Average-risk Group Research Articles

Atherosclerotic vascular lesion in the coal industry workers of average and high fatal risk groups

Introduction. Experts do not take into account the presence of subclinical atherosclerosis when stratifying risk on the SCORE scale, however, it is the main substrate for the occurrence of cardiovascular disasters. Most primary cardiovascular events occur in low cardiovascular risk groups, which requires timely detection of atherosclerosis and preventive measures to preserve the working population's ability to work and reduce the economic burden of treatment of cardiovascular diseases. The study aims to research the incidence of atherosclerosis in workers of the main professions of the coal industry in the South of Kuzbass in groups of medium and high risk of fatal events on the SCORE scale. Materials and methods. We divided the subjects into two groups using the SCORE scale: high-risk (main) — from 5 to 9%, which included 60 people, and moderate-risk group — from 2 to 4% (comparison) — 70 employees. The average age of the first was 50.98±0.43 years, the comparison group was 49.96±0.35 years (p=0.070). The scientists examined the indicators of blood pressure, lipid, carbohydrate and purine metabolism, and performed an ultrasound examination of the main arteries. Results. The incidence of atherosclerotic plaques in at least one vascular basin was 80.0% in the main group and 78.6% in the comparison group, p=0.845. The frequency of carotid artery atheromas in the high-risk group on the SCORE scale (52.7%) did not significantly differ from the comparison group (54.3%), p=0.862; a similar pattern in the arteries of the lower extremities: 80.0% vs. 70.0%, respectively, p=0.203. The frequency of carotid artery atheromas in the high-risk group on the SCORE scale (52.7%) did not significantly differ from the comparison group (54.3%), p=0.862; a similar pattern in the arteries of the lower extremities: 80.0% vs. 70.0%, respectively, p=0.203. The combination of thickening of the intima of vessels and the presence of atheromas tended to be more frequent in the main group — 83.6% compared with those in the comparison group — 70.1%, p=0.076 Limitations. The study is limited by the number of examined patients who underwent periodic medical examination at the Scientific Research Institute of Complex Problems of Hygiene and Occupational Diseases. Conclusion. The incidence of atherosclerosis among employees of coal enterprises turned out to be very high and did not statistically differ in the groups of medium and high fatal risk stratified on the SCORE scale, which requires more thorough screening and measures of enhanced angioprotective prevention, even in people with a low risk of fatal cardiovascular disasters. Ethics. All the subjects signed an informed consent to participate in the study, the Protocol of which corresponded to the requirements of the Bioethical Committee of the Research Institute of Complex Problems of Hygiene and Occupational Diseases, executed in accordance with the Helsinki Declaration of the World Medical Association "Ethical Principles of conducting medical research with human participation as a subject" as amended in 2013 and the "Rules of Good Clinical Practice" approved by the order Ministry of Health of the Russian Federation No. 200n dated April 1, 2016.

Colorectal cancer screening: Modalities and adherence

In the last decade, several studies have explored various modalities and strategies for colorectal cancer (CRC) screening, taking into account epidemiological data, individual characteristics, and socioeconomic factors. In this editorial, we comment further on a retrospective study by Agatsuma et al published in the recent issue of the World Journal of Gastroenterology . Our focus is on screening trends, particularly in relation to efforts to improve the currently suboptimal uptake among the general population worldwide, aiming to enhance early diagnosis rates of CRC. There is a need to raise awareness through health edu-cation programs and to consider the use of readily available, non-invasive screening methods. These strategies are crucial for attracting screen-eligible populations to participate in first-line screening, especially those in high- or average-risk groups and in regions with limited resources. Liquid biopsies and biomarkers represent rapidly evolving trends in screening and diagnosis; however, their clinical relevance has yet to be standardized.

Screening for Breast Cancer: A Comparative Review of Guidelines.

Breast cancer is the most common malignancy diagnosed in the female population worldwide and the leading cause of death among perimenopausal women. Screening is essential, since earlier detection in combination with improvements in breast cancer treatment can reduce the associated mortality. The aim of this study was to review and compare the recommendations from published guidelines on breast cancer screening. A total of 14 guidelines on breast cancer screening issued between 2014 and 2022 were identified. A descriptive review of relevant guidelines by the World Health Organization (WHO), the U.S. Preventive Services Task Force (USPSTF), the American Cancer Society (ACS), the National Comprehensive Cancer Network (NCCN), the American College of Obstetricians and Gynecologists (ACOG), the American Society of Breast Surgeons (ASBrS), the American College of Radiology (ACR), the Task Force on Preventive Health Care (CTFPHC), the European Commission Initiative on Breast Cancer (ECIBC), the European Society for Medical Oncology (ESMO), the Royal Australian College of General Practitioners (RACGP) and the Japanese Journal of Clinical Oncology (JJCO) for women both at average and high-risk was carried out. There is a consensus among all the reviewed guidelines that mammography is the gold standard screening modality for average-risk women. For this risk group, most of the guidelines suggest annual or biennial mammographic screening at 40-74 years, while screening should particularly focus at 50-69 years. Most of the guidelines suggest that the age limit to stop screening should be determined based on the women's health status and life expectancy. For women at high-risk, most guidelines recommend the use of annual mammography or magnetic resonance imaging, while the starting age should be earlier than the average-risk group, depending on the risk factor. There is discrepancy among the recommendations regarding the age at onset of screening in the various high-risk categories. The development of consistent international practice protocols for the most appropriate breast cancer screening programs seems of major importance to reduce mortality rates and safely guide everyday clinical practice.

