National Cancer Center Research Articles

Clinicopathological Findings and Treatment Outcomes of Patients with Primary Hepatobiliary Neuroendocrine Neoplasms: A Retrospective Single-institution Analysis.

Objective Primary hepatobiliary neuroendocrine neoplasms (NENs) are rare tumors exhibiting several morphological and behavioral characteristics. Considering the lack of relevant data on this topic, we evaluated the clinicopathological features and treatment outcomes of patients with primary hepatobiliary NENs. Methods/Patients We examined 43 consecutive patients treated at the National Cancer Center Hospital with pathological diagnoses of primary hepatobiliary NEN between 1980 and 2016. Results Nine patients were diagnosed with neuroendocrine tumor (NET) G1, 9 with NET G2, and 25 with neuroendocrine carcinoma (NEC) based on the World Health Organization 2019 classification. Patients with NEC had primary sites across the hepatobiliary organs, although sites in patients with NET G1 and NET G2 only included the liver and ampulla of Vater. Patients with primary extrahepatic bile duct or ampulla of Vater NENs tended to be diagnosed earlier than patients with primary gallbladder NENs. The median survival times in the NET G1, NET G2, and NEC groups were 167.9, 97.4, and 11.1 months, respectively. A good performance status, absence of distant metastases, and low tumor grade were identified as independent predictors of a favorable prognosis. Conclusion The NET-to-NEC ratio and tumor stage distribution at the diagnosis differed depending on the primary site. Patients with G1 and G2 NETs who underwent surgical resection had good prognoses, whereas those with NEC exhibited more advanced disease and poorer prognoses. The performance status, staging classification, and tumor grade are important factors to consider when devising an appropriate treatment strategy and predicting the prognoses of patients with primary hepatobiliary NEN.

Real-world Experience of Posaconazole Therapeutic Drug Monitoring in Oncology Patients: Clinical Implications of Hypoalbuminemia as a Predictor of Subtherapeutic Posaconazole Levels.

Posaconazole maintains broad antifungal activity and is employed for prevention and treatment of invasive fungal infections in oncology patients. Older formulations required therapeutic drug monitoring, and specific plasma drug levels have been recommended. This study evaluated factors associated with subtherapeutic concentrations with the newer delayed-release tablet formulation. In this retrospective, single-center cohort study at a national comprehensive cancer center, all oncology patients receiving delayed-release posaconazole at standard dosing of 300 mg orally per day from 06/2021 to 07/2023 with plasma drug concentration evaluation were identified. Demographic, clinical, and laboratory data were evaluated to identify risk factors associated with subtherapeutic drug levels at targets of ≥1.25 µg/mL and ≥1.8 µg/mL. Of 110 patients identified, 98 met criteria for inclusion in the study. The median time from initiation of posaconazole to drug level assessment was 13 days, and the median concentration was 1.29 µg/mL. Of the 22 patients receiving posaconazole for prophylaxis, 5 (22.7%) failed to achieve concentrations ≥0.7 µg/mL, and of 76 patients receiving posaconazole for treatment, 38 (50%) failed to achieve concentrations of ≥1.25 µg/mL. In multivariable analysis, albumin of ≤3 g/dL and ideal body weight ≥60 kg were found to be associated with subtherapeutic levels. For a higher target of ≥1.8 µg/mL, only albumin ≤3 g/dL was associated with subtherapeutic levels for the variables evaluated. A higher initial dosing strategy and therapeutic drug monitoring for oncology patients with albumin ≤3 g/dL receiving posaconazole, particularly for the treatment of invasive fungal infection, could be considered.

"The 10th International MDM2 Workshop": Opening up new avenues for MDM2 and p53 research, the First International MDM2 Workshop in Asia.

The 10th International MDM2 Workshop was held at the National Cancer Center Research Institute (NCCRI) in Tokyo, Japan, from October 15 to 18, 2023. It attracted 166 participants from 12 countries. The meeting featured 52 talks and 41 poster presentations. In the first special session, six invited speakers gave educational and outstanding talks on breakthroughs in MDM2 research. Three keynote speakers presented emerging p53-independent functions of MDM2/MDM4, functional association of MDM2/p53 with cancer immunity, and drug discovery targeting the MDM2/MDM4-p53 pathway. Additionally, 19 invited speakers introduced their new findings. Twenty-one presenters, many of whom were young investigators, postdocs, and students, were selected from submitted abstracts and reported their exciting and unpublished results. For poster presenters, outstanding poster awards were given to the best presenters. There were many inspiring questions and discussions throughout the meeting. Social events like a welcome party, a workshop dinner, and an optional tour enabled further scientific interactions among the participants. The meeting successfully provided an exciting platform for scientific exchange. The experience gained from organizing this meeting will be handed over to the next organizers of the 11th International MDM2 Workshop.

Cancer screening programs in Japan: Progress and challenges.

National screening programs for gastric, colorectal, lung, breast, and cervical cancers are offered in Japan. The initial introduction of cancer screening programs was decided based on experts' opinions. Since 2003, the research groups funded by the National Cancer Center have published screening guidelines for gastric, colorectal, lung, prostate, cervical, and breast cancers. Although such guidelines have increasingly contributed to promoting evidence-based screening, it is still insufficient. Cancer screenings have mainly been provided in communities and workplaces. Compared with the average of OECD countries, participation rates in breast and cervical cancer screening are lower. Participation rates cannot be accurately calculated due to a lack of comprehensive cancer screening registries at the national level. Alternatively, estimates are derived from questionnaire surveys conducted on randomly selected samples from the national population. The quality assurance system has been limited to community-based screening and was not adapted to workplace screening until 2018. While there is a long history of cancer screening, the complex program delivery system might be a barrier to increasing the participation rate. Continued efforts are necessary to offer evidence-based cancer screening and establish an effective quality assurance system.

