Learning Objectives • Discuss the benefits, limitations, and potential harms of current cancer-screening recommendations and protocols • Describe how cell-free DNA (cfDNA) can be used for the early detection of multiple cancer types • Evaluate recent clinical data on available and emerging noninvasive multi-cancer screening tests and their utility in early cancer detection • Design a practical protocol for integration of patient counseling and multi-cancer screening into workflow protocols in the primary care setting
ADDRESSING THE UNMET NEEDS OF UNDIAGNOSED CANCERS IN THE US
By the Numbers US Cancer
Cancer is the 2
nd leading cause of death in the US.1
More than
609,000 lives are estimated to be lost to cancer in 2023.2
40
65
of Americans will be diagnosed with cancer in their lifetimes.3
of Americans ≥21 years old are not up-to-date on at least 1 routine cancer screening.4
%
%
US, United States. 1. Murphy SL, et al. NCHS Data Brief. 2021;427:1-8; 2. NCI: SEER*Explorer. https://seer.cancer.gov/statfacts/; 3. National Cancer Institute (NCI). www.cancer.gov/aboutcancer/understanding/statistics; 4. Prevent Cancer Foundation. 2023. www.preventcancer.org/2023/02/65-of-americans-21-years-of-age-and-older-report-not-being-up-to-date-on-atleast-one-routine-cancer-screening/.
5-Year Relative Survival Rates 5-Year Relative Survival Rate, %
Stratified by Age, Race, and Stage
100 80 60 40 20 0
<15
15-39
40-64
Agec,1
65-74
≥75
Whitea
Hispanicb Asian/ Pacific Islander a
Racec,1
Black a
Native Localized Regional American/ Alaska Native a
Staged,2
5-year relative survival rate is 3x higher for tumors detected at a localized stage than for those detected at a distant stage.2 Overall 5-Year Survival Rate With Any Malignancy: 68.7%3 a
Non-Hispanic; bAny race; c2013-2019; d2011-2017. 1. NCI: SEER*Explorer. https://seer.cancer.gov/explorer/; 2. Centers for Disease Control and Prevention. US Cancer Statistics Data Brief, no. 25. 2021. Atlanta, GA. www.cdc.gov/cancer/uscs/about/data-briefs/no25-incidence-relative-survival-stage-diagnosis.htm; 3. NCI: NCI Cancer Stat Facts. https://seer.cancer.gov/statfacts/.
Distant
The USPSTF Recommendations for Screening Asymptomatic Patients1-3 Cancer
Screening
Criteria
Breast
Biennial screening mammography
Women aged 40-74 years
• Cervical cytology every 3 years • Cervical cytology every 3 years OR • High-risk human papillomavirus (hrHPV) every 5 years OR • hrHPV + cervical cytology every 5 years • Stool-based testing – Annual fecal immunochemical test (FIT) or high-sensitivity guaiacbased testing – sDNA-FIT (stool DNA test with FIT) every 1 to 3 years • Colonoscopy every 10 years • Computed tomography colonography every 5 years • Flexible sigmoidoscopy – Every 5 years – Every 10 years + annual FIT
Women aged 21-29 years
Cervical
Colorectal
Lung
Annual LDCT
Prostate
Prostate-specific antigen (PSA) testing
Women aged 30-65 years
• Age 45-75 years • Certain populations aged 76-85 years
Age 50-80 years and ≥20 pack per year history of smoking and currently smoke or quit within the past 15 years Men aged 55-69 years when elected with shared decision-making
Year Published Draft Recommendation Statement (May 2023) 2018; update in progress
2021
2021 2018
USPSTF, US Preventive Services Task Force; LDCT, low-dose computed tomography. 1. USPSTF. www.uspreventiveservicestaskforce.org/uspstf/recommendation-topics/uspstf-a-and-b-recommendations; 2. USPSTF. www.uspreventiveservicestaskforce.org/uspstf/draftupdate-summary/breast-cancer-screening-adults; 3. USPSTF. www.uspreventiveservicestaskforce.org/uspstf/recommendation/prostate-cancer-screening.
USPSTF Recommendations The USPSTF currently recommends AGAINST screening asymptomatic patients for ovarian, pancreatic, testicular, and thyroid cancers (estimated to account for 11% of all cancer deaths in 2023).
