- Email: [email protected]
Clinical Outcomes Following Stereotactic Body Radiation Therapy to Multiple Sites of Intrathoracic Disease
250
International Journal of Radiation Oncology Biology Physics
and disease progression. Further research is needed to understand the mechanism of this finding. Author Disclosure: M. Lan: None. T. Xu: None. D.R. Gomez: None. M.D. Jeter: None. Q. Nguyen: None. W. Deng: None. S.H. Lin: None. R.U. Komaki: None. Z. Liao: None.
Late-Breaking (LB) Abstracts
165 Peripheral Blood Cell Free DNA to Monitor Mutational Response in Epidermal Growth Factor ReceptoreMutant NoneSmall Cell Lung Cancer M. Devitt, R. Hall, and R.D. Gentzler; University of Virginia, Charlottesville, VA Purpose/Objective(s): Detection of epidermal growth factor receptor (EGFR) mutations in nonesmall cell lung cancer (NSCLC) traditionally requires invasive biopsies. As new therapies emerge for acquired resistance to tyrosine kinase inhibitors (TKIs), the need for additional biopsies in routine clinical practice has increased. Peripheral blood testing of circulating cell free DNA (cfDNA) is an alternative method for the detection of genetic alterations. We present 2 cases that highlight the utility of cfDNA along with tissue-based genomic testing in the treatment of EGFR-mutant NSCLC. Materials/Methods: This is a retrospective report of two cases. Guardant360Ò Biopsy-FreeÔ Tumor Sequencing was used for all cfDNA testing. Results: Case #1: A 48-year-old female, never smoker, presented with stage IV lung adenocarcinoma (ADC) metastatic to bone. EGFR L858R mutation was detected by pyrosequencing and she was treated with erlotinib for 1 year with stable disease. At progression, cfDNA testing was obtained and detected L858R and T790M. After treatment with osimertinib and subsequent response, cfDNA was repeated and detected no mutations. She had progression two months later. Percutaneous tissue genomics and cfDNA were performed and revealed L858R without T790M. Case #2: A 66-year-old male, never smoker, developed metastatic recurrence of ADC 3 years after surgical resection and adjuvant chemotherapy. EGFR pyrosequencing revealed 2 mutations in EGFR, L858R and V834L. He was treated with dacomitinib for 3.5 years followed by 6 months of nivolumab. At his next progression, a biopsy was obtained and tissue genomic testing showed emergence of T790M; simultaneous cfDNA testing also detected T790M. He enrolled on a clinical trial and was treated with chemotherapy then crossed over to rocelitinib. He progressed on rocelitinib and repeat cfDNA showed persistence of T790M. He transitioned to osimertinib with stable disease achieved for 2 months. He then developed malignant pericardial and pleural effusions. Next-generation sequencing on pleural fluid and cfDNA both detected L858R and V834 with absence of T790M. Unlike tissue testing, cfDNA detected the emergence of a C797S mutation. Conclusion: These cases highlight several advantages of cfDNA testing. First is the ability to obtain genomic data without the need for tissue. This may eliminate the need for outpatient biopsies and their associated risks. Second is the ability of cfDNA to complement tissue-based genetic testing. In both cases, cfDNA picked up the presence of mutations that were either not detected on tissue biopsy or no tissue biopsy was performed. Finally, both cases demonstrate that cfDNA can show elimination of T790M after treatment with the T790M-specific TKI osimertinib. Tissue-based testing remains the standard for detecting resistance mutations, but these cases demonstrate that cfDNA can obtain actionable information without biopsy in routine clinical practice. Author Disclosure: M. Devitt: Provides advisory role to council on aspects of trainee development within the American Society of Clinical Oncology; American Society of Clinical Oncology Trainee Council. R. Hall: Honoraria; Merck Pharmaceuticals. R.D. Gentzler: Honoraria; Merck. Advisory Board; Ariad.
