• Tuberculosis and Respiratory Diseases
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• 제56권1호
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• pp.40-50
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• 2004

연구배경 : 폐암은 우리 나라에서 점차 증가하고 있으며 발생빈도에 있어서는 위암에 이어서 두 번째이고 암에 의한 사망 원인의 첫 번째 원인이 되고 있다. 수술요법이 가장 좋은 치료이나 대부분의 환자들이 진단 당시 수술을 받지 못할 정도로 진행이 되어서 방사선 치료나 항암 치료를 동반한 방사선치료를 받게 된다. 방사선 치료 중 방사선 폐렴의 발생이 제일 중요한 부작용이다. 폐암으로 진단을 받고 흉부 방사선 치료를 시행 받은 환자에서 방사선 폐렴의 발생률 및 치료. 발생 및 중증도를 예측 할 수 있는 인자, 생존에 미치는 영향에 대해서 후향적 조사를 하였다. 방 법 : 충남대학교병원 호흡기 내과에서 폐암으로 진단을 받고 2000년 12월부터 2002년 12월까지 치료 방사선과에서 흉부 방사선 치료를 시행 받은 환자 90명을 대상으로 조사하였다. 결 과 : 90명의 환자 중 44명(48.9%)이 방사선 폐렴으로 진단을 받았으며 33명(36.6%)은 경증, 11명(12.3%)은 중증의 방사선 폐렴이 발생하였다. 중증의 방사선 폐렴 환자는 모두 부신 피질호르몬제를 사용하였으며 호흡 부전으로 내원한 한 환자를 제외한 나머지 10명의 환자들의 처음 평균 투여량은 prednisolone 34 mg(30~40)이었고, 평균 투여일수는 68일(8~97)이었다. 중증 방사선 폐렴이 발생된 경우에 있어서 경증에 비해 중앙 생존일이 의미 있게 낮았다.(p=0.046) 방사선 폐렴 발생과 관련된 인자는 방사선 투여량이 60 Gy 이상인 경우에 통계적으로 의미가 있었다.(p=0.001) 그 외에 활동도, 폐활량, 나이, 흡연, 조직형, 항암 치료와의 병용여부, 1일 방사선 조사 횟수, 방사선 투여 방식은 방사선 폐렴 발생과 통계적으로 의미가 없었다. 또한 중증의 방사선 폐렴 발생을 예측 할 수 있는 인자로 이용 될 수 있는 혈중 요산과 알부민의 농도와 방사선 폐렴의 중증도와는 통계적으로 의미가 없었다. 결 론 : 본 연구에서 60 Gy이상의 총 방사선 조사량이 방사선 폐렴의 발생과 관련이 있었고 조사량과 중증도와도 연관이 있음을 알 수 있었다. 또한 중증의 방사선 폐렴 발생 시 예후가 경증의 환자에 비해 상대적으로 좋지 못했다.

• Radiation Oncology Journal
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• 제36권1호
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• pp.63-70
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• 2018

Purpose: The objective of this study was to compare dosimetric characteristics of three-dimensional conformal radiotherapy (3D-CRT) and two types of intensity-modulated radiotherapy (IMRT) which are step-and-shoot intensity modulated radiotherapy (s-IMRT) and modulated arc therapy (mARC) for thoracic esophageal cancer and analyze whether IMRT could reduce organ-at-risk (OAR) dose. Materials and Methods: We performed 3D-CRT, s-IMRT, and mARC planning for ten patients with thoracic esophageal cancer. The dose-volume histogram for each plan was extracted and the mean dose and clinically significant parameters were analyzed. Results: Analysis of target coverage showed that the conformity index (CI) and conformation number (CN) in mARC were superior to the other two plans (CI, p = 0.050; CN, p = 0.042). For the comparison of OAR, lung V5 was lowest in s-IMRT, followed by 3D-CRT, and mARC (p = 0.033). s-IMRT and mARC had lower values than 3D-CRT for heart $V_{30}$ (p = 0.039), $V_{40}$ (p = 0.040), and $V_{50}$ (p = 0.032). Conclusion: Effective conservation of the lung and heart in thoracic esophageal cancer could be expected when using s-IMRT. The mARC was lower in lung $V_{10}$, $V_{20}$, and $V_{30}$ than in 3D-CRT, but could not be proven superior in lung $V_5$. In conclusion, low-dose exposure to the lung and heart were expected to be lower in s-IMRT, reducing complications such as radiation pneumonitis or heart-related toxicities.

