小动物放射研究平台在放疗实验中的应用

小动物放射研究平台是为肿瘤放射治疗和放射生物学研究所提供的一个高效研究平台;是有着等中心及非公面适形照射机架等诸多结构和性能优势的精确放射仪,通过其平台上CBCT获取的三维图像,可以实时的进行治疗计划的设计和照射,保证了小动物精确照射和研究的时效性。小动物放射研究平台的广泛使用,在加速临床转化的同时,又推动了放射治疗学和放射生物学等研究领域的发展。     

基于小动物照射研究平台建造C57BL6/J小鼠急性放射性肠炎精准模型研究

目的 基于小动物照射研究平台建造C57BL6/J小鼠放射性肠炎精准模型。方法 将48只雌性小鼠随机均分为空白对照组、6Gy照射组、9Gy照射组及12Gy照射组4组。基于SARRP,照射组小鼠接受全腹单次照射,剂量率为4 Gy/min。观察小鼠一般情况、体重、小肠病理改变。结果 CT扫描后,勾画靶区及正常组织,根据4个预计划靶区剂量分布及脊髓保护,采用等中心水平对穿照射方案。6、9、12Gy组平均照射时间分别为163、252、328s。照射后15天6、9、12Gy组小鼠的生存率分别为100%、100%、50%;照射后第5天6、9、12Gy组小鼠体重较空白对照组明显下降(P=0.035、P=0.002、P<0.001),10天后逐渐上升。随着照射剂量增加,肠黏膜绒毛和腺体损伤逐渐加重。与较空白对照组相比,9、12Gy 组绒毛长度明显缩短(P<0.001);照射组肠壁厚度明显变薄(P<0.001)。结论 SARRP在小鼠放射性肠炎模型建造中能够提供精准的靶区定位、计划的筛选和精确的剂量交付。6~9Gy的单次全腹水平对穿照射能够成功地建造C57BL6/J雌性小鼠的急性放射性肠炎模型。     

ESTRO ACROP: Technology for precision small animal radiotherapy research: Optimal use and challenges

Many radiotherapy research centers have recently installed novel research platforms enabling the investigation of the radiation response of tumors and normal tissues in small animal models, possibly in combination with other treatment modalities. Many more research institutes are expected to follow in the coming years. These novel platforms are capable of mimicking human radiotherapy more closely than older technology. To facilitate the optimal use of these novel integrated precision irradiators and various small animal imaging devices, and to maximize the impact of the associated research, the ESTRO committee on coordinating guidelines ACROP (Advisory Committee in Radiation Oncology Practice) has commissioned a report to review the state of the art of the technology used in this new field of research, and to issue recommendations. This report discusses the combination of precision irradiation systems, small animal imaging (CT, MRI, PET, SPECT, bioluminescence) systems, image registration, treatment planning, and data processing. It also provides guidelines for reporting on studies.     

Treatment of small cell lung cancer with TRA-8 in combination with cisplatin and radiation

Background

Limited stage small cell lung cancer (SCLC) represents a minority of SCLC. Despite extensive clinical trials, standard treatment remains cisplatin-based chemotherapy and thoracic irradiation (TI). This study focused on the interaction of cisplatin/radiation with the anti-human DR5 monoclonal antibody TRA-8 in SCLC cells. TRA-8 binds specifically to DR5 and has been shown to activate apoptosis.

Methods

Four human SCLC cell lines were utilized for experimentation (SCLC-41, SCLC-58, SCLC-68, and SCLC-74). Immunoblot analysis was used to determine relative protein levels of DR5, DR4 and pro-caspase 8 for each cell line. Using a tetrazolium-based assay (XTT), the IC₅₀ values for cisplatin with or without TRA-8 were determined for the SCLC cell lines. Four SCLC lines were assayed with a combination of TRA-8 (10 μg/ml), 2 Gy radiation and various concentrations of cisplatin. Apoptosis was evaluated using Annexin V-FITC and cleaved caspase immunoblotting. Using a SCLC-58 subcutaneous xenograft model, treatment began 21 d after tumor cell injection. Treatment included weekly cisplatin (4 mg/kg) and radiation of 1 Gy (24 h after cisplatin) and TRA-8 (200 μg) was administered i.p. twice weekly for three weeks.

Results

Immunoblot analysis showed similar levels of DR5 for all cell lines with variable levels of DR4. Various concentrations of TRA-8 antibody (?10 μg/ml) induced no significant cytotoxicity in the SCLC cell lines. The in vitro combination treatment with TRA-8 (10 μg/ml), 1.25 μg/ml cisplatin and 2 Gy radiation showed increased cytotoxicity when compared to combinations without TRA-8. Furthermore, the triple combination demonstrated the greatest amount of apoptosis as measured by Annexin V staining. The in vivo studies showed the combination of 1 Gy, cisplatin and TRA-8 extended the tumor doubling time to 44 d as compared to any doublet treatment groups that ranged from 12 to 20 d. Analysis of survival data showed 100% of the combination group (RT + cisplatin + TRA-8) were alive 65d after treatment began whereas all doublet treatment groups showed 50% or less survival.

