Methylation Profile Test (Methylscape) in Body Fluids for Multi-Cancer Detection and Monitoring in Colombia (METHYLSCAPE-CO)
Evaluation of a Rapid Test for the Detection of Methylation Profiles (Methylscape) in Various Body Fluids as a Universal Biomarker for Cancer Detection and Monitoring
DNA methylation changes occur early and broadly during carcinogenesis. Methylscape is a rapid assay that detects global DNA methylation patterns in body fluids (blood, urine, and saliva) and may detect a cancer signal and predict the cancer signal origin (CSO) from a single fluid sample, using the differential interaction between methylated and unmethylated DNA and gold nanoparticles.
This prospective observational study evaluates the diagnostic performance (sensitivity and specificity) of the Methylscape test in Colombian patients with various biopsy-confirmed solid tumors compared with age- and sex-matched cancer-free (healthy) volunteers. The study is conducted in three parts: Phase 1 validates the assay in 250 patients with cancer; Sub-study 2a compares 1,500 patients with cancer against 1,500 matched cancer-free volunteers; and Sub-study 2b uses serial blood and urine sampling in 300 patients with early-stage disease to assess detection of disease relapse during follow-up, in parallel with standard imaging.
The study also estimates positive and negative predictive values (PPV/NPV) and projects the budget impact and cost-effectiveness of Methylscape as a multi-cancer early detection (MCED) tool in an upper-middle-income Latin American setting.
調査の概要
状態
詳細な説明
Background. Most cancers lack reliable screening methods, often leading to advanced-stage diagnosis. Multi-cancer early detection (MCED) tests based on body fluids can screen for several cancer types from a single sample. DNA methylation, which occurs early in carcinogenesis and is tissue-specific, is the most commonly used marker in MCED assays. Methylscape leverages global differences in the genomic distribution of methylation between cancerous and normal tissues, detected electrochemically through differential adsorption of DNA on gold electrodes.
Objective. To determine whether Methylscape can detect the methylation landscape across multiple cancer types with sufficiently high specificity to predict the cancer signal origin (CSO), and to assess its potential application as a population-scale MCED test among Colombians.
Design. Single-center prospective observational study conducted at CTIC (Bogotá, Colombia), with sample processing at CTIC and Columbia University. Phase 1 (N=250 patients with cancer) provides initial validation across solid tumor types selected by local incidence. Sub-study 2a (1,500 patients with cancer and 1,500 matched cancer-free volunteers) provides large-scale clinical validation. Sub-study 2b (N=300 early-stage patients) evaluates serial blood/urine Methylscape testing for relapse detection during follow-up every 6 months. Phase 1 participants may enter Sub-studies 2a/2b only if they meet the corresponding criteria and provide new informed consent; cross-phase participation is flagged in the database to adjust statistical estimates.
Biospecimens & reference standards. Blood/plasma (K2EDTA), urine, saliva, and FFPE tumor tissue are collected and stored at -80 °C in the CTIC biobank. Cancers are coded with WHO ICD-O-3; stage per AJCC 8th edition. Reference standards: histopathology (MCED), RECIST 1.1 or biopsy (relapse), and absence of cancer by record review plus 12-month follow-up (cancer-free).
Statistical analysis. Sensitivity and specificity are estimated overall and by stage/type (expected sensitivity 85-90%, specificity 98%; 95% confidence, 80% power). PPV/NPV are derived via Bayes' theorem with prevalence from GLOBOCAN 2022; 95% CIs by stratified bootstrap (1,000 resamples). Budget impact and cost-effectiveness (QALYs) are projected via microsimulation and Markov models.
研究の種類
入学 (推定)
連絡先と場所
研究連絡先
- 名前：Andrés Cardona, MD, MSc, PhD, MBA
- 電話番号：+573016348173
- メール：acardona@fctic.org
研究場所
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Bogota D.C.
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Bogotá、Bogota D.C.、コロンビア、110131
- 募集
- Fundación CTIC Centro de Tratamiento e Investigación sobre Cáncer Luis Carlos Sarmiento Angulo
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コンタクト：
- Liliana Gutiérrez Babativa, RN, MSc
- 電話番号：+573003768158
- メール：lgutierrez@fctic.org
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参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
サンプリング方法
調査対象母集団
説明
Inclusion Criteria:
- Adults aged 18 years or older.
- Willing and able to participate and to provide the required samples (blood, urine, saliva) and demographic information (age, sex, race/ethnicity, BMI).
- Able to provide written informed consent for participation and for use of biological samples. For CTIC Biobank samples, prior research-use consent is verified.
- Demographic/anthropometric comparability (race, ethnicity, BMI) with other participants; race/ethnicity by self-identification (WHO and national census categories); BMI per WHO categories.