Oral Cancer Risk and Screening Prevalence Among Hospitalized Women.

Background Oral cancer screenings are often on the back burner in the face of other cancer screenings. In high-risk individuals, early detection of oral cancer has a better prognosis and survival. Hospitalization may offer an opportunity to target high-risk populations. This study evaluates the prevalence of women at high risk for oral cancer among hospitalized women and their preference for oral cancer screening. Design and participants Five hundred and ten cancer-free women admitted to the hospital under the internal medicine service at an academic center were enrolled to participate in the study. Three hundred and seventy women were at high risk for developing oral cancer, defined by smoking status, alcohol use, or both. High-risk women received bedside smoking cessation counseling and oral cancer informational handouts and were offered oral screening examinations during hospitalization. Six months after discharge, study participants received a follow-up phone call to determine if these women discussed oral cancer screening with their primary care physicians at the follow-up visit. Results Seventy-three percent of the hospitalized women were at high risk for developing oral cancer. Fifty-seven percent of high-risk women reported having no primary dentist. High-risk women were more likely to be younger, reported a disability, and had a lower comorbidity burden than the average-risk group. Only 41% of high-risk hospitalized women received oral cancer screening examinations during the hospital stay. Post-hospitalization, 66% of high-risk patients discussed oral cancer screening with their primary care. Conclusion Almost three-fourths of hospitalized women are at high risk for developing oral cancer. Hospitalization provides an opportunity to educate and screen high-risk populations.

Development of a Breast Cancer Risk Prediction Model Incorporating Polygenic Risk Scores and Nongenetic Risk Factors for Korean Women.

To develop a breast cancer prediction model for Korean women using published polygenic risk scores (PRS) combined with nongenetic risk factors (NGRF). Thirteen PRS models generated from single or multiple combinations of the Asian and European PRSs were evaluated among 20,434 Korean women. The AUC and increase in OR per SD were compared for each PRS. The PRSs with the highest predictive power were combined with NGRFs; then, an integrated prediction model was established using the Individualized Coherent Absolute Risk Estimation (iCARE) tool. The absolute breast cancer risk was stratified for 18,142 women with available follow-up data. PRS38_ASN+PRS190_EB, a combination of Asian and European PRSs, had the highest AUC (0.621) among PRSs, with an OR per SD increase of 1.45 (95% confidence interval: 1.31-1.61). Compared with the average risk group (35%-65%), women in the top 5% had a 2.5-fold higher risk of breast cancer. Incorporating NGRFs yielded a modest increase in the AUC of women ages >50 years. For PRS38_ASN+PRS190_EB+NGRF, the average absolute risk was 5.06%. The lifetime absolute risk at age 80 years for women in the top 5% was 9.93%, whereas that of women in the lowest 5% was 2.22%. Women at higher risks were more sensitive to NGRF incorporation. Combined Asian and European PRSs were predictive of breast cancer in Korean women. Our findings support the use of these models for personalized screening and prevention of breast cancer. Our study provides insights into genetic susceptibility and NGRFs for predicting breast cancer in Korean women.

Performance of the Fecal Immunochemical Test in Detecting Advanced Colorectal Neoplasms and Colorectal Cancers in People Aged 40-49 Years: A Systematic Review and Meta-Analysis.

