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      Supraglottic NUT Carcinoma: A Case Report and Literature Review

      case-report

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          Abstract

          Nuclear protein of the testis (NUT) carcinoma is a very rare cancer that occurs in relatively young patients. In this study, we experienced a case of laryngeal NUT carcinoma that followed a rapid course. A 22-year-old woman was diagnosed with supraglottic squamous cell carcinoma, cT3N2bM0. She underwent chemoradiotherapy (CRT) (total dose, 70 Gy; 2 Gy × 35 Fr; 80 mg/m<sup>2</sup> every 3 weeks with CDDP) as a curative treatment and achieved a complete response. However, 3 weeks after the completion of CRT, she presented to the outpatient clinic complaining of abdominal pain. Magnetic resonance imaging revealed a huge neoplastic lesion in the right ovary. Abdominal right adnexal resection plus partial retreatment was performed. The pathology of ovarian tumor was poorly differentiated squamous cell carcinoma, and NUT protein was positive. The laryngeal carcinoma was also positive for NUT protein; therefore, we diagnosed ovarian tumor is metastasis from supraglottic carcinoma. Peritoneal dissemination was observed in the early postoperative period. She was refractory to subsequent chemotherapy and had a rapid progression. Subsequently, CT showed further thickening of the peritoneum, increased ascites, and increased metastases. She died 32 weeks after initial diagnosis and 14 weeks after abdominal surgery. NUT carcinoma is difficult to diagnose without suspicion. Therefore, the possibility of NUT carcinoma should be considered in young patients with laryngeal carcinoma.

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          Most cited references14

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          Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients.

          Our previous individual patient data (IPD) meta-analysis showed that chemotherapy improved survival in patients curatively treated for non-metastatic head and neck squamous cell carcinoma (HNSCC), with a higher benefit with concomitant chemotherapy. However the heterogeneity of the results limited the conclusions and prompted us to confirm the results on a more complete database by adding the randomised trials conducted between 1994 and 2000. The updated IPD meta-analysis included trials comparing loco-regional treatment to loco-regional treatment+chemotherapy in HNSCC patients and conducted between 1965 and 2000. The log-rank-test, stratified by trial, was used to compare treatments. The hazard ratios of death were calculated. Twenty-four new trials, most of them of concomitant chemotherapy, were included with a total of 87 trials and 16,485 patients. The hazard ratio of death was 0.88 (p<0.0001) with an absolute benefit for chemotherapy of 4.5% at 5 years, and a significant interaction (p<0.0001) between chemotherapy timing (adjuvant, induction or concomitant) and treatment. Both direct (6 trials) and indirect comparisons showed a more pronounced benefit of the concomitant chemotherapy as compared to induction chemotherapy. For the 50 concomitant trials, the hazard ratio was 0.81 (p<0.0001) and the absolute benefit 6.5% at 5 years. There was a decreasing effect of chemotherapy with age (p=0.003, test for trend). The benefit of concomitant chemotherapy was confirmed and was greater than the benefit of induction chemotherapy.
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            Phase 1 Study of Molibresib (GSK525762), a Bromodomain and Extra-Terminal Domain Protein Inhibitor, in NUT Carcinoma and Other Solid Tumors

            Abstract Background Bromodomain and extra-terminal domain proteins are promising epigenetic anticancer drug targets. This first-in-human study evaluated the safety, recommended phase II dose, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of the bromodomain and extra-terminal domain inhibitor molibresib (GSK525762) in patients with nuclear protein in testis (NUT) carcinoma (NC) and other solid tumors. Methods This was a phase I and II, open-label, dose-escalation study. Molibresib was administered orally once daily. Single-patient dose escalation (from 2 mg/d) was conducted until the first instance of grade 2 or higher drug-related toxicity, followed by a 3 + 3 design. Pharmacokinetic parameters were obtained during weeks 1 and 3. Circulating monocyte chemoattractant protein-1 levels were measured as a pharmacodynamic biomarker. Results Sixty-five patients received molibresib. During dose escalation, 11% experienced dose-limiting toxicities, including six instances of grade 4 thrombocytopenia, all with molibresib 60–100 mg. The most frequent treatment-related adverse events of any grade were thrombocytopenia (51%) and gastrointestinal events, including nausea, vomiting, diarrhea, decreased appetite, and dysgeusia (22%–42%), anemia (22%), and fatigue (20%). Molibresib demonstrated an acceptable safety profile up to 100 mg; 80 mg once daily was selected as the recommended phase II dose. Following single and repeat dosing, molibresib showed rapid absorption and elimination (maximum plasma concentration: 2 hours; t1/2: 3–7 hours). Dose-dependent reductions in circulating monocyte chemoattractant protein-1 levels were observed. Among 19 patients with NC, four achieved either confirmed or unconfirmed partial response, eight had stable disease as best response, and four were progression-free for more than 6 months. Conclusions Once-daily molibresib was tolerated at doses demonstrating target engagement. Preliminary data indicate proof-of-concept in NC.
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              Distant metastases in head and neck cancer.

              Most trials in head and neck cancer emphasize locoregional control, as this is the main pattern of therapy failure. However, up to 15% of patients develop distant metastases. The purpose of this study was to present the investigated factors associated with distant metastasis in a single-center patient cohort.
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                Author and article information

                Journal
                Case Rep Oncol
                Case Rep Oncol
                CRO
                Case Reports in Oncology
                S. Karger AG (Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH–4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.com )
                1662-6575
                Sep-Dec 2022
                8 November 2022
                8 November 2022
                : 15
                : 3
                : 980-987
                Affiliations
                [1] aDepartment of Otorhinolaryngology, Head and Neck Surgery, Osaka Medial and Pharmaceutical University, Takatsuki City, Osaka, Japan
                [2] bDepartment of Pathology, Osaka Medial and Pharmaceutical University, Takatsuki City, Osaka, Japan
                Author notes
                Article
                cro-0015-0980
                10.1159/000526815
                9830291
                36636674
                a9e038c4-4cdc-41ef-a8b6-95ae84ac57e8
                Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial-4.0 International License (CC BY-NC) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes requires written permission.

                History
                : 27 July 2022
                : 22 August 2022
                : 2022
                Page count
                Figures: 4, References: 15, Pages: 8
                Funding
                There is no funding.
                Categories
                Case Report

                Oncology & Radiotherapy
                nut carcinoma,larynx,ovarian metastasis
                Oncology & Radiotherapy
                nut carcinoma, larynx, ovarian metastasis

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