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KRAS mutation is predictive for poor prognosis in rectal cancer patients with neoadjuvant chemoradiotherapy: a systemic review and meta-analysis

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

To investigate the association between KRAS mutation and prognosis in rectal cancer patients with neoadjuvant chemoradiotherapy.

Methods

Literature was searched in the databases including Cochrane Library, EMBASE (Ovid), and MEDLINE (PubMed) from inception to December 16, 2020. The keywords “rectal cancer” or “rectal carcinoma” or “rectal adenocarcinoma” and “KRAS” and “neoadjuvant” were used for preliminary literature retrieval. Pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated for the KRAS mutation and clinical outcomes including overall survival (OS), disease-free survival (DFS), pathologic complete remission (pCR), downstaging of T stages and tumor stages, as well as improvements in tumor regression grading (TRG). Publication bias was assessed by the funnel plots.

Results

A total of 16 articles were included for eligibility. The total number of patients was 3674 cases, with an incidence of KRAS gene mutation of 36.6% (1346/3674). Meta-analysis showed that the pooled OR for KRAS mutation on OS was 1.33 (95%CI: 113–1.56). Consistently, results also indicated that the KRAS mutant was related to the poor DFS (pooled OR=1.55, 95%CI: 1.19–2.02). However, KRAS mutation is not related to the PCR (pooled OR= 0.71, 95%CI: 0.44–1.14), downstaging in T stages (pooled OR= 0.66, 95%CI: 0.42–1.06), tumor stages (pooled OR= 1.18, 95%CI: 0.78–1.78, I2=12.9%), as well as improvement in TRG grades (pooled OR= 0.84, 95%CI: 0.59–1.20).

Conclusion

KRAS mutation is a predictor for the poor prognosis of neoadjuvant chemoradiotherapy in patients with rectal cancer, but it is not related to the responses of tumors after treatment.

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Author information

Authors and Affiliations

  1. Department of TCM Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China

    Junfu Peng

  2. Department of TCM, Aviation General Hospital, Beijing, China

    Jun Lv

  3. Department of TCM Gastroenterology, The Third Affiliated Hospital of Beijing University of Chinese Medicine, No. 51 Anwai Xiaoguan Street, Chaoyang District, Beijing, 100029, China

    Jisheng Peng

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Correspondence to Jisheng Peng.

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Supplementary information

Supplementary Fig. 1

Funnel plot for the evaluation of publication bias of studies exploring the association between KRAS mutation and overall survival (PNG 64 kb)

High resolution image (TIF 3377 kb)

Supplementary Fig. 2

Begg’s test for the evaluation of publication bias of studies exploring the association between KRAS mutation and pathologic complete remission (PNG 38 kb)

High resolution image (TIF 3689 kb)

Supplementary Fig. 3

Egger’s test for the evaluation of publication bias of studies exploring the association between KRAS mutation and pathologic complete remission (PNG 27 kb)

High resolution image (TIF 3689 kb)

Supplementary Fig. 4

Funnel plot for the evaluation of publication bias of studies exploring the association between KRAS mutation and pathologic complete remission (PNG 66 kb)

High resolution image (TIF 3377 kb)

Supplementary Fig. 1

Forest plots of the odds ratios of KRAS mutation to the pathologic complete remission after excluding two studies with inclusion of patients receiving cetuximab (PNG 113 kb)

High resolution image (TIF 3420 kb)

Supplementary Table 1

(DOCX 19 kb)

Supplementary Table 2

(DOCX 17 kb)

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Peng, J., Lv, J. & Peng, J. KRAS mutation is predictive for poor prognosis in rectal cancer patients with neoadjuvant chemoradiotherapy: a systemic review and meta-analysis. Int J Colorectal Dis 36, 1781–1790 (2021). https://doi.org/10.1007/s00384-021-03911-z

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