medRxiv - Oncology最新文献

{"title":"BENCHMARKING VISION ENCODERS FOR SURVIVAL ANALYSIS USING HISTOPATHOLOGICAL IMAGES","authors":"Asad Nizami, Arita Halder","doi":"10.1101/2024.08.23.24312362","DOIUrl":"https://doi.org/10.1101/2024.08.23.24312362","url":null,"abstract":"Cancer is a complex disease characterized by the uncontrolled growth of abnormal cells in the body but can be prevented and even cured when detected early. Advanced medical imaging has introduced Whole Slide Images (WSIs). When combined with deep learning techniques, it can be used to extract meaningful features. These features are useful for various tasks such as classification and segmentation. There have been numerous studies involving the use of WSIs for survival analysis. Hence, it is crucial to determine their effectiveness for specific use cases. In this paper, we compared three publicly available vision encoders- UNI, Phikon and ResNet18 which are trained on millions of histopathological images, to generate feature embedding for survival analysis. WSIs cannot be fed directly to a network due to their size. We have divided them into 256 × 256 pixels patches and used a vision encoder to get feature embeddings. These embeddings were passed into an aggregator function to get representation at the WSI level which was then passed to a Long Short Term Memory (LSTM) based risk prediction head for survival analysis. Using breast cancer data from The Cancer Genome Atlas Program (TCGA) and k-fold cross-validation, we demonstrated that transformer-based models are more effective in survival analysis and achieved better C-index on average than ResNet-based architecture. The code for this study will be made available.","PeriodicalId":501437,"journal":{"name":"medRxiv - Oncology","volume":"63 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of a novel food rich in miraculin on the intestinal microbiome of malnourished patients with cancer and dysgeusia","authors":"Julio Plaza-Diaz, Marco Brandimonte-Hernandez, Bricia Lopez-Plaza, Francisco Javier Ruiz-Ojeda, Ana Isabel Alvarez-Mercado, Lucia Arcos-Castellanos, Jaime Feliu-Batlle, Thomas Hummel, Samara Palma-Milla, Angel Gil","doi":"10.1101/2024.08.20.24312287","DOIUrl":"https://doi.org/10.1101/2024.08.20.24312287","url":null,"abstract":"Dysgeusia contributes to nutritional derangement and worsens the quality of life of patients with cancer. Despite the different strategies, there is no effective treatment for patients suffering from taste disorders provided by the pharmaceutical industry. We developed a novel strategy for re-ducing side effects in cancer patients by providing a novel food supplement with the taste-modifying glycoprotein miraculin, which is approved by the European Union, as an adju-vant to medical-nutritional therapy. A pilot randomized, parallel, triple-blind, and place-bo-controlled intervention clinical trial was carried out in which 31 malnourished patients with cancer and dysgeusia receiving antineoplastic treatment, and were randomized into three arms: standard dose of DMB (150 mg DMB/tablet), high dose of DMB (300 mg DMB/tablet) or placebo (300 mg freeze-dried strawberry) for three months. Patients consumed a DMB or placebo tablet before each main meal (breakfast, lunch and dinner). Using stool samples from patients with can-cer, we analyzed the intestinal microbiome via nanopore methodology. We detected differences in the relative abundances of genera Phocaeicola and Escherichia depending on the treatment. Nev-ertheless, only the Solibaculum genus was more abundant in the standard-dose DMB group after 3 months. At the species level, Bacteroides sp. PHL 2737 presented a relatively low abundance in both DMB groups, and Vescimonas coprocola presented a relatively high abundance in both treat-ment groups after 3 months. Furthermore, a standard dose of DMB was positively associated with TNF-α levels and Lachnoclostridium and Mediterraneibacter abundances, whereas a high dose of DMB was negatively associated with TNF-α levels and the relative abundance of Pho-caeicola. After a high dose of DMB, erythrocyte polyunsaturated