Five-year Survival Rate Of Patients Research Articles

Targeting FGFR1 by β,β-dimethylacrylalkannin suppresses the proliferation of colorectal cancer in cellular and xenograft models

BackgroundColorectal cancer (CRC) continues to be a major global health challenge, ranking as a top cause of cancer-related mortality. Alarmingly, the five-year survival rate for CRC patients hovers around a mere 10–30 %. The disruption of fibroblast growth factor receptor (FGFRs) signaling pathways is significantly implicated in the onset and advancement of CRC, presenting a promising target for therapeutic intervention in CRC management. Further investigation is essential to comprehensively elucidate FGFR1′s function in CRC and to create potent therapies that specifically target FGFR1. PurposeThis study aims to demonstrate the oncogenic role of FGFR1 in colorectal cancer and to explore the potential of β,β-dimethylacrylalkannin (β,β-DMAA) as a therapeutic option to inhibit FGFR1. MethodsIn this research, we employed a comprehensive suite of techniques including tissue array, kinase profiling, computational docking, knockdown assay to predict and explore the inhibitor of FGFR1. Furthermore, we utilized kinase assay, pull-down, cell proliferation tests, and Patient derived xenograft (PDX) mouse models to further investigate a novel FGFR1 inhibitor and its impact on the growth of CRC. ResultsIn our research, we discovered that FGFR1 protein is markedly upregulated in colorectal cancer tissues, suggesting a significant role in regulating cellular proliferation, particularly in patients with colorectal cancer. Furthermore, we conducted a computational docking, kinase profiling analysis, simulation and identified that β,β-DMAA could directly bind with FGFR1 within ATP binding pocket domain. Cell-based assays confirmed that β,β-DMAA effectively inhibited the proliferation of colon cancer cells and also triggered cell cycle arrest, apoptosis, and altered FGFR1-mediated signaling pathways. Moreover, β,β-DMAA effectively attenuated the development of PDX tumors in mice that were FGFR1-positive, with no notable toxicity observed. In summary, our study highlights the pivotal role of FGFR1 in colorectal cancer, suggesting that inhibiting FGFR1 activity could be a promising strategy for therapeutic intervention. We present strong evidence that targeting FGFR1 with β,β-DMAA is a viable approach for the management of colorectal cancer. Given its low toxicity and high efficacy, β,β-DMAA, as an FGFR1 inhibitor, warrants further investigation in clinical settings for the treatment of FGFR1-positive tumors.

Mechanism of Notch Signaling Pathway in Malignant Progression of Glioblastoma and Targeted Therapy.

Glioblastoma multiforme (GBM) is the most aggressive form of glioma and the most common primary tumor of the central nervous system. Despite significant advances in clinical management strategies and diagnostic techniques for GBM in recent years, it remains a fatal disease. The current standard of care includes surgery, radiation, and chemotherapy, but the five-year survival rate for patients is less than 5%. The search for a more precise diagnosis and earlier intervention remains a critical and urgent challenge in clinical practice. The Notch signaling pathway is a critical signaling system that has been extensively studied in the malignant progression of glioblastoma. This highly conserved signaling cascade is central to a variety of biological processes, including growth, proliferation, self-renewal, migration, apoptosis, and metabolism. In GBM, accumulating data suggest that the Notch signaling pathway is hyperactive and contributes to GBM initiation, progression, and treatment resistance. This review summarizes the biological functions and molecular mechanisms of the Notch signaling pathway in GBM, as well as some clinical advances targeting the Notch signaling pathway in cancer and glioblastoma, highlighting its potential as a focus for novel therapeutic strategies.

Five-year recurrence/survival after pancreatoduodenectomy for pancreatic adenocarcinoma: does pre-existing diabetes matter? Results from the Recurrence After Whipple's (RAW) study

ObjectivesDiabetes mellitus (DM) has a complex relationship with pancreatic cancer. This study examines the impact of preoperative DM, both recent-onset and pre-existing, on long-term outcomes following pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). MethodsData were extracted from the Recurrence After Whipple's (RAW) study, a multi-centre cohort of PD performed for pancreatic head malignancy (2012–2015). Recurrence and five-year survival rates of patients with DM were compared to those without. A subgroup analysis was also performed to compare patients with recent-onset DM (less than one year) to patients with established DM. ResultsOut of 758 patients that were included, 187 (24.7%) had DM, of whom, 47 of the 187 (25.1%) had recent-onset DM. There was no difference in the rate of postoperative pancreatic fistula (DM: 5.9% vs no DM 9.8%; p = 0.11), five-year survival (DM: 24.1% vs no DM: 22.9%; p = 0.77) or five-year recurrence (DM: 71.7% vs no DM: 67.4%; p = 0.32). There was also no difference between patients with recent-onset DM and patients with established DM in postoperative outcomes, recurrence, or survival. ConclusionsWe found no difference in five-year recurrence and survival between diabetic patients and those without diabetes. Patients with pre-existing DM should be evaluated for PD on a comparable basis to non-diabetic patients.

