Preliminary survey of 3D image-guided brachytherapy for cervical cancer at representative hospitals in Asian countries.

3D image-guided brachytherapy (3D-IGBT) has become a standard therapy for cervical cancer. However, the use of 3D-IGBT is limited in East and Southeast Asia. This study aimed to clarify the current usage patterns of 3D-IGBT for cervical cancer in East and Southeast Asia. A questionnaire-based survey was performed in 11 countries within the framework of the Forum for Nuclear Cooperation in Asia. The questionnaire collected the treatment information of patients with cervical cancer who underwent 3D-IGBT. The cumulative external beam radiotherapy and 3D-IGBT doses were summarized and normalized to a biological equivalent dose of 2 Gy per fraction (EQD2) using a linear-quadratic model. Of the 11 institutions representing the participating countries, six (55%) responded to the questionnaire. Overall, data of 36 patients were collected from the six institutions. Twenty-one patients underwent whole-pelvic irradiation and 15 underwent whole-pelvic irradiation with central shielding. Patients received a median of four treatment sessions of 3D-IGBT (range, 2-6). All 3D-IGBT sessions were computed tomography (CT)-based and not magnetic resonance image-based. The median doses to the high-risk clinical target volume D90, bladder D2cc, rectum D2cc and sigmoid colon D2cc were 80.9 Gy EQD2 (range, 58.9-105.9), 77.7 Gy EQD2 (range, 56.9-99.1), 68.0 Gy EQD2 (range, 48.6-90.7) and 62.0 Gy EQD2 (range, 39.6-83.7), respectively. This study elucidated the current patterns of 3D-IGBT for the treatment of cervical cancer in East and Southeast Asia. The results indicate the feasibility of observational studies of CT-based 3D-IGBT for cervical cancer in these countries.

Multi-institutional Observational Study of Prophylactic Extended-Field Concurrent Chemoradiation Therapy Using Weekly Cisplatin for Patients With Pelvic Node-Positive Cervical Cancer in East and Southeast Asia.

PURPOSE: This multi-institutional observational study conducted among 11 countries in East and Southeast Asia aimed to assess the clinical outcomes of prophylactic extended-field concurrent chemoradiation therapy using weekly cisplatin for patients with locally advanced cervical cancer. METHODS AND MATERIALS: Between October 2007 and May 2016, 106 patients with untreated squamous cell carcinoma of the cervix were enrolled in the present study. Radiation therapy consisted of pelvic irradiation (total dose, 50 Gy in 25 fractions including central shielding), prophylactic paraortic regional irradiation (36-40 Gy in 20 fractions), and either high- or low-dose-rate intracavitary brachytherapy (ICBT) according to institutional practice. The planned point A dose was 21 to 28 Gy in 3 to 4 fractions for high-dose-rate ICBT and 40 to 41 Gy in 1 to 2 fractions for low-dose-rate ICBT. Five cycles of weekly cisplatin (40 mg/m2) were administered during the radiation therapy course. RESULTS: A total of 106 patients were enrolled. Of these, 9 had major protocol violations and 2 did not receive treatment because of worsened general condition. Thus, 95 patients were evaluable. The median follow-up was 56 months. Of the 95 patients, 76 (80%) received 4 or 5 cycles of chemotherapy. Acute grade 3 leukopenia was observed in 20 of the patients (21%), and late grade 3 gastrointestinal toxicity was observed in 3%. The 2-year local control, progression-free survival, and overall survival rate for all patients were 96%, 78%, and 90%, respectively. CONCLUSIONS: The results indicated that prophylactic extended-field concurrent chemoradiation therapy using weekly cisplatin is feasible and effective for patients with locally advanced cervical cancer in East and Southeast Asia.

Epidemiology of Prostate Cancer in the Republic of Kazakhstan.

