LITHUANIAN UNIVERSITY OF HEALTH SCIENCES LUHS LIBRARY REPOSITORY

Kombinuoto gydymo būdų ir kitų prognozinių veiksnių įtaka išplitusiu kiaušidžių vėžiu sergančių ligonių išgyvenamumui

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dc.contributor.author Simavičius, Andrius
dc.date.accessioned 2017-08-21T08:06:37Z
dc.date.available 2017-08-21T08:06:37Z
dc.date.issued 2006
dc.identifier.uri http://repository.lsmuni.lt/handle/1/60010
dc.description.abstract 1. INTRODUCTION Ovarian cancer is now the most common gynaecological cancer and the fourth the most common cancer among women in Lithuania. Referring to the epidemiological research ovarian cancer has the tendency to become more common: in 1990 there were 345 new cases of ovarian cancer and in 2004 - already 406 new cases. In 2004 ovarian cancer morbidity was 22.2/100 000 of inhabitants in Lithuania. Ovarian cancer is in the fifth position in the structure of death to cancer.Since there are no specific early symptoms and effective diagnostics of ovarian cancer so even 70 percent of diagnosed cases were stages III or IV. After the cytoreduction surgery and adjuvant chemotherapy with cysplatin / cyclophosphamide (CP) the survival among stage III cases was 10-20 percent and among stage IV cases not even 10 percent. In the structure of death to cancer ovarian cancer is in the sixth position - 16.1/100 000 of women. Since there is no effective prevention so the only way to prolong survival of patients is to optimise the treatment. It has been set that the optimal cytoreduction surgery could be performed only for about 50 percent of patients with stages III or IV ovarian cancer. As an alternative to conventional surgery for this group of patients the neoadjuvant chemotherapy - medical cytoreduction was applied. It could lead to the optimal conditions for cytoreduction surgery and further to prolongation of the survival. Referring to the literature the influence of neoadjuvant chemotherapy upon treating ovarian cancer is not clear. The prospective trial is not carried yet. The results of neoadjuvant chemotherapy of retrospective studies of ovarian cancer are contradictory. The survival results of patients treated with neoadjuvant chemotherapy following the cytoreduction surgery in retrospective trials are similar to those who started the treatment with the cytoreduction surgery. Therefore it would be logical to treat with neoadjuvant chemotherapy the patients with big non resectable metastases. Though this problem is discussed in the international conferences of oncologists and gynaecologists but it is supported only by little retrospective studies. Usually six courses of chemotherapy are applied for treating advanced ovarian cancer. After that the remission follows but for many patients it recurrences. In order to prolong the disease-free period and survival it has been proposed to apply maintenance chemotherapy (more course of chemotherapy, biological therapy). However there is no enough proof that maintenance chemotherapy prolongs survival of advanced ovarian cancer patients. There is no united opinion regarding the optimal number of chemotherapy courses. The work was aimed to optimise treatment of advanced ovarian cancer using the experience of hospitals and forward-looking at the new treatment trends analysed by ovarian cancer experts. 2. AIM The aim of this study was to evaluate the influence of different treatment methods and prognostic factors to the overall and disease free survival of the advanced ovarian cancer patients. 3. OBJECTIVES 1. To evaluate the role of neoadjuvant chemotherapy in advanced ovarian cancer patients comparing with adjuvant chemotherapy. 2. To determine the impact of the neoadjuvant chemotherapy to the optimisation of cytoreductive surgery. 3. To analyse the influence of the cytoreductive operation to the outcome of the advanced ovarian cancer patients. 4. To investigate the effect of two additional chemotherapy cycles (6 vs 8) to the overall and disease free survival of advanced ovarian cancer patients. 5. To evaluate the influence of prognostic factors to the outcome of ovarian cancer patients. 4. NOVELITY AND ORIGINALITY OF WORK During the recent years it is more and more discussed about application of neoadjuvant chemotherapy for advanced ovarian cancer patients. In order to analyse this problem the retrospective clinical trials was analysed and the ideas for new clinical research were searched. Due to favorable situation that it was a tradition to apply neoadjuvant chemotherapy in Lithuania and in order to perform radical surgery, in the context of today relevancy, the problem of neoadjuvant treatment was analysed referring to the experience of hospitals providing oncological help. Another relevant problem was to analyse if the prolonged treatment with chemotherapy influences to patients' overall and disease-free survival. This question while treating ovarian cancer has not been answered. This problem was not analysed in Lithuania yet. Taking in mind contraversion of data and its lack in Lithuania, the analysis of this problem is also new and useful managing questions of optimal treatment. For the first time the analysis of almost all advanced ovarian cancer patients that were treated in hospitals in Lithuania was performed. The dependency of patients' survival on the treatment methods and prognostic factors were analysed. It was determined that the real survival was different from the results referred in the literature sources. Therefore there appear possibilities to view limitations of treatment and look for strategy of optimal treatment. 