CHRONIC OBSTRUCTIVE PULMONARY DISEASE: RATE OF THERAPIOTIC ADHERENCE IN OUTPATIENT PRACTICE

The adherence of a patient with chronic obstructive pulmonary disease (COPD) to treatment is of utmost importance as it prevents the disease progression and the delayed complication development that determine the quality of life and life span.
 The purpose of the study is to assess the level of adherence for patients with COPD to drug therapy with respiratory drugs, to identify factors influencing the adherence, and study 5-year survival rate based on adherence level.
 Materials and Methods. The study enrolled 150 patients with COPD (87 men, and 63 women, mean age 58.3±0.86 years). Pulmonary function (FEV1, FVC, FEV1/FVC), severity of respiratory symptoms (mMRS scale, CAT questionnaire), and disease severity were assessed (GOLD, 2022). Adherence to COPD treatment was determined according to the Morisky-Green test (1986). Five-year survival rate of patients was analyzed.
 Results. Low adherence to treatment in patients with COPD was revealed: 1 month after the initiation or correction of respiratory therapy, only 32 patients (21.3 %) were assessed as adherent, 56 patients (37.3 %) were insufficiently adherent, and 62 patients (41.3 %) were non-adherent to treatment. Adherence to treatment was associated with age, disease severity, severity of respiratory symptoms, FEV1 and did not depend on gender. In five years, survival rate in the group of non-adherent patients (89.5 %) and insufficiently adherent patients (80.4 %) was significantly higher than in the group of adherent one (61.9 %). It is associated with a more severe status of patients who are adherent to therapy.
 Conclusion. The authors identified an insufficient adherence level in patients with COPD. Elderly patients with a more severe course of the disease, low FEV1 levels, and severe exacerbations are more adherent to respiratory drug therapy. Worse five-year survival rates were observed in the group of patients who were adherent to therapy. It was associated with more severe clinical status, age and comorbidity.

Abstract 3331: Preclinical combination of ONC206 with radiotherapy and temozolomide in a GBM mouse orthotopic model

Abstract Glioblastoma multiforme (GBM) is the most common form of primary malignant brain tumor in adults. It is also the most aggressive and lethal. Standard of care therapy comprises maximal safe surgical resection followed by adjuvant alkylating agent temozolomide (TMZ) and radiotherapy (RT). There have only been five drugs and one device ever approved by the FDA for the treatment of GBM. The five-year survival rate for GBM patients has shown no notable improvement in the last three decades. We previously reported that the first-in-class imipridone small-molecule Dordaviprone (ONC201) decreases protein chaperone ClpX to unleash mitochondrial protease ClpP activity, integrated stress response and cell death. Preclinical combination of ONC201 (100 mg/kg weekly) with radiotherapy and Temozolomide in a GBM mouse orthotopic model results in reduced tumor burden and prolonged survival. The second generation imipridone ONC206 also activates integrated stress response and decreases ClpX in GBM cells but ONC206 is approximately 20 times more potent than its parent imipridone ONC201. ONC206 0.08 uM in combination with 12.5 uM TMZ and 2 Gy RT reduced the cell viability of GBM cells significantly compared to all single treatments and double treatments. During a short-term treatment of a GBM mouse orthotopic model, ONC206 (50 mg/kg weekly, half of ONC201 doses) synergizes with TMZ and RT to induce more tumor cell apoptosis and inhibits more tumor cell proliferation compared to other groups with single or double treatments. There are two ongoing clinical trials with ONC206: single weekly or multiple-day weekly dose regimens of single-agent, oral ONC206 in patients with recurrent, primary central nervous system (CNS) neoplasms (NCT04541082) and ONC206 alone or in combination with radiation therapy in treating patients with diffuse midline gliomas that is newly diagnosed or has come back (recurrent) or other recurrent primary malignant CNS tumors (NCT04732065). Future studies evaluating the role of immune function, mitochondrial metabolism, dopamine receptors, the ISR and TRAIL pathway in the synergistic effect would support further development of the triple combination regimen of ONC206, TMZ and radiation therapy for GBM clinical trial. Citation Format: Lanlan Zhou, Leiqing Zhang, Jun Zhang, Shengliang Zhang, Wafik S. El-Deiry. Preclinical combination of ONC206 with radiotherapy and temozolomide in a GBM mouse orthotopic model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3331.

