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WHAT’S NEW IN METASTATIC COLON CANCER TREATMENT?

Year 2021, Volume: 84 Issue: 3, 425 - 429, 31.07.2021
https://doi.org/10.26650/IUITFD.2020.0086

Abstract

In this review, we present the current innovations in the field of metastatic colon cancer (mCRC). Tumor placement is important in the mCRC treatment decision, and KRAS, NRAS, BRAF mutation analysis is performed in terms of prognosis/predictivity. Immunotherapy is the treatment option in patients with 5-6% and dMMR/MSI. The concept of NeoRAS will become more on the agenda in the near future as high-level evidence becomes available. Molecular evaluations have become extremely important in terms of prognosis and predictions in the treatment of mCRC, as in many tumors today.

References

  • 1. Weinberg BA, Marshall JL, E Salem M. The Growing Challenge of Young Adults With Colorectal Cancer. Oncology (Williston Park) 2017;31(5):381-9.
  • 2. Cremolini C, Antoniotti C, Lonardi S, Bergamo F, Cortesi E, Tomasello G, et al. Primary Tumor Sidedness and Benefit From FOLFOXIRI Plus Bevacizumab as Initial Therapy for Metastatic Colorectal Cancer. Retrospective Analysis of the TRIBE Trial by GONO. Ann Oncol 2018;29(7):1528-34. [CrossRef]
  • 3. D Arnold , B Lueza , J-Y Douillard , M Peeters , H-J Lenz , A Venook , et al. Prognostic and Predictive Value of Primary Tumour Side in Patients With RAS Wild-Type Metastatic Colorectal Cancer Treated With Chemotherapy and EGFR Directed Antibodies in Six Randomized Trials. Ann Oncol 2017;28(8):1713-29. [CrossRef]
  • 4. Holchet JW, Ricard I, Stintzing S, Modest DP, Heinemann V, et al. The Relevance of Primary Tumour Location in Patients With Metastatic Colorectal Cancer: A Meta-Analysis of First- Line Clinical Trials. Eur J Cancer 2017;70:87-98. [CrossRef]
  • 5. Lenz HJ, Ou FS, Venook AP, Hochster HS, Niedzwiecki D, Goldberg RM, et al. Impact of Consensus Molecular Subtype on Survival in Patients With Metastatic Colorectal Cancer: Results From CALGB/SWOG 80405 (Alliance). J Clin Oncol 2019;37(22):1876-85. [CrossRef]
  • 6. Innocenti F, Fang-Shu Ou FS, Qu X, Zemla TJ, Niedzwiecki D, Tam R, et al. Mutational Analysis of Patients With Colorectal Cancer in CALGB/SWOG 80405 Identifies New Roles of Microsatellite Instability and Tumor Mutational Burden for Patient Outcome. J Clin Oncol 2019;37(14):1217- 27. [CrossRef]
  • 7. Boeckx N, Koukakis R, Op de Beeck K, Rolfo C, Van Camp G, Siena S, et al. Effect of Primary Tumor Location on Second- Or Later-line Treatment Outcomes in Patients With RAS Wild-type Metastatic Colorectal Cancer and All Treatment Lines in Patients With RAS Mutations in Four Randomized Panitumumab Studies. Clin Colorectal Cancer 2018;17(3):170-8. [CrossRef]
  • 8. Bennouna J, Hiret S, Bertaut A, Bouché O , Deplanque G, Borel C, et al. Continuation of Bevacizumab vs Cetuximab Plus Chemotherapy After First Progression in KRAS Wild-Type Metastatic Colorectal Cancer: The UNICANCER PRODIGE18 Randomized Clinical Trial. JAMA Oncol 2019;5(1):83-90. [CrossRef]
  • 9. Cremolini C, Loupakis F, Antoniotti C, Lupi C, Sensi E, Lonardi S, et al. FOLFOXIRI Plus Bevacizumab Versus FOLFIRI Plus Bevacizumab as First-Line Treatment of Patients With Metastatic Colorectal Cancer: Updated Overall Survival and Molecular Subgroup Analyses of the Open-Label, Phase 3 TRIBE Study. Lancet Oncol 2015;16(13):1306-15. [CrossRef]
  • 10. Avallone A, Giuliani F. TRIBE2 results and toxicity. Lancet Oncol. 2020;21(6):e299. [CrossRef]
  • 11. Fornaro L, Lonardi S, Masi G, Loupakis F, Bergamo F, Salvatore L, et al. FOLFOXIRI in Combination With Panitumumab as First-Line Treatment in Quadruple Wild- Type (KRAS, NRAS, HRAS, BRAF) Metastatic Colorectal Cancer Patients: A Phase II Trial by the Gruppo Oncologico Nord Ovest (GONO). Ann Oncol2013;24(8):2062-7. [CrossRef]
  • 12. Borelli B, Moretto R, Lonardi S, Bonetti A, Antoniotti C, Pietrantonio, F et al. TRIPLETE: A Randomised Phase III Study of Modified FOLFOXIRI Plus Panitumumab Versus mFOLFOX6 Plus Panitumumab as Initial Therapy for Patients With Unresectable RAS and BRAF Wild-Type Metastatic Colorectal Cancer. ESMO Open 2018;3(4):e000403. [CrossRef]
  • 13. Pietrantonio F, Morano F, Corallo S, Miceli R, Lonardi S, Raimondi A, et al. Maintenance Therapy With Panitumumab Alone vs Panitumumab Plus Fluorouracil- Leucovorin in Patients With RAS Wild-Type Metastatic Colorectal CancerA Phase 2 Randomized Clinical Trial. JAMA Oncol 2019;5(9):1268-75. [CrossRef]
