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T..J. Yang
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P2.05 - Poster Session with Presenters Present (ID 463)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Radiotherapy
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.05-003 - PIK3CA Mutation is Associated with Increased Local Failure in Lung Stereotactic Body Radiation Therapy (SBRT) (ID 5251)
14:30 - 14:30 | Author(s): T..J. Yang
- Abstract
Background:
Hyperactivation of the phosphatidylinositol-3-kinase (PI3K) pathway has been associated with radioresistance. It is unclear whether such mutations also 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 134 patients who underwent SBRT to primary or metastatic lung lesions from 2007-2015 for whom molecular testing data was available for EGFR, AKT, and PIK3CA genes. For tumors of lung origin (n=122), molecular testing data was included from the lung tumor. For metastatic tumors to the lung (n=12), molecular testing data from either a primary or metastatic tumor site was used. Association between clinical factors, including molecular mutation status, and LF was evaluated with Cox regression analysis. The Kaplan-Meier method was used to assess differences in LF rates based on PIK3CA mutation status.
Results:
The most common histology was adenocarcinoma (90%) among all tumors. Six patients (4%) had PIK3CA mutation, 31 patients (23%) had EGFR mutation, and one patient (0.7%) had AKT mutation. Median lesion size was 2.0 cm (range, 0.6–5.6 cm), median dose was 48 Gy (range 30–70 Gy), and median number of fractions was 4 (range, 3–10). Median follow-up was 20 months (range, 0.2–70 months). LF was observed for 16 patients (12%). Median time to local failure was 15 months (range, 7–31 months). On univariate analysis, PIK3CA mutation presence was associated with LF (HR 5.3 [95% CI 1.1-25.0], p=0.03), while tumor histology (adenocarcinoma vs. other), tumor size (≤2cm vs. >2cm), primary tumor site (lung vs. other), and EGFR or AKT mutation presence were not. By multivariate analysis, PIK3CA mutation trended toward association with LF (HR 5.0 [95% CI 1.0-25.3], p=0.051). At one year, probability of LF in lesions with PIK3CA mutations was 12.4% vs. 5.7% in lesions without mutations (p=0.02). Lesions with PIK3CA mutations were associated with a decreased time to LF (mean 17.9 months [95% CI 12.7–23.2 months]) compared to those without PIK3CA mutation (mean 58.6 months [95% CI 52.6–64.7 months]).
Conclusion:
We explored EGFR/AKT/PI3KCA pathway mutations and found that patients with PIK3CA mutations are at higher risk for LF after lung SBRT. Due to the limitation of small numbers, this data needs to be validated in a larger patient cohort. Nonetheless, this is a novel finding and hypothesis-generating for future studies.
