Our data on detailing metastasis localization and subtype characteristics in metastatic colorectal cancer patients treated with Bevacizumab

Pınar Akdur; Nazan Çiledağ; Burcu Savran; Ayşe Ocak Duran

doi:10.32322/jhsm.1341618

Research Article

Our data on detailing metastasis localization and subtype characteristics in metastatic colorectal cancer patients treated with Bevacizumab

Year 2023, Volume: 6 Issue: 6, 1277 - 1284, 29.10.2023

Pınar Akdur Nazan Çiledağ Burcu Savran Ayşe Ocak Duran

https://doi.org/10.32322/jhsm.1341618

Abstract

Aims: Our aim in this study was to determine the relationship between metastasis types and mutation subtypes in patients who were followed up in our center and received bevacizumab treatment, to determine the survival rates according to metastasis types, and to contribute to the literature on this subject.
Methods: In our study, we retrospectively evaluated 42 consecutive metastatic colorectal cancer patients who were admitted to our hospital and diagnosed with colorectal cancer, thorax-abdominal CT scans were performed in our clinic to detect possible metastases, and the presence of metastases in one or more localizations was detected and treated with Bevacizumab.
Results: The majority of colorectal cancers included in our study had the histopathological subtype of adenocarcinoma (90.5%). Genetic analyses revealed that 47.6% (20 patients) had mutant KRAS gene types, while 52.4% (22 patients) had wild type. The distribution of metastases was as follows; 31 (73.8%) cases with liver involvement, 12 (28.6%) with peritoneal involvement and 24 (57.1%) with lung involvement. In our study, median overall survival was 19 months and median disease-free survival was 7 months.
Conclusion: The results of studies to date will be useful to help predict prognosis and to select appropriate regimens for treatment. We aimed to contribute to this process by presenting our own data in our own study. However, the true role of RAS genes as prognostic markers continues to be questioned, and multicenter studies are needed on the predictive and prognostic factors of colorectal cancers.