• Nutrition Research and Practice
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• 제12권1호
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• pp.41-46
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• 2018

BACKGROUND/OBJECTIVES: Exposure of the normal lung tissue around the cancerous tumor during radiotherapy causes serious side effects such as pneumonitis and pulmonary fibrosis. Radioprotectors used during cancer radiotherapy could protect the patient from side effects induced by radiation injury of the normal tissue. Delphinidin has strong antioxidant properties, and it works as the driving force of a radioprotective effect by scavenging radiation-induced reactive oxygen species (ROS). However, no studies have been conducted on the radioprotective effect of delphinidin against high linear energy transfer radiation. Therefore, this study was undertaken to evaluate the radioprotective effects of delphinidin on human lung cells against a proton beam. MATERIALS/METHODS: Normal human lung cells (HEL 299 cells) were used for in vitro experiments. The 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay assessed the cytotoxicity of delphinidin and cell viability. The expression of radiation induced cellular ROS was measured by the 2'-7'-dicholordihydrofluorescein diacetate assay. Superoxide dismutase activity assay and catalase activity assay were used for evaluating the activity of corresponding enzymes. In addition, radioprotective effects on DNA damage-induced cellular apoptosis were evaluated by Western blot assay. RESULTS: Experimental analysis, including cell survival assay, MTT assay, and Western blot assay, revealed the radioprotective effects of delphinidin. These include restoring the activities of antioxidant enzymes of damaged cells, increase in the levels of pro-survival protein, and decrease of pro-apoptosis proteins. The results from different experiments were compatible with each to provide a substantial conclusion. CONCLUSION: Low concentration ($2.5{\mu}M/mL$) of delphinidin administration prior to radiation exposure was radioprotective against a low dose of proton beam exposure. Hence, delphinidin is a promising shielding agent against radiation, protecting the normal tissues around a cancerous tumor, which are unintentionally exposed to low doses of radiation during proton therapy.

• Radiation Oncology Journal
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• 제35권1호
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• pp.55-64
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• 2017

Purpose: The outcomes and toxicities of locoregionally recurrent non-small-cell lung cancer (NSCLC) patients treated with curative radiotherapy were evaluated in the modern era. Materials and Methods: Fifty-seven patients receiving radical radiotherapy for locoregionally recurrent NSCLC without distant metastasis after surgery from 2004 to 2014 were reviewed. Forty-two patients were treated with concurrent chemoradiotherapy (CCRT), and 15 patients with radiotherapy alone. The median radiation dose was 66 Gy (range, 45 to 70 Gy). Lung function change after radiotherapy was evaluated by comparing pulmonary function tests before and at 1, 6, and 12 months after radiotherapy. Results: Median follow-up was 53.6 months (range, 12.0 to 107.5 months) among the survivors. The median overall survival (OS) and progression-free survival (PFS) were 54.8 months (range, 3.0 to 116.9 months) and 12.2 months (range, 0.8 to 100.2 months), respectively. Multivariate analyses revealed that single locoregional recurrence focus and use of concurrent chemotherapy were significant prognostic factors for OS (p = 0.048 and p = 0.001, respectively) and PFS (p = 0.002 and p = 0.026, respectively). There was no significant change in predicted forced expiratory volume in one second after radiotherapy. Although diffusing lung capacity for carbon monoxide decreased significantly at 1 month after radiotherapy (p < 0.001), it recovered to pretreatment levels within 12 months. Acute grade 3 radiation pneumonitis and esophagitis were observed in 3 and 2 patients, respectively. There was no chronic complication observed in all patients. Conclusion: Salvage radiotherapy showed good survival outcomes without severe complications in postoperative locoregionally recurrent NSCLC patients. A single locoregional recurrent focus and the use of CCRT chemotherapy were associated with improved survival. CCRT should be considered as a salvage treatment in patients with good prognostic factors.

