• Radiation Oncology Journal
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• v.5 no.2
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• pp.119-129
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• 1987

With the introduction of X-rays of higher energy that have higher penetrability, it has become possible to treat the deep-seated tumor with increased local control rate. But at the same time it has incrased the damage to the deep seated organs, especially to the lung which is known to be the less radiotolerable tissue in the body. This study analyses the 66 patients who were exposed to the irradiation of the lung, and examines the development of radiation pneumonitis and its related factors. The results of the study are summarized as follows: 1, The 66 patients were consisted of 40 cases of lung cancer, 15 cases of breast cancer and 11 cases of mediastinal tumors. There were 37 males and 29 females with the male to female ratio 1.3: 1. A male to female ratio in the lung cancer was 3: 1. 2. Among 66 patients, 26 patients $(39\%)$ developed the radiographical changes of acute radiation pneumonitis and 13 out of 26 patients $(50\%)$ showed the clinical features of acute radiation pneumonitis. 3. The onest of acute radiation pneumonitis ranged from 10 days to 6 months after the completion of radiotherapy. 4. There was a statistically significant close relationship between the development of radiation pneumonitis and the radiation dose. 5. As the irradiated lung volume increased, the development of radiation pneumonitis increased. But the statistical significance was not strong. 6. The increased incidence of radiation pneumonitis was observed when the chemotherapy was given before or concomittantly with radiotherapy. 7 There was no significant correlation between the development of radiation pneumonitis and the age, smoking and the presence of underlying lung disease.

• Radiation Oncology Journal
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• v.29 no.3
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• pp.181-190
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• 2011

Purpose: Thoracic radiotherapy is a major treatment modality of stage III non-small cell lung cancer. The normal lung tissue is sensitive to radiation and radiation pneumonitis is the most important dose-limiting complication of thoracic radiation therapy. This study was performed to identify the clinical and dosimetric parameters related to the risk of radiation pneumonitis after definitive radiotherapy in stage III non-small cell cancer patients. Materials and Methods: The medical records were reviewed for 49 patients who completed definitive radiation therapy for locally advanced non-small cell lung cancer from August 2000 to February 2010. Radiation therapy was delivered with the daily dose of 1.8 Gy to 2.0 Gy and the total radiation dose ranged from 50.0 Gy to 70.2 Gy (median, 61.2 Gy). Elective nodal irradiation was delivered at a dose of 45.0 Gy to 50.0 Gy. Seven patients (14.3%) were treated with radiation therapy alone and forty two patients (85.7%) were treated with chemotherapy either sequentially or concurrently. Results: Twenty-five cases (51.0%) out of 49 cases experienced radiation pneumonitis. According to the radiation pneumonitis grade, 10 (20.4%) were grade 1, 9 (18.4%) were grade 2, 4 (8.2%) were grade 3, and 2 (4.1%) were grade 4. In the univariate analyses, no clinical factors including age, sex, performance status, smoking history, underlying lung disease, tumor location, total radiation dose and chemotherapy were associated with grade ${\geq}2$ radiation pneumonitis. In the subgroup analysis of the chemotherapy group, concurrent rather than sequential chemotherapy was significantly related to grade ${\geq}2$ radiation pneumonitis comparing sequential chemotherapy. In the univariate analysis with dosimetric factors, mean lung dose (MLD), $V_{20}$, $V_{30}$, $V_{40}$, MLDipsi, $V_{20}$ipsi, $V_{30}$ipsi, and $V_{40}$ipsi were associated with grade ${\geq}2$ radiation pneumonitis. In addition, multivariate analysis showed that MLD and V30 were independent predicting factors for grade ${\geq}2$ radiation pneumonitis. Conclusion: Concurrent chemotherapy, MLD and $V_{30}$ were statistically significant predictors of grade ${\geq}2$ radiation pneumonitis in patients with stage III non-small cell lung cancer undergoing definitive radiotherapy. The cutoff values for MLD and $V_{30}$ were 16 Gy and 18%, respectively.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4763-4767
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• 2012

Radiation pneumonitis and pulmonary fibrosis are the main complications with radiotherapy for thoracic neoplasms, directly limiting the efficient dose in clinical application and currently there are few medicines that effectively function as radioprotectants. However, a TLR5 agonist, CBLB502, was confirmed to have protective efficacy against hematopoietic and gastrointestinal radiation syndromes in mice and primates. This study points to a new direction for protection against thoracic radiation-induced pulmonary syndromes and skin injury by CBLB502. We utilized the TUNEL assay, pathological analysis and immunohistochemistry to obtain evidence thatCBLB502 could alleviate the occurrence of radiation pneumonitis and pulmonary fibrosis as well as radiation-induced skin injury. It may thus play a promising role in facilitating clinical radiotherapy of thoracic neoplasms.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2613-2617
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• 2015