Keywords

colorectal cancer, Kras, metastasis, prognosis

References

Engstrand J, Nilsson H, Strömberg C, Jonas E, Freedman J. Colorectal cancer liver metastases-a population-based study on incidence, management and survival. BMC Cancer. 2018;18(1):78.
Done JZ, Fang HS. Young-onset colorectal cancer. World J Gastrointest Oncol. 2021;13(8):856-866.
He K, Wang Y, Zhong Y, Pan X, Si L, Lu J. KRAS codon 12 mutation is associated with more aggressive invasiveness in synchronous metastatic colorectal cancer (mCRC): retrospective research. Onco Targets Ther. 2020;13:12601-12613.
Gasser E, Braunwarth E, Riedmann M, et al. Primary tumour location affects survival after resection of colorectal liver metastases:A two-institutional cohort study with international validation, systematic meta-analysis and a clinical risk score. PLoS One. 2019;14(5):e0217411.
5.Yamashita S, Chun YS, Kopetz SE, Vauthey JN. Biomarkers in colorectal liver metastases. Br J Surg. 2018;105(6):618-627.
Dinu D, Dobre M, Panaitescu E, et al. Prognostic significance of KRAS gene mutations in colorectal cancer-preliminary study. J Med Life. 2014;7(4):581-587.
Franko J. Therapeutic efficacy of systemic therapy for colorectal peritoneal carcinomatosis: surgeon's perspective. Pleura Peritoneum. 2018;3(1):20180102.
Franko J, Shi Q, Meyers JP, et al. Prognosis of patients with peritoneal metastatic colorectal cancer given systemic therapy: an analysis of individual patient data from prospective randomised trials from the Analysis and Research in Cancers of the Digestive System (ARCAD) database. Lancet Oncol. 2016;17(12):1709-1719.
Kranenburg O, van der Speeten K, de Hingh I. Peritoneal metastases from colorectal cancer: defining and addressing the challenges. Front Oncol. 2021;11:650098.
Hugen N, van de Velde CJH, de Wilt JHW, Nagtegaal ID. Metastatic pattern in colorectal cancer is strongly influenced by histological subtype. Ann Oncol. 2014;25(3):651-657.
Sadeghi B, Arvieux C, Glehen O, et al. Peritoneal carcinomatosis from non-gynecologic malignancies: results of the EVOCAPE 1 multicentric prospective study. Cancer. 2000;88(2):358-363.
Nadler A, McCart JA, Govindarajan A. Peritoneal carcinomatosis from colon cancer: a systematic review of the data for cytoreduction and intraperitoneal chemotherapy. Clin Colon Rectal Surg. 2015;28(4):234-246.
Glockzin G, Zeman F, Croner RS, et al. Perioperative systemic chemotherapy, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy in patients with colorectal peritoneal metastasis: results of the prospective multicenter phase 2 COMBATAC trial. Clin Colorectal Cancer. 2018; 17(4):285-296.
Wang X, Liu Z, Yin X, Yang C, Zhang J. A radiomics model fusing clinical features to predict microsatellite status preoperatively in colorectal cancer liver metastasis. BMC Gastroenterol. 2023;23(1):308.
Valderrama-Treviño AI, Barrera-Mera B, Ceballos-Villalva JC, Montalvo-Javé EE. Hepatic metastasis from colorectal cancer. Euroasian J Hepatogastroenterol. 2017;7(2):166-175.
Kow AWC. Hepatic metastasis from colorectal cancer. J Gastrointest Oncol. 2019;10(6):1274-1298.
Heinemann V, von Weikersthal LF, Decker T, et al. FOLFIRI plus cetuximab or bevacizumab for advanced colorectal cancer:final survival and per-protocol analysis of FIRE-3, a randomised clinical trial. Br J Cancer. 2021;124(3):587-594.
Schubbert S, Shannon K, Bollag G. Hyperactive Ras in developmental disorders and cancer. Nat Rev Cancer. 2007;7(4): 295-308.
Malumbres M, Barbacid M. RAS oncogenes: the first 30 years.. Nat Rev Cancer. 2003;3(6):459-465.
Tanaka H, Deng G, Matsuzaki K, et al. BRAF mutation, CpG island methylator phenotype and microsatellite instability occur more frequently and concordantly in mucinous than non-mucinous colorectal cancer. Int J Cancer. 2006;118(11):2765-2771.
Koulouridi A, Karagianni M, Messaritakis I, et al. Prognostic value of KRAS mutations in colorectal cancer patients cancers (Basel). 2022;14(14):3320.
Lievre A, Bachet J, Le Corre D, et al. KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res. 2006;66(8):3992-3995.
Russo A, Bazan V, Agnese V, Rodolico V, Gebbia N. Prognostic and predictive factors in colorectal cancer: Kirsten Ras in CRC (RASCAL) and TP53CRC collaborative studies. Ann Oncol. 2005;16(Suppl 4):iv44-iv49.
Fariña-Sarasqueta A, an Lijnschoten G, Moerland E, et al. The BRAF V600E mutation is an independent prognostic factor for survival in stage II and stage III colon cancer patients. Ann Oncol. 2010;21(12):2396-2402.
Bennecke M, Kriegl L, Bajbouj M, et al. . Ink4a/Arf and oncogene-induced senescence prevent tumor progression during alternative colorectal tumorigenesis. Cancer Cell. 2010;18(2):135-146.
Guo T, Wu Y, Tan C, et al. Clinicopathologic features and prognostic value of KRAS, NRAS and BRAF mutations and DNA mismatch repair status: a single-center retrospective study of 1,834 Chinese patients with Stage I-IV colorectal cancer. Int J Cancer. 2019;145(6):1625-1634.
Lin YL, Liau JY, Yu SC, et al. KRAS mutation is a predictor of oxaliplatin sensitivity in colon cancer. Cells PLoS ONE. 2012;7(11):e50701.
Tol J, Nagtegaal ID, Punt CJ. BRAF mutation in metastatic colorectal cancer. N Engl J Med. 2009;361:98-99
Foltran L, Maglio GD, Pella N, et al. Prognostic role of KRAS, NRAS, BRAF and PIK3CA mutations in advanced colorectal cancer. Future Oncol. 2015;11(4):629-640.
Liu J, Zeng W, Huang C, Wang J, Yang D, Ma D. Predictive and prognostic implications of mutation profiling and microsatellite instability status in patients with metastatic colorectal carcinoma. Gastroenterol Res Pract. 2018;2018:4585802.
Alkader MS, Altaha RZ, Badwan SA, et al. Impact of KRAS mutation on survival outcome of patients with metastatic colorectal cancer in Jordan. Cureus. 2023;15(1):e33736.
Garcia-Carbonero N, Martinez-Useros J, Li W, et al. KRAS and BRAF mutations as prognostic and predictive biomarkers for standard chemotherapy response in metastatic colorectal cancer: a single institutional study. Cells. 2020;9(1):219.
Ucar G, Ergun Y, Aktürk Esen S, et al. Prognostic and predictive value of KRAS mutation number in metastatic colorectal. Cancer Med. 2020;99(39):e22407
Brudvik KW, Mise Y, Chung MH, et al. RAS mutation predicts positive resection margins and narrower resection margins in patients undergoing resection of colorectal liver metastases. Ann Surg Oncol. 2016;23(8):2635-2643.
Kawaguchi Y, Lillemoe HA, Panettieri E, et al. Conditional recurrence-free survival after resection of colorectal liver metastases: persistent deleterious association with RAS and TP53 co-mutation. J Am Coll Surg. 2019;229(3):286-294.
Zeineddine FA, Zeineddine MA, Yousef A, et al. Survival improvement for patients with metastatic colorectal cancer over twenty years. NPJ Precis Onc. 2023;7:16. https://doi.org/10.1038/s41698-023-00353-4

