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.

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.

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.

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.

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.

Comparison of breast cancer and cervical cancer stage distributions in ten newly independent states of the former Soviet Union: a population-based study.

BACKGROUND: Screening for breast cancer and cervical cancer in the newly independent states of the former Soviet Union is largely opportunistic, and countries in the region have among the highest cervical cancer incidence in the WHO European Region. We aimed to compare the stage-specific distributions and changes over time in breast cancer and cervical cancer incidence in the newly independent states of the former Soviet Union. METHODS: We collected breast cancer and cervical cancer incidence data from official statistics from Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Republic of Moldova, Russian Federation, Ukraine, and Uzbekistan for the years 2008-17 by tumour, node, metastasis (TNM) stage, and by age where population-based cancer registry data were available. We used log-linear regression to quantify the changes over time in age-standardised rates. FINDINGS: During the period 2013-17, more than 50% of breast cancer cases across the analysed countries, and more than 75% of breast cancer cases in Belarus, Kazakhstan, and Ukraine, were registered at stages I-II. The proportion of stage I breast cancer cases was highest in the screening age group (50-69 years) compared with other ages in Moldova and the Russian registries, but was highest in those aged 15-49 years in Georgia and Ukraine. Breast cancer stage-specific incidence rates increased over time, most prominently for stage I cancers. For cervical cancer, the proportions of cancers diagnosed at a late stage (stages III and IV) were high, particularly in Moldova and Armenia (>50%). The proportion of stage I cervical cancer cases decreased with age in all countries, whereas the proportions of late stage cancers increased with age. Stage-specific incidence rates of cervical cancer generally increased over the period 2008-17. INTERPRETATION: Our results suggest modest progress in early detection of breast cancer in the newly independent states of the former Soviet Union. The high proportions of early-stage disease in the absence of mammography screening (eg, in Belarus) provide a benchmark for what is achievable with rapid diagnosis. For cervical cancer, there is a need to tackle the high burden and unfavourable stage-specific changes over time in the region. A radical shift in national policies away from opportunistic screening toward organised, population-based, quality-assured human papillomavirus vaccination and screening programmes is urgently needed. FUNDING: Union for International Cancer Control, WHO Regional Office for Europe, and Ministry of Health of Ukraine.

Radical hysterectomy in early cervical cancer in Europe: characteristics, outcomes and evaluation of ESGO quality indicators.

INTRODUCTION: Comprehensive updated information on cervical cancer surgical treatment in Europe is scarce. OBJECTIVE: To evaluate baseline characteristics of women with early cervical cancer and to analyze the outcomes of the ESGO quality indicators after radical hysterectomy in the SUCCOR database. METHODS: The SUCCOR database consisted of 1272 patients who underwent radical hysterectomy for stage IB1 cervical cancer (FIGO 2009) between January 2013 and December 2014. After exclusion criteria, the final sample included 1156 patients. This study first described the clinical, surgical, pathological, and follow-up variables of this population and then analyzed the outcomes (disease-free survival and overall survival) after radical hysterectomy. Surgical-related ESGO quality indicators were assessed and the accomplishment of the stated recommendations was verified. RESULTS: The mean age of the patients was 47.1 years (SD 10.8), with a mean body mass index of 25.4 kg/m2 (SD 4.9). A total of 423 (36.6%) patients had a previous cone biopsy. Tumor size (clinical examination) <2 cm was observed in 667 (57.7%) patients. The most frequent histology type was squamous carcinoma (794 (68.7%) patients), and positive lymph nodes were found in 143 (12.4%) patients. A total of 633 (54.8%) patients were operated by open abdominal surgery. Intra-operative complications occurred in 108 (9.3%) patients, and post-operative complications during the first month occurred in 249 (21.5%) patients, with bladder dysfunction as the most frequent event (119 (10.3%) patients). Clavien-Dindo grade III or higher complication occurred in 56 (4.8%) patients. A total of 510 (44.1%) patients received adjuvant therapy. After a median follow-up of 58 months (range 0-84), the 5-year disease-free survival was 88.3%, and the overall survival was 94.9%. In our population, 10 of the 11 surgical-related quality indicators currently recommended by ESGO were fully fulfilled 5 years before its implementation. CONCLUSIONS: In this European cohort, the rate of adjuvant therapy after radical hysterectomy is higher than for most similar patients reported in the literature. The majority of centers were already following the European recommendations even 5 years prior to the ESGO quality indicator implementations.