• Radiation Oncology Journal
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• 제19권2호
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• pp.190-198
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• 2001

목적 : Captopril을 방사선조사와 병용하여 조기 폐손상을 감소시킬 수 있는 방사선보호제로서의 역할을 확인하고 $TNF\alpha$와 $TGF\beta1$이 방사선 보호기전에 관여하는지를 알아보고자 하였다. 대상 및 방법 : 실험동물(Sprague-Dawley 흰쥐)은 정상대조군, 실험군(방사선 단독군, Captopril과 방사선 병용군)으로 분류하였다. 실험군은 12.5 Gy의 방사선을 좌측 흉곽에 단일조사 하였다. Captopril과 방사선 병용군은 Captopril (50 mg/kg/d)을 방사선조사 1주전부터 실험종료시인 8주까지 식수에 섞어 경구 투여하였다. 실험결과는 방사선조사 2주와 8주 후에 병리조직 소견을 분석하였고 면역조직화학염색으로 $TNF\alpha$와 $TGF\beta1$의 발현을 관찰하였다. 결과 : 방사선조사 2주 후에, Captopril과 방사선 병용군은 방사선 단독군에 비해 폐포강내 출혈, 폐포 상피세포 변화, 기관지 상피세포 변화, 혈관변화, 혈관주위 부종과 같은 조직소견의 정도가 현저히 감소되었다. 방사선조사 8주 후에는 기관지 상피세포 변화와 혈관주위 부종이 방사선 단독군에 비해 적었다. Captopril과 방사선 병용군에서 방사선조사 2주후 $TNF\alpha$의 발현은 방사선 단독군과 비교시 폐포 상피세포(p<0.01) 및 폐포강의 대식세포(p<0.01)에서 현저히 감소되었고, 기관지 주변의 림프조직(p=0.06)에서는 감소하는 경향이었다. $TGF\beta1$은 폐포상피세포(p<0.02) 및 폐포강의 대식세포(p<0.02)에서 양성세포가 현저히 감소되었다. 방사선 단독군과 비해 8주후 Captopril과 방사선 병용군의 $TNF\alpha$는 차이가 없었고, $TGF\beta1$의 발현은 폐포강의 대식세포(p=0.09)에서만 감소하는 경향이었다. 결론 : 흰쥐의 폐에 Captopril을 방사선과 병용투여하여 병리조직 소견을 관찰한 결과 방사선에 의한 조기 폐손상이 감소됨을 확인할 수 있었다. 또한 방사선조사 2주 후는 $TNF\alpha$와 $TGF\beta1$의 발현이 감소하고, 8주 후에는 $TGF\beta1$ 발현의 감소가 관찰되어, Captopril이 조기 폐손상을 억제하는 방사선보호제로서 기전의 일부에 $TNF\alpha$와 $TGF\beta1$이 관여함을 확인할 수 있었다.

• Radiation Oncology Journal
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• 제29권1호
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• pp.44-52
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• 2011