The incidence of early-onset colorectal cancer (CRC) is increasing. Many guidelines recommend initiating screening at 45 years. This study investigated the detection rate of advanced colorectal neoplasm (ACRN) by using fecal immunochemical tests (FITs) in individuals aged 40-49 years. PubMed, Embase, and Cochrane Library databases were searched from inception to May 2022. The primary outcomes were the detection rates and positive predictive values of FITs for ACRN and CRC in people aged 40-49 (younger age group) and ≥50 years (average risk group). Ten studies with 664,159 FITs were included. The FIT positivity rate was 4.9% and 7.3% for the younger age and average risk groups, respectively. Younger individuals with positive FIT results had significantly higher risks of ACRN (odds ratio [OR] 2.58, 95% confidence interval [CI] 1.79-3.73) or CRC (OR 2.86, 95% CI 1.59-5.13) than did individuals in the average-risk group, regardless of FIT results. Individuals aged 45-49 years with positive FIT results had a similar risk of ACRN (OR 0.80, 95% CI 0.49-1.29) to that of people aged 50-59 years with positive FIT results, although significant heterogeneity was observed. The positive predictive values of the FIT were 10-28.1% for ACRN and 2.7-6.8% for CRC in the younger age group. The detection rate of ACRN and CRC based on FITs in individuals aged 40-49 years is acceptable, and the yield of ACRN might be similar between individuals aged 45-49 and 50-59 years. Further prospective cohort and cost-effective analysis are warranted.

Trends in the Prevalence of Diabetes Mellitus in Pregnancy during the Past Two Decades in Northern Thailand.

Background: The prevalence of gestational diabetes mellitus (GDM) and pre-gestational diabetes mellitus (PDM) has increased dramatically in the past decade in all ethnic groups. The prevalence also varies markedly among different ethnic groups. Each ethnic group must have its own data about GDM/PDM for improvement in women's health care. We conducted this study with the main objective of assessing recent trends in the prevalence of PDM/GDM among pregnant women in the northern part of Thailand during the past two decades. The secondary objective is to identify the risk factors influencing the prevalence of DM in pregnancies. Patients and Methods: The maternal-fetal medicine database was accessed to retrieve consecutive obstetric records of women who gave birth in Chiang Mai University Hospital, Thailand, from January 2003 to December 2022. This is a 20-year study period of the same protocol of GDM screening policy, using the 50 g glucose challenge test as a screening test for the average risk group and the 100 g OGTT as a diagnostic test. The women were categorized into GDM, PDM and non-DM groups. Trends or percentage changes in the prevalence of GDM/PDM during the study period were evaluated. Risk factors related to GDM/PDM were identified. Results: Among 37,027 women who gave birth during the study period, the prevalence of DM in pregnancy was 11.4% (4223 cases), including 214 cases of PDM (0.6%) and 4009 cases of GDM (10.8%). The prevalence of PDM significantly increased from 0.3% in 2003 to 1.5% in 2022; also, the prevalence of GDM significantly increased, dramatically, from 3.4% in 2003 to 22.0% in 2022. The prevalence of GDM increased in recent years in all age groups (adolescent, reproductive and elderly groups), while that of PDM did not significantly change in the adolescent group during the study period. Maternal age and pre-pregnancy BMI significantly increased in the more recent years. Independent factors significantly associated with the prevalence of PDM/GDM include maternal age, pre-pregnancy BMI, higher socio-economic status, and urban areas of residence. Recent time is still an independent risk factor after adjustment for other known factors. Conclusions: Relatively, GDM and PDM are highly prevalent in the northern part of Thailand, and their prevalence continuously increased during the past two decades. The trend of increased prevalence was evident in all age groups. Increasing maternal age and pre-pregnancy BMI mainly contributed to the increase in the prevalence of GDM and PDM in recent years. Recent time is still an independent risk factor after adjustment for other known factors, indicating that some other unexplained risk factors are associated with the increase in prevalence of DM in recent years, possibly the increase in sedentary lifestyle. Modification of lifestyle, especially reducing pre-pregnancy BMI among reproductive women, may reduce the prevalence of DM in pregnancy.

High Sensitivity C-Reactive Protein as a Prognostic Indicator of Cardiovascular Disease in Severe Non-Diabetic COVID-19 Patients.

The long-term extrapulmonary sequelae of COVID-19 after recovery from the critical stage at the intensive care unit (ICU) are still unclear. Some post-COVID symptoms are prevalent even after a one-year follow-up. To explore the relationship between high sensitivity C-reactive protein (hs-CRP) and hyperglycemia with cardiovascular diseases in non-diabetic COVID-19 patients. To determine whether increased fasting blood sugar (FBS) levels are associated with elevated hs-CRP and to explore whether hs-CRP can serve as a prognostic indicator to predict cardiovascular outcome. FBS and hs-CRP values of 26 non-diabetic COVID-19 patients were collected from their medical records at JIPMER hospital. In one-year follow-up of these 26 patients, 2mL of blood sample was collected for the analysis of FBS, HbA1c, and hs-CRP. hs-CRP increased in 23% of follow-up patients who were at high risk, and 42.3% of participants were at average risk for cardiovascular disease. High and average-risk groups of survivors showed a positive correlation of hs-CRP with FBS and HbA1c levels, and these patients should be carefully monitored. ICU survivors with elevated hs-CRP need periodic check-ups for cardiovascular diseases. We suggest that hs-CRP could be used as an early prognostic indicator of cardiovascular diseases and can reduce the risk.

PEDT-19 RECENT PROGRESS IN CHILDHOOD BRAIN TUMORS RESEARCH

Abstract The multidisciplinary standard of care for medulloblastoma, a typical pediatric malignant brain tumor of cerebellar primary origin, has been established by large RCTs in the United States. The results of the Phase III RCTs sponsored by Children's Oncology Group's for newly-diagnosed medulloblastoma in children 3 years of age and older, ACNS0331, which attempted radiotherapy reduction for the average-risk group, and ACNS0332, which attempted intensified treatment with carboplatin as a radiosensitizer and isotretinoin as an apoptosis inducer for high-risk group are discussed.It has recently been reported that some infantile glioma cells have activating fusion genes with tyrosine kinase receptor genes, including NTRK, and that TRK inhibitors are effective against these tumors, and two TRK inhibitors have been used with cancer genome panel tests as companion diagnostics, Two TRK inhibitors can now be available for glioma treatment in Japanese practice. The results of clinical trials on the efficacy of these targeting agents in brain tumors with NTRK mutations will be presented.CAR-T cell therapy was developed for GD2 following HER2, which had attracted attention as an immunotherapeutic target for pediatric glioma, and its efficacy was demonstrated in clinical trials. We will examine the results of clinical trials of this immunotherapy, a promising treatment for DMS/DIPG, the disease with absolutely poor prognosis with no effective drug therapy, although it is used in a small number of cases.

Update of a prognostic survival model in head and neck squamous cell carcinoma patients treated with immune checkpoint inhibitors using an expansion cohort

BackgroundImmune checkpoint inhibitors (ICI) treatment in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) offers new therapeutic venues. We have previously developed a predictive survival model in this patient population based on clinical parameters, and the purpose of this study was to expand the study cohort and internally validate the model.MethodsA single institutional retrospective analysis of R/M HNSCC patients treated with ICI. Clinical parameters collected included p-16 status, hemoglobin (Hb), albumin (Alb), lactate dehydrogenase (LDH), neutrophil, lymphocyte and platelet counts. Cox proportional hazard regression was used to assess the impact of patient characteristics and clinical variables on survival. A nomogram was created using the rms package to generate individualized survival prediction.Results201 patients were included, 47 females (23%), 154 males (77%). Median age was 61 years (IQR: 55-68). P-16 negative (66%). Median OS was 12 months (95% CI: 9.4, 14.9). Updated OS model included age, sex, absolute neutrophil count, absolute lymphocyte count, albumin, hemoglobin, LDH, and p-16 status. We stratified patients into three risk groups based on this model at the 0.33 and 0.66 quantiles. Median OS in the optimal risk group reached 23.7 months (CI: 18.5, NR), 13.8 months (CI: 11.1, 20.3) in the average risk group, and 2.3 months (CI: 1.7, 4.4) in the high-risk group. Following internal validation, the discriminatory power of the model reached a c-index of 0.72 and calibration slope of 0.79.ConclusionsOur updated nomogram could assist in the precise selection of patients for which ICI could be beneficial and cost-effective.

Colorectal cancer screening participation among citizens not recommended to be screened: a cohort study

BackgroundGuidelines on colorectal cancer (CRC) screening recommend screening of average-risk adults only. In addition, screening of individuals with active inflammatory bowel disease (IBD) might result in too many false-positive cases. However, the organisers of CRC screening programmes are often uninformed of whom to exclude due to an elevated CRC risk or active IBD. It is therefore unknown how often high-risk individuals (i.e. individuals with a previous diagnosis of CRC or polyps associated with hereditary CRC syndromes and certain patient groups with a diagnosis of inflammatory bowel disease (IBD) or multiple polyps) and individuals with active IBD participate in CRC screening following invitation.Materials and methodsWe used data from the first two years of the Danish CRC screening programme (2014–2015). Information on invitations, participations and FIT test results were obtained from the national screening database, while information on previous CRC, hereditary CRC syndromes, IBD or multiple polyps diagnoses were obtained from the Danish Cancer Registry and the Danish Patient Register. Screening participation rates and FIT-positive rates were calculated and compared for high-risk invitees, invitees having IBD and an average risk group of remaining invitees not diagnosed with colorectal polyps in 10 years preceding the invitation.ResultsWhen invited to CRC screening, 28–48% of high-risk residents (N: 29; 316; 5584) and 55% of residents with IBD (N: 2217; 6927) chose to participate. The participation rate was significantly higher (67%) among residents without previous colorectal disease, i.e. the average risk group (N = 585,624). In this average group 6.7% of the participants had a positive FIT test. The proportion of positive FIT results was higher among all disease groups (7.7–14.8%), though not statistically significant for participants with prior CRC diagnosis and participants with high-risk IBD.ConclusionWhen high-risk residents and residents with IBD receive an invitation to CRC screening, many participate despite being recommended not to. The screening program was not intended for these groups and further research is needed as several of these groups have a higher rate of positive screening result than the average risk population.