fatty acids were positively cor-related with Lachnoclostridium and Roseburia, and there was a positive association between Pho-caeicola and the acetic acid concentration of feces. The intake of DMB together with nutritional treatment and individualized dietary advice results in positive changes in the intestinal micro-biome of patients with cancer and dysgeusia There was a negative association between the rela-tive abundance of Phocaeicola and taste perception in the DMB high dose group. Changes observed in the intestinal microbiota might contribute to maintaining an appropriate immune response of cancer patients. Since the present pilot study involved only a few participants, further research is needed to draw robust conclusions.","PeriodicalId":501437,"journal":{"name":"medRxiv - Oncology","volume":"63 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142226194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the diagnostic value of YiDiXie™-SS and YiDiXie™-HS in gastric cancer","authors":"Huimei Zhou, Chen Sun, Yanrong Qi, Yutong Wu, Xutai Li, Zhenjian Ge, Wenkang Chen, Yingqi Li, Pengwu Zhang, Shengjie Lin, Wuping Wang, Siwei Chen, Wei Li, Xi Li, Ling Ji, Yongqing Lai","doi":"10.1101/2024.08.21.24312336","DOIUrl":"https://doi.org/10.1101/2024.08.21.24312336","url":null,"abstract":"Background: Gastric cancer poses a severe risk to public health and has a substantial financial impact. Tumor markers such as CEA, CA125, CA19-9, and others, as well as the fecal occult blood test (FOBT), are frequently utilized for gastric cancer screening and initial diagnosis. however, False-positive results of FOBT and other markers will cause needless mental suffering, costly examination costs, examination injuries, and other unfavorable consequences. False-negative results of FOBT and other markers will cause treatment to be delayed, which will force patients to suffer from a poor prognosis, high treatment costs, a low quality of life, and a short survival period. Finding practical, affordable, and non-invasive diagnostic techniques is crucial to lowering the false-positive and false-negative rates of FOBT and other markers. The aim of this study was to evaluate the diagnostic value of YiDiXie™-SS and YiDiXie™-HS in gastric cancer.\u0000Patients and methods: This study included 602 subjects (Malignant group, n=222; Benign group, n=380 cases). The remaining serum samples of the subjects were collected and the sensitivity and specificity of the YiDiXie™-SS and YiDiXie™-HS were evaluated using the YiDiXie™ all-cancer detection kit. Results: The sensitivity of YiDiXie™-SS in patients with positive FOBT, CEA, CA125, and CA19-9 were 100% (95% CI: 77.2%-100%), 96.7% (95% CI: 83.3% - 99.8%), 95.5% (95% CI: 78.2%- 99.8%), 97.1% (95% CI: 85.1%- 99.8%); The Specificity degrees were 75.0% (95% CI: 30.1%- 98.7%), 73.3% (95% CI: 48.0%- 89.1%), 66.7% (95% CI: 30.0%- 94.1%), 66.7% (95% CI: 35.4%-87.9%). This means that the application of YiDiXie™-SS, without basically increasing the missed diagnosis of malignant tumors, reduced the false-positive rates of FOBT, CEA, CA125, and CA19-9 by 75.0% (95% CI: 30.1%-98.7%), 73.3% (95% CI: 48.0% - 89.1%), 66.7% (95% CI: 30.0% -94.1%), 66.7% (95% CI: 35.4% -87.9%). The sensitivity of YiDiXie™-HS in FOBT, CEA, CA125, and CA19-9 negative patients was 96.5% (95%CI: 90.2-99.0%) and 96.8% (95%CI: 93.2% - 98.5%), 97.3% (95% CI: 93.8%- 98.8%), 96.7% (95% CI: 93.0%- 98.5%); The specific degrees were 86.4% (95% CI: 66.7%- 95.3%), 89.3% (95% CI: 85.7%- 92.1%), 89.5% (95% CI: 84.6%- 93.0%), 90.4% (95% CI: 86.8%-93.1%). This means that YiDiXie™-HS reduced false-negatives for FOBT, CEA, CA125, and CA19-9 by 96.5% (95% CI: 90.2% to 99.0%) and 96.8% (95% CI: 93.2% - 98.5%), 97.3% (95% CI: 93.8%- 98.8%), 96.7% (95% CI: 93.0%- 98.5%).