BACKGROUND: The incidence and mortality from prostate cancer in most native Asian populations remain low although a gradual increase is observed over the last years. METHODS: The statistical analysis of official data on prostate cancer mortality and morbidity was performed for the whole country and for Pavlodar Region. RESULTS: The increase in the incidence of prostate cancer among the population of Kazakhstan is observed, which may be attributed to the introduction of screening program based on serum PSA. Still, the crude incidence rates in Kazakhstan are below world indices. Over the last few years, the decreasing prostate cancer mortality is observed that might be influenced by early diagnosis. The age-standardized incidence rates show that the majority of prostate cancer cases occur in advanced ages (70 years and older). CONCLUSION: More research is needed to determine the risk factors for prostate cancer, as well as ethnic and geographical trends for the population of Kazakhstan.

Clinical, Histopathological and Molecular Characteristics of Metastatic Breast Cancer in North-Eastern Kazakhstan: a 10 Year Retrospective Study

Background: Breast cancer (BC) is the top cancer among women worldwide and has been the most frequent malignancy among Kazakhstan women over the past few decades. Information on clinical and histopathological features of metastatic breast cancer (MBC), as well as the distribution of molecular subtypes is limited for Kazakh people. Materials and Methods: The present observational retrospective study was carried out at Regional Oncologic Dispensaries in the North-East Region of Kazakhstan (in Semey and Pavlodar cities). Сlinical and histopathological data were obtained for a total of 570 MBC patients in the 10 year period from 2004-2013, for whom data on molecular subtype were available for 253. Data from hospital charts were entered into SPSS 20 for analysis by one-way ANOVA analysis of associations of different variables with 1-5 year survival. Pearson correlation and linear regression models were used to examine the relation between parameters with a p-value < 0.05 considered statistically significant. Results: No significant relationships were evident between molecular subtype and survival, site of metastases, stage or ethnicity. Young females below the age of 44 were slightly more likely to have triple negative lesions. While the ductal type greatly predomonated, luminal A and B cases had a higher percentage with lobular morphology. Conclusions: In this select group of metastatice brease cancer, no links were noted for survival with molecular subtype, in contrast to much of the literature.

Disorder of Endothelia Vessels' Functional State with Malignant Tumors in Patients Exposed Anthropogenic Radiation.

The aim of this research is to determine the characteristics of endothelial factors and the hemostatic system conditions with malignant neoplasms patients, which were exposed to ionizing radiation. Total number of examined people is 223, 153 of them are patients with gastrointestinal tract oncopathology. The article presents the results of the analysis of numerical indicators of endothelial condition and platelet hemostasis of patients, who had cancer. They lived in the regions of Kazakhstan, subjected to contamination of radionuclides as a result of nuclear weapons tests, which took place in this region from 1949 to 1989. These results then were compared to cancer patients and healthy individuals with no radiation risk. The study revealed the presence of higher levels of endothelial dysfunction and following trigger of the hemostatic system in patients with malignant tumors of the gastrointestinal tract. In particular, the defined high degree of endothelial dysfunction include endothelium- dependent vasodilation, content desquamated endothelial cells in peripheral blood and von Willebrand factor. These indicators have a clear correlation with the degree of disorder of studied parameters of the hemostasis, which can cause the development of thrombotic complications.

Temporal Epidemiological Assessment of Colorectal Cancer Incidence and Mortality in East Kazakhstan, 2004-2013.

Colorectal cancer incidence and mortality in Kazakhstan are relatively high but exact statistics have hitherto been lacking and trends over time are unclear. The present study was therefore undertaken to retrospectively assess data for East Kazakhstan, accessed from the central registration office, for the period 2004-2013. Approximate age standardized data for incidence and mortality were generated and compared across age groups, gender and year. It was determined that during the studied period 3,417 new cases of colorectal cancer were registered and 2,259 died of this pathology. Average cancer cancer incidence and mortality over the ten years were 24.1/105 and 15.9/105 respectively, and the overall ratio of mortality/incidence (M/I) was 0.69:1 (range 0.58-0.73). Both incidence and mortality tended to remain constant in both males and females. The male to female ratios also did not significantly vary over time but a trend for improvement of the mortality to incidence ratio was observed, especially for rectum. Whether this might be related to screening remains unclear. These preliminary data indicate that whereas colorectal cancer continues to be important, change in environmental factors are not having a great impact on incidence in East Kazakhstan.

