AbstractPurposeTo establish a simple and noninvasive screening test for sleep apnea (SA) that imposes less burden on potential patients. The specific objective of this study was to verify the effectiveness of past and future single-lead electrocardiogram (ECG) data from SA occurrence sites in improving the estimation accuracy of SA and sleep apnea syndrome (SAS) using machine learning.MethodsThe Apnea-ECG dataset comprising 70 ECG recordings was used to construct various machine-learning models. The time window size was adjusted based on the accuracy of SA detection, and the performance of SA detection and SAS diagnosis (apnea‒hypopnea index ≥ 5 was considered SAS) was compared.ResultsUsing ECG data from a few minutes before and after the occurrence of SAs improved the estimation accuracy of SA and SAS in all machine learning models. The optimal range of the time window and achieved accuracy for SAS varied by model; however, the sensitivity ranged from 95.7 to 100%, and the specificity ranged from 91.7 to 100%.ConclusionsECG data from a few minutes before and after SA occurrence were effective in SA detection and SAS diagnosis, confirming that SA is a continuous phenomenon and that SA affects heart function over a few minutes before and after SA occurrence. Screening tests for SAS, using data obtained from single-lead ECGs with appropriate past and future time windows, should be performed with clinical-level accuracy.

21 Apr 2025·Cancer Research

Abstract 1198: Global analysis of incidence and mortality trends in early-onset and later-onset cancers

Author: Ugai, Tomotaka ; Terashima, Miyu ; Ugai, Satoko ; Nakayama, Kota ; Kawachi, Ichiro ; Shirai, Sora ; Sasamoto, Naoko ; Mizuno, Hiroki ; Lee, Hwa-Young ; Giovanucci, Edward ; Song, Minkyo

AbstractBackground:The global increase in the incidence of early-onset cancers (defined as cancers diagnosed at 20-49 years) is a serious public health problem. It remains inadequately explored whether trends in the incidence of early-onset cancers differ from those of later-onset cancers (defined as cancers diagnosed at age 50 and above). Also, considering the potential over-detection of clinically non-significant cancers by screening, it is crucial to examine whether early-onset cancer incidence has increased concurrently with mortality.Method:We retrieved age-standardized incidence and mortality rates of early-onset and later-onset cancers diagnosed between 2000 and 2017 in 31 countries from data available in the GLOBOCAN database. Using joinpoint regression models, we assessed average annual percentage changes (AAPCs) in cancer incidence and mortality for each cancer type in each country, with statistical significance corresponding to a positive 95% CI that does not include zero (indicating an increasing trend). We examined 1) whether trends in the incidence of early-onset cancers differ from those of later-onset cancers, and 2) whether both incidence and mortality of early-onset cancers have increased concurrently. Differences in AAPCs were assessed by comparing 95% CIs, where nonoverlapping 95% CIs were considered statistically significantly different.Results:We observed that 9 female and 6 male early-onset cancers had statistically significant positive AAPCs in at least 10 countries. Among these, the following early-onset cancer types had significantly higher AAPCs than later-onset cancer types: colorectal cancer (7 countries; AAPC range: 1.8%-3.8%), kidney cancer (5 countries; AAPC range: 2.1%-7.5%), multiple myeloma (5 countries; AAPC range: 3.1%-9.8%), and uterine cancer (4 countries; AAPC range: 1.5%-10.3%) in females; prostate cancer (13 countries; AAPC range: 2.7%-13.2%), colorectal cancer (8 countries; AAPC range: 1.0%-4.1%), and kidney cancer (8 countries; AAPC range: 2.8%-9.7%) in males. Additionally, we observed statistically significant positive AAPCs in both the incidence and mortality of the following early-onset cancer types: colorectal cancer (4 countries), kidney cancer (4 countries), and uterine cancer (3 countries) in females; colorectal cancer (8 countries) in males.Conclusion:Our study highlights global differences in cancer incidence trends between early-onset and later-onset cancer types. Notably, the incidence of certain early-onset types, such as obesity-related cancers, including colorectal, kidney, uterine cancer, and myeloma showed more dramatic increases compared to later-onset cancer types in North America, Oceania, and parts of Europe. Additionally, we noted concurrent rises in incidence and mortality for several early-onset cancer types, including colorectal, kidney, and uterine cancer.Citation Format:Miyu Terashima, Kota Nakayama, Sora Shirai, Hwa-Young Lee, Satoko Ugai, Hiroki Mizuno, Minkyo Song, Naoko Sasamoto, Ichiro Kawachi, Edward Giovanucci, Tomotaka Ugai. Global analysis of incidence and mortality trends in early-onset and later-onset cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1198.

