Validation of a high performing blood test for multiple major cancer screenings.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10561-10561
Author(s):  
Linhao Xu ◽  
Jun Wang ◽  
Weifeng Ma ◽  
Xin Liu ◽  
Sihui Li ◽  
...  
Keyword(s):  
Cancer Screening ◽  
Blood Test ◽  
Retrospective Cohort ◽  
Early Stage ◽  
Stage I ◽  
Cancer Type ◽  
Data Set ◽  
Specificity And Sensitivity ◽  
Cancer Types ◽  
Stage Stage

10561 Background: Early detection at the localized stage is pivotal for the successful treatment of various cancer types. Although several cancers already have routine screening approaches, the comprehensive utilities are impeded for various reasons, e.g., low accuracy, high cost, limited availability of required facilities, especially in the developing countries. Therefore, an accurate, cost-effective, and non-invasive test for multiple major cancer screening is in high demand. We previously reported a cfDNA methylation test, which can detect five major cancer types with high specificity and sensitivity, especially at the early stage (stage I). These five major cancers, including lung cancer (LC), breast cancer (BC), colorectal cancer (CRC), gastric cancer (GC), and esophageal cancer (EC), account for 56% of new cancer cases and 60% of cancer-related deaths yearly in China. Here, we report the result in an independent cohort as a further validation of this multi-cancer screening test. Methods: The high-throughput targeted methylation profiling platform, Aurora, was used to analyze the plasma samples from an independent retrospective cohort containing 505 healthy controls and ̃200 cases for each cancer type. A locked model based on our previous pilot study (reported in AACR 2020 and 2021) was applied to this data set to assess the overall performance. Results: The Area Under Curves (AUC) of the classifier for LC, BC, CRC, GC and EC are 97.3%, 96.2%, 92.0%, 94.0% and 93.5%, respectively. At a fixed specificity of 99%, the sensitivities for LC, BC, CRC, GC and EC are 84%, 75%, 82%, 85% and 78%, respectively. Conclusions: A methylation blood test for five major cancer screening has been validated in a large retrospective cohort. Its high sensitivity for each cancer type, especially at the early stage (stage I), and easy to use suggests it can be implemented in real clinical world. A large prospective clinical trial is undergoing to further validate this test in asymptomatic populations.

scholarly journals Noncoding RNAs and Deep Learning Neural Network Discriminate Multi-Cancer Types

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 352
Author(s):  
Anyou Wang ◽  
Rong Hai ◽  
Paul J. Rider ◽  
Qianchuan He
Keyword(s):  
Neural Network ◽  
Deep Learning ◽  
Cancer Screening ◽  
Detection System ◽  
Population Level ◽  
Cancer Type ◽  
Multiple Cancer ◽  
Data Set ◽  
Cancer Types ◽  
Deep Learning Neural Network

Detecting cancers at early stages can dramatically reduce mortality rates. Therefore, practical cancer screening at the population level is needed. To develop a comprehensive detection system to classify multiple cancer types. We integrated an artificial intelligence deep learning neural network and noncoding RNA biomarkers selected from massive data. Our system can accurately detect cancer vs. healthy objects with 96.3% of AUC of ROC (Area Under Curve of a Receiver Operating Characteristic curve), and it surprisingly reaches 78.77% of AUC when validated by real-world raw data from a completely independent data set. Even validating with raw exosome data from blood, our system can reach 72% of AUC. Moreover, our system significantly outperforms conventional machine learning models, such as random forest. Intriguingly, with no more than six biomarkers, our approach can easily discriminate any individual cancer type vs. normal with 99% to 100% AUC. Furthermore, a comprehensive marker panel can simultaneously multi-classify common cancers with a stable 82.15% accuracy rate for heterogeneous cancerous tissues and conditions.: This detection system provides a promising practical framework for automatic cancer screening at population level. Key points: (1) We developed a practical cancer screening system, which is simple, accurate, affordable, and easy to operate. (2) Our system binarily classify cancers vs. normal with >96% AUC. (3) In total, 26 individual cancer types can be easily detected by our system with 99 to 100% AUC. (4) The system can detect multiple cancer types simultaneously with >82% accuracy.

