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61'2'3 Shelekhov A.V., 123Dvomichenko V. V.,13 Rasulov R. I., 1Radostev S. I., Morikov D.D.,1 Zakharov A. G., Medvednikov A. A.,1,3 Ushakova I. V.
1State Budgetary Institution of Health Care " Regional Oncological Hospital" Chief medical officer Professor Victoria Dvornichenko V.
2Irkutsk state medical University Department of Oncology and radiation therapy Head of the Department doctor of medical Sciences, Professor Viktoriia Dvornichenko 3Irkutsk state medical Academy ofpostgraduate education head of the Department doctor of medical Sciences, Professor Viktoriia Dvornichenko
COMPARATIVE ANALYSIS OF CYTOREDUCTIVE OPERATIONS IN OVARIAN CANCER 3C
STAGE.
Relevance of the problem:
Ovarian cancer occupies the 5th place in the structure of cancer mortality in women, and the mortality rate of patients with ovarian cancer in the first year after diagnosis is 35%. The incidence of ovarian cancer increased from 56.9 cases per 100,000 population in 2003 to 74.6 in 2017 [1] in Russia. In 75% of cases, the disease is diagnosed at stage III-IV in young patients. Standard surgical treatment of ovarian cancer is commonly understood as the following operational scope: the extirpation of the uterus with appendages and omentektomiya (which in practice is performed in the amount of resection of the greater omentum, para-aortic and pelvic lymph node dissection, combined with multifocal biopsy of the peritoneum [2]. This surgical volume is indicated in I-II stages of the disease, but in most patients at the time of diagnosis, stage III of the disease is noted, where extirpation of the uterus and resection of the greater omentum can not be an adequate surgical option. An increasing number of oncological surgeons are inclined to choose the maximum possible cytoreductive intervention, with the removal of all visually defined foci of tumor screening [3], which qualitatively affects the overall life expectancy and relapse-free survival [4].
The aim of the work: introduction to the practice of Irkutsk Regional Oncology Hospital the application of cytoreductive surgery for ovarian cancer stage 3C.
Material and methods: present study is prospective in nature, made on the basis of Irkutsk Regional Oncology Hospital, the operation period of 2013 — 2018. The study included 85 patients diagnosed with stage 3 ovarian cancer.
All patients before the treatment stage were examined by standard organs and systems, including verification of malignant process.
The following regimen was used as neoadjuvant and adjuvant chemotherapy regimen: Docetaxel 75 mg/ m2 /1 hour per 1 day, cisplatin 75 mg / m2/ 2 hours per 1 day every 3 weeks.
In addition to the use of standard and combined surgical procedures, we applied the procedure of hyperthermic intraperitoneal chemotherapy (HIPEC).
The procedure HIPEC was carried out on the apparatus of the Performer HT® [RAND, Medolla (MO), Italy].
The temperature conditions at the procedure of HIPEC ranged from 40,50 to 42,50 C according to the sensor installed in the abdominal cavity. Drugs of
choice were justified by a number of studies [5,6]. We used the drug Cisplatin from a dosage of 75 mg / m2 [7].
The method of the procedure was selection of the optimal volume of lavage fluid, as well as selection and calculation of the dosage of the chemotherapy drug [5]. Then, after the implementation of the surgical volume, the drainage systems were set up: 2 drainage along the diaphragmatic surface (installed on the solution supply) and 2 drains in the small pelvis (installed on aspiration). The temperature probes were placed on the inlet and outlet of the drainage system, 1 sensor was installed in the abdominal cavity, and 1 sensor was installed in the esophagus. After reaching the required temperature of the liquid (of the order of 41.5 - 42 0C) began the process of filling the abdomen and holding the circulation of the solution before reaching the phase of "plateau". Approximately this period of time varies within 15-30 minutes depending on the growth-weight indicators. An additional point of the intraoperative benefit is the additional heating of the patient with an air gun at a temperature of 450 ° C. After reaching the desired temperature, the necessary dosage of the chemotherapy drug was introduced into the circulating medium. The course of the working procedure in all cases was 90 min, the flow rate ranged from 1000-1500 ml / min. After the procedure circulation, sampling was performed of the solution from the cavity of the abdomen without further rinsing with sterile solutions. Drains were installed for discharge, the average term of their setting was 4-6 days.
