Management of advanced melanoma

master's thesis

• Title (croatian): Liječenje uznapredovalog melanoma
• Author: Carmen Margrit Thurid Roeper
• Mentor: Romana Čeović (mentor)
• Committee member: Romana Čeović (predsjednik povjerenstva)
• Committee member: Mihael Skerlev (član povjerenstva)
• Committee member: Suzana Ljubojević Hadžavdić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2021-11-25, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Dermatovenerology

Abstract

The management of advanced melanoma is complex and differs according to the stage of the tumor. The stage is defined by the 2018 American Joint Committee on Cancer (AJCC) melanoma staging system and utilizes the TNM classification. Complete excision of the primary tumor with one to two-centimeter margins is the gold standard. According to tumor thickness and ulceration, a sentinel lymph node biopsy may be performed. The result from this procedure has the greatest overall prognostic value compared with other prognostic factors. If a sentinel lymph node biopsy exhibits micrometastases, a complete lymph node dissection, nodal observation, or adjuvant therapy may be indicated. Metastatic melanoma requires most often systemic therapy. With a number of immune and targeted therapy medications receiving FDA approval during the last ten years, the prognosis of patients with advanced melanoma has significantly improved from an overall survival rate of less than 10 % to values ranging between 34 and 60 %. Immune therapy agents such as the PD-1 blocking antibodies Pembrolizumab and Nivolumab, and the CTLA-4 blocking antibody Ipilimumab and their specific combination have shown great results in phase III randomized clinical trials. Targeted therapy aims at melanomas with BRAF V600 mutations. The MEK inhibitors Trametinib, Cobimetinib, and Binimetinib and the BRAF inhibitors Vemurafenib, Dabrafenib, and Encorafenib are preferably administered in combination as this has shown to increase response duration compared with monotherapy. Patients with advanced melanoma may undergo follow-up examinations every three to twelve months depending on the stage of the tumor and the time that passed from their initial diagnosis. Adoptive cell transfer and a melanoma vaccine are therapies in development. They have not shown clinical outcomes that prompted their adaption to clinical routine practice. The European Society for Medical Oncology (ESMO) has formulated clear recommendations for the management of melanoma patients during the COVID-19 pandemic. Generally, as many visits as possible should be conducted via telemedicine, and patients are categorized as low, medium, and high priority.

Abstract (croatian)

Liječenje uznapredovalog melanoma je složeno i razlikuje se ovisno o stadiju tumora. Stadij je definiran prema sustavu za određivanje stadija melanoma Američkog zajedničkog odbora za rak (engl. American Joint Committee on Cancer, AJCC) iz 2018.godine i koristi TNM klasifikaciju. Potpuna ekscizija primarnog tumora s rubom od jednog do dva centimetra zlatni je standard. S obzirom na debljinu i ulceraciju tumora, možda će biti potrebno napraviti biopsiju sentinel limfnog čvora. Rezultat ovog postupka ima najveću ukupnu prognostičku vrijednost u usporedbi s ostalim prognostičkim čimbenicima. Ako biopsija sentinel limfnog čvora pokaže mikrometastaze, može biti indicirana disekcija cijelog limfnog čvora, opservacija čvora ili adjuvantna terapija. Metastatski melanom zahtijeva najčešće sistemsku terapiju. Uz niz imunoloških i lijekova za ciljanu terapiju koje je odobrila FDA tijekom posljednjih deset godina, prognoza pacijenata s uznapredovalim melanomom značajno se poboljšala u odnosu na ukupnu stopu preživljavanja manju od 10% do vrijednosti u rasponu od 34 do 60%. Agensi imunoterapije kao što su antitijela koja blokiraju PD-1 pembrolizumab i nivolumab, i CTLA-4 blokirajuće antitijelo ipilimumab i njihova specifična kombinacija pokazali su odlične rezultate u randomiziranim kliničkim ispitivanjima faze III. Ciljana terapija usmjerena je na melanome s BRAF V600 mutacijama. MEK inhibitore trametinib, kobimetinib i binimetinib i BRAF inhibitore vemurafenib dabrafenib i encorafenib poželjno je koristiti u kombinaciji jer je ta praksa pokazala povećanje trajanja odgovora u usporedbi s monoterapijom. Pacijenti s uznapredovalim melanomom mogu se podvrgnuti kontrolnim pregledima svaka tri do dvanaest mjeseci ovisno o stadiju tumora i vremenu koje je prošlo od postavljanja njihove dijagnoze. Adoptivni prijenos stanica i cjepivo protiv melanoma su terapije u razvoju. Nisu pokazali kliničke rezultate koji bi potaknuli njihovu prilagodbu kliničkoj rutinskoj praksi. Europsko društvo za medicinsku onkologiju (engl. European Society for Medical Oncology, ESMO) je formuliralo jasne preporuke za liječenje oboljelih od melanoma tijekom pandemije COVID-19. Općenito, posjeti bi se trebali provoditi putem telemedicine što je više moguće, a pacijenti su kategorizirani po prioritetu kao niski, srednji i visoki prioriteti.

• Keywords: advanced melanoma; melanoma; sentinel lymph node biopsy; surgical management; adjuvant therapy; immunotherapy; targeted therapy
• Keywords (croatian): uznapredovali melanom; melanom; biopsija sentinel limfnog čvora; kirurško liječenje; adjuvantna terapija; imunoterapija; ciljana terapija
• Language: english
• URN:NBN: urn:nbn:hr:105:618650
• Study programme: Title: Medicine (in English language); Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-12-22 10:03:44