  • 14. Kopetz S, Grothey A, Van Cutsem E, Yaeger R, Wasan HS et al. Encorafenib plus cetuximab with or without binimetinib for BRAF V600E metastatic colorectal cancer: Updated survival results from a randomized, three-arm, phase III study versus choice of either irinotecan or FOLFIRI plus cetuximab (BEACON CRC). J Clin Oncol 2020;38(15_ suppl): 4001-4001. [CrossRef]
  • 15. Sartore-Bianchi A, Trusolino L, Martino C, Bencardino K, Lonardi S, Bergamo F, et al. Dual-targeted therapy with trastuzumab and lapatinib in treatmentrefractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-ofconcept, multicentre, open-label, phase 2 trial. Lancet Oncol 2016;17(6):738-46. [CrossRef]
  • 16. Meric-Bernstam F, Hurwitz H, Raghav KPS, McWilliams RR, Fakih M, VanderWalde A, et al. Pertuzumab Plus Trastuzumab for HER2-amplified Metastatic Colorectal Cancer (MyPathway): An Updated Report From a Multicentre, Open-Label, Phase 2a, Multiple Basket Study. Lancet Oncol 2019;20(4):518-30. [CrossRef]
  • 17. Siena S, Di Bartolomeo M, Raghav KPS, Masuishi T, Loupakis F, et al. A phase II, multicenter, open-label study of trastuzumab deruxtecan (T-DXd; DS-8201) in patients (pts) with HER2-expressing metastatic colorectal cancer (mCRC): DESTINY-CRC01. J Clin Oncol 2020;38(15_ suppl):4000-4000. [CrossRef]
  • 18. Okamura R, Boichard A, Kato S, Sicklick JK, Bazhenova L, Kurzrock R. Analysis of NTRK Alterations in Pan- Cancer Adult and Pediatric Malignancies: Implications for NTRK-Targeted Therapeutics. JCO Precis Oncol 2018;2018:10.1200/PO.18.00183. [CrossRef]
  • 19. Federman N, McDermott R. Larotrectinib, a highly selective tropomyosin receptor kinase (TRK) inhibitor for the treatment of TRK fusion cancer. Expert Rev Clin Pharmacol 2019;12(10):931-9. [CrossRef]
  • 20. Müller MF, Ibrahim AE, Arends MJ. Molecular Pathological Classification of Colorectal Cancer. Virchows Arch 2016;469(2):125-34. [CrossRef]
  • 21. Grothey A, Van Cutsem E, Sobrero A, Siena S, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): a,n international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013;381(9863):303-12. [CrossRef]
  • 22. Mayer RJ, Van Cutsem E, Falcone A, Yoshino T, Garcia- Carbonero R, Mizunuma N, et al. Randomized Trial of TAS- 102 for Refractory Metastatic Colorectal Cancer. N Engl J Med 2015;372:1909-19. [CrossRef]
  • 23. Karapeti CS , Khambata-Ford S, Jonker DJ, O’Callaghan CJ, Tu D, Tebbutt NC, et al. K-ras Mutations and Benefit From Cetuximab in Advanced Colorectal Cancer. N Engl J Med 2008;359(17):1757-65. [CrossRef]
  • 24. Amado RG, Wolf M, Peeters M, Cutsem EV, Siena S, Freeman DJ, et al. Wild-type KRAS Is Required for Panitumumab Efficacy in Patients With Metastatic Colorectal Cancer. JCO 2008;26(10):1626-34. [CrossRef]
  • 25. Masuishi T, Taniguchi H, Kawakami T, Kawamoto Y, Kadowaki S, Onozawa Y, et al. Impact of Tumour Growth Rate During Preceding Treatment on Tumour Response to Regorafenib or trifluridine/tipiracil in Refractory Metastatic Colorectal Cancer Esmo open 2019;4(6):e000584. [CrossRef]
  • 26. Pfeiffer P, Yilmaz M, Möller S, Zitnjak D, Krogh M, Petersen LN, et al. TAS-102 With or Without Bevacizumab in Patients With Chemorefractory Metastatic Colorectal Cancer: An Investigator-Initiated, Open-Label, Randomised, Phase 2 Trial. Lancet Oncol 2020;21(3):412-20. [CrossRef]
  • 27. Klein-Scory S, Maslova M, Pohl M, Eilert-Micus C, Schroers R, Schmiegel W, et al. Significance of Liquid Biopsy for Monitoring and Therapy Decision of Colorectal Cancer. Transl Oncol 2018;11(2):213-20. [CrossRef]
  • 28. Satake H, Sunakawa Y, Miyamoto Y, Nakamura M, Nakayama H, Shiozawa M, et al. A Phase II Trial of 1st-line modified- FOLFOXIRI Plus Bevacizumab Treatment for Metastatic Colorectal Cancer Harboring RAS Mutation: JACCRO CC- 11. Oncotarget 2018;9(27):18811-20. [CrossRef]
  • 29. Diaz La, Dung TL,Won Kim T, et al. Pembrolizumab monotheraphy for patients with advanced MSI-H colorectal cancer: Longer-term follow up phase II. Keynote-164 study. 2020;38(15_suppl):4032-4032. [CrossRef]
  • 30. Lenz HJ, Lonardi S, Zagonel V, et al. Nivolumab (NIVO) + low dose ipilimumab (IPI) as after first-line (1L) therapy in microsatellite insitability-high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): Two years clinical update. J Clin Oncol 2020;38(15_ suppl):4040-4040. [CrossRef]
  • 31. Thierry Andre, Kai-Keen Shiu, Won Kim T, Jensen BV, Jensen LH, Cornelis J. A et al. Pembrolizumab versus chemotherapy for microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer: The phase 3 KEYNOTE-177 Study. J Clin Oncol 2020;38(18_suppl): LBA4- LBA4. [CrossRef]
  • 32. Jiang T, Chen X, Chunxia Su, Ren S, Zhou C. Pancancer analysis of ARID1A Alterations as Biomarkers for Immunotherapy Outcomes. J Cancer. 2020;11(4):776-780. [CrossRef]