LB1 Effects of Motion on Radiomics Analysis of Thoracic Cancers F.F. Yin,1 K. Lafata,2 J.C. Hong,3 and C.R. Kelsey3; 1Duke University, Durham, NC, 2Duke University Medical Physics Graduate Program, Durham, NC, 3Duke University Medical Center, Durham, NC Purpose/Objective(s): To investigate the effects of motion on radiomics analysis of thoracic cancers. Our in-house computational radiomics infrastructure has been retrospectively integrated into our clinic’s lung SBRT workflow to study three primary areas of radiomics research: (1) Feature Extraction, (2) Feature Characterization, and (3) Predictive Modeling. Materials/Methods: Thirty-one patients were retrospectively identified as meeting three data availability requirements: (1) an existing free-breathing 3DCT, (2) an existing 4DCT, and (3) a known tumor histology. Investigation of inherent feature variability was performed by studying (a) the effects of motion using a dynamic digital phantom, (b) the differences between 3DCT and 4DCT acquisitions, and (c) the stability of daily CBCT-derived features. Radiomic features were extracted using our in-house software, and classified into 4 categories: (1) Morphological, (2) Intensity, (3) Coarse Texture, and (4) Fine Texture. A paired-sample t-test was used to determine which features demonstrated different mean values when extracted from 3D and 4D imaging modalities. We then used a task-based approach to quantitatively demonstrate how feature variability can ultimately perturb predictive modeling. Specifically, a logistic regression algorithm was developed and trained to classify tumor histology (adenocarcinoma vs squamous cell) based on features derived first from each patient’s free-breathing 3DCT (FBCT), followed by the corresponding average-intensity-projection 4DCT (AIPCT). Fitting parameters were determined by minimizing a regularized cost function, of which optimization was performed via gradient descent, and the model was evaluated with a 4-fold bootstrapping technique. Results: Digital phantom results suggested that some texture features change non-monotonically with respiratory motion magnitude, indicating a motion-induced cancelling effect of certain feature magnitudes. Comparison of 3DCT with 4DCT demonstrated that motion blurring may severely alter heterogeneity tumor measurements. Further, FBCT-derived features demonstrated better histological classification (AUCZ0.66) relative to AIPCT-derived features (AUCZ0.59). However, when the most variable features (i.e., those which demonstrated a paired-sample t-test p-value < 5%) were removed from the feature spaces, both models converged to an AUC value of 0.63. Conclusion: A computational radiomics infrastructure has been developed and applied to our lung SBRT clinical workflow. Respiratory motioneinduced feature variability using both a computational phantom and patient data demonstrated perturbative modeling effects for tumor histology classification. Author Disclosure: F. Yin: Research Grant; Varian Medical Systems, NIH.
LB2 Clinical Outcomes Following Stereotactic Body Radiation Therapy to Multiple Sites of Intrathoracic Disease C. Goodman,1 P. Dalal,2 D. Cutright,2 N. Paudel,2 T. Kim,2 M.S. Gentile,2 and T.J. Kruser2; 1Northwestern University, Chicago, IL, United States, 2 Northwestern Feinberg School of Medicine, Chicago, IL Purpose/Objective(s): Second primary lung cancers are common in patients with inoperable lung cancer. Little data exist on the safety and efficacy of stereotactic body radiation therapy (SBRT) to multiple sites of intrathoracic disease. We sought to examine clinical outcomes for patients receiving SBRT to multiple intrathoracic sites.
