Reduced radiation exposure to circulating blood cells in proton therapy compared with X-ray therapy in locally advanced lung cancer: Computational simulation based on circulating blood cells.

Background: We estimated the dose of circulating blood cells (CBCs) in patients with locally advanced non-small cell lung cancer for predicting severe radiation-induced lymphopenia (SRIL) and compared pencil-beam scanning proton therapy (PBSPT) and intensity-modulated (photon) radiotherapy (IMRT). Materials and methods: After reviewing 325 patients who received definitive chemoradiotherapy with PBSPT (n = 37) or IMRT (n = 164). SRIL was diagnosed when two or more events of an absolute lymphocyte count < 200 µL occurred during the treatment course. Dose information for the heart and lungs was utilized for the time-dependent computational dose calculation of CBCs. Results: The dose distribution of CBCs was significantly lesser in the PBSPT group than that in the IMRT group. Overall, 75 (37.3%) patients experienced SRIL during the treatment course; 72 and 3 patients were treated with IMRT and PBSPT, respectively. SRIL was associated with poor progression-free and overall survival outcomes. Upon incorporating the dose information of CBCs for predicting SRIL, CBC D90% > 2.6 GyE was associated with the development of SRIL with the baseline lymphocyte count and target volume. Furthermore, PBSPT significantly reduced the dose of CBC D90% (odds ratio = 0.11; p = 0.004) compared with IMRT. Conclusion: The results of this study demonstrate the significance of the dose distribution of CBCs in predicting SRIL. Furthermore, reducing the dose of CBCs after PBSPT minimized the risk of SRIL. Lymphocyte-sparing radiotherapy in PBSPT could improve outcomes, particularly in the setting of maintenance immunotherapy.

Clinical Outcomes of Pencil Beam Scanning Proton Therapy in Locally Advanced Non-Small Cell Lung Cancer: Propensity Score Analysis.

This study compared the efficacy and safety of pencil beam scanning proton therapy (PBSPT) versus intensity-modulated (photon) radiotherapy (IMRT) in patients with stage III non-small cell lung cancer (NSCLC). We retrospectively reviewed 219 patients with stage III NSCLC who received definitive concurrent chemoradiotherapy between November 2016 and December 2018. Twenty-five patients (11.4%) underwent PBSPT (23 with single-field optimization) and 194 patients (88.6%) underwent IMRT. Rates of locoregional control (LRC), overall survival, and acute/late toxicities were compared between the groups using propensity score-adjusted analyses. Patients treated with PBSPT were older (median: 67 vs. 62 years) and had worse pulmonary function at baseline (both FEV1 and DLCO) compared to those treated with IMRT. With comparable target coverage, PBSPT exhibited superior sparing of the lung, heart, and spinal cord to radiation exposure compared to IMRT. At a median follow-up of 21.7 (interquartile range: 16.8-26.8) months, the 2-year LRC rates were 72.1% and 84.1% in the IMRT and PBSPT groups, respectively (p = 0.287). The rates of grade ≥ 3 esophagitis were 8.2% and 20.0% after IMRT and PBSPT (p = 0.073), respectively, while corresponding rates of grade ≥ 2 radiation pneumonitis were 28.9% and 16.0%, respectively (p = 0.263). PBSPT appears to be an effective and safe treatment technique even for patients with poor lung function, and it does not jeopardize LRC.

Proton beam therapy reduces the risk of severe radiation-induced lymphopenia during chemoradiotherapy for locally advanced non-small cell lung cancer: A comparative analysis of proton versus photon therapy.

HYPOTHESIS: We investigated differences in severe radiation-induced lymphopenia (SRL) after pencil beam scanning proton therapy (PBSPT) or intensity-modulated (photon) radiotherapy (IMRT) for patients with locally advanced non-small cell lung cancer. METHODS: We retrospectively reviewed 223 patients who received definitive concurrent chemoradiotherapy with PBSPT (n = 29) or IMRT (n = 194). SRL was defined when ≥2 events of absolute lymphocyte counts (ALCs) of <200 cells/µL were observed in weekly laboratory tests conducted during treatment. Stepwise multivariate logistic regression with 10-fold cross-validation was performed to identify predictive values of SRL. Furthermore, 1:2 propensity score matching (PSM) analysis was performed between the PBSPT and IMRT groups. RESULTS: Baseline ALC was comparable between the PBSPT and IMRT groups (median, 2130 vs. 2040 cells/µL; p = 0.983). Lung volumes receiving ≥ 5-20 GyE and the mean dose were significantly lower in patients receiving PBSPT than those receiving IMRT (p < 0.001). Among 72 (32.3%) patients with SRL; 69 (95.8%) and 3 (4.2%) patients were treated with IMRT and PBSPT, respectively. After multivariable analysis, PBSPT reduced SRL compared to IMRT (odds ratio [OR] 0.13, p = 0.003). Specifically, lung V5Gy were identified as the strongest predictor of SRL before (OR 1.11) and after PSM (OR, 1.07) (p < 0.05). With a median follow-up of 23.0 months, the 2-year overall survival in patients with SRL was worse than that those without SRL (63.4% vs. 79.9%; p = 0.003). CONCLUSIONS: Reduced irradiated lung volumes of PBSPT consequently reduced SRL. In addition, lung V5Gy contributed to the SRL. Reduction of SRL through the optimized RT might be essential to improve the outcomes.