\u0000Conclusion: YiDiXie™-SS significantly reduced false-positive rates of FOBT, CEA, CA125 and CA19-9 without substantially increasing delayed treatment of malignant tumors. YiDiXie™-HS significantly reduced false-negative rates for FOBT, CEA, CA125 and CA19-9. YiDiXie™-SS and YiDiXie™-HS have important diagnostic value in gastric cancer, and are expected to solve the two problems of \"high false-positive rate of FOBT and other markers\" and \"high false-negative rate of FOBT and other markers\" in gastric cancer. C","PeriodicalId":501437,"journal":{"name":"medRxiv - Oncology","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fecal microbiota transplantation promotes immunotherapy sensitivity in refractory gastrointestinal cancer patients: open label, single-arm, single center, phase 1 study","authors":"Yifan Zhang, Xiaomin Xu, Shulin Wang, Xiaochen Yin, Bohan Zhang, Zhengnong Zhu, Rujie Ji, Jing Zhu, Hermione He, Siyuan Cheng, Zihan Han, Tong Xie, Xiaotian Zhang, Yakun Wang, Si Shen, Yan Kou, Siyu Bao, Yingyu Liu, Baoran Cao, Christophe Bonny, Eran Segal, Yan Tan, Lin Shen, Zhi Peng","doi":"10.1101/2024.08.21.24312340","DOIUrl":"https://doi.org/10.1101/2024.08.21.24312340","url":null,"abstract":"Background: The discovery and therapeutic application of immune checkpoint inhibitors (ICIs) has significantly improved clinical outcomes in cancer treatment. However, the response rate is still low in gastrointestinal (GI) cancers. The gut microbiome's impact on immune modulation is a promising area for enhancing ICI efficacy.\u0000Methods: This study (NCT04130763) is an open label, single-arm, single center, phase 1 study assessing the safety and efficacy of fecal microbiota transplantation (FMT) from healthy donors in ten advanced GI cancer patients resistant to anti-PD-(L)1 treatment. Patients received initial FMT treatment via oral capsules, followed by a combination therapy phase, where maintenance FMT was paired with nivolumab at 3mg/kg every two weeks for six cycles. Serial biomarker assessments were conducted through both fecal and blood sampling.\u0000Findings: The combination of FMT and anti-PD1 treatment was well tolerated with no serious adverse reactions observed among all 10 patients. The objective response rate was 20% and the disease control rate was 40%. The progression-free survival of these two responders were 15 and more than 19 months respectively. Clinical benefits were associated with colonization of donor-derived immunogenic microbes, and an activated immune status reflected by peripheral immune cell populations. Responder-enriched microbes interacted closely as a butyrate-functional guild, while non-responder-enriched microbes interacted sparsely and had higher fraction of oral-originated microbes. Donor-specific microbial traits that influence clinical efficacy of FMT were validated in an independent cohort.\u0000Interpretation: The current study demonstrates the feasibility of FMT for ICI-refractory GI cancer patients and provides a foundation for live biotherapeutic product (LBP) development to enhance ICI efficacy.","PeriodicalId":501437,"journal":{"name":"medRxiv - Oncology","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Health-Seeking Behavior and Anxiety of Cancer Patients in Bangladesh during the COVID-19 Pandemic: A Cross-Sectional Study","authors":"Nur-A-Safrina Rahman, Munmun Mustafa, Tahsin Tasneem Tabassum, Sumona Haque Simu, Mridul Gupta, Sumaiya Afrin, Maisha Samiha, Shahra Tanjim Moulee, Faisal Abdullah, Sifat Sharmin, Bilkis Akhter Loken, Sadia Mahmud Trisha, Md Saimon, Vivek Podder, Priya Singhania, ANM Shamsul Islam","doi":"10.1101/2024.08.19.24312282","DOIUrl":"https://doi.org/10.1101/2024.08.19.24312282","url":null,"abstract":"Background: The COVID-19 pandemic has posed unique challenges for cancer patients, who not only require ongoing medical care but also face an elevated risk of infection. Investigating the health-seeking behavior and barriers among adult cancer patients during this global crisis is crucial for ensuring their access to essential care amidst the pandemic's complexities.\u0000Objective: This cross-sectional study aimed to assess the health-seeking behavior, perceived barriers, and anxiety among adult cancer patients during the COVID-19 pandemic.