Volume 98 Number 1 2017 Materials/Methods: Eighteen patients with 38 synchronous or metachronous lung nodules were treated between 2010 and 2016 at a tertiary hospital with SBRT. Demographic and clinicopathologic data as well as dosimetry for target volume coverage and organs at risk were collected. Pre-treatment, acute (<90 days), and late (>90 days) toxicities were retrospectively reviewed using standardized CTCAE 4.0 criteria. Radiographic and clinical pneumonitis was recorded. Local control (treatment field and ipsilateral lobe), regional control (ipsilateral lung or mediastinum), metastasis-free survival, progression-free survival, and overall survival were calculated. Results: Sixteen patients received SBRT to 2 sites, while two patients were treated at 3 sites. Six patients were treated for synchronous tumors, while 12 patients were treated for metachronous tumors. The median age at first treatment was 77 years (IQR: 68.5-79.8) and for metachronous lesions the median time interval between SBRT courses was 14.2 months (95% CI: 6.8-21.6). The majority (76.3%) of the treated nodules were primary lung tumors, while 23.7% were metastatic nodules of varying histologies. Forty percent of second or third SBRT courses were to nodules in the contralateral lung, while 40% were to nodules in the same lobe. The most common fractionation scheme was 50Gy in 5 fractions (cumulative range: 3000-6000 in 3-8 fractions). The mean treated nodule size was 2.0 cm (95% CI: 1.6-2.4). At median follow-up of 56.0 months from initial SBRT, local failure occurred in 10.8% of lesions. Median overall survival was 31.8 months (95% CI: 27.6-47.2) while median progression-free survival was 25.7 months (95% CI: 17.2-34.1). Six patients (16.6%) developed grade 1 pneumonitis, two patients (11.1%) developed grade 2 pneumonitis after their first SBRT course, while one patient (5.5%) developed grade 3 pneumonitis after her second course of SBRT. Conclusion: SBRT to synchronous or metachronous pulmonary malignancies appears to yield oncologic and toxicity outcomes similar to solitary lesion SBRT. Receipt of previous SBRT should not preclude consideration of further SBRT. Author Disclosure: C. Goodman: None.
LB3 Patterns of Care and Survival Outcomes in Stage II NoneSmall Cell Lung Cancer: An Analysis of the National Cancer Database S.X. Yan,1 M.M. Qureshi,2,3 M.T. Truong,2,3 and K.S. Mak2,3; 1Boston Medical Center, Boston, MA, 2Department of Radiation Oncology, Boston Medical Center, Boston, MA, 3Boston University School of Medicine, Boston, MA Purpose/Objective(s): Stage II nonesmall cell lung cancer (NSCLC) can be treated with primary surgery or radiation, with or without chemotherapy. This study delineates practice patterns in treating Stage II NSCLC in a national patient registry, and evaluates survival by management approach. Materials/Methods: Patients diagnosed with stage II NSCLC treated with radiation alone, chemoradiation therapy, or surgery with or without neoadjuvant or adjuvant chemotherapy, radiation, or chemoradiation therapy were identified using the National Cancer Database (NCDB). Survival rates for each treatment approach were estimated using Kaplan-Meier analysis. Univariate and multivariate Cox regression models were used to identify factors with significant impact on survival. Results: Between 2004 and 2013, a total of 26,732 patients were identified who met study criteria: 4,111 (15.4%) received radiation alone; 6,903 (25.8%) were treated with chemoradiation therapy; and 15,718 (58.8%) patients underwent surgery-based therapy. The percentage of patients receiving surgery increased over the 10-year study period, while those receiving radiation and chemoradiation therapy decreased (p<0.0001). Patients who received
Late-Breaking (LB) Abstracts
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radiation tended to be older, with more comorbidities, Medicare rather than private insurance, and T2N2M0 stage (all p<0.0001). With median follow-up of 23.2 months, median survival was 13.7 months, 20.9 months, and 50.1 months in the radiation, chemoradiation, and surgery groups, respectively (p<0.0001). Five-year overall survival was 8.5%, 18.7%, and 45.0%, respectively. Age, gender, race, insurance status, Charlson-Deyo comorbidity score, year of diagnosis, treatment facility type, T and N stage, and treatment approach were identified to be independent predictors of survival on multivariate analysis. Surgery was associated with improved survival versus chemoradiation therapy on multivariate analysis (hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.54-0.59; p<0.0001). Both surgery (HR 0.38, 95% CI 0.37-0.40; p<0.0001) and chemoradiation therapy (HR 0.68, 95% confidence interval CI 0.65-0.71; p<0.0001) were associated with improved survival over radiation therapy alone on multivariate analysis. Conclusion: Data from the NCDB demonstrates increasing use of surgery-based treatment for Stage II NSCLC over time. Surgery-based therapy was associated with improved survival compared to chemoradiation or radiation alone. Author Disclosure: M.M. Qureshi: None.
LB4 Development of a Transcriptomic Signature Associated With Lung Adenocarcinoma Recurrence and Survival E.D. Brooks,1 G. Micevic,2 and J.Y. Chang1; 1Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 2Yale University School of Medicine, New Haven, CT, United States Purpose/Objective(s): Lung adenocarcinoma patients within AJCC substages exhibit great variability in survival, underscoring the need for more accurate prognostic approaches. Aberrant promoter DNA methylation is a key feature of cancers, including melanoma. Identification of transcriptional signature has been useful in predicting prognosis, diagnosis, and response to treatment in a variety of tumor types. The purpose of this study is to develop a transcriptomic prognostic tool for patients with lung adenocarcinoma, who currently exhibit great variability in survival even within AJCC subgroups. Materials/Methods: We used transcriptomic (RNA-Seq) data from a portion of lung adenocarcinoma samples from The Cancer Genome Atlas and subdivided it into two groups (nZ 170 each), based on disease relapse, into a rapidly progressive and better prognosis cohort. We performed an unbiased differential transcriptomic analysis and identified a ranked list of genes exhibiting differential expression between the two cohorts. Top ranking genes were used to build a 7-gene survival prediction score using multiple logistic regression. Results: In the test cohort, consisting of lung adenocarcinoma samples from The Cancer Genome Atlas not used for discovery (nZ200), a beneficial score was associated with a significantly longer 5-year overall survival (p<0.001, log-rank test). A high score was associated with high G2/M checkpoint gene expression (q<0.0001), mitotic spindle assembly gene expression (qZ0.003), E2F transcription factor targets, and activation of mTORC1 signaling (qZ0.013). Conclusion: In this study, we define a transcriptomic-based lung adenocarcinoma survival prediction tool which can potentially identify the subgroup of patients with aggressive disease who rapidly progress. Identification of this high risk group can contribute to improved care of lung cancer patients and provision of most appropriate therapies, including radiation therapy. For early-stage disease, identifying such patients helps to determine who could potentially benefit from upfront systemic therapy. Author Disclosure: G. Micevic: None.
International Journal of Radiation Oncology Biology Physics
and disease progression. Further research is needed to understand the mechanism of this finding. Author Disclosure: M. Lan: None. T. Xu: None. D.R. Gomez: None. M.D. Jeter: None. Q. Nguyen: None. W. Deng: None. S.H. Lin: None. R.U. Komaki: None. Z. Liao: None.
Late-Breaking (LB) Abstracts
165 Peripheral Blood Cell Free DNA to Monitor Mutational Response in Epidermal Growth Factor ReceptoreMutant NoneSmall Cell Lung Cancer M. Devitt, R. Hall, and R.D. Gentzler; University of Virginia, Charlottesville, VA Purpose/Objective(s): Detection of epidermal growth factor receptor (EGFR) mutations in nonesmall cell lung cancer (NSCLC) traditionally requires invasive biopsies. As new therapies emerge for acquired resistance to tyrosine kinase inhibitors (TKIs), the need for additional biopsies in routine clinical practice has increased. Peripheral blood testing of circulating cell free DNA (cfDNA) is an alternative method for the detection of genetic alterations. We present 2 cases that highlight the utility of cfDNA along with tissue-based genomic testing in the treatment of EGFR-mutant NSCLC. Materials/Methods: This is a retrospective report of two cases. Guardant360Ò Biopsy-FreeÔ Tumor Sequencing was used for all cfDNA testing. Results: Case #1: A 48-year-old female, never smoker, presented with stage IV lung adenocarcinoma (ADC) metastatic to bone. EGFR L858R mutation was detected by pyrosequencing and she was treated with erlotinib for 1 year with stable disease. At progression, cfDNA testing was obtained and detected L858R and T790M. After treatment with osimertinib and subsequent response, cfDNA was repeated and detected no mutations. She had progression two months later. Percutaneous tissue genomics and cfDNA were performed and revealed L858R without T790M. Case #2: A 66-year-old male, never smoker, developed metastatic recurrence of ADC 3 years after surgical resection and adjuvant chemotherapy. EGFR pyrosequencing revealed 2 mutations in EGFR, L858R and V834L. He was treated with dacomitinib for 3.5 years followed by 6 months of nivolumab. At his next progression, a biopsy was obtained and tissue genomic testing showed emergence of