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Karimova Nargiza Sunnatullayevna, radiation oncologist Department of Radiotherapy of State Institution Republican Specialized Scientific-Practical Medical Center of Oncology and Radiology of Uzbekistan
Tashkent, Uzbekistan E-mail: [email protected] Mamadaliyeva Yashnar Saliyevna, Head of the Department of Oncology with a course of ultrasound diagnostics at the Tashkent Institute of Advanced Medical Studies, Professor, Dhd., Tashkent, Uzbekistan E-mail: [email protected] Nishanov Daniyar Anarbayevich, Head of the Department of Pathology State Institution Republican Specialized Scientific-Practical Medical Center of Oncology and Radiology of Uzbekistan, Dhd.,
Tashkent, Uzbekistan E-mail: [email protected] Ismailiva Munojat Xayatovna, Head of the Department of Clinical radiology at the Tashkent Medical Academy, docent, Phd.,
Tashkent, Uzbekistan E-mail: [email protected]
MULTISLICE TOMOGRAPHY IN THE COMPARATIVE ASSESSMENT OF THE RATE OF PRIMARY TUMOR REGRESSION AGAINST THE BACKGROUND OF CHEMORADIATION THERAPY FOR LOCALLY ADVANCED CERVICAL CANCER
Abstract. To evaluate possibilities of multislice tomography in determining the estimate of the rate of regression of chemoradiation therapy in patients with locally advanced cervical cancer.
Rationale: Multislice tomography and magnetic resonance tomography, as some non-invasive methods of radio-diagnostics, can greatly facilitate the evaluation of the prevalence of this localization of malignant process allowing to increase the accuracy of the clinical staging and evaluate the effectiveness of the selected treatment.
Materials and Methods: The work is based on the results of a survey of 42 patients in the period 2016-2017. MSCT was performed at Somatom Definition AS20 (Siemens, Germany 2015). The work is based on the results of a survey of 42 patients in the period 2016-2017. Multispiral tomography was performed on Somatom Definition AS20 (Siemens, Germany 2015).
Results: When analyzing the diagnostic value of multislice tomography, the technique is a highly informative method that can be used for monitoring in the process of complex chemoradiation treatment for patients with cervical cancer. Multislice imaging performed on the SOMATOM DEFINITION AS20 (SIEMENS, Germany, 2015.), it allows you to receive objective information about the dynamics of tumor regression, the rate of change of its blood supply and changes in metastatic regional lymph nodes during treatment.
Conclusion: The obtained data allows us to optimize the timing of MSCT monitoring for the chemoradiation treatment of locally advanced cervical cancer.
Keywords: locally advanced cervical cancer, multislice tomography, tumor regression.
Introduction. Malignant tumors of the female genital the most common malignant tumors in women [1]. Every organs occupy a special place in clinical oncology: they are year 12.7 million new cases of cancer are registered in the
world, ofwhich more than 1 million are diseases of the female genitalia [10]. Among the countries of Central Asia and the Russian Federation for the period 1991-2016. the increase in the absolute number of cases of cervical cancer ranged from 9% (in Belarus) to 44-92% (in the Russian Federation, Kazakhstan, Kyrgyzstan). In 2016, the highest incidence rates were registered in the Russian Federation, Kazakhstan and Kyrgyzstan (15.4 and 16.4 per 100 thousand of the female population); at the level of 10-11 per 100 thousand - in Armenia, Uzbekistan, Moldova and Tajikistan; less than 7 per 100,000 - in the Republic ofAzerbaijan [2]. Long-term results of treating patients with cervical cancer are not satisfactory, relapses after special treatment often occur after 12-20 months. and observed in 32-78.3% of cases. Up to 45% of patients die within the first 5 years of disease progression [7].