Incorporating Polygenic Risk Scores and Nongenetic Risk Factors for Breast Cancer Risk Prediction Among Asian Women

Polygenic risk scores (PRSs) have shown promise in breast cancer risk prediction; however, limited studies have been conducted among Asian women. To develop breast cancer risk prediction models for Asian women incorporating PRSs and nongenetic risk factors. This diagnostic study included women of Asian ancestry from the Asia Breast Cancer Consortium. PRSs were developed using data from genomewide association studies (GWASs) of breast cancer conducted among 123 041 women with Asian ancestry (including 18 650 women with breast cancer) using 3 approaches: (1) reported PRS for women with European ancestry; (2) breast cancer-associated single-nucleotide variations (SNVs) identified by fine-mapping of GWAS-identified risk loci; and (3) genomewide risk prediction algorithms. A nongenetic risk score (NGRS) was built, including 7 well-established nongenetic risk factors, using data of 416 case participants and 1558 control participants from a prospective cohort study. PRSs were initially validated in an independent data set including 1426 case participants and 1323 control participants and further evaluated, along with the NGRS, in the second data set including 368 case participants and 736 control participants nested within a prospective cohort study. Logistic regression was used to examine associations of risk scores with breast cancer risk to estimate odds ratios (ORs) with 95% CIs and area under the receiver operating characteristic curve (AUC). A total of 126 894 women of Asian ancestry were included; 20 444 (16.1%) had breast cancer. The mean (SD) age ranged from 49.1 (10.8) to 54.4 (10.4) years for case participants and 50.6 (9.5) to 54.0 (7.4) years for control participants among studies that provided demographic characteristics. In the prospective cohort, a PRS with 111 SNVs developed using the fine-mapping approach (PRS111) showed a prediction performance comparable with a genomewide PRS that included more than 855 000 SNVs. The OR per SD increase of PRS111 score was 1.67 (95% CI, 1.46-1.92), with an AUC of 0.639 (95% CI, 0.604-0.674). The NGRS had a limited predictive ability (AUC, 0.565; 95% CI, 0.529-0.601). Compared with the average risk group (40th-60th percentile), women in the top 5% of PRS111 and NGRS were at a 3.84-fold (95% CI, 2.30-6.46) and 2.10-fold (95% CI, 1.22-3.62) higher risk of breast cancer, respectively. The prediction model including both PRS111 and NGRS achieved the highest prediction accuracy (AUC, 0.648; 95% CI, 0.613-0.682). In this study, PRSs derived using breast cancer risk-associated SNVs had similar predictive performance in Asian and European women. Including nongenetic risk factors in models further improved prediction accuracy. These findings support the utility of these models in developing personalized screening and prevention strategies.

Abstract P3-19-16: Impact of targeted intraoperative (TARGIT-IORT) tumor bed boost during breast conserving surgery for early breast cancer on breast cancer associated and non-breast cancer associated mortality and morbidity

