Assessment of safety and tolerability of subcutaneous trastuzumab in patients with HER2-positive early breast cancer: Results of an open-label, randomized, multicenter, phase IIIB ESCAPE trial.

AIM: To assess the safety and tolerability of subcutaneous (SC) trastuzumab (Herceptin) administered either with a single-use injection device (SID) or manually from a vial using a hand-held syringe. METHODS: The ESCAPE trial (NCT02194166) included 90 women aged 18 years or older with HER2-positive early breast cancer who underwent surgical treatment and completed (neo) adjuvant chemotherapy and radiotherapy (if indicated). Patients enrolled in the study were first subjected to 4 cycles of trastuzumab IV (8 mg/kg loading dose followed by 6 mg/kg maintenance dose, q3w) prior to being randomized into groups: [A] SC trastuzumab (fixed dose 600 mg, q3w) administered through a hand-held syringe followed by 7 cycles of SC trastuzumab administered with an SID or [B] the reverse sequence. RESULTS: Patient-reported outcomes revealed that 78 (94.0 % [95 % CI: 90.4-99.0]) out of 83 patients preferred SC trastuzumab over IV trastuzumab, among whom 28 patients indicated a strong preference. Sixteen out of 17 HCPs (94.1 %) were very satisfied with the use of SC trastuzumab, while 1/17 (5.9 %) remained uncertain. The mean time spent for IV vs. SC trastuzumab administration, including pre- and postinjection procedures, was 93.8 and 22 min, respectively. A total of 49 (54.4 %) patients reported 164 AEs. CONCLUSIONS: In this trial, SC trastuzumab was preferred over IV trastuzumab. The duration of SC trastuzumab administration was significantly shorter than that of IV trastuzumab, saving patients and HCPs time. Safety and efficacy results were consistent with other published trials and were not associated with any new safety signal.

Alternative blood transfusion triggers: a narrative review.

BACKGROUND: Anemia, characterized by low hemoglobin levels, is a global public health concern. Anemia is an independent factor worsening outcomes in various patient groups. Blood transfusion has been the traditional treatment for anemia; its triggers, primarily based on hemoglobin levels; however, hemoglobin level is not always an ideal trigger for blood transfusion. Additionally, blood transfusion worsens clinical outcomes in certain patient groups. This narrative review explores alternative triggers for red blood cell transfusion and their physiological basis. MAIN TEXT: The review delves into the physiology of oxygen transport and highlights the limitations of using hemoglobin levels alone as transfusion trigger. The main aim of blood transfusion is to optimize oxygen delivery, necessitating an individualized approach based on clinical signs of anemia and the balance between oxygen delivery and consumption, reflected by the oxygen extraction rate. The narrative review covers different alternative triggers. It presents insights into their diagnostic value and clinical applications, emphasizing the need for personalized transfusion strategies. CONCLUSION: Anemia and blood transfusion are significant factors affecting patient outcomes. While restrictive transfusion strategies are widely recommended, they may not account for the nuances of specific patient populations. The search for alternative transfusion triggers is essential to tailor transfusion therapy effectively, especially in patients with comorbidities or unique clinical profiles. Investigating alternative triggers not only enhances patient care by identifying more precise indicators but also minimizes transfusion-related risks, optimizes blood product utilization, and ensures availability when needed. Personalized transfusion strategies based on alternative triggers hold the potential to improve outcomes in various clinical scenarios, addressing anemia's complex challenges in healthcare. Further research and evidence are needed to refine these alternative triggers and guide their implementation in clinical practice.

Vaccination Effectiveness against Human Papillomavirus in Kazakhstan.

OBJECTIVE: The purpose was to determine the effectiveness of human papillomavirus immunization and its impact on cervical cancer development in Kazakhstan. METHODS: The current research is a case-control study with two groups: a main group and a control group. A total of 725 subjects participated in the research. RESULTS: The association between vaccination and cervical cancer development was calculated both for the two groups as a whole and for individual patients, who were selected based on criteria of residence, presence of immunodeficiency or chronic cardiac or renal pathology, as well as analysis of age at which the vaccine dose was received. There was a statistically significant association between the absence of the human papillomavirus vaccine and the risk of cervical cancer in all groups. When considering the entire cohort, the chance of finding a risk factor (lack of vaccination) was almost 7 times higher in the main group than in the control group. Thus, an association between vaccination and cervical cancer risk was found in each of the pairs of subjects. CONCLUSION: The effectiveness of vaccination in preventing cervical cancer was not observed in patients who were vaccinated after 18 years of age, while most patients in the control group were vaccinated in their teens. The practical significance of the research is not only to further study the problem of human papillomavirus (HPV) vaccination in Kazakhstan but also to popularize HPV immunization to prevent cervical cancer (CC).

Association of Genetic Markers with the Risk of Early-Onset Breast Cancer in Kazakh Women.

Breast cancer is a global health problem. It is an age-dependent disease, but cases of early-onset breast cancer (eBC) are gradually increasing. There are many unresolved questions regarding eBC risk factors, mechanisms of development and screening. Only 10% of eBC cases are due to mutations in the BRCA1/BRCA2 genes, and 90% have a more complex genetic background. This poses a significant challenge to timely cancer detection in young women and highlights the need for research and awareness. Therefore, identifying genetic risk factors for eBC is essential to solving these problems. This study represents an association analysis of 144 eBC cases and 163 control participants to identify genetic markers associated with eBC risks in Kazakh women. We performed a two-stage approach in association analysis to assess genetic predisposition to eBC. First-stage genome-wide association analysis revealed two risk intronic loci in the CHI3L2 gene (p = 5.2 × 10-6) and MGAT5 gene (p = 8.4 × 10-6). Second-stage exonic polymorphisms haplotype analysis showed significant risks for seven haplotypes (p < 9.4 × 10-4). These results point to the importance of studying medium- and low-penetrant genetic markers in their haplotype combinations for a detailed understanding of the role of detected genetic markers in eBC development and prediction.

Natural killer cell activity level in colorectal cancer screening in an average risk population.

Introduction: Increased natural killer cell activity (NKCA) is linked to reduced risk of colorectal cancer (CRC). Several prior studies have investigated the association of NKCA and the incidence of CRC in high-risk subjects. The aim of our study was to investigate NKCA sensitivity in diagnosing advanced neoplasia (AN) and CRC in an average risk population. Material and methods: NKCA was assessed by an enzyme-linked immunosorbent assay (ELISA) blood test in average risk subjects with a range of 25-2500 pg/ml set for ELISA. NKCA higher than 200 pg/ml was defined as negative. The performance of NKCA was evaluated using measures such as sensitivity, specificity, negative and positive predictive values (NPV, PPV), clinical utility index, etc. In addition, odds ratios for developing CRC using logistic regression models were calculated. Results: NKCA was evaluated in 354 average risk individuals (mean age: 58.5 years; 36.2% male). The diagnostic accuracy of NKCA for CRC and AN was 75.5% and 72.3% respectively, with 96.4% NPV. The NKCA test demonstrated a good negative clinical utility index for CRC and AN (0.664 and 0.741, respectively). Individuals with low NKCA had 6.84 times higher odds of having CRC (95% CI: 2.31-20.27; p < 0.001). NKCA was higher in men vs. women (548.5 pg/ml vs. 500.0 pg/ml) and lower in smokers (412 pg/ml vs. 544 pg/ml), non-exercisers (413 pg/ml vs. 653.5 pg/ml), alcohol users (389 pg/ml vs. 476 pg/ml), and native Kazakhs and other Asian ethnic groups (446 pg/ml vs. 514 pg/ml). Conclusions: A high NKCA level has potential ability to rule out CRC and AN in an average risk population.

Five-year overall survival of patients with advanced bladder cancer in Kazakhstan: OSURK registry study.