According to the State Institution Republican Specialized Scientific-Practical Medical Center of Oncology and Radiology, in 2017 the number of women with malignant tumor diseases in the population was the highest in cases of breast cancer - 9.9; cervical cancer-4,8; 2.4 ovarian cancer, respectively. From 2013 to 2017, 7201 new cases of cervical cancer were detected in the Republic of Uzbekistan. The average incidence rate was 4.6 per 100,000 population. Despite the progress made in the diagnosis and treatment of this localization, there is an increase in the incidence and an increase in the aggressiveness of the course of the disease. There is a decrease in 5-year survival in the period from 2013 to 2017 from 45.3 to 42.6, and the mortality rate increased from 2.4 to 2.6 per 100.000 population (Cancer register). This requires improving the quality of early diagnosis and improving the treatment of locally advanced forms of cervical cancer in order to predict the recurrence of the disease. Multislice tomography and magnetic resonance tomography, as some non-invasive methods of radiodiagnostics, can greatly facilitate the evaluation of the prevalence of this localization of malignant process allowing to increase the accuracy of the clinical staging and evaluate the effectiveness of the selected treatment [4; 16; 17].
In 2009, the International Federation of Obstetricians and Gynecologists recommended for the first time to take into account data of computer tomography and / or magnetic resonance imaging in planning the treatment of cervical cancer patients [14]. It was established that the tumor volume, the spread of the tumor on the body of the uterus, the state of the pelvic and retroperitoneal lymph nodes, as determined by MSCT, MRI are independent predictors of overall and without recurrent survival with locally advanced cervical cancer [6; 12].
The possibility of using MSCT to reliably exclude the spread of the tumor to the adjacent pelvic organs, identify the level and determine the cause of the obstruction of the ureters led to a decrease in the need for the use of X-ray diagnostic methods.
MSCT proved to be useful in planning and preparing for radiation treatment [5; 18]. The presence of metastases in the regional lymph nodes is an extremely unfavorable prognostic factor that significantly reduces survival in cervical cancer. However, the possibilities of using pathological studies to assess the state of lymph nodes are significantly limited, since many patients with cervical cancer do not show surgical treatment, and therefore non-invasive diagnostic methods become relevant [13]. The analysis will improve the effectiveness of clinical examination and qualitatively influence the tactics of patient management, depending on the results obtained. The analysis of literature data indicates a significant variability of the results ofMSCT, the complexity of interpreting the visual picture in the monitoring of chemoradiation treatment in order to assess its effectiveness.
The aim of the study was the possibilities of MSCT, a comparative assessment of the rate of regression of the primary tumor on the background of chemoradiation therapy and the closest prognosis for locally advanced forms of cervical cancer.
Material and methods: The work is based on a survey of 42 patients with cervical cancer, IIB-IIIAB stages of FIGO classification (2009), who received chemoradiotherapy in the State Institution Republican Specialized Scientific-Practical Medical Center of Oncology and Radiology of Uzbekistan from 2016 to 2017. The diagnosis of the disease in all cases is verified histologically. Morphologically, all women were diagnosed with squamous cell carcinoma. The age of 72.4% of patients accounted for 4-5 decades of life. All patients received chemoradiotherapy; 3 courses of neoadjuvant chemotherapy (cisplatin + 5 ftorouracil), followed by a course of combined radiation therapy, including remote gamma therapy, SFD of 2 Gy, TFD of 46 Gy (TERABALT type 80 model SCS2012 Czech Republic) and intracavitary radiation therapy (BEBIG apparatus Multisourse Co 602013. Germany) SFD5 Gy, eq TFD to point A 70-90 Gy, to point B50-58 Gy.
