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Tumor Location Correlates with Radiation Pneumonitis after Stereotactic Body Radiation Therapy (SBRT) for Primary and Oligometastatic Lesions of the Lung
I. J. Radiation Oncology d Biology d Physics
S626
Volume 81, Number 2, Supplement, 2011
only; the initial dose was delivered to the CTV+5 mm margin, and the boost to the CTVonly (no margin). The nominal total dose to the CTVs was 75 Gy in 15 fractions. At an alpha/beta ratio of 10, the tumor dose equivalent at 2 Gy per fraction of the proposed regimen is 96 Gy. The plans were generated via a Varian Eclipse system. The normal tissue constraints were not based on the prescribed total dose (i.e. 75 Gy in 15 fractions), but for actual doses in each organ at risk (OAR) in each plan, e.g. if the spinal cord maximum dose was 30 Gy, then the plan would be acceptable for 15 fractions. The dosimetric endpoints included spinal cord maximum dose, esophagus mean dose, heart mean dose, % volume of total lung-PTV receiving 15 Gy, total lung-PTV mean dose, skin V50, tracheobronchial tree V50, brachial plexus V45. Results: Overall, only one of the 14 plans was considered unacceptable; lung and heart constraints were significantly exceeded. This case had the largest tumor burden and was in the lower lobe. In addition, 3 cases had the tracheobronchial tree V50 only marginally exceeding the set limit; these were ultimately considered acceptable plans. The spinal cord maximum constraint was met in all cases. The average spinal cord maximal dose was 32 Gy, with a range of 18 - 43 Gy. The esophageal mean constraint was met in all cases (average dose was13 Gy, range 6 - 22). The heart mean dose was 7 Gy (range 1 - 33). The % volume of total lung-PTV receiving 15 Gy was 27% (range 17 - 50). The total lung-PTV mean dose was 11 Gy (range 6 - 17). The skin V50 Gy was negligible. The tracheobronchial tree constraint (the tracheobronchial tree V50) was set at 15 cc and was met in 11 of the 14 cases; 3 cases marginally exceeded the limit at 19, 20 and 21 cc. The average tracheobronchial tree V50 Gy was 9 cc (range 1 - 21). The brachial plexus was relevant for 3 patients, with an average V45 Gy of 0.6 cc (range 0 - 8). Conclusions: This study showed that a hypofractionated regimen consisting of 4 Gy x 10, 7 Gy x 5 is dosimetrically feasible in a majority of Stage III lung cancer patients, except in patients with large tumor burdens. Author Disclosure: C. Huang: None. P. Kupelian: None. S. Tenn: None. S. Alexander: None. C. Lee: None. R. Huang: None. P. Lee: None.
2866
Tumor Location Correlates with Radiation Pneumonitis after Stereotactic Body Radiation Therapy (SBRT) for Primary and Oligometastatic Lesions of the Lung
A. R. Bhirud, N. Dunlap, K. Sheng, P. Read, J. Larner University of Virginia, Charlottesville, VA Purpose/Objective(s): To determine the incidence of radiation pneumonitis (RP) and identify associated clinical and dosimetric factors in patients treated with stereotactic body radiation therapy for early stage lung cancer. Materials/Methods: A retrospective analysis was performed on 51 consecutive patients treated with SBRT for primary NSCLC or oligometastatic lesion of the lung. Central lesions, as defined by the RTOG criteria, were excluded. Patients were treated with 3 - 5 fractions of 12 - 20 Gy SBRT with a median BED of 132 Gy. Clinical symptoms were graded by Common Terminology Criteria for Adverse Events, version 3.0 (CTCAE v3). Symptoms were evaluated at 1 month, 3 months, and then 3 month intervals for 2 years after completion of treatment. Univariate and binary logistic regression analyses were completed to analyze relationships with clinical and dosimetric factors. Results: Median follow up was 16.5 months (range 2.0 - 37.0). Twelve patients (23.5%) developed RP grade 2 and three patients (5.8%) developed RP grade 3. No patients developed grade 4 or 5 RP. Age, gender, PTV volume, tumor size, V5, V10, V20, V30, mean lung dose (MLD), and R50 were not correlated with RP . = 2. Treatment of tumors in the right lower lobe compared to the right upper lobe predicted for RP. = 2 (OR = 5.650, p = .044). A similar relationship was not seen between the upper and lower lobes in the left lung. Conclusions: SBRT for early stage peripheral NSCLC resulted in a low rate (5.8%) of high grade pneumonitis (RP. = 3). Right lower lobe tumors may be correlated with a higher incidence of clinical radiation pneumonitis, possibly due to the increased role of the right lung and lower lobe in gaseous exchange. Author Disclosure: A.R. Bhirud: None. N. Dunlap: None. K. Sheng: None. P. Read: None. J. Larner: None.