목적: 본 연구는 근치적 절제술 후 병기 3의 비소세포성 폐암에서 방사선 치료의 결과와 이에 영향을 주는 예후 인자를 분석해 보고자 하였다. 대상 및 방법: 2000년부터 2007년까지 88명의 환자가 비소세포성 폐암으로 근치적 절제술 후 병기 3기로 진단받았고, 수술 후 방사선 치료를 시행 받았다 이중 80명의 환자가 병기 3A였으며, 8명의 환자가 병기 3B였다. 83명의 환자는 림프절 병기 N2였으며 이들 중 56명은 단일 부위(single-station)의 종격동 림프절 전이였다. 76명은 2차원, 12명은 3차원 입체조형치료로 수술 후 망사선 치료를 받았다. 총 선량은 30.6에서 63 Gy 였으며 중앙값은 54 Gy였다. 36명의 환자가 항암치료를 시행받았다. 결 과: 생존기간은 26~77개월이었다(중앙값, 54개월). 5년 생존율 및 무병생존율은 각각 45%, 38%였다. 전이된 림프절개수가 생존율에 영향을 미치는 인자로 분석되었다(hazard ratio, 1.037; p=0.040). 5년 국소제어율 및 원격 전이제어율은 각각 88%, 48%였다. 종격동 림프절 부위의 전이가 단일 부위(single-station)인 경우가 무병생존율(p=0.0014)과 원격전이제어율(p=0.0044)을 의미 있게 증가시켰다. 총 51명의 재발이 발생하였으며 국소구역 재발은 10명, 원격전이는 41명이었다. 10명의 국소구역 재발 중에 6명은 방사선 치료 범위 내에서 재발하였다. Radiation Therapy Oncology Group(RTOG) 2도의 방사선 폐렴은 3명의 환자에서 보였으며 증상은 진해성 약제만으로도 조절이 잘 되었다. CTCAE 2도의 방사선 식도염은 11명의 환자에서 관찰되었다. 수술 후 방사선 치료로 인한 3도 이상의 심각한 부작용은 관찰되지 않았다. 결 론: 본 연구에서 국소 진행 비소세포성 폐암에서 근치적 수술 후 방사선 치료는 안전하고 임상적으로 적용 가능한 치료법이며, 국소제어를 증가시킬 수 있는 것으로 분석되었다. 예후인자로는 전이된 림프절 개수와 종격동 림프절 부위가 생존율에 영향을 미치는 것으로 분석되었다. 또한 국소 진행 비소세포성 폐암의 대부분의 재발 형태인 원격 전이를 감소시키기 위한 추가적인 노력이 필요할 것으로 생각된다.

• Radiation Oncology Journal
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• 제33권2호
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• pp.89-97
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• 2015

Purpose: To evaluate the treatment results in early stage non-small cell lung cancer patients who have undergone fiducial-less CyberKnife radiosurgery (CKRS). Materials and Methods: From June 2011 to November 2013, 58 patients underwent CKRS at Asan Medical Center for stage I lung cancer. After excluding 14 patients, we retrospectively reviewed the records of the remaining 44 patients. All analyses were performed using SPSS ver. 21. Results: The median age at diagnosis was 75 years. Most patients had inoperable primary lung cancer with a poor pulmonary function test with comorbidity or old age. The clinical stage was IA in 30 patients (68.2%), IB in 14 (31.8%). The mean tumor size was 2.6 cm (range, 1.2 to 4.8 cm), and the tumor was smaller than 2 cm in 12 patients (27.3%). The radiation dose given was 48-60 Gy in 3-4 fractions. In a median follow-up of 23.1 months, local recurrence occurred in three patients (2-year local recurrence-free survival rate, 90.4%) and distant metastasis occurred in 13 patients. All patients tolerated the radiosurgery well, only two patients developing grade 3 dyspnea. The most common complications were radiation-induced fibrosis and pneumonitis. Eight patients died due to cancer progression. Conclusion: The results showed that fiducial-less CKRS shows comparable local tumor control and survival rates to those of LINAC-based SABR or CKRS with a fiducial marker. Thus, fiducial-less CKRS using Xsight lung tracking system can be effectively and safely performed for patients with medically inoperable stage I non-small cell lung cancer without any risk of procedure-related complication.

• BMB Reports
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• 제34권6호
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• pp.544-550
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• 2001

In pre-transplant total-body irradiation (TBI), the lung is a critical dose-limiting organ. Also, the possible role of oxidative stress was suggested in the development of TBI-induced lung damage. This study explores the association between TBI-induced oxidative stress and the induction of lung pathogenesis by investigating TBI-induced oxidative stress in the lungs of male C57BL/6 mice after a single dose of 10 Gy TBI. We showed significant increases of reactive oxygen species (ROS) formation and lipid peroxidation, and also a depletion and oxidation of glutathione after TBI. There is evidence that pretreatment with 1,10-phenanthroline (o-phen) significantly reduces oxidative stress in the lung. This indicates that the TBI-induced ROS generation involves a metal-catalyzed Fenton-type reaction. A pretreatment of buthionine sulfoximine (BSO) augmented the glutathione depletion and oxidation, but had no effect on the ROS formation and lipid peroxidation up to 6 h after TBI. Histopathological features that are consistent with pneumonitis were observed in the BSO pretreated-mice 1 week after irradiation. The results suggest that TBI-induced oxidative stress in the lung involves a generation of ROS through a Fenton-type reaction. Also, glutathione plays an important inhibitory role in the radiation-induced lung pathogenesis by participating in the self-amplifying cascade subsequent to the ROS generation by irradiation.