Discovery of a core-panel of markers for a blood-assay for cancer detection utilizing cfDNA methylation changes.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1522-1522
Author(s):  
Lasika Seneviratne ◽  
Steven Evans ◽  
Juvairiya Pulicharam ◽  
Nadir Arber ◽  
Jacob Kuint
Keyword(s):  
Cancer Screening ◽  
Cancer Detection ◽  
Screening Test ◽  
Early Stage ◽  
Smoking History ◽  
Training Set ◽  
Blood Draw ◽  
Multicenter Observational Study ◽  
Specificity And Sensitivity ◽  
Cancer Types

1522 Background: Cancer screening is limited to several cancers despite improved outcome A screening test should be acceptable, safe, and relatively inexpensive1 Tumors shed cfDNA to the blood where abundant tumor-specific methylation changes can be detected 1https://www.who.int/cancer/detection/variouscancer/en/. Methods: This is a prospective, multicenter, observational study under two protocols NCT04264767, NCT04264754. Plasma was collected from 1,255 subjects: 586 treatment-naïve cancer patients and 639 controls, in 21 sites and biobanks. Training set I (211 cases/99 controls) was used to select the 6 final markers for the core panel, training set II (200 controls) was used to lock the algorithm, and set the threshold to a score yielding specificity of 95%. The validation set (342 cases/310 controls) was performed utilizing the pre-specified algorithm and threshold. Plasma was separated from a single EDTA tube within 4 hours of blood draw. EpiCheck’s reagents and methylation-sensitive enzymes (Nucleix, Israel) were used for DNA extraction, digestion, and amplification in real-time PCR (ABI 7500 Fast Dx, Applied Biosystems). Results: Age was comparable but sex and smoking history were different (more women in cases, more smokers in controls). In the validation cohort twelve cancer types were included, with prominent representation of major cancer types (19% Breast, 14% colorectal and 21% lung) and stages I&II (56%). Specificity and sensitivity were maintained high at 94% and 62%. Highest sensitivity was demonstrated in GI cancers (77% colorectal, 83% esophageal, 100% gastric) and non-solid malignancies (83%). Sensitivity in early stage cancers (stages I, II & IIIA) was 71%, led by Sarcoma (83%) esophageal (76%) and colorectal (61%). Conclusions: This 6-marker blood-based methylation assay is a promising initial component in a future cancer screening test, generating significant signal in early cancers and utilizing simple and inexpensive PCR technology. Clinical trial information: NCT04264767, NCT04264754. [Table: see text]

LOW-DOSE COMPUTED TOMOGRAPHY IN MOSCOW FOR LUNG CANCER SCREENING (LDCT-MLCS): BASELINE RESULTS

2019 ◽  
Vol 65 (2) ◽  
pp. 224-233
Author(s):  
Sergey Morozov ◽  
Viktor Gombolevskiy ◽  
Anton Vladzimirskiy ◽  
Albina Laypan ◽  
Pavel Kononets ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Lung Cancer ◽  
Cancer Screening ◽  
Low Dose ◽  
Early Stage ◽  
Lung Cancer Screening ◽  
Stage I ◽  
Malignant Neoplasms ◽  
Number Needed To Screen ◽  
Low Dose Computed Tomography

Study aim. To justify selective lung cancer screening via low-dose computed tomography and evaluate its effectiveness. Materials and methods. In 2017 we have concluded the baseline stage of “Lowdose computed tomography in Moscow for lung cancer screening (LDCT-MLCS)” trial. The trial included 10 outpatient clinics with 64-detector CT units (Toshiba Aquilion 64 and Toshiba CLX). Special low-dose protocols have been developed for each unit with maximum effective dose of 1 mSv (in accordance with the requirements of paragraph 2.2.1, Sanitary Regulations 2.6.1.1192-03). The study involved 5,310 patients (53% men, 47% women) aged 18-92 years (mean age 62 years). Diagnosis verification was carried out in the specialized medical organizations via consultations, additional instrumental, laboratory as well as pathohistological studies. The results were then entered into the “National Cancer Registry”. Results. 5310 patients (53% men, 47% women) aged 18 to 92 years (an average of 62 years) participated in the LDCT-MLCS. The final cohort was comprised of 4762 (89.6%) patients. We have detected 291 (6.1%) Lung-RADS 3 lesions, 228 (4.8%) Lung- RADS 4A lesions and 196 (4.1%) Lung-RADS 4B/4X lesions. All 4B and 4X lesions were routed in accordance with the project's methodology and legislative documents. Malignant neoplasms were verified in 84 cases (1.76% of the cohort). Stage I-II lung cancer was actively detected in 40.3% of these individuals. For the first time in the Russian Federation we have calculated the number needed to screen (NNS) to identify one lung cancer (NNS=57) and to detect one Stage I lung cancer (NNS=207). Conclusions. Based on the global experience and our own practices, we argue that selective LDCT is the most systematic solution to the problem of early-stage lung cancer screening.

