Clinicopathologic features and long-term outcomes of NUT midline carcinoma.
OBJECTIVE
NUT midline carcinoma (NMC) is a poorly differentiated squamous cancer characterized by rearrangement of the NUT gene. Research advances have provided opportunities for targeted therapy in NMC, yet the clinical features of this rare disease have not been systematically characterized. We report on a large population of such patients to identify the disease characteristics and treatments, correlate them with outcome, and to consider clinical recommendations.


METHODS
A clinical database was established using retrospective demographic and outcomes data available on all known cases of NMC. Questionnaires were completed by treating physicians. Pathologic, demographic, and clinical variables were assessed for 63 patients, the largest cohort of patients with NMC studied to date. Outcome data from 54 patients were available for survival analyses.


RESULTS
The diagnosis of NMC has increased annually since 2007. Since 2009, there has been an observed increase in the age at diagnosis (P < 0.05). Geographic distribution of patients with NMC has been concentrated in the United States (n = 41, 65%). The median overall survival for patients with NMC was 6.7 months. The 2-year progression-free survival (PFS) was 9% with a 95% confidence interval (CI) of 1% to 17% [1-year PFS 15% (5-24%) and 2-year overall survival (OS) was 19% with a 95% CI of 7%-31% (1-year OS: 30% (27-34%)]. Multivariate analysis suggested that extent of surgical resection and initial radiotherapy were independent predictors of PFS and OS. Notably, no chemotherapeutic regimen was associated with improved outcome.


CONCLUSIONS
NMC portends a poor prognosis among all squamous cell neoplasms and seems to be frequently unrecognized. The finding that conventional chemotherapy has been inadequate indicates a pressing need for the development of targeted therapeutics. Intensive local therapies such as gross total resection and radiotherapy might be associated with enhanced survival.
Department of Pediatric Oncology, Dana-Farber Cancer Institute, and Division of Hematology/Oncology, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA.
Daniel E
DE
Bauer
Chelsey M
CM
Mitchell
Kelly M
KM
Strait
Christopher S
CS
Lathan
Edward B
EB
Stelow
Sonja C
SC
Lüer
Somala
S
Muhammed
Andrew G
AG
Evans
Lynette M
LM
Sholl
Juan
J
Rosai
Eugenia
E
Giraldi
Richard P
RP
Oakley
Carlos
C
Rodriguez-Galindo
Wendy B
WB
London
Stephen E
SE
Sallan
James E
JE
Bradner
Christopher A
CA
French
D000293:Adolescent; D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics / Q000473:pathology / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins; D009687:Nuclear Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
C000630260:NUTM1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins