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Pattern of Failure in Metastatic EGFR-Mutant NSCLC Treated With Erlotinib: A Role for Upfront Radiation Therapy?
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Volume 90 Number 1S Supplement 2014 180 cc (average 316.4 cc of 122 patients) and 200 cc (average 342.9 cc of 102 patients) were 14.8 and 14.75 months. The median OS was 22 months for 134 patients receiving dose of 63 Gy, and 25.9 months for 129 patients receiving dose greater than 70 Gy. For patients with < 200 cc GTV the median OS were 26.5 months (87 patients) and 29.8 months for 63Gy group and 70 Gy group (101 patients), respectively. For patients with GTV < 150 cc the median OS times were 33.5 months and 31.9 months for 63 Gy group (71 patients) and 70 Gy group (88 patients), respectively. Conclusions: We found that GTV is the dominate predictor for the OS of NSCLC patients treated using IMRT in our institution. A model to estimate the median survival based on the GTV was provided. This model can potentially be used to understand the various survival data reported in the literature and to be used as a guide for the personalized prescription of individual patient. Author Disclosure: J. Sun: None. X. Zhang: None. J.Y. Chang: None. D. Gomez: None. S. Jiang: None. P. Wang: None. Z. Yuan: None. L. Zhao: None. L. Wang: None. Z. Hui: None. Z. Liao: None.
3096 Pattern of Failure in Metastatic EGFR-Mutant NSCLC Treated With Erlotinib: A Role for Upfront Radiation Therapy? S. Patel, A. Rimner, A. Foster, Z. Zhang, K.M. Woo, H.A. Yu, G.J. Riely, and A.J. Wu; Memorial Sloan-Kettering Cancer Center, New York, NY Purpose/Objective(s): Molecular therapies such as erlotinib have significantly improved outcomes in metastatic EGFR-mutant (EGFRmt) NSCLC. However, the pattern of disease progression on erlotinib is incompletely characterized. We hypothesized that the pattern of first progression in many patients is in their initial disease sites only, such that upfront local therapy might improve progression-free survival (PFS). We therefore analyzed patterns of failure and survival in these patients, to identify patients who may benefit from upfront local therapy. Materials/Methods: We retrospectively analyzed 190 consecutive patients who presented with metastatic EGFRmt NSCLC and were treated with erlotinib from 2004 to 2013 at our institution. We recorded locations of first progression, excluding brain metastasis, and classified pattern of failure as involving initial sites only (ISF), new sites only (NSF), or the combination (CSF). Competing-risks regression was used to assess ISF and progressionfree survival (PFS). Baseline clinical factors including gender, age, performance status, CNS involvement, intrathoracic disease burden (T and N stage), number of metastases, and EGFR mutation type were included in univariate analysis (UVA). Candidate factors on UVA were incorporated into multivariate analysis (MVA) of ISF, PFS and overall survival (OS). Results: Of 171 patients who progressed, 103 (60.2%) had ISF, 30 (17.5%) had NSF, and 38 (22.2%) had CSF. Younger age was associated with ISF on UVA (p Z 0.014). On MVA, age (p Z 0.036) and lack of CNS involvement (HR 1.60, p Z 0.027) independently correlated with ISF, with a trend for higher T and N stage (HR 1.63 for intrathoracic Stage III vs I/II, p Z 0.057). Higher T and N stage was a significant predictor of PFS on MVA (HR 1.75, p Z 0.026). Factors predicting shorter OS on MVA were: female gender (HR 1.96, p Z 0.002), weight loss >5% (HR 1.64, p Z 0.028), CNS involvement (HR 1.63, p Z 0.011), and 4 extracranial metastases (HR 1.72, p Z 0.017). Intrathoracic primary disease progression was a component of first failure for 60% of patients who progressed, and was the only site of first failure in 30% of patients who progressed. Conclusions: The predominant pattern of first progression in metastatic EGFRmt patients on erlotinib is progression in the initial sites of disease. Younger patients and those without CNS involvement are particularly likely to develop ISF. Greater intrathoracic disease burden is associated with ISF and shorter PFS. Female gender, weight loss, initial CNS involvement, and more initial metastatic lesions predict for worse survival. Since most patients develop ISF, and initial disease burden and location correlate with progression and survival, there may be a role for upfront radiation therapy in selected patients with metastatic EGFRmt NSCLC treated with erlotinib. Author Disclosure: S. Patel: None. A. Rimner: E. Research Grant; Varian Medical Systems. G. Consultant; General Electric. A. Foster: None. Z.
