xRead - Nasal Obstruction (September 2024) Full Articles

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ICAR SINONASAL TUMORS

Bimodality and trimodality treatments confer an oncological advantage over single-modality therapy (Table XXIV.B.1). Most, but not all, studies found that trimodality therapy was superior to bimodality. There are sufficient data to support the use of neoadjuvant chemotherapy response as a guide for treatment. Patients who respond to neoadjuvant chemotherapy followed by definitive chemoradiation appear to do particularly well. Elective treatment of the neck with either surgery and/or radiation is recommended for T3–4 disease. A radiation dose greater than 60 Gy is optimal. Treatment of SNUC

partly due to the higher use of cytogenetic analysis in this age group. Patients typically present with nonspe cific complaints of nasal obstruction, epistaxis, orbital symptoms, and pain. 1418 The disease occurs in slightly more female than male patients. 1418,1420 On imaging, the tumor appears as an aggressive, infiltrating mass, often with orbital and dural invasion. MRI shows hypointensity on T1 and heterogeneity on T2. 1192 Bony hyperostosis has been described. Histological evaluation typically reveals nests of tumor cells in the submucosa without surface epithelial involve ment. The hallmarks of NUT carcinoma are lack of pleomorphism, monotonous primitive round cells, and areas of abrupt keratinization. 1419 These tumors harbor a characteristic translocation involving NUTM1 onchromo some 15q14.6 with the bromodomain-containing protein 4 ( BRD4 ) gene on 19p13.1. 1421 BRD4::NUTM1 gene rearrange ment identified with FISH is considered the gold standard for diagnosis. 1422 Alternatively, NUT nuclear immunohis tochemical stain can be used and has a reported sensi tivity and specificity, respectively, of 100% and 87%. 1419 Patients with non- BRD4::NUTM1 fusions (BRD3- or NSD3 NUTM1) have significantly better survival than those with BRD4::NUTM1 fusions, independent of metastatic disease extent at presentation. 1423 NUT carcinomas are among the most aggressive tumors of the sinonasal tract. The NUT carcinoma registry (www. nmcregistry.org) is a central repository for cases and has contributed to studies that assisted with NUT carcinoma being considered a unique entity by the WHO. 17,1068 This registry was used for the largest series, which included 29 cases. 1420 Half of the patients with this disease have locoregional or distant metastases at diagnosis. 1420,1424 Due to the small number of reported cases, treatment data are limited. The single published cohort study reported a survival benefit in patients who underwent surgery with adjuvant CRT rather than definitive CRT. 1420 Notably, sur gical resection with negative resection margins conferred a 2-year OS of 80%, superior than resection with pos itive margins or debulking. A sample of patients who underwent neoadjuvant chemotherapy appears to have better OS outcomes than previously reported cohorts, but comparative analysis was restricted by sample size. 1425 One recent case described a short-lived response with a regimen for Ewing sarcoma (i.e., vincristine, cyclophos phamide, and doxorubicin). 1426 However, platinum com pounds are the most commonly used chemotherapeutic agents. 1420 BET bromodomain inhibitors, which target the BRD4 portion of BRD4::NUTM1 , demonstrated promise in a xenograft model, and clinical trials are currently ongoing (e.g., NCT03936465). 1427,1428 Nevertheless, NUT carcinoma is almost uniformly fatal. The median survival is 5–13 months. 1420,1424,1425

Aggregate grade of evidence

B (Level 2: three studies; Level 3: six studies; Level 4: 24 studies) Bimodality, and more so trimodality, therapy is beneficial over single modality. Elective neck treatment is associated with lower regional recurrence rates, most commonly with levels I-III. Single-modality treatment yields poorer OS and RFS. Greater regional recurrence rates occur in patients without elective neck treatment. Not evaluated in current studies. Preponderance of benefits over harms. While early studies suggested the greatest benefit was associated with surgery with adjuvant therapy, more recent studies have supported trimodality treatment or neoadjuvant chemotherapy followed by CRT in responders, especially in patients who cannot be resected with negative margins or without significant morbidity.

Benefit

Harm

Cost

Benefits–harm assessment

Value

judgments

Policy level Recommendation. Intervention Multimodal treatment with elective neck

treatment for SNUC is recommended. Neoadjuvant chemotherapy response as a guide for treatment can be considered.

2 NUT carcinoma NUT carcinoma represents 1%–2% of SNM (Table XXIV.B.2). 1417,1418 The disease is named for its characteristic translocation of the nuclear protein on the testis (NUTM1). The previous name, NUT midline carci noma, was changed because the tumor is not restricted to midline structures. NUT carcinoma can also occur in the lungs, salivary gland, pancreas, genitourinary structures, bone, and soft tissues. 1419 It predominantly affects teens and young adults, aged 10–30 years, although this be