The effects of primary tumour location on patients with all stages of colorectal cancer

Abstract

Abstract:

Purpose:The aim of this study was to examine the effects of tumor localization in early and advanced stage colon cancer patients.

Materials and Methods :This retrospective study enrolled  249 primary colorectal cancer (CRC) patients at medical oncology department of Adnan Menderes University between 2013-2017.

Results:In early stage, left sided tumors were significantly more common in males(p=0.027). In right sided tumours recurrence developed earlier in female patients(p=0.043) and female sex,young age were unfavorable prognostic factors for the relapse time.  Positive and unknown PANRAS mutation status were found to be unfavorable prognostic factors for both side. In metastatic stage, patients with PANRAS mutant left sided tumors lived longer than PANRAS negative patients(49.0 vs 25.5 months respectively, p <0.001). OS was 11 months and PFS was 1.8 months longer with anti-EGFR agents than anti-VEGFR agents, in right sided tumors.In left sided tumors, there was no difference, only PFS was longer with anti-VEGFR agents(13 months vs 6.3 months). In PANRAS positive patients, OS and PFS were longer with anti-VEGFR treatment in the left side tumors(OS 49.0 months vs 30.6 months PFS, 13.2 months vs 7.2 months, p=0.784).

Conclusions: In our study, the efficacy results of the treatment which was given according to the primary tumor location were not compatible with the literature. Primer tumor location is a transition period for understanding of molecular subtypes at the colon cancer. The on-going studies of genomic differences between right and left sided tumors will able to better clarifying of the biologic explanation of the observed difference.

Keywords

• Colorectal cancer,tumour location,early stage,metastatic stage

Kolorektal kanserde primer tümör lokalizasyonunun tüm evrelerdeki etkileri

Abstract

Amaç: Bu çalışmanın amacı erken ve ileri evre kolon kanseri hastalarında tümör lokalizasyonunun etkilerini incelemektir.

Gereç ve Yöntem: 2013-2017 arasında Adnan Menderes Üniversitesi'nin tıbbi onkoloji bölümüne başvuran  primer kolorektal kanser tanılı hastaları retrospektif olarak taradık ve 249 hastayı çalışmaya dahil ettik.

Bulgular: Erken evrede, sol taraftaki kolorektal kanserler  erkeklerde anlamlı olarak daha yaygındı (p = 0.027). Sağ taraftaki tümörlerde nüks  kadın hastalarda daha erken gelişti (p = 0.043) ve kadın cinsiyet, genç yaş nüks süresi için bağımsız prognostik faktörlerdi. PANRAS pozitif ve bilinmeyen mutasyon durumunun her iki taraftaki tümörler için olumsuz prognostik faktörler olduğu bulundu.

Metastatik evrede, sol taraftaki tümörlerde PANRAS mutant olan hastalar daha uzun süre yaşadılar (sırasıyla 49.0'a 25.5 ay, p <0.001). Birinci basamak tedavide anti-EGFR ajanları alan sağ kolon kanseri hastalarında anti-VEGFR ajanları alanlara göre ortalama yaşam süresi(OS) 11 ay, progresyona kadar geçen süre(PFS) 1.8 ay daha uzundu. Sol kolon  tümörlerinde, ilk basamak tedavide fark yoktu yalnızca PFS anti-VEGFR ajanlarıyla daha uzundu (13 ay vs 6.3 ay ). PANRAS pozitif antiVEGFR tedavisi alan hastalar içinde sol kolon yerleşimli tümörlerde OS ve PFS daha uzundu (OS 49.0 ay - 30.6 ay PFS, 13.2 ay ve 7.2 ay, p = 0.784).

Sonuç: Çalışmamızda primer tümör lokasyonuna göre verilen tedavinin etkinlik sonuçları literatürle uyumlu değildi. Primer tümörün yeri, kolon kanserinde moleküler alt tiplerin anlaşılması için bir geçiş dönemidir. Sağ ve sol taraftaki tümörler arasında genomik farklılıkları araştıran çalışmalar, gözlenen farkın biyolojik açıklamasının daha iyi anlaşılmasını mümkün kılacaktır.

Keywords

• kolorektal kanser,tümör lokalizasyonu,erken evre,metastatik evre

References

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin 2018;68:7-30
2. Holch JW, Ricard I, Stintzing S, Modest DP, Heinemann V. The relevance of primary tumour location in patients with metastatic colorectal cancer: A meta-analysis of first-line clinical trials. Eur J Cancer. 2017 Jan;70:87-98.
3. Stintzing S, Tejpar S, Gibbs P, Thiebach L, Lenz HJ. Understanding the role of primary tumour localisation in colorectal cancer treatment and outcomes. Eur J Cancer. 2017 Oct;84:69-80.
4. Arnold D, Lueza B, Douillard JY, Peeters M, Lenz HJ, Venook A, Heinemann V, Van Cutsem E, Pignon JP, Tabernero J, Cervantes A, Ciardiello F. 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 Aug 1;28(8):1713-1729.
5. Loree JM, Pereira AAL, Lam M, Willauer AN, Raghav K, Dasari A, Morris VK, Advani S, Menter DG, Eng C, Shaw K, Broaddus R, Routbort MJ, Liu Y, Morris JS, Luthra R, Meric-Bernstam F, Overman MJ, Maru D, Kopetz S. Classifying Colorectal Cancer by Tumor Location Rather than Sidedness Highlights a Continuum in Mutation Profiles and Consensus Molecular Subtypes. Clin Cancer Res; 24(5) March 1, 2018
6. Kim ST, Lee SJ, Lee J, Park SH, Park JO, Lim HY, Kang WK, Park YS. The Impact of Microsatellite Instability Status and Sidedness of the Primary Tumor on the Effect of Cetuximab-Containing Chemotherapy in Patients with Metastatic Colorectal Cancer. J Cancer. 2017 Aug 23;8(14):2809-2815.
7. Weiss JM, Pfau PR, O'Connor ES, King J, LoConte N, Kennedy G, Smith MA. Mortality by stage for right- versus left-sided colon cancer: analysis of surveillance, epidemiology, and end results--Medicare data. J Clin Oncol. 2011 Nov 20;29(33):4401-9.
8. Sinicrope FA, Mahoney MR, Yoon HH, Smyrk TC, Thibodeau SN, Goldberg RM, et al. Analysis of molecular markers by anatomic tumor site in stage III colon carcinomas from adjuvant chemotherapy trial NCCTG N0147 (alliance). Clin Cancer Res 2015;21(23):5294e304.

9. Lim DR, Kuk JK, Kim T, Shin EJ. Comparison of oncological outcomes of right-sided colon cancer versus left-sided colon cancer after curative resection: Which side is better outcome? Medicine (Baltimore). 2017 Oct;96(42):e8241.
10. Qin Q, Yang L, Sun YK, Ying JM, Song Y, Zhang W, Wang JW, Zhou AP. Comparison of 627 patients with right- and left-sided colon cancer in China: Differences in clinicopathology, recurrence, and survival. Chronic Dis Transl Med. 2017 Mar 13;3(1):51-59.