After a comprehensive treatment, all patients undergo follow-up with mandatory control of the level of tumor markers in the dynamics, the implementation of the entire volume of the necessary diagnostic procedures. The first control examination in patients is carried out 4 weeks after the end of adjuvant chemotherapy. In the future, the multiplicity of the examination is 3 months during the first year after treatment, and the next two years 1 every 4 months.
The calculation of the parameters of the effectiveness of the proposed treatment methods was performed in accordance with the requirements of the CONSORT (Consolidated Standards of Reporting Trials). Survival of patients in clinical groups was calculated by Kaplan-Meier method.
Result of work:
Patients included in the study were divided into 2 groups.
Control group (CG): patients diagnosed with ovarian cancer stage III-53 people, where the first stage was performed 3 courses of neoadjuvant chemotherapy; then surgery was performed in the volume of extirpation of the uterus with appendages, resection of the greater omentum. Then, in the same scheme in the postoperative period, adjuvant chemotherapy was carried out in the amount of 3 courses. This group recruited over the period 2013-2018. This treatment strategy up to 2016 was the main.
The basic group ( BG) were patients diagnosed with ovarian cancer stage III (n = 32), where the mandatory component of the operation was cytoreductive intervention, including not only extirpation of the uterus with appendages, omentectomy, but also removal of parts of the organs involved in the tumor process. This group was recruited for the period 20162018.
BG was subdivided into the basic group 1 (BG 1), 18 patients who underwent only cytoreductive surgery (CS), after 3 courses of neoadjuvant chemotherapy; then surgery was performed; then, according to the same scheme, in the postoperative period, adjuvant chemotherapy was carried out in the amount of 3 courses.
The basic group 2 (BG 2) - patients diagnosed with ovarian cancer stage III, 14 people who first
stage performed cytoreductive surgery with HIPEC technology, then in the postoperative period 6 courses of adjuvant chemotherapy.
All patients of the basic group underwent diagnostic laparoscopy with mandatory calculation of peritoneal carcinomatosis index (PCI). PCI was the main criterion for distribution of patients in the main group by subgroups 1 and 2. The maximum size of the tumor node for each of the 13 regions of the parietal and visceral peritoneum was calculated to determine it.
At the peritoneal carcinomatosis index up to 14 patients were distributed to the basic group 2, where the first stage was performed by CS. In PCI more than 14 patients were included in the basic group 1, where treatment began with 3 courses of neoadjuvant chemotherapy, as the implementation of patients in this group of complete or optimal cytoreduction was doubtful.
Ovarian cancer staging was conducted according to the classification of FIGO (2010 edition).
Median age in the CG was 55 years, in the BG — 56 years. The comparative analysis of CG and BG (BG1+BG2) we have not identified significant differences in the distribution of patients by age.
To analyze the results of neoadjuvant chemotherapy in CG and BG 1, we used the RECIST system 1.1.
Table 1.
Analysis of the results of neoadjuvant chemotherapy in the study groups at the system RECIST 1. 1
Groups Answer
Partial Stabilization Progress
CG 14 35 4
BG1 7 18 3
In the comparative analysis of the results of neoadjuvant chemotherapy in CG and BG, we did not reveal significant differences.
Table 2.
The volume of cytoreduction in the study groups.
The amount of debulking
Groups Full (macroscopically, the tumor is not determined) Optimal (residual tumor size <10 mm) Suboptimal (residual tumor size >1 cm)
CG 0 0 53
BG 30 2 0
The results of cytoreduction in BG are significantly different from those in CG.
Table 3.
The median duration of the operation, PCI, days postoperative hospital stay in the studied groups.
