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7Следовательно, при длительной окклюзии панкреатического протока при исследовании ткани ПЖ на 6 сутки эксперимента выявляли признаки воспаления: лимфоцитарную и эозинофильную инфильтрацию внутри- и междольковых септ, очаги некроза. На 15 сутки отмечалась дилатация протоков и атрофия ацинарных клеток. На 30 сутки формировалась рыхлая и плотная фиброзная ткань вокруг магистральных и внутридольковых протоков. Эндокринные островки сохраняли нормальную структуру и состояли преимущественно из В-клеток.
Таким образом, полученные при экспериментальных исследованиях данные подтверждают, что при длительной окклюзии главного панкреатического протока развивался деструктивный процесс в ПЖ дистальнее уровня обструкции, который сопровождался увеличением в плазме крови концентрации МДА и снижением активности энзимов, усилением коллагенообразования. Отмечали разрушение паренхимы ПЖ и через 30 суток после перевязки дистального отдела панкреатического протока наблюдалось только частичное сохранение структуры ПЖ с атрофией паренхимы, образованием плотной фиброзной ткани вокруг магистральных и внутридолевых протоков, рыхлой фиброзной ткани в междольковом пространстве и сохранением структуры эндокринных островков.
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SURVIVAL RATE OF PATIENTS WITH PROSTATE CANCER DURING RADIOTHERAPY
Paliy M.
National Cancer Institute, Kyiv, Ukraine Stoliarova O.
DM, Professor, National Cancer Institute, Kyiv, Ukraine
Dumanskiy Yu.
DM, Professor, Institute of Experimental Pathology, Oncology and Radiobiology, Kyiv, Ukraine
Syniachenko O.
DM, Professor, Donetsk National Medical University, Lyman, Ukraine
Iermolaieva M.
DM, Professor, Donetsk National Medical University, Lyman, Ukraine
Abstract
The five-year survival rate of patients with prostate cancer depends on the initial level of Gleason score, the method of radiation therapy applied, the concurrent administration of hormonal therapy and chemotherapy, and the life expectancy of deceased patients is inversely related to the timing of the onset of radiotherapy after prostatectomy and directly correlates with the power of radiation, and the blood level of tumor markers decreases in the process of ongoing therapeutic measures, which determines the nature of the initial course of the disease. The medical technology of early radiation therapy of prostate cancer suggested by us made it possible to significantly
increase the five-year survival rate of patients by 1/3, and the life expectancy of deceased patients after the diagnosis of the disease was increased by 1.5 times.
Keywords: cancer, prostate, treatment, radiation therapy.
Introduction. Prostate cancer (PC) is considered to be one of the primary problems of oncology [1, 114; 2, 422], which is explained by the late diagnosis of the disease, the anatomical and topographical features of the organ affected by the tumor, and the low effectiveness of existing treatment methods [3, 467; 4, 11]. PC ranks first in the structure of cancer incidence [5, 353; 6, 660] and is one of the leading causes of death [7, 131; 8, 27223; 9, 847].
The aim of the study was to increase the efficacy of radiation therapy (RT) in patients with PC, to improve the quality of control over the ongoing treatment. In this regard, the following tasks were set: 1) to study the 5-year survival rate and life expectancy of deceased patients with PC with different course of the disease, the role of medical RT technology, the parallel administration of hormonal therapy (HT) and chemotherapy (CT), as well as the nature of the dynamics of tumor markers in the course of treatment; 2) to establish the efficacy of "early radiation therapy" of severe PC immediately after radical prostatectomy, the effect of this treatment approach on the tumor recurrence rate, survival rates of patients and the number of RT complications; 3) to evaluate the 5-year survival rate and life expectancy of deceased patients with PC in the process of different RT technologies, to create an optimal algorithm for the use of RT, taking into account the peculiarities of the clinical and laboratory course of the tumor process, to increase the efficacy of therapeutic measures.
Patients and methods. The work was performed in accordance with the World Medical Association Declaration of Helsinki, and the patients gave their informed consent to the study approved by the National Cancer Institute Bioethics Commission. The study included 195 men with PC aged 52 to 82 years old (66 ± 6.9 years on average). The duration from the moment of diagnosis of the disease ranged from 5 months to 17 years (3 ± 0.2 years on average). pT2 was established in 27.7% of the patients, pT2a - in 3.1%, pT2b - in 7.7%, pT2c - in 20.0%, pT3 - in 13.9%, pT3a - in 3.1%, pT3b - in 20.0%, pT3c - in 3.1%, pT4 - in 4.6%. The pN1, pN2 and pN3 parameters were found in 21.5%, 9.2% and 7.7% of cases, respectively, pM1 and pM2 - in 26.2% and 16.9%. Cancer expansion parameters were 3.2 ± 0.12 points, tumor size was 1.9 ± 0.06 points, Gleason score (GS) was 6.4 ± 0.08 points. The ratio of peripheral to central PC form was 3:1, tumor localization in the posterior part of the prostate was found in 56.9% of the cases, in the lateral part - in 36.9%, in the anterior part - in 6.2%. Adenocarcinoma was diagnosed in 93.9% of the examined patients, and giant cell carcinoma was diagnosed in 6.2%.
The integral index of PC staging (STT) was 3.0 ± 0.07 relative units, maturity (GDT) - 2.5 ± 0.05 points, severity of the course (IWT) - 17.2 ± 1.18 relative units. Metastases in lymph nodes were found in
38.5% of patients, in distant organs - in 18.6%, in the skeleton - in 28.0%, the formation of which was diagnosed on average after 49.4 ± 5.14, 69.0 ± 9.36 and 50.0 ± 4.56 months after the onset of the tumor process in the prostate gland. Among the PC complications, ascending obstructive pyelonephritis was found in 9.2% of the cases, hydronephrosis in 4.6% of the cases, tumor invasion into the bladder in 3.1% of the cases, invasion into the rectum in 1.5% of the cases, macrohematuria in 1.0% of the cases. Comorbid additional tumors in the examined patients with PC were as follows: papillary bladder carcinoma occurred in 3.1% of cases, clear cell renal carcinoma - in 2.6%, breast adenocarcinoma - in 1.0%, squamous cell carcinoma of the skin - in 0.5%.