USPSTF. www.uspreventiveservicestaskforce.org/uspstf/recommendation-topics.
Successes of Cancer Screening
Reductions in Age-Adjusted Mortality Rates 2011-20201 BREAST CANCER
LUNG CANCER
ê 1.3% annually Since its peak in 1989, female screening resulted in a 20% ê in overall mortality2
ê 4.1% annually Early diagnosis ê mortality rates at 10 years by 39% compared with no intervention3
COLORECTAL CANCER
PROSTATE CANCER
ê 2.0% annually
ê 1.2% annually
1. NCI Cancer Stat Facts. https://seer.cancer.gov/statfacts/; 2. Beau AB, et al. J Clin Oncol. 2018;36(30):2988-2994; 3. Pastorino U, et al. Ann Oncol. 2019;30(7):1162-1169.
Many Cancers Are Not Detected by a Preventive Screening Test
25%
• Current screening recommendation is ”one organ at a time”2 • Some populations are not benefiting from current guideline recommendations because they are not included in the guidelines
18%
– eg, mortality rate among adults <50 years with colorectal cancer é 1.2% annually (2004-2020)3
% Cancers1 Diagnosed cancers with no preventive screening test
57%
Detected via conventional screening
Screenable cancers not detected by screening
• Only 1/3 of cancers found in the National Lung Screening Trial (NLST) were lung cancera,4
a
N=53,299 people in the US. 1. NORC at the University of Chicago. 2021. www.norc.org/PDFs/GRAIL/State-Specific%20PCDSs%20chart%201213.pdf; 2. Ahlquist DA. NPJ Precis Oncol. 2018;2:23; NCI SEER*Explorer. https://seer.cancer.gov/explorer/; 4. Chang ET, et al. J Clin Oncol. 2023;41(suppl 16):10633.
3.
Modeled Data Demonstrate Late-Stage Cancer Diagnoses and Deaths Can Be Reduced by Adding MCED to Usual Care Deaths Within 5 Yearsa,1 Averted vs No MCED N %
MCED Screening Interval
N
Annual
308
85
21
Biennial
324
69
17
None
393
0
0
The addition of MCED to routine cancer would result in 3x as many cancers diagnosed as routine screening alone, with at least 17% fewer cancer deaths per year.b,2 a
Deaths within 5 years of original diagnosis to account for lead time; bindividuals aged 50-79 years who have been screened. 1. Sasieni P, et al. Ann Oncol. 2021;32(suppl 5):1135P; 2. Sasieni P, et al. Br J Cancer. 2023;129(1):72-80.
MCED Testing Could Detect Cancers Not Assessed by Traditional Single Organ Screening Modalities
Many Cancers Are Potentially Missed With Conventional Screening Crude Incidence Rate Per 100,000a
1250 1000
Invasive cancer targeted via conventional screening Invasive cancers not targeted by screening
973
12X
750
3X
500
25X
250 0
326
323 90
13 Cervical b (30-65 Years)
a
1067
Colorectal c (50-74 Years)
Breast d (50-74 Years)
All rates are crude per 100,000 from Surveillance, Epidemiology and End Results; bRecommended cervical cancer screening every 3 years with cytology alone, every 5 years with highrisk HPV testing alone, or every 5 years with cotesting; cRecommended colorectal cancer screening choice of approved modality; dRecommended breast cancer screening biennial mammography. Clarke CA, et al. Cancer Cell. 2021;39(4):447-448.
Adding MCED to Recommended Screening Could Detect More Cancers and Be More Cost-effective Current Screening (67M)
With Added MCED screening (Estimated)
Total diagnostic costs1
$16.9 billion
$3.0 billion
Cost per cancer found1
$89,042
$7,060
An MCED test ordered during a preventive care exam could have detected up to an additional 11% of breast cancer cases and up to 58% of unscreened cancers that are the leading causes of cancer death.2 1. Hackshaw A, et al. Br J Cancer. 2021;125(10):1432-1442; 2. Hathaway C, et al. Front Oncol. 2021;11:688455.