T790M; simultaneous cfDNA testing also detected T790M. He enrolled on a clinical trial and was treated with chemotherapy then crossed over to rocelitinib. He progressed on rocelitinib and repeat cfDNA showed persistence of T790M. He transitioned to osimertinib with stable disease achieved for 2 months. He then developed malignant pericardial and pleural effusions. Next-generation sequencing on pleural fluid and cfDNA both detected L858R and V834 with absence of T790M. Unlike tissue testing, cfDNA detected the emergence of a C797S mutation. Conclusion: These cases highlight several advantages of cfDNA testing. First is the ability to obtain genomic data without the need for tissue. This may eliminate the need for outpatient biopsies and their associated risks. Second is the ability of cfDNA to complement tissue-based genetic testing. In both cases, cfDNA picked up the presence of mutations that were either not detected on tissue biopsy or no tissue biopsy was performed. Finally, both cases demonstrate that cfDNA can show elimination of T790M after treatment with the T790M-specific TKI osimertinib. Tissue-based testing remains the standard for detecting resistance mutations, but these cases demonstrate that cfDNA can obtain actionable information without biopsy in routine clinical practice. Author Disclosure: M. Devitt: Provides advisory role to council on aspects of trainee development within the American Society of Clinical Oncology; American Society of Clinical Oncology Trainee Council. R. Hall: Honoraria; Merck Pharmaceuticals. R.D. Gentzler: Honoraria; Merck. Advisory Board; Ariad.
LB1 Effects of Motion on Radiomics Analysis of Thoracic Cancers F.F. Yin,1 K. Lafata,2 J.C. Hong,3 and C.R. Kelsey3; 1Duke University, Durham, NC, 2Duke University Medical Physics Graduate Program, Durham, NC, 3Duke University Medical Center, Durham, NC Purpose/Objective(s): To investigate the effects of motion on radiomics analysis of thoracic cancers. Our in-house computational radiomics infrastructure has been retrospectively integrated into our clinic’s lung SBRT workflow to study three primary areas of radiomics research: (1) Feature Extraction, (2) Feature Characterization, and (3) Predictive Modeling. Materials/Methods: Thirty-one patients were retrospectively identified as meeting three data availability requirements: (1) an existing free-breathing 3DCT, (2) an existing 4DCT, and (3) a known tumor histology. Investigation of inherent feature variability was performed by studying (a) the effects of motion using a dynamic digital phantom, (b) the differences between 3DCT and 4DCT acquisitions, and (c) the stability of daily CBCT-derived features. Radiomic features were extracted using our in-house software, and classified into 4 categories: (1) Morphological, (2) Intensity, (3) Coarse Texture, and (4) Fine Texture. A paired-sample t-test was used to determine which features demonstrated different mean values when extracted from 3D and 4D imaging modalities. We then used a task-based approach to quantitatively demonstrate how feature variability can ultimately perturb predictive modeling. Specifically, a logistic regression algorithm was developed and trained to classify tumor histology (adenocarcinoma vs squamous cell) based on features derived first from each patient’s free-breathing 3DCT (FBCT), followed by the corresponding average-intensity-projection 4DCT (AIPCT). Fitting parameters were determined by minimizing a regularized cost function, of which optimization was performed via gradient descent, and the model was evaluated with a 4-fold bootstrapping technique. Results: Digital phantom results suggested that some texture features change non-monotonically with respiratory motion magnitude, indicating a motion-induced cancelling effect of certain feature magnitudes. Comparison of 3DCT with 4DCT demonstrated that motion blurring may severely alter heterogeneity tumor measurements. Further, FBCT-derived features demonstrated better histological classification (AUCZ0.66) relative to AIPCT-derived features (AUCZ0.59). However, when the most variable features (i.e., those which demonstrated a paired-sample t-test p-value < 5%) were removed from the feature spaces, both models converged to an AUC value of 0.63. Conclusion: A computational radiomics infrastructure has been developed and applied to our lung SBRT clinical workflow. Respiratory motioneinduced feature variability using both a computational phantom and patient data demonstrated perturbative modeling effects for tumor histology classification. Author Disclosure: F. Yin: Research Grant; Varian Medical Systems, NIH.
