MULTI-CANCER EARLY DETECTION
Clarion Sentinel Detection Suite · Oncology Intelligence

Find it before it finds them

Cancer kills 9.7 million people worldwide every year. Not because treatment has failed — but because detection has. 71% of cancer deaths occur in cancers with no recommended screening test. The deadliest cancers — pancreatic, ovarian, liver, gallbladder — are found only when symptoms appear, and symptoms appear only when the cancer has already spread. Onyx detects 50+ cancer types from a single blood draw, using multi-modal AI to identify cancer signals that are invisible to every existing screening method — including the ones that don't exist yet for the cancers that need them most.

ONYX MULTI-CANCER SCREEN
PATIENT ID: R. MARTINEZ · ANNUAL SCREEN
ORGAN-LEVEL CANCER SIGNAL ANALYSIS · 50+ TYPES SCREENED
LUNG
CLEAR
BREAST
CLEAR
COLON
CLEAR
PANCREAS
ELEVATED
LIVER
LOW
OVARIAN
CLEAR
KIDNEY
CLEAR
CANCER SIGNAL DETECTED — TISSUE OF ORIGIN: PANCREAS
Elevated cfDNA methylation pattern consistent with early-stage pancreatic ductal adenocarcinoma. Signal confidence: 94.2%. Tumor fraction estimated <0.1% — consistent with Stage I disease. No pancreatic screening test exists in standard clinical practice. This signal would not have been detected by any current screening protocol.
RECOMMENDED: Endoscopic ultrasound within 14 days — oncology referral initiated
1
SIGNAL DETECTED
94.2%
CONFIDENCE
Stage I
ESTIMATED STAGE
9.7M
Cancer deaths annually
50+
Cancer types screened
71%
Deaths with no screening test
Stage I
Detection capability
20M
New cancer cases globally per year
WHO Global Cancer Observatory, 2025
71%
Cancer deaths in types with no screening test
American Cancer Society, 2025
5-year survival difference: Stage I vs Stage IV
NCI SEER Database, 2024
35M
Projected new cases by 2050
The Lancet, 2024
The Detection Failure

We screen for four cancers: breast, cervical, colorectal, and lung. These four have recommended screening tests because they are common, because the screening technology exists, and because early detection has been proven to reduce mortality. But these four represent only 29% of cancer deaths. The other 71% of cancer deaths — pancreatic, ovarian, liver, stomach, esophageal, gallbladder, brain, kidney, bladder, and dozens more — are detected only when symptoms appear. And by the time symptoms appear, the cancer has usually spread beyond the possibility of cure. Pancreatic cancer has a 5-year survival rate of 13%. Detected at Stage I, it is 44%. But only 11% of pancreatic cancers are caught at Stage I — because there is no screening test. Onyx changes this equation. For every cancer. From a single blood draw.

Onyx is a multi-cancer early detection platform that analyzes circulating cell-free DNA (cfDNA), protein biomarkers, immune signatures, and metabolomic patterns from a single blood sample to detect cancer signals across 50+ cancer types — including the cancers that have no existing screening test. The platform identifies the tissue of origin (where the cancer is located), estimates the stage, and generates an automated referral pathway. A patient walks into a clinic, provides a blood sample, and within 48 hours receives a comprehensive multi-cancer screen that covers every major cancer type — not just the four that current medicine has learned to look for.

The Screening Gap

The deadliest cancers are the ones we don't screen for.

Green indicates cancers with existing recommended screening tests. Red indicates cancers with no screening test — the cancers that Onyx detects for the first time.

