Safi Seyer, Beckhove Philipp, Warth Arne, Benner Axel, Roeder Falk, Rieken Stefan, Debus Juergen, Dienemann Hendrik, Hoffmann Hans, Huber Peter E
Department of Thoracic Surgery, Thoraxklinik, Heidelberg University Hospital, Heidelberg, Germany.
Translational Immunology Unit, German Cancer Research Center, Heidelberg, Germany.
BMC Cancer. 2015 Dec 19;15:988. doi: 10.1186/s12885-015-2006-2.
Lung cancer is the leading cause of cancer deaths worldwide. Surgery, radiotherapy at conventional and high dose and chemotherapy are the mainstay for lung cancer treatment. Insufficient migration and activation of tumour specific effector T cells seem to be important reasons for inadequate host anti-tumour immune response. Ionizing radiation can induce a variety of immune responses. The goal of this randomized trial is to assess if a preoperative single fraction low dose radiation is able to improve anti-tumour immune response in operable early stage lung cancer.
METHODS/DESIGN: This trial has been designed as an investigator-initiated, prospective, randomized, 2-armed phase II trial. Patients who are candidates for elective resection of early stage non-small cell lung cancer will be randomized into 2 arms. A total of 36 patients will be enrolled. The patients receive either 2 Gy or no radiation prescribed to their primary tumour. Radiation will be delivered by external beam radiotherapy using 3D radiotherapy or intensity-modulated radiation technique (IMRT) 7 days prior to surgical resection. The primary objective is to compare CD8+ T cell counts detected by immunohistochemistry in resected tumours following preoperative radiotherapy versus no radiotherapy. Secondary objectives include the association between CD8+ T cell counts and progression free survival, the correlation of CD8+ T cell counts quantified by immunohistochemistry and flow cytometry, local tumour control and recurrence patterns, survival, radiogenic treatment toxicity and postoperative morbidity and mortality. Further, frequencies of tumour reactive T cells in blood and bone marrow as well as whole blood cell transcriptomics and plasma-proteomics will be correlated with clinical outcome.
This unique intervention combining preoperative low dose radiation and surgical removal of early stage non-small cell lung cancer is designed to address the problem of inadequate host anti-tumour immune response. If successful, this study may affect the role of radiotherapy in lung cancer treatment.
NCT02319408;
December 29, 2014.
肺癌是全球癌症死亡的主要原因。手术、常规及高剂量放疗和化疗是肺癌治疗的主要手段。肿瘤特异性效应T细胞迁移和激活不足似乎是宿主抗肿瘤免疫反应不足的重要原因。电离辐射可诱导多种免疫反应。本随机试验的目的是评估术前单次低剂量辐射能否改善可手术早期肺癌的抗肿瘤免疫反应。
方法/设计：本试验设计为一项研究者发起的前瞻性随机双臂II期试验。符合早期非小细胞肺癌择期切除条件的患者将被随机分为两组。共招募36例患者。患者接受对其原发肿瘤给予2 Gy辐射或不进行辐射。辐射将在手术切除前7天通过外照射放疗使用三维放疗或调强放疗技术（IMRT）进行。主要目的是比较术前放疗与未放疗后切除肿瘤中通过免疫组织化学检测的CD8+T细胞计数。次要目的包括CD8+T细胞计数与无进展生存期的关联、通过免疫组织化学和流式细胞术定量的CD8+T细胞计数的相关性、局部肿瘤控制和复发模式、生存率、放射治疗毒性以及术后发病率和死亡率。此外，血液和骨髓中肿瘤反应性T细胞的频率以及全血细胞转录组学和血浆蛋白质组学将与临床结果相关联。
这种将术前低剂量辐射与早期非小细胞肺癌手术切除相结合的独特干预措施旨在解决宿主抗肿瘤免疫反应不足的问题。如果成功，本研究可能会影响放疗在肺癌治疗中的作用。
NCT02319408；
2014年12月29日。
