Impact of Induction Chemotherapy on Estimated Risk of Radiation Pneumonitis in Small Cell (SCLC) and Non-small Cell Lung (NSCLC) Cancer

Abstract

Purpose/Objective(s)Concurrent chemoradiation for patients (pts) with bulky SCLC or NSCLC can lead to a high risk of radiation pneumonitis (RP), which is correlated with the volume of irradiated normal lung. Induction chemotherapy (chemo) in such patients could lead to decreased tumor burden, thus smaller radiation fields and less radiation to normal lung. This study used virtual radiation therapy (RT) plans on the pre- and post- chemo CT scans of stage IV SCLC and NSCLC patients who received platin-based chemo alone, to measure the change in gross tumor volume (GTV), percent of lung receiving ≥ 20 Gy (V20), mean lung dose (MLD), and estimated risk of RP.Materials/MethodsAt the University of Colorado between 2003 and 2009, 23 pts with stage IV SCLC and 25 pts with stage IV NSCLC were treated with chemo alone (no surgery or RT) and had CT scans pre- and post- 2 cycles of platin-based chemo. Virtual RT plans were created as if to deliver 45 Gy and 66 Gy to the pre- and post-chemo thoracic disease in SCLC and NSCLC pts, respectively. Normal Tissue Complication Probability (NTCP) calculations were used to predict the pre- and post-chemo risk of pneumonitis ≥ Gr 2 based on simulated plans.ResultsEighteen of 23 (78%) SCLC pts had ≥ 30% reduction in GTV using volumetric measurements. The other 5 pts had stable disease. Among responders, mean decrease in GTV, V20, MLD and NTCP was 70% (range, 30-93%), 7.4% (range, -6.6 to 34%, p<0.01), 3.3 Gy (-0.13 to 12.1 Gy, p<0.01), and 5.5% (-0.1 to 28.5%, p<0.01), respectively. The mean relative reduction in GTV, V20, MLD, and NTCP was 70% (30 to 93%), 17% (-37 to 54%), 18% (-1 to 43%) and 28% (-1 to 65%), respectively. The absolute estimated risk of pneumonitis ≥ Gr 2 was decreased by ≥ 5% in 8 (35%) pts, while the relative risk was decreased by ≥30% in 8 (35%) pts. In total, there were 12 (52%) pts with either ≥ 5% absolute and/or ≥30% relative reduction in NTCP after induction chemo. Patients with bulky mediastinal lymphadenopathy and initial NTCP > 15% had a greater reduction in GTV and post-chemo NTCP (8.2% vs. 1.8%, p = 0.03) when compared to patients who had initial NTCP ≤ 15%. 8/25 (32%) NSCLC pts had ≥ 20% reduction in GTV (mean 44% [range 20 to 62%]) and 2/25 (8%) had > 25% progression, while 15 had stable disease. Pre- and post-chemo RT plans are pending.ConclusionsPatients with bulky limited SCLC will likely have a reduction in the risk of treatment related pneumonitis ≥ Gr 2 if treatment is planned following two cycles of induction chemotherapy. Patients with bulky mediastinal lymphadenopathy benefited more from induction chemotherapy with a significant reduction in estimated risk of RP. Induction chemo is less likely to significantly reduce risk of RP in NSCLC pts. Purpose/Objective(s)Concurrent chemoradiation for patients (pts) with bulky SCLC or NSCLC can lead to a high risk of radiation pneumonitis (RP), which is correlated with the volume of irradiated normal lung. Induction chemotherapy (chemo) in such patients could lead to decreased tumor burden, thus smaller radiation fields and less radiation to normal lung. This study used virtual radiation therapy (RT) plans on the pre- and post- chemo CT scans of stage IV SCLC and NSCLC patients who received platin-based chemo alone, to measure the change in gross tumor volume (GTV), percent of lung receiving ≥ 20 Gy (V20), mean lung dose (MLD), and estimated risk of RP. Concurrent chemoradiation for patients (pts) with bulky SCLC or NSCLC can lead to a high risk of radiation pneumonitis (RP), which is correlated with the volume of irradiated normal lung. Induction chemotherapy (chemo) in such patients could lead to decreased tumor burden, thus smaller radiation fields and less radiation to normal lung. This study used virtual radiation therapy (RT) plans on the pre- and post- chemo CT scans of stage IV SCLC and NSCLC patients who received platin-based chemo alone, to measure the change in gross tumor volume (GTV), percent of lung receiving ≥ 20 Gy (V20), mean lung dose (MLD), and