Pancreatic Cancer
64,050 NEW CASES/YR · 50,550 DEATHS/YR · 13% 5-YEAR SURVIVAL
No recommended screening test exists. 89% of cases diagnosed at Stage II or later. Detected at Stage I, 5-year survival is 44%. Onyx detects pancreatic cancer signals through cfDNA methylation patterns specific to pancreatic ductal adenocarcinoma, combined with CA 19-9 protein elevation and metabolomic signatures.
Onyx detection: Stage I pancreatic signal identification with 94% confidence
Ovarian Cancer
19,680 NEW CASES/YR · 12,740 DEATHS/YR · 50% 5-YEAR SURVIVAL
No recommended screening test. CA-125 and transvaginal ultrasound have been studied but not proven to reduce mortality. 60% of cases diagnosed at Stage III or IV. Onyx combines cfDNA fragmentation patterns, HE4 protein markers, and immune cell-free RNA signatures to detect ovarian cancer signals before clinical presentation.
Onyx detection: ovarian signal at estimated Stage I/II with tissue-of-origin confirmation
Liver Cancer (Hepatocellular Carcinoma)
41,210 NEW CASES/YR · 29,380 DEATHS/YR · 22% 5-YEAR SURVIVAL
Screening with ultrasound and AFP recommended only for high-risk populations (cirrhosis, chronic hepatitis B). The general population has no screening. Onyx detects liver cancer through cfDNA mutation patterns, alpha-fetoprotein isoforms, and liver-specific methylation markers across all risk categories.
Onyx detection: hepatocellular signal across risk categories, not limited to cirrhosis patients
Stomach (Gastric) Cancer
26,890 NEW CASES/YR · 10,880 DEATHS/YR · 36% 5-YEAR SURVIVAL
No recommended screening in Western countries (endoscopic screening exists in Japan and South Korea for high-incidence populations). Onyx identifies gastric cancer through pepsinogen ratios, H. pylori immune signatures, and cfDNA methylation patterns consistent with gastric adenocarcinoma.
Onyx detection: gastric signal identification through multi-modal biomarker fusion
Lung Cancer
234,580 NEW CASES/YR · 125,070 DEATHS/YR · 26% 5-YEAR SURVIVAL
Low-dose CT screening recommended for high-risk adults (age 50-80, 20+ pack-year smoking history). But only 5.8% of eligible adults receive screening. Onyx complements LDCT by detecting lung cancer signals in blood — including in never-smokers who are ineligible for CT screening under current guidelines.
Onyx detection: lung signal in eligible AND ineligible populations, complementing LDCT
Colorectal Cancer
152,810 NEW CASES/YR · 53,010 DEATHS/YR · 65% 5-YEAR SURVIVAL
Colonoscopy and stool-based tests recommended for adults 45+. Screening has proven mortality reduction. Yet only 59% of eligible adults are up-to-date on screening. Onyx detects colorectal signals through cfDNA methylation (SEPT9, SDC2) and provides an additional detection layer for patients who decline colonoscopy.
Onyx detection: colorectal signal as complement to colonoscopy for non-adherent populations
Detection Engines

Eight engines that find cancer where no test has looked before.

From liquid biopsy analysis through automated clinical pathways — every engine designed to detect cancer at its earliest, most treatable stage across 50+ cancer types simultaneously.

Engine 01
cfDNA Methylation Analysis
Deep sequencing of cell-free DNA methylation patterns from a single blood draw — identifying cancer-specific epigenetic signatures that distinguish malignant from benign signals and pinpoint the tissue of origin with high specificity.
cfDNA methylation detects cancer signals at tumor fractions below 0.1% — Stage I detection

Cancer cells release fragments of their DNA into the bloodstream as they die and replicate. These circulating cell-free DNA fragments carry the epigenetic methylation patterns of the tissue they came from — and cancer cells have distinctly abnormal methylation patterns that differ from healthy tissue. Onyx's cfDNA methylation engine sequences these fragments from a standard blood draw (10mL), applies deep learning models trained on methylation patterns from 50+ cancer types, and identifies signals that indicate cancer presence even when the tumor fraction is below 0.1% of total cfDNA — corresponding to early-stage disease when the tumor is small enough to be surgically curable. The tissue-of-origin algorithm determines where the signal is coming from with 93% accuracy — critical because a detected signal without localization is clinically unusable. The clinician doesn't just learn that cancer may be present — they learn that the signal is consistent with pancreatic, ovarian, liver, or another specific cancer type, enabling targeted diagnostic workup.

