PIK3CA mutation is associated with increased local failure in lung stereotactic body radiation therapy (SBRT). (December 2017)

• Record Type: Journal Article
• Authors: Lockney, Natalie A.; Yang, T. Jonathan; Barron, David; Gelb, Emily; Gelblum, Daphna Y.; Yorke, Ellen; Shi, Weiji; Zhang, Zhigang; Rimner, Andreas; Wu, Abraham J.
• Is Part Of: Clinical and translational radiation oncology. Volume 7(2017)
• Page Start: 91
• Page End: 93
• Publication Date: 2017-12
• Subjects: PI3K phosphatidylinositol-3-kinases -- PIP2 phosphatidylinositol-4, 5-biphosphate -- PIP3 phosphatidylinositol-3, 4, 5-triphosphate -- SBRT stereotactic body radiation therapy -- AKT protein kinase B -- CT computed tomography -- GTV gross tumor volume -- ITV internal target volume -- CTV clinical target volume -- PTV planning target volume -- BED biologically effective dose -- LF local failure; Lung stereotactic body radiation therapy (SBRT) -- PIK3CA -- Radiation resistance -- Local failure; Cancer -- Radiotherapy -- Periodicals; Oncology -- Periodicals; Cancer -- Radiotherapy; Oncology; Radiation Oncology; Neoplasms -- radiotherapy; Translational Medical Research; Periodicals; Electronic journals; Periodicals; 616.9940642
• DOI: 10.1016/j.ctro.2017.11.002
• Languages: English
• ISSNs: 2405-6308

Abstract

Highlights: An examination of mutations in PIK3CA signaling pathways and radioresistance. PIK3CA mutation was found to be associated with local failure after lung SBRT. This is a small study and there is need for further validation. Abstract: Objectives: Hyperactivation of the phosphatidylinositol-3-kinase (PI3K) pathway has been associated with radioresistance. It is unclear whether such mutations confer suboptimal local control for patients who receive lung stereotactic body radiation therapy (SBRT). Our objective was to examine whether mutations in the EGFR/AKT/PIK3CA signaling pathway are associated with local failure (LF) after lung SBRT. Methods: We retrospectively reviewed 166 patients who underwent SBRT to primary or metastatic lung lesions from 2007 to 2015 for whom genetic testing data was available for EGFR, AKT, and PIK3CA genes. Association between clinical factors, including molecular mutation status, and LF was evaluated. Results: Six patients (4%) had PIK3CA mutation, 36 patients (22%) had EGFR mutation, and one patient (0.6%) had AKT1 mutation. Median lesion size was 2.0 cm (range, 0.6–5.6 cm); median dose was 48 Gy in 4 fractions (range, 30–70 Gy in 3–10 fractions). Median follow-up for survivors was 27.3 months (range, 3.8–66.7 months). LF occurred in 16 patients (10%). On univariate analysis, PIK3CA mutation was associated with LF (HR 10.44 [95% CI 2.16–50.46], p = .003), while tumor histology, tumor size, primary tumor site, BED and EGFR mutation were not. At one year, probability of LF in lesions with PIK3CA mutation was 20.0% vs. 2.9% in lesions without mutation (p < .001 by log rank test). Conclusion: Although the number of patients affected was small, PIK3CA mutation was significantly associated with higher risk of LF in patients undergoing lung SBRT. This association has not previously been reported for lung SBRT and indicates the need for further validation.