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Assessment of Response After Stereotactic Ablative Radiation Therapy (SABR) for Lung Cancer: Can Advanced CT Image Feature Analysis Predict Recurrence?
Volume 87 Number 2S Supplement 2013
24 Performance of PET in Evaluating Local Recurrence After Stereotactic Ablative Radiation Therapy for Early Lung Cancer S.M. Hiniker, L.A. Modlin, J.P. Harris, N. Trakul, A. Quon, P.G. Maxim, E.E. Graves, M. Diehn, and B.W. Loo; Stanford University, Stanford, CA Purpose/Objective(s): Differentiating local recurrence (LR) from posttreatment changes on PET scans following stereotactic ablative radiation therapy (SABR) for lung tumors is challenging. We sought to evaluate the performance of post-SABR PET in patients treated definitively for stage I-II non-small cell lung cancer (NSCLC), and to identify factors associated with false-positive PET. Materials/Methods: This retrospective study included patients with stage I-II NSCLC treated definitively with SABR and followed with surveillance PET scans between 2004 and 2011. PET reports were coded as 0 (minimal concern for LR) or 1 (substantial concern for LR) and correlated with biopsy and/or clinical outcomes. Prognostic factors for false-positive PET were assessed with logistic regression models. Cochran-Armitage trend test and Pearson correlation were used to evaluate rates of false-positive PET over time. Results: We identified 145 patients who met inclusion criteria. Thirty-nine of 145 (26.9%) had PET concerning for LR between 3 and 24 months postSABR. Four of 39 (10%) received salvage therapy presumptively. Seven of 39 (18%) underwent immediate biopsy, and 6 were positive for LR. Twenty-eight of 39 (72%) were initially followed with repeat PET; 23 improved by the next scan and were re-coded as not concerning, and 5 had scans interpreted as increasingly concerning. Four of 5 were subsequently biopsied, with 3 positive and 1 nondiagnostic; the fifth patient declined biopsy and was diagnosed with LR presumptively. In total, 11/39 (28%) were biopsied, and 9/11 (82%) biopsies were positive; 5 patients were diagnosed with LR on imaging findings alone. The PPV of PET concerning for LR was 14/39 (36%). All 14 patients who experienced LR in our cohort had a concerning PET. Factors significantly associated with false-positive PET were occurrence of the concerning PET at the earliest post-treatment time point (3 months) (OR 15.5, p Z 0.014) and younger age (OR 1.7, p Z 0.03). The rate of false-positive PET significantly decreased over time from 2004 to 2011 (r Z -0.38, p Z 0.018) Conclusions: Our analysis indicates that the PPV of a concerning PET post-SABR remains relatively low but is improving over time, perhaps due to increased recognition of SABR-induced imaging changes. Having a concerning PET early (at 3 months post-SABR) is associated with falsepositivity, as is younger age, potentially due to a more robust inflammatory response in younger patients. To our knowledge, this is the first study reporting improved accuracy of post-SABR PET over time and defining features of false-positive scans. Still, our findings underscore the need for improved surveillance imaging techniques to avoid unnecessary invasive biopsies, as well as to avoid delay in diagnosis of local recurrence and potentially curative salvage therapy. Author Disclosure: S.M. Hiniker: None. L.A. Modlin: None. J.P. Harris: None. N. Trakul: None. A. Quon: None. P.G. Maxim: None. E.E. Graves: None. M. Diehn: E. Research Grant; Varian Medical Systems. B.W. Loo: E. Research Grant; Varian Medical Systems. F. Honoraria; Varian Medical Systems.