LB2 Clinical Outcomes Following Stereotactic Body Radiation Therapy to Multiple Sites of Intrathoracic Disease C. Goodman,1 P. Dalal,2 D. Cutright,2 N. Paudel,2 T. Kim,2 M.S. Gentile,2 and T.J. Kruser2; 1Northwestern University, Chicago, IL, United States, 2 Northwestern Feinberg School of Medicine, Chicago, IL Purpose/Objective(s): Second primary lung cancers are common in patients with inoperable lung cancer. Little data exist on the safety and efficacy of stereotactic body radiation therapy (SBRT) to multiple sites of intrathoracic disease. We sought to examine clinical outcomes for patients receiving SBRT to multiple intrathoracic sites.
Volume 98 Number 1 2017 Materials/Methods: Eighteen patients with 38 synchronous or metachronous lung nodules were treated between 2010 and 2016 at a tertiary hospital with SBRT. Demographic and clinicopathologic data as well as dosimetry for target volume coverage and organs at risk were collected. Pre-treatment, acute (<90 days), and late (>90 days) toxicities were retrospectively reviewed using standardized CTCAE 4.0 criteria. Radiographic and clinical pneumonitis was recorded. Local control (treatment field and ipsilateral lobe), regional control (ipsilateral lung or mediastinum), metastasis-free survival, progression-free survival, and overall survival were calculated. Results: Sixteen patients received SBRT to 2 sites, while two patients were treated at 3 sites. Six patients were treated for synchronous tumors, while 12 patients were treated for metachronous tumors. The median age at first treatment was 77 years (IQR: 68.5-79.8) and for metachronous lesions the median time interval between SBRT courses was 14.2 months (95% CI: 6.8-21.6). The majority (76.3%) of the treated nodules were primary lung tumors, while 23.7% were metastatic nodules of varying histologies. Forty percent of second or third SBRT courses were to nodules in the contralateral lung, while 40% were to nodules in the same lobe. The most common fractionation scheme was 50Gy in 5 fractions (cumulative range: 3000-6000 in 3-8 fractions). The mean treated nodule size was 2.0 cm (95% CI: 1.6-2.4). At median follow-up of 56.0 months from initial SBRT, local failure occurred in 10.8% of lesions. Median overall survival was 31.8 months (95% CI: 27.6-47.2) while median progression-free survival was 25.7 months (95% CI: 17.2-34.1). Six patients (16.6%) developed grade 1 pneumonitis, two patients (11.1%) developed grade 2 pneumonitis after their first SBRT course, while one patient (5.5%) developed grade 3 pneumonitis after her second course of SBRT. Conclusion: SBRT to synchronous or metachronous pulmonary malignancies appears to yield oncologic and toxicity outcomes similar to solitary lesion SBRT. Receipt of previous SBRT should not preclude consideration of further SBRT. Author Disclosure: C. Goodman: None.