Contrast-enhanced spectral mammography without and with a delayed image for diagnosing malignancy among mass lesions in dense breast.

AIM OF THE STUDY: To analyse the diagnostic performance of contrast-enhanced spectral mammography (CESM) based on morphologic and enhancement patterns of mass lesions in dense breast using different protocols: CESM without delayed image and CESM with delayed image. MATERIAL AND METHODS: A total of 151 informed women with suspicious for malignancy mass lesions in dense breast were included in this study. All of them underwent CESM using 2 protocols. A total of 155 lesions were pathomorphologically verified. We analysed morphologic patterns on low-energy (LE) images and recombined images (RI) by defining the shape, margin, and dynamic patterns based on delayed images. RESULTS: The comparative analysis revealed that the shape and margins on RI were more significant than those on LE images. The dynamic indicators of CESM were found to be highly significant in dense breasts. The correlation between kinetic curve and histological results demonstrated that a persistent type of curve was common for benign lesions, accounting for 15/22 (68.1%); plateau and washout - for malignant lesions, accounting for 24/89 (26.9%) and 61/89 (68.5%), respectively. Delayed image leads to an increase of specificity up to 12.4%, which is statistically significant. The area under the curve (AUC) in CESM with delayed image is larger than that in CESM without delayed image (p < 0.01). CONCLUSIONS: CESM is sensitive for the differential diagnosis of breast lesions. CESM with delayed image has higher specificity than CESM without delayed image. Delayed images with plateau and washout are typical for malignancy.

Single-centre evaluation and staging of rectal carcinoma on a 3-Tesla magnetic resonance imaging and correlation with histological profile.

PURPOSE: To assess magnetic resonance imaging (MRI) features of rectal carcinoma in correlation with pathology, and to evaluate the diagnostic accuracy of 3-Tesla MRI. MATERIAL AND METHODS: A total of 86 patients were included. 3T MR imaging was conducted pre-operatively, with imaging data correlated to pathology results. High-resolution, 2-dimensional, T2-weighted fast-spin echo sequences in the sagittal, axial, and coronal planes used to tumour staging. Diffusion-weighted images were used to increase the accuracy of tumour evaluation. RESULTS: Rectal carcinoma was staged as T3 in 45.3% of all patients (n = 39), without involvement of the mesorectal fascia in 31.4% (n = 27), and with a possible or obvious invasion in 14% of patients (n = 12). The diagnostic accuracy of 3T MRI was 97.6% for the T1 stage, 92.1% for T2, 89% for T3, and 90% for T4 tumours. MR-derived extramural vascular invasion (EMVI) was found in 16.2% (n = 14), with an estimated diagnostic accuracy of 95%. Diffusion-weighted images and apparent diffusion coefficient were estimated for the different histology types of rectal carcinoma. The average apparent diffusion coefficient for adenocarcinoma was 0.846 ± 0.17, for mucinous adenocarcinoma it was 1.17 ± 0.08, and for signet cell and squamous carcinomas it was 0.91 ± 0.11 and 0.796 ± 0.21 mm2/s, respectively. CONCLUSIONS: 3T MRI enables high levels of diagnostic accuracy in local rectal carcinoma staging, including assessment of mesorectal fascia infiltration and EMVI-status with high accuracy.

SUCCOR study: an international European cohort observational study comparing minimally invasive surgery versus open abdominal radical hysterectomy in patients with stage IB1 cervical cancer.