\u0000Materials and Methods: The study, conducted from August 2020 to December 2020, involved 210 participants purposively selected from the National Institute of Cancer Research and Hospital and Ahsania Mission Cancer and General Hospital in Dhaka. Data was collected through face-to-face interviews using a pre-tested semi-structured questionnaire and analyzed using SPSS (Version 26).\u0000Results: Among the 210 participants, 56.2% were male, 28.6% aged 46-55, and 36.7% had no formal education. Approximately 52.3% preferred public healthcare facilities, while 6.2% sought homeopathy or pharmacy advice for symptoms. Significant differences emerged in post-pandemic healthcare provider contact (p-0.0). Notably, 88.1% missed appointments, with 78.3% taking no action. Barriers included transport issues (77.1%), reduced income (59%), and lacking financial (53.4%) and mental support (56.6%). Conversely, respondents downplayed public awareness (80%), infection risk from others (84.7%), healthcare provider infection risk (82.4%), and hospital overcrowding (64.8%). Fear of hospitals correlated with public awareness (p-0.0). On the GAD-7 scale, most had minimal anxiety (53.8%), with a weak provider contact-anxiety correlation (p-0.03). Healthcare providers excelled in precautions (99.5%) and health status communication (85.3%).\u0000Conclusion:\u0000Despite the barriers and risks posed by the pandemic, cancer patients prioritized their care. Given the need for continued cancer care and the elevated risk of COVID-19 among cancer patients, adapting measures to align with the population's real needs could prove highly beneficial.","PeriodicalId":501437,"journal":{"name":"medRxiv - Oncology","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the diagnostic value of YiDiXie™-SS and YiDiXie™-HS in colorectal cancer","authors":"Xutai Li, Chen Sun, Rui Xiong, Yutong Wu, Huimei Zhou, Zhenjian Ge, Yingqi Li, Wenkang Chen, Wuping Wang, Pengwu Zhang, Shengjie Lin, Siwei Chen, Wei Li, Guoqing Lv, Ling Ji, Yongqing Lai","doi":"10.1101/2024.08.20.24312286","DOIUrl":"https://doi.org/10.1101/2024.08.20.24312286","url":null,"abstract":"Background: Colorectal cancer poses a severe risk to public health and has a substantial financial impact. Tumor markers such as CEA, CA125, CA19-9, and others, as well as the fecal occult blood test (FOBT), are frequently utilized for colorectal cancer screening and initial diagnosis. False-negative results of FOBT and other indicators, on the other hand, will cause treatment to be delayed, which will force patients to suffer from a poor prognosis, high treatment costs, a low quality of life, and a short survival period. False-positive results of FOBT and other indicators, however, will cause needless mental suffering, costly examination costs, examination injuries, and other unfavorable consequences. Finding practical, affordable, and non-invasive diagnostic techniques is crucial to lowering the false-positive and false-negative rates of FOBT and other indicators. The aim of this study was to evaluate the diagnostic value of YiDiXie™-SS and YiDiXie™-HS in colorectal cancer.\u0000Patients and methods: This study eventually included 916 participants (602 in the malignant group and 314 in the benign group). Serum samples from individuals were obtained and examined using the YiDiXie™ all-cancer detection kit to assess the sensitivity and specificity of YiDiXie™-SS and YiDiXie™-HS, respectively. Results: The sensitivity of YiDiXie™-SS was 99.0% (95% CI: 96.6% - 99.8%), 99.0% (95% CI: 96.4% - 99.8%), 100% (95% CI: 89.8% - 100%) and 98.6% (95% CI: 92.5% - 99.9%) in FOBT, CEA, CA125, and CA19-9 positive patients; and its specificity was 63.6% (95% CI: 43.0% - 80.3%), 65.0% (95% CI: 43.3% - 81.9%), 60.0% (95% CI: 23.1% - 92.9%) and 66.7% (95% CI: 35.4% - 87.9%), respectively. YiDiXie™-SS reduced false positives for FOBT, CEA, CA125, and CA19-9 by 63.6% (95% CI: 43.0% - 80.3%), 65.0% (95% CI: 43.3% - 81.9%), 60.0% (95% CI: 23.1% - 92.9%) and 66.7% (95% CI: 35.4% - 87.9%). YiDiXie™-HS demonstrated a sensitivity of 94.5% (95% CI: 87.8% - 97.6%), 93.7% (95% CI: 90.8% - 95.8%), 94.5% (95% CI: 92.2% - 96.2%) and 93.9% (95% CI: 91.5% - 95.7%) in FOBT, CEA, CA125, and CA19-9 negative patients, respectively; their specificities were 87.5% (95% CI: 69.0% - 95.7%), 86.7% (95% CI: 82.3% - 90.1%), 84.9% (95% CI: 79.1% - 89.3%) and 85.7% (95% CI: 81.1% - 89.3%). This indicates that 94.5% (95% CI: 87.8% - 97.6%), 93.7% (95% CI: 90.8% - 95.8%), 94.5% (95% CI: 92.2% - 96.2%) and 93.9% (95% CI: 91.5% - 95.7%) of false negatives for FOBT, CEA, CA125, and CA19-9 were reduced by YiDiXie™-HS, respectively.