Evaluation of the effectiveness of chemoradiation treatment was carried out according to RECIST criteria using MSCT. On sagittal sections, the spread of the tumor along the long axis of the uterus, its transition to the body, as well as the relationship between the tumor and the posterior wall of the bladder and / or the anterior wall of the rectum was evaluated. Axial and coronary sections were used to assess the transition of the tumor to the walls of the pelvis and visualize the lymph nodes. The best visualization of the parametric invasion was achieved using oblique axial slices oriented perpendicular to the long axis of the cervix. At MSCT, infiltration was manifested by tyazhy consolidations of the structure of parametric fiber and an increase in the densitometric density of tissues by 40-70 X units. The obstruction of the ureters was well defined using the CT-urography technique (obtaining a thick section in the coronary plane). This technique allowed for a few seconds, without
resorting to contrast, to obtain an image of the bladder and dilated ureters. A good contrast between the lymph nodes and the surrounding fatty tissue provided the lymph nodes better differentiated from skeletal muscles, ovaries and blood vessels. The advantage of the frontal plane was the ability to explore the retroperitoneal space from the pubic symphysis to the level of the renal vessels. Sagittal images were used to visualize enlarged aortic lymph nodes. Axial sections for adequate assessment of the structure of the lymph nodes covered the region from the pubic symphysis to the renal vessels.
When performing MSCT to reduce artifacts from intestinal motility, patients were advised to abstain from food intake for 5-6 hours prior to the study using antiperistaltic drugs the evening before. Artifacts from the respiratory movements of the anterior abdominal wall were eliminated by software (using a saturation band) or mechanical compression of the abdomen with an elastic belt.
In all cases, the control CT of the pelvic organs was performed after 3 courses of neoadjuvant chemotherapy, before and after combined radiation therapy and 3, 6, 9 and 12 months after treatment. Statistical data analysis was per-
software package. Data are presented as absolute frequencies and percentages.
Research results and discussion: Evaluation of the effectiveness of the treatment was carried out taking into account the analysis of changes in the following parameters: tumor size, the degree of para infiltration of cervical fiber, involvement of the uterus and neighboring organs, the state of regional lymph nodes. Before treatment, in all cases there was a lesion of the cervical stroma, characterized by a lesion that ruptures the hypointensive stroma ring. Tumor sizes ranged from 5 to 60 mm, on average - 32 ± 3 mm. The transition of the cervical tumor to the body of the uterus was determined in 40.5% (17) cases, while on the tomograms the tumor masses were visualized through the internal pharynx into the uterine cavity with disruption of its normal zonal anatomy with a change in section. During the MSCT, in all cases, bilateral infiltration was detected, while the defeat of one of the parties in some cases was significantly greater than the opposite. Infiltration of the paracervical tissue was perched in 59.5% (25) patients. Using MSCT, invasion of the bladder in the form of local uneven thickening of its wall and tumor invasion of the rectum was suspected in 21.4% (9).
formed using Microsoft Excel and the SPSS13.0 statistical
Table 1. - Dynamics of regression of the primary tumor in patients with cervical cancer
invasion of adjacent organs
body of the uterus paracervical fiber cervical stroma
0%
10% 20% 30% 40% 50% 60% 70% 80%
90% 100%
cervical stroma paracervical fiber body of the uterus invasion of adjacent organs
■ before treatment 42 25 17 9
■ after 3 courses of chemotherapy 40 23 16 8
■ before radiation therapy 39 22 16 8
■ after radiation therapy 32 18 12 5
■ after 3 months 30 13 11 4
■ after 6 months 27 9 8 1
■ after 9 months 24 4 5 1
■ after 12 months 24 4 5 1
I before treatment after radiation therapy I after 9 months
after 3 courses of chemotherapy ■ before radiation therapy 1 after 3 months ■ after 6 months
I after 12 months
After 3 courses of neoadjuvant chemotherapy, before and after combined radiation therapy, the size of cervical stroma infiltration according to MSCT was 95.2% (40), 92.8% (39), 76.2% (32), respectively. Preservation of vapor infiltration of cervical fiber during treatment 54.7% (23), 52.4% (22), 42.8% (18) cases. The transition of the cervical tumor to the uterus body after 3 courses of neoadjuvant chemotherapy disappeared to 2.5% (l), 2.5% (l) and 12% (5), respectively, show before and after combined radiation therapy.
