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Predictors Associated with Severe Acute Esophagitis in Non-small Cell Lung Cancer (NSCLC) Patients Treated with Concomitant Boost Chemoradiation
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Volume 99 Number 2S Supplement 2017 improves sparing of critical structures. Our data demonstrate that treatment with this technique is well tolerated and survival is comparable with previous reports. Author Disclosure: M.R. Thompson: None. S. Lazarev: None. V.A. Dumane: None. K. Rosenzweig: None.
3181 Immunotherapy Improves Survival in Nonesmall Cell Lung Cancer Patients who Require Systemic Therapy for Recurrent Disease After Definitive Multimodality Treatment K.R. Voong,1 C. Hooker,2 J. Senter,3 P. Forde,4 M. Lang,1 M. Brock,2 and R.K. Hales1; 1Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 2Division of Thoracic Surgery, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, 3The Johns Hopkins University School of Medicine, Baltimore, MD, 4Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD Purpose/Objective(s): Immunotherapy has transformed the management of metastatic non-small cell lung cancer (NSCLC). Recently, three immune checkpoint antibodies have been FDA-approved for the second and first line treatment of metastatic NSCLC with an overall survival (OS) benefit. In this analysis, we explore the relationship between survival and the type of systemic therapy used in NSCLC patients who experience failure after multimodality treatment (MMT). Materials/Methods: Patients with stage II-III NSCLC who received initial MMT from 2007 to 2014 were included in this retrospective IRB-approved study performed at a single, tertiary academic center. These patients were seen both within and outside of our one-day thoracic oncology multidisciplinary clinic (MDC). Baseline clinicopathologic and treatment details were obtained from chart review. Chi-squared test, Fisher’s exact test, Wilcoxon Rank-sum were used to compare groups. OS was estimated with Kaplan-Meier methodology. Results: Between 2007-2014, 96 patients received salvage systemic therapy after MMT. Median age was 63 (IQR, 55-69), 52.4% are male, and 59.4% are white. Majority are former (68.7%) or current smokers (14.6%), with a median 40 pack year history (IQR 25-40). 92.7% had initial stage III disease (IIIA nZ47; IIIB nZ32; II nZ7). Histologies included adenocarcinoma (57.3%), squamous cell (31.2%), and other (11.5%). After MMT, 52% (nZ50) had 1 line of salvage systemic therapy, 24% had 2 lines, and 24% had 3 or more lines of systemic therapy. Salvage systemic therapies included chemotherapy (75%, nZ72), targeted therapy (22.9%, nZ22), IT (28%, nZ27) and investigational therapy (14.6%, nZ14). The most common targetable mutation seen was EGFR (16%), ALK (4%), and other (6%). Patients who received salvage IT received initial MMT during a later time period (median 2013, range 09-14 vs. no IT: median 2011, range 07-14; p<0.01). These patients also were less likely to receive any chemotherapy (55.6% vs. 82.6%), more likely to participate in clinical trials (48.1% vs. 10.1 %), more likely to receive 2 or more salvage lines, and more likely to receive other investigational salvage treatments (33% versus 7.2%), (all p<0.05). These patients were also more likely to have been initially seen though the MDC (70.4% versus 39.1%; p<0.01). These two groups were otherwise well balanced. The median survival of those who had any salvage IT was 34.8 months versus 22.3 months for those who did not receive salvage IT for failure after initial cancer treatment (pZ0.03). In this cohort, the median survival of those who received salvage targeted therapies was not reached versus 22.3 months for those who did not receive salvage targeted therapy (p<0.01). Conclusion: For those patients who developed treatment failure after MMT requiring systemic therapy, receipt of salvage IT improved overall survival. Author Disclosure: K.R. Voong: None. C. Hooker: None. J. Senter: None. P. Forde: Research Grant; Bristol-Myers Squibb. Consulting or advisory role; AstraZeneca, Boehringer, Celgene, EMD-Serono, Inivata. M. Lang: None. M. Brock: None. R.K. Hales: None.
