악성 폐종양의 사이버나이프 방사선수술 후 방사선 폐손상의 CT 소견

서재영,조영준,이선영,김금원,황철목,김대호,김호준 대한영상의학회 2011 대한영상의학회지 Vol.65 No.3

Purpose: To evaluate the CT appearance of radiation-induced pulmonary injury in patients who have undergone cyberknife radiosurgery for lung malignancy. Materials and Methods: Thirty-four patients with 39 malignant lung tumors who underwent cyberknife radiosurgery were enrolled for evaluation. A total of 24-60 Gy was administered in 3 fractions. We evaluated the CT appearance of radiation pneumonitis and radiation fibrosis. We also evaluated the location of radiation pneumonitis and the minimal dose which causes radiation pneumonitis. Results: Radiation pneumonitis and radiation fibrosis occurred in 95% and 90% of cases, respectively. CT patterns of radiation pneumonitis demonstrated 20 cases (54%) as ground glass opacities (GGO). GGO included only 7 cases (19%), while 6 cases (16%) had patchy consolidations and 4 cases (11%) were diffuse consolidations, respectively. Radiation pneumonitis demonstrated 30 cases (81%) as concentric patterns surrounding the tumor, while 7 cases (19%) included the eccentric patterns. The radiation pneumonitis appeared within the 13-38 Gy (mean 21 Gy). CT findings of radiation fibrosis demonstrated as the modified conventional patterns, which decreased to 17 cases (65%), while 7 cases (27%) had mass-like patterns and 2 cases (8%) had scar-like patterns, respectively. Conclusion: Radiation pneumonitis after cyberknife radiosurgery commonly develops as concentric patterns surrounding a tumor. The mass-like pattern of radiation fibrosis was sometimes difficult to distinguish from tumor recurrence. Thus, knowledge of the CT finding of radiation-induced lung injury might be helpful in distinguishing pulmonary changes from tumor recurrence. 목적: 악성 폐종양으로 사이버나이프 방사선수술을 받은 환자들에서 방사선 폐손상의 CT 소견에 대해 분석하고자 하였다. 대상과 방법: 본원에서 사이버나이프 방사선수술을 시행 받은 34명의 환자의 39개 악성 폐종양을 대상으로 하였다. 모든 환자는 총방사선량 24~60 Gy(평균 50 Gy)를 3회 분할하여 치료하였다. 방사선폐렴의 CT 소견은 방사선 조사부위 폐의 간유리 음영과 경화의 존재로 평가하였고, 방사선섬유증은 경화, 견인성 기관지확장증 그리고 폐용적 감소의 여부로 평가하였다. 또한 추적 CT에서 방사선폐렴의 위치와 발생하는 부위의 최소 방사선량을 각각 평가하였다. 결과: 방사선폐렴과 방사선섬유증은 각각 95%(37/39)와 90%(26/29)에서 발생하였다. 방사선폐렴의 CT 소견은 간유리 음영과 경화의 혼합음영이 20예(54%), 간유리음영이 7예(19%), 반점상경화 6예(16%), 미만성경화 4예(11%)였다. 방사선폐렴은 종양에 대해 동심성이 30예(81%)로 편심성 7예(19%)에 비해 많이 발생하였다. 방사선폐렴이 발생한 최소 방사선량은 13~38 Gy(평균 21 Gy)였다. 방사선섬유증은 변형된 고식적 형태의 섬유화가 17예(65%)로 가장 많이 발생하였고, 종양 유사 섬유화와 반흔 유사 섬유화가 각각 7예(27%), 2예(8%)에서 관찰되었다. 결론: 사이버나이프 방사선수술 후 방사선폐렴은 종양 주위에서 동심성으로 많이 발생하였다. 방사선섬유증 중 종양 유사 형태의 섬유화는 때때로 재발성 종양과 감별이 어려우므로 방사선 폐손상의 CT 소견에 대해 아는 것이 재발성 종양과 방사선 폐손상을 감별하는 데 도움이 될 수 있다.