2867
M867, A Selective Caspases Inhibitor, Sensitizes Lung Cancer to Radiotherapy, and Reduces Radiationinduced Lung Injury
B. Li, A. Torossian, B. Lu Vanderbilt University, Nashville, TN Purpose/Objective(s): Radiotherapy is one of the principal treatment modalities in treating locally advanced NSCLC, radiationinduced lung injury remains a major impediment in radiotherapy. Previous studies show M867 is able to sensitize radiation-induced tumor inhibition in ectopic mouse model, we, in this study, used a novel orthotopic mouse model to investigate efficacy of M867 on lung cancer and normal lung after radiotherapy. Materials/Methods: H460-Luc cells were implanted in mediastinum of athymic nude mice, mice in each group (n = 5) received: (1) none; (2) M867 2mg/kg, i.p. x 7 days; (3) RT (2Gy) x 5 days; and (4) combination. Tumor growth was followed by bioluminescence imaging (BLI); Western blotting is used for the detection of Apoptosis-Inducing Factor (AIF) of cytoplasm and nucleus. TUNEL assay was applied for the detection of total apoptosis in tumor tissue and cell culture. Immunohistochemistry staining was used to detect cleaved caspase 3 in tumor and normal lung tissue; lung injury was measured by phosphor-smad 2/3 staining and TUNEL staining. Results: Tumor growth was significantly inhibited in combination-treated mice in comparison with M867 along or RT along (decrease in 15, 1.8 and 5.8 folds relative to control mice, respectively). Cleaved caspase 3 in tumor has shown significantly higher percentage in RT-treated mouse than combination-treated mouse (35% vs 19%, p = 0.002); however, TUNEL staining has shown significantly higher percentage in combination-treated mouse than RT-treated mouse (48% vs 27%, p = 0.0051). Cleaved caspase 3 in lung tissue showed higher percentage of apoptosis in RT (29%) than in combination (15%), while TUNEL staining did not show significant difference between RT and combination. Data also showed that phosphor-smad2/3 is significantly higher in mouse lung treated with RT than combination (31% vs 16%, p = 0.001). Western blot showed the higher cleaved caspase 3 level
S626
Volume 81, Number 2, Supplement, 2011
only; the initial dose was delivered to the CTV+5 mm margin, and the boost to the CTVonly (no margin). The nominal total dose to the CTVs was 75 Gy in 15 fractions. At an alpha/beta ratio of 10, the tumor dose equivalent at 2 Gy per fraction of the proposed regimen is 96 Gy. The plans were generated via a Varian Eclipse system. The normal tissue constraints were not based on the prescribed total dose (i.e. 75 Gy in 15 fractions), but for actual doses in each organ at risk (OAR) in each plan, e.g. if the spinal cord maximum dose was 30 Gy, then the plan would be acceptable for 15 fractions. The dosimetric endpoints included spinal cord maximum dose, esophagus mean dose, heart mean dose, % volume of total lung-PTV receiving 15 Gy, total lung-PTV mean dose, skin V50, tracheobronchial tree V50, brachial plexus V45. Results: Overall, only one of the 14 plans was considered unacceptable; lung and heart constraints were significantly exceeded. This case had the largest tumor burden and was in the lower lobe. In addition, 3 cases had the tracheobronchial tree V50 only marginally exceeding the set limit; these were ultimately considered acceptable plans. The spinal cord maximum constraint was met in all cases. The average spinal cord maximal dose was 32 Gy, with a range of 18 - 43 Gy. The esophageal mean constraint was met in all cases (average dose was13 Gy, range 6 - 22). The heart mean dose was 7 Gy (range 1 - 33). The % volume of total lung-PTV receiving 15 Gy was 27% (range 17 - 50). The total lung-PTV mean dose was 11 Gy (range 6 - 17). The skin V50 Gy was negligible. The tracheobronchial tree constraint (the tracheobronchial tree V50) was set at 15 cc and was met in 11 of the 14 cases; 3 cases marginally exceeded the limit at 19, 20 and 21 cc. The average tracheobronchial tree V50 Gy was 9 cc (range 1 - 21). The brachial plexus was relevant for 3 patients, with an average V45 Gy of 0.6 cc (range 0 - 8). Conclusions: This study showed that a hypofractionated regimen consisting of 4 Gy x 10, 7 Gy x 5 is dosimetrically feasible in a majority of Stage III lung cancer patients, except in patients with large tumor burdens. Author Disclosure: C. Huang: None. P. Kupelian: None. S. Tenn: None. S. Alexander: None. C. Lee: None. R. Huang: None. P. Lee: None.