Abstract Introduction: Targeted intraoperative radiotherapy (TARGIT - IORT) as a tumor bed boost during breast conserving surgery is an established option for women with early breast cancer. In a previous study our group could demonstrate a beneficial effect of TARGIT-IORT on overall survival after neoadjuvant chemotherapy driven by non-breast cancer mortality, especially from cardiac or pulmonary diseases. This was in line with results of TARGIT-A trial that demonstrated an improved overall survival after TARGIT-IORT that was driven by other causes of death than breast cancer but in our analysis we could not exclude a selection bias because we had no data regarding pulmonary and cardiac co-morbidities. In this study we present an analysis of breast cancer associated and non-breast cancer associated mortality and morbidity in a lower risk population treated with TARGIT-IORT boost or external boost (EBRT) and with a complete dataset of pulmonary and cardiac co-morbidities at baseline. Material/Methods: In this non-randomized cohort study involving 125 patients with early breast cancer we compared outcomes of 59 patients who received a tumor bed boost with IORT (TARGIT-IORT) during lumpectomy versus 66 patients with external (EBRT) boost. All patients received whole breast radiotherapy. Local recurrence rates, distant recurrence rates, mortality, causes of death and incidence of new pulmonary and cardiac morbidity were compared. The small event rate did not allow a formal comparison, so the results are reported descriptively. Results: There were no statistically significant differences between the two groups regarding age, menopausal status, nodal status, ER status, PR status, HER2 status, tumor size, grading, cardiac or pulmonary diseases and hypertension. Median follow up was 60 months. Local recurrence occurred in 3 cases in the EBRT group (4.5%) and 4 cases in the TARGIT-IORT group (6.8%). Distant recurrences were observed in 5 cases in the EBR group (7.6%) and 3 cases in the TARGIT-IORT group (5.1%). 9 patients in the EBRT group (13.6%) died in the follow-up of 60 months and 6 patients (10.2%) in the TARGIT-IORT group. No death from a pulmonary disease occurred and the incidence of new pulmonary and new cardiac diseases showed no difference between both groups with 3 cases in the EBRT group (4.5%) and 2 cases in the TARGIT-IORT group (3.4%). Death from cardiac disease occurred with an incidence of 7 cases in the EBRT group (10.6%) and only 2 cases in the TARGIT-IORT group (3.4%). 2 patients in the EBRT group died of breast cancer (3.0%) whereas this did not happen at all in the TARGIT-IORT group. Conclusion: This analysis of an average risk group of breast cancer patients well balanced for pulmonary and cardiac co-morbidities demonstrates that TARGIT-IORT as an anticipated boost is not inferior to external beam radiotherapy boost. Trends for an improved overall survival after TARGIT-IORT have been reported before. The trend for a lower incidence of death from cardiac disease is in line with earlier considerations that TARGIT-IORT may induce miR-223 in the peritumoral breast tissue resulting in a downregulation of the local expression of epidermal growth factor (EGF) and a decreased activation of epidermal growth factor receptor (EGFR). This mechanism could explain an effect of TARGIT-IORT on the vascular system. In the currently recruiting TARGIT-B study this aspect will be prospectively investigated. Citation Format: Hans-Christin Kolberg, Stephanie Gutberlet, Jayant S Vaidya, Maja Krajewska, György Lövey, Oliver Hoffmann, Miltiades Stephanou, Cornelia Kolberg-Liedtke. Impact of targeted intraoperative (TARGIT-IORT) tumor bed boost during breast conserving surgery for early breast cancer on breast cancer associated and non-breast cancer associated mortality and morbidity [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-16.

Medulloblastoma

Current treatment protocols for medulloblastomas(MBs)stratify patients into high and average risk groups according to their age, metastatic status, and residual tumor volume after resection. Recent genetic and molecular biological reserach revealed that MBs are classified into at least four core subgroups - WNT, SHH, Group 3, and Group 4 - based on differences in their cytogenetics, mutational spectra, and gene expression signatures, as well as in their clinical phenotypes and prognosis. Latest studies suggest more distinct subtypes of MBs by DNA methylation profiles. In addition to conventional clinical risk stratification, new molecular risk stratification using molecular subgroups/subtypes, cytogenetic features and copy number aberrations help understand the outcome of current standard and/or experimental therapies. To achieve further improvement in prognosis and reduce treatment-related adverse events, the efficiency and safety of low-dose craniospinal irradiation and novel molecular targeted drugs, including SMO inhibitors, cyclin-dependent kinases 4/6, or checkpoint kinase 1/2 inhibitors, have been examined with respect to the molecular properties of each tumor. The molecular information of each MB is indispensable for precision medicine of MBs, strongly promoting the development of advanced therapeutic strategies of MBs.

Medulloblastoma outcomes in tertiary care set-up in India using contemporary treatment protocols - A retrospective study.

Medulloblastoma is the commonest embryonal brain tumor in children. It has shown improved outcomes with combined modality treatment. We aimed to study patient characteristics and survival outcomes of patients with this disease across two tertiary care centers in India. We analyzed data of patients with histological diagnosis of medulloblastoma treated from January 2010 to January 2016. Patient characteristics and follow-up data were retrieved from hospital records. Descriptive statistics were used to describe clinical and pathological characteristics. Overall survival (OS) was calculated from date of diagnosis to death due to any cause. Relapse-free survival (RFS) was calculated from date of diagnosis to occurrence of relapse or death. Out of 26 patients treated, 24 were children and 2 were adults. Median age was 10 years (range = 0.8-22 years). Twenty (76.9%) patients were male. Fifteen (57.7%) patients were stratified as high-risk (HR), rest 11 (42.3%) were categorized as average risk (AR). Histopathology showed classical variety in majority of patients except for 4 (15%) cases, 3 with desmoplastic and 1 with anaplastic subtype. Median follow-up was 49.7 months (range= 4.2-102.5 months). Overall, eight (30.8%) patients relapsed and six (23%) deaths occurred. Five (33.3%) patients in HR category and 3 (27.3%) patients in AR group showed relapse. Median RFS and OS were not yet reached. Five-year RFS was 69.2% whereas five-year OS was 76.9%. This study highlighted patient characteristics and treatment outcomes in Indian patients. With adherence to standard treatment, high remission rates and improvement in mortality rates were achieved.