METASTATİK KOLON KANSERİ TEDAVİSİNDEKİ YENİLİKLER

Year 2021, Volume: 84 Issue: 3, 425 - 429, 31.07.2021
https://doi.org/10.26650/IUITFD.2020.0086

Abstract

Bu derlemede metastatik kolon kanseri (mKRK)’ndeki medikal alandaki güncel yenilikler değerlendirildi. mKRK tedavi kararında tümör yerleşimi önemlidir ve KRAS, NRAS, BRAF mutasyon analizi prognoz/prediktivite açısından yapılmaktadır. İmmünoterapi %5-6 ve dMMR/MSI olan hasta grubunda tedavi seçeneğidir. NeoRAS kavramı, kanıt düzeyi yüksek bilgiler artıkça yakın gelecekte daha fazla gündemde olacaktır. Günümüzdeki birçok tümör tedavisinde olduğu gibi mKRK tedavisinde de moleküler değerlendirmeler prognoz ve prediktif açıdan son derece önemli hale gelmiştir.

References

  • 1. Weinberg BA, Marshall JL, E Salem M. The Growing Challenge of Young Adults With Colorectal Cancer. Oncology (Williston Park) 2017;31(5):381-9.
  • 2. Cremolini C, Antoniotti C, Lonardi S, Bergamo F, Cortesi E, Tomasello G, et al. Primary Tumor Sidedness and Benefit From FOLFOXIRI Plus Bevacizumab as Initial Therapy for Metastatic Colorectal Cancer. Retrospective Analysis of the TRIBE Trial by GONO. Ann Oncol 2018;29(7):1528-34. [CrossRef]
  • 3. D Arnold , B Lueza , J-Y Douillard , M Peeters , H-J Lenz , A Venook , et al. Prognostic and Predictive Value of Primary Tumour Side in Patients With RAS Wild-Type Metastatic Colorectal Cancer Treated With Chemotherapy and EGFR Directed Antibodies in Six Randomized Trials. Ann Oncol 2017;28(8):1713-29. [CrossRef]
  • 4. Holchet JW, Ricard I, Stintzing S, Modest DP, Heinemann V, et al. The Relevance of Primary Tumour Location in Patients With Metastatic Colorectal Cancer: A Meta-Analysis of First- Line Clinical Trials. Eur J Cancer 2017;70:87-98. [CrossRef]
  • 5. Lenz HJ, Ou FS, Venook AP, Hochster HS, Niedzwiecki D, Goldberg RM, et al. Impact of Consensus Molecular Subtype on Survival in Patients With Metastatic Colorectal Cancer: Results From CALGB/SWOG 80405 (Alliance). J Clin Oncol 2019;37(22):1876-85. [CrossRef]
  • 6. Innocenti F, Fang-Shu Ou FS, Qu X, Zemla TJ, Niedzwiecki D, Tam R, et al. Mutational Analysis of Patients With Colorectal Cancer in CALGB/SWOG 80405 Identifies New Roles of Microsatellite Instability and Tumor Mutational Burden for Patient Outcome. J Clin Oncol 2019;37(14):1217- 27. [CrossRef]
  • 7. Boeckx N, Koukakis R, Op de Beeck K, Rolfo C, Van Camp G, Siena S, et al. Effect of Primary Tumor Location on Second- Or Later-line Treatment Outcomes in Patients With RAS Wild-type Metastatic Colorectal Cancer and All Treatment Lines in Patients With RAS Mutations in Four Randomized Panitumumab Studies. Clin Colorectal Cancer 2018;17(3):170-8. [CrossRef]
  • 8. Bennouna J, Hiret S, Bertaut A, Bouché O , Deplanque G, Borel C, et al. Continuation of Bevacizumab vs Cetuximab Plus Chemotherapy After First Progression in KRAS Wild-Type Metastatic Colorectal Cancer: The UNICANCER PRODIGE18 Randomized Clinical Trial. JAMA Oncol 2019;5(1):83-90. [CrossRef]
