EXPERT SYSTEM TECHNOLOGIES FOR DIAGNOSIS AND PROGNOSIS OF MALIGNANCIES

Oleg Kshivets, MD, PhD Omsk Cancer Center, Thoracic Surgery Department,

Russia

National Cancer Institute of The USA

Washington, DC, The USA, 1997

Main Problem of Analysis of Living Supersystems: Phenomenon of

«Combinatorial Explosion»

• Average Number of Routine Blood Parameters:………………………………… 28

• Number of Possible Combination for Random Search:……….. n!=28!=3.049e+29

• Computer Operation Time of The 7G Teracomputer (1000TFLOPS) (The 21st Century)…………………… 9.7 Million Years

Basis

• NP RP P • n! n*n*2(e+n) or n log n n

• AI CSA+S+B SM

Model «Cancer Cells(Cr)--Human Killer Cells(Kl)»

• Ćr=Cr(1-Kl·μCr/λKl);• Ќl=(Kl·μCr/λKl)·[25·Cr/(4.189+• +2.5·Cr)-Cr-1];

Phase Transitions in System «Homeostasis-Malignancy»

Regularities of Cell Population Dynamics in Human Host

Samplings

• Early and Differential Oncodiagnosis and Immunooncodiagnosis……12162

• Corrected Oncodiagnosis and Immunooncodiagnosis……….….6013

• Immunooncodiagnosis and Immunostaging of Malignancy…1743

• Oncoprognosis..……..……………1429

Sampling Structure

• Cancer Patients with the I-IV Stage (T1-4N0-2M0-1)…………………….6721

• Patients with Non-Malignant Pathology…………………………..3977

• Practically Healthy Old People…1464

• In All…….…………………………12162

Samplings

• Control Samplings…………..3509• Learning Samplings………...8653• Control Histologic Early Cancer

Patients (T1N0M0)…………….373 • Learning Histologic Early Cancer

Patients (T1N0M0)…………….428

Phase Transition Early Malignancy into Invasive Cancer

Cluster-Analysis of Data of Early and Invasive Lung Cancer Patients

The Three Phase Transitions in the System «Malignancy-Human’s

Organism»

Early and Differential Diagnosis of Malignancies

The Results of Multiple Correspondence and Claster Analysis of Blood Indexes in

Oncoscreening

Interdependencies between Blood Parameters, Indexes and Cancer Cell

Population

Interdependencies between Blood Indexes and Immune System of Cancer

Patients

Prognostic Role of Cancer Diameter

Prognosis of Cancer Patients Survival Rate

Trajectories of Interdependencies between Tumor’s Characteristics and 5-year Cancer Patients Survival

