«Colorectal cancer screening

in the regions of the Russian Federation:

Stanislav Konovalov Leading expert in HTSA Plus program

The structure of mortality rate in Russia

from various diseases

1 place

2 place

3 place

• Diseases of the circulatory system

• Malignant neoplasms

• Injuries and poisonings

Colorectal cancer (CRC) occupies leading positions in the oncology rates of all developed countries

Relevance of the problem

Mortality rate from malignant neoplasms among the Russian population (both sexes, 13.6%)

Trachea, bronchi, lungs 17,3

Stomach 10,3

Colon 7,9

Breast 7,8

Pancreas 5,9

Rectum 5,7

Relevance of the problem

Performance: 300 tests/hour

High-performance analyzer

Fully automated

Unique specimen collection container (Provides stability of Hb and Tf)

Reagent containing colloid gold

Quantitative immunochemical FOBT (FIT) test HTSA (Hemoglobin Transferrin Simultaneous Assay)*

* HTSA (Hemoglobin Transferrin Simultaneous Assay) - a combination of the quantitative detection of fecal hemoglobin (Hb) and fecal transferrin (Tf) currently has the highest accuracy level: 96% for patients with cancer and 88% for patients

with precancerous stages.

The first pilot project in the Russian Federation in Khanty-Mansiysk region, in which the CRC screening program was launched and has

been successfully implemented since 2011

Нефтеюганск Нижневартовск Ханты-Мансийск

1400 км

Сургут

Test for Tf confirms false-negative test for Hb

Ascending colon

Rectum

Sigmoid colon

Descending colon

Bleeding Hb, Tf

Denatured Hb, Tf

Ascending colon

Traverse colon

Hb, Tf

Bleeding Hb, Tf

The cancer of the ascending colon is virtually asymptomatic and at its early stages its detection is difficult. This neoplasm occurs mostly among people older than 50, and the incidence rate is growing each year. This calls for a need for new methods of detection of this type of cancer. Transferrin Test (Tf) can be an effective and reliable method for diagnosing colorectal cancer.

Traverse colon

Rectum

Sigmoid colon

Descending colon

(Hemoglobin Transferrin Simultaneous Assay) a combination of the quantification of fecal hemoglobin (Hb) and fecal transferrin (Tf)

has the highest current accuracy level: 96% for patients with cancer and 88% for patients with precancerous conditions.

HTSA Fecal Occult Blood Test using the immunochemical IFOBT/FIT method in Khanty-Mansiysk Region - Yugra

Immunochemical fecal occult blood test

iFOBT/FIT

OCCULT bleeding in various intestine areas DETECTION

Hb

Tf

Fecal Hemoglobin (Hb) – high levels of Hb indicate the damage of lower areas of intestine.

Fecal Transferrin (Tf) - high levels of Tf indicate the damage of higher areas of intestine . Besides, Fecal Tf

allows avoiding the false-negative results for Hb.

© “Diagnosis” Yoshinori Takashima, Takao Shimada, Tamotsu Yokozawa – 2015; 2(1): 53-59.

In may 2017 fecal transferrin was introduced to the international

database and universal standard for identification of medical doctor’s

and laboratory examinations – LOINC, and it was given a code 86271-4.

LOINC is used for standardized presentation of medical

terminology in the field of laboratory research and clinical observation for

the purpose of electronic exchange and the collection of clinical data

obtained from various information systems.

Transferrin – in the LOINC system

181058

28480

11501

25454;

14,1%

Positive results («+»), people

Обследовано человек положительных результатов

положительных на Hb положительных на Tf

Quantitative detection of fecal transferrin and hemoglobin (for occult blood) using a two-day HTSA method in the pilot project "colorectal cancer screening in

the Khanty-Mansiysk region - Ugra" on the NS-Plus analyzer

Surgut Khanty-Mansiysk Nizhnevartovsk Nefteyugansk TOTAL

People examined 88685 19396 47309 25668 181058

Positive results («+»), people 10222 11,5% 3380 17,4% 7842 16,6% 4010 15,6% 25454 14,1%

Positive results («+»), tests 16282 5261 12538 5900 39981

«+» for Hb (Day 1 and Day 2) 11880 73,0% 3703 70,4% 8602 68,6% 4295 72,8% 28480 71,2%

«+» for Hb Day 1 6253 52,6% 1909 51,6% 4470 52,0% 2228 51,9% 14860 52,2%

«+» for Hb Day 2 5627 47,4% 1794 48,4% 4132 48,0% 2067 48,1% 13620 47,8%

«+»for Tf (Day 1 and Day 2) 4402 27,0% 1558 29,6% 3936 31,4% 1605 27,2% 11501 28,8%