BACKGROUND: Minimally invasive surgery in cervical cancer has demonstrated in recent publications worse outcomes than open surgery. The primary objective of the SUCCOR study, a European, multicenter, retrospective, observational cohort study was to evaluate disease-free survival in patients with stage IB1 (FIGO 2009) cervical cancer undergoing open vs minimally invasive radical hysterectomy. As a secondary objective, we aimed to investigate the association between protective surgical maneuvers and the risk of relapse. METHODS: We obtained data from 1272 patients that underwent a radical hysterectomy by open or minimally invasive surgery for stage IB1 cervical cancer (FIGO 2009) from January 2013 to December 2014. After applying all the inclusion-exclusion criteria, we used an inverse probability weighting to construct a weighted cohort of 693 patients to compare outcomes (minimally invasive surgery vs open). The first endpoint compared disease-free survival at 4.5 years in both groups. Secondary endpoints compared overall survival among groups and the impact of the use of a uterine manipulator and protective closure of the colpotomy over the tumor in the minimally invasive surgery group. RESULTS: Mean age was 48.3 years (range; 23-83) while the mean BMI was 25.7 kg/m2 (range; 15-49). The risk of recurrence for patients who underwent minimally invasive surgery was twice as high as that in the open surgery group (HR, 2.07; 95% CI, 1.35 to 3.15; P=0.001). Similarly, the risk of death was 2.42-times higher than in the open surgery group (HR, 2.45; 95% CI, 1.30 to 4.60, P=0.005). Patients that underwent minimally invasive surgery using a uterine manipulator had a 2.76-times higher hazard of relapse (HR, 2.76; 95% CI, 1.75 to 4.33; P<0.001) and those without the use of a uterine manipulator had similar disease-free-survival to the open surgery group (HR, 1.58; 95% CI, 0.79 to 3.15; P=0.20). Moreover, patients that underwent minimally invasive surgery with protective vaginal closure had similar rates of relapse to those who underwent open surgery (HR, 0.63; 95% CI, 0.15 to 2.59; P<0.52). CONCLUSIONS: Minimally invasive surgery in cervical cancer increased the risk of relapse and death compared with open surgery. In this study, avoiding the uterine manipulator and using maneuvers to avoid tumor spread at the time of colpotomy in minimally invasive surgery was associated with similar outcomes to open surgery. Further prospective studies are warranted.

SATEN III-Splitting Adjuvant Treatment of stage III ENdometrial cancers: an international, multicenter study.

INTRODUCTION: The purposes of this study were to compare adjuvant treatment modalities and to determine prognostic factors in stage III endometrioid endometrial cancer (EC). METHODS: SATEN III was a retrospective study involving 13 centers from 10 countries. Patients who had been operated on between 1998 and 2018 and diagnosed with stage III endometrioid EC were analyzed. RESULTS: A total of 990 women were identified; 317 with stage IIIA, 18 with stage IIIB, and 655 with stage IIIC diseases. The median follow-up was 42 months. The 5-year disease-free survival (DFS) of patients with stage III EC by adjuvant treatment modality was 68.5% for radiotherapy (RT), 54.6% for chemotherapy (CT), and 69.4% for chemoradiation (CRT) (p=0.11). The 5-year overall survival (OS) for those patients was 75.6% for RT, 75% for CT, and 80.7% for CRT (p=0.48). For patients with stage IIIA disease treated by RT versus CT versus CRT, the 5-year OS rates were 75.6%, 75.0%, and 80.7%, respectively (p=0.48). Negative peritoneal cytology (HR: 0.45, 95% CI: 0.23 to 0.86; p=0.02) and performance of lymphadenectomy (HR: 0.33, 95% CI: 0.16 to 0.77, p=0.001) were independent predictors for improved OS for stage IIIA EC. For women with stage IIIC EC treated by RT, CT, and CRT, the 5-year OS rates were 78.9%, 67.0%, and 69.8%, respectively (p=0.08). Independent prognostic factors for better OS for stage IIIC disease were age <60 (HR: 0.50, 95%CI: 0.36 to 0.69, p<0.001), grade 1 or 2 disease (HR: 0.59, 95% CI: 0.37 to 0.94, p=0.014; and HR: 0.65, 95%CI: 0.46 to 0.91, p=0.014, respectively), absence of cervical stromal involvement (HR: 063, 95% CI: 0.46 to 0.86, p=0.004) and performance of para-aortic lymphadenectomy (HR: 0.52, 95% CI: 0.35 to 0.72, p<0.001). DISCUSSION: Although not statistically significant, CRT seemed to be a better adjuvant treatment option for stage IIIA endometrioid EC. Systematic lymphadenectomy seemed to improve survival outcomes in stage III endometrioid EC.

