Araştırma Makalesi
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METASTATİK KOLOREKTAL KANSERLİ HASTALARIN EGFR YA DA VEGF İNHİBİTÖRÜ KULLANIM DURUMLARINA GÖRE KLİNİK ÖZELLİKLERİNİN İNCELENMESİ

Yıl 2023, Cilt: 24 Sayı: 4, 466 - 474, 09.10.2023

Metin Deniz Karakoç Özden Özer

https://doi.org/10.18229/kocatepetip.1192194

Öz

AMAÇ: Çalışmada yüksek bir insidansa sahip olan metastatik kolorektal kanser (mKRK) tanılı hastalardaki çeşitli klinik özelliklerin RAS (Rat Sarkom Virüs Geni) mutasyon durumları ve tedavide kullanılan monoklonal antikorlar açısından değerlendirilmesi amaçlanmıştır.
GEREÇ VE YÖNTEM: Kesitsel araştırmamız bir onkoloji merkezinde 01.01.2014 - 01.01.2022 dönemini kapsayan retrospektif bir arşiv taraması olarak gerçekleştirilmiştir. Çalışmanın evrenini 18 yaşını doldurmuş, tedavi sürecinde VEGF inhitibitörü (bevasizumab) ya da EGFR inhitibitörü (setuksimab / panitumumab) monoklonal antikor ilaç uygulanan toplam 187 mKRK tanılı hasta oluşturmaktadır. Verilerin toplanmasında hasta arşiv dosyalarından ve hastane bilgi yönetim otomasyon sisteminden yararlanılmıştır.
BULGULAR: RAS wild tip bireylerde ikinci en yüksek metastaz görülen organın periton, mutant bireylerde ise akciğer olduğu ve aralarındaki farkın istatistiksel olarak önemli olduğu tespit edilmiştir (p=0,003). Bireylerin tanı aşamasındaki serum karsinoembriyonik antijen (CEA) ve karbonhidrat antijeni 19-9 (CA19-9) seviyelerinin RAS wild tip hastalarda mutant olanlara göre nispeten daha düşük olduğu tespit edilmiştir. RAS wild grupta medyan sağ kalım süresinin 36 ay ve mutant grupta ise 27 ay olduğu saptanmıştır (p=0,001).
SONUÇ: Çalışmada RAS mutasyonu varlığının genel sağ kalım süresine negatif yönde etkisi olduğu saptanmıştır. Diğer yandan sağ kalım süresine katkı anlamında monoklonal antikor ilaçlar arasında anlamlı bir fark olmadığı tespit edilmiştir. Ülkemizdeki mKRK’lı hastalarda RAS mutasyonları ile serum tümör biyobelirteçleri seviyeleri arasındaki ilişkilerin daha net ortaya konulabilmesi ve tedavi seçeneklerinin sağ kalım süresine katkıları konusunda çok merkezli ve geniş katılımlı çalışmalara ihtiyaç bulunmaktadır.

Anahtar Kelimeler

Bevasizumab Setuksimab Kolorektal kanser RAS mutasyonları Panitumumab

Destekleyen Kurum

Çalışma için hiçbir şahıs, şirket ya da kuruluştan herhangi bir maddi destek alınmamıştır.

Proje Numarası

-

Teşekkür

Hasta dosyalarının düzenli tasnifini sağlayan ve erişimimiz için her türlü kolaylığı gösteren Denizli Devlet Hastanesi Onkoloji Merkezinde görevli tüm hemşirelere teşekkür ederiz.

