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Risk Factor Study of Radiation Pneumonitis Focused on Subclinical Interstitial Lung Disease in Definitive Radiation Therapy for Non–Small Cell Lung Cancer: A Single-Institution Experience
Oral Scientific Sessions S131
Volume 96 Number 2S Supplement 2016 operating characteristics (ROC) analysis was used to determine the optimal cutpoint for dosimetric parameters. Results: We included 138 cases: 73 men (53.0%); median age 63 years (range, 42-83); predominantly NSCLC (N Z 114, 82.6%). Most patients received either platinum/etoposide (N Z 83, 60.1%) or carboplatin/taxol (N Z 48, 34.8%). Median RT dose was 61.2 Gy (range, 45-70 Gy). The rate of HT3+ was 41.3% (n Z 57). Increasing mean TVB dose (per Gy) was associated with a higher odds of developing HT3+ (OR Z 1.06, 95% CI Z 1.01-1.10, P Z 0.012). Increasing TVB V5-V40 was all significantly correlated with increased odds of developing HT3+. ROC analysis found that the optimal cutpoint for mean TVB dose was 23 Gy. The OR for developing HT3+ was 2.80-fold higher in patients with mean TVB dose >23 Gy compared to 23 Gy (95% CI Z 2.80-5.63, P Z 0.001). On multivariate analysis, increasing mean TVB dose, increasing age, and decreasing BMI were all statistically significantly associated with increased odds of developing HT3+. When excluding patients with SCLC, mean TVB dose and V5-V20 remained significantly associated with HT3+. Conclusion: We found that increasing TVB dose was associated with clinically significant HT in patients with lung cancer treated with CRT. This suggests that efforts to spare dose to the TVB may reduce rates of HT and potentially improve patient outcomes. Further prospective validation of these results is needed. Author Disclosure: C. Barney: None. N. Scoville: None. K.E. Haglund: None. J.C. Grecula: None. T.M. Williams: None. M.X. Welliver: None. G. Otterson: None. J.G. Bazan: None.
294 Risk Factor Study of Radiation Pneumonitis Focused on Subclinical Interstitial Lung Disease in Definitive Radiation Therapy for NoneSmall Cell Lung Cancer: A Single-Institution Experience Y. Li, S. Liang, Z. Zhou, Y. Cai, Y. Chen, and F. Li; Department of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Purpose/Objective(s): The widespread use of high-resolution computed tomography in clinical and research settings has increased the detection of interstitial lung abnormalities in asymptomatic and undiagnosed individuals. We evaluated the association between subclinical interstitial lung disease (ILD) and radiation pneumonitis (RP) in patients for with IIIA or IIIB NoneSmall-Cell Lung Cancer (NSCLC) treated with definitive radiotherapy (RT). Materials/Methods: All IIIA or IIIB NSCLC patients treated with thoracic definitive RT from January 2014 to May 2015 were analyzed. One hundred eighty-six consecutive patients with NSCLC were treated by thoracic RT at our institution. The presence, extent, and distribution of subclinical ILD on CT findings at pre-thoracic RT were reviewed and scored. Pre-thoracic RT CT findings were reviewed by two chest radiologists as no evidence of ILD (score Z 0), slight ILD (score Z 1), mild ILD (score Z 2), or moderate ILD (score Z 3). Slight ILD was defined as focal or unilateral groundglass attenuation, focal or unilateral reticulation and patchy ground-glass abnormalities (<5% of the lung). Mild ILD was defined as follows: nondependent ground-glass abnormality affecting more than 5% of any lung zone, nondependent reticular abnormality, diffuse centrilobular nodularity with ground-glass abnormality, honeycombing, traction bronchiectasis, non-emphysematous cysts and architectural distortion. Moderate ILD was defined as bilateral fibrosis in multiple lobes associated with honeycombing and traction bronchiectasis with a sub-pleural distribution. The median total dose was 60 Gy (range Z 58-66 Gy). The fraction dose was 1.8-2.25 Gy (median Z 2.0 Gy). The Complete DVH data were available for all patients. The relationships between RP and clinical factors including subclinical ILD were investigated. Results: Grade 2 RP was recognized in 50 (26.9%) patients including 1 patients (0.5%) with fatal RP (Grade 5), and Grade 3 RP occurred in 19 patients (10.2%). Twenty cases of 2 RP was found in 25 subclinical ILD patients including 1 RP grade 5. In 161 patients free of subclinical ILD, 30 (18.6%) cases of 2 RP were recognized. Spearman correlations revealed that subclinical ILD was significantly correlated with RP (rho Z 0.472; P
Z 0.000). Gender, primary tumor location (upper versus lower lobes), smoking history, forced expiratory volume in 1 second (FEV1), T stage, N stage, Gross Tumor Volume, and chemotherapy modality (sequential or concurrent) were not related to the risk of developing RP. Univariate analyses revealed that age and subclinical ILD were related to the risk of developing RP (P Z 0.040, 0.000, respectively) and no dosimetric factors were significant. Multivariate analyses demonstrated that only subclinical ILD was independent predictor (b Z 2.861, SE Z 0.566, Wald Z 25.540, P Z 0.000, RR Z 17.473, 95% CI Z 5.762-52.990). Conclusion: In this study, RP tended to be much more common in the patients with subclinical ILD. Author Disclosure: Y. Li: None. S. Liang: None. Z. Zhou: None. Y. Cai: None. Y. Chen: None. F. Li: None.
