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Tumor Discovery Expert consensus of NUT carcinoma

Some studies suggest an association between chemotherapy At present, no prospective randomized controlled
and improved survival rates, but consensus has not trials demonstrate induction chemotherapy’s effectiveness
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been reached on the optimal chemotherapy regimen and in improving survival outcomes for NUT carcinoma.
timing. Relying solely on chemotherapy is often ineffective For operable NUT carcinoma patients undergoing
in controlling the progression of NUT carcinoma. induction chemotherapy, close monitoring of tumor
size is necessary to prevent rapid progression and loss of
At present, the effective chemotherapy regimens used for
achieving some degree of relief in multimodal treatments surgical opportunities. For inoperable NUT carcinoma,
a comprehensive treatment model combining induction
– combined with surgery, radiotherapy, and targeted chemotherapy with radiotherapy may be considered.
therapy – are primarily based on anthracyclines, alkylating However, no prospective randomized controlled trials
agents, and platinum compounds. 69,70 In a cohort study of have demonstrated that adjuvant chemotherapy improves
118 NUT carcinoma patients, the objective response rate survival in NUT carcinoma after radiotherapy. Given
with chemotherapy, including IFO, was 75%, compared the high recurrence rate of NUT carcinoma, traditional
to only 31% with platinum compounds; however, both treatment (surgery, radiotherapy, and chemotherapy)
regimens showed no difference in OS and PFS. Some generally only temporarily controls disease progression.
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reported cases suggest that patients achieved favorable It is, therefore, recommended to consider appropriate
outcomes using high-dose etoposide+doxorubicin+IFO systemic treatments after concurrent chemoradiotherapy
(VAI) and cisplatin+doxorubicin+IFO (PAI) as part of or radiotherapy, depending on factors such as the patient’s
the Scandinavian Sarcoma Group IX (SSG IX) protocol overall condition. Considering chemotherapy’s toxicity, a
for sarcoma. 72,73 For example, a patient with BRD3::NUT pre-chemotherapy assessment and consideration of the
head-and-neck NUT carcinoma (stage T4bN0M0) cumulative chemotherapy dose is necessary to reduce both
achieved partial response (PR) after alternating treatment acute and long-term side effects. Effective chemotherapy
with VAI and PAI, followed by radiotherapy and a total of regimens for NUT carcinoma remain limited, and clinical
4 cycles of chemotherapy. On resection, no residual cancer trials for rare disease chemotherapy regimens should
was found, indicating a pathological complete response. be prioritized to identify potentially effective first-line
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Another patient with a vast mediastinal mass showed treatments.
tumor shrinkage after one cycle of EP and the SSG IX
regimen, but the tumor progressed again after 1 month. (a) Recommendation 6
Clinicians may consider selecting chemotherapy drugs
Despite subsequent treatments with radiotherapy, primarily based on IFO or platinum-based agents or
anlotinib, bevacizumab, paclitaxel chemotherapy, and combining them with chemotherapy regimens used for
pembrolizumab immunotherapy, the patient passed away other types of malignancies in corresponding anatomical
4.7 months after diagnosis. Among these treatments, sites of NUT carcinoma (level of evidence: level 4;
only radiotherapy, the EP regimen, and the SSG IX recommendation grade: strongly recommended). High-
chemotherapy regimen alleviated the patient’s pain and throughput sequencing can be considered to identify
temporarily controlled tumor progression. Two pediatric potentially sensitive personalized drug regimens (level of
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patients with head-and-neck NUT carcinoma maintained evidence: level 5; recommendation grade: recommended).
tumor remission for at least 6 years and 8 months, For inoperable NUT carcinoma, a comprehensive
respectively, after receiving three cycles of SSG IX treatment model combining induction chemotherapy with
chemotherapy regimen, along with surgical resection and radiotherapy should be considered (level of evidence: level 4;
radiotherapy. At present, the most effective chemotherapy recommendation grade: strongly recommended). Specific
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regimens reported for NUT carcinoma are those related chemotherapy regimens should be evaluated based on the
to sarcoma treatment protocols. However, there are patient’s condition after concurrent chemoradiotherapy
relatively few documented cases of effective chemotherapy (level of evidence: level 4; recommendation grade: strongly
specifically for NUT carcinoma, warranting further recommended).
exploration. It is recommended that chemotherapy drugs
be selected based on anthracyclines, alkylating agents, and 4.8.4. Immunotherapy
platinum compounds in combination with chemotherapy The NUT carcinoma is driven by the fusion of the NUT
regimens for other types of malignancies in corresponding oncogenic protein, which is typically associated with
anatomical sites of NUT carcinoma. In addition, patients a low tumor mutation burden, and the tumor is often
should actively consider high-throughput sequencing insensitive to immunotherapy. Only a subset of NUT
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to help identify potentially sensitive personalized drug carcinoma patients expresses programmed cell death
therapy regimens. ligand 1 (PD-L1). Aside from a few reported cases, there

Volume 3 Issue 4 (2024) 20 doi: 10.36922/td.4904