Lung Cancer

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TU_26_3576 - Angiogenesis Biomarkers are Associated With Distant Metastasis Free Survival in Early-Stage Non-Small Cell Lung Cancer Treated with Stereotactic Body Radiation Therapy (SBRT)

Tuesday, October 23
2:45 PM - 4:15 PM
Location: Innovation Hub, Exhibit Hall 3

Angiogenesis Biomarkers are Associated With Distant Metastasis Free Survival in Early-Stage Non-Small Cell Lung Cancer Treated with Stereotactic Body Radiation Therapy (SBRT)
J. Bloom1, J. Borgia2, P. A. Blumenfeld2, T. Beck2, and G. Marwaha3; 1Rush University Medical Center, Chiago, IL, 2Rush University Medical Center, Chicago, IL, 3Department of Radiation Oncology, Rush University Medical Center, Chicago, IL

Purpose/Objective(s): Elevated levels of circulating angiogenesis biomarkers have previously been shown to be significantly associated with NSCLC disease progression after definitive intent SBRT. We seek to update our experience and follow-up in early stage NSCLC patients treated with SBRT, and identify biomarkers that may correlate with inferior distant metastasis free survival (DMFS).

Materials/Methods: Patients treated with definitive intent SBRT at a single institution were evaluated (n=23). Peripheral blood was collected just prior to SBRT. An angiogenesis biomarker panel was run for each patient as part of the Human Angiogenesis/Growth Factor Panel from EMD Millipore. Assays were completed on Luminex platform. Seventeen biomarkers were tested including: angiopoietin-2, BMP-9, EGF, endoglin, endothelin-1, FGF-1, FGF-2, follistatin, G-CSF, HB-EGF, HGF, IL-8, leptin, PLGF, VEGF-A, VEGF-C, and VEGF-D. Log-rank tests were performed to calculate DMFS. Cutoff thresholds for individual biomarkers were calculated to optimize the significance of the log-rank test findings using an in-house algorithm. The cox proportional hazard model was used to estimate the hazard ratio per unit change in serum level.

Results: The median age of the patient cohort was 70.8 years, with median follow-up of 23 months (Range(R): 3.2-49.7). Median dose of SBRT was 54 Gy (R: 34-60 Gy). Twenty-one (91%) patients had a positive smoking history. Six (26%) patients developed distant metastases; 4 (17%) patients developed local recurrence. The progression free survival (freedom from any local, regional or distant progression) at 23 months was 61%. Two (12%) biomarkers: follistatin (p=0.0264) and G-CSF (p=0.0468) were significantly associated with DMFS. Patients with follistatin levels below 852.16 pg/mL had a median DMFS of 7.05 (mean 10.56) months, while those above this threshold had a median DMFS of 4.93 (mean 4.93) months. With follistatin fit to a continuous model, a difference of 100 points of serum follistatin carried a 51.1% (p=0.0051) greater risk of DMFS. For G-CSF, a level below 33.76 pg/mL had a median DMFS of 7.39 (mean 11.98) months, while those above had a median DMFS of 6.24 (mean 5.39) months. With G-CSF fit to a continuous model, a difference of 100 points of G-CSF carried an 87.3% (p=0.0315) greater risk of DMFS.

Conclusion: At two-year follow up, 2 of the 17 angiogenesis biomarkers assayed in this analysis, follistatin and G-CSF, correlated with inferior DMFS in patients who underwent SBRT for NSCLC. These findings, with further analysis and validation, suggest a potential role in disease prognostication and/or guidance for adjuvant therapy early in the appropriate patient’s treatment course.

Author Disclosure: J. Bloom: None. J. Borgia: None. P.A. Blumenfeld: None. T. Beck: None. G. Marwaha: None.

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