BACKGROUND: The goals of the OSURK registry study were to assess 5-year overall survival (OS) in patients with metastatic urothelial cancer diagnosed in 2017 in Kazakhstan and collect data on the use of various treatment options in routine clinical practice. METHODS: Patients with newly diagnosed metastatic bladder cancer (BC) were retrospectively identified in the national register of Kazakhstan (ERCP) between January 2017 and January 2018. ERCP is the biggest register in the country and includes patient data from 17 regions. Investigators collected patient information and processed records online on the following anonymised data: demographical characteristics, received treatment and outcomes. Patients were included in the study if mBC was confirmed histologically and they had at least one visit to the cancer center during the follow-up period. The outcomes of interest were overall survival (OS), patient characteristics and treatment patterns. RESULTS: Totally 480 adult patients with metastatic BC were included. Mean number of patients in one region per year was 28.2. Median age at diagnosis of mBC was 70.0 years (range, 30-100). Patients were predominantly male (81.3%), histological subtype of BC (urothelial carcinoma, etc.) was determined in 41%. Overall, 187 (39%) patients received systemic therapy for metastatic disease. Platinum-based chemotherapy was prescribed in 147 (76.8%) patients who received systemic treatment. The majority of treatment was with cisplatin (N=132, 70.6%). Sixty-four (13.3%) patients received ≥2 treatment lines. After median 60.5 months of follow-up the 5-year OS in patients with metastatic BC was 2.7%. The 1-, and 3-year OS rates were 31.0% and 9.8%, respectively. Median OS from the start of treatment was 7.3 months (95% CI 6.5-8.1). CONCLUSIONS: The results of the OSURK study indicate the need for further implementation of innovative drugs in real practice in order to significantly increase the OS of patients with metastatic BC.

Characteristic Mutational Damages in Gastric and Colorectal Adenocarcinomas.

INTRODUCTION: Gastric and colorectal adenocarcinomas are prevalent malignancies characterized by mutations in genes such as p53, RAS, and MDM2, which play crucial roles in tumorigenesis and cancer progression. Understanding the specific mutational patterns and their implications in these cancers was essential for identifying potential therapeutic targets. AIM: To identify the nature of mutational disorders in the p53, p21Waf1, RAS and MDM2 genes, depending on the degree of cell differentiation by adenocarcinomas of the gastrointestinal tract. METHODS: Genomic DNA was isolated from 200 samples of stomach tissue and 233 samples of colon and rectum adenocarcinomas. A total of 433 samples, including gastric adenocarcinomas, colon and rectum adenocarcinomas and adjacent tissues, were collected. RESULTS: Genomic DNA was isolated, and mutational analysis of p53, RAS (HRAS, KRAS, NRAS), and MDM2 genes was performed using polymerase chain reaction, gel electrophoresis, and restriction enzyme analysis. The deletion of p53 exon-intron 5-6, as well as HRAS 12 and HRAS 61 mutations, were detected in 78% of poorly differentiated adenocarcinomas. The deletions of p53 exon-intron 7-9 - in 100% of moderately differentiated adenocarcinomas and 50-60% of adjacent tissues. The loss of WAF1 gene expression was registered in almost 90% of poorly differentiated adenocarcinomas and 20% of adjacent tissue samples. The KRAS and NRAS mutations in almost 63.9% of studied colon and rectal samples indicated autonomous cell growth. This explains the aggressive and metastatic growth of tumours and the ineffectiveness of growth factor inhibitors in colorectal cancer. Finding ways to influence specific substitutions in RAS genes could prevent and eliminate uncontrolled invasive tumour growth. CONCLUSION: By identifying specific gene mutations and differences in genetic markers, the study provided insights for the development of targeted diagnostic methods and personalised treatment strategies, ultimately improving the clinical outcomes in the field of oncology.

Determination of genetic predisposition to early breast cancer in women of Kazakh ethnicity.