Kaynakça

  • 1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-49.
  • 2. Van Cutsem E, Cervantes A, Nordlinger B, Arnold D; ESMO Guidelines Working Group. Metastatic colorectal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(3):1-9.
  • 3. Biller LH, Schrag D. Diagnosis and Treatment of Metastatic Colorectal Cancer: A Review. JAMA. 2021;325(7):669-85.
  • 4. Brenner H, Kloor M, Pox CP. Colorectal cancer. Lancet. 2014;383(9927):1490-1502.
  • 5. Kasi PM, Hubbard JM, Grothey A. Selection of biologics for patients with metastatic colorectal cancer: the role of predictive markers. Expert Rev Gastroenterol Hepatol. 2015;9(3):273-6.
  • 6. Pathak S, Sushmitha S, Banerjee A, et al. Review on comparative efficacy of bevacizumab, panitumumab and cetuximab antibody therapy with combination of FOLFOX-4 in KRAS-mutated colorectal cancer patients. Oncotarget. 2017;9(7):7739-48.
  • 7. Chen J, Wang J, Ni T, He H, Zheng Q. Meta-analysis on the risk of fatal adverse events by bevacizumab, cetuximab, and panitumumab in 31 randomized trials including 25,000 patients with colorectal carcinoma. Medicine (Baltimore). 2020;99(25):e19908.
  • 8. Van Cutsem E, Cervantes A, Adam R, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;27:1386–422.
  • 9. Modest DP, Pant S, Sartore-Bianchi A. Treatment sequencing in metastatic colorectal cancer. Eur J Cancer. 2019;109:70-83.
  • 10. Rui Y, Wang C, Zhou Z, Zhong X, Yu Y. K-Ras mutation and prognosis of colorectal cancer: a meta-analysis. Hepatogastroenterology. 2015;62(137):19-24.
  • 11. Heinemann V, Rivera F, O'Neil BH, et al. A study-level meta-analysis of efficacy data from head-to-head first-line trials of epidermal growth factor receptor inhibitors versus bevacizumab in patients with RAS wild-type metastatic colorectal cancer. Eur J Cancer. 2016;67:11-20.
  • 12. Zhou M, Yu P, Qu J, et al. Efficacy of bevacizumab in the first-line treatment of patients with RAS mutations metastatic colorectal cancer: a systematic review and network meta-analysis. Cell Physiol Biochem. 2016;40(1):361-69.
  • 13. Bonnot PE, Passot G. RAS mutation: site of disease and recurrence pattern in colorectal cancer. Chin Clin Oncol. 2019;8(5):55.
  • 14. Patelli G, Tosi F, Amatu A, et al. Strategies to tackle RAS-mutated metastatic colorectal cancer. ESMO Open. 2021;6(3):100156.
  • 15. Levi M, Prayogi G, Sastranagara F, et al. Clinicopathological associations of K-RAS and N-RAS mutations in Indonesian colorectal cancer cohort. J Gastrointest Cancer. 2018;49(2):124-31.
  • 16. Akman T, Oztop I, Baskin Y, et al. The association of clinicopathological features and survival in colorectal cancer patients with kras mutation status. J Cancer Res Ther. 2016;12(1):96-102.
  • 17. Sezen M, Araz M. Metastatik kolorektal kanserli hastaların RAS mutasyon durumuna göre klinik ve patolojik özellikleri. Uludağ Üniversitesi Tıp Fakültesi Dergisi. 2019;45(2):131-36.
  • 18. Ribeiro KB, Ribeiro KB, Feres O, et al. Clinical-pathological correlation of KRAS mutation status in metastatic colorectal adenocarcinoma. World J Oncol. 2013;4(4):179-87.
  • 19. Morris VK, Lucas FAS, Overman MJ, et al. Clinicopathologic characteristics and gene expression analyses of non-KRAS 12/13, RAS-mutated metastatic colorectal cancer. Ann Oncol. 2014;25(10):2008-14.
  • 20. Kawazoe A, Shitara K, Fukuoka S, et al. A retrospective observational study of clinicopathological features of KRAS, NRAS, BRAF and PIK3CA mutations in Japanese patients with metastatic colorectal cancer. BMC Cancer. 2015;15:258.
  • 21. Peeters M, Kafatos G, Taylor A, et al. Prevalence of RAS mutations and individual variation patterns among patients with metastatic colorectal cancer: a pooled analysis of randomised controlled trials. Eur J Cancer. 2015;51(13):1704-13.
  • 22. Phua LC, Ng HW, Yeo AH, et al. Prevalence of KRAS, BRAF, PI3K and EGFR mutations among Asian patients with metastatic colorectal cancer. Oncol Lett. 2015;10(4):2519-26.
  • 23. Philipovskiy A, Ghafouri R, Dwivedi AK, et al. Association between tumor mutation profile and clinical outcomes among hispanic-latino patients with metastatic colorectal cancer. Front Oncol. 2022;11:772225.
  • 24. Diergaarde B, Vrieling A, van Kraats AA, van Muijen GN, Kok FJ, Kampman E. Cigarette smoking and genetic alterations in sporadic colon carcinomas. Carcinogenesis. 2003;24(3):565-71.
  • 25. Porta M, Crous-Bou M, Wark PA, et al. Cigarette smoking and K-ras mutations in pancreas, lung and colorectal adenocarcinomas: etiopathogenic similarities, differences and paradoxes. Mutat Res. 2009;682(2):83-93.
  • 26. Aggarwal H, Sheffield KM, Li L, et al. Primary tumor location and survival in colorectal cancer: a retrospective cohort study. World J Gastrointest Oncol. 2020;12(4):405-23.
  • 27. Tejpar S, Stintzing S, Ciardiello F, et al. Prognostic and predictive relevance of primary tumor location in patients with RAS wild-type metastatic colorectal cancer: retrospective analyses of the CRYSTAL and FIRE-3 trials. JAMA Oncol. 2017;3(2):194-201.
  • 28. Widder J, Klinkenberg TJ, Ubbels JF, Wiegman EM, Groen HJ, Langendijk JA. Pulmonary oligometastases: metastasectomy or stereotactic ablative radiotherapy? Radiother Oncol. 2013;107(3):409-13.
  • 29. Kinj R, Bondiau PY, François E, et al. Radiosensitivity of colon and rectal lung oligometastasis treated with stereotactic ablative radiotherapy. Clin Colorectal Cancer. 2017;16(3):e211-e220.
  • 30. Parnaby CN, Bailey W, Balasingam A, et al. Pulmonary staging in colorectal cancer: a review. Colorectal Dis. 2012;14(6):660-70.
  • 31. Van der Geest LG, Lam-Boer J, Koopman M, et al. Nationwide trends in incidence, treatment and survival of colorectal cancer patients with synchronous metastases. Clin Exp Metastasis. 2015;32(5):457-65.
  • 32. Gao Y, Wang J, Zhou Y, et al. Evaluation of serum CEA, CA19-9, CA72-4, CA125 and ferritin as diagnostic markers and factors of clinical parameters for colorectal cancer. Sci Rep. 2018;8(1):2732.
  • 33. Tang W, Liu Y, Ji M, et al. Association of RAS/BRAF status and prognosis of metastatic colorectal cancer: analysis of 1002 consecutive cases. Ann Surg Oncol. 2022;29(6):3593-3603.
  • 34. Selcukbiricik F, Bilici A, Tural D, et al. Are high initial CEA and CA 19-9 levels associated with the presence of K-ras mutation in patients with metastatic colorectal cancer? Tumour Biol. 2013;34(4):2233-9.
  • 35. Sajid KM, Parveen R, Durr-e-S, et al. Carcinoembryonic antigen (CEA) levels in hookah smokers, cigarette smokers and non-smokers. J Pak Med Assoc. 2007;57(12):595-9.
  • 36. Shibata C, Nakano T, Yasumoto A, et al. Comparison of CEA and CA19-9 as a predictive factor for recurrence after curative gastrectomy in gastric cancer. BMC Surg. 2022;22(1):213.