Radiation induced lung injury has long been considered a treatment limiting factor for patients requiring thoracic radiation. This radiation induced lung injury happens early as well as late. Radiation induced lung injury can occur in two phases viz. early (< 6 months) when it is called radiation pneumonitis and late (>6 months) when it is called radiation induced lung fibrosis. There are multiple factors that can be patient, disease or treatment related that predict the incidence and severity of radiation pneumonitis. Radiation induced damage to the type I pneumocytes is the triggering factor to initiate such reactions. Over the years, radiation therapy has witnessed a paradigm shift in radiation planning and delivery and successfully reduced the incidence of lung injury. Radiation pneumonitis is usually a diagnosis of exclusion. Steroids, ACE inhibitors and pentoxyphylline constitute the cornerstone of therapy. Radiation induced lung fibrosis is another challenging aspect. The pathophysiology of radiation fibrosis includes continuing inflammation and microvascular changes due to pro-angiogenic and profibrogenic stimuli resembling those in adult bronchiectasis. General supportive management, mobilization of airway secretions, anti-inflammatory therapy and management of acute exacerbations remains the treatment option. Radiation induced lung injury is an inevitable accompaniment of thoracic radiation.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.321-330
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• 1993

Purpose: A retrospective analysis was performed to evaluate the incidence of radiation induced lung damage after the radiation therapy for the patients with carcinoma of the lung. Method and Materials: Sixty-six patients with lung cancer (squamous cell carcinoma 27, adenocarcinoma 14, large cell carcinoma 2, small cell carcinoma 13, unknown 10) were treated with definitive, postoperative or palliative radiation therapy with or without chemotherapy between July 1987 and December 1991. There were 50 males and 16 females with median age of 63 years (range: 33~80 years). Total lung doses ranged from 500 to 6,660 cGy (median 3960 cGy) given in 2 to 38 fractions (median 20) over a range or 2 to 150 days (median in days) using 6 MV or 15 MV linear accelerator. To represent different fractionation schedules of equivalent biological effect, the estimated single dose (ED) model, $ED=D{\dot}N^{-0.377}{\dot}T^{-0.058}$ was used in which D was the lung dose in cGy, N was the number of fractions, and T was the overall treatment time in days. The range of ED was 370 to 1357. The endpoint was a visible increase in lung density within the irradiated volume on chest X-ray as observed independently by three diagnostic radiologists. Patients were grouped according to ED, treatment duration, treatment modality and age, and the percent incidence of pulmonary damage for each group was determined. Result: In 40 of 66 patients, radiation induced change was seen on chest radiographs between 11 days and 314 days after initiation of radiation therapy. The incidence of radiation pneumonitis was increased according to increased ED, which was statistically significant (p=0.001). Roentgenographic changes consistent with radiation pneumonitis were seen in $100\%$ of patients receiving radiotherapy after lobectomy or pneumonectomy, which was not statistically significant. In 32 patients who also received chemotherapy, there was no difference in the incidence of radiation induced change between the group with radiation alone and the group with radiation and chemotherapy, among the sequence of chemotherapy No correlation was seen between incidence of radiation pneumonitis and age or sex. Conclusions: The occurrence of radiation pneumonitis varies. The incidence of radiation pneumonitis depends on radiation total dose, nature of fractionation, duration of therapy, and modifying factors such as lobectomy or pneumonectomy.

• Radiation Oncology Journal
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• v.18 no.4
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• pp.314-320
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• 2000