Breast cancer (BC) is the most common type of cancer among women in Kazakhstan. To date, little data are available on the spectrum of genetic variation in Kazakh women with BC. We aimed to identify population-specific genetic markers associated with the risk of developing early-onset BC and test their association with clinical and prognostic factors. The study included 224 Kazakh women diagnosed with BC (≤40 age). Entire coding regions (>1700 exons) and the flanking noncoding regions of 94 cancer-associated genes were sequenced from blood DNA using MiSeq platform. We identified 38 unique pathogenic variants (PVs) in 13 different cancer-predisposing genes among 57 patients (25.4%), of which 6 variants were novel. In total, 12 of the 38 distinct PVs were detected recurrently, including BRCA1 c.5266dup, c.5278-2del, and c.2T>C, and BRCA2 c.9409dup and c.9253del that may be founder in this population. BRCA1 carriers were significantly more likely to develop triple-negative BC (OR = 6.61, 95% CI 2.44-17.91, p = 0.0002) and have family history of BC (OR = 3.17, 95% CI 1.14-8.76, p = 0.03) compared to non-carriers. This study allowed the identification of PVs specific to early-onset BC, which may be used as a foundation to develop regional expertise and diagnostic tools for early detection of BC in young Kazakh women.

Corrigendum: Systemic treatment of breast cancer. 1st Central-Eastern European professional Consensus Statement on breast cancer.

[This corrects the article DOI: 10.3389/pore.2022.1610383.].

LGR5 As a Potential Therapeutic Target for Breast Cancer: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVE: Breast cancer is the world's most common malignancy. Despite significant advances in the diagnosis and treatment of the disease, the associated mortality rate is still high. Tumor initiating cells known as cancer stem cells with unique abilities are suspected responsible for therapy failure and poor prognosis. Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a cancer stem cell marker that promotes aggressive features in breast cancer cells. So, the aim of this study was to perform a systematic review and meta-analysis to evaluate LGR5 as a therapeutic target for breast cancer. METHODS: This systematic review and meta-analysis were performed using databases of Web of Science, Scopus, and PubMed. We searched these databases with LGR5 and Breast Cancer and related keywords based on the mesh database until Oct12, 2021. All studies that reported the rate of LGR5 high expression with Immunohistochemistry in breast cancer patients were included in this review. We used the STATA and random effect models for data analysis. RESULTS: Finally, 7 studies including 2632 breast cancer samples were studied. The pooled prevalence of LGR5 high expression in breast cancer was 48.6 % (CI95%: 40.5-56.7%, I2=0.0) and in triple negative was 48.6% (CI95%: 38.4-58.7%, I2= 0.0). CONCLUSION: Our findings show that the rate of LGR5 high expression in breast cancer in general and especially in triple-negative was considerable and it seems that this is a potential therapeutic target for breast cancer.

SUCCOR quality: validation of ESGO quality indicators for surgical treatment of cervical cancer.

OBJECTIVE: To evaluate whether compliance with European Society of Gynaecological Oncology (ESGO) surgery quality indicators impacts disease-free survival in patients undergoing radical hysterectomy for cervical cancer. METHODS: In this retrospective cohort study, 15 ESGO quality indicators were assessed in the SUCCOR database (patients who underwent radical hysterectomy for International Federation of Gynecology and Obstetrics (FIGO) stage 2009 IB1, FIGO 2018 IB1, and IB2 cervical cancer between January 2013 and December 2014), and the final score ranged between 0 and 16 points. Centers with more than 13 points were classified as high-quality indicator compliance centers. We constructed a weighted cohort using inverse probability weighting to adjust for the variables. We compared disease-free survival and overall survival using Cox proportional hazards regression analysis in the weighted cohort. RESULTS: A total of 838 patients were included in the study. The mean number of quality indicators compliance in this cohort was 13.6 (SD 1.45). A total of 479 (57.2%) patients were operated on at high compliance centers and 359 (42.8%) patients at low compliance centers. High compliance centers performed more open surgeries (58.4% vs 36.7%, p<0.01). Women who were operated on at centers with high compliance with quality indicators had a significantly lower risk of relapse (HR=0.39; 95% CI 0.25 to 0.61; p<0.001). The association was reduced, but remained significant, after further adjustment for conization, surgical approach, and use of manipulator surgery (HR=0.48; 95% CI 0.30 to 0.75; p=0.001) and adjustment for adjuvant therapy (HR=0.47; 95% CI 0.30 to 0.74; p=0.001). Risk of death from disease was significantly lower in women operated on at centers with high adherence to quality indicators (HR=0.43; 95% CI 0.19 to 0.97; p=0.041). However, the association was not significant after adjustment for conization, surgical approach, use of manipulator surgery, and adjuvant therapy. CONCLUSIONS: Patients with early cervical cancer who underwent radical hysterectomy in centers with high compliance with ESGO quality indicators had a lower risk of recurrence and death.