  • 9. Cremolini C, Loupakis F, Antoniotti C, Lupi C, Sensi E, Lonardi S, et al. FOLFOXIRI Plus Bevacizumab Versus FOLFIRI Plus Bevacizumab as First-Line Treatment of Patients With Metastatic Colorectal Cancer: Updated Overall Survival and Molecular Subgroup Analyses of the Open-Label, Phase 3 TRIBE Study. Lancet Oncol 2015;16(13):1306-15. [CrossRef]
  • 10. Avallone A, Giuliani F. TRIBE2 results and toxicity. Lancet Oncol. 2020;21(6):e299. [CrossRef]
  • 11. Fornaro L, Lonardi S, Masi G, Loupakis F, Bergamo F, Salvatore L, et al. FOLFOXIRI in Combination With Panitumumab as First-Line Treatment in Quadruple Wild- Type (KRAS, NRAS, HRAS, BRAF) Metastatic Colorectal Cancer Patients: A Phase II Trial by the Gruppo Oncologico Nord Ovest (GONO). Ann Oncol2013;24(8):2062-7. [CrossRef]
  • 12. Borelli B, Moretto R, Lonardi S, Bonetti A, Antoniotti C, Pietrantonio, F et al. TRIPLETE: A Randomised Phase III Study of Modified FOLFOXIRI Plus Panitumumab Versus mFOLFOX6 Plus Panitumumab as Initial Therapy for Patients With Unresectable RAS and BRAF Wild-Type Metastatic Colorectal Cancer. ESMO Open 2018;3(4):e000403. [CrossRef]
  • 13. Pietrantonio F, Morano F, Corallo S, Miceli R, Lonardi S, Raimondi A, et al. Maintenance Therapy With Panitumumab Alone vs Panitumumab Plus Fluorouracil- Leucovorin in Patients With RAS Wild-Type Metastatic Colorectal CancerA Phase 2 Randomized Clinical Trial. JAMA Oncol 2019;5(9):1268-75. [CrossRef]
  • 14. Kopetz S, Grothey A, Van Cutsem E, Yaeger R, Wasan HS et al. Encorafenib plus cetuximab with or without binimetinib for BRAF V600E metastatic colorectal cancer: Updated survival results from a randomized, three-arm, phase III study versus choice of either irinotecan or FOLFIRI plus cetuximab (BEACON CRC). J Clin Oncol 2020;38(15_ suppl): 4001-4001. [CrossRef]
  • 15. Sartore-Bianchi A, Trusolino L, Martino C, Bencardino K, Lonardi S, Bergamo F, et al. Dual-targeted therapy with trastuzumab and lapatinib in treatmentrefractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-ofconcept, multicentre, open-label, phase 2 trial. Lancet Oncol 2016;17(6):738-46. [CrossRef]
  • 16. Meric-Bernstam F, Hurwitz H, Raghav KPS, McWilliams RR, Fakih M, VanderWalde A, et al. Pertuzumab Plus Trastuzumab for HER2-amplified Metastatic Colorectal Cancer (MyPathway): An Updated Report From a Multicentre, Open-Label, Phase 2a, Multiple Basket Study. Lancet Oncol 2019;20(4):518-30. [CrossRef]
  • 17. Siena S, Di Bartolomeo M, Raghav KPS, Masuishi T, Loupakis F, et al. A phase II, multicenter, open-label study of trastuzumab deruxtecan (T-DXd; DS-8201) in patients (pts) with HER2-expressing metastatic colorectal cancer (mCRC): DESTINY-CRC01. J Clin Oncol 2020;38(15_ suppl):4000-4000. [CrossRef]
  • 18. Okamura R, Boichard A, Kato S, Sicklick JK, Bazhenova L, Kurzrock R. Analysis of NTRK Alterations in Pan- Cancer Adult and Pediatric Malignancies: Implications for NTRK-Targeted Therapeutics. JCO Precis Oncol 2018;2018:10.1200/PO.18.00183. [CrossRef]
  • 19. Federman N, McDermott R. Larotrectinib, a highly selective tropomyosin receptor kinase (TRK) inhibitor for the treatment of TRK fusion cancer. Expert Rev Clin Pharmacol 2019;12(10):931-9. [CrossRef]
