ArticleFrontiers in oncology2026
Primary pulmonary NUT carcinoma with NSD3-NUTM1 fusion treated with dose-escalated adaptive radiotherapy and multimodal therapy: case report.
Article in Frontiers in oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
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 × 3 Gy, followed by 15 × 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 × 2 Gy, achieving a cumulative tumor-effect EQD2α/β10Gy 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.
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