\u0000Conclusion: YiDiXie™-SS lowers false-positive rates for FOBT, CEA, CA125, and CA19-9, with no increase in delayed treatment of malignant tumors. YiDiXie™-HS dramatically reduces false-negative rates for FOBT, CEA, CA125, and CA19-9. YiDiXie™-SS and YiDiXie™-HS offer significant diagnostic value in colorectal cancer and are predicted to address the two challenges of \"high false-positive rate of FOBT and other indicators\" and \"high false-negative rate of FOBT and other indicators","PeriodicalId":501437,"journal":{"name":"medRxiv - Oncology","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Different treatment durations of loperamide in preventing pyrotinib-induced diarrhea: A randomized, parallel-group sub-study of the phase II PHAEDRA trial","authors":"Changjun Wang, Yan Lin, Ying Xu, Feng Mao, Jinghong Guan, Xuejing Wang, Yanna Zhang, Xiaohui Zhang, Songjie Shen, Ying Zhong, Bo Pan, Li Peng, Xin Huang, Xi Cao, Ru Yao, Xintong Zhou, Zecheng He, Yuhan Liu, Jie Lang, Chenggang Li, Yidong Zhou, Qiang Sun","doi":"10.1101/2024.08.19.24311958","DOIUrl":"https://doi.org/10.1101/2024.08.19.24311958","url":null,"abstract":"Background: Pyrotinib, a pan-HER tyrosine kinase inhibitor, demonstrates efficacy in the treatment of HER2-positive breast cancer. However, the frequent occurrence of treatment-emergent diarrhea necessitating discontinuation, impacts patient outcomes.\u0000Methods: In this multicenter, open-label, phase II PHAEDRA study enrolling early stage HER2-positive patients for postoperative treatment with nab-paclitaxel and pyrotinib, 120 patients were included for a sub-study and randomly divided into two groups to receive 21 days and 42 days of loperamide for primary prophylaxis of diarrhea, followed by as-needed usage. The primary outcome was the incidence of grade ≥3 diarrhea. Results: Fifty-eight patients in the 21-day group and 59 patients in the 42-day group received at least one dose of pyrotinib. With a median follow-up of 12.1 months, all patients experienced diarrhea of any grade, with grade ≥3 events in 39.7% of the 21-day group and 42.4% of the 42-day group (relative risk: 0.94; 95% confidence interval: 0.61-1.45). The most common treatment-emergent adverse events, other than diarrhea, were hypoesthesia, vomiting, nausea, and rash, mostly grade 1-2, except for one case of grade ≥3 decreased neutrophil count in each group. Conclusion: No significant differences were observed between 21-day and 42-day loperamide durations in preventing grade ≥3 diarrhea. Considering the economic cost and patient compliance, 21-day loperamide prophylaxis might represent a more pragmatic and appropriate approach for clinical application.","PeriodicalId":501437,"journal":{"name":"medRxiv - Oncology","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiac dose-volume analysis of 9,411 patients with registry data for cardiovascular disease and overall survival.","authors":"Nora Forbes, Cynthia Terrones-Campos, Abraham Smith, Joanne Reekie, Sune Darkner, Maja Maraldo, Mette P/ohl, Signe Risumlund, Lena Specht, Soren M Bentzen, Jens Petersen, Ivan R Vogelius","doi":"10.1101/2024.08.16.24312108","DOIUrl":"https://doi.org/10.1101/2024.08.16.24312108","url":null,"abstract":"Abstract\u0000Background and purpose Radiation therapy (RT) to the thorax poses risks of radiation-induced cardiotoxicity, potentially increasing cardiovascular diseases (CVD) incidence. Advances in RT strive to minimize these risks by reducing heart radiation dose exposure. This study integrates detailed 3D dosimetry on individually delineated hearts with registry-based outcome data to assess the impact of radiation dose on cardiovascular morbidity and overall survival (OS) across multiple cancer types. It also