Risk of radiation-induced pneumonitis after helical and static-port tomotherapy in lung cancer patients and experimental rats

Abstract

BackgroundRadiotherapy (RT) is one of the major non-operative treatment modalities for treating lung cancer. Tomotherapy is an advanced type of intensity-modulated radiotherapy (IMRT) in which radiation may be delivered in a helical fashion. However, unexpected pneumonitis may occur in patients treated with tomotherapy, especially in combination with chemotherapy, as a result of extensive low-dose radiation of large lung volumes. The aim of our study was to investigate the risk of radiation-induced pneumonitis after helical-mode and static-mode tomotherapy in patients with lung cancer and in an animal model.MethodA total of 63 patients with primary lung cancer who were treated with static or helical tomotherapy with or without concurrent chemoradiotherapy (CCRT) were analyzed. Additionally, rats with radiation-induced pulmonary toxicity, which was induced by the application of helical or static tomography with or without CCRT, were evaluated.ResultsHelical-mode tomotherapy resulted in a significantly higher rate of late radiation pneumonitis in lung cancer patients than static-mode tomotherapy when evaluated by the Radiation Therapy Oncology Group (RTOG) and National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) scoring system. In the animal model, helical tomotherapy alone induced significantly higher expression of interleukin (IL)-1α, IL-1β, IL-6, and transforming growth factor (TGF)-β in lung specimens, especially on the untreated side, compared to static tomotherapy alone. Additionally, rats treated with helical tomotherapy and CCRT demonstrated significantly higher expression of inflammatory cytokines compared to those treated with static tomotherapy and CCRT.ConclusionRat models treated with tomotherapy with or without CCRT could present similar patterns of pulmonary toxicity to those shown in lung cancer patients. The models can be used in further investigations of radiation induced pulmonary toxicity.

Treatment outcome for locally advanced non‐small‐cell lung cancer using TomoDirect plan and its characteristics compared to the TomoHelical plan

“…It was suspected that this toxicity was related to increased lung volumes exposed to low‐dose (≤20 Gy) radiation because the radiation beam of this modality was delivered in 360°. Indeed, Zhang et al, reported that grade ≥2 acute and late pneumonitis occurred more frequently in patients treated with TH than in those treated with TD. Our findings also suggested that TD may effectively reduce low‐dose areas than TH, an indication that TD may have the potential to become one of the options for lung cancer radiation therapy.…”

Cytokines and radiation-induced pulmonary injuries

“… Zhou et al [ 218 ] IL-1α, IL-1β SD Right lung X-ray/15 Gy [tomotherapy and CCRT (static/helical)] 1, 2 and 3 w RT-PCR Plasma No significant differences in the levels of expression of IL-1α or IL-1β were found between the groups at Weeks 1 or 2. There were, however, significant differences in the expression of IL-1α and IL-1β between the tomotherapy and CCRT groups at 3 w. Zhang et al [ 219 ] HGF, TGF-β1, IL-10, TNF-α SD Right lung X-ray/15 Gy 3 d, 1, 2, 4, 12 and 24 w ELISA Serum, BALF The secretion of TGF-β1 in serum exhibited two peaks, with the highest concentrations at 24 w post-irradiation. TNF-α in serum was increased at intervals of 1 w and 4 w after irradiation.…”

Markers Useful in Monitoring Radiation-Induced Lung Injury in Lung Cancer Patients: A Review

“…The severity of RP depends on multiple factors, including treatment factors (dosimetric parameters—total radiation dose, number of fractions, volume of irradiated parenchyma), physiologic factors (age, gender), and genetic factors (genetic variants that confer radiosensitivity) [ 2 , 15 , 25 , 28 ]. Typical symptoms of RILI include dry cough, dyspnea, low-grade fever, shortness of breath, chest pain and discomfort, the radiologic findings on chest X-ray and computed tomography (CT) scan are typical symptoms of RILI [ 29 ]. Clinical research showed that interleukin (Il)-1, Il-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β and platelet-derived growth factor (PDGF) are associated with the occurrence of radiation pneumonitis [ 30 ].…”