SCIENCE OF MCED
Traditional Tissue vs Liquid Biopsy Traditional Tissue Biopsy1,2
Liquid Biopsy3-5
• Usually invasive • Only possible if tumor is visible and accessible • Can be costly, risky, and potentially painful • Only provides detailed information about cancer at the site and the time of biopsy
• Noninvasive • Can characterize across all tumor stages • Can produce real-time information for diagnosis, metastases, prognoses • May indicate potential treatment response
1. Sharma S, et al. Pathology. 2021;53(7):809-817; 2. Rodríguez J, et al. Oncol Ther. 2021;9(1):89-110; 3. Mathai RA, et al. J Clin Med. 2019;8(3):372-373; 4. Aarthy R, et al. Mol Diagn Ther. 2015;19(6):339-350; 5. Pinzani P, et al. Clin Chem Lab Med. 2021;59(7):1181-1200.
Cell-Free DNA (cfDNA) Apoptosis
Apoptotic bodies Point mutations Copy number alterations Protein biomarkers
Necrosis
Rearrangements CH3
Secretion
Methylation changes
CH3
Exosomal DNA
CH3, methyl group. Cisneros-Villanueva M, et al. Br J Cancer. 2022;126(3):391-400; Wan JCM, et al. Nat Rev Cancer. 2017;17(4):223-238.
cfDNA anomalies that can be measured and characterized in assays
DNA Methylation as a Tumor Biomarker • Cancer is associated with epigenetic changes (eg, DNA methylation) that can alter: – The 3-dimensional conformation of the genome – Protein-DNA interactions – Expression patterns (silencing, activation)
• Changes in DNA methylation patterns: – Can contribute to tumorigenesis or progression • ctDNA ctDNA, circulating tumor DNA; Me, methylation. Locke WJ, et al. Front Genet. 2019;10:1150.
– Can be identified and characterized via nextgeneration sequencing + machine learning
MCED vs Genetic Testing • MCED Testing is SCREENING • Genetic Testing is RISK CALCULATION
Validation of the Assays
Understanding Sensitivity & Specificity Sensitivity
Specificity
Examples
the test's ability to detect a truepositive sample (eg, a patient with a particular cancer)
the test’s ability to detect a true negative (eg, a patient who does not have that particular cancer)
98% Sensitivity would
Negative Predictive Values (NPV)
98% Specificity would
Positive Predictive Values (PPV) assessment of the utility of the test in clinical practice, measured as the percentage of all positive samples that are true positives Trevethan R. Front Public Health. 2017;5:307.
percentage of all negative samples that are true negatives
produce 2 false-negative results for every 100 samples from patients with cancer.
result in 2 false-positive signals for every 100 samples from patients with no cancer.
The Power of Aggregate Prevalence for Selected Cancers 1000
PPV, %
60
600
Liver (588) Pancreas (500)
400
0
1
40
95%
0 2
Prevalence, % GI, gastrointestinal; NNS, number needed to screen. Ahlquist, DA. NPJ Precis Oncol. 2018;2:23.
97%
Universal (33)
Pan-GI (83)
0
99%
20
Colorectal (167)
200
Specificity
l Esophagus l Stomach l Liver l Pancreas l Colorectal l Pancreas-GI l Universal
Stomach (833)
800
NNS
80
Esophagus (1000)
3
0
1
2
Prevalence, %
3
cfDNA-Based MCED Assays That Have Received FDA Breakthrough Device Designationa Tumor Protein biomarkers
CancerSEEK1,2 § 8 cancers § Methylated cfDNA (16 genes) + protein biomarkers
OverC MCDBT2,3 § 5+ cancers § Deep methylation sequencing Me
Galleri1,2 § >50 cancers § >100,000 differentially methylated regions
cfDNA biomarkers
aAs of September 2023, Galleri is the only commercially available test in the US that analyzes cfDNA methylation patterns.
MCDBT, multi-cancer detection blood test. 1. Hackshaw A, et al. Cancer Cell. 2022;40(2):109-113; 2. Liu MC. Br J Cancer 2021;124(9):1475-1477; 3. Gao Q, et al. J Clin Oncol. 2021;39(suppl 3):459.
