Open Access

Lara Schulz, Matthias Zähringer, Klaus-Henning Kahl, Nikolaos Balagiannis, Bertram Jehs, Johannes Doescher, Johannes Zenk, Georg Stüben, Maria Neu

• Background: NUT carcinoma (NUTc) is a rare, aggressive squamous carcinoma defined by NUTM1 rearrangements. Outcomes in head and neck (H&N) disease are poor, and no uniform treatment standard exists; available evidence largely derives from case reports and small series. Methods: We performed a structured narrative review of H&N NUTc with an emphasis on radiotherapy (RT) dose concepts, chemotherapy regimens, and outcome signals. Results: Published evidence indicates poor overall survival, particularly in metastatic disease. Long-term remissions have been described in selected patients with non-metastatic disease treated with multimodal approaches combining surgery, multi-agent chemotherapy, and early integrated RT. Across reports, use of RT in first-line management and delivery of definitive-dose RT are repeatedly associated with better outcomes. Evidence for immune checkpoint inhibitors is limited to anecdotal single-patient reports. Case vignette: A 19-year-old man with locallyBackground: NUT carcinoma (NUTc) is a rare, aggressive squamous carcinoma defined by NUTM1 rearrangements. Outcomes in head and neck (H&N) disease are poor, and no uniform treatment standard exists; available evidence largely derives from case reports and small series. Methods: We performed a structured narrative review of H&N NUTc with an emphasis on radiotherapy (RT) dose concepts, chemotherapy regimens, and outcome signals. Results: Published evidence indicates poor overall survival, particularly in metastatic disease. Long-term remissions have been described in selected patients with non-metastatic disease treated with multimodal approaches combining surgery, multi-agent chemotherapy, and early integrated RT. Across reports, use of RT in first-line management and delivery of definitive-dose RT are repeatedly associated with better outcomes. Evidence for immune checkpoint inhibitors is limited to anecdotal single-patient reports. Case vignette: A 19-year-old man with locally advanced supraglottic NUTc and bilateral cervical nodal disease (M0) presented with dysphagia and otalgia. Following laser debulking and temporary tracheostomy, induction cisplatin/doxorubicin/ifosfamide led to a complete metabolic response in positron-emission tomography/computed tomography (PET/CT) after two cycles of chemotherapy. Definitive PET/CT-guided intensity-modulated (IM)RT/image-guided (IG)RT was delivered to 73.2 Gy using an accelerated twice-daily schedule (2.0 Gy to the planning target volume [PTV] in the morning and 1.6 Gy boost to the initial gross target volume [GTV] in the afternoon; ≥ 8-hour interval). Acute toxicity was grade 3 dermatitis and grade 2 mucositis (CTCAE v5.0). After RT, chemotherapy was continued as consolidation and completed with vincristine/doxorubicin/ifosfamide (six cycles) due to acute kidney injury. Complete remission is ongoing at > 7 years, with persistent xerostomia and dysgeusia. Conclusion: In selected non-metastatic H&N NUTc, durable control has been reported with timely systemic therapy plus curative-intent RT, often exceeding 50 Gy. This review summarizes dose concepts and case-based systemic regimens and provides a comparative table to support individualized treatment planning.…