Genome-wide cell-free DNA (cfDNA) methylation signatures and effect on tissue of origin (TOO) performance.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3049-3049 ◽  
Author(s):  
Minetta C. Liu ◽  
Arash Jamshidi ◽  
Oliver Venn ◽  
Alexander P. Fields ◽  
M. Cyrus Maher ◽  
...  
Keyword(s):  
Cancer Detection ◽  
Early Stage ◽  
Stage Iv ◽  
Stage I ◽  
Multiple Cancer ◽  
Isolated Cells ◽  
Genome Wide ◽  
Ffpe Tumor ◽  
Formalin Fixed Paraffin Embedded ◽  
Cancer Types

3049 Background: For multi-cancer detection using cfDNA, TOO determination is critical to enable safe and efficient diagnostic follow-up. Previous array-based studies captured < 2% of genomic CpGs. Here, we report genome-wide fragment-level methylation patterns across 811 cancer cell methylomes representing 21 tumor types (97% of SEER cancer incidence), and define effects of this methylation database on TOO prediction within a machine learning framework. Methods: Genomic DNA from 655 formalin-fixed paraffin-embedded (FFPE) tumor tissues and 156 isolated cells from tumors was subjected to a prototype 30x whole-genome bisulfite sequencing (WGBS) assay, as previously reported in the Circulating Cell-free Genome Atlas (CCGA) study (NCT02889978). Two independent TOO models, one with and one without the methylation database, were fitted on training samples; each was used to predict on the test set. A WGBS classifier was used to detect cancer at 98% specificity; reported TOO results reflect percent agreement between predicted and true TOO among those detected cancers (166 cases: 81 stage I-III, 69 stage IV, 16 non-informative). Results: Genome-wide methylation data generated from this database allowed fragment-level analysis and coverage of ~30 million CpGs across the genome (~60-fold greater than array-based approaches). Incorrect TOO assignments decreased by 35% (20% to 13%) after incorporating methylation database information into TOO classification. Improvement was observed across all cancer types and was consistent in early-stage cancers (stage I-III). Respective performances in breast cancer (n = 23) were 87% vs 96%; in lung cancer (n = 32) were 85% vs 88%; in hepatobiliary (n = 10) were 70% vs 90%; and in pancreatic cancer (n = 17) were 94% vs 100%. Results using an optimized approach informed by these results in a large cohort of CCGA participants will be reported. Conclusions: Incorporating data from a large methylation database improved TOO performance in multiple cancer types. This supports feasibility of this methylation-based approach as an early cancer detection test across cancer types. Clinical trial information: NCT02889978.

scholarly journals Breast Cancer Among the Oldest Old: Tumor Characteristics, Treatment Choices, and Survival

2010 ◽  
Vol 28 (12) ◽  
pp. 2038-2045 ◽  
Author(s):  
Mara A. Schonberg ◽  
Edward R. Marcantonio ◽  
Donglin Li ◽  
Rebecca A. Silliman ◽  
Long Ngo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Oldest Old ◽  
Age Groups ◽  
Breast Conserving Surgery ◽  
Stage I ◽  
Tumor Characteristics ◽  
Data Set ◽  
Younger Women ◽  
The Impact

Purpose Few data are available on breast cancer characteristics, treatment, and survival for women age 80 years or older. Patients and Methods We used the linked Surveillance, Epidemiology and End Results-Medicare data set from 1992 to 2003 to examine tumor characteristics, treatments (mastectomy, breast-conserving surgery [BCS] with radiation therapy or alone, or no surgery), and outcomes of women age 80 years or older (80 to 84, 85 to 89, ≥ 90 years) with stage I/II breast cancer compared with younger women (age 67 to 79 years). We used Cox proportional hazard models to examine the impact of age on breast cancer–related and other causes of death. Analyses were performed within stage, adjusted for tumor and sociodemographic characteristics, treatments received, and comorbidities. Results In total, 49,616 women age 67 years or older with stage I/II disease were included. Tumor characteristics (grade, hormone receptivity) were similar across age groups. Treatment with BCS alone increased with age, especially after age 80. The risk of dying from breast cancer increased with age, significantly after age 80. For stage I disease, the adjusted hazard ratio of dying from breast cancer for women age ≥ 90 years compared with women age 67 to 69 years was 2.6 (range, 2.0 to 3.4). Types of treatments received were significantly associated with age and comorbidity, with age as the stronger predictor (26% of women age ≥ 80 years without comorbidity received BCS alone or no surgery compared with 6% of women age 67 to 79 years). Conclusion Women age ≥ 80 years have breast cancer characteristics similar to those of younger women yet receive less aggressive treatment and experience higher mortality from early-stage breast cancer. Future studies should focus on identifying tumor and patient characteristics to help target treatments to the oldest women most likely to benefit.