295 Risk Factors Associated With Fatal Radiation Pneumonitis after Concurrent Chemoradiation Therapy for Non-Small Cell Lung Cancer K. Tsujino, H. Kubota, H. Kawaguchi, Y. Matsumoto, Y. Ota, and T. Soejima; Hyogo Cancer Center, Akashi, Japan Purpose/Objective(s): We have previously proposed a new predictive risk score (PRS) for predicting severe (aNCI-CTC grade 3) radiation pneumonitis (RP) after concurrent chemoradiotherapy (CCRT) for non-small cell lung cancer (NSCLC) (JTO 9:983-990, 2014). This PRS is calculated from age, pulmonary fibrosis score (PFS) on baseline chest CT scan, lung V20, and VS5 (absolute lung volume spared from a 5-Gy dose); PRS Z 3 (if age 68 years) + 5 (if PFS 2) + 3 (if V20 26%) + 6 (if VS5 < 1500 cc). The purposes of the current study are (1) to validate the reliability of this PRS for predicting RP G3 with larger numbers of patients, and (2) to investigate the risk factors including PRS associated with G5 (fatal) RP. Materials/Methods: We retrospectively analyzed data from 250 patients with inoperable locally advanced NSCLC treated with CCRT at our institution from 2001 to 2013. (1) The PRSs were analyzed for correlation with the occurrence of RP G3. (2) DVH metrics including total lung volume, V5, V20, VS5, and mean lung dose were analyzed for an association with fatal RP. Age, sex, smoking status, stage, tumor location, chemotherapy regimen, pulmonary fibrosis score (PFS), pulmonary emphysema score (PES) on baseline chest CT scan, and PRS were also analyzed. Results: Twenty-three patients (9.2%) developed RP G3 and fatal RP occurred in 5 patients (2.0%). The PRS ranged from 0 to 17 (median 3). (1) PRS was significantly related to the incidence of RP G3 (P < 0.001). The occurrence rate of RP G3 according to PRS were 1.0%, 7.4%, 24.3%, and 30% when PRS were 0 (n Z 98), 3-5 (n Z 95), 6-8 (n Z 37), 9-17 (n Z 20), respectively. (2) Univariate analysis by Pearson’s chi-square test revealed that PFS, PES, total lung volume, VS5 and PRS were significantly (P < 0.05) associated with the occurrence of fatal RP. Multivariate analysis by forwardstepwise logistic regression test revealed PRS was an only significant risk factor (P Z 0.001, 95% CI Z 1.214-2.007). The ROC (receiver operating characteristic) curve of PRS indicated good predictive value (AUC Z 0.853) for fatal RP. The incidence rate of fatal RP according to PRS were 0%, 1.1%, 2.7%, and 15.0% when PRS were 0, 3-5, 6-8, and 9-17, respectively. Conclusion: The reliability of the PRS in predicting severe ( G3) RP was validated in larger numbers of patients and warrants further prospective investigation. The PRS also significantly associated with the occurrence of fatal RP. Author Disclosure: K. Tsujino: None. H. Kubota: None. H. Kawaguchi: None. Y. Matsumoto: None. Y. Ota: None. T. Soejima: None.
