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: To assess clinical factors and volumetric parameters associated with clinically significant symptomatic radiation pneumonitis (RP), which requires steroid medication after radiotherapy (RT). METHODS: Medical records of 204 irradiated breast cancer patients were reviewed. Percent lung volume (PLV) receiving more than 20 Gy was measured from CT-based treatment plan and was correlated with the central lung distance (CLD) of local and regional fields. PLV was also evaluated as a predictive factor of symptomatic RP, along with other previously reported clinical factors. RESULTS: Average (+/-standard deviation) actual irradiated lung volume and PLV for breast/chest wall irradiation were 169 (+/-50.6) cm3 and 14.9 (+/-3.8)%, respectively. Addition of regional irradiation resulted in increase of 183 (+/-80.2) cm3 in actual irradiated lung volume and 16.5 (+/-6.2)% in PLV. The correlation between CLD of the local fields and PLV was significant, with 1 cm of CLD corresponding to approximately 6% of PLV. CLD of the regional field was also significantly associated with PLV: a CLD of 3 cm corresponds to a PLV of approximately 13%; a CLD of 4 cm, approximately 17%; and a CLD of 5 cm, approximately 21%. RP developed in 11 patients (5.4%). There was an increased incidence of RP among patients who underwent local RT vs local and regional RT (2.4% vs 12.1%, p=0.0192). In terms of PLV, total PLV > or =23% was associated with the development of RP (p=0.0467). Previously reported clinical factors failed to show statistically significant association. CONCLUSION: Correlation between CLD and PLV for local and regional fields was significant on volumetric analysis. Although symptomatic RP requiring steroid medication was a rare complication, regional irradiation increased the incidence of RP, and such relationship can be expressed with a volumetric parameter of PLV.
Breast ; Breast Neoplasms ; Humans ; Incidence ; Lung ; Medical Records ; Radiation Pneumonitis ; Radiotherapy, Adjuvant

PURPOSE: To describe soft-tissue radiographic and high-resolution CT findings of radiation-induced lung injury of rabbit over time and to correlate them with pathologic findings. MATERIALS AND METHODS: 15 rabbits were irradiated in the right lung with one fraction of 2000 cGy. After 4, 6, 12, 20, 24 weeks, 3 rabbits in each group were sacrificed and soft-tissue radiographs and high-resolution CT of their lung tissue were obtained. Radiological findings were correlated with pathologic findings. RESULTS: On soft- tissue radiogram, radiation pneumonitis shown as consolidation with air-bronchogram occurred in 3 cases after 6 weeks, and in 1 case after 12 weeks of irradiation. In addition, pneumonic consolidation with adjacent pleural contraction was seen in 2 cases after 12 weeks of irradiation. Fibrotic changes indicated by decreased volume occurred after 20 weeks and combined bronchiectatic change and bronchial wall thickening appeared after 20 weeks(N=1), and 24 weeks(N=3). HRCT findings of radiation pneumonitis were homogeneous, increased attenuation after 4 weeks(N=3), 6 and 12 weeks (each N=I), patchy consolidation after 6 and 12 weeks(each N=2), discrete consolidation after 12, 20 and 24 weeks(each N=I) and solid consolidation after 20 and 24 weeks(each N=2). Pathologically radiation pneumonitis and pulmonary congestion were seen after 4 and 6 weeks. After 6 weeks, collagen and reticulin fibers were detected along alveolar wall. Mixed radiation pneumonitis and fibrosis were detected after 12 weeks. 20 weeks after irradiation, fibrosis was well defined in interstitium and in 24 weeks, decreased number of alveoli and thickening of bronchial wall were defined. CONCLUSION: Radiation pneumonitis was provoked 4 weeks after irradiation on rabbit lung and progressed into radiation fibrosis 20 weeks after irradiation on soft-tissue radiographs and high-resolution CT. High-resolution CT is more precise in detecting early radiation pneumonitis and detailed pathologic findings.
Collagen ; Estrogens, Conjugated (USP) ; Fibrosis ; Lung Injury ; Lung* ; Rabbits ; Radiation Pneumonitis ; Reticulin

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: 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