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I N F O R M AT I O N F O R P H Y S I C I A N S
Early Detection of Colorectal Cancer
Made Easy with a Blood Test
Epi pro Colon 2.0 ® :
2nd Generation Septin 9 Test
CRC SCREENING SAVES LIVES
Colorectal cancer is a major health problem in the industrialized world. More than 148,000
people in Europe and about 50,000 in the U. S. die of the disease every year, making
colorectal cancer the second most common cause of cancer-related deaths (Figure 1).1, 2
Death from colorectal cancer vs. traffic accidents
27,000 deaths
from colorectal cancer
< 4,000 deaths
by traffic accidents
Figure 1: Deaths from colorectal
cancer and deaths by car accidents
in Germany. Source: Felix Burda
Foundation, 2009
Colorectal cancer is curable if diagnosed early
Early detection can save the lives of people suffering from colorectal cancer. Most cases of
colorectal cancer (CRC) are curable if diagnosed early enough. However, the chances of
survival decrease , when the disease is diagnosed in more progressed stages (Figure 2).
1
Survival Rate [%]
0.8
0.6
0.4
0.2
Stage I
Stage II
Figure 2: Survival rate for colorectal
Stage III
Stage IV
Cancer Institute, PDQ, Treatment,
cancer by stage. Source: National
Health Professionals.
www.meds.com/pdq/colon_pro.html
0
0
1
2
3
Years
4
5
6
Colorectal cancer screening
There is a variety of alternative procedures for CRC screening that may be divided into
invasive and non-invasive methods. Established invasive methods comprise colonoscopic
and sigmoidoscopic examination, while conventional methods include fecal occult blood
testing (FOBT) by either guaiac-based (gFOBT) or immunochemical-based stool tests (fecal
immunochemical test, FIT) detection.
All CRC screening methods have been proven to be effective in the battle against colorectal
cancer. However, the majority of patients avoid such examinations, thus depriving themselves of the chance of early detection and a potential cure.
Compliance to CRC screening – a blood test makes
the difference
Despite numerous educational and informational campaigns, colorectal cancer screening
is still not well-accepted: less than half of all eligible individuals participate in colorectal
cancer screening today.
A nationwide telephone survey in the United States with 1,304 participants aged 50 +
conducted for Colorectal Cancer Alliance demonstrated that 75 % of the participants would
get regular screening if a blood-based CRC screening assay was available.3 In France 86 %
of patients would agree to do regular screening with the blood test.4 For these people the
Septin 9 blood test is a viable alternative.
THE SEPTIN 9 BLOOD TESTS: Early detection of
colorectal cancer in the blood
With Septin 9 blood tests, such as Epi pro Colon®
2.0 CE, you can offer your patients a simple and
safe alternative for early detection of colorectal
cancer.
The test detects the epigenetic biomarker Septin 9
in blood plasma. This biomarker – methylated
DNA of the Septin 9 gene – correlates strongly
with the presence of colorectal cancer.
As the Septin 9 blood tests can be performed at any time and without discomfort to the patient, it offers considerable potential for
increased patient acceptance and a real opportunity to lower the
mortality rate from colorectal cancer.
IMPORTANT FOR YOUR PATIENTS:
The Septin 9 blood tests can be performed at any time and can easily be
included in a general health checkup.
No dietary restrictions are required
before performing the test. Both
blood sampling and discussion of test
result are handeled in the physician’s
office with an average time for testing of around one week.
Study data
Epi pro Colon® 2.0 CE is a 2nd generation Septin 9 blood test with substantially increased
clinical performance compared to the first generation test. Performance evaluation studies
demonstrated > 80 % sensitivity to colorectal cancer with 99 % specificity (Figure 3).
The effectiveness of the Septin 9 blood test was determined in numerous studies involving
thousands of participants including a prospective evaluation in a screening cohort of 8,000
subjects.5 – 7
The first generation Septin 9 blood test, Epi pro Colon®, has been available as a CE-marked kit
since Oct 2009 in Europe. The Septin 9 blood test therefore offers a well established, safe and
patient-friendly option of taking part in colorectal cancer screening that so often saves lives.
