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

Abstract

Background: Radiotherapy (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.

Method: A 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.

Results: Helical-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.

Conclusion: Rat 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.

Fig. 1

Plasma levels of a IL-1α and b IL-1β according to the experimental rat groups. There were significant differences among the groups at 3 weeks after tomotherapy or CCRT. ^* p <0.05; NS, not significant; IL, interleukin; CCRT, concurrent chemoradiotherapy

Fig. 2

Tissue expression of IL-1α. a Right lung samples demonstrated higher tissue IL-1α expression compared to the untreated control samples. b Left lung samples revealed upregulated tissue IL-1α expression. Immunohistochemical staining with anti-IL-1α antibody of c normal control and d right lung sample treated with helical tomotherapy with CCRT. ^* p <0.05; NS, not significant; IL, interleukin; CCRT, concurrent chemoradiotherapy; bars = 200 μm

Fig. 3

Tissue expression of IL-1β. a Right lung samples demonstrated higher tissue IL-1β expression compared to the untreated control samples. b Left lung samples revealed upregulated tissue IL-1β expression. Immunohistochemical staining with anti-IL-1β antibody of c normal control and d right lung sample treated with helical tomotherapy with CCRT. ^* p <0.05; NS, not significant; IL, interleukin; CCRT, concurrent chemoradiotherapy; bars = 200 μm

Fig. 4

Tissue expression of IL-6. a Right lung samples demonstrated higher tissue IL-6 expression compared to the untreated control samples. b Left lung samples revealed upregulated tissue IL-6 expression. Immunohistochemical staining with anti-IL-6 antibody of c normal control and d right lung sample treated with helical tomotherapy with CCRT. ^* p <0.05; ^** p <0.01; IL, interleukin; CCRT, concurrent chemoradiotherapy; bars = 200 μm

Fig. 5

Tissue expression of TGF-β. a Right lung samples demonstrated higher tissue TGF-β expression compared to the untreated control samples. b Left lung samples revealed upregulated tissue TGF-β expression. Immunohistochemical staining with anti-TGF-β antibody of c normal control and d right lung sample treated with helical tomotherapy with CCRT. ^* p <0.05; ^** p <0.01; NS, not significant; TGF, transforming growth factor; CCRT, concurrent chemoradiotherapy; bars = 200 μm