Preliminary result of definitive radiotherapy in patients with non-small cell lung cancer who have underlying idiopathic pulmonary fibrosis: comparison between X-ray and proton therapy.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is associated with fatal complications after radiotherapy (RT) for lung cancer patients; however, the role of proton therapy to reduce the incidence of life-threatening complications is unclear. Herein, we present the preliminary results of early-stage lung cancer patients having IPF and treated with RT, with a focus on the comparison between X-ray and proton therapy. METHODS: From January 2010 to October 2017, we retrospectively reviewed the medical records of 264 patients with stage I-II non-small cell lung cancer (NSCLC) treated with definitive RT alone. Ultimately, 30 patients (11.4%) who had underlying IPF were analyzed. Among these, X-ray and proton RT were delivered to 22 and 8 patients, respectively. Treatment-related complications and survival outcomes were compared between X-ray and proton therapy. RESULTS: The median follow-up duration was 11 months (range, 2 to 51 months). All living patients were followed-up at least 9 months. Treatment-related death occurred in four patients (18.2%) treated with X-ray but none with proton therapy. Most patients died within one month after the onset of pulmonary symptoms in spite of aggressive treatment. In addition, the 1-year overall survival (OS) rate in patients treated with X-ray and proton was 46.4 and 66.7%, respectively, and patients treated with proton therapy showed a tendency of better survival compared to X-ray (p = 0.081). Especially, in GAP stage II and III subgroups, patients treated with proton therapy showed significantly increased survival outcomes compared to X-ray (1-year OS rate; 50.0% versus 26.4%, p = 0.036) in univariate analysis. CONCLUSIONS: RT is associated with serious treatment-related complications in patients with IPF. Proton therapy may be helpful to reduce these acute and fatal complications. TRIAL REGISTRATION: retrospectively registered.

Impact Of Underlying Pulmonary Diseases On Treatment Outcomes In Early-Stage Non-Small Cell Lung Cancer Treated With Definitive Radiotherapy.

Purpose: Current guidelines recommend definitive radiotherapy for patients with medically inoperable early-stage non-small cell lung cancer (NSCLC). However, the impact of underlying pulmonary diseases on survival in those patients remains unclear. Methods: We retrospectively reviewed the medical records of 234 patients with stage I-II NSCLC treated with definitive radiotherapy alone at Samsung Medical Center between January 2010 and October 2017. We compared survival outcomes according to the presence of underlying pulmonary diseases, including chronic obstructive pulmonary disease (COPD), combined pulmonary fibrosis and emphysema (CPFE), and idiopathic pulmonary fibrosis (IPF). The control group in this study was stage I-II NSCLC patients who were non-COPD, non-CPFE, and non-IPF. Results: The median follow-up duration was 17 (range, 1-92) months. The median survival times of the control, COPD, CPFE, and IPF groups were 32, 49, 17, and 12 months, respectively (P<0.001). In a Cox proportional hazards analysis for factors associated with overall survival, patients with COPD showed a similar risk of death (adjusted hazard ratio [HR], 1.306; 95% confidence interval [CI], 0.723-2.358; P=0.376) compared to that of the control group, while patients with CPFE (adjusted HR, 3.382; 95% CI, 1.472-7.769; P=0.004) and IPF (adjusted HR, 4.061; 95% CI, 1.963-8.403; P<0.001) showed an increased risk of death. Conclusion: Definitive radiotherapy may be a tolerable treatment for early-stage NSCLC with COPD. However, poor survival in early-stage NSCLC patients with IPF or CPFE requires further study to identify and develop patient selection criteria as well as an optimal radiotherapy modality.