Repeated iodine-125 seed implantations combined with external beam radiotherapy for the treatment of locally recurrent or metastatic stage III/IV non-small cell lung cancer: a retrospective study

Li et al. Radiation Oncology (2016) 11:119 DOI 10.1186/s13014-016-0688-5 RESEARCH Open Access Repeated iodine-125 seed implantations combined with external beam radiotherapy for the treatment of locally recurrent or metastatic stage III/IV non-small cell lung cancer: a retrospective study Wei Li, Gang Dan, Jianqing Jiang, Yifeng Zheng, Xiushan Zheng and Dan Deng* Abstract Background: Recurrent or metastatic lung cancer is difficult to manage. This retrospective study aimed to assess the efficacy of repeated iodine-125 seed implantations combined with external beam radiotherapy (EBRT) for locally recurrent or metastatic stage-III/IV non-small cell lung cancer (NSCLC). Methods: Eighteen previously treated stage-III/IV NSCLC patients with local or metastatic recurrences underwent 1to-3 iodine-125 implantations. Six of these patients received palliative EBRT and six patients received combined chemotherapy using gemcitabine and cisplatin. Near-term treatment efficacy was evaluated 3 months after seed implantation by comparing changes in tumor size on computed tomography images; the evaluated outcomes were complete response, partial response, stable disease, and local tumor control rate. Long-term efficacy was assessed based on 1- and 2-year survival rates. Results: Patients were followed up for 6 to 50 months. The overall (i.e., complete + partial) response rate was 87. 4 %. The local control rates after the first, second, and third years were 94.1, 58.8 and 41.2 %, respectively. Conclusions: The results of this study demonstrated that repeated implantation of radioactive particles combined with EBRT is a safe treatment that effectively controlled local recurrence and metastasis of stage III/IV NSCLC. Keywords: Non-small cell lung cancer, I125 seed implantation, External beam radiotherapy, Metastasis, Recurrence, Brachytherapy Introduction Lung cancer is the leading cause of cancer death in both men and women worldwide, and its prevalence is increasing [1]. Conventional treatment for lung cancer includes palliative radiotherapy and chemotherapy, which has shown limited potential in increasing long-term survival rates [2]. Using external beam radiotherapy (EBRT) alone, it is difficult to deliver a sufficient radiation dose to patients with large or advanced tumors, in order to avoid damage to adjacent normal tissues [3]. Repeated EBRT has limited efficacy for these patients and is associated with increased side effects because of the low tolerance of the surrounding normal tissue [4]. Furthermore, because a large proportion of lung cancers are diagnosed at an advanced stage, the main challenges to treatment are recurrence and metastasis, which is difficult to manage. Extensive resection of a locally recurrent lung cancer is associated with high recurrence risk and significant mortality. Mediastinal metastasis and metastasis in the brain, bone, or distant * Correspondence: Department of Thoracic Surgery, PLA Chengdu Military General Hospital, Chengdu 610083, People’s Republic of China © 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Li et al. Radiation Oncology (2016) 11:119 Page 2 of 8 organs are common in patients with advanced lung cancer [5]. Controlling the size of these metastatic tumors may help to improve long-term survival rate. Radioactive seed implantation, which is a form of brachytherapy, can be performed repeatedly. It has been successfully applied for treating inoperable solitary lung cancers, while avoiding excessive radiation exposure to surrounding tissues [6–8]. Clinically, brachytherapy using iodine-125 seed implantation is capable of delivering a sufficient dose of radiation to the tumor mass. However, in many recurrent and metastatic lung cancers, important organs, large vessels, or bone structures often block the pathway to the lesions, making these tumors inaccessible to needle puncture, and leading to an unsatisfactory distribution of the implanted iodine-125 seeds [9, 10]. In addition, brachytherapy would become very risky when conducting implantation in metastatic lymph nodes located near the mediastinal macrovascular area. In this retrospective study, we investigated the efficacy of combining iodine-125 seed implantations with EBRT for salvage treatment of advanced lung cancers. Eighteen recurrent advanced non-small cell lung cancer (NSCLC) patients who previously underwent iodine-125 seed implantations received computed tomography (CT)-guided iodine-125 seed reimplantations in combination with EBRT. Materials and methods Patients The Institutional Review Board and Ethics Committee of General Hospital of Chengdu Military Region of the PLA (#08-00125) approved this study. All patients provided written informed consent. Between October 2006 and September 2014, 18 patients with recurrent or metastatic stage III/IV NSCLC (Table 1) underwent CT-guided iodine-125 seed reimplantations, with or without EBRT, at the General Hospital of Chengdu Military Region of PLA. All of the 18 patients enrolled in this study had a history of iodine-125 seed implantations and met the following criteria: NSCLC was confirmed by histopathological examination; a CT scan indicated a solid mass or nodule in the lung area, or nearby the mediastinum; local recurrence or restricted metastasis at <3 regions; the Karnofsky Performance Status score was ≥60. Treatment Among the 18 patients evaluated (Tables 1 and 2), two patients with vertebral metastasis (Patients 8 and 17) and great pain and one patient with metastasis in the lymph nodes of the mediastinum (Patient 13) received palliative EBRT at 20–30 Gy. In addition, three patients with mediastinum metastasis (Patients 5, 10, and 18) received palliative EBRT at the lymph nodes of the mediastinum. Two patients with brain Table 1 Clinical features of the present 18-patient cohort No. Age, y Gender TNM KPS a Tumors Size, cm3 Seeds b; activity, mCi MPD, Gy 1 72 M T3N1M0 70 L, lung SCC 6×5×5 72/59/43; 0.7–0.8 130 2 57 F T3N1M0 80 R, lower lung adenocarcinoma 6×6×5 76/45/52; 0.8 140 3 59 M T3N1M1 70 L, lower lung adenocarcinoma 6×5×4 77/20; 0.7 140 4 59 M T3N2M0 70 L, lung SCC 5×5×4 66/62; 0.8 150 5 73 M T2N2M0 80 R, lower lung adenocarcinoma with mediastinal LNM 6×7×6 63/24; 0.8 140 6 70 M T3N1M1 70 L, lung SCC with brain metastases 5×5×4 45; 0.7 130 7 54 M T3N1M0 60 L, lung poorly differentiated SCC (...truncated)