21 Apr 2025·Cancer Research

Abstract 2211: A novel combined immunotherapy of gut microbial metabolite butyrate and oncolytic adenovirus in colorectal cancer

Author: Katayama, Tetsuya ; Kagawa, Shunsuke ; Takeda, Eri ; Mikane, Yu ; Urata, Yasuo ; Kadowaki, Daisuke ; Hashimoto, Masashi ; Kakiuchi, Yoshihiko ; Kuroda, Shinji ; Yoshida, Yusuke Yoshida ; Kanaya, Nobuhiko ; Sakamoto, Masaki Sakamoto ; Fujiwara, Toshiyoshi ; Hanzawa, Shunya ; Kikuchi, Satoru ; Tazawa, Hiroshi

AbstractButyrate, a short-chain fatty acid (SCFA) produced by gut bacteria in the colon, serves as a critical energy source for colonocytes. Gut microbiota and its primary metabolite, butyrate, have been reported to potentially modulate tumor sensitivity to chemotherapy or immunotherapy, although the underlying mechanisms remain unclear. Oncolytic virotherapy is a promising antitumor treatment that selectively induces oncolytic cell death in tumor cells. Previously, we developed OBP-702, a telomerase-specific oncolytic adenovirus armed with the p53 tumor suppressor gene, which demonstrated potent antitumor effects across various cancer types. Oncolytic virotherapy is also known to stimulate antitumor immunity. In this study, we investigated the combined effects of OBP-702 and butyrate on colorectal cancer and elucidated the underlying mechanisms. In vitro, the combination of OBP-702 and butyrate exhibited synergistic cytotoxicity against various human and murine colorectal cancer cell lines. In vivo, the combination therapy significantly suppressed tumor growth in HCT116 and CT26 subcutaneous tumor models compared to monotherapy with either OBP-702 or butyrate alone. These synergistic effects were mediated by butyrate enhancing OBP-702's efficacy through the upregulation of coxsackievirus and adenovirus receptor (CAR) and integrin expression on tumor cells, improving viral infection efficiency. Butyrate also increased MHC-I expression on tumor cells through activation of the cGAS-STING pathway, leading to enhanced CXCL10 expression. This, in turn, activated antitumor immunity by recruiting CD8-positive T cells to the tumor microenvironment. The synergistic effects of butyrate and OBP-702 were further confirmed in an orthotopic colorectal tumor model with liver metastases using luciferase-expressing CT26 cells. In this model, the combination therapy not only reduced tumor growth but also improved survival by enhancing antitumor immunity mediated by CD8-positive T cells. To translate these findings into a more clinically relevant approach, butyrate-producing bacteria, Clostridium butyricum Miyairi 588 (CBM588), were used in place of butyrate. The combination therapy of CBM588 and OBP-702 demonstrated similar synergistic antitumor effects in mouse subcutaneous and rectal tumor models. In conclusion, the combination of OBP-702 and butyrate shows promise as a synergistic antitumor strategy and may represent a novel therapeutic approach for colorectal cancer.Citation Format:Tetsuya Katayama, Shinji Kuroda, Masaki Sakamoto Sakamoto, Eri Takeda, Yu Mikane, Shunya Hanzawa, Daisuke Kadowaki, Yusuke Yoshida Yoshida, Masashi Hashimoto, Nobuhiko Kanaya, Yoshihiko Kakiuchi, Satoru Kikuchi, Shunsuke Kagawa, Hiroshi Tazawa, Yasuo Urata, Toshiyoshi Fujiwara. A novel combined immunotherapy of gut microbial metabolite butyrate and oncolytic adenovirus in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2211.

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