3182 Predictors Associated with Severe Acute Esophagitis in Non-small Cell Lung Cancer (NSCLC) Patients Treated with Concomitant Boost Chemoradiation K. Wada, N. Kishi, N. Kanayama, T. Hirata, Y. Kawaguchi, K. Konishi, and T. Teshima; Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka City, Japan Purpose/Objective(s): The purpose of this study is to identify the clinical and dosimetric predictors of severe acute radiation esophagitis (RE) in NSCLC patients treated with concomitant boost radiation (ccbRT) and concurrent chemotherapy. Materials/Methods: We retrospectively selected 157 patients with NSCLC who underwent ccbRT in our institution from 2004 to 2015. Patients who received ccbRT without concurrent chemotherapy, and simultaneous radiotherapy on different treatment plans were excluded. A total of 141 patients were included. All the patients were treated with three-dimensional conformal radiotherapy. The prescribed doses were 64Gy/40fr bid over 4 weeks (phase 1: 40Gy/20 fractions/4 weeks to gross tumors and elective nodal regions and phase 2: 24 Gy/20 fractions/4 weeks to only gross tumors as a second daily fraction after a 6h gap). Acute RE was designated grade 3 or higher (by the CTCAE version 4.0). Clinical factors included sex, age, ECOG performance status, tumor histology, stage and chemotherapy status (adjuvant and neoadjuvant chemotherapy use and concurrent chemotherapy regimen), and dosimetric parameters included maximum dose, mean dose, rV10, rV20, rV30, rV40, rV45, rV50, rV55, rV60 (the relative volume of esophagus receiving at least x Gy) and L10, L20, L30, L40, L50, L60 (the partial irradiation length of the esophagus, defined as the length of the esophagus receiving at least mean dose of x Gy). Univariable and multivariable logistic regression analysis was conducted to identify predictive factors of RE. ROC analysis was performed and the area under the curve (AUC) was calculated for each variable. Results: Of the 141 patients, there were 80.9% male and 19.1% female with a median age of 62. Vinorelbine/cisplatin and carboplatin/ paclitaxel were delivered as concurrent chemotherapy in 76.6% and 18.4% of the patients respectively. Neoadjuvant chemotherapy and adjuvant chemotherapy were delivered in 51.8% and 78.7% of them. There were no reports of grade 4 RE. Univariable analysis revealed that all dosimetrics except rV10 and L10 were significant risk factors for grade 3 RE (p < 0.05). On multivariable analysis, the model using rV60, selected by Akaike information criterion, was optimal (AIC Z 100.68; OR 1.09 95%CI 1.05 to 1.13; p < .0001). Clinical factors were not significant as the predictor variable in the univariable or multivariable analysis. On ROC analysis, the rate of grade 3 S RE for patients with rV60 & 15.4% was 6.7% vs 34.1% for those with rV60 > 15.4% (AUC Z 0.80). Conclusion: rV60 was found to be the most significant risk factor for severe acute RE in ccbRT with concurrent chemotherapy in NSCLC. Author Disclosure: K. Wada: None. N. Kishi: None. N. Kanayama: None. T. Hirata: None. Y. Kawaguchi: None. K. Konishi: None. T. Teshima: None.
3183 Tumor Volume Dynamics on kV-CBCT During Definitive Radiation Therapy for Locally Advanced NSCLC: Implications for Prognosis and Adaptive Radiation Therapy P.M. Wald,1 X. Mo,2 C. Barney,1 J.C. Grecula,1 T.M. Williams,1 K.E. Haglund,1 J.G. Bazan,1 and M.X. Welliver1; 1The Ohio State University Wexner Medical Center, Department of Radiation Oncology, Columbus, OH, 2The Ohio State University Wexner Medical Center, Department of Biostatistics, Columbus, OH Purpose/Objective(s): Standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC) is concurrent chemoradiotherapy (CRT). Locoregional control (LRC) and overall survival (OS) are unacceptably
Volume 99 Number 2S Supplement 2017 improves sparing of critical structures. Our data demonstrate that treatment with this technique is well tolerated and survival is comparable with previous reports. Author Disclosure: M.R. Thompson: None. S. Lazarev: None. V.A. Dumane: None. K. Rosenzweig: None.