«+» for Tf Day 1 2178 49,5% 777 49,9% 1970 50,1% 831 51,8% 5756 50,0%

«+» for Tf Day 2 2224 50,5% 781 50,1% 1966 49,9% 774 48,2% 5745 50,0%

«+» for both markers 449 2,8% 160 3,0% 447 3,6% 145 2,5% 1201 3,0%

«+»for Hb and Tf Day 1 1167 13,8% 398 14,8% 1078 16,7% 454 14,8% 3097 15,0%

«+»for Hb and Tf Day 2 1106 14,1% 414 16,1% 1076 17,6% 389 13,7% 2985 15,4%

71,2 % 28,8 %

3,0 %

Positive results («+»), tests

«+» на Hb «+» на Tf из них «+» на оба маркера

People examined

Hb positive

Positive results

Tf positive Both markers

* - «Condition of the oncology aid to the population in 2011-2015» – - edited by A.D. Caprin, V.V. Starinski, G.V. Petrova - Moscow, 2012-2016

CRC Colon (С18)

Rectum, recto-sigmoid junction, anus (С19-21)

2015 64 314 36 494 (56,7%) 27 820 (43,3%)

2014 61 874 35 089 (56,7%) 26 785 (43,3%)

2013 58 406 32 931 (56,4%) 25 475 (43,6%)

2012 58 099 32 528 (56,0%) 25 571 (44,0%)

2011 57 047 32 014 (56,1%) 25 033 (43,9%)

Malignant neoplasms registered

Of those had the following stage of disease (%):

Colon (С18) Rectum, recto-sigmoid junction, anus (С19-

21)

I ll lll lV l ll lll lV

2015 8,0 37,3 25,1 27,7 10,6 40,3 24,2 22,6

2014 7,4 35,7 26,6 27,7 10,2 38,8 24,8 23,5

2013 6,8 35,1 27,6 27,6 9,3 38,8 25,1 23,7

2012 6,7 35,3 27,5 27,5 9,0 38,6 26,0 23,2

2011 5,6 34,4 28,4 28,0 8,8 39,3 25,2 23,4

Detection rate of early stages of tumor in Russia in 2011 - 2015*

Mortality in the first year after making a diagnosis: 2015

Colon (С18)

27,4 23,8

Rectum, recto-sigmoid

junction, anus (С19-21)

2014 28,4 24,9

2013 28,4 25,7

2012 29,6 25,8

2011 30,5 27,7

3%

in

yea

r

Conclusions: In the tables there are data over the 5-year period. In comparison with Khanty-Mansiysk region in Russia the detection rate on the first stage has grown only by 2.4% in colon. In rectum detection rate of malignants has grown by 1.8%.

* «Condition of the oncology aid to the population in 2013-2015» - edited by A.D. Caprin, V.V. Starinski, G.V. Petrova - Moscow, 2012-2016

CRC Colon (С18)

Rectum, rectosigmoid, anus (С19-21)

2015 585 317 (54,2%) 268 (45,8%)

2014 476 258 (54,2%) 218 (45,8%)

2013 479 265 (55,3%) 214 (44,7%)

2012 447 246 (55,0%) 201 (45,0%)

2011 390 195 (50,0%) 195 (50,0%)

Malignant neoplasms registered

Of those had the following stage of disease (%):

Colon (С18) Rectum, recto-sigmoid junction, anus (С19-21)

I ll lll lV l ll lll lV

2015 25,6 26,5 17,7 29,3 19,8 33,6 22,8 21,6

2014 17,8 32,9 21,7 25,6 25,7 27,1 22,0 21,1

2013 12,6 33,2 19,6 24,9 12,6 33,2 19,6 31,8

2012 14,6 32,9 15,9 34,1 16,9 38,3 20,4 23,4

2011 8,2 37,4 23,1 25,1 11,3 40,5 20,0 21,5

Statistics after implementation of immunochemical iFOBT (FIT) test by HTSA method in Khanty-Mansyisk Autonomous Okrug — Yugra

Mortality in the first year after making a diagnosis:

2015

Colon (С18)

22,8 15,4

Rectum, recto-sigmoid

junction, anus (С19-21)

2014 19,0 23,0

2013 23,3 14,6

2012 24,9 13,8

2011 26,3 30,5

Conclusions: The data over the 5 year period in Khanty-Mansiysk region are represented above. Due to the 2-days HTSA method use (fecal hemoglobin and transferrin simultaneous assay) detection of colon cancer at the 1 stage has grown three times. Two-days HTSA method helped to increase detection of rectum cancer two times. As a result CRC mortality rate remained at a low level.

• Results of the two-days immunochemical test - iFOBT (FIT) using the HTSA method

(fecal hemoglobin (Hb) and transferrin (Tf) simultaneous assay ) (for the entire period).