25 Assessment of Response After Stereotactic Ablative Radiation Therapy (SABR) for Lung Cancer: Can Advanced CT Image Feature Analysis Predict Recurrence? S. Mattonen,1 D.A. Palma,1,2 C.J. Haasbeek,3 S. Senan,3 and A.D. Ward1; 1 Western University, London, ON, Canada, 2London Regional Cancer Program, London, ON, Canada, 3VU University Medical Center, Amsterdam, Netherlands Purpose/Objective(s): Stereotactic ablative radiation therapy (SABR) is becoming the standard treatment option for patients with early-stage nonsmall cell lung cancer who are medically inoperable or refuse surgery. However, benign CT changes due to radiation-induced lung injury (RILI)
Oral Scientific Sessions
S11
are common post-SABR, and difficult to differentiate from recurrence. The goal of this study was to measure the utility and predictive power of CT image features in differentiating RILI from recurrence at different time intervals post-treatment. Materials/Methods: A total 22 patients, with 24 lesions, treated with SABR were selected (11 with recurrence [73% biopsy proven], 13 without recurrence but with substantial benign RILI). Common changes postSABR were manually contoured on each follow-up CT: consolidative and ground glass opacity (GGO). Contours were completed by a single investigator and approved by a thoracic radiation oncologist. Response Evaluation Criteria In Solid Tumors (RECIST) measurements were also taken for the consolidative regions. For each lesion, regions were analyzed for the mean and variation in Hounsfield unit (HU) density (measuring image texture), 3D volume, and RECIST at specific follow-up time intervals. The classification performance of the measures was determined using leave-one-out cross validation of a quadratic classifier. Results: One hundred thirty-six CT scans were reviewed (median imaging follow-up of 26 months). Within a 3-5 month follow-up interval, patients with recurrence had significantly denser GGO changes compared to patients with RILI (p Z .035). The combined features of GGO image texture and density yielded the best recurrence prediction at 3-5 months, with a cross validation accuracy of 81.0% (false negative [FN] Z 18.2%, false positive [FP] Z 20.0%). At 6-8 months, patients with recurrence had significantly denser consolidative changes (p Z .021) and increased variability of CT densities within the GGO (p Z .0019). At this time point, GGO texture alone was the best predictor with an accuracy of 81.8% (FN Z 25.0%, FP Z 10.0%). RECIST and 3D volume did not significantly distinguish the groups within either time period, and classification accuracies using these metrics did not exceed 50%. Conclusions: Our results suggest that important changes in the appearance of the tissue surrounding the consolidation regions precede changes in size and have the potential to distinguish individual patients with recurrence from those with RILI within 5 months post-SABR. If validated on a larger dataset, this could lead to a clinically useful computer-aided diagnosis tool which could allow for earlier salvage of patients with recurrence, and result in fewer investigations of benign RILI. Author Disclosure: S. Mattonen: None. D.A. Palma: None. C.J. Haasbeek: None. S. Senan: F. Honoraria; Varian Medical Systems. G. Consultant; Varian Medical Systems. A.D. Ward: None.
26 PET Predicts Survival Following Stereotactic Body Radiation Therapy for Non-Small Cell Lung Cancer B.R. Mancini,1 N.J. Giacalone,2 C.E. Rutter,1 S. Aneja,1 R.H. Decker,1 and Z.A. Husain1; 1Yale School of Medicine, Yale University, New Haven, CT, 2Vanderbilt University School of Medicine, Nashville, TN Purpose/Objective(s): The prognostic importance of positron emission tomography (PET) standardized uptake value maximum (SUVm) scores for patients with early stage non-small cell lung carcinoma (ES-NSCLC) treated with stereotactic body radiation therapy (SBRT) is unclear. This study aims to address this uncertainty. Materials/Methods: Records of patients diagnosed with ES-NSCLC and treated with SBRT between September 2007 and May 2012 were retrospectively reviewed. Mediastinoscopy was used