# Samples
100 %
1/149
79/98
18/27
25/29
27/31
9/11
99 %
81%
67 %
86 %
87 %
82 %
Stage I
Stage II
Positivity
80 %
60 %
40 %
20 %
0%
CVNs *
All CRC **
* Colonoscopy verified normals
Stage III
Stage IV
** Colorectal cancer
Figure 3: Detection rates of the Epi proColon® 2.0 CE blood-based 2 nd generation Septin 9 blood test by stage from
three case-control studies.
Comparison of Epi pro Colon® 2.0 CE with
non-invasive screening tests
The most widely used non-invasive CRC screening methods are the guaiac FOBT and
variations of the OC-Sensa Micro Test, an immunological FOBT. Compared to those
methods the Epi pro Colon® 2.0 CE has an unmatched positive predictive value at an
equally high negative predictive value. On average one out of two positive tested
patients has cancer and the probability of a true negative result is 99.9 %.
Epi pro Colon® 2.0 CE provides the most accurate option for non-invasive CRC screening
combined with the unprecedented convenience of a blood test.
METHOD
2nd Generation
Septin 9 Test
Epi pro Colon ® 2.0
SPECIFICITY
SENSITIVITY
NEGATIVE
POSITIVE
PREDICTIVE
PREDICTIVE
VALUE
VALUE §
99.3 %
80.6 %
99.9 %
45.7 %
Guiac
Fecal-Occult
Blood Test 8
97.7 %
37.1 %
99.6 %
10.1 %
OC-Sensa
Micro qFIT1x 9
93.7 %
69.2 %
99.8 %
7.5 %
OC-Sensa
Micro qFIT3x 9
89.8 %
84.6 %
99.9 %
5.6 %
§
7
CRC with positive test result,
healthy with positive test result assuming a prevalence for CRC of 0.7 %
Septin 9 performance in polyps
Normal epithelium
SEPTIN 9
POSITIVE FR ACTION
10
HEALTHY
Large adenoma
ADVANCED
ADENOM A
Colon carcinoma
CANCER
Tissue
8%
100 %
100 %
Plasma
15 %
35 %
75 %
Figure 4: Detection rates of Septin 9 in plasma from patients suffering from advanced adenomas and cancer.
Tissue samples from both adenomas and cancer were 100 % positive. The data were generated by Tóth et al.10 with
a modified Epi proColon 1.0 assay.
Simple performance in the medical practice
The Septin 9 blood test allows you to offer your patients a new, reliable alternative for
early detection of colorectal cancer. No intestinal preparation is required before performing the test. There are no restrictions with regard to food or drug intake. The patient can
be tested at any time by a simple blood draw which can easily be included in a general
health checkup.
Sampling for the test and communication and explaination of the test result is in the hand
of the physician (Figure 5).
Patient with average
risk of colorectal cancer
Blood sample
Laboratory
Test report
Physician
Figure 5: Schematic of Septin 9 clinical work-up
Blood sampling for the test
In order to perform the Epi pro Colon® 2.0 CE blood test, a blood sample is taken using
a 9.5 ml EDTA tube or a 8.5 ml CPDA tube and sent to a diagnostic laboratory which
measures and evaluates Septin 9. Within approximately one week the test result is returned
to the physician.
Who should take the test ?
The test is suitable for everyone with an average risk of colorectal cancer, who has no
symptoms, but wants to take part in colorectal cancer screening. The purpose of the test
is not to replace screening colonoscopy. Instead, it is aimed at people looking for a safe
alternative that enables them to take part in colorectal cancer screening.
Test costs
The Septin 9 blood test is a diagnostic method that, at present, may not or only partially
be reimbursed in your country. Thus, the patient may have to bear all or part of the test
costs. Please contact your local laboratory for the exact price. For a list of laboratories, which
perform the test, please contact Epigenomics.