Risk Stratification of Childhood Medulloblastoma Using Integrated Diagnosis: Discrepancies with Clinical Risk Stratification.

BackgroundRecent genomic studies identified four discrete molecular subgroups of medulloblastoma (MB), and the risk stratification of childhood MB in the context of subgroups was refined in 2015. In this study, we investigated the effect of molecular subgroups on the risk stratification of childhood MB.MethodsThe nCounter® system and a customized cancer panel were used for molecular subgrouping and risk stratification in archived tissues.ResultsA total of 44 patients were included in this study. In clinical risk stratification, based on the presence of residual tumor/metastasis and histological findings, 24 and 20 patients were classified into the average-risk and high-risk groups, respectively. Molecular subgroups were successfully defined in 37 patients using limited gene expression analysis, and DNA panel sequencing additionally classified the molecular subgroups in three patients. Collectively, 40 patients were classified into molecular subgroups as follows: WNT (n = 7), SHH (n = 4), Group 3 (n = 8), and Group 4 (n = 21). Excluding the four patients whose molecular subgroups could not be determined, among the 17 average-risk group patients in clinical risk stratification, one patient in the SHH group with the TP53 variant was reclassified as very-high-risk using the new risk classification system. In addition, 5 out of 23 patients who were initially classified as high-risk group in clinical risk stratification were reclassified into the low- or standard-risk groups in the new risk classification system.ConclusionThe new risk stratification incorporating integrated diagnosis showed some discrepancies with clinical risk stratification. Risk stratification based on precise molecular subgrouping is needed for the tailored treatment of MB patients.

C-Reactive Protein Levels in relation to Incidence of Hypertension in Chinese Adults: Longitudinal Analyses from the China Health and Nutrition Survey.

Objective To explore the association between high sensitivity C-reactive protein (hs-CRP) levels and incident hypertension, as well as the association between hs-CRP levels and related covariates, in a Chinese adult population. Methods This study was based on the China Health and Nutrition Survey, a continuing open, large-scale prospective cohort study. Adult participants who were free of hypertension were included at baseline survey in 2009 and were followed up in 2015 (follow-up rate: 77.45%). The hs-CRP was measured using the immunoturbidimetric method and divided into three groups: low-risk group (0 ≤ hs-CRP <1 mg/L), average-risk group (1 ≤ hs-CRP <3 mg/L), and high-risk group (3 ≤ hs-CRP ≤10 mg/L). Definite diagnosis of hypertension in the follow-up survey in 2015 was the endpoint event of this study. The areas under the curve (AUC) of the receiver operating characteristic (ROC) curve analyses were used to evaluate the predictive value of the hs-CRP. Results 3794 participants were finally included as study sample, of whom 912 developed hypertension during a 6-year follow-up period (incidence: 24.1%). The incidences of hypertension in hs-CRP low-risk, average-risk, and high-risk groups were 17.6% (200/1135), 25.9% (521/2015), and 29.7% (191/644), respectively. Spearman's correlation analyses showed that there was significant positive correlation between hs-CRP levels and waist circumference, total triglycerides, total cholesterol, age, body mass index, and homeostasis model assessment of insulin resistance index. Stepwise regression analyses showed that participants in the hs-CRP high-risk group had a 46.2% higher risk of developing hypertension compared with those in the hs-CRP low-risk group (odds ratio: 1.462, 95% confidence interval: 1.018–2.101). Baseline systolic and diastolic blood pressure levels and waist circumference contributed the most to the development of hypertension with R2 of 0.076, 0.052, and 0.039, respectively, while hs-CRP had lower area under the curve (AUC) for hypertension, adding baseline BP and WC to the prediction model increased the AUC to 0.708 (95% CI: 0.681–0.735). Conclusion This study revealed a weak positive association between CRP levels and future incidence of hypertension in the Chinese population. The combination of hs-CRP with baseline BP and waist circumference (WC) had a higher predictive value for hypertension (AUC: 0.708), but the predictive value was still limited.

