Lung Cancer

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TU_26_3577 - Predictors of Nodal And Metastatic Failure in Early Stage Non-Small Cell Lung Cancer After Stereotactic Body Radiation Therapy

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

Predictors of Nodal And Metastatic Failure in Early Stage Non-Small Cell Lung Cancer After Stereotactic Body Radiation Therapy
A. Cerra-Franco1, S. Liu2, M. Azar3, K. Shiue1, N. C. Estabrook III4, K. Diab5, F. M. Kong6, J. Wan2, and T. Lautenschlaeger1; 1Department of Radiation Oncology, Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, 2Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, 3Department of Internal Medicine, Indiana University School of Medicine, Indianapolis, IN, 4Department of Radiation Oncology, Indiana University Health Arnett Hospital, Lafayette, IN, 5Department of pulmonary, Indiana University School of Medicine, Indianapolis, IN, 6Indiana University Radiation Oncology, Indianapolis, IN

Purpose/Objective(s): Up to 30% of early stage non-small cell lung cancer (NSCLC) patients undergoing stereotactic body radiation therapy (SBRT) develop metastatic disease. While lung parenchymal failures after lung SBRT are thought to be salvageable if detected early, development of nodal and distant metastases are challenging situations that can seriously compromise patient outcomes. We sought to identify factors predictive of metastasis after lung SBRT.

Materials/Methods: Overall, 363 patients with early-stage NSCLC (T1a, T1b and T2a N0 M0 as per AJCC 7th edition) that received SBRT in 3-5 fractions were included in this retrospective analysis. Multiple patient and tumor factors were analyzed for their association with time to a combined nodal and/or distant metastatic failure: sex; age; lobe involved; previous history of NSCLC; gross tumor volume (GTV); T stage; histology (adenocarcinoma, squamous cell carcinoma, NSCLC not otherwise specified, or no pathology); radiation dose (biologically equivalent dose using alpha/beta=10 [BED10]); prescription dose; minimum, maximum, and mean dose to GTV; and parenchymal lung sites of failure (in-field, same lobe but not in-field, different ispilateral lobe, and contralateral lung). A metastasis risk score linear model using beta coefficients from a multivariate Cox model as weighting factors was built for variables significant on multivariate analysis.

Results: GTV and radiation dose were significant on univariate analysis. A previous history of NSCLC (p=0.84), histology (p=0.45), T stage (p=0.49), and subsequent lung parenchymal failures (p>0.11) did not increase the risk of metastasis. On multivariate Cox proportional hazards modeling, GTV and radiation dose remained significantly associated with time to metastasis (p<0.001 and p=0.044, respectively). A metastasis risk score model using GTV and radiation dose was built: [Risk score = (0.01611 x GTV) – (0.00525 x prescription dose (BED10))]. Two risk score cutoffs separating the cohort into low risk and high risk were examined. Using a cutoff identifying patients with the highest risk scores in the cohort, a significant difference in time to metastases was identified between 325 low risk and 38 high risk patients (p<0.001) with 2-year metastases-free estimates of 82.5% (95% CI 77.5-87.8%) and 48.8% (95% CI 32.8-72.7%). Using a less stringent cutoff separating our cohort into 248 low risk patients and 115 high risk patients revealed similar results (p=0.0087) with 2-year estimates of metastases-free survival of 85.4% (95% CI 80.1-91.1%) and 65.4% (95% CI 55.5-76.9%). Based on the model, a 25cc tumor would require 153 Gy BED10 to keep the 2-year metastases-free survival at 85%.

Conclusion: GTV and radiation dose are associated with time to metastasis. A risk score can be used to identify patients at high risk for metastasis after SBRT for early stage NSCLC.

Author Disclosure: A. Cerra-Franco: None. S. Liu: None. M. Azar: None. K. Shiue: None. N.C. Estabrook: None. F.(. Kong: Research Grant; Varian, NCI/NIH. Founding President and Board of Director; Sino-American Network for Therapeutic Radiation On. President 2015; American Association of Women Radiologists (AAWR). President 2012-2013; Association for Chinese Professors. Founding Board Member; Sino-American Network for Therapeutic Radiology. T. Lautenschlaeger: None.

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