International radical trachelectomy assessment: IRTA study.

BACKGROUND: Radical trachelectomy is considered a viable option for fertility preservation in patients with low-risk, early-stage cervical cancer. Standard approaches include laparotomy or minimally invasive surgery when performing radical trachelectomy. PRIMARY OBJECTIVE: To compare disease-free survival between patients with FIGO (2009) stage IA2 or IB1 (≤2cm) cervical cancer who underwent open versus minimally invasive (laparoscopic or robotic) radical trachelectomy. STUDY HYPOTHESIS: We hypothesize that minimally invasive radical trachelectomy has similar oncologic outcomes to those of the open approach. STUDY DESIGN: This is a collaborative, multi-institutional, international, retrospective study. Patients who underwent a radical trachelectomy and lymphadenectomy between January 1, 2005 and December 31, 2017 will be included. Institutional review board approval will be required. Each institution will be provided access to a study-specific REDCap (Research Electronic Data Capture) database maintained by MD Anderson Cancer Center and will be responsible for entering patient data. INCLUSION CRITERIA: Patients with squamous, adenocarcinoma, or adenosquamous cervical cancer FIGO (2009) stages IA2 and IB1 (≤2 cm) will be included. Surgery performed by the open approach or minimally invasive approach (laparoscopy or robotics). Tumor size ≤2 cm, by physical examination, ultrasound, MRI, CT, or positron emission tomography (at least one should confirm a tumor size ≤2 cm). Centers must contribute at least 15 cases of radical trachelectomy (open, minimally invasive, or both). EXCLUSION CRITERIA: Prior neoadjuvant chemotherapy or radiotherapy to the pelvis for cervical cancer at any time, prior lymphadenectomy, or pelvic retroperitoneal surgery, pregnant patients, aborted trachelectomy (intra-operative conversion to radical hysterectomy), or vaginal approach. PRIMARY ENDPOINT: The primary endpoint is disease-free survival measured as the time from surgery until recurrence or death due to disease. To evaluate the primary objective, we will compare disease-free survival among patients with FIGO (2009) stage IA2 or IB1 (≤2cm) cervical cancer who underwent open versus minimally invasive radical trachelectomy. SAMPLE SIZE: An estimated 535 patients will be included; 256 open and 279 minimally invasive radical trachelectomy. Previous studies have shown that recurrence rates in the open group range from 3.8% to 7.6%. Assuming that the 4.5-year disease-free survival rate for patients who underwent open surgery is 95.0%, we have 80% power to detect a 0.44 HR using α level 0.10. This corresponds to an 89.0% disease-free survival rate at 4.5 years in the minimally invasive group.

Association of DCC, MLH1, GSTT1, GSTM1, and TP53 gene polymorphisms with colorectal cancer in Kazakhstan.