BRCA1 and BRCA2 Gene Mutations Screening In Sporadic Breast Cancer Patients In Kazakhstan.

BACKGROUND: A large number of distinct mutations in the BRCA1 and BRCA2 genes have been reported worldwide, but little is known regarding the role of these inherited susceptibility genes in breast cancer risk among Kazakhstan women. AIM: To evaluate the role of BRCA1/2 mutations in Kazakhstan women presenting with sporadic breast cancer. METHODS: We investigated the distribution and nature of polymorphisms in BRCA1 and BRCA2 entire coding regions in 156 Kazakhstan sporadic breast cancer cases and 112 age-matched controls using automatic direct sequencing. RESULTS: We identified 22 distinct variants, including 16 missense mutations and 6 polymorphisms in BRCA1/2 genes. In BRCA1, 9 missense mutations and 3 synonymous polymorphisms were observed. In BRCA2, 7 missense mutations and 3 polymorphisms were detected. There was a higher prevalence of observed mutations in Caucasian breast cancer cases compared to Asian cases (p<0.05); higher frequencies of sequence variants were observed in Asian controls. No recurrent or founder mutations were observed in BRCA1/2 genes. There were no statistically significant differences in age at diagnosis, tumor histology, size of tumor, and lymph node involvement between women with breast cancer with or without the BRCA sequence alterations. CONCLUSIONS: Considering the majority of breast cancer cases are sporadic, the present study will be helpful in the evaluation of the need for the genetic screening of BRCA1/2 mutations and reliable genetic counseling for Kazakhstan sporadic breast cancer patients. Evaluation of common polymorphisms and mutations and breast cancer risk in families with genetic predisposition to breast cancer is ongoing in another current investigation.

Vitamin D Receptor Gene Polymorphisms and Breast Cancer Risk in Kazakhstan.

INTRODUCTION: The steroid hormone 1,25-dihydroxyvitamin D3 is thought to protect against breast cancer. The activity of 1,25-dihydroxyvitamin D3 is mediated via the vitamin D receptor (VDR), and a number of polymorphisms in the VDR gene have been identified. These result in distinct genotypes, some of which may alter susceptibility to breast cancer. Two common single nucleotide polymorphisms (SNP) in the VDR gene (VDR), rs1544410 (BsmI) and rs2228570 (FokI), have been inconsistently associated with breast cancer risk. Increased risk has been reported for the FokI ff genotype, which encodes a less transcriptionally active isoform of VDR. A reduced risk has been reported for the BsmI BB genotype which may influence VDR mRNA stability. AIM: We have investigated whether specific VDR gene polymorphisms are associated with breast cancer risk in Kazakhstan women. MATERIAL AND METHODS: In a case-control study, female breast cancer patients (315) and a female control group (n=604) were tested for two VDR polymorphisms. Statistical analysis was conducted using SPSS19.0. RESULTS: : The VDR rs2228570 (FokI) polymorphism was associated with an increased occurence of BC [rs2228570 (folk) ff vs. FF genotype: OR=1.71; 95% CI=1.21-2.43]. No association was noted between rs1544410 (BsmI) BB and breast cancer risk [OR=0.68; 95% CI=0.49-0.95]. CONCLUSION: : Although the factors that increase breast cancer susceptibility remain uncertain, future large studies should integrate genetic variation in VDR with biomarkers of vitamin D status. Additional testing on the effect of varying genotypes on the functional mechanisms of the VDR could help to improve future testing and treatment of woman at risk for breast cancer.