Inclusion - Cancer cohort:
- Cancer diagnosis confirmed within 90 days prior to sample collection.
- Biopsy-proven malignancy with radiological staging.
- No anticancer treatment at the time of collection or within the previous 3 years.
- Inclusion - Cancer-free (healthy) cohort:
- No cancer diagnosis or treatment in the previous 3 years (ICD-O-3 behavior code 2 or 3).
- Not under evaluation for suspected cancer (verified by medical record review or additional medical evaluation).
- Subjects with benign tumors (code 0) or tumors of uncertain behavior (code 1) may be included if there is no clinical evidence of progression or malignancy.
Additional criteria - tumor-burden monitoring (Sub-study 2b):
- Biopsy-confirmed cancer.
- ECOG performance status ≤ 2.
Exclusion Criteria (both cohorts):
- Failure to meet the general or cohort-specific inclusion criteria.
- Pregnancy.
- Organ transplant recipients.
- Use of demethylating agents (azacitidine, decitabine) or cytotoxic agents (including for autoimmune/inflammatory conditions).
- Prior or ongoing anticancer therapy: cancer surgery beyond that needed for diagnosis; local, regional, or systemic chemotherapy (including chemoembolization); targeted therapy; immunotherapy (including cancer vaccines); hormonal therapy; or radiotherapy.
研究計画
研究はどのように設計されていますか？
デザインの詳細
コホートと介入
グループ/コホート |
介入・治療 |
|---|---|
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Patients with cancer
Colombian adults (≥18 y) with biopsy-confirmed solid tumors (behavior code 3, ICD-O-3) diagnosed within 90 days and untreated.
Provide blood, urine, saliva, and FFPE tumor tissue for Methylscape testing.
An early-stage subset is followed with serial blood/urine sampling for relapse detection (Sub-study 2b).
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Rapid assay measuring global DNA methylation patterns in body fluids (blood/plasma, urine, saliva) and FFPE tumor tissue via differential adsorption of methylated vs. unmethylated DNA on gold electrodes (differential pulse voltammetry), to detect a cancer signal and predict the cancer signal origin (CSO).
Applied to both groups; no therapeutic intervention is administered.
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Cancer-free (healthy) volunteers
Colombian adults (≥18 y) without cancer diagnosis or treatment in the prior 3 years, matched to cancer patients by sex, age, race/ethnicity, and BMI.
Provide blood, urine, and saliva for Methylscape testing (Sub-study 2a).
|
Rapid assay measuring global DNA methylation patterns in body fluids (blood/plasma, urine, saliva) and FFPE tumor tissue via differential adsorption of methylated vs. unmethylated DNA on gold electrodes (differential pulse voltammetry), to detect a cancer signal and predict the cancer signal origin (CSO).
Applied to both groups; no therapeutic intervention is administered.
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Sensitivity of the Methylscape test for cancer-signal detection, as assessed against histopathological confirmation as the reference standard
時間枠：Baseline
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Percentage of participants with biopsy-confirmed cancer who have a positive Methylscape result (cancer signal detected).
Reported overall and by subgroup (cancer stage per AJCC 8th ed. and cancer type per ICD-O); all subgroups use the same unit.
Adjusted by GLOBOCAN 2022 incidence.
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Baseline
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Specificity of the Methylscape test for cancer-signal detection, as assessed against absence of cancer confirmed by medical-record review and 12-month follow-up
時間枠：12 months
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Percentage of confirmed cancer-free volunteers who have a negative Methylscape result (no cancer signal detected).
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12 months
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Accuracy of Methylscape cancer-signal-origin (CSO) prediction, measured as the percentage of cases in which the predicted tissue of origin matches the histopathologically confirmed primary tumor site
時間枠：Baseline
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Among participants with a positive Methylscape cancer signal, the percentage in which the Methylscape-predicted tissue of origin agrees with the confirmed primary site (ICD-O morphology code).
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Baseline
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Sensitivity and specificity of serial Methylscape testing for detection of disease relapse, as assessed against imaging response (RECIST 1.1) or biopsy of local recurrence
時間枠：At 6, 12, 18, and 24 months
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In early-stage participants under follow-up (Sub-study 2b), sensitivity and specificity of serial blood/urine Methylscape testing for detecting disease relapse.
Sensitivity and specificity are both reported as percentages (same unit of measure); the reference standard is radiological progression per RECIST 1.1 or biopsy-confirmed local recurrence.
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At 6, 12, 18, and 24 months
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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Positive and negative predictive value (PPV and NPV) of Methylscape for cancer-signal detection
時間枠：Up to 12 months
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Positive predictive value (PPV) and negative predictive value (NPV) of the Methylscape cancer-signal result, both reported as percentages.
