Clinical features, treatment, and survival outcome of primary pulmonary NUT midline carcinoma

Abstract

Objective: NUT midline carcinoma (NMC), a rare type of squamous cell carcinoma, is genetically characterised by NUT midline carcinoma family member 1 (NUTM1) gene rearrangement. NMC can arise from the lungs; however, there is no standard for the management of primary pulmonary NMC. This study aimed to confirm the clinical features and report the treatments, especially with immune checkpoint inhibitors (ICIs), and outcomes of patients with primary pulmonary NMC. Methods: A retrospective review of patients with primary pulmonary NMC was performed in the First Affiliated Hospital of Guangzhou Medical University between January 2015 and December 2018. Clinical manifestations as well as radiographic and pathological findings were recorded. Whole-exome sequencing (WES), a predictor for ICI response, was used to determine the tumour mutational burden (TMB). Treatments, especially by immune checkpoint blockade, and patient survival were analysed.Results: Seven patients with primary pulmonary mass (four men and three women) with a mean age of 42 years (range, 23–74) who were diagnosed with NMC according to NUT immunohistochemistry staining were included for analysis. One patient had a rare fusion of CHRM5-NUTM1 by tumour sequencing. A wide range of TMB (1.75–73.81 mutations/Mbp) was observed. The initial treatments included chemotherapy (5/7, 71.4%), surgery (1/7, 14.3%), and radiotherapy (1/7, 14.3%). Five patients (5/7, 71.4%) received ICIs (programmed cell death protein 1 [PD1]/programmed cell death ligand 1 [PDL1] monoclonal antibody) as second- or higher-line treatments. The median overall survival (OS) was 4.1 months (range, 1.5–26.7 months). Conclusions: Patients with primary pulmonary NMC have a poor prognosis and chemotherapy is often preferred. Checkpoint immunotherapy is a good option as the second- or higher-line treatment. TMB seems to be not associated with OS.

Primary pulmonary NUT midline carcinoma and its diagnostic challenges: A case report

“…A retrospective review reported seven cases of primary pulmonary NMC between 2015 and 2018. 17 Similar to the reported cases in that cohort, our patient also presented with a primary tumor in the lung. The gender and age of our patient are consistent with the demographics of that series, which showed an age range of 23-74 years and consisted of both males and females.…”

“…9 However, the median survival within this retrospective review of patients with lung masses was 2.75 months, suggesting that, despite receiving multiple treatments, primary pulmonary NMC may be more aggressive than NMC located at other sites. 17 Unfortunately, our patient survived only five months following initial presentation.…”

“…Surgical resection and radiotherapy may be successful treatments for prolonging patient survival. 17 Yet, advanced disease progression can hinder clinical management and lead to a grave prognosis.…”

Case report: Immunovirotherapy as a novel add-on treatment in a patient with thoracic NUT carcinoma

“…In another case series of five NC patients treated with ICIs, the response rate to immunotherapy could be improved by previous radiation therapy, whereas one patient with high TMB did not respond to immunotherapy (12). A further case analysis of twelve patients also supported the hypothesis that radiotherapy followed by immunotherapy results in beneficial outcomes.…”

“…However, ifosfamide-based regimens and additional radiation therapy have shown some promising results, with published cases of some very rare partial or complete responses in non-thoracic NC (6,(8)(9)(10)(11). The combination of carboplatin and paclitaxel is frequently used in thoracic NC, but with only limited success and progression free survival rates below 3 months (12)(13)(14).…”