PURPOSE: To develop the dose volume histogram (DVH) management software which guides the evaluation of radiotherapy (RT) plan of a new case according to the biological consequences of the DVHs from the previously treated patients. MATERIALS AND METHODS: We determined the radiation pneumonitis (RP) as an biological response parameter in order to develop DVH management software. We retrospectively reviewed the medical records of lung cancer patients treated with curative 3-dimensional conformal radiation therapy (3D-CRT). The biological event was defined as RP of the Radiation Therapy Oncology Group (RTOG) grade III or more. RESULTS: The DVH management software consisted of three parts (pre-existing DVH database, graphical tool, and Pinnacle3 script). The pre-existing DVH data were retrieved from 128 patients. RP events were tagged to the specific DVH data through retrospective review of patients' medical records. The graphical tool was developed to present the complication histogram derived from the pre-existing database (DVH and RP) and was implemented into the radiation treatment planning (RTP) system, Pinnacle3 v8.0 (Phillips Healthcare). The software was designed for the pre-existing database to be updated easily by tagging the specific DVH data with the new incidence of RP events at the time of patients' follow-up. CONCLUSION: We developed the DVH management software as an effective tool to incorporate the phenomenological consequences derived from the pre-existing database in the evaluation of a new RT plan. It can be used not only for lung cancer patients but also for the other disease site with different toxicity parameters.
Humans ; Incidence ; Lung Neoplasms ; Medical Records ; Radiation Pneumonitis ; Retrospective Studies

The damage which radiation produces in tissues such as the lungs can be discussed at the molecular, biophysical, cellular, and organ levels. The cellular effects of irradiating the lungs are related to the histologic and clinical sequelae. In the present study the right lung of rabbits were exposed to single dose of 20 Gy of X-irradiation. Animals from each group were sacrificed monthly for 6 months postexposure. Sections of lung were examined by light microscopy(LM) and by transmission electron microscopy(TEM). Multiple exudative lesions were seen at 2 months after the 20Gy irradiation, and they progressed to a proliferative and then reparative fibrotic lesion by 6 months. Changes in epithelial lining of lung components, particulary the presence of type II pneumocytes were found by both LM and TEM. Capillary endothelial damages were less pronounced. The possible implication of cellular components in radiation pneumonitis and fibrosis is discussed.
Animals ; Capillaries ; Fibrosis ; Lung* ; Pneumocytes ; Rabbits ; Radiation Pneumonitis

Radiologic findings of the 29 cases of radiation pneumonitis and fibrosis diagnosed by chest radiography atSeoul National University Hospital were evaluated and compared with clinical symptoms according to the passage oftime after radiation therapy. The resuls were as follows; 1. The first radiographic signs of radiation pneumonitisand fibrosis were observed 7.6 weeks and 19.3 weeks after radiation therapy respectively. Especially in 8 cases ofsmall cell ca., they were found 5.6 weeks and 10.4 weeks, appearing slinghtly earlier than those of 12 cases ofsquamous cell ca. of lung. 2. The appearing time and severity of the radiographic changes of radiation pneumonitisand fibrosis had no specific relationship with field size, tumor dose or time-dose-fractionation factors of thetreatment. 3. The most constant and characteristic radiological finding of radiation pneumonitis was the sharp andstraight margin of the lesion, which was not that of normal anatomical structures of the lung. Other findings werediffuse haziness, indistinct normal pulmonary markings, alveolar and nodular densities, air-bronchograms andindistinctness of heart border. In radiation fibrosis stage, the lesion characteristic and constant finding. Otherfindings were indistinctness of heart border, diaphragmatic tenting and compensatory emphysema.
Emphysema ; Fibrosis ; Heart ; Lung ; Radiation Pneumonitis ; Radiography ; Thorax

PURPOSE: NOS2 induce NO production and NO activate TGF-beta. The TGF-beta is a inhibitor of NOS2. If this negative feedback mechanism operating in radiation pneumonitis model, NOS2 inhibitor may play a role in TGF-beta suppression. We planned this study to evaluate the expression patterns of NO, NOS2 and TGF-beta in vivo radiation pneumonitis model. MATERIALS AND METHODS: Sixty sprague-Dawley rat were irradiated 5 Gy or 20 Gy. They were sacrificed 3, 7, 14, 28 and 56 days after irradiation. During sacrifice, we performed broncho-alveolar lavage (BAL). The BAL fluids were centrifuged and supernatents were used for measure NO and TGF-beta, and the cells were used for RT-PCR. RESULTS: After 5 Gy of radiation, NO in BAL fluid increased at 28 days in both lung and TGF-beta in left lung at 56 days. NO increased in BAL fluid at 28 days in both lung after irradiation and TGF-beta in right lung at 28-56 days after 20 Gy of radiation. After 5 Gy of radiation, NOS2 expression was increased in right lung at 14 days, in both lung at 28 days and in left lung at 56 days. TGF-beta expression was reduced in both lung at 28 days and increased in left lung at 56 days. CONCLUSIONS: The proposed feedback mechanism of NO, NOS2 and TGF-beta was operated in vivo radiation pneumonitis model. At 56 days, however, NOS2 and TGF-beta expressed concurrently in left lung after 5 Gy and in both lung after 20 Gy of radiation.
Animals ; Lung* ; Radiation Effects* ; Radiation Pneumonitis ; Rats* ; Rats, Sprague-Dawley ; Therapeutic Irrigation ; Transforming Growth Factor beta*