흰쥐 장에서 Cis-Diammine Dichloro Platinum(Ⅱ)의 방사선손상에 대한 효과

이경자,이정식 梨花女子大學校 醫科大學 醫科學硏究所 1995 EMJ (Ewha medical journal) Vol.18 No.4

목적 : 흰쥐의 복부에 방사선조사와 cis-DDP를 투여하여 소장과 대장의 조직학적 소견을 토대로 하여 cis-DDP가 장관에서 방사선손상에 미치는 영향을 관찰 한다. 방법 : 흰쥐의 복부에 방사선조사군(6~10 Gy), cia-DDP(2.5mg/kg)투여군, 방사선조사와 cis-DDP 병행군으로 분류하였다. 방사선조사군은 전복부에 선형가속기를 이용하여 단일조사하고 cis-DDP투여군은 복강내 1회 주입하였다. 병행군은 방사선조사 전 30분에 cis-DDP투여군과 방사선조사 직후 cis-DDP투여군으로 분류하며 cis-DDP는복강내 주입하였다 실험완료 후 30일에 동물은 개복하여소장과 대장의 조직학적 소견을 광학현미경과 전자현미경으로 비교 관찰하였다. 결과 : 소장에서 cis-DDP단독군은 점막에 경도의 염증세포침윤과 국소적인 괴사가 관찰되었다. 방사선조사 단독군에서 점막의 괴사는 8 Gy, 방사선 조사와 cia-DDP병행군의 6 Gy에서 관찰되었다. 점막하조직의 섬유화는 방사선조사 단독군은 10 Gy, 방사선조사 전 cis-DDP 투여군은8 Gy, 방사선조사 후 cis-DDP 투여군은 6 Gy에서 나타나기 시작하였으며 근층의 괴사는 3군 모두 8 Gy에서 관찰되었다 소장에서 점막하조직의 섬유화를 정량적 종말점으로 하여 증강율은 방사선조사 전 cis-DDP투여군은1.67, 방사선조사 후 cis-DDP 투여군은 1.25이었다 대장에서 점막하조직의 섬유화는 방사선조사 단독군과 방사선조사 후 cis-DDP투여군의 8 Gy에서 관찰되었으며 방사선조사 전 cis-DDP투여군의 6 Gy에서 관찰되었으며 점막하조직의 섬유화를 정량적 종말점으로 하여 증강율은방사선조사 전 cis-DDP 투여군은 1.33, 방사선조사 후투여군은 1.0이었다. 결론 : 점막하조직의 섬유화를 정량적 종말점으로 하여 증강율이 소장에서 방사선조사 전 cis-DDP투여군은 1.67, 방사선조사 후 cis-DDP투여군은 1.25이었다. 대장에서 증강율은 방사선조사 전 cis-DDP투여군은 1.33, 방사선조사후 cis-DDP투여군은 1.0이었다. Cis-DDP는 소장과 대장에서 방사선의 효과를 증강시키며 특히 cis-DDP를 방사선조사 전에 투여한 경우 방사선손상이 증가되었다. 0bjective : This experimental study was performed for evaluate the effects of cis-di-amminedichloroplatinum(Ⅱ) (cis-DDP) on the radiation injury of rat bowel by histopathologic changes. Method and materials : Rats were exposed to entire abdomen by a single doses of X-ray(6-10 Gy) without or witn cis-DDP(2.5mg/kg). Rats were divided into 3 groups such as radiationalone, cis-DDP alone and combined group. In combined group, cis-DDP was given 30minutes before or immediately after irradiation. Results : Cis-DDP induced the inflammatory cell infiltrations with focal necrosis of the mucosa in the small bowel and no abnormal change in the large bowel. In radiation alone group,mucosal necrosis, subrnucosal fibrosis and muscular necrosis were prominent changes in smallbowel and submucosal fibrosis in the large bowel. The submucosal fibrosis in the small bowelwas appealed in 10 Gy of radiation alone group and 8 Gy of cis-DDP infusion after radiationand 6 Gy of cis-DDP infusion before radiation of combined group. In the large bowel, submucosal fibrosis was noted in 8 Gy of radiation alone group and 8 Gy of cis-DDP infusion after radiation and 6 Gy of cis-DDP infusion before radiation of combined group. In the smallbowel, the enhancement ratio was 1.67 in a group of cis-DDP infusion before radiation and 125 in a group of cis-DDP infusion after radiation as the end point was the submucosal fibrosis,In the large bowel, the enhancement ratio was 1.33 in a group of cis-DDP infusion before radiation and 1.0 in a cup of cis-DDP infusion after radiation as e end point was e submucosal fibrosis. Conclusion : This study suggested that cis-DDP enhance the radiation effect in the small andlarge bowel especially when cis-DDP was infused before radiation.