Evolution of the joint International Atomic Energy Agency (IAEA), International Agency for Research on Cancer (IARC), and WHO cancer control assessments (imPACT Reviews).

Before 2005, cancer and other non-communicable diseases were not yet health and development agenda priorities. Since the 2005 World Health Assembly Resolution, which encouraged WHO, the International Agency for Research on Cancer (IARC), and the International Atomic Energy Agency (IAEA) to jointly work on cancer control, progress was achieved in low-income and middle-income countries on a small scale. Recently, rapid acceleration in UN collaboration and global cancer activities has focused attention in global cancer control. This Policy Review presents the evolution of the IAEA, IARC, and WHO joint advisory service to help countries assess needs and capacities throughout the comprehensive cancer control continuum. We also highlight examples per country, showcasing a snapshot of global good practices to foster an exchange of experiences for continuous improvement in the integrated mission of Programme of Action for Cancer Therapy (imPACT) reviews and follow-up support. The future success of progress in cancer control lies in the high-level political and financial commitments. Linking the improvement of cancer services to the strengthening of health systems after the COVID-19 pandemic will also ensure ongoing advances in the delivery of care across the cancer control continuum.

Early integration of palliative care into oncological care: a focus on patient-important outcomes.

BACKGROUND: Globally, cancer remains one of the leading causes of mortality. Palliative care is designed to meet a range of cancer patients' priority issues, including the management of pain and other cancer-associated symptoms. Routine palliative care envisages the provision of not just medical therapy, but also psychological support, social support and spiritual assistance. What constitutes the best model for palliative care remains a matter of debate. AIM: This review was undertaken with the aim to discuss different aspects of early integration of palliative care into oncological care, with a focus on patient-important outcomes. METHODS: A comprehensive search of publications was conducted with a focus on integrative palliative care for incurable cancer patients. For this purpose, the following databases and search engines were used: Scopus, PubMed, Cochrane Library, Research Gate, Google Scholar, eLIBRARY and Cyberleninka. RESULTS: A comprehensive approach with early integration of different medical services appears to be the most promising. Integrative palliative care is best provided via specialised interdisciplinary teams, given that all members maintain systemic communications and regularly exchange information. This model ensures that timely and adequate interventions are provided to address the needs of patients. CONCLUSION: Further research is needed to pinpoint the most optimal strategies to deliver palliative care and make it as tailored to the patient's demands as possible.

Effects of metastatic CRC predictors on treatment outcomes.

