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: The purpose of this study is to evaluate the correlation between the conventional plan parameters and dosimetric parameters obtained from conformal radiotherapy (RT) planning, and between these parameters and radiation pneumontitis (RP) incidence. METHODS: Clinical and dosimetric data of 122 patients that were treated with mastectomy and adjuvant 3D conformal RT (39% received 2-field RT [2-FRT], and in addition, 61% received 4-field RT [4-FRT]) were retrospectively analyzed. Central lung depth (CLD), maximum lung depth (MLD), and lung length were measured by the conventional plan. Lung dose-volume histograms (DVH) were created with conformal planning, and the lung volumes receiving 5 to 50 Gy (V5Gy to V50Gy) were calculated. Minimum (Dmin), maximum (Dmax), and mean doses (Dmean) for the ipsilateral lung and bilateral lungs were measured by DVH. Correlations between 3D dosimetric data and 2D radiographic parameters were analyzed. RESULTS: The conventional plan parameters did not significantly differ between 2-FRT and 4-FRT. The conformal plan Dmin, Dmax, and Dmean values were higher in 4-FRT versus 2-FRT. CLD and MLD were correlated with DVH parameter V5Gy to V45Gy values for ipsilateral, as well as bilateral lungs for 2-FRT. MLD and ipsilateral Dmean via 2-FRT planning had the strongest positive correlation (r=0.76, p<0.01). Moderate correlations existed between CLD and ipsilateral and bilateral lung V5Gy-45Gy, and between MLD and bilateral lung V5Gy-45Gy values in 2-FRT. Only four patients developed symptomatic RP, 4 with 4-FRT and one with 2-FRT. CONCLUSION: The conformal plan parameters were strongly correlated with dose-volume parameters for breast 2-FRT. With only 4 cases of Grade 3 RP observed, our study is limited in its ability to provide definitive guidance, however assuming that CLD is an indicator for RP, V20Gy could be used as a predictor for RP and for 2-FRT. A well-defined parameters are still required to predict RP in 4-FRT.
Breast ; Breast Neoplasms ; Humans ; Lung ; Mastectomy ; Radiation Pneumonitis ; Radiotherapy, Adjuvant ; Radiotherapy, Conformal ; Retrospective Studies

PURPOSE: To reduce the irradiation dose to the lungs and heart in the case of chest wall irradiation using an oppositional electron beam, we used an individualized custom bolus, which was precisely designed to compensate for the differences in chest wall thickness. The benefits were evaluated by comparing the normal tissue complication probabilities (NTCPs) and dose statistics both with and without boluses. MATERIALS AND METHODS: Boluses were made, and their effects evaluated in ten patients treated using the reverse hockey-stick technique. The electron beam energy was determined so as to administer 80% of the irradiation prescription dose to the deepest lung-chest wall border, which was usually located at the internal mammary lymph node chain. An individualized custom bolus was prepared to compensate for a chest wall thinner than the prescription depth by meticulously measuring the chest wall thickness at 1 cm2 intervals on the planning CT images. A second planning CT was obtained overlying the individualized custom bolus for each patient's chest wall. 3-D treatment planning was performed using ADAC-Pinnacle3 for all patients with and without bolus. NTCPs based on "the Lyman-Kutcher" model were analyzed and the mean, maximum, minimum doses, V50 and V95 for the heart and lungs were computed. RESULTS: The average NTCPs in the ipsilateral lung showed a statistically significant reduction (p<0.01), from 80.2+/-3.43% to 47.7+/-4.61%, with the use of the individualized custom boluses. The mean lung irradiation dose to the ipsilateral lung was also significantly reduced by about 430 cGy, from 2757 cGy to 2,327 cGy (p<0.01). The V50 and V95 in the ipsilateral lung markedly decreased from the averages of 54.5 and 17.4% to 45.3 and 11.0%, respectively. The V50 and V95 in the heart also decreased from the averages of 16.8 and 6.1% to 9.8% and 2.2%, respectively. The NTCP in the contralateral lung and the heart were 0%, even for the cases with no bolus because of the small effective mean radiation volume values of 4.4 and 7.1%, respectively. CONCLUSION: The use of an individualized custom bolus in the radiotherapy of postmastectomy chest wall reduced the NTCP of the ipsilateral lung by about 24.5 to 40.5%, which can improve the complication free cure probability of breast cancer patients.
Breast Neoplasms ; Heart ; Humans ; Lung ; Lymph Nodes ; Prescriptions ; Radiation Pneumonitis ; Radiotherapy ; Thoracic Wall

Radiation therapy is one of the most important therapeutic modalities for the treatment of lung cancer. Radiation pneumonitis is one of the important complications associated with radiotherapy for lung cancer. Radiation pneumonitis is generally limited to the irradiated lung and is manifested by the insidious onset of dry cough, dyspnea, and mild fever, resulting in damage and edematous changes of alveolar structures on histologic inspection. Clinically, diffuse bilateral radiation pneumonitis accompanied with acute symptoms after unilateral thoracic irradiation appears very rarely. Histopathologic examinations for the diagnosis of out-of-field radiation pneumonitis are rarely performed. We herein describe a case of extensive bilateral radiation pneumonitis which developed acutely after salvage radiotherapy for squamous cell carcinoma in the left upper lobe of the lung. The condition was confirmed by a diagnostic help of histopathologic findings.
Carcinoma, Squamous Cell ; Cough ; Dyspnea ; Fever ; Lung ; Lung Neoplasms ; Radiation Pneumonitis

PURPOSE: To evaluate the effect of high-dose-rate endobronchial brachytherapy for symptomatic relief, tumor response and overall survival of advanced non-small cell lung carcinoma (NSCLC). MATERIALS AND METHODS: Between July 1992 and July 2001, 37 patients with advanced NSCLC were analysed retrospectively. Group A patients (palliative aim, n=25) were treated using brachytherapy alone due to relapse after external beam radiation therapy (EBRT). Group B patients (curative aim, n=12) were treated using brachytherapy alone or combined EBRT due to untreated inoperable NSCLC or positive resection margin after radical resection. The dose per fraction was 3~6 Gy at a radius of 1cm from the center of the source and each patient received 2~3 fractions. The total dose of brachytherapy was 9~18 Gy (median 15 Gy). Each fraction separated by 1 week interval. RESULTS: Symptomatic relief was obtained for cough (58.3% & 72.7%), dyspnea (56.3% & 75%) and hemoptysis (86.7% & 100%) in group A and B, respectively. The tumor improvement on bronchoscopy was obtained for complete response (28% & 60%) and partial response (64% & 40%) in group A and B, respectively. Median overall survival was 7 and 17.2 months for Group A and B, respectively. In group A, mediastinal node metastasis (p=0.039) and Karnofsky performance scale (p=0.062) was independent prognostic factor by univariate analysis. After radical therapy, 7 symptomatic radiation pneumonitis, 4 hemoptysis and 1 pneumothorax were observed. CONCLUSION: Endobronchial brachytherapy was effective for symptomatic relief of hemoptysis. In curative aim, we think that survival improvement may be expected in some selected patients
Brachytherapy* ; Bronchoscopy ; Cough ; Dyspnea ; Hemoptysis ; Humans ; Lung* ; Neoplasm Metastasis ; Pneumothorax ; Radiation Pneumonitis ; Radius ; Recurrence ; Retrospective Studies