Cancer incidence and mortality in China, 2022

Objective: The National Central Cancer Registry estimates the number of new cancer cases and deaths in China in 2022, using incidence and mortality data collected by the National Cancer Center. Methods: According to the data of 700 cancer registries in 2018 and the data of 106 cancer registries from 2010 to 2018, the age-period-cohort model was used to estimate the incidence rate and mortality rate of all cancers and 23 types of cancer in 2022, stratified by gender and urban and rural areas. We estimated the number of new cancer cases and deaths in China in 2022 based on the estimated rate and population data in 2022. Results: The estimated results showed that in 2022, there were approximately 4 824 700 new cancer cases in China (2 533 900 in males and 2 290 800 in females), with an age-standardized incidence rate of Chinese population (ASIR) of 208.58 per 100 000 (212.67 per 100 000 for males and 208.08 per 100 000 for females). Approximately 2 903 900 new cancer cases occurred in urban areas, with an ASIR of 212.95 per 100 000. It was estimated about 1 920 800 new cancer cases in rural areas, and the ASIR was 199.65 per 100 000. The top five cancers (lung cancer 1 060 600, colorectal cancer 517 100, thyroid cancer 466 100, liver cancer 367 700 and female breast cancer 357 200) accounted for 57.4% of all new cases. The estimated number of deaths from cancer in China in 2022 was 2 574 200 (1 629 300 in males and 944 900 in females), with an age-standardized mortality rate of Chinese population (ASMR) of 97.08 per 100 000 (127.70 per 100 000 in males and 68.67 per 100 000 in females). The number of deaths from cancer in urban and rural areas was about 1 400 600 and 1 173 400, with the ASMR of 92.37 and 103.97 per 100 000 in urban and rural areas, respectively. The top five leading cause of cancers death (lung cancer 733 300, liver cancer 316 500, gastric cancer 260 400, colorectal cancer 240 000 and esophageal cancer 187 500) accounted for 67.5% of all cancer deaths. Lung cancer ranked first in the incidence and mortality in men and women. The incidence rate in urban areas was higher than that in rural areas, while the mortality rate was lower than that in rural areas. Conclusions: The burden of cancer in China is still relatively heavy, with significant differences in cancer patterns in gender, urban-rural, and regional. The burden of cancer presents a coexistence of developed and developing countries, and the situation of cancer prevention and control is still serious in China.

Abstract 7338: Prevalence and risk factors of PALB2 germline pathogenic variants

Abstract Background: PALB2, located on chromosome 16, plays a vital role in DNA damage repair as a partner and localizer of BRCA2. PALB2 germline pathogenic variant has been known to increase the risks of breast cancer, pancreatic cancer, and ovarian cancer. However, the prevalence of PALB2 germline variants in Korean patients has not been thoroughly investigated. This study aimed to evaluate the prevalence of PALB2 germline variants and the risk factors in Korean population. Methods: We analyzed the data of 3755 patients who performed hereditary cancer germline next generation sequencing (NGS) panels, including PALB2, at the National Cancer Center in Korea between 2008 and 2022. Genetic variants were classified using a five-tier system following the American College of Medical Genetics and Genomics guidelines as follows: pathogenic (PV), likely pathogenic (LPV), variants of uncertain significance (VUS), likely benign, and benign. We retrospectively reviewed 102 individuals who were confirmed to have the PALB2 germline variant with PV, LPV and VUS. Also, we analyzed the clinical characteristics of patients with PALB2 heterozygous PV or LPV. Results: A total of 102 patients (2.7%, 102/3755) represented PALB2 germline variants with 81 (79.4%) VUS, 14 (13.7%) LPV, and 7 (6.9%) PV. Detected twelve germline PALB2 LPV or PV were as followings; c.3350+5G>A (n=6), c.454A>T (n=3), c.1048C>T (n=2), c.2016dup (n=2), c.1424C>G (n=1), c.1976_1977del (n=1), c.2095dup (n=1), c.2834+2T>C (n=1), c.2920_2921delAA (n=1), c.3317delT (n=1), c.902delA (n=1), and exon 11 deletion (n=1). 35 PALB2 VUS were detected in 81 patients. Among 21 female patients with LPV or PV (median diagnosis age 50 years; 25-69), 18 carriers (85.7%) and 3 carriers (14.3%) were diagnosed with breast cancer and ovarian cancer, respectively. For 18 breast cancer patients, 3 patients had bilateral breast cancer and 3 patients had multi-organ cancers (ovary, thyroid, or colorectal and gastric cancer).Also, 15 carriers (71.4%) have first-degree relatives with breast, ovarian, pancreatic, lung, gastric, liver, thyroid, and colorectal cancer and 10 carriers (47.6%) have second-degree relatives with breast, pancreatic, lung, gastric, liver, prostate, lymphoma, laryngeal, and uterine cancer. Conclusion: In our study, PALB2 germline PV or LPV were detected at a low frequency of 0.56% in Korean cancer patients. Family history was an important risk factor for suspected germline pathogenic variants, and bilateral breast cancer was observed in 16.7% of breast cancer patients who harbored PALB2 PV or LPV. This study was supported by grant from the National Cancer Center. (grant number HA23C0419; NCC- 23F1850; NCC-2110181). Citation Format: Min-Chae Kang, Ye-Ryeong Jung, Seeyoun Lee, Han-Sung Kang, So-Youn Jung, Myong Cheol Lim, Keun Seok Lee, Eun-Gyeong Lee, Sun-Young Kong. Prevalence and risk factors of PALB2 germline pathogenic variants [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 7338.

Abstract 7332: Healthcare professionals' perceptions and educational needs in genetic counseling for cancer risk management: An integrated mixed-methods systematic review