뇌 조직내 근접 방사선 조사시 뇌손상에 대한 21-Aminosteroid의 방사선 방어효과 : 조직 병리학적 관찰 Histopathological study

최창락,이경진,주원일 한국뇌학회 2002 한국뇌학회지 Vol.2 No.2

본 실험에서 21-aminosteroid를 방사선 방어약제로 하여 뇌 간질내 근접 방사선 조사를 시행한 후 급성기에 나타나는 뇌부종의 예방에 좋은 효과를 보여 21-aminosteroid의 임상적 적용이 방사선 방어효과에 좋은 결과를 볼 수 있을 것으로 생각된다. The 21-aminteroid or razaroids represents a new class steroid virtually without mineralocorticoid or glucocorticoid activity, a prototype of the series, has been shown to stabilize cellular membrane by inhibiting iron-catalyzed lipid peroxidation.. Radiation protection effect was studied in a rat brain injury by brachytherapy. Radiation changes were made by using stereotactic brachytherapy with high-does Ir-192 seed on the frontal lobe of rats. A minimum doses of 80 Gy were delivered to a 5-㎜ radius volume. The pathologic changes of acute and subcute radiation injury were evaluated 24 hours and 6 months after the brachytherapy. Treated rats received the 5 mg/kg of 21-aminosteroid U-74389F, intravenously every 6 hours during the experiment. Control rats were administered with normal saline only. Image analysis processing system and program to the major ischemic damage in rat CNS_e method were used to calculate the volume of acute and subacute radiation injury. . . In acute radiation injury group, the mean volumes of radiation damage in control animals and 21-aminosteroid treated animals were 59.2±7.3㎣3 and 25.5±3.4 ㎣3, respectively(P<0.01). In subacute radiation injury group, the mean volume of radiation damage in control animals and drug-treated animals were 52.8±11.5 ㎣ and 49.0±16.7 ㎣, respectively. Pathologic changes in acute radiation injury showed edematous tissue damage with acute inflammatory cells. The only difference between the control and 21-aminosteroid treated groups for acute effect model were the extent of the damage in brain. Subacute radiation injury model showed tissue necrosis and vascular thrombosis in both control and treated groups without any significant difference. Our experimental results indicate that 21-aminosteroid has radiation protective effect on acute radiation injury in the brain of the rat.

Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials

Jae Ho Kim,Kenneth A. Jenrow,Stephen L. Brown 대한방사선종양학회 2014 Radiation Oncology Journal Vol.32 No.3

To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. Advances in radiation delivery using megavoltage and intensity-modulated radiation therapy have permitted delivery of higher doses of radiation to well-defined tumor target tissues. Injury to critical normal tissues and organs, however, poses substantial risks in the curative treatment of cancers, especially when radiation is administered in combination with chemotherapy. The principal pathogenesis is initiated by depletion of tissue stem cells and progenitor cells and damage to vascular endothelial microvessels. Emerging concepts of radiation-induced normal tissue toxicity suggest that the recovery and repopulation of stromal stem cells remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure. Better understanding the mechanisms mediating interactions among excessive generation of reactive oxygen species, production of pro-inflammatory cytokines and activated macrophages, and role of bone marrow-derived progenitor and stem cells may provide novel insight on the pathogenesis of radiation-induced injury of tissues. Further understanding the molecular signaling pathways of cytokines and chemokines would reveal novel targets for protecting or mitigating radiation injury of tissues and organs.

Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials

Kim, Jae Ho,Jenrow, Kenneth A.,Brown, Stephen L. The Korean Society for Radiation Oncology 2014 Radiation Oncology Journal Vol.32 No.3

To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. Advances in radiation delivery using megavoltage and intensity-modulated radiation therapy have permitted delivery of higher doses of radiation to well-defined tumor target tissues. Injury to critical normal tissues and organs, however, poses substantial risks in the curative treatment of cancers, especially when radiation is administered in combination with chemotherapy. The principal pathogenesis is initiated by depletion of tissue stem cells and progenitor cells and damage to vascular endothelial microvessels. Emerging concepts of radiation-induced normal tissue toxicity suggest that the recovery and repopulation of stromal stem cells remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure. Better understanding the mechanisms mediating interactions among excessive generation of reactive oxygen species, production of pro-inflammatory cytokines and activated macrophages, and role of bone marrow-derived progenitor and stem cells may provide novel insight on the pathogenesis of radiation-induced injury of tissues. Further understanding the molecular signaling pathways of cytokines and chemokines would reveal novel targets for protecting or mitigating radiation injury of tissues and organs.