This study presents the first results of a molecular-genetic study of colorectal cancer (CRC) in Kazakhstan. Blood samples were collected from patients diagnosed with rectal or colon cancer (249 individuals) as well as a control cohort of healthy volunteers (245 individuals), taking into account the age, gender, ethnicity, and smoking habits of the CRC patients. Combined analysis of data obtained from individuals of either Kazakh or Russian decent showed a significant association with increased CRC risk in the following genotypes: DCC (32008376G/G and G/A versus A/A; OR = 3.45, 95 % confidence interval (95 %CI) = 1.75-6.81, χ (2) = 14.07, p < 0.0002), MLH1 (-93G/G versus G/A and A/A; OR = 1.45, 95 %CI = 1.02-2.07, χ (2) = 4.21, p < 0.04), TP53 (Pro72Pro; OR = 3.80, 95 %CI = 2.46-5.88, χ (2) = 61.27, p < 0.0001), combination GSTT1 deletions with heterozygotes versus normal homozygotes (OR = 1.43, 95 %CI = 1.00-2.04, χ (2) = 3.90, p < 0.05), and GSTM1 deletions (OR = 1.83, 95 %CI = 1.28-2.63, χ (2) = 11.04, p < .001). Analysis for ethnicity and smoking for each of the investigated polymorphisms showed that some genotypes can have a predictive value for susceptibility to CRC, at least those that demonstrate statistically significant ORs either for the combined mixed population of Kazakhstan or for both main ethnic groups separately (Kazakhs and Russians): TP53 Pro72Pro homozygous (for Kazakh-OR = 3.40, 95 %CI = 1.63-7.06, χ (2) = 11.35, p < 0.003; for Russian-OR = 4.69, 95 %CI = 2.53-8.66, χ (2) = 53.19, p < 0.0001) and GSTM1 deletions (for Kazakh-OR = 2.30, 95 %CI = 1.21-4.40, χ (2) = 8.42, p < 0.01; for Russian-OR = 1.64, 95 %CI = 1.01-2.66, χ (2) = 7.82, p < 0.02).

Challenges to effective cancer control in China, India, and Russia.

Cancer is one of the major non-communicable diseases posing a threat to world health. Unfortunately, improvements in socioeconomic conditions are usually associated with increased cancer incidence. In this Commission, we focus on China, India, and Russia, which share rapidly rising cancer incidence and have cancer mortality rates that are nearly twice as high as in the UK or the USA, vast geographies, growing economies, ageing populations, increasingly westernised lifestyles, relatively disenfranchised subpopulations, serious contamination of the environment, and uncontrolled cancer-causing communicable infections. We describe the overall state of health and cancer control in each country and additional specific issues for consideration: for China, access to care, contamination of the environment, and cancer fatalism and traditional medicine; for India, affordability of care, provision of adequate health personnel, and sociocultural barriers to cancer control; and for Russia, monitoring of the burden of cancer, societal attitudes towards cancer prevention, effects of inequitable treatment and access to medicine, and a need for improved international engagement.

EGFR T790M mutation detection in NSCLC patients resistant to tyrosine kinase inhibitor therapy.

BACKGROUND: The finding of mutations that activate epidermal growth factor receptor (EGFR) in people with lung adenocarcinoma resulted in the creation of a new class of biological treatments called tyrosine kinase inhibitors (TKI). These medications have changed how patients with EGFR mutations are clinically managed, nearly doubling their survival rate compared to standard chemotherapy. Though 1st and 2nd generation EGFR TKIs are initially highly effective, typically within 9-14 months all tumors with the mutation progress due to secondary resistance mutations involving alternative molecular pathways. In most cases (up to 60%), this is due to the T790M mutation emerging in the EGFR gene. METHODS: The study included 85 patients with NSCLC with progression of the disease after treatment with TKI 1st and 2nd generation. The T790M mutation was determined by digital polymerase chain reaction (PCR) on the QIAcuity One 5plex digital PCR system and traditional real-time PCR. Real-time PCR analysis of the presence of the T790M mutation was performed using the Therascreen EGFR Plasma RGQ PCR Kit (Qiagen). Using a digital PCR system in QIAcuity One (Qiagen) nanoplanets, the T790M mutation was analysed by digital PCR. The age of the patients ranged from 37 to 85 years. RESULTS AND CONCLUSIONS: Of 85 patients with NSCLC with disease progression after TKI treatment, T790M mutations were detected during digital PCR in 30 of 85 patients, which is 35.2% of the sample, and with traditional real-time PCR, positive mutations came out only in 3 out of 85 patients.

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).

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.

Cancer Incidence Relation to Heavy Metals in Soils of Kyzylorda Region of Kazakhstan.