The test result
The Septin 9 blood test result is either negative or positive with respect to the presence of
Septin 9 in plasma (Figure 6).
A negative test result means that the likelihood of the patient having colorectal cancer
is extremely low. For Epi pro Colon® 2.0 CE a negative test result indicates a probability of
99.9 % that the patient does not suffer from colorectal cancer (99.9 % negative predictive
value). Nevertheless, as colorectal cancer can develop spontaneously over time, the patient
should be advised to repeat the test every one or two years similar to conventional stool tests.
A positive Septin 9 blood test result means that the likelihood of the patient having colorectal cancer is increased. For Epi pro Colon® 2.0 CE a positive test results indicates a probability
of 45 % that the patient suffers from cancer (45 % positive predictive value). These patients
are strongly advised to undergo colonoscopy for establishing the diagnosis and initialization
of treatment.
Septin9 Test Result
Septin9 Test Result
Analysis Report:
Analysis Report:
Test Description: The Septin9 test Epi proColon
Colon detects presence of methylated Septin9 DNA
(mSEPT9) in a plasma sample of a patient.
Test Methods: DNA purification from plasma, bisulfate conversion, duplex real-time PCR.
Test Result: The blood plasma sample no.
was analysed with the Septin9-Test
Epi proColon.
Colon. The analysis was done in replicate. A sample is classified as positive, when at least
one of the two measurements was tests positive for mSEPT9.
The sample submitted for analysis was classified as:
Test Description: The Septin9 test Epi proColon detects presence of methylated Septin9 DNA
(mSEPT9) in a plasma sample of a patient.
Test Methods: DNA purification from plasma, bisulfate conversion, duplex real-time PCR.
Test Result: The blood plasma sample no.
was analysed with the Septin9-Test
Epi proColon. The analysis was done in replicate. A sample is classified as positive, when at least
one of the two measurements was tests positive for mSEPT9.
TEST RESULT: NEGATIVE
Epi proColon® 2.0 CE negative patients
are correctly classified as healthy with
99.9 % probability. Screening should
be done regularly.
The sample submitted for analysis was classified as:
Negative
Positive
for the presence of
m
SEPT9 in blood plasma.
Test Analysis: It has been validated in several clinical studies that there is a strong association
between detection of mSEPT9 in blood plasma with presence of colorectal cancer.
for the presence of
Comment on positive test result: a positive test result means that there is an increased likelihood for the presence of CRC. Individuals with positive test results are encouraged to undergo
a diagnostic colonoscopy. From 20 positive tests, an average of 1 person will be diagnosed with
CRC and 7 will be diagnosed with polyps.
Test Analysis: It has been validated in several clinical studies that there is a strong association
between detection of mSEPT9 in blood plasma with presence of colorectal cancer.
Comment on negative test result: a negative test result means that SEPT9 methylation
could not be detected, so with this method, there is no indication for increased likelihood for the
presence of CRC. Individuals with negative test results are correctly classified as being CRC
m
negative 99.7 % of the time.
1. Lofton-Day et al, DNA-Methylation Biomarkers for Blood-Based Colorectal Cancer Screening, Clin. Chem, 2008;54:414-23.
2. Grützmann et al, Sensitive detection of colorectal cancer in peripheral blood by septin 9 DNA methylation assay, PLOS One, 2008;3(11):e3759
3. DeVos T. et al, Circulation methylated SEPT9 DNA in Plasma as a Biomarker for Colorectal Cancer, Clin. Chem, 2009;55:7m 1337-1346
4. Weiss G. and T. Rösch, Potenital of a new blood Test for Colorectal Cancer Screening-the Septin9 Gene Biomarker, European Oncology, Volume 6, Issue 1, (2010)
5. Church et al, Prospective clinical validation of an assay for methylated Septin 9 DNA in human plasma as a colorectal cancer screening tool in average risk men and women 50 years and older, Oral Presentation at DDW, Chicago, IL, 2010
6. mS9 real-time PCR Assay, Gebrauchsanleitung, Abbott Molecular, 2009
7. Rösch et al, Prospective Clinical Validation of a Biomarker, Methylated SEPT 9 DNA, for Colorectal Cancer Detection in Plasma of Average Risk Men and Women Over the Age of 50, Poster Presentation at UEGW, Barcelona, Spain, 2010
m
SEPT9 in blood plasma.
