xRead - Nasal Obstruction (September 2024) Full Articles

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KUANetal.

TABLE XXIV.D.2 Evidence surrounding impact of cutaneous melanoma markers and genetic mutations.

Clinical endpoints

Study

Year LOE Study design Study groups

Conclusion

1. BRAF (32%) most common mutation; KIT and RAS next most common 2. 28% had evidence of UV damage versus 90% in cutaneous melanoma 3. Nine out of 11 (82%) patients with high mitotic rate had pathologic mutation 1. Mutation status was not correlated with survival 2. 40% of cases with identifiable mutation 3. NRAS (30%) most common mutation, then BRAF (8%) and KIT (5%) (in contrast to 1. NRAS (22%) and KIT (13%)most common 2. Amplification of RREB1 (100%) and loss of MYB (765) in many cases 3. KIT expression (97%) 4. MAPK and PI3K/Akt pathway activated in all cases (100%) 5. No mutational profile associated with survival difference 1. No difference in OS based on mutation 2. NRAS (14%) most common mutation, followed by BRAF and KIT (4%each) 3. More likely to have mutation ( NRAS , KIT , or BRAF ) in paranasal sinus primary 4. Worse survival in paranasal sinus primary cutaneous melanoma where BRAF mutation is present 50%–70% of cases)

1. Mutational profile 2. DNA damage analysis for UV radiation

Colombino and Paliogiannis 122

2019 4

Retrospective case series

SNMM patients with tissue available for 25-gene panel ( n = 25)

induced damage 3. Genetic

mutation correlation withhigh mitotic rate

Amit et al. 1520

2017 4

Retrospective case series

SNMM patients with tissue available for genomic DNA extraction ( n = 66)

1. OS 2. Mutation status

Turri-Zanoni et al. 123

1. Mutational profile 2. OSby mutation

2013 4

Retrospective case series

SNMM patients with tissue available for

IHC, FISH, and DNA sequencing ( n = 32)

Zebary et al. 124

2013 4

Retrospective case series

SNMM patients with tissue available for mutation screening ( n = 56)

1. OSby

mutation 2. Mutational profileby primary site 3. OSby primary site

Abbreviations: OS, overall survival; SNMM, sinonasal mucosal melanoma.

in the mucosal melanoma tumor microenvironment is both a prognostic and predictive biomarker. 1543,1544 PD-L1 expression in the tumor microenvironment is present in 44% of mucosal melanomas, which is slightly higher than that of cutaneous melanomas. Pembrolizumab and nivolumab are targeted mono clonal antibodies that bind and block PD-1 on lympho cytes, thus preventing binding of PD-L1 ligands, subse quently preventing deactivation of the immune response.

The end effect is increased immune system activation and destruction of tumor cells. 1545 These agents were approved in 2014 for use in patients with metastatic or unresectable cutaneous melanoma after demonstrating an improve ment in OS. 1546–1548 Subsequent studies have increased the indications for these agents to include nonsmall-cell lung cancer, recurrent head and neck squamous cell car cinoma, renal cell cancer, and others. 1549–1552 Given the efficacy in cutaneous melanoma, there has been recent