estimated risk of RP. Materials/MethodsAt the University of Colorado between 2003 and 2009, 23 pts with stage IV SCLC and 25 pts with stage IV NSCLC were treated with chemo alone (no surgery or RT) and had CT scans pre- and post- 2 cycles of platin-based chemo. Virtual RT plans were created as if to deliver 45 Gy and 66 Gy to the pre- and post-chemo thoracic disease in SCLC and NSCLC pts, respectively. Normal Tissue Complication Probability (NTCP) calculations were used to predict the pre- and post-chemo risk of pneumonitis ≥ Gr 2 based on simulated plans. At the University of Colorado between 2003 and 2009, 23 pts with stage IV SCLC and 25 pts with stage IV NSCLC were treated with chemo alone (no surgery or RT) and had CT scans pre- and post- 2 cycles of platin-based chemo. Virtual RT plans were created as if to deliver 45 Gy and 66 Gy to the pre- and post-chemo thoracic disease in SCLC and NSCLC pts, respectively. Normal Tissue Complication Probability (NTCP) calculations were used to predict the pre- and post-chemo risk of pneumonitis ≥ Gr 2 based on simulated plans. ResultsEighteen of 23 (78%) SCLC pts had ≥ 30% reduction in GTV using volumetric measurements. The other 5 pts had stable disease. Among responders, mean decrease in GTV, V20, MLD and NTCP was 70% (range, 30-93%), 7.4% (range, -6.6 to 34%, p<0.01), 3.3 Gy (-0.13 to 12.1 Gy, p<0.01), and 5.5% (-0.1 to 28.5%, p<0.01), respectively. The mean relative reduction in GTV, V20, MLD, and NTCP was 70% (30 to 93%), 17% (-37 to 54%), 18% (-1 to 43%) and 28% (-1 to 65%), respectively. The absolute estimated risk of pneumonitis ≥ Gr 2 was decreased by ≥ 5% in 8 (35%) pts, while the relative risk was decreased by ≥30% in 8 (35%) pts. In total, there were 12 (52%) pts with either ≥ 5% absolute and/or ≥30% relative reduction in NTCP after induction chemo. Patients with bulky mediastinal lymphadenopathy and initial NTCP > 15% had a greater reduction in GTV and post-chemo NTCP (8.2% vs. 1.8%, p = 0.03) when compared to patients who had initial NTCP ≤ 15%. 8/25 (32%) NSCLC pts had ≥ 20% reduction in GTV (mean 44% [range 20 to 62%]) and 2/25 (8%) had > 25% progression, while 15 had stable disease. Pre- and post-chemo RT plans are pending. Eighteen of 23 (78%) SCLC pts had ≥ 30% reduction in GTV using volumetric measurements. The other 5 pts had stable disease. Among responders, mean decrease in GTV, V20, MLD and NTCP was 70% (range, 30-93%), 7.4% (range, -6.6 to 34%, p<0.01), 3.3 Gy (-0.13 to 12.1 Gy, p<0.01), and 5.5% (-0.1 to 28.5%, p<0.01), respectively. The mean relative reduction in GTV, V20, MLD, and NTCP was 70% (30 to 93%), 17% (-37 to 54%), 18% (-1 to 43%) and 28% (-1 to 65%), respectively. The absolute estimated risk of pneumonitis ≥ Gr 2 was decreased by ≥ 5% in 8 (35%) pts, while the relative risk was decreased by ≥30% in 8 (35%) pts. In total, there were 12 (52%) pts with either ≥ 5% absolute and/or ≥30% relative reduction in NTCP after induction chemo. Patients with bulky mediastinal lymphadenopathy and initial NTCP > 15% had a greater reduction in GTV and post-chemo NTCP (8.2% vs. 1.8%, p = 0.03) when compared to patients who had initial NTCP ≤ 15%. 8/25 (32%) NSCLC pts had ≥ 20% reduction in GTV (mean 44% [range 20 to 62%]) and 2/25 (8%) had > 25% progression, while 15 had stable disease. Pre- and post-chemo RT plans are pending. ConclusionsPatients with bulky limited SCLC will likely have a reduction in the risk of treatment related pneumonitis ≥ Gr 2 if treatment is planned following two cycles of induction chemotherapy. Patients with bulky mediastinal lymphadenopathy benefited more from induction chemotherapy with a significant reduction in estimated risk of RP. Induction chemo is less likely to significantly reduce risk of RP in NSCLC pts. Patients with bulky limited SCLC will likely have a reduction in the risk of treatment related pneumonitis ≥ Gr 2 if treatment is planned following two cycles of induction chemotherapy. Patients with bulky mediastinal lymphadenopathy benefited more from induction chemotherapy with a significant reduction in estimated risk of RP. Induction chemo is less likely to significantly reduce risk of RP in NSCLC pts.