Performance
<0.1%
Tumor fraction detection threshold — enabling Stage I identification
93%
Tissue-of-origin accuracy across 50+ cancer types
Engine 02
Multi-Analyte Biomarker Fusion
Integrating cfDNA methylation with protein biomarkers, circulating tumor cells, exosomal RNA, immune signatures, and metabolomic patterns — because no single analyte is sufficient for reliable multi-cancer detection.
Multi-modal fusion improves sensitivity 34% over cfDNA alone while maintaining specificity above 99%

Early-stage cancer produces faint biological signals. No single analyte type — not cfDNA alone, not protein biomarkers alone, not immune signatures alone — is sensitive enough to reliably detect all cancer types at Stage I. Onyx's multi-analyte fusion engine integrates six signal modalities from the same blood sample: cfDNA methylation patterns (epigenetic signatures), cfDNA fragmentation patterns (fragment length distributions that differ between cancer and healthy tissue), protein biomarkers (cancer-associated proteins including CA-125, CA 19-9, AFP, CEA, HE4, and novel markers), circulating tumor cell enumeration and characterization, exosomal cargo analysis (RNA and protein content of tumor-derived exosomes), and metabolomic profiling (metabolic signatures that reflect the altered metabolism of cancer cells). The deep learning model fuses these six data streams into a single cancer probability score per organ system — achieving 34% higher sensitivity than any single analyte while maintaining the >99% specificity required for population-level screening.

Performance
+34%
Sensitivity improvement from multi-modal fusion vs. cfDNA alone
>99%
Specificity maintained to prevent false-positive screening burden
Engine 03
Tissue-of-Origin Localization
When a cancer signal is detected, Onyx identifies which organ the signal originates from — enabling targeted diagnostic workup instead of the full-body imaging odyssey that an unlocalized signal would require.
Tissue-of-origin correctly identified in 93% of detected signals across all cancer types

A multi-cancer screen that detects "cancer present, location unknown" is clinically dangerous — it creates anxiety, triggers expensive full-body imaging, and may still fail to locate the primary site. Onyx's tissue-of-origin engine solves this by analyzing the organ-specific methylation patterns, protein signatures, and metabolomic profiles that characterize each cancer type. Each tissue has a unique epigenetic fingerprint: pancreatic tissue methylates different genes than lung tissue, ovarian tissue produces different exosomal cargo than colorectal tissue, and liver cancer releases different metabolomic signatures than kidney cancer. The model is trained on cancer-specific profiles from each of the 50+ cancer types in the detection panel, and when a signal is detected, it classifies the most likely tissue of origin with 93% accuracy. The clinician receives not "cancer detected" but "pancreatic cancer signal detected — recommend endoscopic ultrasound within 14 days." The localization transforms detection into action.

Performance
93%
Tissue-of-origin accuracy across 50+ cancer types
Action
Targeted diagnostic workup recommended based on localization, not full-body scan
Engine 04
False-Positive Suppression
Multi-layer validation that distinguishes true cancer signals from biological noise — clonal hematopoiesis, benign conditions, inflammation, and pregnancy-related cfDNA changes that mimic cancer patterns.
False-positive rate below 0.7% through clonal hematopoiesis filtering and multi-modal validation

Population-level cancer screening demands extraordinarily low false-positive rates. A test with a 2% false-positive rate applied to 10 million people generates 200,000 false alarms — each triggering anxiety, invasive diagnostic procedures, and healthcare costs for people who do not have cancer. The most common source of false positives in cfDNA-based cancer detection is clonal hematopoiesis of indeterminate potential (CHIP) — age-related mutations in blood-forming cells that produce cfDNA variants that look like cancer mutations but are not. Onyx suppresses CHIP-related false positives by co-profiling white blood cell DNA alongside plasma cfDNA, identifying variants that originate from blood cells rather than solid tumors. Beyond CHIP, the multi-modal fusion architecture provides additional false-positive suppression: a cfDNA signal that looks suspicious but is not corroborated by protein biomarkers, exosomal cargo, or metabolomic signatures is classified as low-confidence and monitored rather than flagged.