Zhang: None. K.M. Woo: None. H.A. Yu: None. G.J. Riely: None. A.J. Wu: G. Consultant; Pfizer, Inc.
3097 Re-Stereotactic Body Radiation Therapy (SBRT) for Local Recurrence of Lung Cancer Previously Treated With SBRT H. Nonaka,1 H. Onishi,1 M. Ozaki,2 L. Tominaga,1 K. Kuriyama,1 T. Komiyama,1 and M. Oguri1; 1University of Yamanashi, Yamanashi, Japan, 2Shizuoka City Shimizu Hospital, Shizuoka, Japan Purpose/Objective(s): The purpose of the study was to assess the efficacy and toxicity after re-stereotactic body radiation therapy (SBRT) for local recurrence of lung cancer previously treated with SBRT. Materials/Methods: Twelve patients (9 men, 3 women), with 12 tumors that locally regrew after initial SBRT were re-irradiated with SBRT. Median age at time of re-SBRT was 81 (range, 59-89) years old. Eight tumors were primary lung cancer, 3 were metastatic lung tumors, 1 was local recurrence of primary lung cancer after conventional irradiation. Tumor histology was squamous cell carcinoma in 9 tumors, adenocarcinoma in 2 and small cell carcinoma in 1. Median tumor size at time of re-SBRT was 34 (range, 15-41) mm. The accumulated dose was calculated by using rigid registration. Using the linear quadratic model, all doses were recalculated to an equivalent dose in 2 Gy fraction (EQD2) with an a/b value of 10Gy for tumor dose and an a/b value of 3Gy for late effects. Toxicity was scored according to NCI-CTCAE, version 4.0, overall survival (OS) and local control (LC) were based on Kaplan Meier estimates. Results: Median interval between initial and re-SBRT was 15 (range, 8-54) months. Median dose of initial SBRT was 48 (range, 48-70) Gy at 6-12.5 Gy/ fraction, and that of re-SBRT was 49 (range, 36-70) Gy at 5-12.5 Gy/fraction. Median EQD2 of initial and re-SBRT was 88 (range, 66.7-99.1) Gy, and 81.5 (range, 60-99.1) Gy, respectively. The median follow-up duration after re-SBRT was 15 (range, 3-44) months. The 1- and 2- year OS rate after re-SBRT was 66% and 40%, respectively (median survival time, 17 months). The 1-year and 2- year LC rate after re-SBRT was 54% and 27%, respectively (median LC time, 14 months). Median of mean lung EQD2 in the summed plan was 10.6 (range, 4.0-19.6) Gy, and the percentage of normal lung volume receiving 20 Gy or more (V20) was 12.4 (range, 3.618.2) %. Median EQD2 of other organs at risk in the summed plan was esophagus:D1 cc (the minimum dose to the most irradiated volume of 1 cc) Z 30.2 (range, 4.2-54.5) Gy, stomach: D10 cc Z 0.1 (range, 0.01-115.6) Gy, trachea and main bronchus:D1 cc Z 13.8 (range, 0.2-126.3) Gy, skin: D10 cc Z 38.3 (range, 7.5-143.0) Gy, chest wall: D30 cc Z 136.8 (range, 25.6-254.3) Gy, spinal cord:maximum dose Z 17.4 (range, 4.3-72.5) Gy. One patient with a recurrent left lung tumor locating near the diaphragm died of Grade 5 gastric perforation. The stomach EQD2 for this patient was D10 cc:115.6 Gy in the summed plan. One had Grade 4 radiation dermatitis, 3 had Grade 3 radiation-induced pneumonitis, and 4 developed Grade 2 rib fractures. Severe toxicity for other normal organs was not observed. Conclusions: Re-SBRT for local recurrence of lung cancer after initial SBRT needs careful attention on the accumulated dose on normal organs and hardly achieves local control. Author Disclosure: H. Nonaka: None. H. Onishi: None. M. Ozaki: None. L. Tominaga: None. K. Kuriyama: None. T. Komiyama: None. M. Oguri: None.
