Prognostic importance of primary tumor location in RAS mutant metastatic colorectal cancer

Year 2019, Volume: 46 Issue: 2, 247 - 253, 11.06.2019

Nadiye Akdeniz , Muhammet Ali Kaplan Mehmet Küçüköner Zuhat Urakçı Yasin Sezgin Senar Ebinç Erkan Bilen Oğur Karhan Şahin Laçin Hüseyin Büyükbayram Abdurrahman Işıkdoğan

https://doi.org/10.5798/dicletip.539998

Cited By: 1

Abstract

Objective:
The prognostic value of tumor location in patients with metastatic colorectal
cancer (mCRC) was reported by recent analyses in RAS wild-type patients.
However, there is no enough specific data regarding prognostic value of primary
tumor location in RAS mutated mCRC patients. We aimed to find if there is any
relation between tumor prognosis and primary tumor location in patients with
RAS mutated mCRC.

Method: This
retrospective study included 57 patients with mCRC who were diagnosed and
treated in our hospital between January 2011 and December 2017. Characteristics
features of the patients were obtained from our institution patient medical
records. Patients were included to the present study if KRAS or NRAS mutation
was detected in tumor tissues.

Results: Twenty-nine
(50.9%) of patients were female and the median age of all patients was 52
(18-80) years. Forty (70.2%) of 57 patients were defined as left side (LS) and
17 (29.8%) of patients were located in the right side (RS). As first line
systemic treatment, twenty-five (43.9%) patients had received oxaliplatin-based
chemotherapy while 32 (56.1%) patients had received irinotecan-based
chemotherapy. Tumor sidedness did not affect on PFS (mPFS, 10.9 months for LS
vs 8.1 months for RS, p=0.400) and OS (mOS, 20.9 months for LS vs 20.8 months
for RS, p=0.930).The patients who had oxaliplatin based chemotherapy regimens
showed better OS rate than irinotecan based regimens (28.7months vs16.3 months,
p=0.017, respectively).

Conclusion:
Our study results support the thought that claims the sidedness of primary CRC
in metastatic setting does not have effect on PFS and OS in patients with RAS
mutant mCRC. However, our findings also underline the necessity of studies with
larger patient populations and subgroup analyzes to evaluate potential
prognostic and molecular features to determine the standart approach to this
specific subgroup of the disease.

Keywords

Colorectal cancer, tumor location, RAS mutation

References

• 1. Ferlay J, Soerjomataram I, Dikshit R, et all. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015; 136: 359–86.
• 2. Guinney J, Dienstmann R, Wang X,et all. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015; 21: 1350–6.
• 3. Auclin E, Zaanan A, Vernerey D,et all. Subgroups and prognostication in stage III colon cancer: future perspectives for adjuvant therapy. Ann Oncol Off JEur Soc Med Oncol. 2017; 28: 958–68.
• 4. Lie`vre A, Bachet J-B, Boige V, et all. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol Off J Am Soc Clin Oncol. 2008; 26: 374–9.
• 5. Rothberg PG, Spandorfer JM, Erisman MD, et all. Evidence that c-myc expression defines two genetically distinct forms of colorectal adenocarcinoma. Br J Cancer. 1985; 52: 629–32.
• 6. Meza R, Jeon J, Renehan AG, Luebeck EG. Colorectal cancer incidence trends in the United States and United Kingdom: evidence of right- to left-sided biological gradients with implications for screening. Cancer Res 2010; 70: 5419–29.
• 7. Van Cutsem E, Cervantes A, Adam R et all. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol 2016; 27: 1386–1422.
• 8. Venook AP, Niedzwiecki D, Innocenti F, et al. Impact of primary (1°) tumor location on overall survival (OS) and progression-free survival (PFS) in patients (pts) with metastatic colorectal cancer (mCRC): analysis of CALGB/SWOG 80405 (Alliance). J Clin Oncol. 2016; 34: 3504.
• 9. Tejpar S, Stinzing S, Ciardello F, et all. 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. 2016
• 10. Boeckx N, Koukakis R, Op de Beeck K, et all. Primary tumor sidedness has an impact on prognosis and treatment outcome in metastatic colorectal cancer: results from two randomized first-line panitumumab studies. Ann Oncol. 2017; 28: 1862–68.
• 11. Missiaglia E, Jacobs B, D’Ario G et all. Distal and proximal colon cancers differ in terms of molecular, pathological, and clinical features. Ann Oncol 2014; 25: 1995–2001.
• 12. Loupakis F, Schirripa M, Intini R, et all. Another Chapter of the Right Versus Left Story: Is Primary Tumor Location a Prognostic Feature in RAS Mutant Metastatic Colorectal Cancer?.Oncologist. 2018; 3: 1-3.
• 13. Rimbert J, Tachon G, Junca A, et all. Association between clinicopathological characteristics and RAS mutation in colorectal cancer.Mod Pathol. 2018 Mar; 31: 517-26.
• 14. Colucci G, Gebbia V, Paoletti G, et all. Phase III randomized trial of FOLFIRI versus FOLFOX4 in the treatment of advanced colorectal cancer: a multicenter study of the Gruppo Oncologico Dell'Italia Meridionale. J Clin Oncol 2005; 23: 4866-75.
• 15. Cabart M, Frénel JS, Campion L, et all. KRAS mutation does not influence oxaliplatin or irinotecan efficacy, in association with bevacizumab, in first line treatment of metastatic colorectal cancer.Bull Cancer. 2016 Jun; 103: 541-51.