3181 Immunotherapy Improves Survival in Nonesmall Cell Lung Cancer Patients who Require Systemic Therapy for Recurrent Disease After Definitive Multimodality Treatment K.R. Voong,1 C. Hooker,2 J. Senter,3 P. Forde,4 M. Lang,1 M. Brock,2 and R.K. Hales1; 1Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 2Division of Thoracic Surgery, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, 3The Johns Hopkins University School of Medicine, Baltimore, MD, 4Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD Purpose/Objective(s): Immunotherapy has transformed the management of metastatic non-small cell lung cancer (NSCLC). Recently, three immune checkpoint antibodies have been FDA-approved for the second and first line treatment of metastatic NSCLC with an overall survival (OS) benefit. In this analysis, we explore the relationship between survival and the type of systemic therapy used in NSCLC patients who experience failure after multimodality treatment (MMT). Materials/Methods: Patients with stage II-III NSCLC who received initial MMT from 2007 to 2014 were included in this retrospective IRB-approved study performed at a single, tertiary academic center. These patients were seen both within and outside of our one-day thoracic oncology multidisciplinary clinic (MDC). Baseline clinicopathologic and treatment details were obtained from chart review. Chi-squared test, Fisher’s exact test, Wilcoxon Rank-sum were used to compare groups. OS was estimated with Kaplan-Meier methodology. Results: Between 2007-2014, 96 patients received salvage systemic therapy after MMT. Median age was 63 (IQR, 55-69), 52.4% are male, and 59.4% are white. Majority are former (68.7%) or current smokers (14.6%), with a median 40 pack year history (IQR 25-40). 92.7% had initial stage III disease (IIIA nZ47; IIIB nZ32; II nZ7). Histologies included adenocarcinoma (57.3%), squamous cell (31.2%), and other (11.5%). After MMT, 52% (nZ50) had 1 line of salvage systemic therapy, 24% had 2 lines, and 24% had 3 or more lines of systemic therapy. Salvage systemic therapies included chemotherapy (75%, nZ72), targeted therapy (22.9%, nZ22), IT (28%, nZ27) and investigational therapy (14.6%, nZ14). The most common targetable mutation seen was EGFR (16%), ALK (4%), and other (6%). Patients who received salvage IT received initial MMT during a later time period (median 2013, range 09-14 vs. no IT: median 2011, range 07-14; p<0.01). These patients also were less likely to receive any chemotherapy (55.6% vs. 82.6%), more likely to participate in clinical trials (48.1% vs. 10.1 %), more likely to receive 2 or more salvage lines, and more likely to receive other investigational salvage treatments (33% versus 7.2%), (all p<0.05). These patients were also more likely to have been initially seen though the MDC (70.4% versus 39.1%; p<0.01). These two groups were otherwise well balanced. The median survival of those who had any salvage IT was 34.8 months versus 22.3 months for those who did not receive salvage IT for failure after initial cancer treatment (pZ0.03). In this cohort, the median survival of those who received salvage targeted therapies was not reached versus 22.3 months for those who did not receive salvage targeted therapy (p<0.01). Conclusion: For those patients who developed treatment failure after MMT requiring systemic therapy, receipt of salvage IT improved overall survival. Author Disclosure: K.R. Voong: None. C. Hooker: None. J. Senter: None. P. Forde: Research Grant; Bristol-Myers Squibb. Consulting or advisory role; AstraZeneca, Boehringer, Celgene, EMD-Serono, Inivata. M. Lang: None. M. Brock: None. R.K. Hales: None.
