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Novel Imaging Biomarkers in Stage I Non-Small Cell Lung Cancer Treated With Stereotactic Ablative Radiation Therapy
S546
International Journal of Radiation Oncology Biology Physics
Materials/Methods: We identified 27 patients treated between 2007 and 2011 with lung tumor SABR at our institution who had pretreatment pulmonary function testing, at least 6 months of follow-up by CT imaging after SABR, and treatment for a single lesion. We contoured the treated lobe, the untreated adjacent lobe, and the total lung volume on CT images before and after SABR. The volume change of the treated lobe and untreated adjacent lobe was determined relative to the total lung volume. Additionally, we visually scored the severity of emphysema in the treated lobe by CT imaging. We correlated the degree of volume reduction with the volume of lung receiving high biologically effective doses (BED, alpha/beta Z 3 for late effects). Results: We found a positive and linear relationship between volume reduction of the treated lobe and the volume receiving a BED of 60 Gy or more (V60), with r2 Z 0.45 and p Z 0.0001. When analyzing sub-groups based on pretreatment FEV1%, lobar emphysema score, number of fractions, and follow-up CT time the relationship remained significant, with no statistically significant difference in effect size between sub-groups. There was a positive and linear relationship between volume reduction of the treated lobe and volume expansion of the untreated adjacent lobe (r2 Z 0.47, p < 0.0001), indicating compensatory expansion of the untreated lobe. Conclusions: We have identified a dose-volume response relationship of lung volume reduction following SABR for lung tumors. Our results suggest no significantly different sensitivity of emphysematous and normal lung tissues to volume reduction relative to dose. These data serve to inform our recently initiated prospective trial of stereotactic ablative volume reduction (SAVR) for severe heterogeneous emphysema in patients who are not ideal candidates for LVRS. Author Disclosure: M.S. Binkley: None. J.B. Shrager: E. Research Grant; BWL, PGM, JBS, and MD have received research support from Varian Medical Systems. N. Trakul: None. A.N. Leung: None. R. Popat: None. T.F. Atwood: None. P.G. Maxim: E. Research Grant; BWL, PGM, JBS, and MD have received research support from Varian Medical Systems. M. Diehn: E. Research Grant; BWL, PGM, JBS, and MD have received research support from Varian Medical Systems. B.W. Loo: E. Research Grant; BWL, PGM, JBS, and MD have received research support from Varian Medical Systems. F. Honoraria; BWL has received speaking honoraria from Varian Medical Systems.
proportional hazard analysis was used to correlate LF with the presence of FM, GTV, and prescription biologically effective dose (BED) as covariates. Results: Median follow-up was 23.5 months and there were 6 local failures (LFs), 8 regional failures (RFs), and 12 distant failures (DFs). By Wilcoxon rank sum test, GLCM texture and contrast homogeneity were significantly associated with DF (p Z 0.0015, p Z 0.034), but only contrast remained significant in a multivariate regression model which included all other features (cross-validated ROC AUC Z 0.63). In the expanded cohort, Kaplan-Meier 24 month freedom from LF was 91% without FM and 71% with FM (log rank p Z 0.023). On multivariate analysis, FM (HR 0.14, 95% CI 0.031-0.59, p Z 0.0078) and BED (HR 0.96, 95% CI 0.94-0.99, p Z 0.0017) were independently significant. Conclusions: CT imaging features may be useful non-invasive predictive biomarkers for DF and LF in stage I NSCLC patients treated with SABR. In this pilot retrospective study we found the novel contrast and homogeneity GLCM texture imaging features and FM to be significantly prognostic for DF and LF, respectively. These findings will need to be validated prospectively in a larger cohort of patients with longer follow-up. Author Disclosure: T.A. Aguilera: None. G.I. Daniel: None. D.B. Shultz: None. N. Trakul: None. P.G. Maxim: E. Research Grant; Varian, RaySearch. F. Honoraria; Varian. D.L. Rubin: None. B.W. Loo: E. Research Grant; Varian, RaySearch. F. Honoraria; Varian. M. Diehn: E. Research Grant; Varian.