Abstract Background: The role of healthcare professionals (HCPs) is crucial in the genetic counseling process for managing hereditary cancer risks. However, HCPs face challenges due to a lack of specialized training and confidence, particularly in communicating genetic risks to patients. Hence, it becomes paramount to identify the essential skills and expertise required by HCPs for genetic counseling. Additionally, gaining insight into their perspectives regarding the content of genetic counseling that should be provided to patients is of utmost importance. Methods: An integrated mixed-methods systematic review and content analysis were performed across five databases on 23 May 2023, employing predetermined search strategies. The quality of selected studies was assessed using the Mixed Method Appraisal Tool (MMAT), and data analysis was conducted using a deductive content analysis approach with MAXQDA 2020. Results: The review encompassed 14 studies from seven countries, revealing moderate risk of bias. It was perceived by HCPs that hereditary cancer families require information in seven specific categories including, cancer risk-reducing strategies; personalized cancer risk; family implications of hereditary cancer; psychological issues; genetic testing; the role of pathogenic genes in hereditary cancers; and social issues related to genetic testing. The study also highlighted the educational needs of HCPs, pinpointing areas such as method for supporting decision-making; clinical management in hereditary cancer families; resources for supporting hereditary cancer families; guidance to support familial communication; genetic testing; the role of each profession; and methods for supporting psychological aspects. Conclusion: The findings underscore the need for specialized training programs to equip HCPs with the necessary skills and knowledge for effective genetic counseling. Additionally, understanding HCPs’ perspectives on the content of genetic counseling is vital for tailoring educational resources and enhancing the genetic counseling process in managing cancer risks. Grants: This research was supported by a grant of the Korean Cancer Survivors Healthcare R&D Project through the National Cancer Center, funded by the Ministry of Health & Welfare, Republic of Korea (grant number: NCC 23F1940-1) Citation Format: So-Youn Jung, Sun-Young Park, Eun-Gyeong Lee, Heejung Chae, Mi-Jin An, Yeon-Joo Kim, Yoon-Jung Choi, Kum Hei Ryu, Sun-Young Kong. Healthcare professionals' perceptions and educational needs in genetic counseling for cancer risk management: An integrated mixed-methods systematic review [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 7332.

Abstract 7336: Exploring the impact of cancer predisposition gene variants by functional analysis and whole genome sequencing analysis in hereditary cancer patients

Abstract Background: Hereditary cancer confirmed by germline pathogenic variant has been increased with increasing next generation sequencing (NGS) panel tests in recent years. However, some cases who were suspected hereditary cancer represented having variant of uncertain significance (VUS) or no variants even though they had family members with many cancers. The aim of this study was to investigate variants function especially in splicing variants and to explore other candidate genes by whole genome sequencing (WGS) in suspected hereditary cancer patients. Methods: Total of 44 patients who clinically suspected hereditary cancer without defined pathogenic variants after NGS panel test were enrolled. Among them 11 patients had intronic variants and their variant effects were predicted by SpliceAI, a deep learning-based tool. To define alternative splicing, total RNA was extracted from patients buffy coats and cDNA was synthesized using oligo dT. Then the cDNA was amplified by specific primers and performed sequencing. Also, WGS was performed in 15 patients then comprehensive analysis encompassing 392 unique genes was performed including 282 well-established hereditary cancer predisposition genes and 228 DNA repair-related genes. We confirmed the variant by various type of studies and predicted impact on protein by analysis. Results: We analyzed intronic variants of 11 patients; ATM c.4611+3A>T(n=1). BRCA1 c.547+30A>G (n=2), BRCA1 c.5152+6T>C(n=1), MSH2 c.2635-7G>A(n=1), MUTYH c.934-2A>G(n=2), NF1 c.1527+4A>C(n=1), NF1 c.3871-14G>T(n=1), PALB2 c.3350+5G>A(n=1), and SMARCA4 c.3546+1G>A(n=1). Though two intronic variants (ATM c.4611+3A>T and SMARCA4:c.3546+1G>A) were observed a likelihood of aberrant splicing aggregate SpliceAI score more than 0.8, we observed three intronic variants induce alternative splicing (ATM c.4611+3A>T, NF1 c.1527+4A>C, and PALB2 c.3350+5G>A).In addition, WGS analysis demonstrated 6 out of 15 patients have germline variants in relevant genes. Four single nucleotide variants (SMARCAL1:c.1632delA, SETMAR:c.441dup, FAN1:c.590C>A, and PRF1:c.445G>A) were validated by sequencing and those were likely pathogenic variant (LPV) by ACMG/AMP criteria of ClinGen. Copy number variations were identified in 2 patients (PMS2 heterozygous deletion and RAD50 duplication) and structure variant of MSH2 was identified in one patient. Conclusion: Our analysis showed in silico analysis results might be different from functional analysis and rare variants in cancer predisposition genes could be confirmed WGS. However, large number of patients study would be needed to confirm necessity of WGS for hereditary cancer. This work was supported by National Cancer Center, Korea (No_NCC-2110181). Citation Format: Hyeji Kim, Jong Eun Park, Gi Yeon Lee, Jung-Ah Hwang, Jin-Sun Ryu, Ye-Ryeong Jung, Seeyoun Lee, Kum Hei Ryu, Dong Ock Lee, So-Youn Jung, Sang-Yoon Park, Wonyoung Choi, Sun-Young Kong. Exploring the impact of cancer predisposition gene variants by functional analysis and whole genome sequencing analysis in hereditary cancer patients [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 7336.

Abstract 7029: Trajectory of DNA methylation in blood up to 18 years prior to lung cancer diagnosis

Abstract Purpose: Lung cancer (LC) has the highest mortality rate in South Korea. As prediction and early detection of lung cancer is pivotal to enhance survival rates, we attempted to investigate the trajectory of DNA methylation (DNAm) several years prior to lung cancer diagnosis by using prediagnostic blood samples. Methods: From National Cancer Center Health Examinee Cohort, established in 2003, we selected study participants who became diagnosed with LC several years after health examination, thereby collecting prediagnostic samples from 18 years to 1 year prior to LC diagnosis. Normal controls (n=150) were matched with patients (n=150) by sex, age, and the time of sample collection. Epigenome-wide DNAm data were obtained by using Infinium Human MethylationEPIC v2.0 Beadchip. We assumed non-linear relationship between DNAm changes and the time-to-diagnosis and estimated an optimal threshold point of non-linear relationship with a piecewise linear regression analysis at each CpG sites (CpGs). We used the ratio of M-values of patients and matched controls to establish the non-linear model composed of two linear models with a threshold point where the slope changes. Then, we performed functional enrichment analysis by each year prior to LC diagnosis using ReactomePA. Results: We identified threshold models with a threshold point where the slope changes from zero (from 18 years prior to LC up to the threshold point) to positive or negative (from threshold point to the point of LC diagnosis), which we termed “flat-to-change model”. Out of 790,048 CpGs, we identified a total of 7214 CpGs showing the “flat-to-change model”, of which 944, 789, 480, 413, 687, 542, 516, 1140, 315, 284, 327, 432, 83, 95, 74, 32, and 23 CpGs were found prior to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, and 17 years before LC diagnosis, respectively. Functional enrichment analysis showed that various pathways were associated at different time point berfore LC diagnosis. CpGs of which DNAm was changed two years before LC diagnosis were associated with telomerase extension by telomerase involving ANKRD28/TERT/TERF2/PPP6R3/WRAP53. Transcriptional regulation by TP53 was associated with DNAm changes before both 5 and 14 years of LC diagnosis via POLR2A. Conclusions: We identified the trajectories of DNA methylation up to 18 years prior to LC diagnosis, and found that a greater number of CpG sites showed DNAm changes adjacent to the time point of LC diagnosis. CpG sites associated with specific time point before LC diagnosis may elucidate the mechanisms of tumorigenesis and also have potential for LC prediction markers. Citation Format: Yoon-Jung Choi, Ki-Jae Hong, Yeon-Su Lee, Woo Jin Kim, Yeol Kim, Sun Ha Jee, Jeongseon Kim. Trajectory of DNA methylation in blood up to 18 years prior to lung cancer diagnosis [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 7029.

