Melanoma

Info

🌱 來自: Huppert’s Notes

Melanoma🚧 施工中

Melanoma

•   Epidemiology: 5th most common cancer in the United States. Risk factors: Older age, sun exposure, fair complexion, red/blonde hair, high nevi count, immunosuppression.

•   Clinical features: Atypical mole – ABCDE criteria (Asymmetry, irregular Border, Color variation, Diameter ≥6 mm, Evolution)

•   Diagnosis: Biopsy. Depth of invasion determines stage.

•   Treatment:

-   Treatment depends on the stage:

•   Stage I/II: Wide local excision and sentinel lymph node biopsy is usually sufficient

•   Stage III: Surgery followed by adjuvant immunotherapy for 1 yr to reduce the risk of recurrence

•   Stage IV (metastatic): Recommend immunotherapy

-   Systemic therapy options:

•   Immunotherapy: Anti-PD1 monotherapy (pembrolizumab or nivolumab) vs. anti-PD1/anti-CTLA4 combination therapy (niviolumab + ipilimumab)

•   Targeted therapy: BRAF inhibitor (vemurafenib, dabrafenib, encorafenib) + MEK inhibitor (cobimetinib, trametinib, binimetinib) if patient has BRAF V600E mutation

-   Radiation: Can be used to treat symptomatic localized area of disease (e.g., brain metastases)

Clinical presentation and workup

(NCCN Guidelines v1.2022) • Suspicious skin lesion (ABCDE: asymm, border, color, diameter >6 mm, evolution) → bx • Staging: I & II = no regional/distant mets. III = regional LN ⊕ or in-transit/satellite mets. Ulceration & thickness confer substage within I–III. IV = distant mets. • Prognosis: excellent if localized dis., ≤1 mm thickness. Varies widely stage IIIA–IIID based on nodal burden (5yr OS 20–70%; ulceration, mitotic rate, & invasion depth predictive). • Molecular diagnostics: check for BRAF V600E (present in ~50% of melanomas)

Treatment

(NCCN Guidelines v1.2022; NEJM 2021;384:2229) • Wide surgical excision + sentinel node mapping (unless in situ or low risk of node ⊕). If sentinel node ⊕, nodal dissection vs. observation. No difference in survival w/ observation (Lancet Oncol 2016;17:757, NEJM 2017;376:2211). • Checkpoint inhibitors (CPI = pembrolizumab, nivolumab, nivolumab/ipilimumab) • BRAF/MEK inhibitors (dabrafenib/trametinib, vemurafenib/cobimetinib, encorafenib/binimetinib) if activating BRAF V600E mutation present • Adjuvant for high-risk node ⊕ disease: CPI (↑ RFS, Lancet Onc 2020;21:1465 & JCO 2020;38:3925) or dabrafenib/trametinib (BRAF ⊕, ↑ OS, NEJM 2020;383:1139) • Metastatic: CPI mono vs. dual (ipi+nivo a/w improved response rate especially for intracranial mets, NEJM 2018;379:722). Consider targeted Rx if BRAF ⊕.