2899 Novel Imaging Biomarkers in Stage I Non-Small Cell Lung Cancer Treated With Stereotactic Ablative Radiation Therapy T.A. Aguilera, G.I. Daniel, D.B. Shultz, N. Trakul, P.G. Maxim, D.L. Rubin, B.W. Loo, and M. Diehn; Stanford University Medical Center, Stanford, CA Purpose/Objective(s): Biomarkers for predicting treatment failure in early stage non-small cell lung cancer (NSCLC) patients treated with stereotactic ablative radiation therapy (SABR) remain lacking. Furthermore, limited tissue availability hinders classic pathologic risk factor evaluation and molecular profiling in these patients. We hypothesize that novel CT imaging features can serve as prognostic biomarkers for treatment failure after SABR. Materials/Methods: We retrospectively identified 66 patients with stage I NSCLC treated with SABR between 2000 and 2011 who had treatment planning CT scans and gross tumor volume (GTV) contours available for analysis. We analyzed six CT-based features of the GTV as potential biomarkers: volume; the mean, variance, skewness, and kurtosis of Hounsfield units within the GTV; and four texture features based on gray-level cooccurrence matrix (GLCM) on a representative slice of each GTV. The features were examined using the Wilcoxon rank sum hypothesis test to compare the medians between failure and no failure groups. Multivariate regression models using lasso regression were used to verify prediction of failure for features found to be significant. Based on the observation that the kurtosis, skewness, and variance were affected by the presence of implanted fiducial markers (FM), we evaluated an expanded cohort of 115 patients with stage I NSCLC treated with SABR during the same time interval in whom the presence or absence of FM was scored. Multivariate Cox regression
2900 Re-irradiation for Locally-Recurrent Non-Small Cell Lung Cancer With Stereotactic Body Radiation Therapy as Initial or Salvage Treatment M.E. Schutzer and E. Weiss; Virginia Commonwealth University, Richmond, VA Purpose/Objective(s): Stereotactic body radiation therapy (SBRT) is among the treatment options for locally recurrent lung cancer previously treated with radiation. However, only limited data exist on thoracic reirradiation for in-field failures when SBRT is used for the first or second course of radiation therapy. We therefore report our institutional experience with this treatment approach. Materials/Methods: A total of 9 patients were treated with thoracic reirradiation with SBRT as initial or salvage treatment. Patients were included if they were treated for recurrent tumors within the high dose region of previous radiation fields. Seven patients received 3D conformal RT (3DCRT) then SBRT, 1 patient SBRT then 3DCRT, and 1 patient SBRT then SBRT. Patients treated in our department underwent 4D CT simulation with ITV-based planning. Five patients received concurrent chemotherapy with 3DCRT, and no chemo was given concurrently with SBRT. Median dose and fraction size for SBRT were 40 Gy (30-48) and 8 Gy (612), respectively. Median dose and fraction size for 3DCRT were 63 Gy (45-68) and 2 Gy (1.8-3.75), respectively. This resulted in a median cumulative biologically effective dose of 148.8 Gy (120-187.2) for alpha/ beta of 10. Toxicity was scored on the RTOG scale, and survival was based on Kaplan Meier estimates. Results: Median age at diagnosis was 63 (48-86), and 2 of 9 patients were male. Stage at diagnosis was I for 4 patients (44%), II for 1 patient (11%), and III for 4 patients (44%). Median time between treatments was 1.6 years (15.2). With median follow-up of 13 months, 7 patients (77%) are alive, and durable local control was achieved in 8 (88%). Median overall survival after completion of all radiation therapy was 2.6 years. During the final course for RT, 1 patient experienced acute grade 1-2 esophagitis (11%), and 1 had pneumonitis (11%). No acute grade 3 toxicity was observed. Two patients suffered rib fractures (22%) at 10 and 19 months after completion of therapy. One of these patients was asymptomatic, and one developed a small pneumothorax and required oral narcotics. No patients had increased oxygen requirement, and no other significant late toxicity was observed. Conclusions: Thoracic re-irradiation with SBRT as initial or salvage therapy achieved high rates of local control with acceptable toxicity profile. Prospective studies are necessary to better define the role of this approach. Author Disclosure: M.E. Schutzer: None. E. Weiss: None.
