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Clinical and Pathological Properties of Patients with Metastatic Colorectal Cancer According to the RAS Mutation Status

Yıl 2019, Cilt: 45 Sayı: 2, 131 - 136, 01.08.2019
https://doi.org/10.32708/uutfd.524758

Öz

We
aimed to compare the clinical and histopathologic features at the time of
diagnosis of patients with metastatic colorectal cancer according to the RAS
mutation status. In this
cross-sectional study, archive records of patients with diagnosing colorectal
cancer who were followed-up and treated at oncology center of an university
hospital in Turkey between 01.04.2012 and 24.08.2017  was analyzed retrospectively. A totally 530
patients' archive records were evaluated. The relationship between the RAS
mutant/wild groups and primary tumor localization, location of metastases at
diagnosis, tumor markers, tumor differentiation grade and overall survival
rates were compared with the literature data.
We
found no statistically significant difference between RAS mutant and wild
groups. When overall survival rates were compared with the RAS mutation status,
the overall survival of 2 years in patients with RAS wild type was 59% while
the 2 year overall survival of RAS mutant patients was 27.8% and this
difference was statistically significant (p = 0.004). However, there was no
statistically significant difference between the median survival of patients
receiving bevacizumab or cetuksimab/panitumumab in th efirst line treatment of
RAS wild patients (57.1% versus 70.7%; p=0.221, respectively).
In
this study, we determined that RAS mutation status of our patients with
metastatic colorectal cancer is more similar to Western countries and the
clinical and pathological characteristics of patients at the time of diagnosis
are independent of RAS mutation status. However, there is still need broader
participation and prospective trials in this subject.

Kaynakça

  • Referans 1. Zeng M, Kikuchi H, Pino MS, Chung DC. Hypoxia activates the K-ras proto-oncogene to stimulate angiogenesis and inhibit apoptosis in colon cancer cells. PLoS One 2010;5(6). e10966.
  • Referans 2. Jiang Y, Mackley H, Cheng H, Ajani JA. Use of K-Ras as a predictive biomarker for selecting anti-EGF receptor/pathway treatment. Biomark Med 2010 Aug; 4(4): 535-41.
  • Referans 3. Kim D, Hong YS, Kim JE, et al. Use of a high-throughput genotyping platform (OncoMap) for RAS mutational analysis to predict cetuximab efficacy in patients with metastatic colorectal cancer. Cancer Res Treat 2017;49(1):37–43.
  • Referans 4. Douillard J-Y, Oliner KS, Siena S, et al. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med 2013;369(11):1023–1034.
  • Referans 5. 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.
  • Referans 6. Levi M, Prayogi G, Sastranagara F, et al.ClinicopathologicalAssociations of K-RAS and N-RAS Mutations in Indonesian Colorectal Cancer Cohort. J Gastrointest Cancer 2017;1–8.
  • Referans 7. Zekri J, Karim SM, Al-Shehri A, Mahrous M, Darwish T, El Taani H. Frequency and clinical impact of KRAS mutations in patients with colorectal cancer from the middle east. J Anal Oncol 2016;5(2):67–74.
  • Referans 8. Ribeiro KB, Feres O, Ribeiro da Rocha JJ, et al.Clinical-pathological correlation of KRAS mutation status in metastatic colorectal adenocarcinoma. World J Oncol 2013;4(4–5):179–187.
  • Referans 9. 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):2008–2014.
  • Referans 10. Phua LC, Ng HW, Yeo AHL, et al. Prevalence of KRAS, BRAF, PI3K and EGFR mutations among Asian patients with metastatic colorectal cancer. Oncol Lett 2015;10(4):2519–2526.
  • Referans 11.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. BioMed Cent Cancer 2015;15:258.
  • Referans 12.Koochak A, Rakhshani N, Karbalaie Niya MH, et al. Mutation Analysis of KRAS and BRAF Genes in Metastatic Colorectal Cancer: a First Large Scale Study from Iran. Asian Pac J Cancer Prev 2016;17(2):603–608.
  • Referans 13.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.
  • Referans 14. Heinemann V, Weikersthal LF Von, Decker T, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): A randomised, open-label, phase 3 trial. LancetOncol 2014;15(10):1065–1075.
  • Referans 15. Venook AP, Niedzwiecki D, Lenz H-J, et al. Metastatic adenocarcinoma of the colon or re CALGB/SWOG 80405: Phase III trial of irinotecan/5-FU/leucovorin (FOLFIRI) oroxaliplatin/5-FU/leucovorin (mFOLFOX6) with bevacizumab (BV) or cetuximab (CET) for patients (pts) with KRAS wild-type (wt) untreated. J Clin Oncol 2014 :20; 32(15_suppl): LBA3-LBA3.
  • Referans 16. 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. In: JAMA Oncology 2017;194–201.