• Radiation Oncology Journal
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• 제37권2호
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• pp.101-109
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• 2019

Purpose: The purpose of this study is to evaluate the safety and efficacy of the multimodality treatment with neoadjuvant intensity-modulated radiotherapy (IMRT) for resectable clinical T1-3N0-1M0 malignant pleural mesothelioma (MPM). Materials and Methods: A total of eleven patients who received neoadjuvant chemotherapy and radiotherapy between March 2016 and June 2018 were reviewed. Patients received 25 Gy in 5 fractions to entire ipsilateral hemithorax with helical tomotherapy. Results: All of patients were men with a median age of 56 years. Epithelioid subtype was found in 10 patients. All patients received neoadjuvant chemotherapy with pemetrexed-cisplatin regimen. Ten patients (90.9%) completed 25 Gy/5 fractions and one (9.0%) completed 20 Gy/4 fractions of radiotherapy. IMRT was well tolerated with only one acute grade 3 radiation pneumonitis. Surgery was performed 1 week (median, 8 days; range, 1 to 15 days) after completing IMRT. Extrapleural pneumonectomy was performed in 4 patients (36.3%), extended pleurectomy/decortication in 2 (18.2%) and pleurectomy/decortications in 5 (63.6%). There was no grade 3+ surgical complication except two deaths after EPP in 1 month. Based on operative findings and pathologic staging, adjuvant chemotherapy was delivered in 7 patients (63.6%), and 2 (18.2%) were decided to add adjuvant radiotherapy. After a median follow-up of 14.6 months (range, 2.8 to 30 months), there were 3 local recurrence (33.3%) and 1 distant metastasis (11.1%). Conclusion: Neoadjuvant entire pleural IMRT can be delivered with a favorable radiation complication. An optimal strategy has to be made in resectable MPM patients who would benefit from neoadjuvant radiation and surgery. Further studies are needed to look at long-term outcomes.

• Radiation Oncology Journal
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• 제32권3호
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• pp.147-155
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• 2014

Purpose: This study was conducted to observe the outcomes of postoperative radiotherapy (PORT) with or without concurrent chemotherapy in resected non-small cell lung cancer (NSCLC) in single institution. Materials and Methods: From 2002 to 2013, 78 patients diagnosed with NSCLC after curative resection were treated with radiotherapy alone (RT, n = 48) or concurrent chemoradiation (CCRT, n = 30). The indications of adjuvant radiation therapy were N2 node positive (n = 31), close or involved resection margin (n = 28), or gross residual disease due to incomplete resection (n = 19). The median radiation dose was 57.6 Gy (range, 29.9 to 66 Gy). Results: Median survival time was 33.7 months (range, 4.4 to 140.3 months). The 5-year overall survival (OS) rate was 49.5% (RT 46% vs. CCRT 55.2%; p = 0.731). The 3-year disease-free survival rate was 45.5% (RT 39.4% vs. CCRT 55.3%; p = 0.130). The 3-year local control rate was 68.1% (RT 64.4% vs. CCRT 77.7%; p = 0.165). The 3-year DMFS rate was 56.1% (RT 52.6% vs. CCRT 61.7%; p = 0.314). In multivariate analysis, age ${\geq}66$ years and pathologic stage III were significant poor prognostic factors for OS. Treatment failure occurred in 40 patients. Four patients had radiologically confirmed grade 3 radiation pneumonitis. Conclusion: In NSCLC, adjuvant RT or CCRT after curative surgery is a safe and feasible modality of treatment. OS gain was seen in patients less than 66 years. Postoperative CCRT showed a propensity of achieving better local control and improved disease-free survival compared to RT alone according to our data.