PURPOSE: The aim of this study is to present the incidence of radiation pneumonitis (RP) reported within 6 months after treatment for breast cancer with or without internal mammary node irradiation (IMNI). METHODS: In the Korean Radiation Oncology Group (KROG) 08-06 phase III randomized trial, patients who were node-positive after surgery were randomly assigned to receive radiotherapy either with or without IMNI. A total of 747 patients were enrolled, and three-dimensional treatment planning with computed tomography simulation was performed for all patients. Of the 747 patients, 722 underwent chest X-rays before and within 6 months after radiotherapy. These 722 patients underwent evaluation, and RP was diagnosed on the basis of chest radiography findings and clinical symptoms. The relationship between the incidence of RP and clinical/dosimetric parameters was analyzed. RESULTS: RP developed in 35 patients (4.8%), including grade 1 RP in 26 patients (3.6%), grade 2 RP in nine patients (1.2%); there was no incidence of grade 3 or higher RP. Grade 2 RP cases were observed in only the IMNI group. The risk of developing RP was influenced by IMNI treatment; pneumonitis occurred in 6.5% of patients (n=23/356) who underwent IMNI and in 3.3% of patients (n=12/366) who did not (p=0.047). The differences in lung dosimetric parameters (mean lung dose, V10–40) were statistically significant between the two groups. CONCLUSION: IMNI treatment resulted in increased radiation exposure to the lung and a higher rate of RP, but the incidence and severity of RP was minimal and acceptable. This minor impact on morbidity should be balanced with the impact on survival outcome in future analyses.
Breast Neoplasms* ; Breast* ; Humans ; Incidence ; Lung ; Lymphatic Irradiation ; Pneumonia ; Radiation Exposure ; Radiation Oncology ; Radiation Pneumonitis* ; Radiography ; Radiotherapy ; Thorax

Radiation-induced lung injury (RILI), including acute radiation pneumonitis and chronic radiation-induced pulmonary fibrosis (RIPF), is a side effect of radiotherapy for lung cancer and esophageal cancer. Pulmonary macrophages, as a kind of natural immune cells maintaining lung homeostasis, play a key role in the whole pathological process of RILI. In the early stage of RILI, classically activated M1 macrophages secrete proinflammatory cytokines to induce inflammation and produce massive reactive oxygen species (ROS) through ROS-induced cascade to further impair lung tissue. In the later stage of RILI, alternatively activated M2 macrophages secrete profibrotic cytokines to promote the development of RIPF. The roles of macrophage in the pathogenesis of RILI and the related potential clinical applications are summarized in this review.
Humans ; Lung/radiation effects* ; Lung Injury/physiopathology* ; Macrophages/metabolism* ; Radiation Injuries ; Radiation Pneumonitis/etiology* ; Radiotherapy/adverse effects*

PURPOSE: This study was designed to determine the optimum radiotherapy technique for internal mammary node (IMN) irradiation after breast-conserving surgery. MATERIALS AND METHODS: We selected ten cases of early stage partial mastectomy for plan comparison. Five of the patients were treated to the right-side breast and the rest of the patients were treated to the left-side breast. For each case, four different treatment plans were made to irradiate the entire breast, IMNs and supraclavicular lymph nodes (SCLs). The four planning techniques include a standard tangential field (STF), wide tangential field (WTF), partially wide tangential field (PWT) and a photon-electron mixed field (PEM). We prescribed a dose of 50.4 Gy to the SCL field at a 3 cm depth and isocenter of the breast field. RESULTS: The dose distribution showed clear characteristics depending on the technique used. All of the techniques covered the breast tissue well. IMN coverage was also good, except for the STF, which was not intended to cover IMNs. For the cases of the left-side breasts, the volume of the heart that received more than 30 Gy was larger (in order) for the WTF, PWT, PEM and STF. For radiation pneumonitis normal tissue complication probability (NTCP), the PWT showed the best results followed by the STF. CONCLUSION: Despite the variety of patient body shapes, the PWT technique showed the best results for coverage of IMNs and for reducing the lung and heart dose.
Breast ; Breast Neoplasms ; Heart ; Humans ; Lung ; Lymph Nodes ; Mastectomy, Segmental ; Planning Techniques ; Radiation Pneumonitis