INVESTIGATION OF CLINICAL PROPERTIES OF PATIENTS WITH METASTATIC COLORECTAL CANCER IN TERMS OF EGFR OR VEGF INHIBITORS USAGE

Yıl 2023, Cilt: 24 Sayı: 4, 466 - 474, 09.10.2023

Metin Deniz Karakoç Özden Özer

https://doi.org/10.18229/kocatepetip.1192194

Öz

OBJECTIVE: In this study, it was aimed to evaluate some clinical features in patients with metastatic colorectal cancer (mCRC) which have a high incidence, in terms of RAS (Rat Sarcoma Virus Gene) mutation status and monoclonal antibodies used in treatment.
MATERIAL AND METHODS: Our cross-sectional study was carried out as a retrospective archive review covering the period between 01.01.2014 and 01.01.2022 in an oncology center. The population of the study consisted of 187 patients who were diagnosed with mCRC, over 18 years of age and administered VEGF inhibitor (bevacizumab) or EGFR inhibitor (cetuximab / panitumumab) monoclonal antibody drugs during the treatment. Patient archive files and hospital information management automation system were used to collect data.
RESULTS: It was determined that the second highest metastasis organ was the peritoneum in RAS wild-type individuals, and the lung in mutant individuals, and the difference between them was statistically significant (p=0.003). It was detected that the serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels of individuals at the diagnosis stage were relatively lower in RAS wild-type patients than in mutant ones. The median survival was 36 months in the RAS wild group and 27 months in the mutant group (p=0.001).
CONCLUSIONS: In the study, it was determined that the presence of RAS mutation had a negative effect on overall survival. On the other hand, it was determined that there was no significant difference between monoclonal antibody drugs in terms of contribution to survival period. There is a need for multicenter and large-participation studies to reveal the relationship between RAS mutation frequency with tumor biomarkers and to contributions of treatment options to the survival in patients with mCRC more clearly in our country.