Year 2023, Volume: 6 Issue: 6, 1277 - 1284, 29.10.2023

Pınar Akdur Nazan Çiledağ Burcu Savran Ayşe Ocak Duran

https://doi.org/10.32322/jhsm.1341618

Abstract

Supporting Institution

yok

References

Engstrand J, Nilsson H, Strömberg C, Jonas E, Freedman J. Colorectal cancer liver metastases-a population-based study on incidence, management and survival. BMC Cancer. 2018;18(1):78.
Done JZ, Fang HS. Young-onset colorectal cancer. World J Gastrointest Oncol. 2021;13(8):856-866.
He K, Wang Y, Zhong Y, Pan X, Si L, Lu J. KRAS codon 12 mutation is associated with more aggressive invasiveness in synchronous metastatic colorectal cancer (mCRC): retrospective research. Onco Targets Ther. 2020;13:12601-12613.
Gasser E, Braunwarth E, Riedmann M, et al. Primary tumour location affects survival after resection of colorectal liver metastases:A two-institutional cohort study with international validation, systematic meta-analysis and a clinical risk score. PLoS One. 2019;14(5):e0217411.
5.Yamashita S, Chun YS, Kopetz SE, Vauthey JN. Biomarkers in colorectal liver metastases. Br J Surg. 2018;105(6):618-627.
Dinu D, Dobre M, Panaitescu E, et al. Prognostic significance of KRAS gene mutations in colorectal cancer-preliminary study. J Med Life. 2014;7(4):581-587.
Franko J. Therapeutic efficacy of systemic therapy for colorectal peritoneal carcinomatosis: surgeon's perspective. Pleura Peritoneum. 2018;3(1):20180102.
Franko J, Shi Q, Meyers JP, et al. Prognosis of patients with peritoneal metastatic colorectal cancer given systemic therapy: an analysis of individual patient data from prospective randomised trials from the Analysis and Research in Cancers of the Digestive System (ARCAD) database. Lancet Oncol. 2016;17(12):1709-1719.
Kranenburg O, van der Speeten K, de Hingh I. Peritoneal metastases from colorectal cancer: defining and addressing the challenges. Front Oncol. 2021;11:650098.
Hugen N, van de Velde CJH, de Wilt JHW, Nagtegaal ID. Metastatic pattern in colorectal cancer is strongly influenced by histological subtype. Ann Oncol. 2014;25(3):651-657.
Sadeghi B, Arvieux C, Glehen O, et al. Peritoneal carcinomatosis from non-gynecologic malignancies: results of the EVOCAPE 1 multicentric prospective study. Cancer. 2000;88(2):358-363.
Nadler A, McCart JA, Govindarajan A. Peritoneal carcinomatosis from colon cancer: a systematic review of the data for cytoreduction and intraperitoneal chemotherapy. Clin Colon Rectal Surg. 2015;28(4):234-246.
Glockzin G, Zeman F, Croner RS, et al. Perioperative systemic chemotherapy, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy in patients with colorectal peritoneal metastasis: results of the prospective multicenter phase 2 COMBATAC trial. Clin Colorectal Cancer. 2018; 17(4):285-296.
Wang X, Liu Z, Yin X, Yang C, Zhang J. A radiomics model fusing clinical features to predict microsatellite status preoperatively in colorectal cancer liver metastasis. BMC Gastroenterol. 2023;23(1):308.
Valderrama-Treviño AI, Barrera-Mera B, Ceballos-Villalva JC, Montalvo-Javé EE. Hepatic metastasis from colorectal cancer. Euroasian J Hepatogastroenterol. 2017;7(2):166-175.
Kow AWC. Hepatic metastasis from colorectal cancer. J Gastrointest Oncol. 2019;10(6):1274-1298.
Heinemann V, von Weikersthal LF, Decker T, et al. FOLFIRI plus cetuximab or bevacizumab for advanced colorectal cancer:final survival and per-protocol analysis of FIRE-3, a randomised clinical trial. Br J Cancer. 2021;124(3):587-594.
Schubbert S, Shannon K, Bollag G. Hyperactive Ras in developmental disorders and cancer. Nat Rev Cancer. 2007;7(4): 295-308.
Malumbres M, Barbacid M. RAS oncogenes: the first 30 years.. Nat Rev Cancer. 2003;3(6):459-465.
Tanaka H, Deng G, Matsuzaki K, et al. BRAF mutation, CpG island methylator phenotype and microsatellite instability occur more frequently and concordantly in mucinous than non-mucinous colorectal cancer. Int J Cancer. 2006;118(11):2765-2771.
