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Elderly Patients Undergoing SBRT for Inoperable Early-Stage NSCLC Achieve Similar Outcomes to Younger Patients
Volume 90 Number 5S Supplement 2014 respiratory phases are acquired for all slices), we performed computer simulations using Real-time Position Management (RPM) respiratory signals of 29 cancer patients to derive the relationship between NR and influencing factors, including number of slices scanned (NS), number of respiratory phases of the 4D-DWI (NP), and starting phase at image acquisition (P0). A frame rate of w2 frames/s was assumed for DWI image acquisition in the simulation. Retrospective sorting and reconstruction of 4D-DWI were achieved using a novel, hybrid (phase and amplitude) sorting algorithm utilizing redundantly acquired images. The techniques for 4D-DWI acquisition and reconstruction were evaluated using both a 4D digital human phantom (XCAT) via computer simulation and healthy volunteer cases under an IRB protocol. Results: Percentage of complete acquisition of all respiratory phases (Cp) increased as NR increased in an inverse-exponential fashion (CpZ100*[1-exp (-0.28*NR)], when NSZ30, NPZ6). The NR needed for 4D-DWI (defined as achieving 95% completion, CpZ95%) showed a linear relationship with NP (NRw1.8xNP, rZ1.0), but was independent of NS and P0. Simulated 4D-DWI on the XCAT phantom showed clear patterns of respiratory motion, consistent with the input signal: the cross-correlation coefficient (CC) and the mean relative difference in motion amplitude (D) were 0.97 and 1.5%, respectively, in the superior-inferior direction, and 0.99 and 0.04% in the anteriorposterior direction. The 4D-DWI of healthy volunteers also revealed respiratory motion of internal organs. The mean relative difference in motion trajectory of a selected region of interest (left kidney) was 2.8% between 4D-DWI and single slice sagittal cine MRI, which was used as reference. Conclusions: A novel 4D-DWI technique has been developed and validated. This has significant potential to improve the visualization and delineation of mobile cancers for radiation therapy. Author Disclosure: Y. Liu: None. F. Yin: None. B. Czito: None. B.R. Mustafa: None. J. Cai: None.
108 WITHDRAWN
109 Quantitative Measurement of BIM Protein in Lung Cancer Diagnosis/Staging B.S. Henick,1 E. Zarrella,1 M. Altan,1 J. McLaughlin,1 K. Schalper,1 V. Velcheti,2 and D.L. Rimm1; 1Yale School of Medicine, New Haven, CT, 2 Cleveland Clinic, Cleveland, OH Purpose/Objective(s): A proportion of EGFR-mutant and ALK-rearranged lung cancers do not respond to tyrosine kinase inhibition for as-yet unknown reasons. The BH3-only Bcl-2 family member BIM has been implicated as a potential biomarker of clinical benefit from kinase inhibitors. Quantifying BIM expression in tumor samples of patients with lung cancer may help to predict outcome, and potentially to guide therapy. Materials/Methods: An index tissue microarray (TMA282) was constructed using cancer cell lines with various BIM levels and human FFPE tumors, and was used for antibody validation and optimal titration. We then measured the levels of BIM in 309 lung carcinomas represented in one TMA (YTMA250) using the rabbit monoclonal clone C34C5 (Cell signaling technology) and quantitative immunofluorescence (QIF). Results: Preliminary data showed that levels of BIM determined by QIF were comparable to those obtained by western blot in the same samples. Lung cancer samples showed a wide range of BIM levels, and were directly related to histological tumor differentiation grade (P<.05). No significant differences in BIM levels were observed according to age, gender, major histology variants, tumor size, and stage. Preliminary survival analysis using the median score as cutpoint demonstrated no association between BIM levels and recurrence-free or overall survival (logrank P>.05). Conclusions: We have validated an immunofluorescence assay for quantitative BIM measurements in FFPE samples. Our preliminary results
Poster Presentations
S11
indicate that BIM is significantly associated with histological grade, but not with other clinical or pathological variables. Preliminary survival analysis suggests that BIM is not prognostic in lung cancer. Validation of these results is ongoing. Future studies will be required to determine the value of BIM measurements to predict response to TKIs in EGFR-mutant lung adenocarcinomas. Author Disclosure: B.S. Henick: None. E. Zarrella: None. M. Altan: None. J. McLaughlin: None. K. Schalper: None. V. Velcheti: None. D.L. Rimm: None.