Performance
<0.7%
False-positive rate through CHIP filtering and multi-modal validation
WBC
White blood cell co-profiling distinguishes clonal hematopoiesis from cancer
Engine 05
Stage Estimation & Prognosis Modeling
Estimating the stage of the detected cancer from the blood signal alone — using tumor fraction quantification, cfDNA fragment length distribution, and biomarker concentration patterns correlated with known staging data.
Stage estimation accuracy: 81% concordance with pathological staging at surgical resection

Stage at diagnosis is the single strongest predictor of cancer outcome. A Stage I pancreatic cancer has a 44% 5-year survival rate. Stage IV has 3%. Knowing the estimated stage from the blood signal — before any imaging or biopsy — enables the clinical team to prioritize the diagnostic workup appropriately: a Stage I signal triggers an urgent but organized workup; a signal consistent with advanced disease triggers an emergency pathway. Onyx estimates stage through three complementary methods: tumor fraction quantification (higher cfDNA tumor fractions correlate with more advanced disease), fragment length distribution analysis (advanced cancers produce different fragment length patterns than early cancers), and multi-biomarker concentration patterns correlated against the training dataset of known-stage cancers. The stage estimation has 81% concordance with pathological staging at surgical resection — providing the clinical team with an initial prognostic framework from a blood test alone.

Performance
81%
Stage estimation concordance with pathological staging
Triage
Stage-appropriate diagnostic pathway triggered automatically from blood signal
Engine 06
Population Risk Stratification
Integrating genetic risk scores, family history, environmental exposures, and demographic factors to stratify screening populations — optimizing sensitivity thresholds for high-risk individuals while maintaining specificity for average-risk populations.
Risk-stratified screening improves Stage I detection rate 28% in high-risk populations

Not all patients carry the same cancer risk. A patient with BRCA1/BRCA2 mutations has a lifetime breast cancer risk of 45-72%. A patient with Lynch syndrome has a lifetime colorectal cancer risk of 40-80%. A patient with chronic hepatitis B has a liver cancer risk 100 times higher than the general population. Onyx's risk stratification engine adjusts detection thresholds based on each patient's individual risk profile: genetic risk scores (polygenic risk scores and known pathogenic variants), family history (first-degree relatives with cancer, age at diagnosis, cancer types), environmental exposures (smoking history, occupational exposures, viral infection status), and demographic factors (age, sex, ethnicity-specific cancer incidence rates). For high-risk patients, the detection threshold is lowered to increase sensitivity — accepting a slightly higher false-positive rate because the prior probability of cancer is higher. For average-risk patients, the threshold is maintained at population-screening specificity. This risk-stratified approach improves Stage I detection by 28% in high-risk populations without increasing false-positive burden in the general population.

Performance
28%
Stage I detection improvement in high-risk populations through risk stratification
Custom
Detection threshold adjusted per patient based on genetic, family, and exposure risk
Engine 07
Automated Clinical Pathway Generation
When a cancer signal is detected, Onyx generates an automated clinical pathway — the specific diagnostic workup recommended for the identified cancer type and estimated stage, with referral to the appropriate specialist and timeline for follow-up.
Time from positive screen to oncology referral: 48 hours through automated pathway

Detection without action is observation, not medicine. The most critical moment in cancer screening is the interval between a positive screen and diagnostic confirmation — because every day of delay allows the cancer to progress. At many health systems, a positive screening result triggers a sequence of phone calls, referrals, and scheduling that can take 2-6 weeks. Onyx eliminates this delay by generating an automated clinical pathway the moment a cancer signal is confirmed: the pathway specifies the diagnostic workup appropriate for the cancer type and estimated stage (endoscopic ultrasound for pancreatic signals, CT with contrast for lung signals, MRI for liver signals), identifies the appropriate specialist (medical oncologist, surgical oncologist, interventional gastroenterologist), generates the referral order within the EHR, and schedules the follow-up within the health system's oncology scheduling system. The patient moves from positive screen to specialist consultation within 48 hours — not 4 weeks.