Abstract 845: Population attributable fraction of cancer incidence due to infectious agents in 2020 in the Republic of Korea

Abstract Purpose: Earlier in 2009, National Cancer Center Korea estimated population attributable fraction (PAF) of cancer incidence due to infectious agents as 24.5% in men and 15.4% in women. This study aimed to investigate the proportion of cancer incidence attributable to infectious agents in the Korean population as of 2020. Materials and Methods: We organized the Consensus Committee to establish strategy and methodology of PAF estimation. Based on the consensus, infectious agents and cancer sites for PAF estimation were selected according to the IARC List of classification with sufficient evidence in human. As a result, infectious agents included hepatitis B and C virus (HBV and HCV), Helicobacter pylori (H. pylori), human papilloma virus (HPV), Clonorchis sinensis (C.sinensis), Epstein Barr virus, and human immunodeficiency virus, and cancer sites included hepatocellular carcinoma (HCC), cholangiocarcinoma (CCC), gastric cancer, pancreatic cancer, cervical cancer, and non-Hodgkin lymphoma. The PAF was calculated by using Levin’s formula including exposure prevalence and relative risks (RRs). Exposure prevalence data were collected from literature review of studies in Korean population in 2005 or earlier, assuming at least 15 years of latent period from risk exposure to cancer development. We performed systematic review for cohort studies and case-control studies which investigated RRs or ORs of cancer due to infectious agents in Korean population. Pooled RRs were estimated by meta-analysis of RRs or ORs by using random-effects model. Results: The fractions of all cancer incidence attributable to infectious agents were estimated to be 13.5% and 7.1% in men and women, respectively. The reduction in PAFs of cancer incidence due to infection in 2020 compared to 2009 is considered due to decrease in exposure prevalence. The major findings regarding infectious agents with large PAFs are as the following. We found that the fractions of HCC cases attributable to HBV infection were 47.7% and 38.4% for cancer incidence in men and women, respectively. The estimated PAFs of gastric cancer due to H. pylori were 40.4% in men and 38.2% in women. C. sinensis was related to 9.8% of CCC cases in men and 5.2% in women. A total of 77.7% of cervical cancer incidence was attributed to HPV infection. Conclusion: Although the total PAF due to infection has decreased over the last decade, infection still contributes a substantial fraction to cancer incidence in Korea. These recent estimates of cancer burden due to infection are important for planning and evaluating the national cancer prevention programs. Citation Format: Kyung-Shin Lee, Hwa Jin Lee, Yoon-Jung Choi, Moran Ki, Aesun Shin, Jong-Hun Kim, Sue-Kyung Park, So-Seul Sung, Sung Ji Moon, Hong Gwan Seo, Jin-Kyoung Oh, Jeong-Soo Im. Population attributable fraction of cancer incidence due to infectious agents in 2020 in the Republic of Korea [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 845.

Abstract 2216: Population attributable fraction of tobacco smoking on cancer incidence in 2020 in the Republic of Korea

Abstract Backgrounds: Cancer is the most common cause of mortality in Korea. According to International Agency for Research on Cancer (IARC), tobacco smoking is the Group I carcinogen, and the National Cancer Center Korea reported in 2009 that 20.9% and 2.3% of total cancer incidence were attributable to tobacco smoking in men and women, respectively. As of 2020, we estimated population attributable fraction (PAF) of cancer incidence due to tobacco smoking. Methods: We organized the Consensus Committee to develop strategy and methodology for PAF estimation. From the consensus, cancer sites for PAF estimation were selected based on the IARC list of classification with sufficient evidence in human. PAF was calculated by using Levin’s formula which includes exposure prevalence and relative risk (RR). Exposure prevalence was collected from the Korea National Health and Nutrition Examination Survey (KNHANES) in 2005, assuming that latent period from risk exposure to cancer development was 15 years. Tobacco smoking was defined as a categorical variable including non-smokers, past smokers, and current smokers. Pooled RRs were estimated from meta-analysis of RRs obtained from Korean Genome and Epidemiology Study, National Health Examination data provided by National Health Insurance Services, Korean Cancer Prevention Study-II, and KNHANES, each of which was linked with Korea Cancer Registry. Cox proportional hazards model were used to estimate RRs, while adjusted by age groups and alcohol consumption. Results: For men, 17.4% of all cancer cases were attributed to smoking, compared to 1.7% for women. Specifically, in men, 57.9% of lung cancer, 36.4% of bladder cancer, 31.9% of esophageal cancer, 39.1% of laryngeal cancer, 25.4% of oral cavity/pharyngeal cancer, 19.7% of liver cancer, and 19.5% of stomach cancer were attributed to tobacco smoking. In women, 51.7% of laryngeal cancer, 15.0% of esophageal cancer, 11.6% of lung cancer, 6.0% of bladder cancer, 5.1% of oral cavity/pharyngeal cancer, 5.0% of cervix cancer, and 4.6% of liver cancer were due to smoking. Conclusion: Tobacco smoking is an important cause of esophageal, laryngeal, and lung cancer in men, and esophageal and laryngeal cancer in women, and comprises a substantial proportion of PAF in cancer incidence. Thus, intervention measures are needed to reduce smoking prevalence for cancer prevention in Korea. Citation Format: Su Jung Byoun, Yoon-Jung Choi, Ye Lin Min, Sue-Kyung Park, Kwang Pil Ko, So_Seul Sung, NaYoung Kim, Keum Ji Jung, Sun Ha Jee, Sung-II Cho, Min Kyung Lim, Sohee Park, Eun Young Park, Hae Dong Woo, Kyu-Won Jung, E Hwa Yun, Byungmi Kim, Jin-Kyoung Oh, Yoonjoo Choi, Bohyun Park, Hong Gwan Seo, Jeong-Soo Im. Population attributable fraction of tobacco smoking on cancer incidence in 2020 in the Republic of Korea [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 2216.