Criteria Important for a Cancer Screening Test Specificity and Sensitivity
Criteria1
High specificity
High sensitivity a
Why Important To minimize falsepositives and thereby reduce unnecessary workup, overdiagnosis, overtreatment
Test
Specificity
Sensitivity (Range)
Cancers investigated
CancerSEEK (+PET-CT)
99.6%
15.6%
All cancers except skin, CNS, leukemias
Galleri
99.5%
40.7% (Stages 1-3) 51.9% (All cancers)
>50 cancer types
PATHFINDERc,4
Galleri
99.5%
51.9%d
>50 cancer types
Thunder IIe,5 Validation Set
OverC MCDBT
98.3%
80.6%
Lung, colon/rectum, liver, ovary, pancreas, and esophagus
Trial DETECT-Aa,2 CCGA Substudy 3b,3
To detect early tumors that may be curable by surgery
N=10,006 women with no prior cancer history; bN=4077 (with cancer=2823) + (noncancer=1254); cN=6578 patients ≥50 years old with or without additional risk factors for cancer (smoking history, genetic predisposition, or prior diagnosis of successfully treated cancer); dSensitivity determined from the CCGA study; eN=639 (with cancer=351) + (noncancer=288). ASCO, American Society of Clinical Oncology; CCGA, Circulating Cell-free Genome Atlas; CNS, central nervous system; ESMO, European Society for Medical Oncology; PET-CT, positron emission tomography-computed tomography. 1. Duffy MJ, et al. Clin Chem Lab Med. 2021;59(8):1353-1361; 2. Lennon AM, et al. Science. 2020;369(6499):eabb9601; 3. Klein EA, et al. Ann Oncol. 2021;32(9):1167-1177; 4. Schrag D, et al. Lancet. 2023;402(10409):1251-1260; 5. Gao Q, et al. J Clin Oncol. 2021;39(suppl 3):459.
Criteria Important for a Cancer Screening Test PPV and NPV
Criteria1
Why Important
Trial DETECT-Aa,2
High PPV
To reduce unnecessary workup, overdiagnosis, overtreatment
High NPV
To reduce the probability of missing potentially curable tumors
Test
PPV
NPV
CancerSEEK (+PET-CT)
28.3%
99.1%
CCGA Substudy 3b,3
Galleri
44.4%
99.4%
PATHFINDERc,4
Galleri
43.1%
98.5%
Thunder IId,5 Validation Set
OverC MCDBT
N/A
N/A
aN=10,006 women with no prior cancer history; bN=4077 (with cancer=2823) + (noncancer=1254); cN=6578 patients ≥50 years old with or without additional risk factors for cancer
(smoking history, genetic predisposition, or prior diagnosis of successfully treated cancer); dN=639 (with cancer=351) + (noncancer=288). AACR, American Association for Cancer Research; N/A, not available. 1. Duffy MJ, et al. Clin Chem Lab Med. 2021;59(8):1353-1361; 2. Lennon AM, et al. Science. 2020;369(6499):eabb9601; 3. Klein EA, et al. Ann Oncol. 2021;32(9):1167-1177; 4. Schrag D, et al. Lancet. 2023;402(10409):1251-1260; 5. Gao Q, et al. J Clin Oncol. 2021;39(3_suppl):459.
Criteria Important for a Cancer Screening Cancer Signal of Origin (CSO) Identification
a
Criteria1
Why Important
Ability to localize site of tumor
To minimize imaging for localizing tumor site
Test
Specificity
Sensitivity (Range)
PPV
NPV
CSO
CancerSEEK (+PET-CT)
99.6%
15.6%
28.3%
99.1%
—
CCGA Substudy 3b,3
Galleri
99.5%
40.7% (Stages 1-3) 51.5% (All cancers)
44.4%
99.4%
88.7%
PATHFINDERc,4
Galleri
99.5%
51.9%d
43.1%
98.5%
88%
Thunder IIe,5 Validation Set
OverC MCDBT
98.3%
80.6%
—
—
81%
Real-World Experiencef,6
Galleri
Trial DETECT-Aa,2
91%
N=10,006 women with no prior cancer history; bN=4077 (with cancer=2823) + (noncancer=1254); cN=6578 patients ≥50 years old with or without additional risk factors for cancer (smoking history, genetic predisposition, or prior diagnosis of successfully treated cancer); dSensitivity determined from the CCGA study; eN=639 (with cancer=351) + (noncancer=288); fN=53,744 MCED tests delivered. 1. Duffy MJ, et al. Clin Chem Lab Med. 2021;59(8):1353-1361; 2. Lennon AM, et al. Science. 2020;369(6499):eabb9601; 3. Klein EA, et al. Ann Oncol. 2021;32(9):1167-1177; 4. Schrag D, et al. Lancet. 2023;402(10409):1251-1260; 5. Gao Q, et al. J Clin Oncol. 2021;39(suppl 3):459; 6. Westgate C, et al. J Clin Oncol. 2023;41(suppl 16):10519.