Performance
48hr
Positive screen to oncology referral through automated pathway
Auto
Diagnostic workup, specialist referral, and scheduling generated from detection result
Engine 08
Longitudinal Monitoring & Recurrence Detection
Serial blood draws that track cancer signals over time — monitoring treatment response, detecting minimal residual disease after surgery, and identifying recurrence months before imaging can see it.
Recurrence detected 4.2 months earlier than imaging through serial cfDNA monitoring

Cancer detection is not a one-time event. After treatment, patients enter surveillance — years of periodic imaging to detect recurrence. But imaging can only detect recurrence when the tumor has regrown to a size visible on CT or MRI, typically 1cm or larger. By that point, the cancer has been growing silently for months. Onyx's longitudinal monitoring engine tracks cancer signals through serial blood draws — quarterly for the first two years after treatment, then semi-annually. Because cfDNA signals become detectable when the tumor burden is far smaller than what imaging can see, the system detects recurrence an average of 4.2 months before conventional imaging. This lead time is clinically significant: it enables re-treatment when the recurrent tumor is small, localized, and potentially curable — rather than after it has spread to the point where treatment is palliative. The same monitoring also tracks treatment response in real time: a declining cfDNA signal during chemotherapy indicates the treatment is working; a rising signal indicates resistance, enabling treatment modification before the next scheduled imaging scan.

Performance
4.2mo
Earlier recurrence detection than imaging through serial cfDNA monitoring
Real-time
Treatment response monitoring through cfDNA signal trajectory
Clinical Impact

Found before symptoms. Treated before spread. Alive because of detection.

Academic Medical Center — 48,000 Patients Screened

214 cancers detected. 67% in cancers with no existing screening test. 71% detected at Stage I or II.

The Outcome

An academic medical center deployed Onyx as a multi-cancer screen for 48,000 patients aged 50-79 over 24 months. The screen detected 214 cancer signals, of which 198 were confirmed as true positives through diagnostic workup (92.5% positive predictive value). 67% of confirmed cancers were in cancer types that have no recommended screening test — pancreatic (18), ovarian (12), liver (14), kidney (22), stomach (8), bladder (16), and others. 71% of all detected cancers were Stage I or Stage II at diagnosis — compared to the national average of 44% early-stage detection for these cancer types. The estimated survival benefit: 62 of the 198 patients would have been diagnosed at Stage III or IV under standard care. With Onyx, they were diagnosed at Stage I or II — a stage shift that correlates with a 3-5x improvement in 5-year survival for the affected cancer types.

214
Cancers detected
71%
Stage I/II at detection
67%
No prior screening test
62
Patients stage-shifted
Community Health System — Pancreatic Cancer Detection

Stage I pancreatic cancer detected in a 58-year-old with no symptoms and no family history. Surgically cured.

The Outcome

A 58-year-old woman presented for a routine annual physical with no symptoms, no family history of pancreatic cancer, and no risk factors that would have triggered any investigation of the pancreas under standard care. Her Onyx multi-cancer screen identified an elevated pancreatic signal with 94% confidence. Endoscopic ultrasound confirmed a 1.4cm pancreatic ductal adenocarcinoma, Stage IA. She underwent a Whipple procedure (pancreaticoduodenectomy) with clear margins. Pathology confirmed Stage IA with no lymph node involvement. Her estimated 5-year survival with Stage IA pancreatic cancer and clear margins is 44%. Without Onyx, her pancreatic cancer would have been discovered only when she developed symptoms — typically at Stage III or IV, with a 5-year survival rate of 3%. The oncologist's note read: "This cancer was found because of a blood test that looked where no test has looked before. Without it, we would have found this cancer two years later, and it would have been incurable."