Abstract 2498: Assessing the clinical value of ctDNA sequencing for initial tumor profiling in metastatic colorectal cancer patients with sufficient tumor tissue

Abstract Introduction Tumor profiling including RAS, BRAF, HER2, and MSI/MMR status, is required to determine the treatment for patients with metastatic colorectal cancer (mCRC) at the time of diagnosis. While comprehensive tumor profiling using tissue-based next-generation sequencing (NGS) is increasingly adopted for initial profiling in mCRC, the role of circulating tumor DNA (ctDNA) NGS as initial testing in patients with sufficient tumor tissue is not clearly understood. We assessed the clinical value of ctDNA sequencing compared to tumor NGS in patients with newly diagnosed mCRC who have sufficient tumor specimens. Methods We prospectively enrolled consecutive patients with newly diagnosed mCRC at the National Cancer Center Korea. As per the institutional protocol for mCRC, initial tumor profiling was performed on primary tumor tissue using an in-house NGS panel (NCC PCP ver.3), which included 525 genes. For ctDNA sequencing, patients were evaluated using the AlphaLiquid®100 comprehensive cancer panel (IMBdx, Inc.), which included 118 genes, before the initiation of chemotherapy. Additionally, immunohistochemical (IHC) testing for HER2 and polymerase chain reaction (PCR)/IHC testing for MSI and/or MMR were performed to assess the accuracy of HER2 and MSI/MMR status. Results A total of 188 patients were enrolled. In 139 eligible patients, 275 potentially actionable mutations were found in 12 selected CRC-related genes (APC, TP53, KRAS, NRAS, BRAF, FBXW7, PIK3CA, ERBB2, SMAD4, NF1, EGFR, MET). Of these, 32% were found both in ctDNA and tissue; 54% were found in ctDNA only; 12% in tissue only, and 2% were discordant. For RAS/BRAF mutations, which are required for anti-EGFR treatment decisions, the concordance rate between ctDNA and tissue NGS was 83.1%, and the concordance was higher in patients with higher ctDNA concentrations. For 9 patients with potentially actionable copy number variations (CNV) in EGFR, HER2, MET, and FGFR1, 3 cases were found by both assays; 4 were found by ctDNA only, and 2 were found by tissue only. ctDNA NGS correctly predicted MSI/MMR status in 2 out of 4 patients with MSI-H/dMMR; in the 2 other patients, the MSI and MMR statuses were different, suggesting potential false positivity. In addition, the fold changes in ctDNA dynamics during treatment significantly correlated with changes in tumor size and CEA levels, as well as with droplet digital PCR copy number fold changes. In a patient with MET amplification, ctDNA NGS identified MET Y1230H as a potential acquired resistance mutation after crizotinib treatment, which responded to cabozantinib but not to capmatinib. Conclusions Initial tumor profiling using ctDNA NGS yielded outcomes comparable to those of tumor tissue NGS in guiding treatment for patients with newly diagnosed mCRC, thereby suggesting its utility as an initial profiling method in mCRC. Citation Format: Yongjun Cha, Bun Kim, Dong Woon Lee, Hyun Yang Yeo, Chang Won Hong, Kyung Su Han, Byung Chang Kim, Hee Jin Chang. Assessing the clinical value of ctDNA sequencing for initial tumor profiling in metastatic colorectal cancer patients with sufficient tumor tissue [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 2498.

Abstract 2201: Population attributable fraction of alcohol consumption on cancer incidence in 2020 in the Republic of Korea

Abstract Backgrounds: Alcohol consumption is the Group I carcinogen according to International Agency for Research on Cancer (IARC). In 2009, National Cancer Center Korea reported that 3.0% and 0.5% of total cancer incidence were attributable to alcohol consumption in men and women, respectively. Herein, we estimated population attributable fraction (PAF) of cancer incidence due to alcohol consumption as of 2020. Methods: We organized the Consensus Committee to establish strategy and methodology of PAF estimation. Based on the consensus, cancer sites for PAF estimation were selected according to the IARC List of classification with sufficient evidence in human. PAF was calculated by using Levin’s formula which incorporates exposure prevalence and relative risk (RR). Exposure prevalence was obtained from the Korea National Health and Nutrition Examination Survey (KNHANES) in 2005, assuming that latent period between exposure to alcohol consumption and diagnosis of cancer would be 15 years. Alcohol consumption was defined as non-drinking (<0.1g/day), light (0.1~30g/day), moderate (30~60g/day), and heavy (60~588g/day) drinking according to the definition by World Health Organization. We estimated RRs from the cohort data established by Korean Genome and Epidemiology Study, National Health Examination data provided by National Health Insurance Services, Korean Cancer Prevention Study-II, and KNHANES, while each cohort was linked with Korea Cancer Registry. RRs were estimated by using Cox proportional hazards model adjusted by age group and smoking status. RRs were then meta-analyzed to yield pooled RR by using random-effects model. Results: A total of 4.1% and 1.2% of all cancer incidence were attributable to alcohol consumption in men and women. By cancer sites, 67.1% of esophageal cancer, 23.8% of oral cavity/pharyngeal cancer, 15.1% of laryngeal cancer, 12.0% of colorectal cancer, and 7.9% of liver cancer were attributable to alcohol consumption in men. In women, 54.1% of liver cancer, 10.3% of colorectal cancer, 7.8% of oral cavity/pharyngeal cancer, and 3.6% of breast cancer were due to alcohol consumption. Conclusion: PAF of cancer incidence due to alcohol consumption has increased in 2020 compared to PAF in 2009. As alcohol consumption is an important cause of oral cavity/pharyngeal, esophageal, and laryngeal cancer in men, and liver and breast cancer in women, prevention measures are required to reduce alcohol consumption for cancer prevention in Korea. Citation Format: Ye Lin Min, YounJu Park, Su Jung Byoun, Sue_Kyung Park, Kwang Pil Ko, So-Seul Sung, Na Young Kim, Keum Ji Jung, Sun Ha Jee, Sung-Il Cho, Min Kyung Lim, Sohee Park, Eun Young Park, Hae Dong Woo, Kyu-Won Jung, E Hwa Yun, Byungmi Kim, Jin-Kyoung Oh, Yoonjoo Choi, Bohyun Park, Hong Gwan Seo, Yoon-Jung Choi, Jeong-Soo Im. Population attributable fraction of alcohol consumption on cancer incidence in 2020 in the Republic of Korea [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 2201.