Criteria Important for a Cancer Screening Cancer Signal of Origin (CSO) Identification
Criteria1
Why Important
Ability to localize site of tumor
To minimize imaging for localizing tumor site
Test
Specificity
Sensitivity (Range)
PPV
NPV
CSO
CancerSEEK (+PET-CT)
99.6%
15.6%
28.3%
99.1%
—
Galleri
99.5%
40.7% (Stages 1-3) 51.5% (All cancers)
44.4%
99.4%
88.7%
PATHFINDERc,4
Galleri
99.5%
51.9%d
43.1%
98.5%
88%
Thunder IIe,5 Validation Set
OverC MCDBT
98.3%
80.6%
—
—
81%
Trial DETECT-Aa,2 CCGA Substudy 3b,3
Real-World Experiencef,6
Galleri
91%
According to the Galleri real-world data presented by Westgate et al at the ASCO 2023 Annual Meeting, the cancer signal of origin (CSO) prediction demonstrated 91% accuracy for 53,744 tests. a
N=10,006 women with no prior cancer history; bN=4077 (with cancer=2823) + (noncancer=1254); cN=6578 patients ≥50 years old with or without additional risk factors for cancer (smoking history, genetic predisposition, or prior diagnosis of successfully treated cancer); dSensitivity determined from the CCGA study; eN=639 (with cancer =351) + (noncancer =288); fN=53744 MCED tests delivered. 1. Duffy MJ, et al. Clin Chem Lab Med. 2021;59(8):1353-1361; 2. Lennon AM, et al. Science. 2020;369(6499):eabb9601; 3. Klein EA, et al. Ann Oncol. 2021;32(9):1167-1177; 4. Schrag D, et al. Lancet. 2023;402(10409):1251-1260; 5. Gao Q, et al. J Clin Oncol. 2021;39(3_suppl):459; 6. Westgate C, et al. J Clin Oncol. 2023;41(suppl 16):10519.
What We’ve Learned About cfDNA-Based MCEDs So Far • Cancer at all stages can be identified by analyzing methylated cfDNA with machine learning • Other notes: – HPV-mediated misdiagnosis of CSO has been reported6 – False positives have resulted from clonal B cell expansion7
Test
Specificity Sensitivity
PPV
NPV
CSO
FPR
FNR
Diagnostic Mammography1,2
88.9%
86.9%
4.4%
—
N/A
12.1%
0.08%
Low-dose CT3-5
>75%
>80%
3.3%43.5%
97.7% -100%
N/A
27%
6.2%
Pap Smear6-8
85.5%
29.7%
62.6%
59.8%
N/A
40.2%
37.4%
FNR, false negative rate; FPR, false positive rate. 1. Lehman CD, et al. Radiology. 2017. 283(1):49-58; 2. Nelson HD, et al. Ann Intern Med. 2016. 164(4):226-235; 3. Jonas DE, et al. JAMA. 2021. 325(10):971-987; 4. Pinsky PF. Lung Cancer Manag. 2014;3(6):491-498; 5. The National Lung Screening Trial Research Team. N Engl J Med. 2013. 368(21):1980-1991. 6. Vahedpoor Z, et al. Taiwan J Obstet Gynecol. 2019. 58(3):345348; 7. Myers DA, Wood B. Cancer Res. 2023;83(suppl 7):6503; 8. Xiang J, et al. Cancer Res. 2023;83(suppl 7):779.
