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Tumor Discovery Expert consensus of NUT carcinoma

fusion partners, including inhibiting DNA binding post-operative TNM staging, pathological findings,
with BET inhibitors or modifying downstream histones surgical resection margins (R0, R1, and R2), and post-
with HDAC inhibitors to disrupt the function of fusion operative lymph node involvement to determine the need
partners. NUT carcinoma is a newly classified tumor for post-operative adjuvant therapy. Surgical treatment
by the WHO, and awareness of it remains limited remains a viable option for patients with localized tumor
globally. At present, most treatment evidence for NUT recurrence, which provided that they are still deemed
carcinoma comes from retrospective analyses and case suitable for surgery. For patients unsuitable for surgery,
reports, with relatively less evidence from treatment- alternative treatment modalities such as radiotherapy
related studies in NUT carcinoma patients. Moreover, and systemic treatment (e.g., chemotherapy and targeted
given that NUT carcinoma can arise in various organs, therapy) may be considered.
treatment guidelines for other tumors in affected Relying solely on chemotherapy is unlikely to result in a
locations may be adopted for NUT carcinoma. Based favorable prognosis. In cases where NUT carcinoma lesions
on relevant literature, clinical experience with NUT are localized without distant metastasis, comprehensive
carcinoma, and expert opinions, this consensus refers surgical resection should be actively considered, as it can
to guidelines for other tumors in the specific locations lead to a better prognosis when followed by radiotherapy
affected by NUT carcinoma. It summarizes the principles and chemotherapy. Some studies on head and neck NUT
for treating NUT carcinoma (Figure 5). Patients with carcinoma suggest that prophylactic cervical lymph node
NUT carcinoma who are candidates for surgery should dissection should be considered even in the absence of
undergo the procedure.
lymph node metastasis (N0). Patients with head-and-
1
For patients unsuitable for surgery or require adjuvant neck NUT carcinoma who undergo surgical resection
therapy post-surgery, other treatment modalities, such as followed by radiotherapy tend to experience longer OS
radiotherapy and systemic therapies (e.g., chemotherapy and progression-free survival (PFS). In head-and-neck
and targeted therapy), can be considered based on the NUT carcinoma, the extent of surgical resection, the
patient’s condition. Considering the rapid progression achievement of negative margins, and the response to
and high malignancy of NUT carcinoma, particularly initial treatment are all significantly associated with better
in cases with poor prognosis, such as those carrying the PFS and OS. For instance, patients who underwent surgery
BRD4::NUTM1 fusion gene, participation in clinical trials had a 2-year OS rate of 50%, compared to just 7% for those
is strongly recommended. Maintenance therapy based on who did not (p=0.003). The degree of surgical resection
prior treatments can continue if lesions stabilize following also correlated with PFS and OS in a graded manner:
initial treatment. In cases of disease progression, potential patients with negative margins had a 2-year OS of 80%,
drugs should be selected based on high-throughput those with gross total resection but positive margins had
sequencing results, with treatment plans tailored to the a 2-year OS of 44%, and those who underwent debulking
patient’s previous treatment history. If necessary, MDT had a 2-year OS of 37%. 30,56 However, these findings
consultations can guide further diagnosis and treatment. require further validation through prospective research.
56
We encourage patients to participate in prospective Palliative surgical debulking may also be an option to
clinical trials and explore potential new treatment improve quality of life. 63
options.
In addition, collaboration among multidisciplinary
4.8.1. Surgery surgical teams may be crucial due to the aggressive nature
of NUT carcinoma, mainly when it affects multiple
Surgery plays a pivotal role in the comprehensive anatomical regions. Following surgery, proactive planning
management of NUT carcinoma. Surgical strategies should should include radiotherapy for the primary tumor site
be developed based on the patient’s overall health, the
extent of tumor invasion, tumor staging, and the feasibility and affected lymph nodes, along with timely systemic
12,56
of resection, which can be assessed through enhanced treatment.
CT or MRI evaluation. Surgery is the primary curative (a) Recommendation 4
method for NUT carcinoma, with surgical techniques Patients with resectable NUT carcinoma should
often adapted from protocols used for similar cancers undergo curative surgery as the primary treatment as
in specific anatomical sites. Before surgery, a specialized early as possible. Post-operative adjuvant therapy should
medical team should evaluate or discuss in an MDT be determined based on pre-operative and post-operative
meeting whether NUT carcinoma patients should undergo TNM staging, pathological conditions, surgical margins
neoadjuvant therapy. Patients eligible for direct surgical (R0, R1, and R2), and post-operative lymph node status
excision should be assessed based on pre-operative and (level of evidence: level 3; recommendation grade: strongly

Volume 3 Issue 4 (2024) 17 doi: 10.36922/td.4904