Raj Shailaja, Bui Marilyn M, Springett Gregory, Conley Anthony, Lavilla-Alonso Sergio, Zhao Xiuhua, Chen Dungsa, Haysek Randy, Gonzalez Ricardo, Letson G Douglas, Finkelstein Steven Eric, Chiappori Alberto A, Gabrilovitch Dmitry I, Antonia Scott J
H. Lee. Moffitt Cancer Center, Tampa, FL 33612, USA.
MD Anderson Cancer Institute, Houston, TX 77030, USA.
Sarcoma. 2015;2015:614736. doi: 10.1155/2015/614736. Epub 2015 Dec 31.
Purpose. Patients with large >5 cm, high-grade resectable soft tissue sarcomas (STS) have the highest risk of distant metastases. Previously we have shown that dendritic cell (DC) based vaccines show consistent immune responses. Methods. This was a Phase I single institution study of neoadjuvant radiation with DC injections on 18 newly diagnosed high-risk STS patients. Neoadjuvant treatment consisted of 50 Gy of external beam radiation (EBRT), given in 25 fractions delivered five days/week, combined with four intratumoral injections of DCs followed by complete resection. The primary endpoint was to establish the immunological response to neoadjuvant therapy and obtain data on its clinical safety and outcomes. Results. There were no unexpected toxicities or serious adverse events. Twelve out of 18 (67%) patients were alive, of which an encouraging 11/18 (61%) were alive with no systemic recurrence over a period of 2-8 years. Favorable immunological responses correlated with clinical responses in some cases. Conclusions. This study provides clinical support to using dendritic cell injections along with radiation in sarcomas, which when used optimally in combination can help clinical outcomes in soft tissue sarcoma. Study registration number is NCT00365872.
目的。肿瘤大小>5厘米的高级别可切除软组织肉瘤（STS）患者发生远处转移的风险最高。此前我们已表明，基于树突状细胞（DC）的疫苗可产生持续的免疫反应。方法。这是一项在单一机构开展的I期研究，对18例新诊断的高危STS患者进行新辅助放疗并注射DC。新辅助治疗包括50 Gy的外照射放疗（EBRT），每周5天，分25次给予，同时进行4次瘤内注射DC，随后进行完整切除。主要终点是确定对新辅助治疗的免疫反应，并获取其临床安全性和结局的数据。结果。未出现意外毒性或严重不良事件。18例患者中有12例（67%）存活，其中令人鼓舞的是，18例中有11例（61%）在2至8年期间存活且无全身复发。在某些情况下，良好的免疫反应与临床反应相关。结论。本研究为在肉瘤中联合使用树突状细胞注射和放疗提供了临床支持，两者优化联合使用有助于改善软组织肉瘤的临床结局。研究注册号为NCT00365872。