Abstract 1560: In vivo CRISPR/Cas9 transcriptional activation screen leads to discovery of INAFM2, a novel driver of metastasis

Abstract Metastasis is the main cause of mortality in cancer patients and accounts for about 90% of cancer deaths, which has not changed in the past 50 years. This indicates a significant need for further study of metastasis pathways to find novel druggable targets. Ewing sarcoma (ES) is an aggressive childhood cancer that occurs in the bones or soft tissue. The five-year survival rate for Ewing sarcoma patients diagnosed with metastatic disease is still only 25%, making ES a good model for studying metastasis. We performed a genome-wide CRISPR/Cas9 transcriptional activation screen in a zebrafish xenograft model to discover genes whose activation leads to increased metastasis. The screen identified a number of genes that may accelerate ES metastasis; we chose INAFM2 for further study because multiple unique INAFM2-targeting gRNAs were enriched in the screen and we discovered a potential link to metastasis and patient survival in publicly available clinical data. Overexpression of INAFM2 in six different cancer cell lines (four ES, one hepatocellular carcinoma, and one stomach adenocarcinoma) caused increased cell migration and chemotaxis in vitro, and increased intravasation in zebrafish xenografts. INAFM2 knockdown in four cancer cell lines (two ES, one clear cell renal cell carcinoma, and one stomach adenocarcinoma) decreased chemotaxis and rescue of INAFM2 expression restored the cells’ ability to migrate. Analysis of patient tumor RNA sequencing data from many different types of cancers revealed correlations between INAFM2 expression and both an increased metastatic phenotype and poor patient survival. Further in vivo studies by tail vein injection of ES cells in immunodeficient mice demonstrated significantly increased gross metastases with INAFM2 overexpression and decreased gross metastases with INAFM2 knockdown compared to the respective control groups. This provides strong evidence for a substantial role of INAFM2 in cancer metastasis. Human INAFM2 is an unstudied gene and our preliminary work has revealed that the INAFM2 protein localizes to the cell membrane, is glycosylated, and may be involved in Wnt and/or MAPK pathway signaling. Inafm2 silencing by morpholino in zebrafish embryos lead to significant mortality, necrosis, and developmental delays/defects including severe cardiac edema. Current studies are focused on further discerning the molecular pathways that mediate the role of INAFM2 in promoting metastasis using in vitro and in vivo models as well as characterizing the functional significance of the direct protein binding partners and post-translational modifications for INAFM2. Citation Format: Anna Molotkova, Emre Deniz, Matthew Swift, Eric Glasgow, Jeffrey Toretsky, Aykut Üren. In vivo CRISPR/Cas9 transcriptional activation screen leads to discovery of INAFM2, a novel driver of metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1560.

The Ross-Konno Procedure With or Without Mitral Valve Surgery: A Systematic Review With Individual Data Pooling.

Background: The Ross-Konno procedure is a technically demanding surgical option to treat multilevel left ventricular outflow tract obstruction. Methods: A systematic review with pooled analyses was conducted according to PRISMA criteria on studies published between January 2000 and May 2022 that assessed outcomes following the Ross-Konno intervention in children. Individual patient data were extracted from published Kaplan-Meier curves using digitalization software. Overall survival and freedom from reintervention were assessed by time-to-event approaches. Determinants of one-year survival were investigated by meta-regression analyses. Results: Ten studies with a total population of 274 patients were included. The overall pooled early (≤30 days) survival rate was 86.9% (95% CI [87.6%-78.4%]). Five-year survival rates in patients without and with (N = 50 [18.2%] of 274 total patients) concomitant mitral valve surgery were 82.5% (95% CI [87.6%-77.4%]) versus 56.1% (95% CI [74.1%-38.1%]), hazard ratio 2.67, 95% CI (1.44-4.93), P < .0001. Five- and ten-year freedom from pulmonary autograft reoperation rates were 93.5% and 90.9%, respectively. Five- and ten-year freedom from right ventricular outflow tract reoperation rates were 74.3% and 57.3%, respectively. By meta-regression analysis, resection of endocardial fibroelastosis (N = 32 [11.7%] of 274 total patients) was associated with superior one-year survival (P = .027). Conclusion: The Ross-Konno procedure is associated with substantial early mortality and gradual attrition thereafter. Mortality is higher in patients with concomitant mitral valve surgery. Resection of endocardial fibroelastosis is associated with superior survival. Right ventricular outflow tract reinterventions are common.