examined the influence of patient-specific factors on cardiotoxicity risk and survival outcomes. Materials and methods\u0000We analyzed data from 9,411 patients receiving RT at Rigshospitalet between 2009 and 2020 for breast, esophageal, lymphoma, and lung cancers. Cumulative incidence of CVD and death in the presence of competing risks was calculated with the Aalen-Johansen estimator. The impact of radiation dose and patient characteristics on ischemic heart disease (IHD) onset and OS were assessed using Kaplan-Meier and Cox Proportional-Hazards Models. Results\u0000Higher mean heart dose (MHD) was associated with poorer OS in breast and lung cancer patients (Hazard ratio 2.8 and 1.2), but no significant relationship was found between MHD and IHD. Established cardiac risk factors (age, sex, and existing IHD) outweighed cardiac dose as a risk factor for subsequent cardiac events for all diagnoses. The risk of death was greater than subsequent CVD, especially in esophageal and lung cancers (cumulative incidence 60% versus 17% and 60% versus 14%), despite comparatively high heart doses. Conclusion The study demonstrates that risk of death from primary cancer is of far greater concern than risk of subsequent cardiac events from cardiac radiation dose exposure in the range achievable with contemporary RT techniques, especially for lung and esophageal cancer patients. Further sparing of the heart should not be prioritized at the expense of adequate treatment of the index cancer. Highlights\u0000- Age and existing heart disease far outweighed heart dose as predictors of ischemic heart disease\u0000- Overall survival is not a useful surrogate for cardiac toxicity in dose-response studies due to confounding by disease stage\u0000- With modern RT techniques, the excess absolute risk attributable to radiotherapy is so small that a statistically significant dose-response could not be observed even in 9,411 patients\u0000- For most patients, good quality contemporary radiotherapy is sufficient to limit heart toxicity as a clinically relevant concern","PeriodicalId":501437,"journal":{"name":"medRxiv - Oncology","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the diagnostic value of YiDiXie™-SS, YiDiXie™-HS and YiDiXie™-D in brain malignant tumors","authors":"Yutong Wu, Chen Sun, Zhenjian Ge, Huimei Zhou, Xutai Li, Wenkang Chen, Yingqi Li, Shengjie Lin, Pengwu Zhang, Wuping Wang, Siwei Chen, Wei Li, Jun Hu, Ling Ji, Yongqing Lai","doi":"10.1101/2024.08.18.24311913","DOIUrl":"https://doi.org/10.1101/2024.08.18.24311913","url":null,"abstract":"Background: Brain malignant tumors is a serious threat to human health and causes heavy economic burden. Enhanced MRI is widely used in the diagnosis of brain tumors. However, false-positive results of enhanced MRI will bring unnecessary mental pain, expensive examination costs, physical injuries, and other adverse consequences; while false-negative results of enhanced MRI bring delayed treatment, and patients will thus have to bear the adverse consequences of poor prognosis, high treatment costs, poor quality of life, and short survival period. There is an urgent need to find convenient, cost-effective and non-invasive diagnostic methods to reduce the false-negative and false-positive rates of brain-enhanced MRI. The aim of this study was to evaluate the diagnostic value of YiDiXie™-SS, YiDiXie™-HS and YiDiXie™-D in brain malignant tumors.\u0000Patients and methods: 235 subjects (malignant group, n=75; benign group, n=160) were finally included in this study. Remaining serum samples from the subjects were collected and tested by applying the YiDiXie™ all-cancer detection kit to evaluate the sensitivity and specificity of YiDiXie™-SS, YiDiXie™-HS and YiDiXie™-D. Results: The sensitivity of YiDiXie™-SS in enhanced MRI-positive patients was 98.4% (95% CI: 91.3% - 99.9%; 60/61) and its specificity was 62.5% (95% CI: 38.6% - 81.5%; 10/16). This means that the application of YiDiXie™-SS reduces the false-positive rate of brain enhanced MRI by 62.5% (95% CI: 38.6% - 81.5%; 10/16) with essentially no increase in malignancy leakage. The