Department of Pediatric Oncology, Dana-Farber Cancer Institute, and Division of Hematology/Oncology, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA.
Clin Cancer Res. 2012 Oct 15;18(20):5773-9. doi: 10.1158/1078-0432.CCR-12-1153. Epub 2012 Aug 15.
NUT midline carcinoma (NMC) is a poorly differentiated squamous cancer characterized by rearrangement of the NUT gene. Research advances have provided opportunities for targeted therapy in NMC, yet the clinical features of this rare disease have not been systematically characterized. We report on a large population of such patients to identify the disease characteristics and treatments, correlate them with outcome, and to consider clinical recommendations.
A clinical database was established using retrospective demographic and outcomes data available on all known cases of NMC. Questionnaires were completed by treating physicians. Pathologic, demographic, and clinical variables were assessed for 63 patients, the largest cohort of patients with NMC studied to date. Outcome data from 54 patients were available for survival analyses.
The diagnosis of NMC has increased annually since 2007. Since 2009, there has been an observed increase in the age at diagnosis (P < 0.05). Geographic distribution of patients with NMC has been concentrated in the United States (n = 41, 65%). The median overall survival for patients with NMC was 6.7 months. The 2-year progression-free survival (PFS) was 9% with a 95% confidence interval (CI) of 1% to 17% [1-year PFS 15% (5-24%) and 2-year overall survival (OS) was 19% with a 95% CI of 7%-31% (1-year OS: 30% (27-34%)]. Multivariate analysis suggested that extent of surgical resection and initial radiotherapy were independent predictors of PFS and OS. Notably, no chemotherapeutic regimen was associated with improved outcome.
NMC portends a poor prognosis among all squamous cell neoplasms and seems to be frequently unrecognized. The finding that conventional chemotherapy has been inadequate indicates a pressing need for the development of targeted therapeutics. Intensive local therapies such as gross total resection and radiotherapy might be associated with enhanced survival.
NUT 中线癌(NMC)是一种低分化鳞状癌,其特征在于 NUT 基因的重排。研究进展为 NMC 的靶向治疗提供了机会,但这种罕见疾病的临床特征尚未得到系统描述。我们报告了一大群此类患者,以确定疾病特征和治疗方法,并将其与结果相关联,同时考虑临床建议。
使用所有已知 NMC 病例的回顾性人口统计学和结果数据,建立了一个临床数据库。由治疗医生完成调查问卷。评估了 63 例患者的病理、人口统计学和临床变量,这是迄今为止研究 NMC 患者最大的队列。54 例患者的生存数据可用于生存分析。
自 2007 年以来,NMC 的诊断每年都在增加。自 2009 年以来,诊断时的年龄呈上升趋势(P < 0.05)。NMC 患者的地理分布主要集中在美国(n = 41,65%)。NMC 患者的中位总生存期为 6.7 个月。2 年无进展生存率(PFS)为 9%,95%置信区间(CI)为 1%至 17%[1 年 PFS 为 15%(5-24%),2 年总生存率(OS)为 19%,95%CI 为 7%-31%(1 年 OS:30%(27-34%)]。多变量分析表明,手术切除范围和初始放疗是 PFS 和 OS 的独立预测因素。值得注意的是,没有化疗方案与改善结果相关。
NMC 在所有鳞状细胞肿瘤中预后不良,似乎经常未被识别。常规化疗效果不佳的发现表明迫切需要开发靶向治疗。强化局部治疗,如完全切除和放疗,可能与生存改善相关。