Radiogenomic analysis of ultrasound phenotypic features coupled to proteomes predicts metastatic risk in primary prostate cancer

BackgroundPrimary prostate cancer with metastasis has a poor prognosis, so assessing its risk of metastasis is essential.MethodsThis study combined comprehensive ultrasound features with tissue proteomic analysis to obtain biomarkers and practical diagnostic image features that signify prostate cancer metastasis.ResultsIn this study, 17 ultrasound image features of benign prostatic hyperplasia (BPH), primary prostate cancer without metastasis (PPCWOM), and primary prostate cancer with metastasis (PPCWM) were comprehensively analyzed and combined with the corresponding tissue proteome data to perform weighted gene co-expression network analysis (WGCNA), which resulted in two modules highly correlated with the ultrasound phenotype. We screened proteins with temporal expression trends based on the progression of the disease from BPH to PPCWOM and ultimately to PPCWM from two modules and obtained a protein that can promote prostate cancer metastasis. Subsequently, four ultrasound image features significantly associated with the metastatic biomarker HNRNPC (Heterogeneous nuclear ribonucleoprotein C) were identified by analyzing the correlation between the protein and ultrasound image features. The biomarker HNRNPC showed a significant difference in the five-year survival rate of prostate cancer patients (p < 0.0053). On the other hand, we validated the diagnostic efficiency of the four ultrasound image features in clinical data from 112 patients with PPCWOM and 150 patients with PPCWM, obtaining a combined diagnostic AUC of 0.904. In summary, using ultrasound imaging features for predicting whether prostate cancer is metastatic has many applications.ConclusionThe above study reveals noninvasive ultrasound image biomarkers and their underlying biological significance, which provide a basis for early diagnosis, treatment, and prognosis of primary prostate cancer with metastasis.

The role of postoperative radiotherapy or chemoradiation in pT1-2N1M0 oral squamous cell carcinoma

BackgroundPostoperative radiotherapy (PORT) and concurrent chemoradiation (CCRT) are indicated for patients with advanced oral cancer. However, the benefits for pT1-2N1 disease without adverse pathological features are controversial. MethodsThis retrospective study using the Taiwan Cancer Registry database included patients with pT1-2N1 oral cancer from January 1, 2011, to December 31, 2017. Overall survival was analyzed in patients receiving surgery alone, PORT, or CCRT. ResultsAmong the 862 patients, the five-year overall survival rate in patients receiving surgery alone, PORT, and CCRT was 62.2%, 58.7%, and 71.1% (P = 0.03), respectively. CCRT was associated with longer survival than PORT (P = 0.008). Survival in patients with pT2 disease was significantly higher with CCRT than PORT (P = 0.001), but no difference was observed in pT1 disease. ConclusionCCRT demonstrated a favorable impact on survival outcomes in patients diagnosed with pT2N1 oral cancer when compared to PORT. However, no significant survival benefits were observed for patients with pT1 disease.

Beneficial Effect of Metformin on the Five-Year Survival in about 40,000 Patients with Head and Neck Cancer.

Even in times of new therapy regimes, the overall survival of patients with head and neck cancer remains low. Since the previous studies showed the beneficial effect of metformin medication on the survival of patients with cancer, our objective was to investigate if-and in which way-metformin medication affects the overall survival of patients with head and neck cancer. Clinical data pertaining to patients diagnosed with head and neck cancer (International Classification of Diseases 10 codes C00-C14, C31, and C32) were retrospectively retrieved from the TriNetX network (TriNetX, Cambridge, MA, USA). The initial cohort extracted from the network was stratified into two groups: patients on metformin medication (cohort I), and individuals not on metformin medication (cohort II). The matching criteria included age, gender, BMI, type 2 diabetes, and risk factors, such as nicotine and alcohol abuse/dependence. Kaplan-Meier analysis, risk analysis, and the calculation of odds and hazard ratios were conducted. Additionally, the Hemoglobin A1c values were subject to analysis. Following matching, each cohort comprised 20,416 patients. Cohort I exhibited a higher five-year survival rate at 75.3%, in contrast to cohort II, which registered a rate of 69.8%. The odds ratio was 0.79 (95% CI = 0.75-0.83), and the hazard ratio was 0.78 (95% CI = 0.75-0.82). Metformin medication may correlate with improved five-year survival rates in patients with head and neck cancer. Since potentially influencing factors such as comorbidities and the initial tumor stage were not available, the results of our retrospectively conducted study must be interpreted with caution.

State of the Art in the Diagnosis and Assessment of Oral Malignant and Potentially Malignant Disorders: Present Insights and Future Outlook-An Overview.

Oral Potentially Malignant Disorder (OPMD) is a significant concern for clinicians due to the risk of malignant transformation. Oral Squamous Cell Carcinoma (OSCC) is a common type of cancer with a low survival rate, causing over 200,000 new cases globally each year. Despite advancements in diagnosis and treatment, the five-year survival rate for OSCC patients remains under 50%. Early diagnosis can greatly improve the chances of survival. Therefore, understanding the development and transformation of OSCC and developing new diagnostic methods is crucial. The field of oral medicine has been advanced by technological and molecular innovations, leading to the integration of new medical technologies into dental practice. This study aims to outline the potential role of non-invasive imaging techniques and molecular signatures for the early detection of Oral Malignant and Potentially Malignant Disorders.