The test results conducted on a Discrete Automated Clinical Chemistry Analyzer NS-Plus C15 (Japan) in Nizhnevartovsk (2011 to 2018)

People examined 47309

Positive results («+»), people 7842 16,6%

Positive results («+»), tests 12538

«+» for Hb (Day 1 and Day 2) 8602 68,6%

«+» for Hb Day 1 4470 52,0%

«+» for Hb Day 2 4132 48,0%

«+»for Tf (Day 1 and Day 2) 3936 31,4%

«+» for Tf Day 1 1970 50,1%

«+» for Tf Day 2 1966 49,9%

«+» for both markers 447 3,6%

«+»for Hb and Tf Day 1 1078 16,7%

«+»for Hb and Tf Day 2 1076 17,6%

16,6

%

Positive Results Positive results («+»), tests

both

«+» for Hb «+» for Tf

«+» for both

markers

Day 1 4470 1970 1078

Day 2 4132 1966 1076

Table 2 Quantitative two-days immunochemical test using the HTSA method

Positive results for Hb: Day 1

and Day 2

Positive results for Tf: Day 1

and Day 2

Hb Day 1

Hb Day 2

Tf Day 1

Tf Day 2

This patient showed a significant excess of Hb

and Tf cut-off in both days. With a positive value

in any of the days or both days, the doctor

assigns an additional examination (for example, a

colonoscopy), and the final diagnosis is reached

based on its results.

Hb Tf Hb Tf

Day 1 Day 1 Day 2 Day 2

Hb Tf Hb Tf

Day 1 Day 1 Day 2 Day 2

Appendix 1. Test results. Quantitative simultaneous Hb and Tf tests using the HTSA method (2018) (two-

days method)

This patient would have been missed when

only conducting a one-day Hb test. For small

and uneven positive Tf values, the patient is

most likely to have an initial form of an upper

intestine disease, so additional tests are

necessary. For example, a colonoscopy.

This patient had positive values only in day 2.

With a one-day study, he would have been

missed. The doctor assigns an additional

examination, which leads to the final

diagnosis.

474 people were examined. 40 positive cases (8.4%) were detected, including: - Women - 24; - Men - 16.

8,4%

Percentage of positive results

Quantitative detection of transferrin and hemoglobin in feces (FOBT) using two-days HTSA method in Moscow Central Polyclinic

Examination revealed:

1. Polyps - 20 people. (by results of cytology, tubular adenoma of various degrees of dysplasia)

2. Colon cancer - 4 people.

3. Diverticular disease of the large intestine - 6 people.

4. Colitis of various etiology - 5 people.

5. Nonspecific ulcerative colitis - 3 people.

6. Crohn's disease - 2 people. 50,0%

10,0%

15,0%

12,5%

7,5% 5,0% Полипы

Рак ободочной кишки

Дивертикулярная болезнь толстого кишечника

Колиты различной этиологии

Неспецифический язвенный колит

Болезнь Крона

Hb «+» Tf «+» Hb Tf «+»

Day 1 19 12 6

Day 2 20 12 7

Quantitative detection of transferrin and hemoglobin in feces (FOBT) using two-days HTSA method in Moscow Central Polyclinic

48,7%

51,3%

Positive results for

Hb 1 day and 2 days

«+» на Hb 1 дня

«+» на Hb 2 дня

50,0%

50,0%

Positive resultsfor

Tf 1 day and 2 days

«+» на Tf 1 дня

«+» на Tf 2 дня

Quantitative detection of transferrin and hemoglobin in feces (FOBT) using two-days HTSA method in Moscow Central Polyclinic

Hb Tf Hb Tf

№ 1 день 1 день 2 день 2 день

3 669 30 17 3

6 239 18

25 42 8 22 99

26 75 8 174 13

28 39 2 81 70

33 0 27 268 79

43 12 2 468 94

45 188 29 107 6

51 309 11 94 8

53 207 4 112 7

55 37 129 7 113

57 41 0 544 1

59 872 172 130 3

60 64 6 357 13

61 27 1 745 5

67 444 70 15 4

81 114 84 53 7

91 11 118 24 37

99 44 7 186 9

100 15 4 124 5

Hb Tf Hb Tf

№ 1 день 1 день 2 день 2 день

3 669 30 17 3

6 239 18

25 42 8 22 99

26 75 8 174 13

28 39 2 81 70

33 0 27 268 79

43 12 2 468 94

45 188 29 107 6

51 309 11 94 8

53 207 4 112 7

55 37 129 7 113

57 41 0 544 1

59 872 172 130 3

60 64 6 357 13

61 27 1 745 5

67 444 70 15 4

81 114 84 53 7

91 11 118 24 37

99 44 7 186 9

100 15 4 124 5

Выводы: For the final diagnosis, patients underwent a colonoscopy and other cytological tests at the second stage of the examination.

• The immunochemical iFOBT (FIT) test by HTSA method will significantly save public funds since detection of patients with early stages of cancer will allow to timely conduct low-cost preventive procedures, to preserve patients’ health, to improve the quality of their life and to avoid complex and expensive treatment and as a result to reduce the incidence (stage III and IV) and mortality related to colorectal cancer.

Conclusions