Ongoing cfDNA-Based MCED Clinical Trials • CancerSEEK: ASCEND1, DETECTASCEND-22 • GALLERI: STRIVE, SUMMIT, PATHFINDER 2, REFLECTION3 • OverC MCDBT: PREDICT, PRESCIENT3 • HarbingerHx: CORE-HH4 • PanSeerX: FuSion Project5 • Guardant LUNAR-2: SHIELD6 1. Duffy MJ, et al. Clin Chem Lab Med. 2021;59(8):1353-1361; 2. WCG CenterWatch. www.centerwatch.com/clinical-trials/listings/290326/ascend-2-detecting-cancers-earlier-throughelective-plasma-based-cancerseek-testing-ascertaining-serial-cancer-patients-to-enable-new-diagnostic-ii-detect-ascend-2/?featured=true. 3. ClinicalTrials.gov. https://clinicaltrials.gov/; 4. Gregg JP, et al. J Clin Oncol. 2023;41(suppl 16):e15035; 5. Suo C, et al. Cancer Res. 2023;83(suppl 7):4194; 6. Nguyen HA, et al. J Clin Oncol. 2023;41(suppl 16):TPS1610.
MCED IMPLEMENTATION INTO PRIMARY CARE PRACTICE
Overcoming Challenges Associated With Lack of MCED Guidelines MCED testing should be used to complement recommended screening approaches to identify cancers they do not cover, NOT in place of current screening. • Who should take an MCED Test?1 • ≥50 years • Family or personal history of cancer • History of childhood cancer • Known genetic mutations • Risk factors
• Who is NOT eligible1 – Pediatric populations (<21 years) – Pregnant patients – Active cancer diagnosis or treated for cancer in last 3 years 1. Putcha G, et al. JCO Precis Oncol. 2021:574-576; 2. Multicancer Early Detection Consortium. June 27, 2023. https://static1.squarespace.com/static/615c87aaea640d19cc98840b/t/6499fcaddf755715cc844f39/168781329396 9/MCED+Consortium+Care+Delivery+Paper_Final.pdf.
Risk Factors2
• Age • Alcohol • Cancer-causing substances (environmental exposures such as tobacco smoke) • Chronic inflammation • Diet • Hormones • Immunosuppression • Infectious agents • Overweight/Obesity • Radiation • Sunlight • Tobacco
Considerations When Discussing MCED With Patients Potential Advantages
Potential Disadvantages
Increased and earlier cancer detection rate, including asymptomatic patients1,2
Currently not covered by most insurance (commercial or government-sponsored)1
Trials demonstrate improving efficiency of testing with increased PPV, decreased NNS1
“No Cancer Detected” does not rule out future cancer diagnosis. Sensitivity limited.
Screening of organ sites currently without a screening modality2
Consequential cancers found sooner, but patient may not live any longer3
Screening for multiple cancers at the same time1
Possible harm from unnecessary diagnostic procedures due to false positives or missed diagnoses due to false negatives1,2
Less invasive procedures and potentially improved success of treatments2
Overdiagnosis and overtreatment of cancers that would have otherwise never bothered the patient2,3
May help reduce health disparities by increasing participation rates through improved access to screening2
Inequities will increase if tests are not widely available, affordable, and acceptable to minority groups2
1. Klein EA, et al. Ann Oncol. 2021;32(9):1167-1177; 2. Multicancer Early Detection Consortium. June 27, 2023. https://static1.squarespace.com/static/615c87aaea640d19cc98840b/t/6499fcaddf755715cc844f39/1687813293969/MCED+Consortium+Care+Delivery+Paper_Final.pdf; 3. Welch HG, Kramer B. STAT. January 12, 2022. www.statnews.com/2022/01/12/medicare-shouldnt-cover-liquid-biopsies-early-cancer-detection/.
MCED Is Not Always Covered by Insurance • Currently covered by a few; out of pocket for Galleri is $949 • Medicare Multi-Cancer Early Detection Screening Coverage (originally 2021, reintroduced March 2023 (House of Representatives) and June (Senate) 20231 – Not passed yet
• Cancer Moonshot Initiative: develop plans to quickly evaluate utility and benefits of MCED tests2 – Early 2022, added goal of reducing cancer death rate by half within 25 years and improving lives of people with cancer and cancer survivors
• National Cancer Institute (NCI) Vanguard Study on Multi-Cancer Detection evaluating MCED assays for purpose of cancer screening 1. Prevent Cancer Foundation. www.preventcancer.org/multi-cancer-early-detection/coverage-and-legislation/#coverage-act; 2. American Association for Cancer Research. Cancer Discov. 2022;12(4):876.