2866
Tumor Location Correlates with Radiation Pneumonitis after Stereotactic Body Radiation Therapy (SBRT) for Primary and Oligometastatic Lesions of the Lung
A. R. Bhirud, N. Dunlap, K. Sheng, P. Read, J. Larner University of Virginia, Charlottesville, VA Purpose/Objective(s): To determine the incidence of radiation pneumonitis (RP) and identify associated clinical and dosimetric factors in patients treated with stereotactic body radiation therapy for early stage lung cancer. Materials/Methods: A retrospective analysis was performed on 51 consecutive patients treated with SBRT for primary NSCLC or oligometastatic lesion of the lung. Central lesions, as defined by the RTOG criteria, were excluded. Patients were treated with 3 - 5 fractions of 12 - 20 Gy SBRT with a median BED of 132 Gy. Clinical symptoms were graded by Common Terminology Criteria for Adverse Events, version 3.0 (CTCAE v3). Symptoms were evaluated at 1 month, 3 months, and then 3 month intervals for 2 years after completion of treatment. Univariate and binary logistic regression analyses were completed to analyze relationships with clinical and dosimetric factors. Results: Median follow up was 16.5 months (range 2.0 - 37.0). Twelve patients (23.5%) developed RP grade 2 and three patients (5.8%) developed RP grade 3. No patients developed grade 4 or 5 RP. Age, gender, PTV volume, tumor size, V5, V10, V20, V30, mean lung dose (MLD), and R50 were not correlated with RP . = 2. Treatment of tumors in the right lower lobe compared to the right upper lobe predicted for RP. = 2 (OR = 5.650, p = .044). A similar relationship was not seen between the upper and lower lobes in the left lung. Conclusions: SBRT for early stage peripheral NSCLC resulted in a low rate (5.8%) of high grade pneumonitis (RP. = 3). Right lower lobe tumors may be correlated with a higher incidence of clinical radiation pneumonitis, possibly due to the increased role of the right lung and lower lobe in gaseous exchange. Author Disclosure: A.R. Bhirud: None. N. Dunlap: None. K. Sheng: None. P. Read: None. J. Larner: None.
2867
M867, A Selective Caspases Inhibitor, Sensitizes Lung Cancer to Radiotherapy, and Reduces Radiationinduced Lung Injury
B. Li, A. Torossian, B. Lu Vanderbilt University, Nashville, TN Purpose/Objective(s): Radiotherapy is one of the principal treatment modalities in treating locally advanced NSCLC, radiationinduced lung injury remains a major impediment in radiotherapy. Previous studies show M867 is able to sensitize radiation-induced tumor inhibition in ectopic mouse model, we, in this study, used a novel orthotopic mouse model to investigate efficacy of M867 on lung cancer and normal lung after radiotherapy. Materials/Methods: H460-Luc cells were implanted in mediastinum of athymic nude mice, mice in each group (n = 5) received: (1) none; (2) M867 2mg/kg, i.p. x 7 days; (3) RT (2Gy) x 5 days; and (4) combination. Tumor growth was followed by bioluminescence imaging (BLI); Western blotting is used for the detection of Apoptosis-Inducing Factor (AIF) of cytoplasm and nucleus. TUNEL assay was applied for the detection of total apoptosis in tumor tissue and cell culture. Immunohistochemistry staining was used to detect cleaved caspase 3 in tumor and normal lung tissue; lung injury was measured by phosphor-smad 2/3 staining and TUNEL staining. Results: Tumor growth was significantly inhibited in combination-treated mice in comparison with M867 along or RT along (decrease in 15, 1.8 and 5.8 folds relative to control mice, respectively). Cleaved caspase 3 in tumor has shown significantly higher percentage in RT-treated mouse than combination-treated mouse (35% vs 19%, p = 0.002); however, TUNEL staining has shown significantly higher percentage in combination-treated mouse than RT-treated mouse (48% vs 27%, p = 0.0051). Cleaved caspase 3 in lung tissue showed higher percentage of apoptosis in RT (29%) than in combination (15%), while TUNEL staining did not show significant difference between RT and combination. Data also showed that phosphor-smad2/3 is significantly higher in mouse lung treated with RT than combination (31% vs 16%, p = 0.001). Western blot showed the higher cleaved caspase 3 level