Risk factors of radiation pneumonitis in patients with NSCLC treated with concomitant chemoradiotherapy––Are we underestimating diabetes?––Turkish oncology group (TOG)/Lung cancer study group

Abstract

Introduction To evaluate the clinical and dosimetric parameters that increase the risk of radiation pneumonitis (RP) in locally advanced non‐small cell lung cancer (NSCLC) patients treated with concomitant chemoradiotherapy of nationwide multicentric data analysis. Methods All data of 268 patients who underwent definitive chemoradiotherapy were retrospectively collected from eight institutes participating in this study. Patient, tumor and treatment‐related factors and dosimetric parameters were analyzed for grade ≥2 RP. The toxicity scoring system of The Radiation Therapy Oncology Group used for grading the severity of pneumonitis. A relationship with the risk of RP with potential predictive factors were evaluated by univariate and multivariate analyses. A recursive partition analysis (RPA) was applied to stratify patients according to the risk of developing RP. Results There were 90 (33.6%) patients who had grade ≥2 RP. The median time to pneumonitis after treatment was 4 months (range:1‐6 months). In univariate analysis, diabetes mellitus (DM), use of cisplatin/etoposide, total and daily radiotherapy (RT) fraction dose, the planning target volume (PTV) size, mean lung dose, V5, V10 and RT technique were associated with the development of pneumonitis. In multivariate analysis, only DM (P = 0.008) was found to be independent risk factors for RP. According to RPA, the risk of developing RP was highest in patients with DM. Conclusions In our study, besides the known dosimetric factors, DM was found to be the most important risk factor causing RP development in multivariate analysis and RPA. The risk is tripled compared to patients without DM.

Risk factors affecting the severity of radiation pneumonitis after intensity-modulated radiation therapy

“…The common dose of radical radiotherapy for advanced lung cancer and esophageal cancer is 60 Gy, as recommended by the clinical guidelines for lung cancer (2021 edition) [30] and the Chinese guidelines for radiation therapy for esophageal cancer (2021 edition) [31] . In this study, the radiation dose was compared using 60 Gy as the boundary, and univariate analysis showed radiation dose ≥ 60 Gy had a higher severity of radiation pneumonitis, which is consistent with the results of several previous studies [5,8,10,13,[34][35][36][37][38][39][40][41] .…”

Clinical features and risk factors for interstitial lung disease spreading in low-dose irradiated areas after definitive radiotherapy with or without durvalumab consolidation therapy for patients with non-small cell lung cancer

“…Although it has long been recognized that the finding of shadows extending outside the high-dose area on CT imaging indicates that RP might be severe, to the best of our knowledge an association with high HbA1c levels has not previously been reported. However, several studies have reported diabetes as a risk factor for RP [ 22 , 23 ]; and it has also been reported that diabetic patients are in a chronic inflammatory state, with increased secretion of inflammatory cytokines such as TNF-α and IL-6 as well as increased production of reactive oxygen species by neutrophils [ 24 – 26 ]. Therefore, it can be inferred that the inflammatory response to radiation [ 15 ] is enhanced in diabetic patients, which may be associated with frequency and severity of RP.…”

Clinical features and risk factors for interstitial lung disease spreading in low-dose irradiated areas after definitive radiotherapy with or without durvalumab consolidation therapy for patients with non-small cell lung cancer

“…Although it has long been recognized that the nding of shadows extending outside the high-dose area on CT imaging indicates that RP might be severe, to the best of our knowledge an association with high HbA1c levels has not previously been reported. However, several studies have reported diabetes as a risk factor for RP [22,23]; and it has also been reported that diabetic patients are in a chronic in ammatory state, with increased secretion of in ammatory cytokines such as TNF-α and IL-6 as well as increased production of reactive oxygen species by neutrophils [24][25][26]. Therefore, it can be inferred that the in ammatory response to radiation [12] is enhanced in diabetic patients, which may be associated with frequency and severity of RP.…”