MCED Workflow (Galleri) • Galleri is the only currently available test • To order an MCED test for eligible patients1: – Order using test requisition via provider portal or email – Kits include 2x 10-mL Streck cfDNA blood collection tubes (fasting not required) • Fill both tubes (samples <3 mL will be rejected)
– Collected blood can be stored at 6°C -37°C (48.2°F-98.6°F) for <7 days (Standard Kit) • Extreme Temperatures Kit – for when samples may be exposed to extreme temperatures in transita
– Results given to provider within 10 business days of sample receipt (via online Provider Portal or automatic fax notification)
Temperatures are considered extreme when <6°C/48.2°F or >37°C/98.6°F. Grail. www.galleri.com/hcp. a
Follow-up for a Positive Cancer Signal Test Result Should Be Individualized • Based on: – Data supporting the specific test, the invasiveness of additional diagnostic evaluations, the potential efficacy of available treatments – Further workups may include laboratory tests, imaging (CT, MRI, PET, US, X-ray) bone scans, or tissue biopsy (see next slide)
CT, computed tomography; MRI, magnetic resonance imaging; PET, positron emission tomography; US, ultrasound. Nadauld LD, et al. Cancers (Basel). 2021;13(14):3501.
Clinical Care Pathways Following a “Signal Detected” Result Cancer Signal Origin Prediction
Proposed First-line Procedures Blood workup including peripheral blood smear, CBC with differential; chemistry tests including creatinine clearance, protein electrophoresis of blood/urine
Multiple myeloma Upper GI (esophagus, stomach) Colorectal Head and neck Pancreas, gallbladder Ovary Lung Liver, bile duct
Endoscopy Colonoscopy Physical exam, fiber optic exam, ultrasound CT abdomen with IV contrast, MRCP, GI referral Abdominal/pelvic exam, ultrasound (preferred) CT chest with or without IV contrast Ultrasound, CT, GI referral
Blood work
Diagnostic mammography with ultrasound (MRI if mammography screening within last 3 months)
Breast Lymphoid neoplasm Indeterminate
CT (neck, chest, abdomen, pelvis) with IV contrast, PET-CT CT (neck, chest, abdomen, pelvis) with IV contrast, PET-CT
For your reference, this chart is on your handout or available at www.ExchangeCME.com for easy download. CBC, complete blood count; IV, intravenous; MRCP, magnetic resonance cholangiopancreatography. Adapted from Nadauld LD, et al. Cancers (Basel). 2021;13(14):3501.
Successful Implementation of MCED Screening in a US-based Health System A Case Study
1
Assess Patient Eligibility
Patient Registration via online form or provider referral
2
Pretest Counseling & Ordering MCED Test
MCED Team notified of eligible patients
3
MCED Test Processing
4
Result Delivery
Patient blood sample taken
Patients Screened for eligibility Patients called for pretest counseling within 2 business days
Blood sent to test manufacturer
Results inputted into test manufacturer portal (~2 weeks after blood received) and delivered to MCED Team
A. “Cancer Signal Detected”
MCED Team develops diagnostic plan within 24 hours
Patient notified and Diagnostic tests scheduled
N=925 MCED test orders (from 3777 total referrals: 2931 patient, 846 provider). CSD, cancer signal detected. Agarwal G, et al. J Clin Oncol. 2023;41(suppl 16):1526.
MCED test ordered for interested patients
B. “No Cancer Signal Detected” Diagnostic results and next steps discussed with patient if confirmed positive
Patient notified and additional health screenings discussed as needed
Median time from CSD result to: • Patient notification of result: 22.8 hours • Initial diagnostic evaluation: 3.1 days • Cancer diagnosis (6/925): 8.7 days • Initiation of treatment or first postdiagnosis specialist visit: 33 days
Summary • MCED can successfully detect a cancer signal and its point of origin • MCED tests are intended to complement other screening strategies, not to be used instead of current cancer screening methods • Statistical modeling indicates that adding MCED testing to usual screening protocols could result in – 3x as many cancers diagnosed compared with routine screening alone – 17% fewer cancer deaths per year
• Lack of guidelines and insurance coverage are significant barriers to overcome