방사선치료에 의한 만성 직장손상

한명식,김진천,유창식,박건춘,최은경,김종춘,공경엽 대한대장항문학회 1996 Annals of Coloproctolgy Vol.12 No.3

Preliminary Study of Protective Effects of Flavonoids against Radiation-induced Lung Injury in Mice

Wang, Juan,Xu, Heng-Wei,Li, Bao-Sheng,Zhang, Jian,Cheng, Jian Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.12

Background: Radiation therapy plays an important role in lung carcinoma treatment. However, the incidence of symptomatic radiation-induced lung injury is high. This study aimed to evaluate radioprotective effects of flavonoids extracted from Astragalus complanatus and mechanisms of action against radiation damage. Methods: Alteration in antioxidant status and levles of several cytokines were investigated in BABL/C mice treated with 4 mg/kg b.wt. flavonoids after exposure to 10Gy thoracic radiation. Results: Serum levels of SOD in the flavonoids+radiation group were significantly higher compared to the radiation control group, while TGF-${\beta}1$ and IL-6 were lower. Mice in the radiation control group displayed more severe lung damage compared with the flavonoids+radiation group. The expression of TGF-${\beta}1$ and TNF-${\alpha}$ in the radiation control group was markedly increased in alveolar epithelial cells and macrophages of the alveolar septum. Conclusions: From the results of the present study, flavonoids could be excellent candidates as protective agents against radiation-induced lung injury.

방사선 조사후 폐 손상 조직에서의 Interleukin-6의 발현

김성숙,하은희,한덕자 大韓産業醫學會 1996 대한직업환경의학회지 Vol.8 No.1

Ionizing radiation has proved to be most valuable in clinical diagnosis and radiotherapy. And also it is used very common in industries especially such as industrial radiography, atomic energy plant, inspectoring by gamma-ray, etc. However, inadvertent exposure to relatively high doses of ionizing radiation is capable of injuring and killing cells. The lungs, because of their rich vascularization, are vulnerable to radiation injury. It is now known that IL-6 is a pleiotrophic cytokine produced by various cells that regulates the immune reponses, acute phase reactions. We performed the immunohistochemical staining of IL-6 on radiation induced lung injury by duration, to clarify the role of IL-6 in tissue damage. IL-6 was strongly expressed in early phase of radiation from alveolar macrophages and damaged endothelial cells. These findings not only have important implications for increasing our understanding of mechanisms of radiation lung injury but they also have an impact on strategies for diagnosis and therapy of radiation damage.

방사선 조사 후 흰 쥐의 폐에서 염증성 Cytokine의 발현 양상

최윤정 ( Yun Jung Choi ),노진경 ( Jin Kyung Rho ),장원석 ( Won Seok Jang ),이선주 ( Seon Joo Lee ),이승숙 ( Seung Sook Lee ),고재수 ( Jae Soo Koh ),김재열 ( Jae Yeol Kim ),김혜련 ( Hye Ryoun Kim ),김철현 ( Cheol Hyeon Kim ),이재철 대한결핵 및 호흡기학회 2009 Tuberculosis and Respiratory Diseases Vol.67 No.1