Comment on positive test result: a positive test result means that there is an increased likelihood for the presence of CRC. Individuals with positive test results are encouraged to undergo
a diagnostic colonoscopy. From 20 positive tests, an average of 1 person will be diagnosed with
CRC and 7 will be diagnosed with polyps.
Comment on negative test result: a negative test result means that mSEPT9 methylation
could not be detected, so with this method, there is no indication for increased likelihood for the
presence of CRC. Individuals with negative test results are correctly classified as being CRC
negative 99.7 % of the time.
8. Heichmann et al, Use of Septin 9 Methylated DNA Biomarker to Detect Cancer in the Blood of Colorectal Cancer Patients Poster Presentation at ASCO-NCI-EORTC Annual Meeting on Molecular Markers, Hollywood, FL, 2010
1. Lofton-Day et al, DNA-Methylation Biomarkers for Blood-Based Colorectal Cancer Screening, Clin. Chem, 2008;54:414-23.
2. Grützmann et al, Sensitive detection of colorectal cancer in peripheral blood by septin 9 DNA methylation assay, PLOS One, 2008;3(11):e3759
3. DeVos T. et al, Circulation methylated SEPT9 DNA in Plasma as a Biomarker for Colorectal Cancer, Clin. Chem, 2009;55:7m 1337-1346
4. Weiss G. and T. Rösch, Potenital of a new blood Test for Colorectal Cancer Screening-the Septin9 Gene Biomarker, European Oncology, Volume 6, Issue 1, (2010)
5. Church et al, Prospective clinical validation of an assay for methylated Septin 9 DNA in human plasma as a colorectal cancer screening tool in average risk men and women 50 years and older, Oral Presentation at DDW, Chicago, IL, 2010
6. mS9 real-time PCR Assay, Gebrauchsanleitung, Abbott Molecular, 2009
7. Rösch et al, Prospective Clinical Validation of a Biomarker, Methylated SEPT 9 DNA, for Colorectal Cancer Detection in Plasma of Average Risk Men and Women Over the Age of 50, Poster Presentation at UEGW, Barcelona, Spain, 2010
8. Heichmann et al, Use of Septin 9 Methylated DNA Biomarker to Detect Cancer in the Blood of Colorectal Cancer Patients Poster Presentation at ASCO-NCI-EORTC Annual Meeting on Molecular Markers, Hollywood, FL, 2010
Figure 6: Example of a laboratory report
LITERATURE
1. American Cancer Society, Colorectal Cancer Facts & Figures, 2011–2013.
2. Globocan 2008, Cancer Fact Sheet, 2008.
3. Telephone survey Colorectal Cancer Alliance. CCA Denver, 2011.
4. Zarca et al. Transversales Biarritz, 2011.
5. Weiss G. and T. Rösch, European Oncology, Volume 6, Issue 1, 2010.
6. Rösch et al. Poster Presentation at UEGW, Barcelona, Spain, 2010.
7. Tetzner et al. UEGW, 2011.
8. Allison et al. NEJM, 1996.
9. Park et al. Am. J. Gastro., 2010.
10. Tóth et al. UEGW, 2011.
TEST RESULT: POSITIVE
An average of one out of two Epi pro
Colon® 2.0 CE positive patients suffer
from colorectal cancer. The probability
is 45 %.
I N F O R M AT I O N F O R P H Y S I C I A N S
You can obtain further information on the Epi pro Colon® 2.0 CE test at:
Phone: + 49 30 24345-111
[email protected]
www.epiprocolon.com
Epigenomics AG
Kleine Praesidentenstr. 1
10178 Berlin
Germany
Not for sale in the United States.
MKT0012GB, rev 2 © 2011 Epigenomics AG