Conclusions

These studies showed increased cytotoxicity when TRA-8 was added to radiation/cisplatin in SCLC. This effect was demonstrated in vitro and in vivo. TRA-8 represents a promising new agent in the treatment of SCLC.     

Partial body irradiation of small laboratory animals with an industrial X-ray tube

AimsDedicated precise small laboratory animal irradiation sources are needed for basic cancer research and to meet this need expensive high precision radiation devices have been developed. To avoid such expenses a cost efficient way is presented to construct a device for partial body irradiation of small laboratory animals by adding specific components to an industrial X-ray tube.Methods and materialsA custom made radiation field tube was added to an industrial 200 kV X-ray tube. A light field display as well as a monitor ionization chamber were implemented. The field size can rapidly be changed by individual inserts of MCP96 that are used for secondary collimation of the beam. Depth dose curves and cross sectional profiles were determined with the use of a custom made water phantom. More components like positioning lasers, a custom made treatment couch, and a commercial isoflurane anesthesia unit were added to complete the system.ResultsWith the accessories described secondary small field sizes down to 10 by 10 mm² (secondary collimator size) could be achieved. The dosimetry of the beam was constructed like those for conventional stereotactical clinical linear accelerators. The water phantom created showed an accuracy of 1 mm and was well suited for all measurements. With the anesthesia unit attached to the custom made treatment couch the system is ideal for the radiation treatment of small laboratory animals like mice.ConclusionIt was feasible to shrink the field size of an industrial X-ray tube from whole animal irradiation to precise partial body irradiation of small laboratory animals. Even smaller secondary collimator sizes than 10 by 10 mm² are feasible with adequate secondary collimator inserts. Our custom made water phantom was well suited for the basic dosimetry of the X-ray tube.     

Late relapse of small cell lung cancer treated with radiation therapy alone — case report

This report describes an unusual case of a long-term survivor with small cell lung cancer (SCLC), treated with radiation therapy alone having a late relapse with solitary brain metastasis 6.5 years after the initial treatment. He received radiation therapy and died of the brain metastasis 8.5 years after the initial treatment. Autopsy revealed no tumor recurrence at the primary site and no distant metastases except for the brain. The histology of the brain tumor was small cell carcinoma.     

A review of treatment planning for precision image-guided photon beam pre-clinical animal radiation studies

Recently, precision irradiators integrated with a high-resolution CT imaging device became available for pre-clinical studies. These research platforms offer significant advantages over older generations of animal irradiators in terms of precision and accuracy of image-guided radiation targeting. These platforms are expected to play a significant role in defining experiments that will allow translation of research findings to the human clinical setting. In the field of radiotherapy, but also others such as neurology, the platforms create unique opportunities to explore e.g. the synergy between radiation and drugs or other agents.To fully exploit the advantages of this new technology, accurate methods are needed to plan the irradiation and to calculate the three-dimensional radiation dose distribution in the specimen. To this end, dedicated treatment planning systems are needed. In this review we will discuss specific issues for precision irradiation of small animals, we will describe the workflow of animal treatment planning, and we will examine several dose calculation algorithms (factorization, superposition-convolution, Monte Carlo simulation) used for animal irradiation with kilovolt photon beams. Issues such as dose reporting methods, photon scatter, tissue segmentation and motion will also be discussed briefly.     

Enhanced radiation reaction following combination chemotherapy for small cell carcinoma of the lung, possibly secondary to VP16-213

A new combined radiation-chemotherapy protocol for the treatment of small cell lung carcinoma has produced unexpectedly severe normal tissue injury during radiation therapy. Thirteen of 23 patients who received radiation treatment plus combination chemotherapy [Vincristine, Adriamycin, Cyclophosphamide and VP16-213 (epipodophyllotoxin)] developed severe epithelial reactions from relatively low radiation doses. Prior experience with combination of radiation and chemotherapy leads us to implicate VP16-213 as the agent responsible for the enhanced radiation reactions.     

Hemibody radiation, an active therapeutic modality for the management of patients with small cell lung cancer

In a previously published paper, the results of a preliminary clinical trial comparing systemic radiation (upper and lower hemibody technique) versus systemic chemotherapy in the management of all stages of small cell lung cancer (SCLC), suggested that hemibody radiation (HBI) was as efficient as systemic chemotherapy, particularly for patients with early disease. We are now presenting the final results of the above trial. The two year survival has shown that as many patients in the HBI as in the chemotherapy arm have reached this endpoint. However, there is a difference in favor of chemotherapy on both the median and one year survival for those patients with advanced stages. Therefore, as of June 1981, we have initiated a study incorporating HBI as a consolidating-maintenance agent for patients with all stages of the disease who have received a 3 1/2 months induction systemic chemotherapy plus local chest irradiation. Up to date, 65 patients have been entered and our median survival for those who received the complete treatment is 62.5 weeks.