296 Failure Pattern of Oligometastatic EGFR-Mutant Non-Small Cell Lung Cancer Treated With Tyrosine Kinase Inhibitors: Implication of Upfront Stereotactic Body Radiation Therapy L. Deng,1 J. Zhang,2 Y. Liu,2 X. Sun,2 M.B. Meng,3 X. Zhou,1 L. Zhou,1 Y. Li,2 B. Zou,2 M. Yu,2 J. Xue,2 Y. Gong,2 J. Zhu,1 Z. Ding,2 J. Wang,2 F. Peng,1 Y. Wang,1 M. Huang,1 L. Ren,2 M. Hou,1 and Y. Lu1; 1 Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University,
Volume 96 Number 2S Supplement 2016 operating characteristics (ROC) analysis was used to determine the optimal cutpoint for dosimetric parameters. Results: We included 138 cases: 73 men (53.0%); median age 63 years (range, 42-83); predominantly NSCLC (N Z 114, 82.6%). Most patients received either platinum/etoposide (N Z 83, 60.1%) or carboplatin/taxol (N Z 48, 34.8%). Median RT dose was 61.2 Gy (range, 45-70 Gy). The rate of HT3+ was 41.3% (n Z 57). Increasing mean TVB dose (per Gy) was associated with a higher odds of developing HT3+ (OR Z 1.06, 95% CI Z 1.01-1.10, P Z 0.012). Increasing TVB V5-V40 was all significantly correlated with increased odds of developing HT3+. ROC analysis found that the optimal cutpoint for mean TVB dose was 23 Gy. The OR for developing HT3+ was 2.80-fold higher in patients with mean TVB dose >23 Gy compared to 23 Gy (95% CI Z 2.80-5.63, P Z 0.001). On multivariate analysis, increasing mean TVB dose, increasing age, and decreasing BMI were all statistically significantly associated with increased odds of developing HT3+. When excluding patients with SCLC, mean TVB dose and V5-V20 remained significantly associated with HT3+. Conclusion: We found that increasing TVB dose was associated with clinically significant HT in patients with lung cancer treated with CRT. This suggests that efforts to spare dose to the TVB may reduce rates of HT and potentially improve patient outcomes. Further prospective validation of these results is needed. Author Disclosure: C. Barney: None. N. Scoville: None. K.E. Haglund: None. J.C. Grecula: None. T.M. Williams: None. M.X. Welliver: None. G. Otterson: None. J.G. Bazan: None.
294 Risk Factor Study of Radiation Pneumonitis Focused on Subclinical Interstitial Lung Disease in Definitive Radiation Therapy for NoneSmall Cell Lung Cancer: A Single-Institution Experience Y. Li, S. Liang, Z. Zhou, Y. Cai, Y. Chen, and F. Li; Department of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Purpose/Objective(s): The widespread use of high-resolution computed tomography in clinical and research settings has increased the detection of interstitial lung abnormalities in asymptomatic and undiagnosed individuals. We evaluated the association between subclinical interstitial lung disease (ILD) and radiation pneumonitis (RP) in patients for with IIIA or IIIB NoneSmall-Cell Lung Cancer (NSCLC) treated with definitive radiotherapy (RT). Materials/Methods: All IIIA or IIIB NSCLC patients treated with thoracic definitive RT from January 2014 to May 2015 were analyzed. One hundred eighty-six consecutive patients with NSCLC were treated by thoracic RT at our institution. The presence, extent, and distribution of subclinical ILD on CT findings at pre-thoracic RT were reviewed and scored. Pre-thoracic RT CT findings were reviewed by two chest radiologists as no evidence of ILD (score Z 0), slight ILD (score Z 1), mild ILD (score Z 2), or moderate ILD (score Z 3). Slight ILD was defined as focal or unilateral groundglass attenuation, focal or unilateral reticulation and patchy ground-glass abnormalities (<5% of the lung). Mild ILD was defined as follows: nondependent ground-glass abnormality affecting more than 5% of any lung zone, nondependent reticular abnormality, diffuse centrilobular nodularity with ground-glass abnormality, honeycombing, traction bronchiectasis, non-emphysematous cysts and architectural distortion. Moderate ILD was defined as bilateral fibrosis in multiple lobes associated with honeycombing and traction bronchiectasis with a sub-pleural distribution. The median total dose was 60 Gy (range Z 58-66 Gy). The fraction dose was 1.8-2.25 Gy (median Z 2.0 Gy). The Complete DVH data were available for all patients. The relationships between RP and clinical factors including subclinical ILD were investigated. Results: Grade 2 RP was recognized in 50 (26.9%) patients including 1 patients (0.5%) with fatal RP (Grade 5), and Grade 3 RP occurred in 19 patients (10.2%). Twenty cases of 2 RP was found in 25 subclinical ILD patients including 1 RP grade 5. In 161 patients free of subclinical ILD, 30 (18.6%) cases of 2 RP were recognized. Spearman correlations revealed that subclinical ILD was significantly correlated with RP (rho Z 0.472; P
Z 0.000). Gender, primary tumor location (upper versus lower lobes), smoking history, forced expiratory volume in 1 second (FEV1), T stage, N stage, Gross Tumor Volume, and chemotherapy modality (sequential or concurrent) were not related to the risk of developing RP. Univariate analyses revealed that age and subclinical ILD were related to the risk of developing RP (P Z 0.040, 0.000, respectively) and no dosimetric factors were significant. Multivariate analyses demonstrated that only subclinical ILD was independent predictor (b Z 2.861, SE Z 0.566, Wald Z 25.540, P Z 0.000, RR Z 17.473, 95% CI Z 5.762-52.990). Conclusion: In this study, RP tended to be much more common in the patients with subclinical ILD. Author Disclosure: Y. Li: None. S. Liang: None. Z. Zhou: None. Y. Cai: None. Y. Chen: None. F. Li: None.