Groups median duration of the operation (min) PCI postoperative hospital stay
CG 105 7,5 7
BG 1 237,5 8 12
BG 2 470 11,5 22
In the analysis of the table presented, in the sequence of CG-BG 1- BG 2, there is an increase in the median duration of surgery, PCI, postoperative hospi-
tal stay, which indicates more difficult conditions for performing cytoreduction in BG 2 (patients without neoadjuvant chemotherapy).
Table 4.
The volume of surgery in the study groups_
Surgery volumes CG (n = 53) BG 1 (n = 18) BG 2 (n = 14)
Extirpation of the uterus with appendages 53 (100%) 18 (100%) 14 (100%)
Omentectomy 53 (100%) 18 (100%) 14 (100%)
Peritoneumecto my 0 18 (100%) 14 (100%)
Rectum resection 0 7 (38,9%) 10 (71,4%)
Colon resection 0 1 (5,5%) 4 (28,6%)
Resection of the small intestine 0 3 (16,7%) 6 (42,8%)
Bladder and ureter resection 0 2 (11,1%) 2 (14,3%)
Splenectomy 0 1 (5,5%) 3 (21,4%)
Appendectomy 0 0 1 (7,1%)
As can be seen from the data presented in the table, the highest percentage of comined operations was performed in BG 2, then in BG 1.
Table 5.
Postoperative complications in the study groups.
Complications CG BG 1 BG 2
Phlegmon of the anterior abdominal wall 1 - -
Intra-abdominal abscess 1 - -
Intra-abdominal hematom - - 1
Failure of anastomosis - - 1
pancytopenia - - 1
myocardial infarction - - 1
Total % of complications 3,8 0 28,6
In the analysis of postoperative complications, a result of postoperative peritonitis (colorectal anas-more complications were diagnosed in BG 2. In the tomosis failure). BG - 2 was death of 1 (7.1%) patient. It was noted as
Table 6.
_Stages of treatment of patients with BG after CS (as of April 2018)._
Stage BG 1 (total 18) BG 2 (total 13) 1-death in postoperative period
Receive chemotherapy 6 (33,3%) 8 (61,5%)
Follow-up 6 (33,3%) 5 (38,5%)
Progression is revealed 4 (22,2%) 0
Did not appear at the reception (missing) 0 0
Died 2 (11,1%) 0
The median follow-up (months.) 8,0 4,5
The analysis of relapses revealed that 31 patients had a relapse of ovarian cancer in 1 year of follow-up in CG, which amounted to 58.5% of patients with the total number of CG, the median of relapse was 6 months.
In BG 1 relapse was detected in 4 patients (22.2%), the median recurrence was 7 months, which is significantly different from the results of CG.
In BG 2 recurrences of the disease at the time of examination were not revealed. The differences in the clinical groups, no significant.
The decrease in the relative risk of relapse in 1 year of follow-up in the BG 1 was 87.6% with a confidence interval of 95% from 1,077 to 6,432 compared to CG.
Pic. 1. The calculation of recurrence-free survival according to the method of Kaplan-Meier
Months from start of observation
Pic.2. Calculation of survival functions in the groups studied by the method of Kaplan-Meier
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- BG1 censored
- CG censored
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Months from start of observation
As follows, from the presented figure, the cumulative share of survivors in BG 2 for 12 months is significantly different from CG and BG 1.
Discussion: it should be understood that the impact on the tumor mass only by the procedure of HIPEC is not a radical treatment. From our point of view, it is advantageous to perform complete cytoreduction at the first stage of complex treatment of ovarian cancer with subsequent adjuvant chemotherapy. Optimal, or better complete
cytoreduction allows to reduce the volume of resistant tumor mass with weak blood flow and to minimize it and to conduct the first course of treatment with chemotherapy on the remaining tumor cells.
Performing an incomplete volume of cytoreduction significantly increases the percentage of recurrence of the disease: 58.5% of recurrences per 1 year of follow-up compared with 22.2% when performing full or optimal cytoreduction, the absence of recurrence of the disease, with the initial complete
cytoreduction. However, the percentage of postoperative complications and cascading increases significantly when performing the primary debulking.