Prevalence of Non-alcoholic Fatty Liver Disease in India: A Systematic Review and Meta-analysis

Non-alcoholic fatty liver disease (NAFLD) contributes to a large proportion of liver disease burden in the world. Several groups have studied the prevalence of NAFLD in the Indian population. A systematic review of the published literature and meta-analysis was carried out to estimate the prevalence of NAFLD in the Indian population. English language literature published until April 2021 was searched from electronic databases. Original data published in any form which had reported NAFLD prevalence in the Indian population were included. The subgroup analysis of prevalence was done based on the age (adults or children) and risk category, i.e., average-risk group (community population, participants of control arm, unselected participants, hypothyroidic individuals, athletes, aviation crew, and army personnel)and high-risk group (obesity or overweight, diabetes mellitus, coronary artery disease, etc.). The prevalence estimates were pooled using the random-effects model. Heterogeneity was assessed with I2. Sixty-two datasets (children 8 and adults 54) from 50 studies were included. The pooled prevalence of NAFLD was estimated from 2903 children and 23,581 adult participants. Among adults, the estimated pooled prevalence was 38.6% (95% CI 32-45.5). The NAFLD prevalence in average-risk and high-risk subgroups was estimated to be 28.1% (95% CI 20.8-36) and 52.8% (95% CI 46.5-59.1), respectively. The estimated NAFLD prevalence was higher in hospital-based data (40.8% [95% CI 32.6-49.3%]) than community-based data (28.2% [95% CI 16.9-41%]). Among children, the estimated pooled prevalence was 35.4% (95% CI 18.2-54.7). The prevalence among non-obese and obese children was 12.4 (95% CI 4.4-23.5) and 63.4 (95% CI 59.4-67.3), respectively. Available data suggest that approximately one in three adults or children have NAFLD in India.

Determination of thresholds of risk in women at average risk of breast cancer to personalize the organized screening program

In France, more than 10 million women at ”average” risk of breast cancer (BC), are included in the organized BC screening. Existing predictive models of BC risk are not adapted to the French population. Thus, we set up a new score in the French Hérault region and looked for subgroups at a graded level of risk in women at ”average” risk. We recruited a retrospective cohort of women, aged 50 to 60, who underwent the organized BC screening, and included 2241 non-cancer women and 527 who developed a BC during a 12-year follow-up period (2006-2018). The risk factors identified were high breast density (ACR BI-RADS grading)(B vs A: HR = 1.41, 95%CI [1.05; 1.9], p = 0.023; C vs A: HR = 1.65 [1.2; 2.27], p = 0.02 ; D vs A: HR = 2.11 [1.25;3.58], p = 0.006), a history of maternal breast cancer (HR = 1.61 [1.24; 2.09], p < 0.001), and socioeconomic difficulties (HR 1.23 [1.09; 1.55], p = 0.003). While early menopause (HR = 0.36 [0.13; 0.99], p = 0.003) and an age at menarche after 12 years (HR = 0.77 [0.63; 0.95], p = 0.047) were protective factors. We identified 3 groups at risk: lower, average, and higher, respectively. A low threshold was characterized at 1.9% of 12-year risk and a high threshold at 4.5% 12-year risk. Mean 12-year risks in the 3 groups of risk were 1.37%, 2.68%, and 5.84%, respectively. Thus, 12% of women presented a level of risk different from the average risk group, corresponding to 600,000 women involved in the French organized BC screening, enabling to propose a new strategy to personalize the national BC screening. On one hand, for women at lower risk, we proposed to reduce the frequency of mammograms and on the other hand, for women at higher risk, we suggested intensifying surveillance.

The classification capability of the Asia Pacific Colorectal Screening score in Korea: an analysis of the Cancer Screenee Cohort.

OBJECTIVESThis study aimed to validate a simple risk assessment tool for estimating the advanced colorectal neoplasia (ACN) risk at colonoscopy screenings and potential factors relevant for implementing this tool in the Korean population.METHODSOur study analyzed data from the Cancer Screenee Cohort Study conducted by the National Cancer Center in Korea. The risk level was assessed using the Asia Pacific Colorectal Screening (APCS) score developed by the Asia-Pacific Working Group on Colorectal Cancer. Logistic regression models were used to examine the associations between colorectal-related outcomes and the risk level by APCS score. The discriminatory performance of the APCS score for various colorectal-related outcomes was assessed using C-statistics.RESULTSIn 12,520 individuals, 317 ACN cases and 4,528 adenoma cases were found. The APCS tool successfully classified the study population into different risk groups, and significant differences in the ACN rate and other outcomes were observed. The APCS score demonstrated acceptable discrimination capability with area under the curve values ranging from 0.62 to 0.65 for various outcomes. The results of the multivariate logistic regression model revealed that the high-risk group had a 3.1-fold higher risk of ACN (95% confidence interval, 2.08 to 4.67) than the average-risk group. Body mass index (BMI) was identified as a significant predictor of ACN in both multivariate and subgroup analyses.CONCLUSIONSOur study highlighted significant differences in colorectal-related screening outcomes by colorectal risk level measured using the APCS score, and BMI could be used to improve the discriminatory capability of the APCS score.