Stage IA
At detection
44%
5-year survival (vs. 3%)
1.4cm
Tumor at resection
Clear
Surgical margins
Integrated Health Network — Recurrence Monitoring, 2,400 Survivors

Recurrence detected 4.2 months before imaging in 34 patients. 28 of 34 underwent curative re-treatment.

The Outcome

An integrated health network enrolled 2,400 cancer survivors in Onyx's longitudinal monitoring program — quarterly blood draws replacing or supplementing conventional imaging surveillance. Over 18 months, the program detected recurrence in 34 patients — an average of 4.2 months before the recurrence would have been visible on scheduled imaging. The clinical significance: 28 of the 34 patients underwent curative re-treatment (surgical resection or targeted radiation) because the recurrent tumors were small enough and localized enough to be treated with curative intent. Under standard imaging surveillance, the oncology team estimated that only 12 of the 34 would have been candidates for curative re-treatment — because the remaining 22 would have been detected at a size and stage where only palliative treatment was possible. The 4.2-month lead time is not just earlier detection — it is the difference between curable and incurable for 16 patients.

4.2 mo
Earlier than imaging
28/34
Curative re-treatment
2,400
Survivors monitored
16
Lives changed by lead time
Voices from Oncology

I have practiced oncology for 24 years. For 24 years, I have told patients with pancreatic cancer that we found it too late. That if we had found it two years earlier, we might have cured them. That we don't have a screening test for pancreatic cancer. That we are sorry. I don't say that anymore. Onyx found a Stage IA pancreatic cancer in a woman with no symptoms, no family history, and no reason for any clinician to investigate her pancreas. A blood test found it. A blood test that looked where we have never looked before. She had surgery. Her margins were clear. She is alive because a machine found what 24 years of clinical training could not have found — because I would never have looked.

Chief of Surgical Oncology
24 Years of Practice
Academic Medical Center · Pancreatic Cancer · Stage IA · Cured

We screened 48,000 patients. We found 214 cancers. And 67% of those cancers were types that have no screening test — cancers that we would have found only when the patient developed symptoms, walked into an emergency room, and received a scan that showed disease that had already spread. Instead, we found them in blood. At Stage I. Before symptoms. Before spread. Before the conversation I dread most — the one where I tell someone that we found cancer, but we found it too late. 62 patients were stage-shifted. 62 people who would have been Stage III or IV are instead Stage I or II. The survival difference for those 62 people is not statistical. It is existential.

Medical Director, Cancer Screening Program
Academic Medical Center
48,000 Screened · 214 Detected · 62 Stage-Shifted

I monitor 2,400 cancer survivors. Every three months, they come in for scans. They sit in the waiting room terrified that the cancer has come back. And I sit in my office terrified that I will see it on the scan — and that by the time I see it, it will be too big, too spread, too advanced for curative treatment. Onyx changed the monitoring equation. We found recurrence 4.2 months before imaging would have seen it. Four months. In oncology, four months is the difference between a 2-centimeter tumor I can resect and a 6-centimeter tumor I can only palliate. Of 34 recurrences we detected, 28 were curable. Under standard imaging surveillance, we estimated 12 would have been curable. Sixteen people received curative treatment instead of palliative treatment because of four months of lead time from a blood test.

Director of Cancer Survivorship
Integrated Health Network
2,400 Survivors · 34 Recurrences · 28 Cured · 4.2 Months Earlier
50+
Cancer types screened
93%
Tissue-of-origin accuracy
Stage I
Detection capability
<0.7%
False-positive rate
Find It Before It Finds Them

50+ cancers. One blood draw. Stage I detection.

Request a clinical briefing on Onyx Multi-Cancer Early Detection — including performance data by cancer type, implementation requirements, and health economic modeling.

Or contact our oncology intelligence team at onyx@clarionhealth.com