Rate after Radically Operation

Estimation of Average Malignant Tumor Diameters in Terms of SOD-Technology

High-Precision Quantitative Prognosis of Cancer Patients Survival

Superoncoscreeng-1.0SUPERONCOSCREENING-1.0

SCREENING ANTHROPOMETRY ANAMNESIS LOCALIZATION

SCR-1 SCR-2

SCR-3

ANT-1 ANT-2

ANT-3

LOC1 LOC12LOC2 LOC13LOC3 LOC14LOC4 LOC15LOC5 LOC16LOC6 LOC17LOC7 LOC18LOV8 LOC19LOC9 LOC20LOC10 LOC21 LOC11

MALIGNANT NEOPLASM STATISTICS

PRECANCER

NORM

LOC22

MALE FEMALE

Superoncodiagnos-1.0SUPERONCODIAGNOSIS-1.0

DIAGNOSIS-1 DIAGNOSIS-2 PRECANCER

NORM

MALIGNANT NEOPLASM LOCALIZATION

POPULATION PHASE TRANSITION STATISTICS

EARLY CANCER INVASIVE CANCER

Superoncodiagnosis of Metastasazing-1.0

SUPERONCODIAGNOSIS OF METASTASING-1.0

MTS-N MTS-M

MET-1 MET-2 DEP-1 DEP-2

LOCALIZATION MTS

LIVER LUNGCANCEROMATOSISBONES BRAINKIDNEY ADRENALSOVARY SKIN

STAGING STATISTICS MTS

POPULATION MC

PHASE TRANSITION

PT1 PT2 PT3

C1 C2GENERALIZATION

ST1 ST2 ST3EARLY MALIGNANCY

INVASIVE MALIGNANCY

MALIGNANCY OF THE II-III STAGES MALIGNANCY OF THE IV STAGE

Superoncoimmunology-1.0

SUPERONCOIMMUNOLOGY-1.0

IMMUNODIAGNOSIS-1 IMMUNODIAGNOSIS-2

IMMUNODEFICIENCY NORMMALIGNANT NEOPLASM

POPULATION PHASE TRANSITION IMMUNOSTAGING

N M G

EARLY CANCER INVASIVE CANCER

Superoncoprognosis-1.0SUPERONCOPROGNOSIS-1.0

PROGNOSIS SURVIVAL-2

PROG-1 PROG-2 PROG-3 E

SURVIVAL LESS 5 YEARS SURVIVAL MORE 5 YEARS

SURVIVAL-1

A B

C

Total Monitoring System

SOS-1.0HEALTHY PEOPLE

PRECANCER

PERSONS FOR SUSPICION OFMALIGNANCY

SOD-1.0

SOI-1.0NONMALIGNANT

PATHOLOGY

MALIGNANCY

SODM-1.0 EARLY CANCER

INVASIVE CANCER SOP-1.0

II-III STAGES IV STAGE

POPULATION OF THE COUNTRY

CONCLUSION• 1. The present research which studied 12162 patients

with malignant neoplasm, pre-cancer and non-malignant pathology of any localization and practically healthy people demonstrated that the parameters of hematological, biochemical and immunological homeostasis and their interconnections of patients with any early oncopathology are changing typically, while these changes are certainly different from the norm, pre-cancer and non-malignant pathology and strictly correlate to the total quantity of malignant cell’s population in the patient’s organism and neoplasm’s prognosis.

• 2. The system analysis of data of 6013 oncopatients made it possible to establish that there is a complex net of stable relationship and interconnections between the hematological, biochemical, immunological homeostasis of a patient and a malignant tumor where factors of the ratio of total quantity of blood cell’s subpopulations, immunocompetent cells and healthy cell’s population to the total quantity of malignant cell’s population in the whole patient’s organism play the main and universal role. The dynamic behavior of the cancer and, in the end, the decease prognosis for the concrete patient are depended on numerical values of this ratio.

• 3. Using complex system analysis and simulation modeling it is found that the system “cancer-patient’s homeostasis” passes through three phase transitions (norm-oncobackground, oncobackground-early oncopathology, early oncopathology-invasive cancer) in the process of which the qualitative characteristics, behavior and aggressiveness of the malignancy, anti-tumor abilities of the patient’s homeostasis and decease prognosis are changing spasmodically.

• 4. Phase transition of an early oncopathology into invasive cancer happens when the quantity of malignant cell’s population reaches 4.189+9 per human organism and the qualitative oncopathology prognosis gets worth.

• 5. The process of regional and distant metastasizing and the generalization of malignancy are typical, their dynamics is influenced by the same hematological, biochemical and immunological factors of human organism’s homeostasis, while these process are stringently interdepended, are of a phase character and are strictly determined by the ratio of total quantity of malignant cell’s population to the total quantity of healthy cells, blood cells and immunocompetent cells in the whole patient’s organism independing on the tumor localization.

• 6. Complex system analysis of the postponed survival rate of 1429 operated oncopatients revealed that prognosis of any malignancy for patient depends on phase transition of early oncopathology into invasive cancer and strictly determined both by the homeostasis data and tumor’s characteristics, while the life duration of radically and non-radically operated oncopatients with the unfavorable decease prognosis practically does not depend on the process localization and is regulated by the same factors of homeostasis and oncopathology.

• 7. The 5-year survival rate of radically operated oncopatients certainly and strictly depends on a whole number of hematological, biochemical and immunological parameters of homeostasis; on cell factors of the ratio of tumor cells to normal cells for a single patient; on malignancy characteristics. This dependence is of a universal and stereotypical character at any oncopathology localization.

• 8. Complex system account of hematological, biochemical, immunological, anthropometrical, clinical, statistical and epidemiological data in terms of expert systems technology allows the detection of malignancies of any localization up to 30% under screening and up to 80% under differential diagnosis and immunodiagnosis and also to improve the accuracy of the process spreading detection up to 96%.

• 9. Complex and system registration of homeostasis parameters, oncopathology characteristics, interdependencies in the system “cancer-human organism”, anthropometric data based on the technology of expert systems allow to make reliable qualitative-quantitative prognosis of postponed survival for every radically operated patient with malignancies of any localization and to estimate the life duration for non-radically operated concrete patient with the accuracy of up to 85%.

• 10. The developed methodologies of early, differential and corrected diagnosis, prognosis, immunodiagnosis and immunostaging of malignant neoplasm oriented for expert systems technology and computers make it possible to detect early and invasive oncopathology of any localization with high accuracy, to identify regional and distant metastasizing, to estimate probable time of relapse and generalization of the process, to select patients for surgical, combined or complex treatment. It creates principally new opportunities for the optimization of the whole diagnosis-treatment process in terms of oncology and allows to reduce financial expenses and volume of instrumental check-ups by 2-3 orders in comparison with existing traditional programs.

Address:• Oleg Kshivets, M.D., Ph.D.• Thoracic Surgeon• Dep. of Thoracic Surgery• Omsk Cancer Center, Russia

• Tilzes:42-16, Siauliai, LT78206, Lithuania• Tel. (37041)416614• okshivets@yahoo.com kshivets@gmail.com• http//:myprofile.cos.com/Kshivets