3098 Risk of Brain Metastasis in EGFR-Mutant NSCLC Treated With Erlotinib: A Role for Prophylactic Cranial Irradiation? S. Patel, A. Rimner, A. Foster, Z. Zhang, K.M. Woo, H.A. Yu, G.J. Riely, and A.J. Wu; Memorial Sloan-Kettering Cancer Center, New York, NY Purpose/Objective(s): The risk of brain metastasis (BM) in EGFRmutant NSCLC remains incompletely characterized. Molecular therapies such as erlotinib have significantly improved outcomes in these patients and may reduce their risk of BM due to erlotinib’s ability to cross the blood-brain barrier. We sought to assess the rate of BM in patients receiving erlotinib and identify predictors for BM in this population, to
Volume 90 Number 1S Supplement 2014 180 cc (average 316.4 cc of 122 patients) and 200 cc (average 342.9 cc of 102 patients) were 14.8 and 14.75 months. The median OS was 22 months for 134 patients receiving dose of 63 Gy, and 25.9 months for 129 patients receiving dose greater than 70 Gy. For patients with < 200 cc GTV the median OS were 26.5 months (87 patients) and 29.8 months for 63Gy group and 70 Gy group (101 patients), respectively. For patients with GTV < 150 cc the median OS times were 33.5 months and 31.9 months for 63 Gy group (71 patients) and 70 Gy group (88 patients), respectively. Conclusions: We found that GTV is the dominate predictor for the OS of NSCLC patients treated using IMRT in our institution. A model to estimate the median survival based on the GTV was provided. This model can potentially be used to understand the various survival data reported in the literature and to be used as a guide for the personalized prescription of individual patient. Author Disclosure: J. Sun: None. X. Zhang: None. J.Y. Chang: None. D. Gomez: None. S. Jiang: None. P. Wang: None. Z. Yuan: None. L. Zhao: None. L. Wang: None. Z. Hui: None. Z. Liao: None.
3096 Pattern of Failure in Metastatic EGFR-Mutant NSCLC Treated With Erlotinib: A Role for Upfront Radiation Therapy? S. Patel, A. Rimner, A. Foster, Z. Zhang, K.M. Woo, H.A. Yu, G.J. Riely, and A.J. Wu; Memorial Sloan-Kettering Cancer Center, New York, NY Purpose/Objective(s): Molecular therapies such as erlotinib have significantly improved outcomes in metastatic EGFR-mutant (EGFRmt) NSCLC. However, the pattern of disease progression on erlotinib is incompletely characterized. We hypothesized that the pattern of first progression in many patients is in their initial disease sites only, such that upfront local therapy might improve progression-free survival (PFS). We therefore analyzed patterns of failure and survival in these patients, to identify patients who may benefit from upfront local therapy. Materials/Methods: We retrospectively analyzed 190 consecutive patients who presented with metastatic EGFRmt NSCLC and were treated with erlotinib from 2004 to 2013 at our institution. We recorded locations of first progression, excluding brain metastasis, and classified pattern of failure as involving initial sites only (ISF), new sites only (NSF), or the combination (CSF). Competing-risks regression was used to assess ISF and progressionfree survival (PFS). Baseline clinical factors including gender, age, performance status, CNS involvement, intrathoracic disease burden (T and N stage), number of metastases, and EGFR mutation type were included in univariate analysis (UVA). Candidate factors on UVA were incorporated into multivariate analysis (MVA) of ISF, PFS and overall survival (OS). Results: Of 171 patients who progressed, 103 (60.2%) had ISF, 30 (17.5%) had NSF, and 38 (22.2%) had CSF. Younger age was associated with ISF on UVA (p Z 0.014). On MVA, age (p Z 0.036) and lack of CNS involvement (HR 1.60, p Z 0.027) independently correlated with ISF, with a trend for higher T and N stage (HR 1.63 for intrathoracic Stage III vs I/II, p Z 0.057). Higher T and N stage was a significant predictor of PFS on MVA (HR 1.75, p Z 0.026). Factors predicting shorter OS on MVA were: female gender (HR 1.96, p Z 0.002), weight loss >5% (HR 1.64, p Z 0.028), CNS involvement (HR 1.63, p Z 0.011), and 4 extracranial metastases (HR 1.72, p Z 0.017). Intrathoracic primary disease progression was a component of first failure for 60% of patients who progressed, and was the only site of first failure in 30% of patients who progressed. Conclusions: The predominant pattern of first progression in metastatic EGFRmt patients on erlotinib is progression in the initial sites of disease. Younger patients and those without CNS involvement are particularly likely to develop ISF. Greater intrathoracic disease burden is associated with ISF and shorter PFS. Female gender, weight loss, initial CNS involvement, and more initial metastatic lesions predict for worse survival. Since most patients develop ISF, and initial disease burden and location correlate with progression and survival, there may be a role for upfront radiation therapy in selected patients with metastatic EGFRmt NSCLC treated with erlotinib. Author Disclosure: S. Patel: None. A. Rimner: E. Research Grant; Varian Medical Systems. G. Consultant; General Electric. A. Foster: None. Z.
Zhang: None. K.M. Woo: None. H.A. Yu: None. G.J. Riely: None. A.J. Wu: G. Consultant; Pfizer, Inc.
