Primary pulmonary NUT carcinoma with NSD3-NUTM1 fusion treated with dose-escalated adaptive radiotherapy and multimodal therapy: case report
FRONTIERS IN ONCOLOGY, cilt.16, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 16
- Basım Tarihi: 2026
- Doi Numarası: 10.3389/fonc.2026.1827995
- Dergi Adı: FRONTIERS IN ONCOLOGY
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, Directory of Open Access Journals
- Dokuz Eylül Üniversitesi Adresli: Evet
Özet
Primary pulmonary NUT carcinoma (PPNC) is an exceptionally rare and aggressive malignancy driven by NUTM1 rearrangements, with a median overall survival (OS) of 5-9 months. While BRD4-NUTM1 accounts for approximately 70% of cases, the rarer NSD3-NUTM1 fusion, reported in approximately 6% of NUT carcinomas, is poorly characterized, and data on optimal radiotherapy (RT) techniques and adaptive strategies remain extremely limited. We describe a 27-year-old man with PPNC harboring an NSD3-NUTM1 fusion (cT4N2M1c), confirmed by next-generation sequencing (NGS) following equivocal NUT immunohistochemistry. Given rapidly progressive post-obstructive atelectasis and airway compromise, a staged, adaptive thoracic RT strategy was employed: urgent hypofractionated IMRT was initiated with 5 & times; 3 Gy, followed by 15 & times; 2 Gy using the initial plan, as early cone-beam CT showed insufficient anatomical change for immediate replanning. Subsequent tumor regression and right lung re-expansion enabled repeat CT simulation and adaptive volumetric modulated arc therapy (VMAT) for the final 9 & times; 2 Gy, achieving a cumulative tumor-effect EQD2 alpha/beta 10Gy of 64.25 Gy. Interim PET/CT revealed in-field thoracic regression but widespread systemic progression; cisplatin-etoposide was added during the remaining RT course, followed by multisite palliative RT and consolidation cisplatin-etoposide-ifosfamide chemotherapy. Despite an initial metabolic response, hepatic progression precluded planned immunotherapy. OS was 8.8 months. This case suggests that staged, dose-escalated adaptive thoracic RT is feasible in selected patients with disseminated PPNC and compromised pulmonary function, providing durable in-field control and meaningful symptom palliation as part of a multimodal treatment approach. Molecular confirmation by NGS is essential for non-BRD4 fusions, and systemic therapy should be incorporated as early as safely feasible to address the high risk of distant dissemination.