NUT carcinomas (NC) are very rare and highly aggressive tumors, molecularly defined by an aberrant gene fusion involving the NUTM1 gene. NCs preferentially arise intrathoracically or in the head and neck region, having a highly adverse prognosis with almost no long-term survivors.

Here, we report on a cohort of 35 adult NC patients who were evaluated at University Hospital Tuebingen in an eight year time span, i.e. between 2016 and 2023. Primary objectives were overall survival (OS) and influence of primary tumor locations, fusion gene types and staging on OS. Secondary objectives were patient baseline characteristics, risk factors, tumor markers, treatment decisions and responses to therapy comparing thoracic vs non-thoracic origins. Further, data from tumor genome sequencing were analyzed.

In this monocentric German cohort, 54 % of patients had thoracic tumors and 65 % harbored a BRD4-NUTM1 fusion gene. Median OS was 7.5 months, being significantly dependent on primary tumor location and nodal status. Initial misdiagnosis was a problem in 31 % of the cases. Surgery was the first treatment in most patients (46 %) and 80 % were treated with polychemotherapies, showing longer progression free survival (PFS) with ifosfamide-based than with platinum-based regimens. Patients treated with an immune checkpoint inhibitor (ICI) in addition to first-line chemotherapy tended to have longer OS. Initial LDH levels could be identified as a prognostic measure for survival prognosis. Sequencing data highlight aberrant NUTM1 fusion genes as unique tumor driver genes.

This is the largest adult European cohort of this orphan tumor disease, showing epidemiologic and molecular features as well as relevant clinical data. Awareness to prevent misdiagnosis, fast contact to a specialized nation-wide center and referral to clinical studies are essential as long-term survival is rarely achieved with any of the current therapeutic regimes.

NUT 癌 (NC) 是非常罕见且高度侵袭性的肿瘤，其分子定义是涉及NUTM1基因的异常基因融合。 NC 优先发生在胸腔内或头颈部区域，预后极差，几乎没有长期幸存者。

在此，我们报告了 35 名成年 NC 患者的队列，这些患者在 8 年的时间内（即 2016 年至 2023 年）在图宾根大学医院接受了评估。主要目标是总生存期 (OS) 以及原发肿瘤位置、融合基因类型的影响并在操作系统上暂存。次要目标是患者基线特征、危险因素、肿瘤标志物、治疗决策以及比较胸部与非胸部起源的治疗反应。此外，还分析了肿瘤基因组测序的数据。

在这个单中心德国队列中，54% 的患者患有胸部肿瘤，65% 的患者携带BRD4-NUTM1融合基因。中位 OS 为 7.5 个月，很大程度上取决于原发肿瘤位置和淋巴结状态。 31% 的病例存在初始误诊问题。大多数患者 (46%) 的首选治疗是手术，80% 的患者接受了多种化疗，显示以异环磷酰胺为基础的治疗方案比以铂类为基础的治疗方案具有更长的无进展生存期 (PFS)。除一线化疗外还接受免疫检查点抑制剂 (ICI) 治疗的患者往往有更长的 OS。初始 LDH 水平可被确定为生存预后的预后指标。测序数据强调异常的NUTM1融合基因是独特的肿瘤驱动基因。

这是这种孤儿肿瘤疾病最大的欧洲成人队列，显示了流行病学和分子特征以及相关的临床数据。预防误诊的意识、快速联系全国范围内的专业中心以及转诊临床研究至关重要，因为目前的任何治疗方案都很少能实现长期生存。