BACKGROUND: Colorectal cancer (CRC) is the third most commonly diagnosed malignant tumor. The problem of mCRC is urgent due to both an increase in the number of metastatic tumors and the implementation of high-tech treatment methods that have significantly improved the results of a 5-year survival. METHODS: The research used the method of experiment and observation. Current study included data of 332 patients with CRC who received comprehensive treatment from 2014 to 2018 in oncology centers of the Republic of Kazakhstan. The patients were treated according to the clinical protocols for the treatment of oncological diseases approved in the Republic of Kazakhstan, including surgical treatment, as well as chemotherapy and radiation therapy, depending on the stage and localization of the process. A comprehensive treatment also included surgical treatment, chemotherapy, targeted chemotherapy and, in some cases, radiation therapy for rectal cancer. The diagnosis was confirmed morphologically in all patients; process dissemination was recorded using standard examination methods. Among the patients, women prevailed - 182 (54.8%) women and 150 men (45.2%) were included; the Caucasian race prevailed - 170 (51.2%) patients and 162 (48.8%) patients were of the Asian race. The mean age of the patients at the time of treatment was 56.4 ± 0.6 years (from 25 to 79 years). Histologically, adenocarcinoma prevailed represented by glandular - in 95.6%, mucous - in 2.9% and trabecular - in 1.5% of cases. A comprehensive treatment was used in 209 (63.0%) patients and other types of treatment were used in 123 (37.0%) patients (PCT, stoma + PCT). Radiation therapy was administered to 13 (3.9%) patients diagnosed with rectal cancer. RESULTS: A comparative analysis of the results of pharmacotherapy in the patients with mCRC showed that of 332 patients, 263 (79.2%) received targeted chemotherapy and 69 (20.8%) received standard polychemotherapy. At the time of the study, 85 (32.3%) patients in the targeted chemotherapy group were still alive, with a median survival of 42.0 ± 1.7 months, 95% CI (38.6-45.4). In the polychemotherapy group, 7 (10.1%) patients were alive, while the median survival rate was 20.0 ± 1.7 months, 95% CI (16.6-23.4). CONCLUSION: Based on the results, it was concluded that targeted chemotherapy schemes increased progression-free survival, compared to standard polychemotherapy schemes.

Systemic Treatment of Breast Cancer. 1st Central-Eastern European Professional Consensus Statement on Breast Cancer.

This text is based on the recommendations accepted by the 4th Hungarian Consensus Conference on Breast Cancer, modified based on the international consultation and conference within the frames of the Central-Eastern European Academy of Oncology. The professional guideline primarily reflects the resolutions and recommendations of the current ESMO, NCCN and ABC5, as well as that of the St. Gallen Consensus Conference statements. The recommendations cover classical prognostic factors and certain multigene tests, which play an important role in therapeutic decision-making. From a didactic point of view, the text first addresses early and then locally advanced breast cancer, followed by locoregionally recurrent and metastatic breast cancer. Within these, we discuss each group according to the available therapeutic options. At the end of the recommendations, we summarize the criteria for treatment in certain rare clinical situations.

Lung Cancer Screening With Low-dose Chest Computed Tomography: Experience From Radon-contaminated Regions in Kazakhstan.

OBJECTIVES: The aim of this study was to present the baseline results of a pilot project conducted to evaluate the effectiveness of lung cancer screening using low-dose chest computed tomography (CT) in regions with excessive radon levels in the Republic of Kazakhstan. METHODS: In total, 3671 participants were screened by low-dose chest CT. Current, former, and never-smokers who resided in regions with elevated levels of radon in drinking water sources and indoor air, aged between 40 and 75 with no history of any cancer, and weighing less than 140 kg were included in the study. All lung nodules were categorized according to the American College of Radiology Lung Imaging Reporting and Data System (Lung-RADS 1.0). RESULTS: Overall, 614 (16.7%) participants had positive baseline CT findings (Lung-RADS categories 3 and 4). Seventy-four cancers were detected, yielding an overall cancer detection rate of 2.0%, with 10.8% (8/74) stage I and a predominance of stage III (59.4%; 44/74). Women never-smokers and men current smokers had the highest cancer detection rates, at 2.9% (12/412) and 6.1% (12/196), respectively. Compared to never-smokers, higher odds ratios (ORs) of lung cancer detection were found in smokers (OR,2.48; 95% confidence interval [CI], 1.52 to 4.05, p<0.001) and former smokers (OR, 2.32; 95% CI, 1.06 to 5.06, p=0.003). The most common histologic type of cancer was adenocarcinoma (58.1%). CONCLUSIONS: Implementation of low-dose CT screening for lung cancer in regions with elevated radon levels is an effective method for both smokers and never-smokers.

OPEC study: An international multicenter study of ovarian preservation in endometrial cancers.