Anahtar Kelimeler

Bevacizumab Cetuximab Colorectal cancer RAS mutations Panitumumab.

Proje Numarası

-

Kaynakça

  • 1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-49.
  • 2. Van Cutsem E, Cervantes A, Nordlinger B, Arnold D; ESMO Guidelines Working Group. Metastatic colorectal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(3):1-9.
  • 3. Biller LH, Schrag D. Diagnosis and Treatment of Metastatic Colorectal Cancer: A Review. JAMA. 2021;325(7):669-85.
  • 4. Brenner H, Kloor M, Pox CP. Colorectal cancer. Lancet. 2014;383(9927):1490-1502.
  • 5. Kasi PM, Hubbard JM, Grothey A. Selection of biologics for patients with metastatic colorectal cancer: the role of predictive markers. Expert Rev Gastroenterol Hepatol. 2015;9(3):273-6.
  • 6. Pathak S, Sushmitha S, Banerjee A, et al. Review on comparative efficacy of bevacizumab, panitumumab and cetuximab antibody therapy with combination of FOLFOX-4 in KRAS-mutated colorectal cancer patients. Oncotarget. 2017;9(7):7739-48.
  • 7. Chen J, Wang J, Ni T, He H, Zheng Q. Meta-analysis on the risk of fatal adverse events by bevacizumab, cetuximab, and panitumumab in 31 randomized trials including 25,000 patients with colorectal carcinoma. Medicine (Baltimore). 2020;99(25):e19908.
  • 8. Van Cutsem E, Cervantes A, Adam R, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;27:1386–422.
  • 9. Modest DP, Pant S, Sartore-Bianchi A. Treatment sequencing in metastatic colorectal cancer. Eur J Cancer. 2019;109:70-83.
  • 10. Rui Y, Wang C, Zhou Z, Zhong X, Yu Y. K-Ras mutation and prognosis of colorectal cancer: a meta-analysis. Hepatogastroenterology. 2015;62(137):19-24.
  • 11. Heinemann V, Rivera F, O'Neil BH, et al. A study-level meta-analysis of efficacy data from head-to-head first-line trials of epidermal growth factor receptor inhibitors versus bevacizumab in patients with RAS wild-type metastatic colorectal cancer. Eur J Cancer. 2016;67:11-20.
  • 12. Zhou M, Yu P, Qu J, et al. Efficacy of bevacizumab in the first-line treatment of patients with RAS mutations metastatic colorectal cancer: a systematic review and network meta-analysis. Cell Physiol Biochem. 2016;40(1):361-69.
  • 13. Bonnot PE, Passot G. RAS mutation: site of disease and recurrence pattern in colorectal cancer. Chin Clin Oncol. 2019;8(5):55.
  • 14. Patelli G, Tosi F, Amatu A, et al. Strategies to tackle RAS-mutated metastatic colorectal cancer. ESMO Open. 2021;6(3):100156.
  • 15. Levi M, Prayogi G, Sastranagara F, et al. Clinicopathological associations of K-RAS and N-RAS mutations in Indonesian colorectal cancer cohort. J Gastrointest Cancer. 2018;49(2):124-31.
  • 16. Akman T, Oztop I, Baskin Y, et al. The association of clinicopathological features and survival in colorectal cancer patients with kras mutation status. J Cancer Res Ther. 2016;12(1):96-102.
  • 17. Sezen M, Araz M. Metastatik kolorektal kanserli hastaların RAS mutasyon durumuna göre klinik ve patolojik özellikleri. Uludağ Üniversitesi Tıp Fakültesi Dergisi. 2019;45(2):131-36.
  • 18. Ribeiro KB, Ribeiro KB, Feres O, et al. Clinical-pathological correlation of KRAS mutation status in metastatic colorectal adenocarcinoma. World J Oncol. 2013;4(4):179-87.
  • 19. Morris VK, Lucas FAS, Overman MJ, et al. Clinicopathologic characteristics and gene expression analyses of non-KRAS 12/13, RAS-mutated metastatic colorectal cancer. Ann Oncol. 2014;25(10):2008-14.
