Clinical features and KRAS mutation in colorectal cancer with bone metastasis

Hyung Soon Park,Joong Bae Ahn,Sang Joon Shin,Jee Hung Kim,Han Sang Kim,You Jin Chun,Seung-Hoon Beom,Choong-Kun Lee

doi:10.1038/s41598-020-78253-x

Abstract

Bone metastasis is known as a poor prognostic factor in colorectal cancer (CRC), but its clinical manifestations and outcomes are uncertain. CRC with bone metastasis was searched from January 2006 to April 2016. Of 11,551 CRC patients, 321 (2.7%) patients had bone metastasis. Bone-only metastasis was found in only 8.7% of patients. Synchronous bone metastasis was present in 147 (45.8%) patients. In patients with metachronous bone metastasis, the median time from CRC diagnosis to bone metastasis (TTB) was 27.2 months. KRAS mutation status was a marginally significant factor affecting TTB (median TTB, KRAS wild-type or mutation: 29 or 25.8 months, respectively, P = 0.068). Skeletal-related events (SREs) were noted in 200 (62.3%) patients. Median overall survival (OS) from diagnosis of bone metastasis was 8.0 months. On multivariate analysis, multi-organ metastasis, peritoneal metastasis, neutrophil-to-lymphocyte ratio (NLR) ≥ 2.7, and alkaline phosphatase (ALP) ≥ 123 were independent factors for OS. Palliative chemotherapy prolonged survival in CRC patients with bone metastasis (HR 0.25, 95% CI 0.2–0.33). In conclusion, bone metastasis of CRC is rare, but it is related to SREs. Most patients have other organ metastasis and survival is 8.0 months. Attention should be paid to bone metastasis in CRC patients.

Highlights

Colorectal cancer (CRC) was the fourth most common cancer in the United States, with a total of 101,420 cases of newly diagnosed colorectal cancer (CRC) in 20191
The aim of this study was to explore the clinical features of CRC patients with bone metastasis, including time to bone metastasis (TTB), metastatic sites of bone, and skeletal-related events (SREs) by KRAS mutation status
Bone metastasis of CRC is rare, but it is related to SREs

Summary

Introduction

Colorectal cancer (CRC) was the fourth most common cancer in the United States, with a total of 101,420 cases of newly diagnosed CRC in 20191. The most common metastatic sites were liver (70%) and lung (37%)[2]. Previous studies have reported that multiple bone metastases, lung metastasis, and elevated carcinoembryonic antigen (CEA) are poor prognostic factors in CRC patients. These factors have not been universally observed in previous reports. Associations between KRAS mutations and bone metastases have not been reported yet. The aim of this study was to explore the clinical features of CRC patients with bone metastasis, including time to bone metastasis (TTB), metastatic sites of bone, and skeletal-related events (SREs) by KRAS mutation status. Prognostic factors for CRC with bone metastasis were evaluated, and a prognostic model for survival was suggested. Palliative CTx (Median, range) Male Female Colon Rectum Left side Right side Synchronous Metachronous Adenocarcinoma SRC Mucinous carcinoma 1 or 2 3 4 Yes No

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