TY - JOUR
T1 - Association of tumor genomic factors and efficacy for metastasis-directed stereotactic body radiotherapy for oligometastatic colorectal cancer
AU - Jethwa, Krishan R.
AU - Jang, Samuel
AU - Mullikin, Trey C.
AU - Harmsen, William S.
AU - Petersen, Molly M.
AU - Olivier, Kenneth R.
AU - Park, Sean S.
AU - Neben-Wittich, Michelle A.
AU - Hubbard, Joleen M.
AU - Sandhyavenu, Harigopal
AU - Whitaker, Thomas J.
AU - Waltman, Lindsey A.
AU - Kipp, Benjamin R.
AU - Merrell, Kenneth W.
AU - Haddock, Michael G.
AU - Hallemeier, Christopher L.
N1 - Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/5
Y1 - 2020/5
N2 - 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.
AB - 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.
KW - Colorectal cancer
KW - KRAS
KW - Oligometastasis
KW - Radiotherapy
KW - TP53
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U2 - 10.1016/j.radonc.2020.02.008
DO - 10.1016/j.radonc.2020.02.008
M3 - Article
C2 - 32114263
AN - SCOPUS:85080079967
SN - 0167-8140
VL - 146
SP - 29
EP - 36
JO - Radiotherapy and Oncology
JF - Radiotherapy and Oncology
ER -