PIK3CA mutation is associated with increased local failure in lung stereotactic body radiation therapy (SBRT) Journal Article


Authors: Lockney, N. A.; Yang, T. J.; Barron, D.; Gelb, E.; Gelblum, D. Y.; Yorke, E.; Shi, W.; Zhang, Z.; Rimner, A.; Wu, A. J.
Article Title: PIK3CA mutation is associated with increased local failure in lung stereotactic body radiation therapy (SBRT)
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. © 2017
Keywords: adult; aged; gene mutation; major clinical study; overall survival; positron emission tomography; mass spectrometry; tumor volume; retrospective study; histology; lung metastasis; radiosensitivity; stereotactic body radiation therapy; genetic screening; local failure; pik3ca; lung insufficiency; radiation resistance; very elderly; local failure free survival; phosphatidylinositol 4,5 bisphosphate 3 kinase; four dimensional computed tomography; human; male; female; priority journal; article; lung stereotactic body radiation therapy (sbrt)
Journal Title: Clinical and Translational Radiation Oncology
Volume: 7
ISSN: 2405-6308
Publisher: Elsevier Inc.  
Date Published: 2017-12-01
Start Page: 91
End Page: 93
Language: English
DOI: 10.1016/j.ctro.2017.11.002
PROVIDER: scopus
PMCID: PMC5830173
PUBMED: 29503876
DOI/URL:
Notes: Article -- Export Date: 1 October 2019 -- Source: Scopus
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MSK Authors
  1. Zhigang Zhang
    428 Zhang
  2. Weiji Shi
    121 Shi
  3. Daphna Y Gelblum
    228 Gelblum
  4. Andreas Rimner
    525 Rimner
  5. Abraham Jing-Ching Wu
    401 Wu
  6. Ellen D Yorke
    450 Yorke
  7. Jonathan T Yang
    166 Yang
  8. David   Barron
    11 Barron
  9. Natalie Ausborn Lockney
    33 Lockney
  10. Emily Helene Gelb
    28 Gelb