Association of tumor genomic factors and efficacy for metastasis-directed stereotactic body radiotherapy for oligometastatic colorectal cancer

Krishan R. Jethwa, Samuel Jang, Trey C. Mullikin, William S. Harmsen, Molly M. Petersen, Kenneth R. Olivier, Sean S. Park, Michelle A. Neben-Wittich, Joleen M. Hubbard, Harigopal Sandhyavenu, Thomas J. Whitaker, Lindsey A. Waltman, Benjamin R. Kipp, Kenneth W. Merrell, Michael G. Haddock, Christopher L. Hallemeier

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Purpose/objective(s): To report tumor genomic factors associated with overall survival (OS) and local failure (LF) for patients with colorectal cancer (CRC) who received metastasis-directed stereotactic body radiation therapy (SBRT). Materials/methods: This was a retrospective review of patients with CRC who received metastasis-directed SBRT. Tumor genomic alterations were identified through KRAS, BRAF, or a 50-gene next generation sequencing panel. OS and LF were estimated using Kaplan-Meier and competing-risk methods. Results: Eighty-five patients and 109 lesions were treated between 2008 and 2018. The median patient follow-up was 50 months (IQR: 28–107). The median and 5-year OS was 34 months and 26% (95% CI: 16–41%), respectively. The 2-year cumulative incidence of LF was 30% (95% CI: 23–41%). Univariate associates with OS included patient age ≥60 years, bone metastasis, increasing tumor size, KRAS mutation, and combined KRAS and TP53 mutation, while increasing tumor size, bone metastasis, biologically effective dose <100 Gy, and combined KRAS and TP53 mutation were associated with LF. Multivariate associates with OS included patient age ≥60 years (HR: 2.4, 95% CI: 1.2–4.8, p = 0.01), lesion size per 1 cm (HR: 1.3, 95% CI: 1.1–1.5, p < 0.01), and KRAS mutation (HR: 2.2, 95% CI: 1.2–4.3, p < 0.01), while no multivariable model for LF retained more than a single variable. Conclusion: Genomic factors, in particular KRAS and TP53 mutation, may assist in patient selection and radiotherapeutic decision-making for patients with oligometastatic CRC. Prospective validation, ideally with genomic correlation of all irradiated metastases, is warranted.

Original languageEnglish (US)
Pages (from-to)29-36
Number of pages8
JournalRadiotherapy and Oncology
Volume146
DOIs
StatePublished - May 2020

Keywords

  • Colorectal cancer
  • KRAS
  • Oligometastasis
  • Radiotherapy
  • TP53

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Radiology Nuclear Medicine and imaging

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    Jethwa, K. R., Jang, S., Mullikin, T. C., Harmsen, W. S., Petersen, M. M., Olivier, K. R., Park, S. S., Neben-Wittich, M. A., Hubbard, J. M., Sandhyavenu, H., Whitaker, T. J., Waltman, L. A., Kipp, B. R., Merrell, K. W., Haddock, M. G., & Hallemeier, C. L. (2020). Association of tumor genomic factors and efficacy for metastasis-directed stereotactic body radiotherapy for oligometastatic colorectal cancer. Radiotherapy and Oncology, 146, 29-36. https://doi.org/10.1016/j.radonc.2020.02.008