Abstract 1192: Diversity of TCR repertoire on peripheral CD8+PD-1+ T-cell predicting the PFS of chemoradiotherapy followed by durvalumab maintenance in unresectable locally advanced NSCLC patients

Abstract Background: Chemoradiotherapy (CRT) followed by Durvalumab consolidation has been the standard treatment for unresectable locally advanced non-small cell lung cancer (LA-NSCLC) patients. This study aimed to evaluate how CRT changes TCR repertoire on peripheral CD8+PD-1+ T-cells, and the change affects the clinical outcomes of CRT followed by durvalumab treatment. Methods: This was a prospective cohort study conducted from November 2019 to May 2021 in three institutes (National Cancer Center Hospital, Kansai Medical University Hospital, and Aichi Cancer Center Hospital) in Japan. We revealed the diversity of TCR repertoire (diversity evenness 50 [DE50]) on PD-1+CD8+ T cells, and CD8+ T cell phenotype in PBMCs before and after CRT treatment. Results: A total of 40 patients treated with CRT were included. Of these patients, 32 patients received durvalumab consolidation treatment after CRT (Durva cohort). The diversity and usage of T cell Receptor Beta Variable (TRBV) and T-cell receptor beta joining gene (TRBJ) usage were significantly positively correlated before and after CRT (TRBV usage: r=0.62, p<0.001, TRBJ usage: r=0.55, p<0.001). Regarding the association of TCR repertoire diversity with CD8+ T cell phenotype, DE50 and frequencies of CD8 naive were significantly positively correlated before CRT (p=0.049), while there was no correlation between PD-L1 expression and TCR repertoire before CRT (r=0.03, p=0.89) In Durva cohort, DE50 in patients with non-recurrence was higher than those with recurrence both before and after CRT (Before CRT: 0.0032 vs. 0.0019, p=0.13, After CRT: 0.0026 vs. 0.0014, p=0.06). The progression-free survival (PFS) of patients with DE50High before CRT was significantly greater than those with DE50Low (NR vs. 14.3 months; p=0.01). Moreover, when the patients were exploratory classified based on the PD-L1 expression status and the diversity of TCR repertoire, the PFS of the CRT followed by durvalumab apparently differed (DE50High, PD-L1 TPS≥1%, NR, and DE50Low, PD-L1 TPS<1%, 5.9 (4.6-7.3) months, p=0.001). Conclusions: TCR diversity of peripheral CD8+PD-1+ T-cell predicted the recurrence in unresectable locally advanced NSCLC patients treated with chemoradiotherapy followed by durvalumab maintenance. Additionally, the TCR diversity combined with PD-L1 expression status could more accurately predict the efficacy of the CRT followed by durvalumab. Citation Format: Masayuki Shirasawa, Tatsuya Yoshida, Yuki Takeyasu, Takaji Matsutani, Shigehiro Yagishita, Shigehisa Kitano, Hiroaki Kuroda, Toyoaki Hida, Takayasu Kurata, Yuichiro Ohe. Diversity of TCR repertoire on peripheral CD8+PD-1+ T-cell predicting the PFS of chemoradiotherapy followed by durvalumab maintenance in unresectable locally advanced NSCLC patients [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 1192.

Abstract 1938: WEE1 inhibition prevents and overcomes resistance to KRAS inhibitors in lung cancer by enhancing MCL1-mediated apoptosis

Abstract Background: While novel covalent inhibitors of KRAS G12C have been approved in non-small-cell lung cancer (NSCLC), their efficacies are known to be limited. To enhance the therapeutic potential of KRAS inhibitors, combination strategies need to be developed. In this study, we conducted a large-scale screening to identify novel combination partners that induced synergistic efficacy with KRAS inhibitors. Additionally, mechanistic analyses were conducted to clarify the synergistic effects in combination and their role in conferring resistance to KRAS inhibitors. Methods: To identify novel combination partners of KRAS inhibitors, we conducted high-throughput screening (HTS) using a chemical library composed of 1,400 kinase inhibitors. Sotorasib was used as a KRAS inhibitor. Anti-proliferative and apoptotic effects in vitro were assessed by ATP-based cell viability assay, and caspase 3/7 assay and/or Annexin V assay, respectively. Protein expression levels were assessed by immunoblotting. In vivo studies were performed using a H358 xenograft nude mouse model and a patient-derived xenograft model (PDX). PDX samples were provided by the National Cancer Center J-PDX library, Japan. Results: HTS identified the WEE1 inhibitor AZD1775, a G2/M checkpoint abrogator in clinical-stage development, as a promising combination partner of KRAS inhibitors in KRAS G12C mutant NSCLC. Synergistic effects of KRAS and WEE1 inhibitors were confirmed across multiple KRAS G12C mutant NSCLC cell lines, independently of their co-occurring oncogenic mutation profiles. The combination treatment enhanced apoptotic cell death, being upregulated pro-apoptotic protein BIM, while downregulated anti-apoptotic protein MCL1. In vivo efficacy studies in combination with sotorasib and AZD1775 also demonstrated remarkable tumor regression and durable response in both CDX and PDX models. We also generated sotorasib-resistant H23 (H23-SR) cells, confirming upregulation of both WEE1 and MCL1 in the resistant cells. Ectopic overexpression of WEE1 in H23, on the contrary, conferred resistance to sotorasib. Furthermore, WEE1 inhibition re-sensitized H23-SR cells to KRAS inhibitors. Conclusion: Our results suggest that the WEE1-MCL1 axis plays an important role in both the initial therapeutic efficacy and the acquired resistance to KRAS inhibitors. These findings could pave the way for a novel therapeutic strategy for KRAS G12C mutant NSCLC. Citation Format: Gaku Yamamoto, Kosuke Tanaka, Ryo Kamata, Takehiro Nakao, Shunta Mori, Jie Liu, Susumu S. Kobayashi, Akihiro Ohashi. WEE1 inhibition prevents and overcomes resistance to KRAS inhibitors in lung cancer by enhancing MCL1-mediated apoptosis [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 1938.

