Intensive treatment and survival outcomes in NUT midline carcinoma of the head and neck

Abstract

Background: NUT midline carcinoma is a rare and aggressive genetically characterized subtype of squamous cell carcinoma frequently arising from the head and neck. The characteristics and optimal management of head and neck NUT midline carcinoma (HNNMC) are unclear.

Methods: A retrospective review of all known cases of HNNMC in the International NUT Midline Carcinoma Registry as of December 31, 2014, was performed. Forty-eight consecutive patients were treated from 1993 to 2014, and clinicopathologic variables and outcomes for 40 patients were available for analyses; they composed the largest HNNMC cohort studied to date. Overall survival (OS) and progression-free survival (PFS) according to patient characteristics and treatment were analyzed.

Results: This study identified a 5-fold increase in the diagnosis of HNNMC from 2011 to 2014. The median age was 21.9 years (range, 0.1-81.7 years); the male and female proportions were 40% and 60%, respectively; and 86% had bromodomain containing 4-nuclear protein in testis (BRD4-NUT) fusion. The initial treatment was initial surgery with or without adjuvant chemoradiation or adjuvant radiation (56%), initial radiation with or without chemotherapy (15%), or initial chemotherapy with or without surgery or radiation (28%). The median PFS was 6.6 months (range, 4.7-8.4 months). The median OS was 9.7 months (range, 6.6-15.6 months). The 2-year PFS rate was 26% (95% confidence interval [CI], 13%-40%). The 2-year OS rate was 30% (95% CI, 16%-46%). Initial surgery with or without postoperative chemoradiation or radiation (P = .04) and complete resection with negative margins (P = .01) were significant predictors of improved OS even after adjustments for age, tumor size, and neck lymphadenopathy. Initial radiation or chemotherapy and the NUT translocation type were not associated with outcomes.

Conclusions: HNNMC portends a poor prognosis. Aggressive initial surgical resection with or without postoperative chemoradiation or radiation is associated with significantly enhanced survival. Chemotherapy or radiation alone is often inadequate. Cancer 2016;122:3632-40. © 2016 American Cancer Society.

Keywords: NUT midline carcinoma; bromodomain containing 3-nuclear protein in testis (BRD3-NUT); bromodomain containing 4-nuclear protein in testis (BRD4-NUT); head and neck cancer; nuclear protein in testis (NUT) protein.

Figure 1

Diagnosis of HNNMC in adult and pediatric patients per year.

Figure 2

Overall survival according to initial treatment strategy. The probability of OS is presented for patients with HNNMC according to the initial treatment strategy consisting of either initial radiation, initial chemotherapy or initial surgery.

Figure 3

Influence of surgical resection on PFS (A) and OS (B) for patients with HNNMC according to primary tumor size (smaller than 6cm, or greater than or equal to 6cm).

Figure 3

Influence of surgical resection on PFS (A) and OS (B) for patients with HNNMC according to primary tumor size (smaller than 6cm, or greater than or equal to 6cm).