  • 20. Kawazoe A, Shitara K, Fukuoka S, et al. A retrospective observational study of clinicopathological features of KRAS, NRAS, BRAF and PIK3CA mutations in Japanese patients with metastatic colorectal cancer. BMC Cancer. 2015;15:258.
  • 21. Peeters M, Kafatos G, Taylor A, et al. Prevalence of RAS mutations and individual variation patterns among patients with metastatic colorectal cancer: a pooled analysis of randomised controlled trials. Eur J Cancer. 2015;51(13):1704-13.
  • 22. Phua LC, Ng HW, Yeo AH, et al. Prevalence of KRAS, BRAF, PI3K and EGFR mutations among Asian patients with metastatic colorectal cancer. Oncol Lett. 2015;10(4):2519-26.
  • 23. Philipovskiy A, Ghafouri R, Dwivedi AK, et al. Association between tumor mutation profile and clinical outcomes among hispanic-latino patients with metastatic colorectal cancer. Front Oncol. 2022;11:772225.
  • 24. Diergaarde B, Vrieling A, van Kraats AA, van Muijen GN, Kok FJ, Kampman E. Cigarette smoking and genetic alterations in sporadic colon carcinomas. Carcinogenesis. 2003;24(3):565-71.
  • 25. Porta M, Crous-Bou M, Wark PA, et al. Cigarette smoking and K-ras mutations in pancreas, lung and colorectal adenocarcinomas: etiopathogenic similarities, differences and paradoxes. Mutat Res. 2009;682(2):83-93.
  • 26. Aggarwal H, Sheffield KM, Li L, et al. Primary tumor location and survival in colorectal cancer: a retrospective cohort study. World J Gastrointest Oncol. 2020;12(4):405-23.
  • 27. Tejpar S, Stintzing S, Ciardiello F, et al. Prognostic and predictive relevance of primary tumor location in patients with RAS wild-type metastatic colorectal cancer: retrospective analyses of the CRYSTAL and FIRE-3 trials. JAMA Oncol. 2017;3(2):194-201.
  • 28. Widder J, Klinkenberg TJ, Ubbels JF, Wiegman EM, Groen HJ, Langendijk JA. Pulmonary oligometastases: metastasectomy or stereotactic ablative radiotherapy? Radiother Oncol. 2013;107(3):409-13.
  • 29. Kinj R, Bondiau PY, François E, et al. Radiosensitivity of colon and rectal lung oligometastasis treated with stereotactic ablative radiotherapy. Clin Colorectal Cancer. 2017;16(3):e211-e220.
  • 30. Parnaby CN, Bailey W, Balasingam A, et al. Pulmonary staging in colorectal cancer: a review. Colorectal Dis. 2012;14(6):660-70.
  • 31. Van der Geest LG, Lam-Boer J, Koopman M, et al. Nationwide trends in incidence, treatment and survival of colorectal cancer patients with synchronous metastases. Clin Exp Metastasis. 2015;32(5):457-65.
  • 32. Gao Y, Wang J, Zhou Y, et al. Evaluation of serum CEA, CA19-9, CA72-4, CA125 and ferritin as diagnostic markers and factors of clinical parameters for colorectal cancer. Sci Rep. 2018;8(1):2732.
  • 33. Tang W, Liu Y, Ji M, et al. Association of RAS/BRAF status and prognosis of metastatic colorectal cancer: analysis of 1002 consecutive cases. Ann Surg Oncol. 2022;29(6):3593-3603.
  • 34. Selcukbiricik F, Bilici A, Tural D, et al. Are high initial CEA and CA 19-9 levels associated with the presence of K-ras mutation in patients with metastatic colorectal cancer? Tumour Biol. 2013;34(4):2233-9.
  • 35. Sajid KM, Parveen R, Durr-e-S, et al. Carcinoembryonic antigen (CEA) levels in hookah smokers, cigarette smokers and non-smokers. J Pak Med Assoc. 2007;57(12):595-9.
  • 36. Shibata C, Nakano T, Yasumoto A, et al. Comparison of CEA and CA19-9 as a predictive factor for recurrence after curative gastrectomy in gastric cancer. BMC Surg. 2022;22(1):213.
Toplam 36 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Klinik Tıp Bilimleri
Bölüm Makaleler-Araştırma Yazıları
Yazarlar