International Journal of Radiation Oncology Biology Physics
Materials/Methods: We identified 27 patients treated between 2007 and 2011 with lung tumor SABR at our institution who had pretreatment pulmonary function testing, at least 6 months of follow-up by CT imaging after SABR, and treatment for a single lesion. We contoured the treated lobe, the untreated adjacent lobe, and the total lung volume on CT images before and after SABR. The volume change of the treated lobe and untreated adjacent lobe was determined relative to the total lung volume. Additionally, we visually scored the severity of emphysema in the treated lobe by CT imaging. We correlated the degree of volume reduction with the volume of lung receiving high biologically effective doses (BED, alpha/beta Z 3 for late effects). Results: We found a positive and linear relationship between volume reduction of the treated lobe and the volume receiving a BED of 60 Gy or more (V60), with r2 Z 0.45 and p Z 0.0001. When analyzing sub-groups based on pretreatment FEV1%, lobar emphysema score, number of fractions, and follow-up CT time the relationship remained significant, with no statistically significant difference in effect size between sub-groups. There was a positive and linear relationship between volume reduction of the treated lobe and volume expansion of the untreated adjacent lobe (r2 Z 0.47, p < 0.0001), indicating compensatory expansion of the untreated lobe. Conclusions: We have identified a dose-volume response relationship of lung volume reduction following SABR for lung tumors. Our results suggest no significantly different sensitivity of emphysematous and normal lung tissues to volume reduction relative to dose. These data serve to inform our recently initiated prospective trial of stereotactic ablative volume reduction (SAVR) for severe heterogeneous emphysema in patients who are not ideal candidates for LVRS. Author Disclosure: M.S. Binkley: None. J.B. Shrager: E. Research Grant; BWL, PGM, JBS, and MD have received research support from Varian Medical Systems. N. Trakul: None. A.N. Leung: None. R. Popat: None. T.F. Atwood: None. P.G. Maxim: E. Research Grant; BWL, PGM, JBS, and MD have received research support from Varian Medical Systems. M. Diehn: E. Research Grant; BWL, PGM, JBS, and MD have received research support from Varian Medical Systems. B.W. Loo: E. Research Grant; BWL, PGM, JBS, and MD have received research support from Varian Medical Systems. F. Honoraria; BWL has received speaking honoraria from Varian Medical Systems.
proportional hazard analysis was used to correlate LF with the presence of FM, GTV, and prescription biologically effective dose (BED) as covariates. Results: Median follow-up was 23.5 months and there were 6 local failures (LFs), 8 regional failures (RFs), and 12 distant failures (DFs). By Wilcoxon rank sum test, GLCM texture and contrast homogeneity were significantly associated with DF (p Z 0.0015, p Z 0.034), but only contrast remained significant in a multivariate regression model which included all other features (cross-validated ROC AUC Z 0.63). In the expanded cohort, Kaplan-Meier 24 month freedom from LF was 91% without FM and 71% with FM (log rank p Z 0.023). On multivariate analysis, FM (HR 0.14, 95% CI 0.031-0.59, p Z 0.0078) and BED (HR 0.96, 95% CI 0.94-0.99, p Z 0.0017) were independently significant. Conclusions: CT imaging features may be useful non-invasive predictive biomarkers for DF and LF in stage I NSCLC patients treated with SABR. In this pilot retrospective study we found the novel contrast and homogeneity GLCM texture imaging features and FM to be significantly prognostic for DF and LF, respectively. These findings will need to be validated prospectively in a larger cohort of patients with longer follow-up. Author Disclosure: T.A. Aguilera: None. G.I. Daniel: None. D.B. Shultz: None. N. Trakul: None. P.G. Maxim: E. Research Grant; Varian, RaySearch. F. Honoraria; Varian. D.L. Rubin: None. B.W. Loo: E. Research Grant; Varian, RaySearch. F. Honoraria; Varian. M. Diehn: E. Research Grant; Varian.
