NUT midline carcinoma is a very rare and aggressive malignancy genetically defined by rearrangements of the NUT gene. In most cases (75%), the NUT gene on chromosome 15q14 is fused with the BRD4 gene on chromosome 19p13, creating chimeric genes that encode the BRD-NUT fusion proteins. In the remaining cases, NUT is fused to BRD3 on chromosome 9q34 or to NSD3 on chromosome 8p11; these tumors are termed NUT-variant.
Childhood midline tract carcinomas (NUT midline carcinomas) arise in midline epithelial structures, typically the mediastinum and upper aerodigestive tract, and present as very aggressive, undifferentiated carcinomas, with or without squamous differentiation.[1,2] Although the original description of this neoplasm was made in children and young adults, individuals of all ages can be affected. A retrospective series with clinicopathological correlation found that the median age at diagnosis of 54 patients was 16 years (range, 0.1–78 years).
Cancer in children and adolescents is rare, although the overall incidence has been slowly increasing since 1975. Referral to medical centers with multidisciplinary teams of cancer specialists experienced in treating cancers that occur in childhood and adolescence should be considered. This multidisciplinary team approach incorporates the skills of the following health care professionals and others to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life:
(Refer to the PDQ Supportive and Palliative Care summaries for specific information about supportive care for children and adolescents with cancer.)
The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer. At these pediatric cancer centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with current standard therapy. Most of the progress made in identifying curative therapy for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.
Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2010, childhood cancer mortality decreased by more than 50%. Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. (Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.)
Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years. The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 people. Therefore, all pediatric cancers are considered rare.
The designation of a rare tumor is not uniform among pediatric and adult groups. In adults, rare cancers are defined as those with an annual incidence of fewer than six cases per 100,000 people. They account for up to 24% of all cancers diagnosed in the European Union and about 20% of all cancers diagnosed in the United States.[5,6] Also, the designation of a pediatric rare tumor is not uniform among international groups, as follows:
Most cancers in subgroup XI are either melanomas or thyroid cancer, with other types accounting for only 1.3% of cancers in children aged 0 to 14 years and 5.3% of cancers in adolescents aged 15 to 19 years.
These rare cancers are extremely challenging to study because of the low number of patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the lack of clinical trials for adolescents with rare cancers.
Information about these tumors may also be found in sources relevant to adults with cancer.
Treatment options for childhood midline tract carcinoma include the following:
Treatment of childhood midline tract carcinoma involving the NUT gene (NUT midline carcinoma) has included a multimodal approach with systemic chemotherapy, surgery, and radiation therapy. Cisplatin, taxanes, and alkylating agents have been used with some success; while early response is common, tumor progression occurs early in the course of the disease.; [Level of evidence: 3iiiB] In a report from the NUT Midline Carcinoma Registry, 40 patients with primary tumors in the head and neck were evaluable. The 2-year overall survival rate was 30%. The three long-term survivors (35, 72, and 78 months) underwent primary gross-total resection and received adjuvant therapy.; [Level of evidence: 3iiA]
Because of the presence of the NUT-BRD4 gene fusion in NUT midline carcinomas, there has been great interest in evaluating BET bromodomain inhibitors for adults and children with this malignancy. Unfortunately, activity for this class of agents has been limited in reported clinical trials:
Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, refer to the ClinicalTrials.gov website.
The following are examples of national and/or institutional clinical trials that are currently being conducted:
Patients with tumors that have molecular variants addressed by treatment arms included in the trial will be offered treatment on Pediatric MATCH. Additional information can be obtained on the NCI website and ClinicalTrials.gov website.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Editorial changes were made to this summary.
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Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood midline tract carcinoma involving the NUT gene (NUT midline carcinoma). It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Childhood Midline Tract Carcinoma Involving the NUT Gene (NUT Midline Carcinoma) Treatment are:
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Levels of Evidence
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PDQ® Pediatric Treatment Editorial Board. PDQ Childhood Midline Tract Carcinoma Involving the NUT Gene (NUT Midline Carcinoma) Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/midline/hp-child-midline-tract-carcinoma-treatment-pdq. Accessed <MM/DD/YYYY>.
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Last Revised: 2022-02-25
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