Purpose :To investigate whether changes in plasma concentrations of transforming growth factor-$\beta$1(TGF-$\beta$1), tumor necrosis factor-alpha (TNF-$\alpha$) and interleukin-6 (IL-6) could be used to identify the development of radiation-induced pneumonitis in the lung cancer patients. Methods and Materials :Seventeen patients with lung cancer (11 NSCLC, 6 SCLC) were enrolled in a prospective study designed to evaluate clinical and molecular biologic correlation of radiation-induced pneumonitis. The study began in May 1998 and completed in July 1999. All patients were treated with radiotherapy with curative intent : 1.8 Gy per day, 5 fractions per week. Serial measurements of plasma TGF-$\beta$1, TNF-$\alpha$ and IL-6 were obtained in all patients before, weekly during radiotherapy and at each follow-up visits after completion of treatment. These measurements were quantified using enzyme linked immunosorbent assay (ELISA). All patients were evaluated for signs and symptoms of pneumonitis at each follow-up visit after completion of radiotherapy. High resolution CT (HRCT) scans were obtained when signs and symptoms of pneumonitis were developed after completion of radiotherapy. Results : Thirteen patients eventually developed signs and symptoms of clinical pneumonitis 씬file four patients did not. TGF-$\beta$ 1 levels were elevated in all 13 patients with pneumonitis, which showed characteristic pattern of elevation (38.45 ng/ml at pretreatment, 13.66 ng/ml during radiotherapy, then 60.63 ng/ml at 2-4 weeks after completion of radiotherapy). The levels of TNF- $\alpha$ and IL-6 were also elevated In the group of patients who developed pneumonitis but the pattern was not characteristic. Conclusions : Changes in plasma TGF$\beta$-1 levels before, during and after radiotherapy appears to be a useful means by which to identify patients at risk for the development of symptomatic pneumonitis. Other cytokines like TNF- $\alpha$ and IL-6 shows no meaningful changes in association with radiation pneumonitis.

• Journal of Korean Traditional Oncology
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• v.18 no.1
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• pp.1-7
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• 2013

Objective : This study is purposed to report 2 cases of cancer patient whose symptoms related to radiation pneumonitis had been controlled with Saengmaek-san treatment. Methods : A 56-year-old female rectal cancer patient was prescribed with Saengmaek-san due to the symptoms which had developed 4 weeks after the completion of her radiotherapy session in both lungs. Her chief complaints were shortness of breath, dry cough and fatigue. Another case, 53-year-old male patient with hepatocellular carcinoma, had also developed symptoms of fatigue, weight loss and dry cough after his radiotherapy session in left upper lung zone. Radiological changes of both patients' chest X-ray suggested radiation pneumonitis. Results : Symptoms of the female patient were improved, especially shortness of breath, after Saengmaek-san treatment, without any aggravation in her chest X-ray result. However, infiltrative opacity in the left upper lung zone of the male patient was aggravated despite the improvement of his clinical symptoms. His remaining symptoms and radiological change were effectively controlled after steroid therapy. Conclusion : Seangmaek-san may be considered as a potential treatment for symptoms related to radiation pneumonitis with proper monitoring.

• Journal of Radiation Protection and Research
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• v.42 no.4
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• pp.177-188
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• 2017

Background: Radiation-induced pneumonitis and pulmonary fibrosis are common dose-limiting complications in patients receiving radiotherapy for lung, breast, and lymphoid cancers. In this study, we investigated the characteristics of effective immune cells related to pneumonitis and fibrosis after irradiation. Materials and Methods: After anesthesia, the whole thorax of C57BL/6 mice was irradiated at 14 Gy. The lung tissue and bronchoalveolar lavage fluid were collected at defined time points post-irradiation for the determination of histological and immunohistochemical analysis and inflammatory cell population infiltrated into the lung. Results and Discussion: Whole thoracic irradiation increased the deposition of extracellular matrix (ECM), lung weight, and pleural effusions, which started to die from 4 months later. At 4 months after irradiation, the numbers of macrophages and lymphocytes as well as neutrophils were increased dramatically in the lung. Interestingly, the macrophages that were recruited into the lung after irradiation had an enlarged foamy morphology. In addition, the expressions of chemokines (CCL-2, CCL-3, CXCL-10) for the attraction of macrophages and T cells were higher in the lung of irradiated mice. The high expressions of these chemokines were sustained up to 6 months following irradiation. In thoracic irradiated mice, infiltrated macrophages into the lung had the high levels of Mac-3 antigens on their surface and upregulated the hallmarks of alternatively activated macrophages such as arginase-1 and CD206. Furthermore, the levels of IL-4 and IL-13 were higher in a BAL fluid of irradiated mice. Conclusion: All results show that thoracic irradiation induces to infiltrate various inflammation-related immune cells, especially alternatively activated macrophages, through enhancing the expression of chemokines, suggesting that alternatively activated macrophages are most likely important for leading to pulmonary fibrosis.