3097 Re-Stereotactic Body Radiation Therapy (SBRT) for Local Recurrence of Lung Cancer Previously Treated With SBRT H. Nonaka,1 H. Onishi,1 M. Ozaki,2 L. Tominaga,1 K. Kuriyama,1 T. Komiyama,1 and M. Oguri1; 1University of Yamanashi, Yamanashi, Japan, 2Shizuoka City Shimizu Hospital, Shizuoka, Japan Purpose/Objective(s): The purpose of the study was to assess the efficacy and toxicity after re-stereotactic body radiation therapy (SBRT) for local recurrence of lung cancer previously treated with SBRT. Materials/Methods: Twelve patients (9 men, 3 women), with 12 tumors that locally regrew after initial SBRT were re-irradiated with SBRT. Median age at time of re-SBRT was 81 (range, 59-89) years old. Eight tumors were primary lung cancer, 3 were metastatic lung tumors, 1 was local recurrence of primary lung cancer after conventional irradiation. Tumor histology was squamous cell carcinoma in 9 tumors, adenocarcinoma in 2 and small cell carcinoma in 1. Median tumor size at time of re-SBRT was 34 (range, 15-41) mm. The accumulated dose was calculated by using rigid registration. Using the linear quadratic model, all doses were recalculated to an equivalent dose in 2 Gy fraction (EQD2) with an a/b value of 10Gy for tumor dose and an a/b value of 3Gy for late effects. Toxicity was scored according to NCI-CTCAE, version 4.0, overall survival (OS) and local control (LC) were based on Kaplan Meier estimates. Results: Median interval between initial and re-SBRT was 15 (range, 8-54) months. Median dose of initial SBRT was 48 (range, 48-70) Gy at 6-12.5 Gy/ fraction, and that of re-SBRT was 49 (range, 36-70) Gy at 5-12.5 Gy/fraction. Median EQD2 of initial and re-SBRT was 88 (range, 66.7-99.1) Gy, and 81.5 (range, 60-99.1) Gy, respectively. The median follow-up duration after re-SBRT was 15 (range, 3-44) months. The 1- and 2- year OS rate after re-SBRT was 66% and 40%, respectively (median survival time, 17 months). The 1-year and 2- year LC rate after re-SBRT was 54% and 27%, respectively (median LC time, 14 months). Median of mean lung EQD2 in the summed plan was 10.6 (range, 4.0-19.6) Gy, and the percentage of normal lung volume receiving 20 Gy or more (V20) was 12.4 (range, 3.618.2) %. Median EQD2 of other organs at risk in the summed plan was esophagus:D1 cc (the minimum dose to the most irradiated volume of 1 cc) Z 30.2 (range, 4.2-54.5) Gy, stomach: D10 cc Z 0.1 (range, 0.01-115.6) Gy, trachea and main bronchus:D1 cc Z 13.8 (range, 0.2-126.3) Gy, skin: D10 cc Z 38.3 (range, 7.5-143.0) Gy, chest wall: D30 cc Z 136.8 (range, 25.6-254.3) Gy, spinal cord:maximum dose Z 17.4 (range, 4.3-72.5) Gy. One patient with a recurrent left lung tumor locating near the diaphragm died of Grade 5 gastric perforation. The stomach EQD2 for this patient was D10 cc:115.6 Gy in the summed plan. One had Grade 4 radiation dermatitis, 3 had Grade 3 radiation-induced pneumonitis, and 4 developed Grade 2 rib fractures. Severe toxicity for other normal organs was not observed. Conclusions: Re-SBRT for local recurrence of lung cancer after initial SBRT needs careful attention on the accumulated dose on normal organs and hardly achieves local control. Author Disclosure: H. Nonaka: None. H. Onishi: None. M. Ozaki: None. L. Tominaga: None. K. Kuriyama: None. T. Komiyama: None. M. Oguri: None.
3098 Risk of Brain Metastasis in EGFR-Mutant NSCLC Treated With Erlotinib: A Role for Prophylactic Cranial Irradiation? S. Patel, A. Rimner, A. Foster, Z. Zhang, K.M. Woo, H.A. Yu, G.J. Riely, and A.J. Wu; Memorial Sloan-Kettering Cancer Center, New York, NY Purpose/Objective(s): The risk of brain metastasis (BM) in EGFRmutant NSCLC remains incompletely characterized. Molecular therapies such as erlotinib have significantly improved outcomes in these patients and may reduce their risk of BM due to erlotinib’s ability to cross the blood-brain barrier. We sought to assess the rate of BM in patients receiving erlotinib and identify predictors for BM in this population, to