OBJECTIVE: The purpose of this study was to investigate the relationship of soil pollution factors such as heavy metal ions with the incidence of cancer in the Kyzylorda region of Kazakhstan. METHODS: Concentrations of heavy metal ions in the soils of different sites of Kyzylorda region, Kazakhstan, were sampled and correlated with incidence of cancer in 2021. RESULTS: Chromium content in the soil exceeded maximum permissible concentration (MPC) in the samples for all sites except Kazaly and Shieli, and the highest excess of 2.8 MPC was found in Terenozek. Content of copper, lead, and cobalt ions was also increased and varied in the range 1.9-15.4, 1.2-4, and 1.2-2.44 MPC, respectively. In addition, lung cancer incidence was statistically significantly correlated with soil concentration to MPC ratio of copper, cobalt, and lead; colorectal cancer was correlated with soil concentration of chromium. Cases of invasive cancer and mutations were recorded Terenozek and Kyzylorda areas. CONCLUSION: The higher the soil concentration correlate with higher cancer incidence in Kyzylorda region, Kazakhstan.

The Performance and Clinical Applicability of HER2 Digital Image Analysis in Breast Cancer: A Systematic Review.

This systematic review aims to address the research gap in the performance of computational algorithms for the digital image analysis of HER2 images in clinical settings. While numerous studies have explored various aspects of these algorithms, there is a lack of comprehensive evaluation regarding their effectiveness in real-world clinical applications. We conducted a search of the Web of Science and PubMed databases for studies published from 31 December 2013 to 30 June 2024, focusing on performance effectiveness and components such as dataset size, diversity and source, ground truth, annotation, and validation methods. The study was registered with PROSPERO (CRD42024525404). Key questions guiding this review include the following: How effective are current computational algorithms at detecting HER2 status in digital images? What are the common validation methods and dataset characteristics used in these studies? Is there standardization of algorithm evaluations of clinical applications that can improve the clinical utility and reliability of computational tools for HER2 detection in digital image analysis? We identified 6833 publications, with 25 meeting the inclusion criteria. The accuracy rate with clinical datasets varied from 84.19% to 97.9%. The highest accuracy was achieved on the publicly available Warwick dataset at 98.8% in synthesized datasets. Only 12% of studies used separate datasets for external validation; 64% of studies used a combination of accuracy, precision, recall, and F1 as a set of performance measures. Despite the high accuracy rates reported in these studies, there is a notable absence of direct evidence supporting their clinical application. To facilitate the integration of these technologies into clinical practice, there is an urgent need to address real-world challenges and overreliance on internal validation. Standardizing study designs on real clinical datasets can enhance the reliability and clinical applicability of computational algorithms in improving the detection of HER2 cancer.

Burden of major cancer types in Almaty, Kazakhstan.

Globally, cancer is the second leading cause of death, with a growing burden also observed in Kazakhstan. This study evaluates the burden of common cancers in Almaty, Kazakhstan's major city, from 2017 to 2021, utilizing data from the Information System of the Ministry of Health. In Kazakhstan, most common cancers among men include lung, stomach, and prostate cancer, while breast, cervical, and colorectal cancers are predominant among women. Employing measures like disability-adjusted life years (DALYs), we found that selected cancer types accounted for a total DALY burden of 25,016.60 in 2021, with mortality contributing more than disability (95.2% vs. 4.7%) with the ratio of non-fatal to fatal outcomes being 1.4 times higher in women than in men. The share of non-fatal burden (YLD) proportion within DALYs increased for almost all selected cancer types, except stomach and cervical cancer over the observed period in Almaty. Despite the overall increase in cancer burden observed during the time period, a downward trend in specific cancers suggests the efficacy of implemented cancer control strategies. Comparison with global trends highlights the significance of targeted interventions. This analysis underscores the need for continuous comprehensive cancer control strategies in Almaty and Kazakhstan, including vaccination against human papillomavirus, stomach cancer screening programs, and increased cancer awareness initiatives.