Evaluation of 5-Year Survival Rate of Patients with Multiple Myeloma Undergoing Bone Marrow Transplantation: A Descriptive Study

Background: Multiple myeloma is a progressive and high mortality neoplasm, and the prevalence increases with aging. The main treatment for new cases aged less than 65 years is high-dose chemotherapy with autologous bone marrow transplantation. This study aims to determine the five-year survival rate of patients with multiple myeloma.&#x0D; Methods: In this descriptive-analytical study, 97 patients with multiple myeloma who underwent bone marrow transplantation between 2011 and 2016 were investigated. Then, information related to gender, age at the time of transplantation, the time interval between diagnosis and transplantation, cases of death and, date of death of the studied patients were collected, and the survival of the patients from the date of diagnosis to the end of the study period (five years) was calculated. Data were analyzed using Cox proportional and chi-square tests.&#x0D; Results: Five-year survival of patients was 59.8%. The median overall survival of patients was 54.22 months, which shows that age (p value = 0.003), gender (p value = 0.591), and the time delay between diagnosis and bone marrow transplantation (p value = 0.005) all affect patient survival. There was a significant relationship between the patient's age and the time interval between diagnosis and transplantation with the five-year survival of the patients.&#x0D; Conclusion: As a result, bone marrow transplantation provides a higher survival rate. Also, the effect of the patient‘s age and time interval between diagnosis and transplantation, early diagnosis of the disease and, earlier bone marrow transplantation can bring longer survival for patients.

Liver Transplantation from Brain-Dead Donors with Hepatitis B or C in South Korea: A 2014-2020 Korean Organ Transplantation Registry Data Analysis.

BACKGROUND According to the current guidelines for liver transplantation (LT) of brain-dead donors with hepatitis B or C virus (HBV or HCV) in Korea, grafts from hepatitis B surface antigen (HBsAg)(+) or HCV antibody (anti-HCV)(+) donors must be transplanted only to HBsAg(+) or anti-HCV(+) recipients, respectively. We aimed to determine the current status and outcomes of brain-dead donor LT with HBV or HCV in Korea. MATERIAL AND METHODS This retrospective observational study included all LTs from brain-dead donors in the Korean Organ Transplantation Registry between April 2014 and December 2020. According to donor hepatitis status, 24 HBV(+), 1 HCV(+), and 1010 HBV(-)/HCV(-) donors were included. RESULTS Baseline/final model for end-stage liver disease score (MELD) for HBV(+), HCV(+), and HBV(-)/HCV(-) were 22.4±9.3/27.8±7.8, 16/11, and 33.0±15.4/35.5±7.1, respectively. MELD score of HBV (+) were lower than those of HBV(-)/HCV(-) (P<0.01). Five-year graft and patient survival rates of HBV(+) and HBV(-)/HCV(-) recipients were 81.7%/85.6%, and 76.6%/76.7%, respectively (P=0.73 and P=0.038). One-year graft and patient survival rates of HCV (+) graft recipients were both 100%. CONCLUSIONS No differences in graft and patient survival rates between HBV(+) and HBV(-)/HCV(-) groups were observed. Although accumulating the results of transplants from HBV (+) or HCV(+) grafts to HBV(-) or HCV(-) recipients is not possible owing to domestic regulations, Korea should conditionally permit transplantations from HBV(+) or HCV(+) grafts to HBV(-) or HCV(-) recipients by considering the risks and benefits based on foreign studies. Thereafter, we can accumulate the data from Korea and analyze the outcomes.

A SERS-assisted 3D organotypic microfluidic chip for in-situ visualization and monitoring breast cancer extravasation process

Extravasation, as one of the key steps in cancer metastasis, refers to the process where tumor cells escape the bloodstream by crossing the vascular endothelium and invade the targeted tissue, which accounts for the low five-year survival rate of cancer patients. Understanding the mechanism of cancer metastasis and inhibiting extravasation are crucial to improve patient prognosis. Here, a 3D organotypic microfluidic chip combined with SERS-based protein imprinted nanomaterials (SPINs) was proposed to study the extravasation process in vitro. The chip consists of a collagen gel channel and a vascular channel where human vein endothelial cells (HUVECs) and breast cancer cells are injected sequentially to induce extravasation. By comparing two subtypes of breast cancer cells (MCF-7 and MDA-MB-231), we successfully observed the difference in extravasation capabilities between two kinds of cells through fluorescence imaging. Meanwhile, thanks to the high specificity of molecular imprinting technology and the high sensitivity of surface enhanced Raman scattering (SERS), SPINs were utilized to analyze the concentration of several cancer secretions (interleukin-6 and interleukin-8) in complex biological fluid in real-time. Further, our model showed that downregulation of secretions by therapeutic drugs can inhibit the extravasation of breast cancers. This microfluidic model may pave the way for the fundamental research of the cancer metastasis and evaluating the therapeutic efficacy of potential drugs.