110 Elderly Patients Undergoing SBRT for Inoperable Early-Stage NSCLC Achieve Similar Outcomes to Younger Patients Early-Stage Non-Small Cell Lung Cancer B.R. Mancini, H.S. Park, E. Harder, C.E. Rutter, C.D. Corso, R.H. Decker, and Z.A. Husain; Yale School of Medicine j Yale University, New Haven, CT Purpose/Objective(s): A recent publication demonstrated that lung resection in patients age >65 with early stage non-small cell lung cancer (NSCLC) was associated with perioperative complications in >50% of cases. This was found to increase with age and was significantly higher for patients age 75. It is unclear if older patients undergoing stereotactic body radiation therapy (SBRT) face a similar increased risk. This study aims to address toxicity and survival achieved with SBRT in the elderly compared to younger patients treated at the same institution. Materials/Methods: Records of patients diagnosed with T1-3N0M0 NSCLC treated with SBRT between Sep 2007 and Aug 2013 were reviewed. SBRT was delivered in 3-5 fractions to 40-60 Gy, with a vast majority of patients receiving 54 Gy in 3 fractions. Patients were divided into 2 cohorts, age 75 and <75. Kaplan-Meier and Cox proportional hazard analyses were used for univariate and multivariate analyses of survival, respectively. Chi-square and logistic regression analyses were used for univariate and multivariate toxicity assessment, respectively. We compared overall survival (OS), local recurrenceefree survival (LRFS), and distant recurrenceefree survival (DRFS) between cohorts. Results: Two hundred fifty-three patients were identified. Of these, 127 were 75 and 126 were <75. Median follow-up was 24.9 mos. There were no differences in gender, ECOG performance status, smoking status, clinical vs pathological diagnosis of NSCLC, histology (adenoca vs all others), T-stage (T1 vs T2-3), peripheral v central tumor, BED, or number of targets between the 2 groups (all P>.05). There was a trend toward less frequent mediastinal staging in the elderly (25.2% vs 34.9%, PZ.10). There was no difference between patients 75 vs <75 in 2-year OS (48.8% vs 60.4%, PZ.95) or LRFS (86.1% vs 88.4%, PZ.97). There was a statistically significant difference in 2-year DRFS (89.9% vs 74.9%, HR 0.44, PZ.02) favoring patients 75. On multivariate Cox proportional hazards analysis, age 75 remained associated with improved DRFS (HR 0.40, PZ.02). There was no difference in acute or late grade 2-3 toxicity for patients age 75 vs <75. Common toxicities included fatigue, chest wall pain, and increased dyspnea/pneumonitis. Rate of grade 3 acute toxicity was 5.5% overall (4.7% age 75 vs 6.3% age <75). Rate of grade 3 late toxicity was 4.0% overall (3.9% age 75 vs 4.0% age <75). Most common acute and late grade 3 toxicity was increased dyspnea/pneumonitis (3.6% and 2.0%, respectively). Two patients had grade 4 acute, 1 had grade 4 late, and 1 had grade 5 late toxicity in the <75 cohort, with no grade 4-5 toxicity in the >75 cohort. Conclusions: To our knowledge, this is the largest single institution study to date evaluating safety and efficacy of SBRT in an elderly population. In our series, elderly patients undergoing SBRT appear to have achieved similar outcomes and toxicity compared to younger patients. Author Disclosure: B.R. Mancini: None. H.S. Park: None. E. Harder: None. C.E. Rutter: None. C.D. Corso: None. R.H. Decker: None. Z.A. Husain: None.
108 WITHDRAWN
109 Quantitative Measurement of BIM Protein in Lung Cancer Diagnosis/Staging B.S. Henick,1 E. Zarrella,1 M. Altan,1 J. McLaughlin,1 K. Schalper,1 V. Velcheti,2 and D.L. Rimm1; 1Yale School of Medicine, New Haven, CT, 2 Cleveland Clinic, Cleveland, OH Purpose/Objective(s): A proportion of EGFR-mutant and ALK-rearranged lung cancers do not respond to tyrosine kinase inhibition for as-yet unknown reasons. The BH3-only Bcl-2 family member BIM has been implicated as a potential biomarker of clinical benefit from kinase inhibitors. Quantifying BIM expression in tumor samples of patients with lung cancer may help to predict outcome, and potentially to guide therapy. Materials/Methods: An index tissue microarray (TMA282) was constructed using cancer cell lines with various BIM levels and human FFPE tumors, and was used for antibody validation and optimal titration. We then measured the levels of BIM in 309 lung carcinomas represented in one TMA (YTMA250) using the rabbit monoclonal clone C34C5 (Cell signaling technology) and quantitative immunofluorescence (QIF). Results: Preliminary data showed that levels of BIM determined by QIF were comparable to those obtained by western blot in the same samples. Lung cancer samples showed a wide range of BIM levels, and were directly related to histological tumor differentiation grade (P<.05). No significant differences in BIM levels were observed according to age, gender, major histology variants, tumor size, and stage. Preliminary survival analysis using the median score as cutpoint demonstrated no association between BIM levels and recurrence-free or overall survival (logrank P>.05). Conclusions: We have validated an immunofluorescence assay for quantitative BIM measurements in FFPE samples. Our preliminary results
Poster Presentations
S11
indicate that BIM is significantly associated with histological grade, but not with other clinical or pathological variables. Preliminary survival analysis suggests that BIM is not prognostic in lung cancer. Validation of these results is ongoing. Future studies will be required to determine the value of BIM measurements to predict response to TKIs in EGFR-mutant lung adenocarcinomas. Author Disclosure: B.S. Henick: None. E. Zarrella: None. M. Altan: None. J. McLaughlin: None. K. Schalper: None. V. Velcheti: None. D.L. Rimm: None.
