Survival of patients with metastatic leiomyosarcoma: the MD Anderson Clinical Center for targeted therapy experience.
Survival of patients with metastatic leiomyosarcoma: the MD Anderson Clinical Center for targeted therapy experience.
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转移性平滑肌肉瘤患者的生存：MD安德森临床中心靶向治疗经验
作者：
Wang Z;Shi N;Naing A;Janku F;Subbiah V;Araujo DM;Patel SR;Ludwig JA;Ramondetta LM;Levenback CF;Ramirez PT;Piha-Paul SA;Hong D;Karp DD;Tsimberidou AM;Meric-Bernstam F;Fu S
晚期平滑肌肉瘤（LMS）无法用当前的全身抗肿瘤疗法治愈。因此，临床上有兴趣探索新的治疗方案来治疗LMS。我们回顾了75例连续的经组织学确诊的转移性淋巴管瘤患者的医疗记录，这些患者已被转诊至MD安德森癌症中心的临床靶向治疗中心。为了为治疗晚期LMS的潜在I期试验奠定基础，我们分析了肿瘤反应和生存结局数据。我们观察到的常见热点基因畸变是通过Sequenom或下一代测序检测到的TP 53突变（65%）和RB 1缺失/突变（45%）。在接受基因畸变相关I期试验治疗的患者中，中位无进展生存期为5.8个月，中位总生存期为15.9个月，显著优于未接受治疗的患者（分别为1.9个月，P = 0.001; 8.7个月，P = 0.013）。预测总生存期较短的独立风险因素包括血红蛋白<10 g/dL、体重指数<30 kg/m2、血清白蛋白<3.5 g/dL和中性粒细胞高于正常上限。有0、1或2和≥3个危险因素者的中位生存期分别为19.9、7.6和0.9个月（P < 0.001）。包括四个独立危险因素的预后评分系统可能预测在I期试验中接受治疗的转移性LMS患者的生存率。基因畸变相关治疗带来了显著更好的临床获益，支持进一步探索新的机制驱动的治疗方案。
Advanced stage leiomyosarcoma (LMS) is incurable with current systemic antitumor therapies. Therefore, there is clinical interest in exploring novel therapeutic regimens to treat LMS. We reviewed the medical records of 75 consecutive patients with histologically confirmed metastatic LMS, who had been referred to the Clinical Center for Targeted Therapy at MD Anderson Cancer Center. To lay the foundation for potential phase I trials for the treatment of advanced LMS, we analyzed tumor response and survival outcome data. The frequent hotspot gene aberrations that we observed were the TP53 mutation (65%) and RB1 loss/mutation (45%) detected by Sequenom or next‐generation sequencing. Among patients treated with gene aberration‐related phase I trial therapy, the median progression‐free survival was 5.8 months and the median overall survival was 15.9 months, significantly better than in patients without therapy (1.9 months, P = 0.001; and 8.7 months, P = 0.013, respectively). Independent risk factors that predicted shorter overall survival included hemoglobin <10 g/dL, body mass index <30 kg/m2, serum albumin <3.5 g/dL, and neutrophil above upper limit of normal. The median survivals were 19.9, 7.6, and 0.9 months for patients with 0, 1 or 2, and ≥3 of the above risk factors, respectively (P < 0.001). A prognostic scoring system that included four independent risk factors might predict survival in patients with metastatic LMS who were treated in a phase I trial. Gene aberration‐related therapies led to significantly better clinical benefits, supporting that further exploration with novel mechanism‐driven therapeutic regimens is warranted.