연구배경: 방사선치료 효율의 증가와 방사선 피폭 환자의 치료에 있어 방사선으로 인한 폐 손상의 기전을 잘 파악하는 것이 무엇보다 중요한 일이다. 최근 염증성 cytokine의 활성화가 초기 방사선 폐렴뿐만 아니라 후기에 생기는 폐 섬유화에도 기여하고 있다는 보고들이 많이 나오고 있다. 저자들은 염증성 cytokine의 역할을 알아보기 위하여 방사선 후 흰 쥐의 폐와 혈청에서 이들의 변화를 관찰하였다. 방법: 90마리의 흰 쥐 폐에 20 Gy의 방사선을 조사한 후 정해진 시간에 폐를 적출하여 병리학적 소견을 관찰하였다. 동시에 혈청과 lung homogenate에서 ELISA kit를 이용하여 염증성 cytokine의 변화를 조사하였다. 결과: 방사선 조사 후 조직에서 염증세포의 침윤이 증가하고 시간이 지남에 따라 폐 섬유화가 생기는 것을 확인할 수 있었다. TNF-α와 IL-1β는 4시간과 3주째 lung homogenate에서 증가하였는데 3주째 더 많이 증가하는 양상을 보여 주었다. 하지만 혈청에서의 변화는 뚜렷하지 않았다. MIP-2의 경우에는 4시간에 lung homogenate에서만 증가한 반면 HMGB1은 3주째 혈청에서만 증가하는 것을 알 수 있었다. 결론: 방사선 조사 후 TNF-α와 IL-1β 등의 염증성 cytokine들이 biphasic expression하는 것을 보여 주었다. 후기 염증성 cytokine들의 증가를 효과적으로 억제할 수 있는 방법이 모색되어야 할 것으로 생각되고 이는 폐 섬유화로 진행하는 만성 합병증을 예방하는 데 기여할 것으로 판단된다. Background: The pathophysiologic mechanisms of radiation-induced lung injury should be elucidated to enhance the therapeutic efficacy of radiotherapy and to manage patients exposed to serious radiation by accident. It has been suggested that pro-inflammatory cytokines play an important role in radiation-induced effect on the lung. This study was aimed to investigate changes in pro-inflammatory cytokines such as TNF-α, MIP-2, IL-1β and HMGB1, a newly recognized inflammatory mediator. Methods: The chests of BALB/c mice were selectively irradiated with single fraction of 20 Gy and then sacrificed at indicated times. Pathologic changes in the lung were examined after H&E staining. The expression level of pro-inflammatory cytokines was evaluated by ELISA kits in lung homogenate and in serum. Results: Radiation induced inflammatory changes and mild fibrosis in lung. Biphasic increase of TNF-α and IL-1β was found in lung homogenate at 4 hours and at 3 weeks after radiation. The elevation in the second phase tended to be more intense. However, there was no similar change in serum. MIP-2 level was slightly increased in lung homogenate at 4 hours, but not at 3 weeks. HMGB1 was increased at 3 weeks in serum while there was no significant change in lung homogenate. Conclusion: Radiation induced a biphasic increase in TNF-α and IL-1β. The effective control of second phase cytokine elevation should contribute to preventing severe lung fibrosis caused by radiation.

Radiation-induced brain injury: retrospective analysis of twelve pathologically proven cases

Lee, Dong-Soo,Yu, Mi-Na,Jang, Hong-Seok,Kim, Yeon-Sil,Choi, Byung-Ock,Kang, Young-Nam,Lee, Youn-Soo,Kim, Dong-Chul,Hong, Yong-Kil,Jeun, Sin-Soo,Yoon, Sei-Chul The Korean Society for Radiation Oncology 2011 Radiation Oncology Journal Vol.29 No.3

Purpose: This study was designed to determine the influencing factors and clinical course of pathologically proven cases of radiation-induced brain injury (RIBI). Materials and Methods: The pathologic records of twelve patients were reviewed; these patients underwent surgery following radiotherapy due to disease progression found by follow-up imaging. However, they were finally diagnosed with RIBI. All patients had been treated with 3-dimensional conventional fractionated radiotherapy and/or radiosurgery for primary or metastatic brain tumors with or without chemotherapy. The histological distribution was as follows: two falx meningioma, six glioblastoma multiform (GBM), two anaplastic oligodendroglioma, one low grade oligodendroglioma, and one small cell lung cancer with brain metastasis. Results: Radiation necrosis was noted in eight patients and the remaining four were diagnosed with radiation change. Gender (p = 0.061) and biologically equivalent dose $(BED)_3$ (p = 0.084) were the only marginally influencing factors of radiation necrosis. Median time to RIBI was 7.3 months (range, 0.5 to 61 months). Three prolonged survivors with GBM were observed. In the subgroup analysis of high grade gliomas, RIBI that developed <6 months after radiotherapy was associated with inferior overall survival rates compared to cases of RIBI that occurred ${\geq}6$ months (p = 0.085). Conclusion: Our study demonstrated that RIBI could occur in early periods after conventional fractionated brain radiotherapy within normal tolerable dose ranges. Studies with a larger number of patients are required to identify the strong influencing factors for RIBI development.