Values are computed via Bayes' theorem using cancer prevalence estimated from GLOBOCAN 2022, with 95% confidence intervals obtained by stratified bootstrap (1,000 resamples).
Reference standard: histopathological confirmation for cancer status and absence of cancer by medical-record review and 12-month follow-up for cancer-free status.
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Up to 12 months
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Diagnostic performance of Methylscape in cancers with versus without established screening programs
時間枠：Up to 12 months
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Sensitivity and specificity of Methylscape, both reported as percentages, compared between cancers with established screening options (e.g., breast, cervical, lung) and cancers without standard screening.
Reference standard: histopathological confirmation (sensitivity) and absence of cancer by medical-record review and 12-month follow-up (specificity).
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Up to 12 months
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Budget impact of implementing Methylscape as a multi-cancer early detection strategy
時間枠：Through study completion, an average of 24 months
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Estimated incremental budget impact of introducing Methylscape as a multi-cancer early detection (MCED) and relapse-detection tool versus current screening and follow-up practice in the Colombian health system, reported in Colombian pesos (COP).
Estimated using microsimulation and Markov models populated with study-derived diagnostic performance.
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Through study completion, an average of 24 months
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Cost-effectiveness of Methylscape (incremental cost-effectiveness ratio)
時間枠：Through study completion, an average of 24 months
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Incremental cost-effectiveness ratio (ICER) of Methylscape versus current practice, reported as cost per quality-adjusted life-year (QALY) gained, in Colombian pesos per QALY (COP/QALY).
Estimated using microsimulation and Markov models populated with study-derived diagnostic performance.
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Through study completion, an average of 24 months
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協力者と研究者
出版物と役立つリンク
一般刊行物
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- Nicholson BD, Oke J, Virdee PS, Harris DA, O'Doherty C, Park JE, Hamady Z, Sehgal V, Millar A, Medley L, Tonner S, Vargova M, Engonidou L, Riahi K, Luan Y, Hiom S, Kumar H, Nandani H, Kurtzman KN, Yu LM, Freestone C, Pearson S, Hobbs FR, Perera R, Middleton MR. Multi-cancer early detection test in symptomatic patients referred for cancer investigation in England and Wales (SYMPLIFY): a large-scale, observational cohort study. Lancet Oncol. 2023 Jul;24(7):733-743. doi: 10.1016/S1470-2045(23)00277-2. Epub 2023 Jun 20.
- Hackshaw A, Clarke CA, Hartman AR. New genomic technologies for multi-cancer early detection: Rethinking the scope of cancer screening. Cancer Cell. 2022 Feb 14;40(2):109-113. doi: 10.1016/j.ccell.2022.01.012. Epub 2022 Feb 3.
- Sina AA, Carrascosa LG, Liang Z, Grewal YS, Wardiana A, Shiddiky MJA, Gardiner RA, Samaratunga H, Gandhi MK, Scott RJ, Korbie D, Trau M. Epigenetically reprogrammed methylation landscape drives the DNA self-assembly and serves as a universal cancer biomarker. Nat Commun. 2018 Dec 4;9(1):4915. doi: 10.1038/s41467-018-07214-w.
- Bretthauer M, Wieszczy P, Loberg M, Kaminski MF, Werner TF, Helsingen LM, Mori Y, Holme O, Adami HO, Kalager M. Estimated Lifetime Gained With Cancer Screening Tests: A Meta-Analysis of Randomized Clinical Trials. JAMA Intern Med. 2023 Nov 1;183(11):1196-1203. doi: 10.1001/jamainternmed.2023.3798.
- Welch HG, Bergmark R. Cancer Screening, Incidental Detection, and Overdiagnosis. Clin Chem. 2024 Jan 4;70(1):179-189. doi: 10.1093/clinchem/hvad127.
- Tafazzoli A, Ramsey SD, Shaul A, Chavan A, Ye W, Kansal AR, Ofman J, Fendrick AM. The Potential Value-Based Price of a Multi-Cancer Early Detection Genomic Blood Test to Complement Current Single Cancer Screening in the USA. Pharmacoeconomics. 2022 Nov;40(11):1107-1117. doi: 10.1007/s40273-022-01181-3. Epub 2022 Aug 30.
- Minasian LM, Pinsky P, Katki HA, Dickherber T, Han PKJ, Harris L, Patriotis C, Srivastava S, Weil CJ, Prorok PC, Castle PE. Study design considerations for trials to evaluate multicancer early detection assays for clinical utility. J Natl Cancer Inst. 2023 Mar 9;115(3):250-257. doi: 10.1093/jnci/djac218.
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研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- Methylscape
- CEI-183 (その他の識別子：Comité de Ética de la Investigación Riesgo de Fractura S.A)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
IPD 共有時間枠
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IPD 共有サポート情報タイプ
- CSR
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