• Radiation Oncology Journal
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• v.25 no.4
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• pp.261-267
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• 2007

Purpose: To evaluate the association between radiation pneumonitis and dose-volume histogram parameters and to provide practical guidelines to prevent radiation pneumonitis following radiotherapy administered for breast cancer including internal mammary lymph nodes. Materials and Methods: Twenty patients with early breast cancer who underwent a partial mastectomy were involved in this study. The entire breast, supraclavicular lymph nodes, and internal mammary lymph nodes were irradiated with a dose of 50.4 Gy in 28 fractions. Radiation pneumonitis was assessed by both radiological pulmonary change (RPC) and by evaluation of symptomatic radiation pneumonitis. Dose-volume histogram parameters were compared between patients with grade <2 RPC and those with grade ${\geq}$2 RPC. The parameters were the mean lung dose, V10 (percent lung volume receiving equal to and more than 10 Gy), V20, V30, V40, and normal tissue complication probability (NTCP). Results: Of the 20 patients, 9 (45%) developed grade 2 RPC and 11 (55%) did not develop RPC (grade 0). Only one patient developed grade 1 symptomatic radiation pneumonitis. Univariate analysis showed that among the dose-volume histogram parameters, NTCP was significantly different between the two RPC grade groups (p<0.05). Fisher's exact test indicated that an NTCP value of 45% was appropriate as an RPC threshold level. Conclusion: This study shows that NTCP can be used as a predictor of RPC after radiotherapy of the internal mammary lymph nodes in breast cancer. Clinically, it indicates that an RPC is likely to develop when the NTCP is greater than 45%.

• Tuberculosis and Respiratory Diseases
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• v.43 no.1
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• pp.75-87
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• 1996

Background: Lung cancer is the second most frequent malignancy in man in Korea. Surgery is the best treatment modality for non-small cell lung cancer, but most patients were presented in far advanced stage. So radiation therapy(RT) with or without chemotherapy is the next choice and radiation-induced pneumonitis and pulmonary fibrosis is the major limiting factor for the curative RT. Radiation pneumonitis is manifested with fever, cough and dyspnea, 2~3 months after the termination of radiotherpy. Chest X ray shows infiltration, typically limited to the radiation field, but occasionally bilateral infiltration was reported. Also Gibson et al reported that BAL lymphocytosis was found in both lungs, even though the radiation was confined to one lung. The aim of this study is to investigate the change of adhesion molecules expression on BAL cells and serum soluble ICAM-1(sICAM-1) level after the RT and its relationship to the development of radiation pneumonitis. The second aim is to confirm the bilaterality of change of BAL cell pattern and adhesion molecule expression. Subjects: BAL and the measurement of sICAM level in serum and BALF were done on 29 patients with lung cancer who received RT with curative intention. The BAL was done before the RT in 16 patients and 1~2 month after RT in 18 patients. 5 patients performed BAL before and after RT. Result: Clinically significant radiation pneumonitis developed in 7 patients. After RT, total cell count in BAL was significantly increased from $(20.2{\pm}10.2){\times}10^6\;cells/ml$ to $(35.3{\pm}21.6){\times}10^6\;cells/ml$ (p=0.0344) and %lymphocyte was also increased from $5.3{\pm}4.2%$ to $39.6{\pm}23.4%$ (p=0.0001) in all patient group. There was no difference between ipsilateral and contraleteral side to RT, and between the patients with and without radiation-pneumonitis. In whole patient group, the level of sICAM-1 showed no significant change after RT(in serum: $378{\pm}148$, $411{\pm}150\;ng/ml$, BALF: $20.2{\pm}12.2$, $45.1{\pm}34.8\;ng/ml$, respectively), but there was a significant difference between the patients with pneumonitis and without pneumonitis (serum: $505{\pm}164$ vs $345{\pm}102\;ng/ml$, p=0.0253, BALF: $67.9{\pm}36.3$ vs $25.2{\pm}17.9\;ng/ml$, p=0.0112). The expression of ICAM-1 on alveolar macrophages (AM) tends to increase after RT (RMFI: from $1.28{\pm}0.479$ to $1.63{\pm}0.539$, p=0.0605), but it was significantly high in patients with pneumonitis ($2.10{\pm}0.390$) compared to the patients without pneumonitis ($1.28{\pm}0.31$, p=0.0002). ICAM-1 expression on lymphocytes and CD 18 (${\beta}2$-integrin) expression tended to be high in the patients with pneumonitis but the difference was statiastically not significant. Conclusion: Subclinical alveolitis on the basis of BAL finding developed bilaterally in all patients after RT. But clinically significant pneumonitis occurred in much smaller fraction and the ICAM-1 expression on AM and the sICAM-1 level in serum were good indicator of it.