It is likely that PCI is an important indicator that determines the treatment tactics and prognosis of the disease.
This article presents the first experience of using the technology in our clinical practice, but now it can be noted that the use of cytoreductive surgery procedure must necessarily reflect a multidisciplinary approach to treatment, with the mandatory participation of doctors of different specialties.
Conclusion: Full results and conclusions on the clinical comparison of the survival of these groups will be presented later. The plans to continue to master this technique, to expand the area of application of technology, to implement its own recommendations.
List of references:
1. edited by A. D. Kaprin, V. V. Starinsky, G. V. Petrova the state of cancer care to the population of Russia in 2017. Moscow: mnioi. P. A. Herzen branch of the Ministry of health of Russia "NMHC radiology", 2018. - 236 p.
2. Aebi S., Castiglione M. Newly and relapsed epithelial ovarian carcinoma: ESMO Clinical Recommendations for diagnosis, treatment and follow-up. Ann Oncol 2009;20(4):21-3.
3. Kormosh N. G., Laktionov K. P., Kerekovska N. With. Optimal cytoreductive surgery in patients with ovarian cancer III-IV stages. Tumors of the female reproductive system. 2010. No. 4. S. 103-111.
4. Winter W.E.3rd, Maxell G.L.,Tian C. et al. Prognostic factors for stage III epithelial ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol 2007;25:3621-7.
5. Savinova A. R., Gataullin I. G. Individual approach to the treatment of ovarian cancer. Kazan medical journal. 2016; 97(3): p. 388-393. doi: 10.17750
6. Pokataev I. A. Kormosh N. G., Mikhina Z. P., Laktionov K. P., Kurganva I. N., Tolentino A. S., Tyulyandin S. A. the Modern concept of treatment of recurrence of ovarian cancer. Experience in surgery, drug treatment, radiation therapy. Bulletin Of The Moscow Cancer Society. 2014. No. 1. C. 3-8
7. Piso P., Dahlke M-H., Loss M., Schlitt H.J. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in peritoneal carcinomatosis from ovarian cancer. World Journal of Surgical Oncology. 2004;2:21. doi:10.1186/1477-7819-2-21.
8. Amanov S. B., Shanazarov N. Ah. Privalov A.V. the Role of hyperthermal intraoperative intra-peritoneal chemoperfusion in the complex treatment of recurrence of malignant tumors and carcinomatosis of the abdominal cavity. Modern problems of science and education. 2013. No. 6. S. 661.
9. Dragula J., Konopacki A., Kwasniewska M., Sokolowski R., Zukow W. The use of surgical cytore-duction in combination with hyperthermic intraperito-neal chemotherapy (HIPEC) in the treatment of cancerous peritonitis in patients with gastric cancer or colon cancer. Journal of Health Sciences. 2013. Т. 3. № 9 (19). с. 077-086.
Khmel O.V.
Ph.D. in Medicine, Head of the Department of Surgical Treatment of Tuberculosis and Nonspecific Pulmonary Diseases State Organization "National Institute Of Phthisiology And Pulmonology Named By F. G.
Yanovsky National Academy Of Medical Sciences Of Ukraine"
Kalabukha I.A.
Doctor of Medicine, Head of the Department of Thoracic Surgery State Organization "National Institute Of Phthisiology And Pulmonology Named By F. G. Yanovsky National Academy Of Medical Sciences Of Ukraine"
Хмель Олег Володимирович
Кандидат медичних наук, зав1дувач вiддiленням хiрургiчного л^вання туберкульозу та НЗЛ Державно'! установи "Нацюнальний тститут фтизiатрii i пульмонологи iM. Ф.Г. Яновського Нацюнальноi академПмедичних наук Украши "
Калабуха 1гор Анатолшович
Доктор медичних наук, професор, завiдувач вiддiленням торакальноi хiрургii Державноiустанови
"Нацюнальний тститут фтизiатрii i пульмонологи iм. Ф.Г. Яновського Нацiональноi академП медичних наук Украши "
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