Under dynamic observation, 3 months after chemora-diation treatment in 28.6% of cases, according to MSCT, inflamed stroma of the cervix disappeared in patients. The incidence of vapor infiltration of cervical fiber was reduced from 59.5 to 30.9% (13). The transition of the tumor process to the body of the uterus was preserved in 26.2% (ll) cases and was visualized as an area of increased intensity without clear contours in the region of the lower segment of the uterus in violation of its normal zonal anatomy. In half of the women with the initial spread of the tumor to adjacent organs, a positive trend was recorded in the form of a decrease in the degree of infiltration.
Table 2. - The degree of regression of after chemoradiation treatment,
After 6 and 9 months after the end of treatment, the phenomena of tumor size regression (from 25 ± 3 mm to 15 ± 3 mm), reduction in the size of vapor infiltration of cervical tissue (in 9.5% (4) patients) continued, and the transition of the tumor process to the body the uterus was preserved in 19% (8) and 11.9% (5) cases, respectively.
After 12 months after treatment, infiltration of the cervical stroma disappeared in 42.9% (18) patients. The spread of the tumor on paracervix was preserved in 9.5% (4) cases. The frequency of transition of the tumor to the body of the uterus decreased from 26.2 (11) to 11.9% (5) cases. A decrease in tumor infiltration into adjacent organs was recorded in 2.4% of cases (Table 1).
According to the MSCT monitoring, a significant regression of the tumor process was noted in the majority of patients. Moreover, a decrease in tumor size after chemoradiation treatment, more than 50% was noted in 20 (47.6%), from 25 to 50% in 13 (30.9%), less than 25% in 9 (21.4%) patients. Complete tumor regression was achieved in 14 (33.3%), partial regression - in 7 (16.6%), process stabilization - in 13 (30.9%) patients (Table 2).
the tumor of the cervix after 12 months depending on the stage and size
According to our data, a decrease in the degree of infiltrative changes was determined during and after treatment. In most patients, tumor size reduction in the process of combined chemo-
radiation treatment occurred in parallel and in proportion to the decrease in the degree of accumulation of the contrast agent, which indicated a decrease in the blood supply to the tumor.
With complete remission, restoration of the normal anatomical structure of the cervix and the proximal part of the vagina was observed, which was determined by the picture of recovery of a homogeneous signal of low intensity from the stroma, visualization of the even mucous membrane against the background of a decrease in the size of the cervix. When conducting a bolus contrast enhancement, it was found that in the projection of a previously defined tumor there was an accumulation of contrast, visually identical to the unchanged stroma.
Assessment of the lymph nodes is also one of the most important tasks of a CT scan in cervical cancer. Unfortunately, the accuracy of traditional MSCT in the diagnosis of lymph node metastatic lesions is assessed as low.
MSCT sensitivity in the diagnosis of lymphadenopathy varies from 83% to 95%, specificity - 88% [15]. The main
criterion for the evaluation of lymph nodes using any to-mographic method is the size, with preference given to the transverse size.
As a separation point, values in the range from 6 to 15 mm are used, but most often the upper limit of the norm for the pelvic lymph node is 10 mm. A minimum diameter of more than 10 mm serves as the most reliable criterion for lymph node metastatic damage, although some authors consider pelvic lymph nodes with a maximum size of more than 10 mm suspicious [3, 9]. In addition, there is evidence that in the metastatic lesion of the lymph node its shape is rounded [8]. Therefore, as an indirect sign of a lymph node metastatic lesion, it is proposed to use the criterion of increasing the ratio of smaller to larger diameter of more than 0.8 [8; 11].