  • 20. Müller MF, Ibrahim AE, Arends MJ. Molecular Pathological Classification of Colorectal Cancer. Virchows Arch 2016;469(2):125-34. [CrossRef]
  • 21. Grothey A, Van Cutsem E, Sobrero A, Siena S, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): a,n international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013;381(9863):303-12. [CrossRef]
  • 22. Mayer RJ, Van Cutsem E, Falcone A, Yoshino T, Garcia- Carbonero R, Mizunuma N, et al. Randomized Trial of TAS- 102 for Refractory Metastatic Colorectal Cancer. N Engl J Med 2015;372:1909-19. [CrossRef]
  • 23. Karapeti CS , Khambata-Ford S, Jonker DJ, O’Callaghan CJ, Tu D, Tebbutt NC, et al. K-ras Mutations and Benefit From Cetuximab in Advanced Colorectal Cancer. N Engl J Med 2008;359(17):1757-65. [CrossRef]
  • 24. Amado RG, Wolf M, Peeters M, Cutsem EV, Siena S, Freeman DJ, et al. Wild-type KRAS Is Required for Panitumumab Efficacy in Patients With Metastatic Colorectal Cancer. JCO 2008;26(10):1626-34. [CrossRef]
  • 25. Masuishi T, Taniguchi H, Kawakami T, Kawamoto Y, Kadowaki S, Onozawa Y, et al. Impact of Tumour Growth Rate During Preceding Treatment on Tumour Response to Regorafenib or trifluridine/tipiracil in Refractory Metastatic Colorectal Cancer Esmo open 2019;4(6):e000584. [CrossRef]
  • 26. Pfeiffer P, Yilmaz M, Möller S, Zitnjak D, Krogh M, Petersen LN, et al. TAS-102 With or Without Bevacizumab in Patients With Chemorefractory Metastatic Colorectal Cancer: An Investigator-Initiated, Open-Label, Randomised, Phase 2 Trial. Lancet Oncol 2020;21(3):412-20. [CrossRef]
  • 27. Klein-Scory S, Maslova M, Pohl M, Eilert-Micus C, Schroers R, Schmiegel W, et al. Significance of Liquid Biopsy for Monitoring and Therapy Decision of Colorectal Cancer. Transl Oncol 2018;11(2):213-20. [CrossRef]
  • 28. Satake H, Sunakawa Y, Miyamoto Y, Nakamura M, Nakayama H, Shiozawa M, et al. A Phase II Trial of 1st-line modified- FOLFOXIRI Plus Bevacizumab Treatment for Metastatic Colorectal Cancer Harboring RAS Mutation: JACCRO CC- 11. Oncotarget 2018;9(27):18811-20. [CrossRef]
  • 29. Diaz La, Dung TL,Won Kim T, et al. Pembrolizumab monotheraphy for patients with advanced MSI-H colorectal cancer: Longer-term follow up phase II. Keynote-164 study. 2020;38(15_suppl):4032-4032. [CrossRef]
  • 30. Lenz HJ, Lonardi S, Zagonel V, et al. Nivolumab (NIVO) + low dose ipilimumab (IPI) as after first-line (1L) therapy in microsatellite insitability-high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): Two years clinical update. J Clin Oncol 2020;38(15_ suppl):4040-4040. [CrossRef]
  • 31. Thierry Andre, Kai-Keen Shiu, Won Kim T, Jensen BV, Jensen LH, Cornelis J. A et al. Pembrolizumab versus chemotherapy for microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer: The phase 3 KEYNOTE-177 Study. J Clin Oncol 2020;38(18_suppl): LBA4- LBA4. [CrossRef]
  • 32. Jiang T, Chen X, Chunxia Su, Ren S, Zhou C. Pancancer analysis of ARID1A Alterations as Biomarkers for Immunotherapy Outcomes. J Cancer. 2020;11(4):776-780. [CrossRef]
There are 32 citations in total.

Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section Reviews
Authors

Senem Karabulut This is me 0000-0003-4740-9973

Mehmet Karabulut This is me 0000-0002-1889-5637

Didem Taştekin This is me 0000-0002-9522-9849

Publication Date July 31, 2021
Submission Date July 13, 2020
Published in Issue Year 2021 Volume: 84 Issue: 3

Cite

APA Karabulut, S., Karabulut, M., & Taştekin, D. (2021). METASTATİK KOLON KANSERİ TEDAVİSİNDEKİ YENİLİKLER. Journal of Istanbul Faculty of Medicine, 84(3), 425-429. https://doi.org/10.26650/IUITFD.2020.0086
AMA Karabulut S, Karabulut M, Taştekin D. METASTATİK KOLON KANSERİ TEDAVİSİNDEKİ YENİLİKLER. İst Tıp Fak Derg. July 2021;84(3):425-429. doi:10.26650/IUITFD.2020.0086
Chicago Karabulut, Senem, Mehmet Karabulut, and Didem Taştekin. “METASTATİK KOLON KANSERİ TEDAVİSİNDEKİ YENİLİKLER”. Journal of Istanbul Faculty of Medicine 84, no. 3 (July 2021): 425-29. https://doi.org/10.26650/IUITFD.2020.0086.
EndNote Karabulut S, Karabulut M, Taştekin D (July 1, 2021) METASTATİK KOLON KANSERİ TEDAVİSİNDEKİ YENİLİKLER. Journal of Istanbul Faculty of Medicine 84 3 425–429.
IEEE S. Karabulut, M. Karabulut, and D. Taştekin, “METASTATİK KOLON KANSERİ TEDAVİSİNDEKİ YENİLİKLER”, İst Tıp Fak Derg, vol. 84, no. 3, pp. 425–429, 2021, doi: 10.26650/IUITFD.2020.0086.
ISNAD Karabulut, Senem et al. “METASTATİK KOLON KANSERİ TEDAVİSİNDEKİ YENİLİKLER”. Journal of Istanbul Faculty of Medicine 84/3 (July 2021), 425-429. https://doi.org/10.26650/IUITFD.2020.0086.
JAMA Karabulut S, Karabulut M, Taştekin D. METASTATİK KOLON KANSERİ TEDAVİSİNDEKİ YENİLİKLER. İst Tıp Fak Derg. 2021;84:425–429.
MLA Karabulut, Senem et al. “METASTATİK KOLON KANSERİ TEDAVİSİNDEKİ YENİLİKLER”. Journal of Istanbul Faculty of Medicine, vol. 84, no. 3, 2021, pp. 425-9, doi:10.26650/IUITFD.2020.0086.
Vancouver Karabulut S, Karabulut M, Taştekin D. METASTATİK KOLON KANSERİ TEDAVİSİNDEKİ YENİLİKLER. İst Tıp Fak Derg. 2021;84(3):425-9.

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