Metin Deniz Karakoç 0000-0003-3188-8738

Özden Özer 0000-0002-8436-2177

Proje Numarası -
Yayımlanma Tarihi 9 Ekim 2023
Kabul Tarihi 8 Şubat 2023
Yayımlandığı Sayı Yıl 2023 Cilt: 24 Sayı: 4

Kaynak Göster

APA Karakoç, M. D., & Özer, Ö. (2023). METASTATİK KOLOREKTAL KANSERLİ HASTALARIN EGFR YA DA VEGF İNHİBİTÖRÜ KULLANIM DURUMLARINA GÖRE KLİNİK ÖZELLİKLERİNİN İNCELENMESİ. Kocatepe Tıp Dergisi, 24(4), 466-474. https://doi.org/10.18229/kocatepetip.1192194
AMA Karakoç MD, Özer Ö. METASTATİK KOLOREKTAL KANSERLİ HASTALARIN EGFR YA DA VEGF İNHİBİTÖRÜ KULLANIM DURUMLARINA GÖRE KLİNİK ÖZELLİKLERİNİN İNCELENMESİ. KTD. Ekim 2023;24(4):466-474. doi:10.18229/kocatepetip.1192194
Chicago Karakoç, Metin Deniz, ve Özden Özer. “METASTATİK KOLOREKTAL KANSERLİ HASTALARIN EGFR YA DA VEGF İNHİBİTÖRÜ KULLANIM DURUMLARINA GÖRE KLİNİK ÖZELLİKLERİNİN İNCELENMESİ”. Kocatepe Tıp Dergisi 24, sy. 4 (Ekim 2023): 466-74. https://doi.org/10.18229/kocatepetip.1192194.
EndNote Karakoç MD, Özer Ö (01 Ekim 2023) METASTATİK KOLOREKTAL KANSERLİ HASTALARIN EGFR YA DA VEGF İNHİBİTÖRÜ KULLANIM DURUMLARINA GÖRE KLİNİK ÖZELLİKLERİNİN İNCELENMESİ. Kocatepe Tıp Dergisi 24 4 466–474.
IEEE M. D. Karakoç ve Ö. Özer, “METASTATİK KOLOREKTAL KANSERLİ HASTALARIN EGFR YA DA VEGF İNHİBİTÖRÜ KULLANIM DURUMLARINA GÖRE KLİNİK ÖZELLİKLERİNİN İNCELENMESİ”, KTD, c. 24, sy. 4, ss. 466–474, 2023, doi: 10.18229/kocatepetip.1192194.
ISNAD Karakoç, Metin Deniz - Özer, Özden. “METASTATİK KOLOREKTAL KANSERLİ HASTALARIN EGFR YA DA VEGF İNHİBİTÖRÜ KULLANIM DURUMLARINA GÖRE KLİNİK ÖZELLİKLERİNİN İNCELENMESİ”. Kocatepe Tıp Dergisi 24/4 (Ekim 2023), 466-474. https://doi.org/10.18229/kocatepetip.1192194.
JAMA Karakoç MD, Özer Ö. METASTATİK KOLOREKTAL KANSERLİ HASTALARIN EGFR YA DA VEGF İNHİBİTÖRÜ KULLANIM DURUMLARINA GÖRE KLİNİK ÖZELLİKLERİNİN İNCELENMESİ. KTD. 2023;24:466–474.
MLA Karakoç, Metin Deniz ve Özden Özer. “METASTATİK KOLOREKTAL KANSERLİ HASTALARIN EGFR YA DA VEGF İNHİBİTÖRÜ KULLANIM DURUMLARINA GÖRE KLİNİK ÖZELLİKLERİNİN İNCELENMESİ”. Kocatepe Tıp Dergisi, c. 24, sy. 4, 2023, ss. 466-74, doi:10.18229/kocatepetip.1192194.
Vancouver Karakoç MD, Özer Ö. METASTATİK KOLOREKTAL KANSERLİ HASTALARIN EGFR YA DA VEGF İNHİBİTÖRÜ KULLANIM DURUMLARINA GÖRE KLİNİK ÖZELLİKLERİNİN İNCELENMESİ. KTD. 2023;24(4):466-74.
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