Diagnosis of PC and its metastases was based on clinical, laboratory, radiation (X-ray, computed tomography, sonographic) and cytological (histological) examination methods. We used devices Multix-Compact-Siemens (Germany), Somazom-Emotion-6-Siemens (Germany), Gygoscan-Intera-Philips (Netherlands), Envisor-Philips (Netherlands). Serum levels of total prostate specific antigen (PSA), testosterone (TS) and luteinizing hormone - LT were tested by immu-nochemical analysis using a Cobas-6000 analyzer and a Roche-Diagnostics test system (Switzerland); acid prostatic phosphatase (APR) activity and insulin-like growth factor 1 (ISF) content was tested by enzyme immunoassay (PR2100-Sanofi diagnostic pasteur reader, France) with a test system Immulite-Siemens-AG (Germany), the activity of glycosyl hydrolase (GH) and alkaline phosphatase (AP) enzymes was tested using a biochemical analyzer Olympus-AU640 (Japan).
Statistical processing of the obtained results was performed using computer variance, nonparametric, correlation, single (ANOVA) and multivariate (ANOVA/MANOVA) dispersion analysis (Microsoft Excel and Statistica (Stat-Soft, USA) programs. We estimated the average values (M), their standard errors (SE) and deviations (SD), the parametric Pearson correlation (r) and nonparametric Kendall (J), coefficients, the Brown-Forsythe (BF), Wilcoxon-Rao (WR), dispersion (D) tests, Student t-test (t) and the reliability of the statistical indices (p). The critical significance level for checking the statistical hypotheses was considered to be 0.05.
Results and discussion. In 2.5 years on average after radical prostatectomy and concomitant different methods of radiation therapy, recurrence of neoplasm is observed in 40% of the prostate cancer patients, which is associated with the baseline pN and GS parameters, the form, localization and expansion of the tumor process, the presence of comorbid papillary carcinoma of the bladder, metastases in lymph nodes, distant viscera and skeleton, and such complications of radiation therapy as dermatitis, polyneuropathy, acute vascular insufficiency and tubulointerstitial ne-
phritis depend on the power and direction of radiation exposure.
The 5-year survival rate of prostate cancer patients depends on the initial level of GS, the method of radiation therapy applied, concurrent prescription of HT and CT, and the life expectancy of deceased pa-
100
tients is inversely related to the timing of the onset of RT after prostatectomy and directly correlates with the radiation power, and the blood level of the tumor process markers decreases during the therapeutic measures applied, which determines the nature of the initial course of the disease.
St, %
80 60 -40 -20 -0 -
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Fig. 1. Survival rate of prostate cancer patients with different baseline GS levels (%).
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Fig. 2. Survival rate of PC patients depending on the development of tumor recurrence (%).
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0 12 24 36 48 60
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0 12 24 36 48 60
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Fig. 3. Survival rate of PC patients depending on different types of RT (%).
Fig. 4. Survival rate of Fig. 5. Survival rate of PC patients depending on PC patients depending on the use of HT (%). the use of CT (%).
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The suggested "early radiation therapy" of a severe form of prostate cancer after radical prostatectomy allows relapses of the tumor process to form significantly less often (by a factor of 5.2) and in more distant terms (by 10 months on average), to eliminate their dependence on the power of the radiation applied and the dose of the bone metastases exposure, with less frequent use of parallel chemotherapy (in particular, antimetabolites), to avoid complications of radi-ochemotherapy more often, including the development of polyneuropathy, acute vascular insufficiency and acute coronary syndrome. Survival rate of patients
with different variants of the course of prostate cancer - Fig. 1-5.
Patients with prostate cancer were divided into 3 groups: the 1st (main) one included 23.1% of patients, 2nd (1st control group) - 50.8% of patients, 3rd (2nd control group) - 26.1% of patients (Fig. 6). Group 1 included patients with GS>7 points who underwent RT immediately after prostatectomy, group 2 (GS>7 points) included patients who started RT after hormonal detection of a relapse, and group 3 included patients who started RT in cases of tumor recurrence after prostatectomy with GS <7 points.
St, %
100 80 60 40 20 0
— 1st 2nd — 3rd
12
24
36
48
60
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Fig. 6. Survival rate of PC patients of different groups (%).
The developed medical technology for early radiotherapy of PC allowed to significantly increase the 5-year survival rate of patients by 1/3, and to increase the life expectancy of patients after diagnosis of the disease by 1.5 times; an algorithm for RT methodology was created, taking into account the size of the tumor, the presence of metastases in distant organs, IWT parameters and tumor markers, use of 6 MEV energy and radiation power.
Conclusion. The five-year survival rate of patients with prostate cancer depends on the initial level of Gleason score, the method of radiation therapy applied, the concurrent administration of hormonal therapy and chemotherapy, and the life expectancy of deceased patients is inversely related to the timing of the onset of radiotherapy after prostatectomy and directly correlates with the power of radiation, and the blood level of tumor markers decreases in the process of ongoing therapeutic measures, which determines the nature of the initial course of the disease. The medical technology of early radiation therapy of prostate cancer suggested by us made it possible to significantly increase the five-year survival rate of patients by 1/3, and the life expectancy of deceased patients after the diagnosis of the disease was increased by 1.5 times.
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