110 Elderly Patients Undergoing SBRT for Inoperable Early-Stage NSCLC Achieve Similar Outcomes to Younger Patients Early-Stage Non-Small Cell Lung Cancer B.R. Mancini, H.S. Park, E. Harder, C.E. Rutter, C.D. Corso, R.H. Decker, and Z.A. Husain; Yale School of Medicine j Yale University, New Haven, CT Purpose/Objective(s): A recent publication demonstrated that lung resection in patients age >65 with early stage non-small cell lung cancer (NSCLC) was associated with perioperative complications in >50% of cases. This was found to increase with age and was significantly higher for patients age 75. It is unclear if older patients undergoing stereotactic body radiation therapy (SBRT) face a similar increased risk. This study aims to address toxicity and survival achieved with SBRT in the elderly compared to younger patients treated at the same institution. Materials/Methods: Records of patients diagnosed with T1-3N0M0 NSCLC treated with SBRT between Sep 2007 and Aug 2013 were reviewed. SBRT was delivered in 3-5 fractions to 40-60 Gy, with a vast majority of patients receiving 54 Gy in 3 fractions. Patients were divided into 2 cohorts, age 75 and <75. Kaplan-Meier and Cox proportional hazard analyses were used for univariate and multivariate analyses of survival, respectively. Chi-square and logistic regression analyses were used for univariate and multivariate toxicity assessment, respectively. We compared overall survival (OS), local recurrenceefree survival (LRFS), and distant recurrenceefree survival (DRFS) between cohorts. Results: Two hundred fifty-three patients were identified. Of these, 127 were 75 and 126 were <75. Median follow-up was 24.9 mos. There were no differences in gender, ECOG performance status, smoking status, clinical vs pathological diagnosis of NSCLC, histology (adenoca vs all others), T-stage (T1 vs T2-3), peripheral v central tumor, BED, or number of targets between the 2 groups (all P>.05). There was a trend toward less frequent mediastinal staging in the elderly (25.2% vs 34.9%, PZ.10). There was no difference between patients 75 vs <75 in 2-year OS (48.8% vs 60.4%, PZ.95) or LRFS (86.1% vs 88.4%, PZ.97). There was a statistically significant difference in 2-year DRFS (89.9% vs 74.9%, HR 0.44, PZ.02) favoring patients 75. On multivariate Cox proportional hazards analysis, age 75 remained associated with improved DRFS (HR 0.40, PZ.02). There was no difference in acute or late grade 2-3 toxicity for patients age 75 vs <75. Common toxicities included fatigue, chest wall pain, and increased dyspnea/pneumonitis. Rate of grade 3 acute toxicity was 5.5% overall (4.7% age 75 vs 6.3% age <75). Rate of grade 3 late toxicity was 4.0% overall (3.9% age 75 vs 4.0% age <75). Most common acute and late grade 3 toxicity was increased dyspnea/pneumonitis (3.6% and 2.0%, respectively). Two patients had grade 4 acute, 1 had grade 4 late, and 1 had grade 5 late toxicity in the <75 cohort, with no grade 4-5 toxicity in the >75 cohort. Conclusions: To our knowledge, this is the largest single institution study to date evaluating safety and efficacy of SBRT in an elderly population. In our series, elderly patients undergoing SBRT appear to have achieved similar outcomes and toxicity compared to younger patients. Author Disclosure: B.R. Mancini: None. H.S. Park: None. E. Harder: None. C.E. Rutter: None. C.D. Corso: None. R.H. Decker: None. Z.A. Husain: None.