Early-stage (stage I) seminoma

2018 ◽  
pp. 407-415
Author(s):  
Sia Daneshmand ◽  
Cory Hugen
Keyword(s):  
Early Stage ◽  
Stage I ◽  
Stage I Seminoma ◽  
Stage Stage

scholarly journals Factors Associated With Follow-Up Care Among Women With Early-Stage Breast Cancer

2019 ◽  
Vol 15 (1) ◽  
pp. e1-e9
Author(s):  
Farah F. Quyyumi ◽  
Jason D. Wright ◽  
Melissa K. Accordino ◽  
Donna Buono ◽  
Cynthia W. Law ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Stage I ◽  
Early Stage Breast Cancer ◽  
Radiation Oncologist ◽  
Medical Oncologist ◽  
Data Set ◽  
Factors Associated ◽  
Follow Up Care

PURPOSE: Follow-up guidelines vary widely among national organizations for patients with early-stage breast cancer treated with curative intent. We sought to evaluate the patterns and predictors of provider follow-up care within the first 5 years after diagnosis. METHODS: Using the SEER-Medicare linked data set, we evaluated patients who were diagnosed with stage I and II breast cancer who underwent breast-conserving surgery from 2002 to 2007 with follow-up until 2012. We defined discontinuation of follow-up as > 12 months from the previous physician visit without a visit claim from either a surgeon, medical oncologist, or radiation oncologist. We performed a multivariable logistic regression and Cox proportional hazards regression analysis to determine factors associated with the discontinuation of follow-up care. RESULTS: Of the 30,053 patients enrolled in our initial cohort, 25,781 (85.8%) saw a medical oncologist and 21,612 (71.9%) saw a radiation oncologist in the first year in addition to a surgeon. Over the 5 years, 6,302 patients (21.0%) discontinued follow-up visits. Discontinuation of physician visits increased with increasing age. Women with stage II cancer ( v stage I) were less likely to discontinue follow-up visits (odds ratio, 0.78; 95% CI, 0.73 to 0.83). Time to early discontinuation was greater for patients with hormone receptor–negative tumors (hazard ratio, 1.14; 95% CI, 1.05 to 1.24). Women who were diagnosed more recently were less likely to discontinue seeing any physician. CONCLUSION: Twenty-one percent of patients with early-stage breast cancer discontinued seeing any oncology provider over the 5 years after diagnosis. Coordination of follow-up care between oncology specialists may reduce discontinuation rates and increase clinical efficiency.

scholarly journals Evaluating Screening Participation, Follow-up, and Outcomes for Breast, Cervical, and Colorectal Cancer in the PROSPR Consortium

2019 ◽  
Vol 112 (3) ◽  
pp. 238-246 ◽  
Author(s):  
William E Barlow ◽  
Elisabeth F Beaber ◽  
Berta M Geller ◽  
Aruna Kamineni ◽  
Yingye Zheng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Screening ◽  
Colorectal Cancer Screening ◽  
Target Population ◽  
Population Based ◽  
Diagnostic Evaluation ◽  
Cancer Type ◽  
Screening Process ◽  
Screening Participation ◽  
Cancer Types

Abstract Background Cancer screening is a complex process encompassing risk assessment, the initial screening examination, diagnostic evaluation, and treatment of cancer precursors or early cancers. Metrics that enable comparisons across different screening targets are needed. We present population-based screening metrics for breast, cervical, and colorectal cancers for nine sites participating in the Population-based Research Optimizing Screening through Personalized Regimens consortium. Methods We describe how selected metrics map to a trans-organ conceptual model of the screening process. For each cancer type, we calculated calendar year 2013 metrics for the screen-eligible target population (breast: ages 40–74 years; cervical: ages 21–64 years; colorectal: ages 50–75 years). Metrics for screening participation, timely diagnostic evaluation, and diagnosed cancers in the screened and total populations are presented for the total eligible population and stratified by age group and cancer type. Results The overall screening-eligible populations in 2013 were 305 568 participants for breast, 3 160 128 for cervical, and 2 363 922 for colorectal cancer screening. Being up-to-date for testing was common for all three cancer types: breast (63.5%), cervical (84.6%), and colorectal (77.5%). The percentage of abnormal screens ranged from 10.7% for breast, 4.4% for cervical, and 4.5% for colorectal cancer screening. Abnormal breast screens were followed up diagnostically in almost all (96.8%) cases, and cervical and colorectal were similar (76.2% and 76.3%, respectively). Cancer rates per 1000 screens were 5.66, 0.17, and 1.46 for breast, cervical, and colorectal cancer, respectively. Conclusions Comprehensive assessment of metrics by the Population-based Research Optimizing Screening through Personalized Regimens consortium enabled systematic identification of screening process steps in need of improvement. We encourage widespread use of common metrics to allow interventions to be tested across cancer types and health-care settings.

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