Kidney Transplantation From Brain-Dead Donors With Hepatitis B or C in South Korea: A 2015 to 2020 Korean Organ Transplantation Registry Data Analysis

According to the current Center for Korean Network for Organ Sharing guidelines for kidney transplantation from brain-dead donors with hepatitis B or C infection, organs from hepatitis B surface antigen-positive (HbsAg+) or anti-hepatitis C virus-positive (HCV+) donors can only be transplanted into HBsAg+ or anti-HCV+ recipients. We aimed to confirm the status and the outcomes of kidney transplantation from brain-dead donors with hepatitis B or C virus in Korea. This retrospective study included all kidney transplantations from brain-dead donors in the Korean Organ Transplantation Registry database between January 2015 and June 2020, divided into 3 groups according to donor hepatitis status. Finally, kidney transplantations from 80 HBV+, 12 HCV+, and 2013 HBV-/HCV- donors were included. No statistically significant differences were observed in the recipient characteristics and the transplant outcomes except the waiting time (HBV+ to HBV-/HCV-, P < .001; HCV+ to HBV-/HCV-, P = .10; HBV+ to HCV+P = .95). Five-year graft survival rates of the HBV+, HCV+, and HBV-/HCV- recipients were 95%, 83%, and 85%, respectively (HBV+ to HCV+, P = .22; HCV+ to HBV-/HCV-, P = .81; HBV+ to HBV-/HCV-, P = .02). Five-year patient survival rates of the HBV+, HCV+, and HBV-/HCV- recipients were 95%, 100%, and 76%, respectively (HBV+ to HCV+, P = .61; HCV+ to HBV-/HCV-, P = .13; HBV+ to HBV-/HCV-, P < .001). HBV+/HCV+ brain-dead donor kidney transplantation outcomes were comparable to HBV-/HCV-. South Korea should consider conditionally permitting transplantation from HBV+ or HCV+ donors to HBV- or HCV- recipients to accumulate new data and conduct further studies.

GASTRIC CANCER: EPIDEMIOLOGY AND PROSPECTS FOR THE DEVELOPMENT AND IMPLEMENTATION OF INNOVATIVE TECHNOLOGIES FOR EARLY DETECTION AND TREATMENT

Relevance: Gastric cancer is a heterogeneous group of malignant epithelial tumors arising from the cells of the gastric mucosa, one of the most common forms of malignant neoplasms in many countries of the world. But, despite repeated attempts, there are no convincing approaches to early large-scale (screening) detection technology for this form of cancer. This causes a high rate of late detection of advanced forms of gastric cancer in most countries of the world, a high one-year mortality rate of patients, and a low five-year survival rate. Currently, full screening for gastric cancer is carried out only in Japan, Korea, and China – countries with high incidence rates.&#x0D; The study aimed to assess the epidemiologically disadvantaged regions of Kazakhstan for cancer to select optimal early detection techniques to improve the treatment results.&#x0D; Methods:For the analysis, we used available epidemiological indicators on GC from the specialized literature, data obtained from annual reporting forms No. 7, approved by the Ministry of Health of the Republic of Kazakhstan, in the country code (ICD 10 – C16), publications with statistical and analytical materials on Kazakhstan. Morbidity and mortality rates were calculated based on data from the Bureau of National Statistics of the Agency for Strategic Planning and Reforms of the Republic of Kazakhstan website on the average annual population by region of Kazakhstan.&#x0D; Results: A long-term decrease in the incidence and mortality from gastric cancer in Kazakhstan since 2021 has been replaced by a stable increase in the incidence of gastric cancer against the backdrop of a high frequency of advanced forms, relatively high mortality, and low fiveyear survival of patients. At the same time, there is experience in the world of certain approaches to screening the population for early detection of gastric cancer.&#x0D; Conclusion: The high morbidity of gastric cancer in most regions of the country in recent years requires the search and development of optimal forms of screening for its early detection; this will reduce mortality from gastric cancer and increase the five-year survival rate of patients.

