randomized controlled clinical trial.
  The first multicenter,randomized,controlled clinical trial of HIPEC for stage III ovarian cancer was reported in the New England journal of medicine on January 18,2018,aiming to explore whether intraperitoneal thermal perfusion chemotherapy combined with cell inactivation could improve the survival of stage III ovarian cancer patients.
  The trial 8 centers in two European countries into the group of 245 patients,according to 1:1 were randomly assigned to the experimental group and the control group,the cells to destroy the loss combined cisplatin chemotherapy group,122 people,not combined cisplatin chemotherapy group,123 people,these patients before after 3 cycles of carboplatin and paclitaxel to at least stable disease,study is the primary end point relapse-free survival,key secondary end point was overall survival and side effects.
  Figure 3.KM curve of survival time without recurrence between HIPEC test group and control group
  The results showed that compared with the operation group alone,the median relapse-free survival time(FIG.3)and the median total survival time(FIG.4)in the operation+HIPEC group were 14.2 months and 45.7 months,respectively,while those in the operation group were 10.7 months and 33.9 months,respectively,which were 3.5 months and 11.8 months longer,respectively.
  There were no statistically significant differences in treatment-related side effects and quality of life between the two groups.The proportion of patients with grade 3 or above adverse events was similar,and more than 90%of the patients completed the entire treatment program.These findings suggest that HIPEC treatment is more acceptable than the regimen recommended in GOG 172 study.The analysis results of each subgroup showed that the operation+HIPEC group was superior to the operation group(figure 5).
  Figure 4.KM curve of the median survival time of HIPEC in ovarian cancer patients in the experimental group and the control group
  Figure 5 analysis results of each subgroup of ovarian cancer HIPEC test group and control group
  In this study,postoperative HIPEC therapy significantly extended the total survival time of patients,but did not show a significant advantage in the median relapse-free survival.The reasons may include:
  Few cases were enrolled in this experiment.
  HIPEC treatment temperature on the low side(40℃),and now is generally accepted that 43℃is the best temperature play HIPEC thermal effect to kill tumor cells;
  Cisplatin single drug HIPEC has limited therapeutic efficacy.
  Based on the results of a 2016 comparative study on the efficacy of paclitaxel/cisplatin HIPEC for ovarian cancer,cisplatin combined with paclitaxel HIPEC may achieve better efficacy and survival.Due to the poor prognosis of the patients enrolled in this study and the inability to directly receive CDS for stage III ovarian cancer patients,all patients received 3 cycles of preoperative chemotherapy with paclitaxel plus carboplatin,which made the satisfactory tumor reduction completion rate of the two groups as high as 97%.
  Combined with the results of two other clinical studies of neoadjuvant chemotherapy,this trial further established the important role of neoadjuvant chemotherapy in advanced ovarian cancer(with heavy tumor load).
  Evidence in the class of the test results as I HIPEC late treatment can prolong relapse-free survival and overall survival in patients with ovarian cancer,but there is less sample size,HIPEC temperature is low and is not used in combination with chemotherapy drugs,so more center,a larger sample size,more accurate control moderate HIPEC when using platinum and paclitaxel combination chemotherapy clinical research plan will become clear HIPEC in advanced ovarian cancer clinical application value of important ways,will rewrite the ovarian cancer clinical guidelines.