to stage patients with synchronous primary lesions, centrally located lesions, and those larger than 3 cm. SBRT was delivered via 3-5 fractions to a dose of 40-60 Gy, with the vast majority of patients receiving 54 Gy in 3 fractions. Univariate and multivariate Cox proportional hazards analyses were used to compare disease progression and overall survival on the basis of preSBRT and post-SBRT SUVm, absolute change in SUVm, age, tumor size, and histology. Results: One hundred twenty-seven patients with a median follow-up of 14 months were identified. Median age was 73.9 years and 54% were male. Histology was adenocarcinoma in 39%, squamous cell carcinoma in 20%, unspecified NSCLC in 20%, and unbiopsied in 21%. Pre-SBRT
24 Performance of PET in Evaluating Local Recurrence After Stereotactic Ablative Radiation Therapy for Early Lung Cancer S.M. Hiniker, L.A. Modlin, J.P. Harris, N. Trakul, A. Quon, P.G. Maxim, E.E. Graves, M. Diehn, and B.W. Loo; Stanford University, Stanford, CA Purpose/Objective(s): Differentiating local recurrence (LR) from posttreatment changes on PET scans following stereotactic ablative radiation therapy (SABR) for lung tumors is challenging. We sought to evaluate the performance of post-SABR PET in patients treated definitively for stage I-II non-small cell lung cancer (NSCLC), and to identify factors associated with false-positive PET. Materials/Methods: This retrospective study included patients with stage I-II NSCLC treated definitively with SABR and followed with surveillance PET scans between 2004 and 2011. PET reports were coded as 0 (minimal concern for LR) or 1 (substantial concern for LR) and correlated with biopsy and/or clinical outcomes. Prognostic factors for false-positive PET were assessed with logistic regression models. Cochran-Armitage trend test and Pearson correlation were used to evaluate rates of false-positive PET over time. Results: We identified 145 patients who met inclusion criteria. Thirty-nine of 145 (26.9%) had PET concerning for LR between 3 and 24 months postSABR. Four of 39 (10%) received salvage therapy presumptively. Seven of 39 (18%) underwent immediate biopsy, and 6 were positive for LR. Twenty-eight of 39 (72%) were initially followed with repeat PET; 23 improved by the next scan and were re-coded as not concerning, and 5 had scans interpreted as increasingly concerning. Four of 5 were subsequently biopsied, with 3 positive and 1 nondiagnostic; the fifth patient declined biopsy and was diagnosed with LR presumptively. In total, 11/39 (28%) were biopsied, and 9/11 (82%) biopsies were positive; 5 patients were diagnosed with LR on imaging findings alone. The PPV of PET concerning for LR was 14/39 (36%). All 14 patients who experienced LR in our cohort had a concerning PET. Factors significantly associated with false-positive PET were occurrence of the concerning PET at the earliest post-treatment time point (3 months) (OR 15.5, p Z 0.014) and younger age (OR 1.7, p Z 0.03). The rate of false-positive PET significantly decreased over time from 2004 to 2011 (r Z -0.38, p Z 0.018) Conclusions: Our analysis indicates that the PPV of a concerning PET post-SABR remains relatively low but is improving over time, perhaps due to increased recognition of SABR-induced imaging changes. Having a concerning PET early (at 3 months post-SABR) is associated with falsepositivity, as is younger age, potentially due to a more robust inflammatory response in younger patients. To our knowledge, this is the first study reporting improved accuracy of post-SABR PET over time and defining features of false-positive scans. Still, our findings underscore the need for improved surveillance imaging techniques to avoid unnecessary invasive biopsies, as well as to avoid delay in diagnosis of local recurrence and potentially curative salvage therapy. Author Disclosure: S.M. Hiniker: None. L.A. Modlin: None. J.P. Harris: None. N. Trakul: None. A. Quon: None. P.G. Maxim: None. E.E. Graves: None. M. Diehn: E. Research Grant; Varian Medical Systems. B.W. Loo: E. Research Grant; Varian Medical Systems. F. Honoraria; Varian Medical Systems.
