Molecular classification CRC_dr Iwan Kristian (distributed).pdf

Molecular classification CRC_dr Iwan Kristian (distributed)
Molecular classification CRC_dr Iwan Kristian (distributed)
Molecular classification CRC_dr Iwan Kristian (distributed)
Molecular classification CRC_dr Iwan Kristian (distributed)

1. MOLECULAR SUBTYPING OF
COLON CANCER : CLINICAL
IMPLICATION
DR.IWAN KRISTIAN SP.B.KBD DEPARTMENT OF
SURGERY DR.SOETOMO HOSPITAL ∕ FACULTY OF
MEDICINE AIRLANGGA UNIVERSITYCOPYRIGHT

2. MOLECULAR CLASSIFICATIONCOPYRIGHT

3. COLORECTAL CANCER IS A HETEROGENEOUS DISEASE
The prognosis and therapeutic options for patients with CRC are associated
with the stage of development at which they are first diagnosed.COPYRIGHT

4. THE DIVERSITY OF MCRC
LOOKS ALIKE BUT NOT THE SAMECOPYRIGHT

5. THE PAST AND PRESENTCOPYRIGHT

6. THE CANCER GENOME ATLASCOPYRIGHT

7. GENE SEQUENCING : COPYRIGHT

8. GENETIC MODEL FOR CRC TUMORGENESIS :
FEARON & VOGELSTEIN( 1990 )
Menter DG et al. Curr Gastroenterol Rep;21(2):5. 2019 COPYRIGHT

9. PUTATIVE CRC TUMORGENESIS
Bettington M et al. hystopathlogy 2013;62:367-386COPYRIGHT

10. MOLECULAR ALTERATION IN CRCCOPYRIGHT

11. COLORECTAL CANCER MOLECULAR SUBTYPE
Vilar , Tabernero . Cancer Discov 2013COPYRIGHT

12. Sinicrope eet al. Gastroenterol 2015;148:88-99COPYRIGHT

13. Sinicrope eet al. Gastroenterol 2015;148:88-99COPYRIGHT

14. MOLECULAR ALTERATION IN CRC
Stinzing et al. European J Of Cancer
2017 (84) COPYRIGHT

15. RIGHT –VERSUS LEFT-SIDED CRC BIOLOGY
1.Mundade R et al .Oncoscience june 2014
2.Shi C et al .Am J Clin Pathol 2012;137 :847-859COPYRIGHT

16. MOLECULAR SUBCLASSIFICATION CRC : GENE EXPRESSION DATA
FROM SIX COHORT STUDIES : 8 % ST 4 , 15 % RECTAL CANCER ,
PRIMARY TUMOR
Menter DG et al. Curr Gastroenterol Rep;21(2):5.
2019 COPYRIGHT

17. Guinney et al Nat Med 2015;21(11 :1350-56COPYRIGHT

18. Fontana E,Easar K, Cervantes A , Salazar R, Sadanandam A. Annals Oncol
2019;30:520-527COPYRIGHT

19. SUBTYPE CMS : LOCATION
Fontana E,Easar K, Cervantes A , Salazar R, Sadanandam A. Annals Oncol 2019;30:520-527COPYRIGHT

20. CLINICAL IMPLICATION : PROGNOSTIC FACTOR ST 2 & 3
Relapse free
survival
Guinney, Dienstmann et al . Nat Med 2015;21 (11) :1350-1356
Survival after
relapseCOPYRIGHT

21. COPYRIGHT

22. SURVIVAL :RASWT VS MUTANTCOPYRIGHT

23. RAS WT (A ) VS RAS MT ( B )COPYRIGHT

24. RAS WT: RIGHT VS LEFT COLONCOPYRIGHT

25. CMS2 had the best OS (median
24.2 months, 95% CI 19.1–27.4)
CMS1 had the worst (8.8 months,
95% CI 6.5–16.0)
CMS3 (17.6 months, 95% CI 11.3–
24.6) and CMS4 (21.4 months, 95%
CI 15.8–23.1) had intermediate OSCOPYRIGHT

26. CMS AS PREDICTIVE FACTORS : BEVA COPYRIGHT

27. DIFFERENT STUDY , DIFFERENT RESULT
•CALBG 80405 (2): OXALIPLATIN BASED
•ONLY CMS 2 BENEFIT FROM CETUXIMAB
•CMS 1 : BEVACIZUMAB BETTER THAN CETUXIMAB
•PETACC 8 TRIAL (3)
•CMS 1 : FOLFOX + CETUXIMAB WORSE THAN FOLFOX ALONE
1.Stinzing S et al Annals Oncol 2019;30
2. Lenz HJ, Ou F-S, Venook A et al. J Clin Oncol 2019; 37: 1876–1885
3.Mariza L,Aydi M, Balgoun R et al. J.Clin Oncol 2017;35COPYRIGHT

28. CLINICAL IMPLICATION : IMUNOTHERAPHY
Spallanzani et al. J Cancer Metastasis Treat 2018;4:28COPYRIGHT

29. Spallanzani et al. J Cancer Metastasis Treat 2018;4:28COPYRIGHT

30. SUMMARY
•MULTIPLEPATHOGENETICMECHANISMS ACCOUNT FOR COLORECTAL
TUMORIGENESIS.
•CMS CLASSIFICATION HAS SIGNIFICANT PROGNOSTIC VALUE BUT NOT
PREDICTIVE VALUE : CMS 1 AND 4 THE WORST AND CMS 2 THE BEST .
•CMS CLASSIFICATION PROVIDES DEEPER INSIGHTS INTO THE BIOLOGY TO CRC,
BUT AT THE PRESENT TIME HAS NO IMPACT ON CLINICAL DECISION MAKIN GCOPYRIGHT