PURPOSE: Although stereotactic ablative body radiotherapy (SABR) is widely used therapeutic technique, predictive factors of radiation pneumonitis (RP) after SABR remain undefined. We aimed to investigate the predictive factors affecting RP in patients with primary or metastatic lung tumors who received SABR. MATERIALS AND METHODS: From 2012 to 2015, we reviewed 59 patients with 72 primary or metastatic lung tumors treated with SABR, and performed analyses of clinical and dosimetric variables related to symptomatic RP. SABR was delivered as 45–60 Gy in 3–4 fractions, which were over 100 Gy in BED when the α/β value was assumed to be 10. Tumor volume and other various dose volume factors were analyzed using median value as a cutoff value. RP was graded per the Common Terminology Criteria for Adverse Events v4.03. RESULTS: At the median follow-up period of 11 months, symptomatic RP was observed in 13 lesions (12 patients, 18.1%), including grade 2 RP in 11 lesions and grade 3 in 2 lesions. Patients with planning target volume (PTV) of ≤14.35 mL had significantly lower rates of symptomatic RP when compared to others (8.6% vs. 27%; p = 0.048). Rates of symptomatic RP in patients with internal gross tumor volume (iGTV) >4.21 mL were higher than with ≤4.21 mL (29.7% vs. 6.1%; p = 0.017). CONCLUSIONS: The incidence of symptomatic RP following treatment with SABR was acceptable with grade 2 RP being observed in most patients. iGTV over 4.21 mL and PTV of over 14.35 mL were significant predictive factors related to symptomatic RP.
Follow-Up Studies ; Humans ; Incidence ; Lung Neoplasms ; Lung* ; Radiation Pneumonitis* ; Radiotherapy* ; Risk Factors ; Tumor Burden

PURPOSE: To evaluate the relationship between the normal tissue complication probability (NTCP) of 3- dimensional (3-D) radiotherapy and the radiographic parameters of 2-dimensional (2-D) radiotherapy such as central lung distance (CLD) and maximal heart distance (MHD). MATERIALS AND METHODS: We analyzed 110 patients who were treated with postoperative radiotherapy for breast cancer. A two-field tangential technique, a three-field technique, and the reverse hockey stick method were used. The radiation dose administered to whole breast or the chest wall was 50.4 Gy, whereas a 45 Gy was administered to the supraclavicular field. The NTCPs of the heart and lung were calculated by the modified Lyman model and the relative seriality model. RESULTS: For all patients, the NTCPs of radiation-induced pneumonitis and cardiac mortality were 0.5% and 0.7%, respectively. The NTCP of radiation-induced pneumonitis was higher in patients treated with the reverse hockey stick method than in those treated by other two techniques (0.0%, 0.0%, 3.1%, p<0.001). The NTCP of radiation-induced pneumonitis increased with CLD. The NTCP of cardiac mortality increased with MHD (R2=0.808). CONCLUSION: We found a close correlation between the NTCP of 3-D radiotherapy and 2-D radiographic parameters. Our results are useful to reanalyze the previous 2-D based clinical reports about breast radiation therapy complications as a viewpoint of NTCP.
Breast ; Breast Neoplasms ; Heart ; Hockey ; Humans ; Lung ; Pneumonia ; Radiation Pneumonitis ; Thoracic Wall

PURPOSE: Prognosis of locally advanced inoperable non-small cell lung cancer (NSCLC) treated with radiation therapy alone has been disappointing. In recent years, concurrent chemoradiation therapy has potential of improving both local and metastatic disease-free survival. This phase II study was undertaken to determine the feasibility, toxicity, response rate, local control rate, and survival duration of locally advanced NSCL patients treated with concurrent chemoradiation using cisplatin and oral etoposide. MATERIAL AND METHODS: Forty-seven patients were enrolled and forty-one patients were evaluable. Chemotheray consisted of cisplatin 50 mg/m2/IV on days 1 and 8 and oral etoposide 100 mg/day on days 1 to 5 and 8 to 12 which was repeated, every 4 weeks for two cycles during radiation therapy. Radiation therapy was administered to a total dose of 6300 cGY. RESULTS: Among 41 evaluable patients, six patients achieved complete response, and twenty had partial response, for an overall response rate of 63.4% (95% confidence interval; 48.4% to 75.4%). Stable disease was reported in 10 patients (24.4%) and another 5 (12.2%) showed disease pro gression. Overall survival rate was 76% at 1 year, 34% at 2 years. Median survival duration was 17 months (range; 3 to 41 ). Eighty-three percents of patients had radiation pneumonitis but only one patients needed medical treatment. CONCLUSION: Concurrent chemoradiation therapy with cisplatin and oral etoposide at this level is a well tolerated and feasible.
Carcinoma, Non-Small-Cell Lung* ; Cisplatin* ; Disease-Free Survival ; Etoposide* ; Humans ; Prognosis ; Radiation Pneumonitis ; Survival Rate