THE RESULTS OF THE JAPANESE GASTRIC CANCER ASSOCIATION MORPHOLOGICAL CLASSIFICATION ADAPTATION FOR THE KAZAKH POPULATION

Relevance: Gastric cancer is a heterogeneous group of malignant epithelial tumors arising from the cells of the gastric mucosa, one of the most common forms of malignant neoplasms in many countries of the world. But, despite repeated attempts, there are no convincing approaches to early large-scale (screening) detection technology for this form of cancer. This causes a high rate of late detection of advanced forms of gastric cancer in most countries of the world, a high one-year mortality rate of patients, and a low five-year survival rate. Currently, full screening for gastric cancer is carried out only in Japan, Korea, and China – countries with high incidence rates.&#x0D; The study aimed to was a retrospective analysis of literary data on the epidemiology of gastric cancer in the world, individual countries, but, above all, our own materials, summarized by specialists of the Joint Stock Company “Kazakh Research Institute of Oncology and Radiology” (JSC “KazNIIOiR”) on the situation with cancer stomach in Kazakhstan; analysis of information on the types and results of screenings for the early detection of gastric cancer in the world.&#x0D; Methods:For the analysis, we used available epidemiological indicators on GC from the specialized literature, data obtained from annual reporting forms No. 7, approved by the Ministry of Health of the Republic of Kazakhstan, in the country code (ICD 10 – C16), publications with statistical and analytical materials on Kazakhstan. Morbidity and mortality rates were calculated based on data from the Bureau of National Statistics of the Agency for Strategic Planning and Reforms of the Republic of Kazakhstan website on the average annual population by region of Kazakhstan.&#x0D; Results: A long-term decrease in the incidence and mortality from gastric cancer in Kazakhstan since 2021 has been replaced by a stable increase in the incidence of gastric cancer against the backdrop of a high frequency of advanced forms, relatively high mortality, and low fiveyear survival of patients. At the same time, there is experience in the world of certain approaches to screening the population for early detection of gastric cancer.&#x0D; Conclusion: The high morbidity of gastric cancer in most regions of the country in recent years requires the search and development of optimal forms of screening for its early detection; this will reduce mortality from gastric cancer and increase the five-year survival rate of patients.

Clinical manifestations and prognosis of giant cell arteritis: A retrospective cohort study

The aim of the study was to evaluate the clinical manifestations and survival of patients with giant cell arteritis (GCA).Methods. A retrospective study included 166 patients with newly diagnosed GCA. Clinical, laboratory and instrumental data, three sets of classification criteria were used to confirm the diagnosis: the American College of Rheumatology (ACR) 1990, the revised ACR criteria of 2016 and/or the new ACR and European Alliance of Associations for Rheumatology (EULAR) 2022 criteria. Some of the patients underwent instrumental investigations: temporal artery ultrasound Doppler (n=61), contrast-enhanced computed tomography (CT) (n=5), CT angiography (n=6), magnetic resonance imaging (n=4), magnetic resonance angiography (n=3) and 18F-FDG positron emission tomography/CT (n=47). Overall and recurrence-free survival were analyzed using survival tables, Kaplan – Meier method.Results. The most frequent first manifestations of GCA were headache (81.8%), weakness (64%), fever (63.8%) and symptoms of rheumatic polymyalgia (56.6%). Changes of temporal arteries in color duplex scanning were detected in 44 out of 61 patients. GCs therapy was performed in all patients who agreed to be treated (n=158), methotrexate was used in 49 out of 158 patients, leflunomide – in 9 patients. In 45 (28.5%) out of 158 patients a stable remission was achieved as a result of GCs monotherapy, in 120 (75.9%) patients long-term maintenance therapy with GCs was required to prevent exacerbations, including 71 (44.9%) patients – in combination with methotrexate or other immunosuppressive drugs. The follow-up period of patients with a history of relapses was 21.0 (8.0–54.0) months. Relapses developed in 73 (46.2%) patients. The overall one-year survival rate was 97.1% [95% confidence interval (CI): 94.3; 99.9], and the five-year survival rate of patients was 94.6% [95% CI: 90.2; 99.0]. The one-year relapse-free survival rate was 86.4% [95% CI: 80.5; 92.3], and the five-year relapse-free survival rate was 52.4% [95% CI: 42.0; 62.8]. 12 (7.2%) of 166 patients died. The cause of death was myocardial infarction in two patients, stroke in two patients, and breast cancer in one patient; in the remaining seven cases, the cause of death was not determined.Conclusion. Given the high frequency of disease exacerbation, patients with GCA require long-term follow-up, especially during the first year after diagnosis.