Abstract 755: Fecal microbial dysbiosis is associated with colorectal cancer risk

Abstract Although there is evidence of an association between the fecal microbiota and colorectal cancer (CRC) risk in epidemiologic studies, there is a lack of data from large-scale population-based studies. To address this gap, we assessed the dysbiosis of the fecal microbiome in a large-scale study in Korea. We recruited 287 CRC patients from the Center for Colorectal Cancer, National Cancer Center Hospital, Korea to perform 16S rRNA gene sequencing of fecal samples. A total of 287 age- and sex-matched healthy participants were selected from 890 cohort of healthy Koreans that are publicly available (PRJEB33905). The microbial dysbiosis index (MDI) was calculated based on the differentially abundant species. The association between MDI and CRC risk was observed using conditional logistic regression. Alpha-diversity indices were not significantly different between CRC cases and controls. The first three principal coordinates derived by a principal coordinate analysis (PCoA) based on weighted UniFrac distance explained 41.24% of the overall microbial diversity, with a significant divergence of the microbial composition between CRC patients and controls (PERMANOVA p=0.001). Three enterotypes were found based on CRC patients’ microbial composition. Those who were in the third tertile of the MDI showed a significantly increased risk of CRC in the total population (OR: 6.59, 95% CI: 3.83-11.33, p-trend<0.001) compared to those in the lowest tertile. Similar results were found for men (OR: 6.58, 95% CI: 3.17-13.63, p-trend<0.001) and women (OR: 6.69, 95% CI: 2.91-15.37, p-trend<0.001). Dysbiosis in the fecal microbiota may be associated with an increased risk of CRC. Due to the potentially modifiable nature of the gut microbiota, our findings may have implications for CRC prevention among Koreans. Key words: Fecal microbiome, 16S rRNA gene sequencing, Microbial dysbiosis, Colorectal cancer Citation Format: Jeongseon Kim, Madhawa Gunathilake, Hyun Yang Yeo, Jae Hwan Oh, Byung Chang Kim, Nayoung Han, Bun Kim, Hyojin Pyun, Mi Young Lim, Young-Do Nam, Hee Jin Chang. Fecal microbial dysbiosis is associated with colorectal cancer risk [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 755.

Abstract 2173: Effect of colored fruits and vegetables intake on gastrointestinal cancer risk: A prospective cohort study

Abstract Background and Aim: Diverse antioxidant compounds found in colored fruits and vegetables have been linked to various health benefits. While anthocyanins, present in purple, red, and blue pigments, and chlorophyll, responsible for green pigments, are recognized for their antioxidant properties, limited evidence exists regarding their preventive effects on gastrointestinal (GI) cancers. In the year 2020, GI cancers constituted 29% of global cancer cases. To address this gap, this prospective cohort study investigates the association between the intake of colored fruits and vegetables and the risk of GI cancer in Korea. Methods: The Cancer Screenee Cohort, comprising adults undergoing check-ups at the National Cancer Center Korea, was analyzed for GI cancer cases diagnosed between October 16, 2007, and December 31, 2020. Of the 10,741 eligible participants, 208 developed GI cancer and 10,533 did not. General and validated semi-quantitative food frequency questionnaires were used to collect demographic data and measure dietary intake. Fruit and vegetable intake (g/day) were categorized into four groups (white, green, orange/yellow, and red/purple) based on the color of the edible parts. Analyses were conducted on total fruits/vegetables, total fruits, total vegetables, and fruits/vegetables in each color category. The intake was divided into quintiles to compare the effects of low and high intake. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). HRs were adjusted for variables, including age, gender, body mass index, smoking status, alcohol drinking, education, occupation, first-degree family history of any cancer, and marital status. Results: High total fruit and vegetable intake was associated with reduced GI cancer risk (HR = 0.64, 95% CI: 0.42-0.98, p for trend = 0.022). No significant associations were found for total fruits, total vegetables, fruits and vegetables together and separately in green and orange/yellow colors in this study. However, a higher intake of white fruits and vegetables was found to be effective in preventing cancer with adjusted HRs (HR = 0.51, 95% CI: 0.31-0.85, p for trend = 0.019). Similarly, the inverse association was observed in red and purple vegetables with adjusted HRs (HR = 0.52, 95% CI: 0.32-0.84, p for trend = 0.022). Conclusions: This cohort study suggests that the consumption of fruits and vegetables in white color, as well as vegetables in red and purple colors, may have a potential protective effect against GI cancer. Key Words: Gastrointestinal (GI) cancer; fruits and vegetables; colors of fruits and vegetables; color food; cohort studies; Korea Citation Format: Yujin Cho, Jeonghee Lee, Madhawa Gunathilake, Jeongseon Kim. Effect of colored fruits and vegetables intake on gastrointestinal cancer risk: A prospective cohort study [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 2173.