Table 3. - Dynamics of changes in the size of regional lymph nodes in patients with cervical cancer
However, even small lymph nodes may be affected by metastases, and enlarged lymph nodes may not contain tumor tissue [8,;11]. At the same time, when large conglomerates of
lymph nodes are detected (more than 20 mm) with the presence of sections of disintegration and hemorrhages in their structure, the metastatic nature of their damage is beyond
doubt. There is evidence that the presence of central necrosis in the lymph node can be used to diagnose its metastatic lesions. The positive predictive value of this feature, regardless of the node size, is 100% [12].
Changes detected by MSCT in the lymph nodes, allowed to adequately stratify the lymphogenous spread of the process according to the criterion N of the TNM system (Table 3). In the series of presented observations for locally advanced cervical cancer, single metastatic lymph nodes or packages of enlarged lymph nodes were more characteristic. Both the first and the second group of lymph nodes were characterized by a round or ovoid shape, clear and even contours, a homogeneous structure and reduced echogenicity. At the same time, in 7.1% of cases an increase in lymph nodes was detected by more than 10 mm in diameter in the pair of cervical cellulose, in 14.3% in rectal cellulose. The lymph nodes along the external iliac vessels were enlarged by 83.3%, along the internal iliac vessels - by 28.6%, along the common iliac vessels - by 54.7% of cases; an increase in the pair of aortic lymph nodes was noted in 40.5%, paracaval - in 9.5%, inguinal - in 45.2% of observations. The contours of the lymph nodes were lumpy in 82%.
During treatment, it became known that after chemoradia-tion therapy, all lymph nodes decreased significantly. Paracervi-cal lymph nodes disappeared. A pair ofrectal 14.3% (6) by 2.4% (1). External iliac lymph nodes decreased 83.3% by 28.6%. After chemoradiation therapy, the internal iliac lymph nodes unsharply decreased 28.6% - 16.6%. General ileal lymphocytes after treatment are almost preserved 54.7% - 40.5% and inguinal lymph nodes 45.2% - 28.6%, respectively. The number of aortic and para lymphatic nodes during treatment decreased by almost two times: 40.5% - 16.2%, 9.5% -7.1%, respectively.
When the control MSCT after 3 months. after treatment, it was found that lymph nodes in a pair of cervical cellulose were not visualized in 100%, in a pair of rectal cellulose lymph
nodes remained in 2.4% (1) of cases. The increase in lymph nodes along the external iliac vessels remained in 28.6%, along the internal iliac vessels - in 16.6%, along the common iliac vessels - in 40.5% of cases, the increase in a pair of aortic lymph nodes continued to be determined in 16.6%, paracaval-ny - in 7.1%, inguinal - in 28.6% of patients.
12 months after treatment, an increase in the lymph nodes along the external iliac vessels was observed in 28.6%, along the internal iliac vessels - in 7.1%, along the common iliac vessels - in 28.6% of cases; an increase in lymph nodes of the aortic group remained in 14.3%, in the paracaval group in 4.7%, and in the inguinal group in 16.6% of patients. The contours of the lymph nodes remained bumpy in 43%.
Conclusion: Thus, the results of the study suggest that MSCT is a highly informative diagnostic method that can be used to monitor the combined chemoradiation treatment of patients with locally advanced cervical cancer, which allows obtaining objective information about the dynamics of regression of the size and condition of regional lymph nodes.
Analysis of the dynamics of tumor prevalence during the monitoring showed that the maximum reduction in the size of the tumor was recorded after chemoradiation therapy, a decrease in the vapor infiltration of cervical fiber and the restoration of the structure of the walls of the uterus body - from 3 to 6 months after treatment. At the same time, in the course of dynamic observation, it was possible to determine the progression of the disease 12 months after treatment, which was manifested by an increase in tumor size by 25% or more and the appearance of multiple liver metastases in 2 (4.7%) patients.
The reaction of lymph nodes after chemoradiation treatment was most pronounced in terms of 3 to 6 months, with the most pronounced changes recorded in groups of external iliac and a pair of rectal / para cervical lymph nodes, which were not visualized 3 months after chemo-radiation therapy.
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