sensitivity of YiDiXie™-HS in enhanced MRI-negative patients was 85.7% (95% CI: 60.1% - 97.5%; 12/14) and its specificity was 84.7% (95% CI: 78.0% - 89.7%; 122/144). This means that the application of YiDiXie™-HS reduces the false-negative rate of brain-enhanced MRI by 85.7% (95% CI: 60.1% - 97.5%; 12/14). The sensitivity of YiDiXie™-D in enhanced MRI-positive patients was 34.4% (95% CI: 23.7% - 47.0%; 21/61) and its specificity was 93.8% (95% CI: 71.7% - 99.7%; 15/16). This means that the application of YiDiXie™-HS reduces the false-positive rate of brain-enhanced MRI by 93.8% (95% CI: 71.7% - 99.7%; 15/16).\u0000Conclusion: YiDiXie™-SS significantly reduces the false-positive rate of brain-enhanced MRI without increasing the delay in treatment of malignant tumors. YiDiXie™-HS dramatically reduces the false-negative rate of brain-enhanced MRI. YiDiXie™-D dramatically reduces the false-positive rate of brain-enhanced MRI. The YiDiXie™ test has significant diagnostic value in brain tumors, and is expected to solve the problems of \"high false-negative rate of enhancement MRI\" and \"high false-positive rate of enhancement MRI\" in brain tumors. Clinical Research Registration Number:ChiCTR2200066840.\u0000Keywords: Brain tumor, Enhanced MRI, False-positive, False-negative, YiDiXie™-SS, YiDiXie™-HS, YiDiXie™-D","PeriodicalId":501437,"journal":{"name":"medRxiv - Oncology","volume":"528 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of PITPNC1 in Lung Adenocarcinoma: Differential Expression, Immune Infiltration, and Prognostic Significance","authors":"Chao Li, Junsong Chen, Ganggang Zhang, Fang Guo, Xin Zhang","doi":"10.1101/2024.08.18.24312183","DOIUrl":"https://doi.org/10.1101/2024.08.18.24312183","url":null,"abstract":"Lung adenocarcinoma (LUAD) is one of the most prevalent and deadly forms of lung cancer, necessitating the identification of novel biomarkers for diagnosis and prognosis. This study aims to explore the differential expression, diagnostic potential, underlying mechanisms, and clinical significance of PITPNC1 (phosphatidylinositol transfer protein, cytoplasmic 1) in LUAD.We utilized data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, comprising 530 LUAD samples and 59 control samples from TCGA-LUAD, as well as GSE10072 and GSE75037 datasets with a total of 224 samples. Data preprocessing included normalization to Fragments Per Kilobase of transcript per Million mapped reads (FPKM) format and batch effect correction using the R package sva. Differential gene expression analysis was performed using DESeq2 for TCGA-LUAD and limma for GEO datasets. Receiver Operating Characteristic (ROC) curve analysis was conducted to assess the diagnostic efficacy of PITPNC1.Our results revealed that PITPNC1 is significantly overexpressed in LUAD samples compared to controls (p < 0.001 in TCGA-LUAD; p < 0.01 in GEO). However, ROC curve analysis indicated moderate diagnostic accuracy with Area Under Curve (AUC) values between 0.5 and 0.7. Differential expression analysis identified 3838 genes associated with PITPNC1 expression, which were further subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. These genes were enriched in pathways related to external stimulus response, hormone level regulation, nitrogen metabolism, and neuroactive ligand-receptor interaction.Gene Set Enrichment Analysis (GSEA) highlighted significant enrichment in IL12 signaling pathway, Notch signaling pathway, MAPK6/MAPK4 signaling pathway, and Hedgehog On State pathway. Immune infiltration analysis using single-sample Gene Set Enrichment Analysis (ssGSEA) showed significant differences in five immune cell types between high and low PITPNC1 expression groups. Cox regression analysis indicated that PITPNC1 expression along with clinical stages are significant predictors of overall survival in LUAD patients.In conclusion, our comprehensive bioinformatics analysis underscores the potential role of PITPNC1 as a biomarker for LUAD diagnosis and prognosis.","PeriodicalId":501437,"journal":{"name":"medRxiv - Oncology","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}