Abstract 5690: Urinary microRNA expression in pancreatic cancer with cachexia

Abstract Background: Cancer cachexia (CC) is a multifactorial syndrome characterized by appetite loss, weight loss and skeletal muscle wasting. It increases functional impairment, treatment-related toxicity, and a lower quality of life. Importantly, CC is one of the leading causes of cancer-related deaths, and its occurrence is particularly prevalent in advanced stages of pancreatic cancer (PC). The syndrome is thought to be associated with systemic inflammation and increased energy expenditure, yet the specific mechanisms remain to be fully understood. Although timely detection and intervention might be crucial in preventing CC’s progression, early diagnosis of this syndrome remains challenging due to the absence of suitable biomarkers. Here, we analyzed urinary microRNAs (miRNAs) as a potential noninvasive biomarkers for detecting CC in patients (pts) with PC. Methods: Clinical information including presence or absence of CC and urine samples were collected from pts with PC treated at National Cancer Center Hospital, Tokyo, Japan from March to October 2022. The diagnosis of CC was made according to the following definitions by Fearon. K et al. (1) weight loss of ≥5% within 6 months; (2) weight loss of ≥2% in pts with a BMI of <20 kg/m2; or (3) weight loss of ≥2% in pts with sarcopenia. In this study, pts who met the definition of CC within 6 months of enrollment were considered to have CC.Urinary miRNA profiles from pts with PC were sequenced by NGS and analyzed using DESeq2 to identify differentially expressed miRNAs (DEMs) between pts with CC and those without. DEMs were further explored for associated pathways and target genes using miRPathDB v.2.0. Results: Of the 64 subjects, 52 pts were included in the analysis after excluding three pts with low urine sample read coverage and nine pts with no information on CC status. Among those, 38 pts were classified as having CC. Patients’ background was as follows (CC/no CC); median age 70 [range: 44-80]/67 [57-74], male and female 19/7 pts, respectively, cStage {I (6/0), II (1/0), III (17/4), IV (14/10)} pts, median BMI (male 22.1 [17.7-27.2]/21.7 [18.2-28.2], female 21.7 [14.6-25.2]/21.9 [16.6-27.4]) kg/m2. Among 307 miRNAs detected in the urine of pts with PC, 49 miRNAs had previously been reported in CC research. The miR-141-5p was differentially expressed between pts with CC and those without CC (Wald test pBH = 0.079). It was down-regulated in pts with CC (Mann-Whitney U test p = 6.4e-4) and most significantly associated with the FoxO signaling pathway (ORA pBH = 1.84e-4), followed by the mTOR signaling pathway (ORA pBH = 0.008). Conclusions: Our study indicates that miR-141-5p holds potential as a noninvasive biomarker for the detection of CC in pts with PC. Although miR-141-5p has not been previously reported in CC, its significant association with the FoxO signaling pathway, which is one of the major pathways regulating skeletal muscle atrophy, underscores the relevance of miR-141-5p in the context of CC. Citation Format: Mao Okada, Shunsuke Kondo, Yukiko Igawa, Tatsuya Yoshida, Milos Havelka, Mika Mizunuma, Yuki Ichikawa, Noboru Yamamoto. Urinary microRNA expression in pancreatic cancer with cachexia [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 5690.

Abstract 6425: Harnessing big data from pan-cancer concerning more than 1300 patients with immune checkpoint inhibitors identifies novel predictive biomarkers

Abstract Immune-checkpoint inhibitors (ICIs) have revolutionized cancer therapy, yet many patients face the challenges of either not benefiting or developing resistance to ICIs. Advances in genome sequencing allow the exploitation of high-dimension oncological data in the research and development of precision immuno-oncology. We conducted a comprehensive literature review involving cancer patients treated with ICIs [anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4), or their combination] and collected available transcriptomic data from pretreatment biopsies along with corresponding clinical outcomes. Biomarkers for ICI response were independently investigated within each study using the logistic regression method and combined with the odds ratio (OR) for meta-analysis. A total of 210 formalin-fixed paraffin-embedded pan-cancer samples with pretreatment biopsies from the National Cancer Center retrospective cohort were collected for validation. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) were employed to validate the stable and clinically applicable utility of the genomic biomarker identified in our analysis. Across 18 studies, we identified 1106 cancer patients who received immunotherapy with pre-treatment transcriptomic data, including melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), stomach adenocarcinoma (STAD), glioblastoma (GBM), and bladder urothelial carcinoma (BLCA), of which 8421 genes were available in all datasets. Meta-analysis based on a common effect model revealed that 332 genes were positively correlated with a favorable response to ICIs, and 404 genes were negatively associated with the therapeutic outcome, with all pooled OR being statistically significant (P <0.05). We identified a novel biomarker, ZBED2 (Zinc Finger BED-Type Containing 2), which demonstrated superior predictive value over other biomarkers for ICI efficacy (pooled OR, 0.596; 95% CI, 0.450-0.788, P =0.002). Similarly, RT-qPCR (AUC: 0.821) and IHC (AUC: 0.789) results further validated the predictive utility for ICI response in the real-world cohort of 210 cancer patients with pretreatment samples receiving ICIs. Additionally, we observed that the expression of ZBED2 was favorably associated with the overall survival of patients receiving immunotherapy (HR: 0.72). In summary, our study provides a in-depth analysis of potentially predictable biomarkers for ICIs in cancer and highlights the potential of large-scale meta-analyses in identifying stable biomarkers. ZBED2 emerges as a novel predictive biomarker for ICIs and may guide the implementation of risk-related therapeutic strategies. Citation Format: Peng Wu, Chaoqi Zhang, Ao Shen, Xuanyu Gu, Nan Sun, Jie He. Harnessing big data from pan-cancer concerning more than 1300 patients with immune checkpoint inhibitors identifies novel predictive biomarkers [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 6425.

Factors associated with recurrence in patients with oral cancer in Mongolia

IntroductionIn Mongolia, there has been limited research on the posttreatment survival rate, recurrence, and occurrence of oral cancer. The goal of this study is to investigate the risk factors that contribute to the recurrence of oral cancer to increase survival rates, facilitate early detection, and improve treatment accuracy.MethodA retrospective cohort method was used, with medical records from 173 patients diagnosed with squamous cell carcinoma of the mouth at the National Cancer Center of Mongolia’s Department of Head and Neck Surgery, Radio, and Chemotherapy between 2012 and 2017. The Mongolian National University of Medical Sciences’ Research Ethics Committee approved the project.ResultsThe findings revealed that 109 cases (63.0%) were men and 64 (37.0%) were females, with a large proportion of patients (28.3%) falling between the ages of 61 and 70. Men had a 3.8 times higher risk of cancer recurrence than women (OR = 3.79, CI = 1.24–11.57). Furthermore, lymph node metastases and treatment were linked to oral cancer recurrence.ConclusionThis study offers light on the factors that influence the recurrence of oral cancer, giving useful insights for improving patient outcomes through early detection and proper treatment.