LB3 Patterns of Care and Survival Outcomes in Stage II NoneSmall Cell Lung Cancer: An Analysis of the National Cancer Database S.X. Yan,1 M.M. Qureshi,2,3 M.T. Truong,2,3 and K.S. Mak2,3; 1Boston Medical Center, Boston, MA, 2Department of Radiation Oncology, Boston Medical Center, Boston, MA, 3Boston University School of Medicine, Boston, MA Purpose/Objective(s): Stage II nonesmall cell lung cancer (NSCLC) can be treated with primary surgery or radiation, with or without chemotherapy. This study delineates practice patterns in treating Stage II NSCLC in a national patient registry, and evaluates survival by management approach. Materials/Methods: Patients diagnosed with stage II NSCLC treated with radiation alone, chemoradiation therapy, or surgery with or without neoadjuvant or adjuvant chemotherapy, radiation, or chemoradiation therapy were identified using the National Cancer Database (NCDB). Survival rates for each treatment approach were estimated using Kaplan-Meier analysis. Univariate and multivariate Cox regression models were used to identify factors with significant impact on survival. Results: Between 2004 and 2013, a total of 26,732 patients were identified who met study criteria: 4,111 (15.4%) received radiation alone; 6,903 (25.8%) were treated with chemoradiation therapy; and 15,718 (58.8%) patients underwent surgery-based therapy. The percentage of patients receiving surgery increased over the 10-year study period, while those receiving radiation and chemoradiation therapy decreased (p<0.0001). Patients who received
Late-Breaking (LB) Abstracts
251
radiation tended to be older, with more comorbidities, Medicare rather than private insurance, and T2N2M0 stage (all p<0.0001). With median follow-up of 23.2 months, median survival was 13.7 months, 20.9 months, and 50.1 months in the radiation, chemoradiation, and surgery groups, respectively (p<0.0001). Five-year overall survival was 8.5%, 18.7%, and 45.0%, respectively. Age, gender, race, insurance status, Charlson-Deyo comorbidity score, year of diagnosis, treatment facility type, T and N stage, and treatment approach were identified to be independent predictors of survival on multivariate analysis. Surgery was associated with improved survival versus chemoradiation therapy on multivariate analysis (hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.54-0.59; p<0.0001). Both surgery (HR 0.38, 95% CI 0.37-0.40; p<0.0001) and chemoradiation therapy (HR 0.68, 95% confidence interval CI 0.65-0.71; p<0.0001) were associated with improved survival over radiation therapy alone on multivariate analysis. Conclusion: Data from the NCDB demonstrates increasing use of surgery-based treatment for Stage II NSCLC over time. Surgery-based therapy was associated with improved survival compared to chemoradiation or radiation alone. Author Disclosure: M.M. Qureshi: None.
LB4 Development of a Transcriptomic Signature Associated With Lung Adenocarcinoma Recurrence and Survival E.D. Brooks,1 G. Micevic,2 and J.Y. Chang1; 1Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 2Yale University School of Medicine, New Haven, CT, United States Purpose/Objective(s): Lung adenocarcinoma patients within AJCC substages exhibit great variability in survival, underscoring the need for more accurate prognostic approaches. Aberrant promoter DNA methylation is a key feature of cancers, including melanoma. Identification of transcriptional signature has been useful in predicting prognosis, diagnosis, and response to treatment in a variety of tumor types. The purpose of this study is to develop a transcriptomic prognostic tool for patients with lung adenocarcinoma, who currently exhibit great variability in survival even within AJCC subgroups. Materials/Methods: We used transcriptomic (RNA-Seq) data from a portion of lung adenocarcinoma samples from The Cancer Genome Atlas and subdivided it into two groups (nZ 170 each), based on disease relapse, into a rapidly progressive and better prognosis cohort. We performed an unbiased differential transcriptomic analysis and identified a ranked list of genes exhibiting differential expression between the two cohorts. Top ranking genes were used to build a 7-gene survival prediction score using multiple logistic regression. Results: In the test cohort, consisting of lung adenocarcinoma samples from The Cancer Genome Atlas not used for discovery (nZ200), a beneficial score was associated with a significantly longer 5-year overall survival (p<0.001, log-rank test). A high score was associated with high G2/M checkpoint gene expression (q<0.0001), mitotic spindle assembly gene expression (qZ0.003), E2F transcription factor targets, and activation of mTORC1 signaling (qZ0.013). Conclusion: In this study, we define a transcriptomic-based lung adenocarcinoma survival prediction tool which can potentially identify the subgroup of patients with aggressive disease who rapidly progress. Identification of this high risk group can contribute to improved care of lung cancer patients and provision of most appropriate therapies, including radiation therapy. For early-stage disease, identifying such patients helps to determine who could potentially benefit from upfront systemic therapy. Author Disclosure: G. Micevic: None.