title: 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.
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors: Nicole G
authors: NG
authors: Chau
authors: Center for Clinical Investigation, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors: Shelley
authors: S
authors: Hurwitz
authors: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors: Chelsey M
authors: CM
authors: Mitchell
authors: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors: Alexandra
authors: A
authors: Aserlind
authors: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors: Noam
authors: N
authors: Grunfeld
authors: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors: Leah
authors: L
authors: Kaplan
authors: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors: Peter
authors: P
authors: Hsi
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.|Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.|Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
authors: Daniel E
authors: DE
authors: Bauer
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors: Christopher S
authors: CS
authors: Lathan
authors: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.|Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
authors: Carlos
authors: C
authors: Rodriguez-Galindo
authors: Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors: Roy B
authors: RB
authors: Tishler
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors: Robert I
authors: RI
authors: Haddad
authors: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.|Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
authors: Stephen E
authors: SE
authors: Sallan
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors: James E
authors: JE
authors: Bradner
authors: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors: Christopher A
authors: CA
authors: French
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000379:methods; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009333:Neck / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: C471990:BRD4-NUT fusion oncogene protein, human; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion
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