3182 Predictors Associated with Severe Acute Esophagitis in Non-small Cell Lung Cancer (NSCLC) Patients Treated with Concomitant Boost Chemoradiation K. Wada, N. Kishi, N. Kanayama, T. Hirata, Y. Kawaguchi, K. Konishi, and T. Teshima; Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka City, Japan Purpose/Objective(s): The purpose of this study is to identify the clinical and dosimetric predictors of severe acute radiation esophagitis (RE) in NSCLC patients treated with concomitant boost radiation (ccbRT) and concurrent chemotherapy. Materials/Methods: We retrospectively selected 157 patients with NSCLC who underwent ccbRT in our institution from 2004 to 2015. Patients who received ccbRT without concurrent chemotherapy, and simultaneous radiotherapy on different treatment plans were excluded. A total of 141 patients were included. All the patients were treated with three-dimensional conformal radiotherapy. The prescribed doses were 64Gy/40fr bid over 4 weeks (phase 1: 40Gy/20 fractions/4 weeks to gross tumors and elective nodal regions and phase 2: 24 Gy/20 fractions/4 weeks to only gross tumors as a second daily fraction after a 6h gap). Acute RE was designated grade 3 or higher (by the CTCAE version 4.0). Clinical factors included sex, age, ECOG performance status, tumor histology, stage and chemotherapy status (adjuvant and neoadjuvant chemotherapy use and concurrent chemotherapy regimen), and dosimetric parameters included maximum dose, mean dose, rV10, rV20, rV30, rV40, rV45, rV50, rV55, rV60 (the relative volume of esophagus receiving at least x Gy) and L10, L20, L30, L40, L50, L60 (the partial irradiation length of the esophagus, defined as the length of the esophagus receiving at least mean dose of x Gy). Univariable and multivariable logistic regression analysis was conducted to identify predictive factors of RE. ROC analysis was performed and the area under the curve (AUC) was calculated for each variable. Results: Of the 141 patients, there were 80.9% male and 19.1% female with a median age of 62. Vinorelbine/cisplatin and carboplatin/ paclitaxel were delivered as concurrent chemotherapy in 76.6% and 18.4% of the patients respectively. Neoadjuvant chemotherapy and adjuvant chemotherapy were delivered in 51.8% and 78.7% of them. There were no reports of grade 4 RE. Univariable analysis revealed that all dosimetrics except rV10 and L10 were significant risk factors for grade 3 RE (p < 0.05). On multivariable analysis, the model using rV60, selected by Akaike information criterion, was optimal (AIC Z 100.68; OR 1.09 95%CI 1.05 to 1.13; p < .0001). Clinical factors were not significant as the predictor variable in the univariable or multivariable analysis. On ROC analysis, the rate of grade 3 S RE for patients with rV60 & 15.4% was 6.7% vs 34.1% for those with rV60 > 15.4% (AUC Z 0.80). Conclusion: rV60 was found to be the most significant risk factor for severe acute RE in ccbRT with concurrent chemotherapy in NSCLC. Author Disclosure: K. Wada: None. N. Kishi: None. N. Kanayama: None. T. Hirata: None. Y. Kawaguchi: None. K. Konishi: None. T. Teshima: None.
3183 Tumor Volume Dynamics on kV-CBCT During Definitive Radiation Therapy for Locally Advanced NSCLC: Implications for Prognosis and Adaptive Radiation Therapy P.M. Wald,1 X. Mo,2 C. Barney,1 J.C. Grecula,1 T.M. Williams,1 K.E. Haglund,1 J.G. Bazan,1 and M.X. Welliver1; 1The Ohio State University Wexner Medical Center, Department of Radiation Oncology, Columbus, OH, 2The Ohio State University Wexner Medical Center, Department of Biostatistics, Columbus, OH Purpose/Objective(s): Standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC) is concurrent chemoradiotherapy (CRT). Locoregional control (LRC) and overall survival (OS) are unacceptably