OBJECTIVE: To evaluate the feasibility and oncological safety of ovarian preservation in early stage endometrial adenocarcinoma (EC) patients aged 40 and below. METHODS: A total of 11 institutions from eight countries participated in the study. 169 of 5898 patients aged ≤40 years were eligible for the study. Patients with EC treated between March 2007 and January 2019 were retrospectively assessed. RESULTS: The median duration of follow-up after EC diagnosis was 59 months (4-187). Among 169 participants, ovarian preservation surgery (OPS) was performed in 54 (31.9%), and BSO was performed in 115 (68.1%) patients. Although patients younger than 30 years of age were more likely to have OPS than patients aged 30 to 40 years (20.4% vs. 9.6%, P = 0.021), there was no significant difference by the mean age. There were no other relevant baseline differences between OPS and BSO groups. The Kaplan-Meier analysis revealed no difference in either the overall survival (P = 0.955) or recurrence-free survival (P = 0.068) among patients who underwent OPS, and BSO. CONCLUSION: OPS appears to be safe without having any adverse impact on survival in women aged ≤40 years with FIGO Stage I EC.

SUCCOR cone study: conization before radical hysterectomy.

OBJECTIVE: To evaluate disease-free survival of cervical conization prior to radical hysterectomy in patients with stage IB1 cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) 2009). METHODS: A multicenter retrospective observational cohort study was conducted including patients from the Surgery in Cervical Cancer Comparing Different Surgical Aproaches in Stage IB1 Cervical Cancer (SUCCOR) database with FIGO 2009 IB1 cervical carcinoma treated with radical hysterectomy between January 1, 2013, and December 31, 2014. We used propensity score matching to minimize the potential allocation biases arising from the retrospective design. Patients who underwent conization but were similar for other measured characteristics were matched 1:1 to patients from the non-cone group using a caliper width ≤0.2 standard deviations of the logit odds of the estimated propensity score. RESULTS: We obtained a weighted cohort of 374 patients (187 patients with prior conization and 187 non-conization patients). We found a 65% reduction in the risk of relapse for patients who had cervical conization prior to radical hysterectomy (hazard ratio (HR) 0.35, 95% confidence interval (CI) 0.16 to 0.75, p=0.007) and a 75% reduction in the risk of death for the same sample (HR 0.25, 95% CI 0.07 to 0.90, p=0.033). In addition, patients who underwent minimally invasive surgery without prior conization had a 5.63 times higher chance of relapse compared with those who had an open approach and previous conization (HR 5.63, 95% CI 1.64 to 19.3, p=0.006). Patients who underwent minimally invasive surgery with prior conization and those who underwent open surgery without prior conization showed no differences in relapse rates compared with those who underwent open surgery with prior cone biopsy (reference) (HR 1.94, 95% CI 0.49 to 7.76, p=0.349 and HR 2.94, 95% CI 0.80 to 10.86, p=0.106 respectively). CONCLUSIONS: In this retrospective study, patients undergoing cervical conization before radical hysterectomy had a significantly lower risk of relapse and death.

Open vs minimally invasive radical trachelectomy in early-stage cervical cancer: International Radical Trachelectomy Assessment Study.