25 Assessment of Response After Stereotactic Ablative Radiation Therapy (SABR) for Lung Cancer: Can Advanced CT Image Feature Analysis Predict Recurrence? S. Mattonen,1 D.A. Palma,1,2 C.J. Haasbeek,3 S. Senan,3 and A.D. Ward1; 1 Western University, London, ON, Canada, 2London Regional Cancer Program, London, ON, Canada, 3VU University Medical Center, Amsterdam, Netherlands Purpose/Objective(s): Stereotactic ablative radiation therapy (SABR) is becoming the standard treatment option for patients with early-stage nonsmall cell lung cancer who are medically inoperable or refuse surgery. However, benign CT changes due to radiation-induced lung injury (RILI)
Oral Scientific Sessions
S11
are common post-SABR, and difficult to differentiate from recurrence. The goal of this study was to measure the utility and predictive power of CT image features in differentiating RILI from recurrence at different time intervals post-treatment. Materials/Methods: A total 22 patients, with 24 lesions, treated with SABR were selected (11 with recurrence [73% biopsy proven], 13 without recurrence but with substantial benign RILI). Common changes postSABR were manually contoured on each follow-up CT: consolidative and ground glass opacity (GGO). Contours were completed by a single investigator and approved by a thoracic radiation oncologist. Response Evaluation Criteria In Solid Tumors (RECIST) measurements were also taken for the consolidative regions. For each lesion, regions were analyzed for the mean and variation in Hounsfield unit (HU) density (measuring image texture), 3D volume, and RECIST at specific follow-up time intervals. The classification performance of the measures was determined using leave-one-out cross validation of a quadratic classifier. Results: One hundred thirty-six CT scans were reviewed (median imaging follow-up of 26 months). Within a 3-5 month follow-up interval, patients with recurrence had significantly denser GGO changes compared to patients with RILI (p Z .035). The combined features of GGO image texture and density yielded the best recurrence prediction at 3-5 months, with a cross validation accuracy of 81.0% (false negative [FN] Z 18.2%, false positive [FP] Z 20.0%). At 6-8 months, patients with recurrence had significantly denser consolidative changes (p Z .021) and increased variability of CT densities within the GGO (p Z .0019). At this time point, GGO texture alone was the best predictor with an accuracy of 81.8% (FN Z 25.0%, FP Z 10.0%). RECIST and 3D volume did not significantly distinguish the groups within either time period, and classification accuracies using these metrics did not exceed 50%. Conclusions: Our results suggest that important changes in the appearance of the tissue surrounding the consolidation regions precede changes in size and have the potential to distinguish individual patients with recurrence from those with RILI within 5 months post-SABR. If validated on a larger dataset, this could lead to a clinically useful computer-aided diagnosis tool which could allow for earlier salvage of patients with recurrence, and result in fewer investigations of benign RILI. Author Disclosure: S. Mattonen: None. D.A. Palma: None. C.J. Haasbeek: None. S. Senan: F. Honoraria; Varian Medical Systems. G. Consultant; Varian Medical Systems. A.D. Ward: None.
26 PET Predicts Survival Following Stereotactic Body Radiation Therapy for Non-Small Cell Lung Cancer B.R. Mancini,1 N.J. Giacalone,2 C.E. Rutter,1 S. Aneja,1 R.H. Decker,1 and Z.A. Husain1; 1Yale School of Medicine, Yale University, New Haven, CT, 2Vanderbilt University School of Medicine, Nashville, TN Purpose/Objective(s): The prognostic importance of positron emission tomography (PET) standardized uptake value maximum (SUVm) scores for patients with early stage non-small cell lung carcinoma (ES-NSCLC) treated with stereotactic body radiation therapy (SBRT) is unclear. This study aims to address this uncertainty. Materials/Methods: Records of patients diagnosed with ES-NSCLC and treated with SBRT between September 2007 and May 2012 were retrospectively reviewed. Mediastinoscopy was used to stage patients with synchronous primary lesions, centrally located lesions, and those larger than 3 cm. SBRT was delivered via 3-5 fractions to a dose of 40-60 Gy, with the vast majority of patients receiving 54 Gy in 3 fractions. Univariate and multivariate Cox proportional hazards analyses were used to compare disease progression and overall survival on the basis of preSBRT and post-SBRT SUVm, absolute change in SUVm, age, tumor size, and histology. Results: One hundred twenty-seven patients with a median follow-up of 14 months were identified. Median age was 73.9 years and 54% were male. Histology was adenocarcinoma in 39%, squamous cell carcinoma in 20%, unspecified NSCLC in 20%, and unbiopsied in 21%. Pre-SBRT