5. MATERIALS AND METHODS 5.1. Material of Research The retrospective analysis was performed for 574 advanced ovarian cancer patients (FIGO stages IIIA - IV), treated in Kaunas Medical University Hospital, Oncological Clinic of Šiauliai Hospital and Oncological Department of Klaipėda Hospital during 1993-2000. The data about the patients for research was used from medical documentation i. e. case-records. The dates of death were specified referring to database of Cancer Register in Lithuania. The stage of disease was determined referring to FIGO and TNM classifications. The combined treatment of cytoreduction surgery and chemotherapy CP scheme (Cisplatin 75mg/m2 + Cyclophosphamide 750mg/m2 with ~28 days brake between the cycles) was applied to all patients. During the period when research was conducted there was no united advanced ovarian cancer management in Lithuania. Adjuvant and neoadjuvant chemotherapy regimens were used. The patients involved in the research were treated according those schemes: neoadjuvant chemotherapy (3 courses of chemotherapy CP, cytoreduction surgery and 3-5 cycles of chemotherapy CP) or adjuvant chemotherapy (cytoreduction surgery and 6-8 cycles of chemotherapy CP). Optimal cytoreduction surgery was considered type total abdominal hysterectomy, bilateral salpingoophorectomy, omentectomy and big tumour metastases excision. Suboptimal cytoreduction surgery was considered as more conservative surgery when hysterectomy, bilateral salpingoophorectomy or omentectomy was not performed. Type of surgery was determined referring to medical documentation. Patients treated with 6-8 cycles of first line chemotherapy were involved into the clinical trial. Characteristics of patients, disease and treatment and their distribution upon stage of disease are shown in the table 1. Table 1 Patients', disease and treatment characteristics Stage IIIA IIIB IIIC IV Total Number of patients 166 152 154 102 574 Treatment: neoadjuvant chemotherapy 57 55 55 48 213 adjuvant chemotherapy 109 97 99 56 361 Number of courses: 6 courses 101 89 104 59 353 8 courses 65 63 50 43 221 Age by year: <65 111 108 93 46 358 ?65 55 43 60 56 214 Histology: Serous 85 78 35 21 219 Mucinous 31 24 36 24 115 endometrioid 42 33 53 39 167 Other types (clear cell, undifferentiated and mixed) 8 17 30 18 73 Cytoreductive surgery: optimal 140 120 87 29 376 suboptimal 26 32 67 73 198 5.2. Scheme of Clinical Research The retrospective-kohort clinical trial involving patients with advanced ovarian cancer was performed. Overall and disease-free survival of patients with stages III and IV was analysed. Overall and disease-free survival of patients was analysed upon stages, applied treatment methods' succession, number of chemotherapy cycles, patients' age, tumours' morphology and type of surgery. Influence of prognostic factors to overall and disease-free survival was analysed. 5.3. Statistical Analysis Patients' observation data was used and summarised on the 31st of December, 2003. All patients have died before research data summation. Using life-tables data was evaluated in one year intervals. In order to receive full match to the method of Kapan Meier when calculating survival the special method that enables to accommodate the presented rate was used. This method enabled to calculate survival rates and their 95 pc. confidential intervals. Overall and progression-free survival rates were calculated by the method of Kapan Meier. The median was calculated to evaluate the survival. Overall and progression-free survival curves were drawn according to the method of Kaplan Meier. The Cox proportional hazards model was used to evaluate prognostic factors to determine the magnitude and significance of their effects on overall survival and disease-free survival. Univariate and multivariate analysis was performed. The Cox proportional hazards model was used to identify independent prognostic factors. Factors of significance in the univariate analysis were included simultaneously and then a backward selection was performed with stepwise exclusion of insignificant variables until the model contained only significant variables. Statistical significance between groups was assessed using 95 pc. CI, ?2 test and log-rank test. The MsExcell, SPSS and STATA statistical software packages were used to perform the analysis. 6. RESULTS 6.1. The influence of stage to overall and disease-free survival In the work it has been set that the median overall survival of stage III patients - 661 days (22 months), the median disease-free survival - 362 days (12 months), the median overal survival of stage IV patients - 480 days (16 months), the median disease-free survival - 278 days (9.3 months). The trial showed that in case of smaller disease stage (stage III compari
dc.language.iso lit
dc.subject Kiaušidžių vėžys
dc.subject Treatment methods
dc.subject Prognostic factors
dc.subject Survival
dc.subject Išgyvenamumas
dc.subject Prognoziniai veiksniai
dc.subject Ovarian cancer
dc.subject Gydymo metodai
dc.title Kombinuoto gydymo būdų ir kitų prognozinių veiksnių įtaka išplitusiu kiaušidžių vėžiu sergančių ligonių išgyvenamumui
dc.title.alternative The influence of combined treatment methods and other prognostic factors to survival of the advanced ovarian cancer patients
dc.type Daktaro disertacija


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