BACKGROUND: Minimally invasive radical trachelectomy has emerged as an alternative to open radical hysterectomy for patients with early-stage cervical cancer desiring future fertility. Recent data suggest worse oncologic outcomes after minimally invasive radical hysterectomy than after open radical hysterectomy in stage I cervical cancer. OBJECTIVE: We aimed to compare 4.5-year disease-free survival after open vs minimally invasive radical trachelectomy. STUDY DESIGN: This was a collaborative, international retrospective study (International Radical Trachelectomy Assessment Study) of patients treated during 2005-2017 at 18 centers in 12 countries. Eligible patients had squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma; had a preoperative tumor size of ≤2 cm; and underwent open or minimally invasive (robotic or laparoscopic) radical trachelectomy with nodal assessment (pelvic lymphadenectomy and/or sentinel lymph node biopsy). The exclusion criteria included neoadjuvant chemotherapy or preoperative pelvic radiotherapy, previous lymphadenectomy or pelvic retroperitoneal surgery, pregnancy, stage IA1 disease with lymphovascular space invasion, aborted trachelectomy (conversion to radical hysterectomy), or vaginal approach. Surgical approach, indication, and adjuvant therapy regimen were at the discretion of the treating institution. A total of 715 patients were entered into the study database. However, 69 patients were excluded, leaving 646 in the analysis. Endpoints were the 4.5-year disease-free survival rate (primary), 4.5-year overall survival rate (secondary), and recurrence rate (secondary). Kaplan-Meier methods were used to estimate disease-free survival and overall survival. A post hoc weighted analysis was performed, comparing the recurrence rates between surgical approaches, with open surgery being considered as standard and minimally invasive surgery as experimental. RESULTS: Of 646 patients, 358 underwent open surgery, and 288 underwent minimally invasive surgery. The median (range) patient age was 32 (20-42) years for open surgery vs 31 (18-45) years for minimally invasive surgery (P=.11). Median (range) pathologic tumor size was 15 (0-31) mm for open surgery and 12 (0.8-40) mm for minimally invasive surgery (P=.33). The rates of pelvic nodal involvement were 5.3% (19 of 358 patients) for open surgery and 4.9% (14 of 288 patients) for minimally invasive surgery (P=.81). Median (range) follow-up time was 5.5 (0.20-16.70) years for open surgery and 3.1 years (0.02-11.10) years for minimally invasive surgery (P<.001). At 4.5 years, 17 of 358 patients (4.7%) with open surgery and 18 of 288 patients (6.2%) with minimally invasive surgery had recurrence (P=.40). The 4.5-year disease-free survival rates were 94.3% (95% confidence interval, 91.6-97.0) for open surgery and 91.5% (95% confidence interval, 87.6-95.6) for minimally invasive surgery (log-rank P=.37). Post hoc propensity score analysis of recurrence risk showed no difference between surgical approaches (P=.42). At 4.5 years, there were 6 disease-related deaths (open surgery, 3; minimally invasive surgery, 3) (log-rank P=.49). The 4.5-year overall survival rates were 99.2% (95% confidence interval, 97.6-99.7) for open surgery and 99.0% (95% confidence interval, 79.0-99.8) for minimally invasive surgery. CONCLUSION: The 4.5-year disease-free survival rates did not differ between open radical trachelectomy and minimally invasive radical trachelectomy. However, recurrence rates in each group were low. Ongoing prospective studies of conservative management of early-stage cervical cancer may help guide future management.

Colorectal Cancer Screening with Computed Tomography Colonography: Single Region Experience in Kazakhstan.

BACKGROUND/AIMS: The aim of our study was to determine the efficacy of computed tomography colonography (CTC) in screening for colorectal cancer (CRC). METHODS: A total of 612 females and 588 males aged 45 to 75 years were enrolled in CTC screening. CTC was performed following standard bowel preparation and colonic insufflation with carbon dioxide. The main outcomes were the detection rate of CRC and advanced adenoma (AA), prevalence of colorectal lesions in relation to socio-demographic and health factors, and overall diagnostic performance of CTC. RESULTS: Overall, 56.5% of the 1,200 invited subjects underwent CTC screening. The sensitivity for CRC and AA was 0.89 and 0.97, respectively, while the specificity was 0.71 and 0.99, respectively. The prevalence of CRC and AA was 3.0% (18/593) and 7.1% (42/593), respectively, with the highest CRC prevalence in the 66-75 age group (≥12 times; odds ratio [OR], 12.11; 95% confidence interval [CI], 4.45-32.92). CRC and AA prevalence were inversely correlated with Asian descent, physical activity, and negative fecal immunochemical test results (OR=0.43; 95% CI, 0.22-0.83; OR=0.16; 95% CI, 0.04-0.68; OR=0.5; 95% CI, 0.07-3.85, respectively). CONCLUSION: Our study revealed high accuracy of CTC in diagnosing colonic neoplasms, good compliance with CTC screening, and high detection rate of CRC.