Koulouridi A, Karagianni M, Messaritakis I, et al. Prognostic value of KRAS mutations in colorectal cancer patients cancers (Basel). 2022;14(14):3320.
Lievre A, Bachet J, Le Corre D, et al. KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res. 2006;66(8):3992-3995.
Russo A, Bazan V, Agnese V, Rodolico V, Gebbia N. Prognostic and predictive factors in colorectal cancer: Kirsten Ras in CRC (RASCAL) and TP53CRC collaborative studies. Ann Oncol. 2005;16(Suppl 4):iv44-iv49.
Fariña-Sarasqueta A, an Lijnschoten G, Moerland E, et al. The BRAF V600E mutation is an independent prognostic factor for survival in stage II and stage III colon cancer patients. Ann Oncol. 2010;21(12):2396-2402.
Bennecke M, Kriegl L, Bajbouj M, et al. . Ink4a/Arf and oncogene-induced senescence prevent tumor progression during alternative colorectal tumorigenesis. Cancer Cell. 2010;18(2):135-146.
Guo T, Wu Y, Tan C, et al. Clinicopathologic features and prognostic value of KRAS, NRAS and BRAF mutations and DNA mismatch repair status: a single-center retrospective study of 1,834 Chinese patients with Stage I-IV colorectal cancer. Int J Cancer. 2019;145(6):1625-1634.
Lin YL, Liau JY, Yu SC, et al. KRAS mutation is a predictor of oxaliplatin sensitivity in colon cancer. Cells PLoS ONE. 2012;7(11):e50701.
Tol J, Nagtegaal ID, Punt CJ. BRAF mutation in metastatic colorectal cancer. N Engl J Med. 2009;361:98-99
Foltran L, Maglio GD, Pella N, et al. Prognostic role of KRAS, NRAS, BRAF and PIK3CA mutations in advanced colorectal cancer. Future Oncol. 2015;11(4):629-640.
Liu J, Zeng W, Huang C, Wang J, Yang D, Ma D. Predictive and prognostic implications of mutation profiling and microsatellite instability status in patients with metastatic colorectal carcinoma. Gastroenterol Res Pract. 2018;2018:4585802.
Alkader MS, Altaha RZ, Badwan SA, et al. Impact of KRAS mutation on survival outcome of patients with metastatic colorectal cancer in Jordan. Cureus. 2023;15(1):e33736.
Garcia-Carbonero N, Martinez-Useros J, Li W, et al. KRAS and BRAF mutations as prognostic and predictive biomarkers for standard chemotherapy response in metastatic colorectal cancer: a single institutional study. Cells. 2020;9(1):219.
Ucar G, Ergun Y, Aktürk Esen S, et al. Prognostic and predictive value of KRAS mutation number in metastatic colorectal. Cancer Med. 2020;99(39):e22407
Brudvik KW, Mise Y, Chung MH, et al. RAS mutation predicts positive resection margins and narrower resection margins in patients undergoing resection of colorectal liver metastases. Ann Surg Oncol. 2016;23(8):2635-2643.
Kawaguchi Y, Lillemoe HA, Panettieri E, et al. Conditional recurrence-free survival after resection of colorectal liver metastases: persistent deleterious association with RAS and TP53 co-mutation. J Am Coll Surg. 2019;229(3):286-294.
Zeineddine FA, Zeineddine MA, Yousef A, et al. Survival improvement for patients with metastatic colorectal cancer over twenty years. NPJ Precis Onc. 2023;7:16. https://doi.org/10.1038/s41698-023-00353-4

There are 36 citations in total.

Details

Primary Language	English
Subjects	Radiology and Organ Imaging
Journal Section	Original Article
Authors	Pınar Akdur 0000-0003-0246-5912 Nazan Çiledağ 0000-0002-4621-0893 Burcu Savran 0000-0003-0150-8618 Ayşe Ocak Duran 0000-0002-1703-726X
Early Pub Date	October 28, 2023
Publication Date	October 29, 2023
Published in Issue	Year 2023 Volume: 6 Issue: 6

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AMA	Akdur P, Çiledağ N, Savran B, Ocak Duran A. Our data on detailing metastasis localization and subtype characteristics in metastatic colorectal cancer patients treated with Bevacizumab. J Health Sci Med / JHSM. October 2023;6(6):1277-1284. doi:10.32322/jhsm.1341618

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