2899 Novel Imaging Biomarkers in Stage I Non-Small Cell Lung Cancer Treated With Stereotactic Ablative Radiation Therapy T.A. Aguilera, G.I. Daniel, D.B. Shultz, N. Trakul, P.G. Maxim, D.L. Rubin, B.W. Loo, and M. Diehn; Stanford University Medical Center, Stanford, CA Purpose/Objective(s): Biomarkers for predicting treatment failure in early stage non-small cell lung cancer (NSCLC) patients treated with stereotactic ablative radiation therapy (SABR) remain lacking. Furthermore, limited tissue availability hinders classic pathologic risk factor evaluation and molecular profiling in these patients. We hypothesize that novel CT imaging features can serve as prognostic biomarkers for treatment failure after SABR. Materials/Methods: We retrospectively identified 66 patients with stage I NSCLC treated with SABR between 2000 and 2011 who had treatment planning CT scans and gross tumor volume (GTV) contours available for analysis. We analyzed six CT-based features of the GTV as potential biomarkers: volume; the mean, variance, skewness, and kurtosis of Hounsfield units within the GTV; and four texture features based on gray-level cooccurrence matrix (GLCM) on a representative slice of each GTV. The features were examined using the Wilcoxon rank sum hypothesis test to compare the medians between failure and no failure groups. Multivariate regression models using lasso regression were used to verify prediction of failure for features found to be significant. Based on the observation that the kurtosis, skewness, and variance were affected by the presence of implanted fiducial markers (FM), we evaluated an expanded cohort of 115 patients with stage I NSCLC treated with SABR during the same time interval in whom the presence or absence of FM was scored. Multivariate Cox regression
2900 Re-irradiation for Locally-Recurrent Non-Small Cell Lung Cancer With Stereotactic Body Radiation Therapy as Initial or Salvage Treatment M.E. Schutzer and E. Weiss; Virginia Commonwealth University, Richmond, VA Purpose/Objective(s): Stereotactic body radiation therapy (SBRT) is among the treatment options for locally recurrent lung cancer previously treated with radiation. However, only limited data exist on thoracic reirradiation for in-field failures when SBRT is used for the first or second course of radiation therapy. We therefore report our institutional experience with this treatment approach. Materials/Methods: A total of 9 patients were treated with thoracic reirradiation with SBRT as initial or salvage treatment. Patients were included if they were treated for recurrent tumors within the high dose region of previous radiation fields. Seven patients received 3D conformal RT (3DCRT) then SBRT, 1 patient SBRT then 3DCRT, and 1 patient SBRT then SBRT. Patients treated in our department underwent 4D CT simulation with ITV-based planning. Five patients received concurrent chemotherapy with 3DCRT, and no chemo was given concurrently with SBRT. Median dose and fraction size for SBRT were 40 Gy (30-48) and 8 Gy (612), respectively. Median dose and fraction size for 3DCRT were 63 Gy (45-68) and 2 Gy (1.8-3.75), respectively. This resulted in a median cumulative biologically effective dose of 148.8 Gy (120-187.2) for alpha/ beta of 10. Toxicity was scored on the RTOG scale, and survival was based on Kaplan Meier estimates. Results: Median age at diagnosis was 63 (48-86), and 2 of 9 patients were male. Stage at diagnosis was I for 4 patients (44%), II for 1 patient (11%), and III for 4 patients (44%). Median time between treatments was 1.6 years (15.2). With median follow-up of 13 months, 7 patients (77%) are alive, and durable local control was achieved in 8 (88%). Median overall survival after completion of all radiation therapy was 2.6 years. During the final course for RT, 1 patient experienced acute grade 1-2 esophagitis (11%), and 1 had pneumonitis (11%). No acute grade 3 toxicity was observed. Two patients suffered rib fractures (22%) at 10 and 19 months after completion of therapy. One of these patients was asymptomatic, and one developed a small pneumothorax and required oral narcotics. No patients had increased oxygen requirement, and no other significant late toxicity was observed. Conclusions: Thoracic re-irradiation with SBRT as initial or salvage therapy achieved high rates of local control with acceptable toxicity profile. Prospective studies are necessary to better define the role of this approach. Author Disclosure: M.E. Schutzer: None. E. Weiss: None.