Childhood nuclear protein of the testis (NUT) carcinomas (also known as midline tract carcinomas) arise in midline epithelial structures, typically the mediastinum and upper aerodigestive tract. These tumors present as very aggressive, undifferentiated carcinomas, with or without squamous differentiation.[1,2]
Although the original description of this neoplasm was reported in children and young adults, individuals of all ages can be affected.[3] A retrospective series with clinicopathological correlation of 54 patients found that the median age at diagnosis was 16 years (range, 0.1–78 years).[4] One study identified 11 patients younger than 18 years with NUT carcinoma in a German registry.[5] The median age was 13.2 years (range, 6.6–17.8 years). Thoracic and mediastinal tumors were found to be the primary site in six patients, head and neck tumors were the primary site in four patients, and one patient had a multifocal tumor with an unknown primary. All patients presented with regional lymph node involvement, and eight patients (72.7%) had distant metastases. Despite treatment with multiple therapies, the median event-free survival was 1.5 months, and the overall survival was 6.5 months.
NUT carcinoma is a very rare and aggressive malignancy that is genetically defined by rearrangements of the NUTM1 gene. In most cases (75%), the NUTM1 gene on chromosome 15q14 is fused with the BRD4 gene on chromosome 19p13, creating chimeric genes that encode BRD4::NUT fusion proteins. In the remaining cases, NUTM1 is fused to other partners, most commonly BRD3 on chromosome 9q34 or NSD3 on chromosome 8p11.[1]
The outcomes of patients with NUT carcinomas are very poor, with a median survival of less than 1 year. Preliminary studies suggested that patients with NUT carcinomas without the typical BRD4::NUTM1 fusion gene may have a better prognosis than patients with other NUT carcinomas.[1,2] A retrospective analysis of 124 patients (including 47 patients younger than 18 years) reported that NUT carcinomas could be divided into three risk groups based on the anatomical location and specific NUTM1 fusion partner. The group with the best prognosis (median overall survival, 36.5 months) consisted of 12 patients (9.7%) with nonthoracic primary tumors and NUTM1 fusions with genes other than BRD4.[3]
Cancer in children and adolescents is rare, although the overall incidence has slowly increased since 1975.[1] Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the following pediatric specialists and others to ensure that children receive treatment, supportive care, and rehabilitation to achieve optimal survival and quality of life:
For specific information about supportive care for children and adolescents with cancer, see the summaries on Supportive and Palliative Care.
The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of children and adolescents with cancer.[2] At these 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. Other types of clinical trials test novel therapies when there is no standard therapy for a cancer diagnosis. Most of the progress in identifying curative therapies 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 2020, childhood cancer mortality decreased by more than 50%.[3-5] Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. For information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors, see Late Effects of Treatment for Childhood Cancer.
Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[6] The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 people in the United States. 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.[7,8] In children and adolescents, the designation of a rare tumor is not uniform among international groups, as follows:
Most cancers in subgroup XI are either melanomas or thyroid cancers, with other cancer types accounting for only 2% of the cancers diagnosed in children aged 0 to 14 years and 9.3% of the cancers diagnosed in adolescents aged 15 to 19 years.
These rare cancers are extremely challenging to study because of the relatively few patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the small number 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 NUT carcinoma include the following:
Treatment of childhood NUT carcinoma includes a multimodal approach with systemic chemotherapy, surgery, and radiation therapy. Cisplatin, taxanes, and alkylating agents have been used with some success. While early response to these agents is common, tumor progression occurs early in the course of the disease.[1]; [2][Level of evidence C1]
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 (with survivals of 35, 72, and 78 months) underwent primary gross-total resection and received adjuvant therapy.[3]; [4][Level of evidence C1]
Because of the presence of the BRD4::NUTM1 gene fusion in NUT carcinomas, there has been increased interest in evaluating BET bromodomain inhibitors for adults and children with this malignancy.[5] 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, see the ClinicalTrials.gov website.
The following are examples of national and/or institutional clinical trials that are currently being conducted:
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This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood NUT 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.
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 NUT Carcinoma Treatment are:
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The preferred citation for this PDQ summary is:
PDQ® Pediatric Treatment Editorial Board. PDQ Childhood NUT 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>. [PMID: 29337479]
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