Metastatik Kolorektal Kanserli Hastaların RAS Mutasyon Durumuna Göre Klinik ve Patolojik Özellikleri

Yıl 2019, Cilt: 45 Sayı: 2, 131 - 136, 01.08.2019
https://doi.org/10.32708/uutfd.524758

Öz

Bu çalışmada metastatik kolorektal
kanserli hastalarda tanı anındaki histopatolojik ve klinik özelliklerin RAS
mutasyon durumuna göre karşılaştırılması amaçlandı. Bu kesitsel çalışma için, 01.04.2012-24.08.2017 tarihleri arasında
bir üniversite hastanesinin onkoloji merkezinde takip ve tedavisi yapılmış
toplam 530 kolorektal kanser tanısı almış hastanın dosyası retrospektif olarak
incelendi. Çalışmaya 18 yaşından büyük, tanı anında metastatik hastalığa sahip
veya takipleri boyunca metastaz gelişen ve RAS mutasyonu bakılmış 75 hasta
dahil edildi. Rasmutant olan ve olmayan hastaların tümör lokalizasyonu, tanı
anındaki metastaz yerleri, tümör belirteçleri, tümör diferansiyasyon derecesi
ve genel sağkalım süreleri arasındaki farklılıklar analiz edildi. RAS mutasyonu
sıklığı %50.7 olarak saptandı.
Klinik ve patolojik özellikler açısından
bakıldığında RAS mutant ve wild gruplar arasında istatistiksel anlamı farklılık
saptamadık. RAS mutasyon durumuna göre genel sağkalım süreleri incelendiğinde,
RAS wild tip olan hastaların 2 yıllık genel sağkalımı% 59 iken, RAS mutant
hastalarımızın 2 yıllık genel sağkalımı %27.8 idi ve bu fark istatiksel olarak
anlamlıydı (p=0.004). Ancak, RAS wild hastaların ilk hat tedavisinde
bevacizumab veya cetuksimab/panitumumab alan hastaların ortalama sağkalımları
arasında (sırasıyla %57.1'e karşı %70.7; p=0.221) istatistiksel fark
saptanmadı. Bu çalışmada, metastatik
kolorektal kanserli hastalarımızın RAS mutasyon durumunun daha ziyade Batılı
ülkelere benzer olduğunu ve hastaların tanı anındaki klinik ve patolojik
özelliklerinin RAS mutasyon durumundan bağımsız olduğunu saptadık. Ancak bu
konuda yapılacak prospektif ve daha geniş katılımlı çalışmalara hala ihtiyaç
duyulmaktadır.

Kaynakça

  • Referans 1. Zeng M, Kikuchi H, Pino MS, Chung DC. Hypoxia activates the K-ras proto-oncogene to stimulate angiogenesis and inhibit apoptosis in colon cancer cells. PLoS One 2010;5(6). e10966.
  • Referans 2. Jiang Y, Mackley H, Cheng H, Ajani JA. Use of K-Ras as a predictive biomarker for selecting anti-EGF receptor/pathway treatment. Biomark Med 2010 Aug; 4(4): 535-41.
  • Referans 3. Kim D, Hong YS, Kim JE, et al. Use of a high-throughput genotyping platform (OncoMap) for RAS mutational analysis to predict cetuximab efficacy in patients with metastatic colorectal cancer. Cancer Res Treat 2017;49(1):37–43.
  • Referans 4. Douillard J-Y, Oliner KS, Siena S, et al. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med 2013;369(11):1023–1034.
  • Referans 5. 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.
  • Referans 6. Levi M, Prayogi G, Sastranagara F, et al.ClinicopathologicalAssociations of K-RAS and N-RAS Mutations in Indonesian Colorectal Cancer Cohort. J Gastrointest Cancer 2017;1–8.
  • Referans 7. Zekri J, Karim SM, Al-Shehri A, Mahrous M, Darwish T, El Taani H. Frequency and clinical impact of KRAS mutations in patients with colorectal cancer from the middle east. J Anal Oncol 2016;5(2):67–74.
  • Referans 8. Ribeiro KB, Feres O, Ribeiro da Rocha JJ, et al.Clinical-pathological correlation of KRAS mutation status in metastatic colorectal adenocarcinoma. World J Oncol 2013;4(4–5):179–187.
  • Referans 9. 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):2008–2014.
  • Referans 10. Phua LC, Ng HW, Yeo AHL, et al. Prevalence of KRAS, BRAF, PI3K and EGFR mutations among Asian patients with metastatic colorectal cancer. Oncol Lett 2015;10(4):2519–2526.
  • Referans 11.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. BioMed Cent Cancer 2015;15:258.
  • Referans 12.Koochak A, Rakhshani N, Karbalaie Niya MH, et al. Mutation Analysis of KRAS and BRAF Genes in Metastatic Colorectal Cancer: a First Large Scale Study from Iran. Asian Pac J Cancer Prev 2016;17(2):603–608.
  • Referans 13.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.
  • Referans 14. Heinemann V, Weikersthal LF Von, Decker T, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): A randomised, open-label, phase 3 trial. LancetOncol 2014;15(10):1065–1075.
  • Referans 15. Venook AP, Niedzwiecki D, Lenz H-J, et al. Metastatic adenocarcinoma of the colon or re CALGB/SWOG 80405: Phase III trial of irinotecan/5-FU/leucovorin (FOLFIRI) oroxaliplatin/5-FU/leucovorin (mFOLFOX6) with bevacizumab (BV) or cetuximab (CET) for patients (pts) with KRAS wild-type (wt) untreated. J Clin Oncol 2014 :20; 32(15_suppl): LBA3-LBA3.
  • Referans 16. 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. In: JAMA Oncology 2017;194–201.
Toplam 16 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Onkoloji ve Karsinogenez
Bölüm Özgün Araştırma Makaleleri
Yazarlar

Mehmet Sezen 0000-0001-5796-6445

Murat Araz 0000-0002-4632-9501

Yayımlanma Tarihi 1 Ağustos 2019
Kabul Tarihi 8 Nisan 2019
Yayımlandığı Sayı Yıl 2019 Cilt: 45 Sayı: 2

Kaynak Göster

APA Sezen, M., & Araz, M. (2019). Metastatik Kolorektal Kanserli Hastaların RAS Mutasyon Durumuna Göre Klinik ve Patolojik Özellikleri. Uludağ Üniversitesi Tıp Fakültesi Dergisi, 45(2), 131-136. https://doi.org/10.32708/uutfd.524758
AMA Sezen M, Araz M. Metastatik Kolorektal Kanserli Hastaların RAS Mutasyon Durumuna Göre Klinik ve Patolojik Özellikleri. Uludağ Tıp Derg. Ağustos 2019;45(2):131-136. doi:10.32708/uutfd.524758
Chicago Sezen, Mehmet, ve Murat Araz. “Metastatik Kolorektal Kanserli Hastaların RAS Mutasyon Durumuna Göre Klinik Ve Patolojik Özellikleri”. Uludağ Üniversitesi Tıp Fakültesi Dergisi 45, sy. 2 (Ağustos 2019): 131-36. https://doi.org/10.32708/uutfd.524758.
EndNote Sezen M, Araz M (01 Ağustos 2019) Metastatik Kolorektal Kanserli Hastaların RAS Mutasyon Durumuna Göre Klinik ve Patolojik Özellikleri. Uludağ Üniversitesi Tıp Fakültesi Dergisi 45 2 131–136.
IEEE M. Sezen ve M. Araz, “Metastatik Kolorektal Kanserli Hastaların RAS Mutasyon Durumuna Göre Klinik ve Patolojik Özellikleri”, Uludağ Tıp Derg, c. 45, sy. 2, ss. 131–136, 2019, doi: 10.32708/uutfd.524758.
ISNAD Sezen, Mehmet - Araz, Murat. “Metastatik Kolorektal Kanserli Hastaların RAS Mutasyon Durumuna Göre Klinik Ve Patolojik Özellikleri”. Uludağ Üniversitesi Tıp Fakültesi Dergisi 45/2 (Ağustos 2019), 131-136. https://doi.org/10.32708/uutfd.524758.
JAMA Sezen M, Araz M. Metastatik Kolorektal Kanserli Hastaların RAS Mutasyon Durumuna Göre Klinik ve Patolojik Özellikleri. Uludağ Tıp Derg. 2019;45:131–136.
MLA Sezen, Mehmet ve Murat Araz. “Metastatik Kolorektal Kanserli Hastaların RAS Mutasyon Durumuna Göre Klinik Ve Patolojik Özellikleri”. Uludağ Üniversitesi Tıp Fakültesi Dergisi, c. 45, sy. 2, 2019, ss. 131-6, doi:10.32708/uutfd.524758.
Vancouver Sezen M, Araz M. Metastatik Kolorektal Kanserli Hastaların RAS Mutasyon Durumuna Göre Klinik ve Patolojik Özellikleri. Uludağ Tıp Derg. 2019;45(2):131-6.

ISSN: 1300-414X, e-ISSN: 2645-9027

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