295 Risk Factors Associated With Fatal Radiation Pneumonitis after Concurrent Chemoradiation Therapy for Non-Small Cell Lung Cancer K. Tsujino, H. Kubota, H. Kawaguchi, Y. Matsumoto, Y. Ota, and T. Soejima; Hyogo Cancer Center, Akashi, Japan Purpose/Objective(s): We have previously proposed a new predictive risk score (PRS) for predicting severe (aNCI-CTC grade 3) radiation pneumonitis (RP) after concurrent chemoradiotherapy (CCRT) for non-small cell lung cancer (NSCLC) (JTO 9:983-990, 2014). This PRS is calculated from age, pulmonary fibrosis score (PFS) on baseline chest CT scan, lung V20, and VS5 (absolute lung volume spared from a 5-Gy dose); PRS Z 3 (if age 68 years) + 5 (if PFS 2) + 3 (if V20 26%) + 6 (if VS5 < 1500 cc). The purposes of the current study are (1) to validate the reliability of this PRS for predicting RP G3 with larger numbers of patients, and (2) to investigate the risk factors including PRS associated with G5 (fatal) RP. Materials/Methods: We retrospectively analyzed data from 250 patients with inoperable locally advanced NSCLC treated with CCRT at our institution from 2001 to 2013. (1) The PRSs were analyzed for correlation with the occurrence of RP G3. (2) DVH metrics including total lung volume, V5, V20, VS5, and mean lung dose were analyzed for an association with fatal RP. Age, sex, smoking status, stage, tumor location, chemotherapy regimen, pulmonary fibrosis score (PFS), pulmonary emphysema score (PES) on baseline chest CT scan, and PRS were also analyzed. Results: Twenty-three patients (9.2%) developed RP G3 and fatal RP occurred in 5 patients (2.0%). The PRS ranged from 0 to 17 (median 3). (1) PRS was significantly related to the incidence of RP G3 (P < 0.001). The occurrence rate of RP G3 according to PRS were 1.0%, 7.4%, 24.3%, and 30% when PRS were 0 (n Z 98), 3-5 (n Z 95), 6-8 (n Z 37), 9-17 (n Z 20), respectively. (2) Univariate analysis by Pearson’s chi-square test revealed that PFS, PES, total lung volume, VS5 and PRS were significantly (P < 0.05) associated with the occurrence of fatal RP. Multivariate analysis by forwardstepwise logistic regression test revealed PRS was an only significant risk factor (P Z 0.001, 95% CI Z 1.214-2.007). The ROC (receiver operating characteristic) curve of PRS indicated good predictive value (AUC Z 0.853) for fatal RP. The incidence rate of fatal RP according to PRS were 0%, 1.1%, 2.7%, and 15.0% when PRS were 0, 3-5, 6-8, and 9-17, respectively. Conclusion: The reliability of the PRS in predicting severe ( G3) RP was validated in larger numbers of patients and warrants further prospective investigation. The PRS also significantly associated with the occurrence of fatal RP. Author Disclosure: K. Tsujino: None. H. Kubota: None. H. Kawaguchi: None. Y. Matsumoto: None. Y. Ota: None. T. Soejima: None.
296 Failure Pattern of Oligometastatic EGFR-Mutant Non-Small Cell Lung Cancer Treated With Tyrosine Kinase Inhibitors: Implication of Upfront Stereotactic Body Radiation Therapy L. Deng,1 J. Zhang,2 Y. Liu,2 X. Sun,2 M.B. Meng,3 X. Zhou,1 L. Zhou,1 Y. Li,2 B. Zou,2 M. Yu,2 J. Xue,2 Y. Gong,2 J. Zhu,1 Z. Ding,2 J. Wang,2 F. Peng,1 Y. Wang,1 M. Huang,1 L. Ren,2 M. Hou,1 and Y. Lu1; 1 Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University,