Abstract A160: The FGFR axis is a potential radiosensitization target

Abstract Background: Establishing methods that sensitize cancers to photons is important for improving the treatment outcome of radiotherapy. Although sequencing has been widely used to identify druggable mutations in various cancers, this strategy have not been used extensively to identify new targets for radiotherapy sensitization. Thus, we performed clinical sequencing of radiotherapy-treated patient samples and investigated whether inhibition of the identified candidate targets resulted in radiosensitization in vitro and in vivo. Material and Methods: Ninety-eight patients with newly diagnosed and pathologically confirmed cervical cancer who had been treated with definitive radiotherapy were analyzed. DNA was extracted from formalin fixed and paraffin embedded pre-treatment tumor biopsy specimens. The exons of 409 cancer-related genes were sequenced using a next generation sequencer. Identified mutations were analyzed for correlations with clinical outcome. The radiosensitization induced by inhibition of the candidate target was investigated in in vitro clonogenic assays and nude mouse xenograft models using radioresistant cancer cell lines and small molecule inhibitors. The in vitro sensitizer enhancement ratio (SER) was calculated as the ratio of radiation dose required to reduce clonogenic cell survival by 50% without drug to that with drug. Results: Recurrent mutations were identified in PIK3CA (35.7%), ARID1A (25.5%), NOTCH1 (19.4%), FGFR3 (16.3%), FBXW7 (19.4%), TP53 (13.3%), EP300 (12.2%), and FGFR4 (10.2%). The prevalence of mutations in FGFR family genes combined (24.5%) was almost as high as that for well-studied PIK3CA and ARID1A. Fifty-five percent (21/38) of the identified FGFR mutations were located in the tyrosine kinase domain. Five-year progression-free survival (PFS) rates for FGFR mutation-positive patients (n = 24) were significantly worse than those for FGFR mutation-negative patients (n = 74) (43.9% vs. 68.5%). Multivariate analysis identified FGFR mutations as significant predictors of worse 5 year PFS, independent of clinicopathological variables. To investigate whether the FGFR axis can be targeted by drugs to increase radiosensitization, the radiosensitizing effect of a human-administrable selective pan-FGFR inhibitor LY2874455 was investigated. LY2874455 (at 100 nM) showed a potent in vitro radiosensitizing effect (SER: 1.62, 1.53, and 1.31 for A549, H1299, and H1703 cells, respectively). In A549 xenograft models, the combination of X-rays (10 Gy on day 1) and LY2874455 (3 mg/kg body weight, once daily, on Day 1–7) led to significantly greater suppression of tumor growth than either treatment with X-rays or LY2874455 alone, with no evidence of toxicities. LY2874455 treatment inhibited ERK signaling, the main target of the FGFR axis, both in vitro and in vivo. Conclusion: These data indicate that targeting the FGFR axis with LY2874455 could potentially be used to sensitize cancers to radiotherapy, which warrants clinical validation. Citation Format: Takahiro Oike, Eisuke Horigome, Akiko Adachi, Narisa Dewi Maulany Darwis, Atsushi Shibata, Tatsuya Ohno. The FGFR axis is a potential radiosensitization target [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A160.

OGC P02 Neutrophil/lymphocyte ratio and long-term survival after pancreatoduodenectomy for malignancy

Abstract Background Previous authors have highlighted that preoperative neutrophil/lymphocyte ratio (NLR) may be of prognostic importance in patients who undergo pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC), ampullary carcinoma (AA) or cholangiocarcinoma (CC) of the pancreatic head/periampullary region. Various cut-off thresholds have been suggested. This study aimed to compare the five-year survival rates of PD patients with high preoperative NLR to those with low preoperative NLR (using thresholds from recent studies). Methods Data was extracted from the Recurrence After Whipple’s (RAW) study, a multicentre retrospective cohort study of outcomes of PD performed for pancreatic head malignancy (29 centres in 8 countries, n=1484). Patients were grouped by their underlying cancer type and divided into “high NLR” (PDAC: ≥ 3.74, AA: ≥3.0, CC: ≥2.75) and “low NLR” (PDAC: &amp;lt;3.74, AA: &amp;lt;3.0, CC: &amp;lt;2.75) groups. Five-year survival rates were compared using Fisher’s exact test. Results Out of 1484 patients, 885 (59.6%) had PDAC, 394 (26.5%) had AA and 205 (13.8%) had CC, and NLR was available in 88.4%, 89.1% and 92.2% of cases, respectively. The median NLR was 2.7 (range: 0.1-34.0), 2.8 (range: 0.3-103.0) and 2.7 (range:0.1-83.3) for patients with PDAC, AA and CC, respectively. Low NLR did not correlate with improved five-year survival rates in any of the studied cancers (PDAC: 24.5% vs 23.8%, p=0.9, AA: 56.1% vs 51.2%, p=0.4, CC: 34.4% vs 25.8%, p=0.2). Conclusions In our multicentre study of PD outcomes, preoperative NLR was not useful for predicting five-year survival in patients with PDAC, AA or CC.